Abstract

Background:Pseudotumor cerebri (PTC), which has a prevalence in the general population of 1 to 2 out of 100,000, presents with raised intracranial pressure (ICP) but generally lacks a space occupying lesion.

Case Description:Patient 1 is a 32-year-old woman with a history of multiple meningiomas. Upon presentation to our institution, her clinical exam was notable for a right sixth nerve palsy. An integrated diagnosis of PTC was made and shunting for the cerebrospinal fluid (CSF) diversion was recommended. Approximately 6 weeks after surgery, the patient exhibited complete symptom resolution and discontinued all medications. Patient 2 is a 40-year-old woman with history of meningioma causing partial obstruction of the right transverse sigmoid sinus. She agreed to undergo surgery for the left ventriculoperitoneal (VP) shunt placement, for management of her PTC. Postoperatively, the patient reported that her vision significantly improved. Patient 3 is a 49-year-old woman with history of meningioma who presented with left visual field cut. A right frontal VP shunt was recommended for the treatment of PTC. Postoperatively, the patient reported significant symptom improvement and resolution of visual complaints.

Conclusion:This case series demonstrates that it is important to keep PTC in the differential diagnosis even when mass lesions such as meningiomas are discovered. Although PTC, as the name indicates, is classically diagnosed in patients without intracranial tumors, it is critical that this not be used as an absolute exclusion criterion. Finally, this case series supports the hypothesis that venous obstruction can result in PTC.

Keywords: Idiopathic intracranial hypertension, meningioma, pseudotumor cerebri, venous outflow obstruction

INTRODUCTION

Pseudotumor cerebri (PTC), which has a prevalence in the general population of 1 to 2 out of 100,000,[ 24 ] presents with raised intracranial pressure (ICP) but generally lacks a space occupying lesion.[ 1 2 3 6 7 9 10 11 14 15 20 21 22 23 24 25 27 29 30 31 33 35 36 39 ] The exact mechanism of this condition is still subject to great debate.[ 6 9 10 14 20 21 23 24 26 29 38 39 41 ] We present three cases of PTC comorbid with meningiomas seen at our institution and discuss the potential causes underlying the mechanism of this condition.

CASE SERIES

Patient 1

The patient is a 32-year-old woman (body mass index [BMI] of 24.8 kg/m²) with a history of multiple meningiomas. She initially complained of severely painful intermittent headaches that lasted approximately 20 seconds. Over the course of a year, these headaches increased in frequency to multiple times per day. Workup of the headaches at an outside hospital (OSH) included a brain magnetic resonance imaging (MRI) that demonstrated multiple lesions, mostly like meningiomas. One of the masses exerted mass effect on the superior sagittal sinus [ Figure 1 ]. Gamma knife was recommended for the treatment, but after a second opinion, she agreed to undergo a craniotomy for resection of the largest lesion. Pathology confirmed a diagnosis of World Health Organization (WHO) Grade I meningioma. For approximately 7 months, she was asymptomatic and reported doing well, after which her headaches returned. She denied any visual symptoms. The headaches were refractory to Diamox, Topamax, and steroids. Six months after the headaches returned, she presented to our institution where a lumbar puncture was performed that revealed high normal opening pressure of 20 cm H₂O. Routine cerebrospinal fluid (CSF) lab studies were unremarkable; however, her clinical exam was notable for a right sixth nerve palsy. Given the high ICP and sixth nerve palsy, an integrated diagnosis of PTC was made and a ventriculoperitoneal (VP) shunt for CSF diversion was placed. Approximately 6 weeks after surgery, the patient exhibited complete symptom resolution and discontinued all medications. She reported feeling the “best she had in the past 2 and a half years.” The patient did agree to eventually undergo gamma knife treatment for the meningiomas.

Figure 1

Coronal (left) and axial (right) T1 postcontrast MRI brain demonstrating meningioma abutting the superior sagittal sinus

Patient 2

The patient is a 40-year-old woman (BMI of 31.31 kg/m²) with history of meningioma causing partial obstruction of the right transverse sigmoid sinus, with no evidence of hydrocephalus [ Figure 2 ]. Her left transverse sigmoid sinus appeared hypoplastic. She presented with nausea and headaches that were responsive to Diamox, Aleve, and Topamax. Ocular examination demonstrated the central and inferior visual field defect in her left eye and papilledema. Lumbar puncture demonstrated an opening pressure of 40 cm H₂O. Routine CSF studies were unremarkable. She agreed to undergo surgery for left VP shunt placement for management of her PTC. Postoperatively, the patient reported that her vision significantly improved, although she did still have intermittent tinnitus in the left ear and intermittent echoing sensation in the right ear. She also reported having headaches at night. ENT consultation found no peripheral auditory pathology. The patient elected to have the meningioma resected 6 months later due to continued nightly headaches and unusual auditory sounds in the right ear.

Figure 2

Left/middle panels: T1 postcontrast axial MRI demonstrating right temporal/right cerebellar meningioma with mass effect on the right transverse sinus before (left) and after (middle) surgical resection. Some residual was noted along the right transverse sinus. Right panel: Axial MR venogram demonstrating R transverse sinus occlusion

Patient 3

The patient is a 49-year-old woman who presented with left visual field cut (BMI of 27.45 kg/m²). Brain MRI revealed right parieto-occipital meningioma that abutted the superior sagittal sinus without hydrocephalus [ Figure 3 ]. She had papilledema thought to be caused by venous obstruction. She denied headaches or tinnitus. The patient deferred lumbar puncture. A right frontal VP shunt was recommended for the treatment of PTC. Postoperatively, the patient reported significant symptom improvement and resolution of visual complaints. She denied any headaches, nausea, or vomiting and discontinued all medications. She returned to full-time work without any issues. At the patient's 1 year follow-up, she remained asymptomatic; however, imaging studies showed that the parieto-occipital meningioma increased in size. She elected to undergo gamma knife radiosurgery for treatment of the meningioma.

Figure 3

T1 postcontrast axial MRI demonstrating left frontal and right parieto-occipital meningiomas abutting the superior sagittal sinus

DISCUSSION

Pseudotumor cerebri or idiopathic intracranial hypertension

The term pseudotumor cerebri, which should be differentiated from idiopathic intracranial hypertension (IIH),[ 5 23 33 ] was coined by Nonne[ 20 21 27 ] and is thought to be the clinical manifestation of excess CSF production, decreased CSF reabsorption, and/or irregular venous outflow. These abnormal CSF dynamics result in elevated ICP without signs of ventriculomegaly or intracranial tumors.[ 4 6 7 10 11 14 15 18 19 23 24 27 30 31 33 35 36 37 38 39 ] The importance of differentiating PTC from IIH has been a topic of great discussion.[ 4 6 10 12 14 19 20 23 24 29 33 34 38 ] PTC includes both primary and secondary PTC.[ 6 23 24 33 34 ] In the primary PTC, which includes IIH, there is no identifiable cause for the symptoms related to PTC. In the secondary PTC, there is an identifiable cause for the patient's symptoms.[ 6 10 12 14 23 24 33 34 ]

Symptoms and incidence

The most common symptoms of PTC are headaches, transient visual obscurations (TVOs), pulsatile tinnitus, and ocular pain.[ 2 13 23 24 30 33 ] These symptoms are present in 90%-94%, 68%-85%, 58%, and 44% of patients, respectively.[ 4 8 15 19 31 37 39 ] It is important to note that routine CSF laboratory studies are normal in most cases of PTC.[ 19 21 22 29 30 33 ] Despite the rare prevalence in the general population (1 to 2 cases out of 100,000),[ 33 ] there is an increased incidence in females, with a ratio of 8:1 female to male cases.[ 13 15 18 19 28 40 ] Females who are overweight and at the child-bearing age seem to have the highest risk of development, with a prevalence of 19.3 cases per 100,000 in this patient population.[ 7 13 18 19 31 37 40 ]

Diagnosis

Correct and thorough diagnosis is crucial when examining patients with symptoms of PTC. Historically, computer tomography (CT) scans have been used to diagnose intracranial pathology. The advent of magnetic resonance (MR) imaging has greatly improved our ability to detect intracranial pathology.[ 2 6 7 9 10 11 15 16 23 33 38 ] In addition, vascular imaging such as MR venography can detect venous sinus obstruction or flow abnormalities.[ 2 6 9 10 11 15 16 18 19 22 23 24 31 33 34 ] Other criteria for the diagnosis of PTC include CSF opening pressure over 25 cm H₂O or 28 cm H₂O for adults and children, respectively.[ 5 10 11 22 23 24 27 ] In addition, routine CSF studies, which are normal in PTC, should be sent to rule out other pathologies.[ 5 7 10 11 27 38 ] The presence of papilledema or sixth nerve palsy is a sign of increased ICP and supports a diagnosis of PTC.[ 5 8 10 11 14 22 24 40 ] It is important to note that diplopia is also a common symptom and may be the first sign of PTC before papilledema develops.[ 5 ] In addition, infections such as meningitis, otitis media, and mastoiditis, among others, should be considered in the differential diagnosis.[ 17 ] If other focal neurological signs are present on diagnostic tests, other diagnoses should be explored.[ 7 ]

Another important tool used for diagnosis is the Modified Dandy Criteria, which uses a set of criteria to exclude alternative diagnosis similar to PTC.[ 2 6 13 14 20 30 33 ] The set of guidelines are shown in Table 1 . Other than the space occupying masses (meningiomas), all patients in this study met the Dandy criteria, with the sole exception of Patient 1 who had no visual deficits prior to treatment.

Table 1

Modified Dandy Criteria for IIH

Management of care

Once diagnosed, a treatment plan must be formulated. Although there is no single treatment option for PTC, there are three forms of management (surgical management, medical management, and life style change—namely weight reduction) which aim for symptom resolution through a reduction of CSF production and/or CSF pressure.

Surgical treatment options focus on reducing ICP by diversion of CSF.[ 3 6 10 11 14 15 17 18 23 24 27 38 39 42 ] Some recommend against surgical treatment as PTC is not life threatening, but the risks and benefits need to be weighed on a case-by-case basis.[ 6 10 14 18 23 ] Performing a lumbar puncture can aid in diagnosis, and temporary relief of symptoms provides justification for the surgical treatment.[ 3 6 11 38 39 40 ]

Medical management includes the use of diuretics such as carbonic anhydrase inhibitors, which decrease the production of CSF.[ 3 6 10 11 14 17 18 20 23 24 26 28 32 34 40 41 ] Other symptoms of PTC, such as headaches, can also be medically managed.[ 3 6 10 11 23 28 38 39 ]

One of the most important treatments for PTC, however, is the life style change. Specifically, weight management is critical, especially in obese women. Some studies show that a significant decrease in weight resolves major symptoms such as papilledema and headaches.[ 3 4 6 7 10 11 13 18 19 20 22 23 24 27 38 39 40 41 ] PTC also has a progressive impact on vision loss, and studies have shown that patients who have higher BMIs should be monitored more closely for decreases in vision.[ 4 6 7 10 41 ]

Pathophysiology of PTC

Although the exact mechanism to PTC is still under debate, there have been several potential mechanisms documented in the literature, and decreased CSF absorption is the most commonly proposed mechanism.[ 4 6 10 11 21 23 24 27 28 31 35 36 37 38 39 ] Some factors that could contribute to this decreased absorption include venous outflow obstruction, defects in the arachnoid villi, increased levels of Vitamin A secondary to obesity, and decreased neurotransmitter production.[ 10 11 23 24 35 38 ] Defects in the arachnoid villi could trigger a decrease in CSF absorption by increasing villi resistance, even in the presence of other abnormalities, such as intracranial venous hypertension.[ 10 18 20 21 23 24 27 28 31 35 36 37 38 39 ] One cause of these defects in the arachnoid villi was attributed to high levels of Vitamin A, which has been shown to contribute to increased resistance during CSF absorption.[ 10 23 24 38 ] Another potential factor is abnormally low neurotransmitter production, specifically serotonin.[ 10 11 ] This decrease in neurotransmitter production increases CSF production in the choroid plexus, which would ultimately raise the CSF pressure due to an increase in CSF volume.[ 6 10 11 20 23 24 27 31 38 ] In addition, dural venous stenosis has been attributed to venous outflow obstruction and is exhibited in 14% to 90% of cases.[ 6 ]

Meningiomas and PTC

The patients described in this case series met the clinical criteria for PTC and symptomatically improved with CSF diversion. Unique to this case series was the presence of meningiomas in these patients. While the vast majority of PTC patients do not have focal lesions on imaging (and although many include this in the diagnostic criteria), this case series demonstrates that patients with benign mass lesions can have PTC. Primary treatment of the meningioma, as was performed in Patient 1, will not resolve the underlying problem. While headache can be a symptom of meningioma, the actual cause of the headache should be investigated further as was performed in Patients 2 and 3. Only after the treatment of the true underlying pathology, PTC, did this patient's condition improve. In this case series, it was interesting to note that only one patient had a BMI over 30 kg/m² (Patient 2, BMI of 31.8 kg/m²). The other two patients (Patients 1 and 3) had a BMI of 24.8 kg/m² and 27.44 kg/m², respectively. No other risk factors were documented. Each patient in this case series had a meningioma that abutted a sinus and resulted in obstruction of venous outflow. Patient 2 underwent MR venogram that definitively demonstrated obstruction of venous outflow in the right transverse sinus [ Figure 2 ]. These cases, hence, support venous outflow obstruction as the mechanism for PTC in these patients. This case series allows for unique insight into the mechanism of PTC. Venous outflow obstruction likely plays a role in PTC even in patients without mass lesions.

CONCLUSIONS

In conclusion, although the prevalence of PTC is quite low in the general population (1 to 2 cases out of 100,000), the strongest incidence is in females who are overweight and at the child-bearing age (19.3 cases per 100,000 in this population). This case series demonstrates that it is important to keep PTC in the differential diagnosis even when mass lesions such as meningiomas are discovered. While PTC, as the name indicates, is classically diagnosed in patients without intracranial tumors, it is critical that this not be used as an absolute exclusion criterion. Furthermore, this case series demonstrates that venous outflow obstruction is a likely cause of PTC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. . A Rare presentation of neurobrucellosis in a child with Recurrent transient ischemic attacks and pseudotumor cerebri (A case report and review of literature). Iran J Child Neurol. 2014. 8: 65-9

2. Bandyopadhyay S, Jacobson DM. Clinical features of late-onset pseudotumor cerebri fulfilling the modified dandy criteria. J Neuroophthalmol. 2002. 22: 9-11

3. Chutorian A. Reactivation of varicella presenting as pseudotumor cerebri: Three cases and a review of the literature. Pediatr Neurol. 2012. 46: 335-

4. Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster ML, Newman NJ. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007. 143: 635-41

5. De Simone R, Ranieri A, Montella S, Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2014. 82: 1011-2

6. Degnan AJ, Levy LM. Pseudotumor cerebri: Brief review of clinical syndrome and imaging findings. AJNR Am J Neuroradiol. 2011. 32: 1986-93

7. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988. 45: 875-7

8. Evans RW, Friedman DI. Expert opinion: The management of pseudotumor cerebri during pregnancy. Headache. 2000. 40: 495-7

9. Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G. Idiopathic intracranial hypertension: The prevalence and morphology of sinovenous stenosis. Neurology. 2003. 60: 1418-24

10. Friedman DI. Pseudotumor cerebri. Neurol Clin. 2004. 22: 99-131

11. Friedman DI. The pseudotumor cerebri syndrome. Neurol Clin. 2014. 32: 363-6

12. Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013. 81: 1159-65

13. Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): A case-control study. Neurology. 1991. 41: 239-44

14. Hainline C, Rucker JC, Balcer LJ. Current concepts in pseudotumor cerebri. Curr Opin Neurol. 2016. 29: 84-93

15. Higgins JN, Cousins C, Owler BK, Sarkies N, Pickard JD. Idiopathic intracranial hypertension: 12 cases treated by venous sinus stenting. J Neurol Neurosurg Psychiatry. 2003. 74: 1662-6

16. Higgins JN, Gillard JH, Owler BK, Harkness K, Pickard JD. MR venography in idiopathic intracranial hypertension: Unappreciated and misunderstood. J Neurol Neurosurg Psychiatry. 2004. 75: 621-5

17. Kan L, Sood SK, Maytal J. Pseudotumor cerebri in Lyme disease: A case report and literature review. Pediatr Neurol. 1998. 18: 439-41

18. Kanagalingam S, Subramanian PS. Cerebral venous sinus stenting for pseudotumor cerebri: A review. Saudi J Ophthalmol. 2015. 29: 3-8

19. Kesler A, Goldhammer Y, Gadoth N. Do men with pseudomotor cerebri share the same characteristics as women?. A retrospective review of 141 cases. J Neuroophthalmol. 2001. 21: 15-7

20. Kravitz J, Frankel R. Head trauma-induced pseudotumor cerebri--a case report and review. J Trauma. 2010. 68: E91-3

21. Levine DN. Ventricular size in pseudotumor cerebri and the theory of impaired CSF absorption. J Neurol Sci. 2000. 177: 85-94

22. Liguori C, Romigi A, Albanese M, Marciani MG, Placidi F, Friedman D. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2014. 82: 1752-3

23. Mallery RM, Friedman DI, Liu GT. Headache and the pseudotumor cerebri syndrome. Curr Pain Headache Rep. 2014. 18: 446-

24. McGeeney BE, Friedman DI. Pseudotumor cerebri pathophysiology. Headache. 2014. 54: 445-58

25. Meredith JM. The elimination of non-surgical lesions in brain tumor suspects; pseudo-tumor cerebri, and papilledema without increased intracranial pressure (optic neuritis). South Med J. 1948. 41: 31-7

26. Mokri B, Jack CR, Petty GW. Pseudotumor syndrome associated with cerebral venous sinus occlusion and antiphospholipid antibodies. Stroke. 1993. 24: 469-72

27. Pearce JM. From pseudotumour cerebri to idiopathic intracranial hypertension. Pract Neurol. 2009. 9: 353-6

28. Peterson CM, Kelly JV. Pseudotumor cerebri in pregnancy. Case reports and review of literature. Obstet Gynecol Surv. 1985. 40: 323-9

29. Ravid S, Shachor-Meyouhas Y, Shahar E, Kra-Oz Z, Kassis I. Reactivation of varicella presenting as pseudotumor cerebri: Three cases and a review of the literature. Pediatr Neurol. 2012. 46: 124-6

30. Rowe FJ, Sarkies NJ. Assessment of visual function in idiopathic intracranial hypertension: A prospective study. Eye (Lond). 1998. 12: 111-8

31. Silberstein SD, McKinstry RC. The death of idiopathic intracranial hypertension?. Neurology. 2003. 60: 1406-7

32. Suttajit S, Wagner AK, Tantipidoke R, Ross-Degnan D, Sitthi-amorn C. Patterns, appropriateness, and predictors of antimicrobial prescribing for adults with upper respiratory infections in urban slum communities of Bangkok. Southeast Asian J Trop Med Public Health. 2005. 36: 489-97

33. Sylaja PN, Ahsan Moosa NV, Radhakrishnan K, Sankara Sarma P, Pradeep Kumar S. Differential diagnosis of patients with intracranial sinus venous thrombosis related isolated intracranial hypertension from those with idiopathic intracranial hypertension. J Neurol Sci. 2003. 215: 9-12

34. Szitkar B. A meningioma exclusively located inside the superior sagittal sinus responsible for intracranial hypertension. AJNR Am J Neuroradiol. 2010. 31: E57-8

35. Tasdemir HA, Dilber C, Totan M, Onder A. Pseudotumor cerebri complicating measles: A case report and literature review. Brain Dev. 2006. 28: 395-7

36. Venable HP. Pseudo-tumor cerebri. J Natl Med Assoc. 1970. 62: 435-40

37. Venable HP. Pseudo-tumor cerebri: Further studies. J Natl Med Assoc. 1973. 65: 194-7

38. Walker RW. Idiopathic intracranial hypertension: Any light on the mechanism of the raised pressure?. J Neurol Neurosurg Psychiatry. 2001. 71: 1-5

39. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 2010. 28: 593-617

40. Wall M. Idiopathic intracranial hypertension. Neurol Clin. 1991. 9: 73-95

41. Wall M. Idiopathic intracranial hypertension and the idiopathic intracranial hypertension treatment trial. J Neuroophthalmol. 2013. 33: 1-3

42. Wall M, George D. Idiopathic intracranial hypertension. A prospective study of 50 patients. Brain. 1991. 114: 155-80

Abstract

Background:Tension pneumocephalus from skull base surgery is a rare occurrence that mandates urgent neurosurgical attention.

Case Description:We describe a case of tension pneumocephalus secondary to an endoscopic endonasal resection of an adamantinomatous craniopharyngioma and how it was successfully managed at our institution.

Conclusion:Our experience reflects that definitive treatment of tension pneumocephalus is required with multilayered dural repair, but temporising measures should be used immediately to prevent neurological deterioration prior to the definitive repair.

Keywords: Dural repair, skull base surgery, tension pneumocephalus

BACKGROUND

Tension pneumocephalus (TP) is a rare complication of skull base surgery and can lead to rapid neurological deterioration. Significant amounts of intracranial air can compress and displace the intracranial structures, necessitating urgent decompression. While options exist for the management of TP, the treatments are only described in case reports or case series. We report here a case of TP secondary to an endoscopic endonasal resection of an adamantinomatous craniopharyngioma, and how it was managed successfully at our institution. We hope to use the information learnt from this case, in combination with a review of the literature, to create a guide for the management of TP secondary to skull base surgery.

CASE REPORT

The patient is a 57-year-old female who presented with 5 months of progressively worsening visual acuity and diabetes insipidus. Magnetic resonance imaging (MRI) showed a heterogeneous rim-enhancing 17 × 13 × 25 mm suprasellar lesion. The patient has no significant medical comorbidities. An endoscopic endonasal resection of the lesion was performed. DURAFOAM dural graft implant was used to close the dura and a nasoseptal flap was placed over the defect. The lesion was confirmed on pathology to be an adamantinomatous craniopharyngioma. Day 1 postoperative computed tomography of the brain (CTB) showed a small bifrontal pneumocephalus [ Figure 1a ]. Two days postoperatively, the patient developed rhinorrhoea and lower limb diplegia. CTB demonstrated an expanding pneumocephalus with mass effect [ Figure 1b ]. This was decompressed via bilateral frontal burr holes and CTB showed a slight reduction in the volume of the pneumocephalus [ Figure 1c ]. Four days after the operation, her Glasgow Coma Scale (GCS) again deteriorated to 10 (M6V1E3) with lower limb diplegia. Percutaneous aspiration of the pneumocephalus via bilateral frontal burr holes was performed. The aspiration continued until the patient started to verbalize and move her lower limbs.

Figure 1

(a) Day 1 post-operative CTB; (b) Expanding pneumocephalus with mass effect; 1c: slight reduction in volume of pneumocephalus; 1d: significant reduction in size of pneumocephalus

A transnasal transphenoidal repair of the dural defect was performed. Dural substitute was removed and a fascia lata graft inlay was used to repair the defect. However, the negative intracranial pressure drew the fascia lata graft intradurally. A fascia lata onlay graft with autologous blood patch was then used and the nasoseptal flap was replaced and secured with a TISSEEL fibrin sealant. Ten hours after the operation, the patient's GCS dropped to 11 (M6V1E4) and CTB again showed re-accumulation of the pneumocephalus. Percutaneous aspiration was performed and the patient returned to her neurological baseline.

Three days after the last percutaneous aspiration, rhinorrhoea was again observed. This was followed 2 days later by another episode of GCS reduction to 13 (M6V3E4) with diplegia. CTB showed an expanding anterior pneumocephalus with mass effect. Percutaneous aspiration was performed with GCS recovery. The following day, GCS dropped to 9 (M6V2E1), and percutaneous aspiration was again performed for improvement in GCS. An endoscopic repair of the CSF leak was performed. During the operation, a leak was found between the leaflets of the previous fascia lata repair. A fat bath plug was placed over the defect with a large single piece of fascia overlaid. The repair was then tested with Valsalva three times. The nasoseptal flap was overlaid and augmented with a left inferior turbinate free mucosal graft. Postoperative CTB showed a significant reduction in the size of the pneumocephalus [ Figure 1d ]. The patient made an uneventful recovery and discharged GCS 15 with no neurological deficit.

DISCUSSION

Pneumocephalus is the presence of air or gas within the cranial vault usually as a result of a breach in the craniodural barrier. It is thus a common entity following neurosurgical intervention with a predominantly clinically benign course and expectant management.[ 2 ] TP is a clinical emergency in which the pneumocephalus produces intracranial hypertension and subsequent mass effect leading to rapid neurological deterioration and herniation that can manifest clinically as reduction in the level of consciousness (LOC), focal neurological symptoms, seizures, and death.[ 17 ] This case contributes to the literature of reported cases of TP complicating skull base surgery and provides additional insight to its management.

There are two proposed mechanisms for the development of TP. The first is a “ball-valve” mechanism that allows air to enter but not exit the cranial vault through a defect during a cough or sneeze. The second is the “inverted pop bottle” mechanism whereby the air enters the intracranial compartment to equalize the pressure differential as cerebrospinal fluid (CSF) exits through the defect.[ 11 ] The mechanism of action behind the formation of TP thus justifies the importance of repairing the dural defect. Even when the defect is 1 mm, the accumulation of air within the intracranial compartment can progress to TP.[ 4 ] While dural repair is the definitive treatment for TP in skull base surgery, and this is certainly reflected in the literature review performed using Medline as shown in Table 1 ,[ 3 6 7 13 14 15 16 ] temporising measures are often required to manage neurological deterioration and prevent permanent neuronal damage prior to the institution of definitive treatment.

Table 1

Cases of tension pneumocephalus due to skull base surgery

A wide range of temporising measures for TP have been described. Conservative approaches include bed rest, raising the bed head, hyperosmolar therapy, and abstaining from Valsalva or similar manoeuvres.[ 1 8 ] The use of normobaric hyperoxia with 100% inspired oxygen facilitates faster resorption of pneumocephalus and has been described in the literature.[ 10 ] However, 100% FiO2 can only be tolerated for 24 to 48 hours due to pulmonary toxicity.[ 12 ] Medical management alone is often inadequate for even temporising the neurological deterioration. Surgical temporising options, which provide rapid decompression of the pneumocephalus, include needle aspiration, drilling of burr holes, craniotomy, and ventriculostomy.[ 10 ]

From the results of the literature review shown in Table 1 and our case, it is evident that the initial closure with a single layer of fascia lata without glue was too not strong enough to repair the defect. The use of multilayered closure with fibrin glue for the second attempt was successful. This finding was echoed in Aksoy et al.'s study whereby multilayered closure with adipose tissue, fascia lata, and glue was used to successfully repair a 1 mm defect. Therefore, we suggest to treat dural defects in TP secondary to skull base surgery via a multilayered technique consolidated by fibrin glue irrespective of the size of the defect.[ 5 ]

Another learning point from our case was the use of the Valsalva manoeuvre intraoperatively following closure of the dural defect to check for CSF leakage. This was not performed during the first operation which was unsuccessful in treating the pneumocephalus, but was performed in the second operation during which the dural defect was successfully closed. Theoretically, Valsalva expels intrathoracic blood to cause an increase in intracerebral pressure (ICP) which promotes spillage of CSF from the intracranial compartment if a dural defect exists.[ 9 ] We thus advocate for its use at the end of the operation to test the integrity of the repair.

TP secondary to skull base surgery is a rare complication that can be accompanied by acute neurological deterioration. The definitive treatment of TP is dural repair, but temporising measures should be used to prevent neurological deterioration prior to the definitive repair. Dural repair should be performed using a multilayered approach with consolidation from fibrin glue, and the Valsalva manoeuvrer should be performed at the end of the repair to assess its integrity.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Funding

No funding was received for this research.

Compliance with ethical standards

Conflicts of interest

There are no conflicts of interest to disclose.

Informed consent Informed consent was obtained from the patient.

References

1. Aksoy F, Dogan R, Ozturan O, Tugrul S, Yildirim YS. Tension pneumocephalus: an extremely small defect leading to an extremely serious problem. Am J Otolaryngol. 2013. 34: 749-52

2. Babl FE, Arnett AM, Barnett E, Brancato JC, Kharasch SJ, Janecka IP. Atraumatic pneumocephalus: A case report and review of the literature. Pediatr Emerg Care. 1999. 15: 106-9

3. Celikoglu E, Hazneci J, Ramazanoglu AF. Tension pneumocephalus causing brain herniation after endoscopic sinus surgery. Asian J Neurosurg. 2016. 11: 309-10

4. Chou S, Ning M, Buonanno F. Focal intraparenchymal tension pneumocephalus. Neurology. 2006. 67: 1485-

5. Church CA, Chiu AG, Vaughan WC. Endoscopic repair of large skull base defects after powered sinus surgery. Otolaryngol Head Neck Surg. 2003. 129: 204-9

6. Clevens RA, Bradford CR, Wolf GT. Tension pneumocephalus after endoscopic sinus surgery. Ann Otol Rhinol Laryngol. 1994. 103: 235-7

7. Emmez H, Durdag E, Uslu S, Pasaoglu A, Ceviker N. Intracerebral tension pneumocephalus complicating endoscopic sinus surgery: Case report. Acta Neurochir (Wien). 2009. 151: 1001-2

8. Goldmann RW. Pneumocephalus as a consequence of barotrauma. JAMA. 1986. 255: 3154-6

9. Haldar R, Khandelwal A, Gupta D, Srivastava S, Rastogi A, Singh PK. Valsalva maneuver: Its implications in clinical neurosurgery. Neurol India. 2016. 64: 1276-80

10. Hong B, Biertz F, Raab P, Scheinichen D, Ertl P, Grosshennig A. Normobaric hyperoxia for treatment of pneumocephalus after posterior fossa surgery in the semisitting position: A prospective randomized controlled trial. PLoS One. 2015. 10: e0125710-

11. Horowitz M. Intracranial Pneumocoele. An Unusual Complication Following Mastoid Surgery. J Laryngol Otol. 1964. 78: 128-34

12. Klein J. Normobaric pulmonary oxygen toxicity. Anesth Analg. 1990. 70: 195-207

13. Mammis A, Agarwal N, Eloy JA, Liu JK. Intraventricular tension pneumocephalus after endoscopic skull base surgery. J Neurol Surg A Cent Eur Neurosurg. 2013. 74: e96-99

14. Pruss H, Klingebiel R, Endres M. Tension pneumocephalus with diplegia and deterioration of consciousness. Case Rep Neurol. 2011. 3: 48-9

15. Ruiz-Juretschke F, Mateo-Sierra O, Iza-Vallejo B, Carrillo-Yague R. Intraventricular tension pneumocephalus after transsphenoidal surgery: A case report and literature review. Neurocirugia (Astur). 2007. 18: 134-7

16. Simmons J, Luks AM. Tension pneumocephalus: An uncommon cause of altered mental status. J Emerg Med. 2013. 44: 340-3

17. Sweni S, Senthilkumaran S, Balamurugan N, Thirumalaikolundusubramanian P. Tension pneumocephalus: A case report with review of literature. Emerg Radiol. 2013. 20: 573-8

Abstract

Background:Accessory breast, also known as supernumerary breasts, polymastia, or mammae erraticae, is a clinical condition of having an additional breast. Accessory breasts are usually seen along the embryonic milk line, with the majority located in the axilla. Polythelia is the presence of an additional nipple. We report a rare case of dorsal accessory ectopic breast with three nipples (two well formed and one rudimentary) occurring along with lipomeningomyelocele and diastematomyelia.

Case Description:We report the case of an 18-year-old female who presented with chief complaints of swelling over the upper back since birth and spastic weakness of bilateral lower limbs with inability to walk since 2 years. Three-dimensional computed tomography scan of the dorsal spine was suggestive of a wide bony defect in the posterior spinal elements from D3 to D9 vertebrae. Diastematomyelia was also seen. Magnetic resonance imaging of the dorsal spine was suggestive of a complex spinal dysraphism with lipomeningomyelocele and diastematomyelia. During surgery, the patient's accessory breast was removed, lipomatous tissue and bony septum were excised, and dural repair was done. Histopathological examination was consistent with accessory ectopic breast with lipomeningomyelocele.

Conclusion:Dorsal accessory breast, although a rare entity, whenever present should alert the clinician regarding the possibility of an underlying occult spinal dysraphism (OSD). Therefore, dorsal accessory breast can also be considered as a marker of OSD.

Keywords: Dorsal, ectopic breast, lipomeningomyelocele, occult spinal dysraphism, polythelia

INTRODUCTION

Accessory breast, also known as supernumerary breasts, polymastia, or mammae erraticae, is a clinical condition of having an additional breast. Accessory breasts are usually seen along the embryonic milk line, with the majority located in the axilla. Polythelia is the presence of an additional nipple. We report a rare case of dorsal accessory ectopic breast with three nipples (two well formed and one rudimentary) occurring along with lipomeningomyelocele and diastematomyelia. The association of dorsal accessory breast with meningomyelocele and diastematomyelia has been reported only once in the world literature, however, the association of dorsal accessory breast with polythelia with lipomeningomyelocele and diastematomyelia has never been reported.[ 4 ]

CASE DESCRIPTION

We report the case of an 18-year-old female who presented with chief complaints of swelling over the upper back since birth and spastic weakness of bilateral lower limbs with an inability to walk since 2 years. On examination, the swelling was soft-to-firm, nontender, midline in location, which started increasing in size at puberty and progressed since then to the present size of 14 cm × 12 cm [ Figure 1 ]. Three-dimensional (3D) computed tomography scan of the dorsal spine was suggestive of a wide bony defect in the posterior spinal elements from D3 to D9 vertebrae. Diastematomyelia was also seen from D3 to D7 vertebrae [ Figure 2 ]. Magnetic resonance imaging (MRI) of the dorsal spine was suggestive of a complex spinal dysraphism with lipomeningomyelocele and diastematomyelia [ Figure 3 ]. At surgery, the patient's accessory breast was removed, lipomatous tissue and bony septum were excised, and dural repair was done. An elliptical vertical skin incision was taken incorporating the reductant skin along with the three nipples. The entry of the fibrolipomatous stalk through the fascial defect was identified. A large lipomatous mass along with the accessory breast was amputated at the level of the stalk to help in the visualization of the spinal cord–lipoma interface. Two hemicords with a dorsal type lipomeningomyelocele was identified [ Figure 4 ]. The penetrating intradural lipomatous tract was identified all around. The osseocartilaginous median septum was drilled. Normal dura of both the hemicords was opened and the openings were carried caudally towards the penetrating tract. Circumferential dissection around the lipomatous tract was continued until the dura was separated completely. The dural opening was then continued caudally. The fatty mass was resected with the help of cavitron ultrasonic surgical aspirator (CUSA). Neurulation of the neural placode was then done. Water tight dural closure (duraplasty) was done for both the hemicords separately with the help of a graft. Histopathological examination was consistent with accessory ectopic breast with lipomeningomyelocele [ Figure 5 ].

Figure 1

(a) Clinical examination of the patient showing a midline dorsal accessory breast with 3 nipples (2 well formed and 1 rudimentary). (b) Close up view

Figure 2

(a and b) 3D Computed Tomography (CT) scan of the dorsal spine showing a wide bony defect in the posterior spinal elements from D3 to D9 vertebrae. (c) Diastematomyelia is also seen

Figure 3

(a) Magnetic Resonance Imaging (MRI) of the dorsal spine suggestive of a complex spinal dysraphism with lipomeningomyelocele. (b) Diastematomyelia is also seen

Figure 4

Schematic diagram showing the relationship of occult spinal dysraphism (OSD) with dorsal accessory ectopic breast

Figure 5

(a) Hematoxylin and eosin stained section (×40) showing normal skin with appendages (single arrow); Subepithelial tissue shows lactiferous duct (double arrow). (b) Hematoxylin and eosin stained section (×80) showing lactiferous duct with secretion inside (single arrow) along with terminal duct lobular units of breast (double arrow). (c and d) Hematoxylin and eosin stained section (×20 and ×40 respectively) showing lipomatous component composed of sheets of mature adipocytes with adjacent dural fibroblasts

The postoperative period was uneventful. Spasticity and power in the lower limbs improved and the patient was able to walk with support at the time of discharge.

DISCUSSION

Multiple theories have been proposed to explain the occurrence of accessory breast. These include Darwin's theory which stated that “traits which have disappeared generations before, can reappear,” Pfeifer's theory of metaplasia of sweat glands or modified sweat glands, Hughes's theory of random migration of primordial breast cells away from the mammary crest, and Schultz's theory of displacement of milk lines, laterally or caudally.[ 2 5 6 7 ]

Studies have shown that an ectopic breast usually increases in size after hormonal stimulation during puberty, pregnancy, or lactation.[ 1 ] In our case also, the swelling started increasing in size after the girl attained puberty. Ectopic breasts, similar to normal breasts, are prone to the risk of developing various types of breast diseases such as abscess, mastitis, fibroadenoma, fibrocystic disease, or breast cancer.[ 8 ]

Occult spinal dysraphism (OSD) is characterized by skin-covered lesions without exposed neural tissue. Cutaneous markers of OSD include lipoma, fibroma pendulum, human or faun tail, dermal sinus, atypical dimple (larger than 5 mm and more than 2.5 cm from the anus), hamartoma, aplasia cutis congenita, deviation of the gluteal furrow, port wine stain, hemangioma, hypertrichosis, and acrochordon (skin tag).[ 3 ] A combination of two or more congenital cutaneous lesions constitutes the strongest marker of OSD.[ 3 ]

CONCLUSION

Dorsal accessory breast, although a rare entity, whenever present should alert the clinician regarding the possibility of an underlying OSD. Therefore, dorsal accessory breast can also be considered as a marker of OSD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Burdick AE, Thomas KA, Welsh E, Powell J, Elgart GW. Axillary polymastia. J Am Acad Dermatol. 2003. 49: 1154-6

2. Darwin C.editors. The descent of man and selection in relation to sex. New York: Appleton and Co; 1892. p. 36-7

3. Guggisberg D, Hadj-Rabia S, Viney C, Bodemer C, Brunelle F, Zerah M. Skin markers of occult spinal dysraphism in children: A review of 54 cases. Arch Dermatol. 2004. 140: 1109-15

4. Gupta VK, Kapoor I, Punia RS, Attri AK. Dorsal ectopic breast in a case of spinal dysraphism: A rare entity. Neurol India. 2015. 63: 392-4

5. Hughes ES. The development of the mammary gland: Arris and Gale Lecture, delivered at the Royal College of Surgeons of England on 25 th October, 1949. Ann R Coll Surg Engl. 1950. 6: 99-119

6. Pfeifer JD, Barr RJ, Wick MR. Ectopic breast tissue and breast-like sweat gland metaplasias: An overlapping spectrum of lesions. J Cutan Pathol. 1999. 26: 190-6

7. Schultz A.editors. Pathologische anatomic der brustdruse In: Handbuch der speziellen Pathologischen Anatomie and Histologie. Berlin: Julius Springer; 1933. p.

8. Shin SJ, Sheikh FS, Allenby PA, Rosen PP. Invasive secretory (juvenile) carcinoma arising in ectopic breast tissue of the axilla. Arch Pathol Lab Med. 2001. 125: 1372-4

Abstract

Background:Trigeminal neuralgia (TN) represents one of the most disabling pain syndromes. Several diseases have been described as etiological triggers of TN, vascular compression of the trigeminal nerve being the most frequent cause. Here, we describe for the first time a rare case of TN caused by an infiltration of an isolated Epstein–Barr virus (EBV) B-cell lymphomatoid granulomatosis (LYG) mass into the Meckel's cave and cavernous sinus.

Case Description:A 51-year-old woman undergoing immunosuppressant treatment for Crohn's disease presented due to right-sided TN. Magnetic resonance imaging (MRI) scans revealed an isolated lesion affecting the right Meckel's cave and lateral wall of the cavernous sinus. We accomplished tumor resection through a subtemporal extradural approach and the patient recovered successfully from surgery. Histological examination revealed an LYG, and a blood test confirmed low but positive EBV counts. The immunosuppressant therapy was discontinued and we assumed a watchful waiting management. During a 41-months’ follow-up there was neither evidence of LYG recurrence nor an increase of EBV counts.

Conclusions:LYG, an angiodestructive disease associated with EBV reactivation in the context of immune dysfunction and often associated with an aggressive behavior or even malignant transformation, should be considered as a rare differential diagnosis of TN associated with skull base lesions. The management of this rare disease is still controversial and varies from limiting the treatment to correcting immune dysfunction up to chemotherapy. In this case of an isolated mass, surgical excision and discontinuation of immunosuppressants were effective to prevent the relapse of the disease in a long-term follow-up.

Keywords: B-cell lymphomatoid granulomatosis, cavernous sinus, Meckel's cave, trigeminal neuralgia

INTRODUCTION

Trigeminal neuralgia (TN) represents one of the most disabling pain syndromes that patients can experience. The identification of its etiology in individual patients is mandatory to rule out diseases that may primarily require special evaluation and treatment besides the pharmacological therapy directed to relief neuropathic pain. TN is associated in a vast majority of cases with a vascular compression of the trigeminal nerve, followed more infrequently by inflammatory and tumor processes affecting the nerve or its central pathways.[ 1 2 5 6 7 9 15 16 18 24 29 33 ] Although granulomatous diseases such as sarcoidosis, tuberculosis, and Wegener's granulomatosis have been described to affect the trigeminal nerve and trigger TN due to infiltration of the skull base.[ 1 2 5 6 7 16 24 33 ] Till now, there are no reports of B-cell lymphomatoid granulomatosis (LYG) showing the infiltration of structures within the middle fossa or causing TN. We present for the first time the case of a 51-year-old woman receiving immunosuppressant treatment due to Crohn's disease and presenting TN caused by an infiltration of a LYG mass into the Meckel's cave and lateral wall of the cavernous sinus. LYG is an angiodestructive disease associated with EBV reactivation in the context of immune dysfunction. Its identification may be critical due to the potential of this disease to show a very aggressive behavior or even malignant transformation.[ 10 23 28 35 ] In this report, we discuss the important clinical and therapeutic implications of recognizing this entity as a rare but possible differential diagnosis of lesions affecting the middle fossa and causing TN. We also review the literature available on LYN to provide an insight into the management and therapy that might be applicable in these cases.

CASE REPORT

A 51-year-old woman presented to our clinic because she had been suffering for the lasts 3 weeks from TN affecting the right V1-V2 branch. The patient reported a strong progression of pain as well as diplopia. Her neurological examination was inconspicuous apart from the presence of a right abducens nerve paresis and sensory loss corresponding to the V1 and V2 dermatome. According to her clinical records, she suffered from Crohn's disease and had received azathioprine as immunosuppressive therapy.

Magnetic resonance imaging (MRI) scans revealed a heterogeneous T1 contrast enhancing lesion in the right Meckel's cave extending to the lateral wall of the cavernous sinus [ Figure 1 ]. The lesion was isointense in T2 and constructive interference in steady state (CISS) sequences and did not show diffusion restriction. There was no evidence of vascular compression of the trigeminal nerve in the cerebellopontine angle [ Figure 2 ]. Blood probes did not show any abnormal values, and protein levels in cerebrospinal fluid (CSF) were slightly increased, especially IgA and IgG antibodies. Oligoclonal bands were not detectable.

Figure 1

Preoperative axial (a), coronal (b), and sagittal (c) MRI scans showing a heterogeneous T1 contrast enhancing lesion involving the right Meckel's cave and the lateral wall of the cavernous sinus corresponding in the histopathological analysis to an Epstein-Barr-virus-associated B-cell lymphomatoid granulomatosis

Figure 2

LYG lesion was isointense in native T1 (a), T2 (b), and CISS (c) sequences and showed no diffusion restriction (d) in preoperative MRI scans

We suggested surgical exploration and trigeminal nerve decompression in the Meckel's cave using a right subtemporal extradural Dolenc approach. During surgery, the lesion was amenable to be separated from the dural envelope of the cavernous sinus and was completely resected [ Figure 3 ]. After surgery, the patient recovered successfully without any new neurological deficits. Although the facial sensory deficit remained unchanged, facial pain and diplopia from the abducens nerve paresis resolved. No corticosteroids were administered to the patient, neither before nor after the surgery.

Figure 3

Axial contrast enhanced T1-weighted MRI immediately postoperative confirmed a successful removal of the lesion (a) and there was no evidence of LYG relapse (b) 6 months after surgery

Histopathological examination established the diagnosis of Epstein–Barr-virus-associated B-cell lymphomatoid granulomatosis (LYG) by showing the typical transmural vascular infiltration of lymphocytes, epithelioid cells, and histiocytes with oval nucleus and discrete nucleoles, necrotic epithelioid, and giant cells on the borders and reticulin fiber infiltration [ Figure 4 ]. Mycobacterial infection was excluded by Ziehl–Neelsen staining, and immunohistochemical analysis revealed T-cells as well as clusters of CD20-positive B- lymphocytes (some of them necrotic), small CD1a- positive and S100- negative cells, and CD68+ macrophages.

Figure 4

Histological tissue sections showing transmural vascular infiltration of lymphocytes, (a) epithelioid cells and histiocytes (b) characteristic of LYG

As expected, analysis of Epstein–Barr virus (EBV) revealed a viral load of 380 copies/mm³ in blood samples. Abdominal and thoracic computed tomography (CT) scans revealed very small intrapulmonary lesions without affecting the lymph nodes. The patient did not present any systemic or respiratory symptoms. A multidisciplinary conference with the colleagues of the hematology and gastroenterology department decided to discontinue azathioprine and start a treatment with rituximab only if the viral load exceeded 10³/mm³. The patient was followed up every 3 months in the first year, every 6 months in the second, and then once yearly. In the follow-ups, no corticosteroids were prescribed.

Under surveillance after resection, there was no cranial granuloma recurrence in further neuroimaging studies performed every 6 months during the follow-up [Figures 3 and 5 ], and EBV load remained lower than 10³/mm³; hence, there was no need of other specific therapies. Pain recurred after a period of approximately 6 months in which the patient was free of TN. A combined pharmacological therapy was initiated to reduce the pain and showed initial success, but unfortunately failed to achieve a complete symptomatic control in the long term. Because MRI scans consistently ruled out a lesion recurrence and EBV load persisted below 10³/mm³, we offered a percutaneous thermocoagulation of the Gasserian ganglion, which was refused by the patient.

Figure 5

Axial (a) and coronal (b) contrast weighted T1 MRI images after 41-months’ follow-up showing no local recurrence of LYG

DISCUSSION

TN is known as one of the most disabling pain syndromes. Although vascular compression of the trigeminal nerve root at the Obersteiner Redlich zone in the cerebellopontine angle can be identified as the cause of TN in 80–90% of the cases, several other conditions, such as demyelinated plaques, tumor and pseudotumor lesions, aneurysms, and arteriovenous malformations, have been identified as triggers of TN.[ 1 2 5 6 7 9 15 16 18 24 29 33 ] Neuroimaging is mandatory to investigate the etiology of trigeminal pain in each individual patient. It rules out diseases that may primarily require special evaluation and treatment exceeding the standard pharmacological therapy to relieve neuropathic pain and contributes to the assessment of the optimal surgical treatment option if the pain becomes refractory to medication.

Among tumor processes which can affect the trigeminal nerve and trigger TN, neurinoma and meningioma are the most common, although many other entities, included lymphoma, have been already described.[ 3 9 12 17 22 25 30 34 36 37 40 ] More rarely, granulomatous diseases, such as Wegener; s granulomatosis,[ 1 7 24 ] tuberculosis,[ 16 ] and sarcoidosis[ 2 5 6 33 ] involving the Meckel's cave have been described as the etiology of TN. However, to our knowledge, there are no previous reports in the literature of LYG affecting the Meckel's cave or describing this entity as an etiological trigger of TN.

LYG constitutes an extremely rare angiocentric and angiodestructive process described for the first time by Liebow and colleagues in the early 1970s. It is characterized by nodular lesions composed of a mixed population of lymphoreticular cells showing vascular infiltration and necrosis.[ 10 28 ] Its natural history can vary from a relatively indolent course up to a rapidly fatal evolution resembling high-grade T-cell lymphomas.[ 23 35 ] Indeed, cases of true transformation into an aggressive lymphoma have been documented.[ 14 23 28 ] Therefore, the suspicion and correct diagnosis of this entity is fundamental for the adequate management of each individual patient.

More than 90% of patients suffering from LYG show a symptomatic bilateral involvement of the lungs.[ 23 35 ] Most patients consult due to systemic complains such as fever, weight loss, and malaise, which are followed by respiratory symptoms such as cough and shortness of breath and present in approximately 50% and 30% of cases, respectively.[ 23 ] Blood examinations usually show normal leucocyte counts and inflammatory parameters.[ 35 ] We may remark that no systemic or pulmonary symptomatology was present in our patient at the time of diagnosis or during the follow-up. Other organs such as the kidneys, skin, and central nervous system (CNS) are also frequently affected by LYG. Indeed, an involvement of CNS might occur in 25–50% of patients,[ 23 35 ] although in such cases affection of the CNS has been always described either as multiple, small, intraparenchymatous brain lesions, as larger heterogeneous ring-enhancing brain masses, or as a leptomeningeal infiltration along the basal cisternal space.[ 32 ] These lesions are characterized by abnormally increased signal intensity on FLAIR and T2-weighted MR images, as well as by punctate or linear central contrast enhancement in T1 sequences.[ 32 ] If leptomeninges are affected, MRI scans will show a diffuse contrast enhancement within the basal cisterns. In the series published by Patsalides et al., only one patient developed a lesion in the suprasellar area.[ 32 ] An isolated affection of the skull base, as in our patient, has not been reported yet in LYG patients.

Confusion, ataxia, hemiparesis, and seizures are among the most common manifestations of neurological involvement. Others, including cranial nerve dysfunction and peripheral neuropathy affecting usually the lower extremities, have been reported only sporadically. Bell's palsy, diplopia, transient blindness, proptosis, deafness, and vertigo are already described manifestations of cranial nerve dysfunction associated with LYG.[ 23 35 ] In all patients, leptomeningeal involvement was responsible for the symptoms, not isolated masses within the skull base, as in our patient. No case of TN has been reported earlier in the published series of LYG and the only case existing of trigeminal infiltration was again caused by a leptomeningeal involvement of the basal cisterns.[ 23 35 ]

In the histological examination, mononuclear cells comprising T-lymphocytes, plasma cells, and histiocytes are accompanied by only a small number of B-lymphocytes showing EBV positivity. However, the key feature comprehends the angiocentric and angiodestructive nature of the lesions with transmural vascular infiltration of T-cells and histiocytes showing various degrees of necrosis.[ 10 35 ] These characteristics should be meticulously considered to differentiate this entity from other diseases which can affect the cavernous sinus or Meckel's cave, can trigger TN, and may histopathologically resemble some features of LYG, such as sarcoidosis, Wegener's granulomatosis, or lymphoma.

The pathophysiology of this disease has been linked to a lack of control of EBV-infected B-cells. In this context, it is agreed that recruitment of intravascular T-cells induced by EBV infection may mediate the vascular damage seen in histological specimens.[ 20 ] Apart from EBV load counts, a search for IgG and IgM antibodies directed against EBV should be performed in all patients. Underlying this EBV reactivation, a functional immune dysregulation has been seen in almost all patients suffering from LYG[ 20 41 ] and, consistent with this observation, the occurrence of LYG has been associated with several autoimmune diseases, congenital immunodeficiencies, and conditions following either leukemia therapy or organ transplantation.[ 23 27 31 ] In addition, discontinuing immunosuppressants has been observed to induce a remission in patients with LYG, and this option may be considered for each patient, if reasonable.[ 35 ] In more severe cases with evidence of a progressive disease, patients have been treated with corticosteroids, rituximab, interferon-α-2b, and chemotherapeutic agents such as prednisone, etoposide, vincristine, cyclophosphamide, and doxorubcin.[ 4 8 13 14 19 21 23 38 ] Although progression and malignant transformation justify the use of these strategies, because an immunodeficiency underlies the pathophysiology of this disease, there are concerns whether treatment with corticosteroids and chemotherapy could also have the potential of worsening the clinical course. Unfortunately, due to the infrequent presentation of this disease, there is a lack of medical studies systematically proving the effectiveness of these treatments, and a few published series have reported conflicting results. Furthermore, lack of cases reporting an involvement of the skull base makes it difficult to predict the effectiveness of these agents for the treatment of patients like the one we present in this article. Discontinuation of azathioprine, regular control of EBV viral counts, as well as clinical and neuroimaging follow-up seem to have been a reasonable strategy for our patient who did not show evidence of relapse or progressive disease during 41-months of follow-up. We assumed that the recurrence of TN after 6 months must have been associated with postsurgical adhesions/scarring and not to a relapse of LYG or EBV reactivation. It is important to consider that MRI scans performed at the time of pain recurrence and further on repeatedly demonstrated no LYG mass relapse. Furthermore, EBV counts remained 3/mm³, and there were no clinical features of active systemic EBV infection along the complete follow-up. Although a local EBV reactivation cannot be completely excluded as a possible cause of TN recurrence (due to the fact that EBV counts had already been 3/mm³ at the time of diagnosis), in a scenario of local EBV activation we would have expected progressive findings in consecutive MRI scans as well as a further neurological deterioration of the patient, neither had occurred.

The role of surgery may be debated in cases such as the one presented. First, in our patient, surgery was clearly indicated to obtain material for histopathological diagnosis. The atypical localization of a LYG lesion within the Meckel's cave and cavernous sinus had not been described before, thus making the preoperative tentative diagnosis of this disease unlikely in our case. Furthermore, the MRI characteristics shown by this lesion were unspecific. The inhomogeneous contrast enhancement in T1-weighted images resembled features that are commonly described in other diseases which have been reported to affect the cavernous sinus and surrounding structures, such as lymphoma, tuberculoma, sarcoidosis, or Wegener's granulomatosis.[ 1 2 5 6 7 16 24 26 33 ] Furthermore, the nodular involvement of the lungs is also a common feature that might occur in all these diseases. Interestingly, we may remark the absence of diffusion restriction in MRI shown by the LYG mass in our patient. Although unspecific, a restriction in diffusion-weighted MRI is usually observed in inflammatory processes such as sarcoidosis or tuberculosis, as well as frequently in dense cellular tumors such as lymphomas.[ 26 ] Far from being able to generalize our findings, this characteristic, albeit nonspecific feature could eventually help to suspect this disease in future cases. Perhaps MRI spectroscopy performed on similar lesions could be of great interest in the future to identify possible key features that may be helpful to differentiate and individualize these lesions.

In addition, the determination of EBV antibodies or a positive viral load can be helpful to suspect this disease, however, these parameters do not replace the need of histopathological examination. EBV infection infect the majority of world population and remains asymptomatic in most cases.[ 11 39 ] Furthermore, other entities which have been described to affect the cavernous sinus, such as Burkitt lymphoma, can be also associated with EBV infection, making the differentiation of these entities possible only by tissue examination.[ 12 17 22 40 ]

As surgery was indicated in our patient, the next dilemma we faced was whether just a biopsy for diagnostic purposes or an attempt to remove the mass, followed in both cases by immunosuppressant discontinuation and/or chemotherapy, would be the most reasonable approach for cases similar to the one we describe. This question may be difficult to answer given the infrequent presentation of LYG and it is consequentially difficult to predict a response by only adopting a conservative strategy, considering the relatively poor knowledge we have about the natural history of the disease as well as the lack of similar cases affecting the skull base. Although there have been sporadic reports of LYG remission after discontinuing immunosuppressants or chemotherapy,[ 35 ] none of these cases were dealing with lesions located in the skull base. On one hand, in our experience, the feasibility to remove the mass by an experienced neurosurgeon enabled us not only to get enough material for histopathological analysis but also to resolve the problem of mass effect versus relevant neurovascular structures as well as to avoid leaving behind in situ a lesion which is known to have the potential of aggressive malignant transformation.[ 14 23 28 ] On the other hand, biopsy and immunosuppressant discontinuation added or not to chemotherapy and followed by a narrow wait-and-see strategy could be reasonable in case of lesions difficult to remove. In those cases, a strict follow-up with MRI at short-term intervals must be mandatory.

CONCLUSIONS

The case we present here provides relevant clinical and therapeutic implications. We describe for the first time LYG as a rare but existing differential diagnosis of Meckel's cave and cavernous sinus masses associated with TN. As the perioperative evaluation and treatment may significantly differ between LYG and other tumor and inflammatory entities, we recommend being aware of this disease, especially in patients with a prior history of EBV infection, autoimmune disease, and/or undergoing immunosuppressive therapy. In such patients, the presence of systemic symptoms as well as signs of pulmonary, skin, kidney, eye, or even intracerebral and leptomeningeal involvement may be helpful to suspect the diagnosis, but their absence does not rule out LYG, as has been observed in our patient. If LYG is suspected, searching for EBV titers may also be useful to orientate the diagnosis, along with thoracic and abdominal CT scans to detect whether other organs, especially the lungs, are affected. However, in all cases, a histopathological examination is mandatory to confirm the diagnosis.

In our case, we have observed that the removal of LYG localized in the Meckel's cave and cavernous sinus may be feasible and safe. Performed by experienced hands, surgery may correlate with transient pain relief. In our patient, discontinuing immunosuppressive therapy was followed by the reduction and stabilization of EBV counts and a prevention of a relapse or progression of the disease. Whether corticosteroids, rituximab, interferon-α-2b, or chemotherapy should be considered in case of recurrent disease is still an open question. We cannot provide any recommendation for the use of these agents based on our experience.

Ethical standards and conflict of interest

The manuscript does not contain clinical studies or identity patient data and the authors declare that they have no conflict of interest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Andrews JT, Kountakis SE. Wegener's granulomatosis of the skull base. Am J Otolaryngol. 1996. 17: 349-52

2. Arias M, Iglesias A, Vila O, Brasa J, Conde C. MR imaging findings of neurosarcoidosis of the gasserian ganglion: An unusual presentation. Eur Radiol. 2002. 12: 2723-5

3. Arimoto H, Shirotani T, Nakau H, Hashizume K, Sakai Y, Matsukuma S. Primary malignant lymphoma of the cavernous sinus-case report. Neurol Med Chir (Tokyo). 2000. 40: 275-9

4. Armitage JO. My treatment approach to patients with diffuse large B-cell lymphoma. Mayo Clin Proc. 2012. 87: 161-71

5. Bangiyev L, Kornacki S, Mikolaenko I. Rare isolated trigeminal nerve sarcoidosis mimicking schwannoma. Clin Imaging. 2015. 39: 133-5

6. Braksick S1, Shah-Haque S, El-Haddad B, Moussa R. Neurosarcoidosis presenting as trigeminal neuralgia: A case report and review of the literature. Sarcoidosis Vasc Diffuse Lung Dis. 2013. 30: 153-6

7. Carpentier AS, Riehm S, Charpiot A, Onea A, Debry C, Schultz P. Wegener's granulomatosis of the temporal bone and skull base that mimicked an inflammatory myofibroblastic tumour: A case report. B-ENT. 2010. 6: 135-8

8. Castrale C, El Haggan W, Chapon F, Reman O, Lobbedez T, Ryckelynck JP. Lymphomatoid granulomatosis treated successfully with rituximab in a renal transplant patient. Journal of Transplantation. 2011. 2011: 1-5

9. Cheng TM, Cascino TL, Onofrio BM. Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors. Neurology. 1993. 43: 2298-

10. Colby T. Current histological diagnosis of lymphomatoid granulomatosis, Modern Pathology. 2012. 25: 39-42

11. Condon LM, Cederberg LE, Rabinovitch MD, Liebo RV, Go JC, Delaney AS. Age-specific prevalence of Epstein-Barr virus infection among Minnesota children: effects of race/ethnicity and family environment. Clin Infect Dis. 2014. 59: 501-8

12. Dufour H, Diaz A, Metellus P, Fuentes S, Chinot O, Figarella-Branger D. Burkitt lymphoma of the cavernous sinus. Apropos of a case. Neurochirurgie. 2001. 47: 564-7

13. Dunleavy K, Chattopadhyay P, Kawada J, Calattini S, Gostick E, Price D. Immune characteristics associated with lymphomatoid granulomatosis and outcome following treatment with interferon-alpha. Blood. 2010. 116: 424-

14. Fauci AS, Haynes BF, Costa J, Katz P, Wolff SM. Lymphomatoid granulomatosis. Prospective clinical and therapeutic experience over 10 years. N Engl J Med. 1982. 306: 68-74

15. Figueiredo PC, Brock M, De Oliveira AM, Prill A. Arteriovenous malformation in the cerebellopontine angle presenting as trigeminal neuralgia. Arq Neuropsiquiatr. 1989. 47: 61-

16. Goel A, Nadkarni T, Desai AP. Tuberculoma in the Meckel's cave: A case report. Neurol India. 1999. 47: 238-40

17. Huisman TA, Tschirch F, Schneider JF, Niggli F, Martin-Fiori E, Willi UV. Burkitt's lymphoma with bilateral cavernous sinus and mediastinal involvement in a child. Pediatr Radiol. 2003. 33: 719-21

18. Ildan F, Göçer AI, Baǧdatoǧlu H, Uzuneyüpoǧlu Z, Tuna M, Cetinalp E. Isolated trigeminal neuralgia secondary to distal anterior inferior cerebellar artery aneurysm. Neurosurg Rev. 1996. 19: 43-

19. Jaffe ES, Wilson WH. Lymphomatoid granulomatosis: Pathogenesis pathology and clinical implications. Cancer Surv. 1997. 30: 233-48

20. Jaffre S, Jardin F, Dominique S, Duet E, Hubscher P, Genevois A. Fatal haemoptysis in a case of lymphomatoid granulomatosis treated with rituximab. Eur Respir J. 2006. 27: 644-6

21. Jung KH, Sung HJ, Lee JH, Lee KY, Shin JS, Kim KM. A case of pulmonary lymphomatoid granulomatosis successfully treated by combination chemotherapy with rituximab. Chemotherapy. 2009. 55: 386-90

22. Kalina P, Black K, Woldenberg R. Burkitt's lymphoma of the skull base presenting as cavernous sinus syndrome in early childhood. Pediatr Radiol. 1996. 26: 416-7

23. Katzenstein AL, Carrington C, Liebow A. Lymphomatoid granulomatosis: A clinicopathologic study of 152 cases. Cancer. 1979. p. 360-73

24. Keni SP, Wiley EL, Dutra JC, Mellott AL, Barr WG, Altman KW. Skull base Wegener's granulomatosis resulting in multiple cranial neuropathies. Am J Otolaryngol. 2005. 26: 146-9

25. Ko F, Subramanian PS. Orbital and Cavernous Sinus Lymphoma Masquerading as Post-Herpetic Neuralgia. Neuroophthalmology. 2011. 35: 27-31

26. Koubska E, Weichet J, Malikova H. Central nervous system lymphoma: A morphological MRI study. Neuro Endocrinol Lett. 2016. 37: 318-24

27. Kwon EJ, Katz KA, Draft KS, Seykora JT, Rook AH, Wasik MA. Posttransplantation lymphoproliferative disease with features of lymphomatoid granulomatosis in a lung transplant patient. J Am Acad Dermatol. 2006. 54: 657-63

28. Liebow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol. 1972. 3: 457-8

29. Love S, Coakham HB. Trigeminal neuralgia: pathology and pathogenesis. Brain. 2001. 124: 2347-

30. Matthies C, Samii M. Management of 1000 vestibular schwannomas (acoustic neuromas): clinical presentation. Neurosurgery. 1997. 40: 1-10

31. Moertel CL, Carlson-Green B, Watterson J, Simonton SC. Lymphomatoid granulomatosis after childhood acute lymphoblastic leukemia: Report of effective therapy Pediatrics. 2001. 107: 82-

32. Patsalides A, Atac G, Hedge U, Janik J, Grant N, Jaffe E, Dwyer A. Lymphomatoid Granulomatosis: Abnormalities of the Brain at MR Imaging. Radiology. 2005. 237: 265-73

33. Quinones-Hinojosa A, Chang EF, Khan SA, McDermott MW. Isolated trigeminal nerve sarcoid granuloma mimicking trigeminal schwannoma: Case report. Neurosurgery. 2003. 52: 700-5

34. Rasper M, Kesari S. Burkitt lymphoma presenting as a rapidly evolving cavernous sinus syndrome. Arch Neurol. 2008. 65: 1668-

35. Roschewski M, Wilson W. Lymphomatoid granulomatosis. The Cancer Journal. 2012. 18: 469-74

36. Sadruddin S, Medeiros LJ, DeMonte F. Primary T-cell lymphoblastic lymphoma of the cavernous sinus. J Neurosurg Pediatr. 2010. 5: 94-7

37. Sanjeevi A, Krishnan J, Bailey PR, Catlett J. Extranodal marginal zone B-cell lymphoma of malt type involving the cavernous sinus. Leuk Lymphoma. 2001. 42: 1133-7

38. Shapiro RS, Chauvenet A, McGuire W, Pearson A, Craft AW, McGlave P. Treatment of B-cell lymphoproliferative disorders with interferon alfa and intravenous gamma globulin. N Engl J Med. 1988. p. 318-1334

39. Stanfield BA, Luftig MA. Recent advances in understanding Epstein-Barr virus. p.

40. Vaphiades MS, Lee AG. Burkitt lymphoma presenting with gingival pain and a cavernous sinus syndrome in an adult. J Neuroophthalmol. 2005. 25: 249-50

41. Wilson WH, Kingma DW, Raffeld M, Wittes RE, Jaffe ES. Association of lymphomatoid granulomatosis with Epstein-Barr viral infection of B lymphocytes and response to interferon-alpha 2b. Blood. 1996. 87: 4531-7

A 69-year-old male patient presented with multiple episodes of fall for 6 months. Magnetic resonance imaging of the brain showed T1 isointensity, T2 hyperintensity, and homogenous enhancement on contrast [Figure 1a – f ]. Intraoperatively, the tumor was completely intraventricular without any attachment to the surrounding thalamus or tela choroidea. This unique case was managed as (according to history and imaging) meningioma, but biopsy came out as metastatic deposit of squamous cell carcinoma from the lung [Figure 2a – d ].

Figure 1

(a-c) Contrast-enhanced brain MRI (axial, coronal and sagittal sequences, respectively) showing homogenously enhancing lesion at the posterior third ventricular region. (d) Axial T2 brain MRI sequence showing hyperintense mass attached to tela choroidea. (e) FLAIR sequence of brain MRI showing hyperintense lesion. (f) DWI sequence of brain MRI showing diffusion restriction in the lesion

Figure 2

(a) Microphotograph showing tumor cell population (H and E, ×100). (b-d) High-power view (H and E, ×400) of the carcinoma cells with focal keratinization

Intraventricular metastasis presents with various aspects of enhancement (uniform, punctate, ring) which can often lead to misdiagnosis of meningioma.[ 1 2 ] This case is educational for both neurosurgeons and radiologist as missing proper diagnosis can affect both the management and outcome of patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Tagle P, Villanueva P, Torrealba G, Huete I. Intracranial metastasis or meningioma?. An uncommon clinical diagnostic dilemma. Surg Neurol. 2002. 58: 241-5

2. Brant WE, Helms CA.editors. Fundamentals of diagnostic radiology. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 143-

Abstract

Background:Orbital mature teratoma is a rare congenital tumor.

Case Description:A 37-year-old woman presented with ophthalmalgia predated by years of progressive incongruous right eye position, diplopia, and restricted extraocular movement. Neuroimages revealed a right orbital mass originating from the orbital roof. After resection, histopathology revealed the mature teratoma.

Conclusion:To the authors’ best knowledge, this is the first documented diploic origin of mature teratoma at the orbital roof.

Keywords: Diplopic origin, orbit, teratoma

INTRODUCTION

Craniofacial teratomas are rare tumors and they are believed to be congenital lesions due to the abnormal distribution of germ cells during the 3^rd to 5^th weeks of gestation.[ 1 ] Occasionally, they could be slow growing leading to presentation in the adulthood.[ 7 ]

Orbital teratomas account for 1% of all orbital tumors in childhood and are usually localized within orbit and without bony involvement.[ 3 5 ] We present a very rare case of diploic mature teratoma originating from the orbital roof in a young woman.

CASE HISTORY

A 37-year-old woman presented with a history of right eye pain of few days duration. There was, however, a background history of incongruous position of her eyes and diplopia of over 10 years duration. The protrusion was noted to have worsened weeks leading to presentation to a hospital where cranial computed tomography (CT) and magnetic resonance imaging (MRI) showed a right orbital mass causing exophthalmos. The mass was partly enhanced and it was predominantly intraosseous located at the orbital roof [Figures 1 and 2 ]. She was subsequently referred to our service. On presentation, she had lagophthalmos. Her visual acuity was 20/16 in the right eye and 20/20 in the left eye. No visual field defect was detected. She had diplopia at upward and downward gaze only. She subsequently underwent a surgery through the right frontotemporal craniotomy and superior orbitotomy. The tumor originated from the intraosseous region but the periorbit was intact. The tumor was completely removed. Postoperatively, the exophthalmos, eye pain, lagophthalmos, and diplopia improved. The histopathologic diagnosis was compatible with mature teratoma [ Figure 3 ]. There has been no recurrence for 6 months after surgery.

Figure 1

Preoperative computed tomography showing the right-sided exophthalmos (a) and diploic mass at the right orbital roof (b: axial image, c: coronal image, d: sagittal image)

Figure 2

Magnetic resonance imaging showing the mixed intensity mass (a: T1-weighted image, b: T2-weighted image) with peripheral enhancement (c: coronal T1-weighted image, d: enhanced coronal T1-weighted image). Arrows indicating the enhanced lesion

Figure 3

Photomicrographs of a mature teratoma showing squamous epithelium (left, hematoxylin and eosin, X15) and bone tissue (right, hematoxylin and eosin, X9)

DISCUSSION

Here, we report a rare case of mature teratoma that originated from the diploic orbital roof. Orbital teratomas are rare, usually presenting with unilateral proptosis of eyeball in neonates.[ 3 5 ] They are rapidly progressive and induce secondary damage to eyeball due to mass effect.[ 3 5 ] A slight predominance of the left orbit was reported and the female sex was also predominantly affected.[ 2 ] Histologically, orbital teratomas are usually benign with well differentiated tissues representing two or three germinal layers.[ 2 3 5 ]

In general, orbital mature teratomas are purely orbital location without intracranial involvement.[ 2 ] The intracranial extension is rarely reported.[ 3 5 ] In addition, mature teratoma rarely develops at the calvarium.[ 4 ] Therefore, diploic mature teratoma originating from the orbital roof is an extremely rare entity. To our knowledge, this is the first report of diploic mature teratoma originating from the orbital roof. We speculate that the abnormal migration of primordial germ cells into diploic tissue of the orbital roof might be responsible for the occurrence of diploic mature teratoma.

The mature teratoma usually consists of solid tissues with encapsulated cyst. Radiologic features of mature teratoma are nonspecific because they depend on containing different well-differentiated components such as soft tissue, cartilage, or bone. Therefore, mature teratomas have mixed density and intensity on computed tomography and magnetic resonance imaging, respectively, whereas contrast enhancement is variable.[ 7 ] In addition, calcification is found in half of the reported cases of mature teratoma. In the present case, neither calcification nor encapsulated cyst were found on CT and MRI. The only peripheral enhancement was seen on MRI.

Complete resection for mature teratoma leads to a surgical cure and prognosis is good.[ 6 7 ] If teratoma contains immature tissues, chemotherapy, and radiotherapy are recommended.

CONCLUSION

An extremely rare case of diploic mature teratoma arising from the orbital roof was presented.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Anderson PJ, David DJ. Teratomas of the head and neck region. J Craniomaxillofac Surg. 2003. 31: 369-77

2. Grube-Pagola P, Hobart-Hernandez RI, Martinez-Hernandez MA, Gomez-Dorantes SM, Alderete-Vazquez G. Congenital proptosis secondary to orbital teratoma. Clinicopathological study. Arch Soc Esp Oftalmol. 2013. 88: 153-6

3. Kharosekar HU, Jasmit S, Velho V, Palande DA. Congenital orbital teratoma up to posterior fossa. J Pediatr Neurosci. 2014. 9: 182-4

4. Lloret I, Server A, Taksdal I. Calvarial lesions: A radiological approach to diagnosis. Acta Radiol. 2009. 50: 531-42

5. Morris DS, Fayers T, Dolman PJ. Orbital teratoma: Case report and management review. J AAPOS. 2009. 13: 605-7

6. Selcuki M, Attar A, Yuceer N, Tuna H, Cakiroglu E. Mature teratoma of the lateral ventricle: Report of two cases. Acta Neurochir (Wien). 1998. 140: 171-4

7. Zhao J, Wang H, Yu J, Zhong Y, Ge P. Cerebral falx mature teratoma with rare imaging in an adult. Int J Med Sci. 2012. 9: 269-73

Abstract

Background:Teratocarcinosarcoma (TCS) is a rare malignant neoplasm with epithelial and mesenchymal components such as fibroblasts, cartilage, bone and smooth muscle. With less than 100 total reported cases, this malignant neoplasm is rarely encountered by neurosurgeons because it primarily involves the nasal cavity and paranasal sinuses.

Case Description:A 55-year-old male with chronic frontal headaches was found to have a frontal mass with involvement of nasal sinus and right ethmoid sinus. The patient underwent preoperative embolization of tumor followed by bilateral frontal craniotomy for near total resection of the tumor. Patient did well postoperatively without new neurological deficits.

Conclusion:Although cases with intracranial involvement are scarce, treatment with surgical resection with or without adjuvant treatments of chemotherapy and radiation therapy is the most widely accepted with goal for gross total resection. In our case, we achieved near total resection and the patient continues to do well without any gross neurological deficits.

Keywords: Brain tumor, neuro-oncology, neurosurgery, oncology, teratocarcinosarcoma

INTRODUCTION

Teratocarcinosarcoma (TCS) is a rare malignant neoplasm with epithelial and mesenchymal components, such as fibroblasts, cartilage, bone, and smooth muscle, with less than 100 cases described in the literature.[ 1 ] The term was first coined in 1984 by Heffner and Hyams, the key features to properly diagnose TCS are the presence of “fetal-appearing” clear-cell squamous epithelium and organoid structures such as tubular or glandular formations.[ 2 5 ] Germ cell components are absent in TCS.[ 16 18 ] Benign and malignant epithelial, mesenchymal, and neural elements are present, which include immature tissue with teratoid features.[ 4 5 ]

Nearly all reported cases of TCS arise within the nasal cavity or paranasal sinuses, with a few reports having described intracranial invasion into the dura mater or the frontal lobe at presentation or progression, as in our case.[ 5 15 16 ] Misra et al. reviewed 86 reported cases of sinonasal teratocarcinosarcoma (SNTCS) and found a strong male predilection (87%), mean age of 54.5 years; 18/86 (20.9%) cases described intracranial extension, cribriform plate, and anterior cranial fossa involvement.[ 10 ] Mean survival has been reported at 1.7 years with a 60% mortality rate within 3 years.[ 4 ] One case series of 10 patients (100% male) had no cases with intracranial and dural/or dural extension.[ 14 ] Given the rarity of intracranial involvement of this neoplasm, this tumor is rarely encountered by the neurosurgeon. We report a case of TCS and describe the surgical approach and postoperative care.

CASE REPORT

History and presentation

A 55-year-old male presented with frontal headaches 3 times a week with progressive memory problems, word-finding difficulties, and new-onset seizures. Magnetic resonance imaging (MRI) of the brain revealed a 7.0 × 6.2 × 4.4 cm enhancing mass extending across the cribriform plate and into the right anterior cranial fossa and right nasal cavity [ Figure 1 ]. The patient was initially referred to ENT for biopsy which revealed TCS; he was then referred to the neurosurgical service for further evaluation.

Figure 1

Postcontrast MRI post-contrast with AP (a) and sagittal (b) images showing enhancing lesion extending from nasal sinus to anterior cranial fossa with frontal lobe invasion. Post-operative postcontrast MRI post-contrast shows Axial axial (c) and AP (d) views with near total resection of mass

Operative intervention

Given the preoperative diagnosis via transnasal biopsy and presumed hypervascularity of the neoplasm, the patient underwent preoperative embolization followed by bilateral frontal craniotomy via a bicoronal incision with pericranial flap preservation. ENT assisted with exposure of the tumor using the transglabellar subcranial approach. Tumor was found to be pale and hypervascular with a dural breach in the low frontal plane with involvement of the superior ethmoid sinus [ Figure 2 ]. Endonasally, the right middle turbinate and remaining ethmoid sinuses were resected. Gross total resection was achieved with significant decrease in blood loss once the tumor was completely removed. The inferior right anterior pole of the dura just above the superior ethmoids appeared to have tumor invasion. This area of dura was resected and reconstructed using dural repair graft. Then, tisseal was placed within each intervening layer of dural graft and duragen, which was placed over the dural closure. The pericranial flap was placed in the nasoethmoidal defect and an additional 10-cc tisseal was applied. The frontal sinuses were fully cranialized bilaterally. Excess pericranium flap on the left was replaced over the frontal bone.

Figure 2

Intra-operative images delineating our designated craniotomy (a). The dysplastic appearing dura visualized once craniotomy performed (b)

Histological staining

Staining was positive for CK-PanAE1-3CAM52, vimentin, EMA, S100, CK 5/6, P63, synaptophysin, chromogranin, and GFAP. Staining negative for CD99 and neurofilament [ Figure 3 ].

Figure 3

H and E stain (a) shows carcinoma and sarcoma components, p63 stain (b) highlights the carcinoma with squamous differentiation, PAN-CK stain (c) highlights carcinoma components, vimentin (d) highlights sarcoma, and undifferentiated tumor component

Postoperative course

The postoperative course was significant for pulmonary embolism and was otherwise unremarkable. Twenty-four months postoperatively the patient is and doing well without any seizure-like activity with return to baseline neurological status. MRI showed no evidence of recurrence with expected postoperative changes [ Figure 1 ]. He completed adjuvant chemotherapy with three rounds of cisplatin therapy and radiation therapy consisting of 60 Gy in 30 fractions to the nasal cavity, frontal sinuses, and partial brain. He is back to work and is currently being weaned from antiepileptics.

DISCUSSION

TCS is a rare malignant neoplasm with epithelial and mesenchymal components. The most common presenting signs and symptoms are nasal obstruction and epistaxis, found in ~75% to 90% of documented cases.[ 4 10 13 14 ] Given the primarily intracranial involvement in our case, the presenting symptoms were neurological in nature, which is rare for this type of neoplasm. To our knowledge, this is the only documented case with seizure as a presenting symptom.

A review of literature revealed 11 cases of TCS with intracranial invasion [ Table 1 ].[ 3 6 7 8 9 16 17 19 20 21 ] Although the documented cases with predominant intracranial involvement are scarce, treatment with surgical resection with or without adjuvant treatments of chemotherapy and radiation therapy is the most widely accepted with goal for gross total resection. Despite few intracranial cases described in the literature, patients undergoing gross total resection fare better than those with subtotal resection. Further areas of research should focus on whether neo-adjuvant treatment with chemotherapy/radiation therapy can prolong life expectancy by reducing preoperative tumor burden and limiting surgical complications from blood loss and healthy tissue destruction resecting larger tumors. A case by Tchoyoson et al. described residual periventricular tumor leading to craniospinal dissemination and patient death less than 6 months after initial surgical resection, emphasizing the importance of gross total resection.[ 16 ]

Table 1

Reported cases of teratocarcinosarcoma with intracranial invasion

Given the multitude of cell types in this neoplasm, biopsy alone is not of high yield. TCS requires adequate sampling for proper diagnosis. Possible erroneous diagnosis include olfactory neuroblastoma, squamous cell carcinoma, undifferentiated carcinoma, adenocarcinoma, malignant craniopharyngioma, malignant mixed tumor of salivary gland type, mucoepidermoid carcinoma, adenosquamous carcinoma, and transitional carcinoma of Schneiderian type.[ 12 ] In our case, the benefit of preoperative diagnosis was utilized as an advantage to plan for preoperative embolization given the vascularity of the neoplasm.

The combined transglabellar/subcranial approach gives simultaneous exposure of the upper and lower limits of the tumor in the anterior fossa, ethmoid sinus, and sphenoid sinus for improved completeness of resection.[ 11 ] Furthermore, a standard bifrontal craniotomy allowed for limited brain retraction, adequate exposure for resection of dura along the frontal skull base with duroplasty, and gross total resection. Given the tumor's inherent predilection to the nasofrontoethmoidal cavities, adequate cranialization, exenteration, and obliteration of frontal sinus is essential. When dural invasion is suspected, as was seen in our case, it is imperative to obtain a water-tight closure to prevent pseudomeningocele formation.

CONCLUSIONS

TCS is a rare neoplasm rarely encountered by the neurosurgeon given its predilection for sinonasal involvement with majority of cases presenting with sinonasal obstruction and/or epistaxis. Neurological signs and symptoms are very rare with this neoplasm. To our knowledge, this is the first reported case with seizure as a presenting sign. Diagnosis requires ample tissue sample. Once diagnosis is established, the surgeon can plan for the optimal surgical approach to facilitate gross total resection. Goal of gross total surgical resection is standard with or without chemotherapy and/or radiation therapy. Combined ENT and neurosurgical approaches can limit the number of surgical procedures required for gross total resection. Metastasis is uncommon but has been reported in cases with postoperative residual mass

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Agrawal N, Chintagumpala M, Hicks J, Eldin K, Paulino AC. Sinonasal teratocarcinosarcoma in an adolescent male. J Pediatr Hematol Oncol. 2012. 34: e304-7

2. Cardesa A, Luna MA, Barnes L, Evenson JW, Reichart P, Sidransky D.editors. Germ cell tumors. Pathology and Genetics of Head and Neck Tumors. Lyon: IARC; 2005. 9: 76-7

3. Endo H, Hirose T, Kuwamura KI, Sano T. Case report: Sinonasal teratocarcinosarcoma. Pathol Int. 2001. 51: 107-12

4. Fatima SS, Minhas K, Din NU, Fatima S, Ahmed A, Ahmad Z. Sinonasal teratocarcinosarcoma: A clinicopathologic and immunohistochemical study of 6 cases. Ann Diagn Pathol. 2013. 17: 313-8

5. Heffner DK, Hyams VJ. Teratocarcinosarcoma (malignant teratoma?) of the nasal cavity and paranasal sinuses A clinicopathologic study of 20 cases. Cancer. 1984. 53: 2140-54

6. Joshi A, Dhumal SB, Manickam DR, Noronha V, Bal M, Patil VM. Recurrent sinonasal teratocarcinosarcoma with intracranial extension: Case report. Indian J Cancer. 2014. 51: 398-400

7. Joshi A, Noronha V, Sharma M, Dhumal S, Juvekar S, Patil VM. Neoadjuvant chemotherapy in advanced sinonasal teratocarcinosarcoma with intracranial extension: Report of two cases with literature review. J Cancer Res Ther. 2015. 11: 1003-5

8. Kim JH, Maeng YH, Lee JS, Jung S, Lim SC, Lee MC. Sinonasal teratocarcinosarcoma with rhabdoid features. Pathol Int. 2011. 61: 762-7

9. Kleinschmidt-DeMasters BK, Pflaumer SM, Mulgrew TD, Lillehei KO. Sinonasal teratocarcinosarcoma (“mixed olfactory neuroblastoma-craniopharyngioma”) presenting with syndrome of inappropriate secretion of antidiuretic hormone. Clin Neuropathol. 2000. 19: 63-9

10. Misra P, Husain Q, Svider PF, Sanghvi S, Liu JK, Eloy JA. Management of sinonasal teratocarcinosarcoma: A systematic review. Am J Otolaryngol. 2014. 35: 5-11

11. Raveh J, Vuillemin T, Sutter F. Subcranial management of 395 combined frontobasal-midface fractures. Arch Otolaryngol Head Neck Surg. 1988. 114: 1114-22

12. Shanmugaratnam K, Kunaratnam N, Chia KB, Chiang GS, Sinniah R. Teratocarcinosarcoma of the paranasal sinuses. Pathology. 1983. 15: 413-9

13. Shorter C, Nourbakhsh A, Dean M, Thomas-Ogunniyi J, Lian TS, Guthikonda B. Intracerebral metastasis of a sinonasal teratocarcinosarcoma: A case report. Skull Base. 2010. 20: 393-6

14. Smith SL, Hessel AC, Luna MA, Malpica A, Rosenthal DI, El-Naggar AK. Sinonasal teratocarcinosarcoma of the head and neck: A report of 10 patients treated at a single institution and comparison with reported series. Arch Otolaryngol Head Neck Surg. 2008. 134: 592-5

15. Sweety Vijay S, Kumar TD, Srikant B, Vithal SH, Vijay KS, Gurunath P. Intracranial presentation of teratocarcinosarcoma. J Clin Neurosci. 2010. 17: 1347-9

16. Takasaki K, Sakihama N, Takahashi H. A case with sinonasal teratocarcinosarcoma in the nasal cavity and ethmoid sinus. Eur Arch Otorhinolaryngol. 2006. 263: 586-91

17. Tchoyoson Lim CC, Thiagarajan A, Sim CS, Khoo ML, Shakespeare TP, Ng I. Craniospinal dissemination in teratocarcinosarcoma. J Neurosurg. 2008. 109: 321-4

18. Terasaka S, Medary MB, Whiting DM, Fukushima T, Espejo EJ, Nathan G. Prolonged survival in a patient with sinonasal teratocarcinosarcoma with cranial extension. Case report. J Neurosurg. 1998. 88: 753-6

19. Thomas J, Adegboyega P, Iloabachie K, Mooring JW, Lian T. Sinonasal teratocarcinosarcoma with yolk sac elements: A neoplasm of somatic or germ cell origin?. Ann Diagn Pathol. 2011. 15: 135-9

20. Weinberg BD, Newell KL, Wang F. A case of a beta-human chorionic gonadotropin secreting sinonasal teratocarcinosarcoma. J Neurol Surg Rep. 2014. 75: e103-7

21. Wellman M, Kerr PD, Battistuzzi S, Cristante L. Paranasal sinus teratocarcinosarcoma with intradural extension. J Otolaryngol. 2002. 31: 173-6

Abstract

Background:Brain metastases from laryngeal squamous cell carcinoma (SCC) are rare, and there are no standardized treatments. Here we reported on a case of brain metastasis from laryngeal SCC and performed a literature review on these cases. Moreover, by plotting Kaplan–Meier curves, we carried out a survival analysis to provide an estimation of overall survival (OS) and to find possible prognostic factors.

Case Description:A 65-year-old male was admitted to our department with a large left occipital lesion. Three years ago, the patient had undergone total laryngectomy with bilateral neck dissection with a diagnosis of a poor differentiated SCC. The occipital lesion was totally removed. A diagnosis of a brain metastasis from laryngeal SCC was made. The patient was submitted to adjuvant chemotherapy and radiation therapy. He is in good clinical conditions at 7-month follow-up with a still ongoing chemotherapy. From survival analysis, we have found that surgery and/or radiochemotherapy increase the OS of these patients compared with untreated cases. Moreover, Karnofsky performance status (KPS) score ≥70 and recursive partitioning analysis (RPA) classes I and II were associated with better OS in these patients.

Conclusion:Brain metastases from laryngeal SCC are rare. This is the first study in which a survival analysis of these cases has been performed. Surgery and/or radio-chemotherapy increase the survival of these patients compared with untreated cases. Moreover, KPS score and RPA class affect the outcome of these patients.

Keywords: Brain metastasis, laryngeal squamous cell carcinoma, literature review, overall survival, prognosis

INTRODUCTION

Head and neck squamous cell carcinoma (HNSCC) can arise from the oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx. There are well-known risk factors for these tumors such as sustained exposure to tobacco and tobacco-like products, cigarette smoking, and alcohol abuse. Moreover, exposure to high-risk oncogenic human papillomavirus increases the risk of development of oropharyngeal SCC. Overall, about 644,000 new cases each year are reported worldwide.[ 8 ] HNSCC frequently spreads to regional lymph nodes and, at late stages, may also metastasize to distant organs such as the brain. The incidence of clinically detected distant metastases from HNSCC ranges from 9% to 11%,[ 7 ] and from 2% to 8% are located in the brain.[ 9 ] Differently from this wide group of tumors, distant metastases from SCC originating exclusively in the larynx are less frequent with a reported incidence less than 4% of cases.[ 1 ] Moreover, to our knowledge, only few cases of intracranial metastases from laryngeal SCC have been reported in the literature.[ 2 4 5 10 12 13 14 15 16 ] As a result, it is difficult to collect a wide series of brain metastasis form laryngeal SCC to give indications about the prognosis and the treatment of this condition. Moreover, we cannot find any literature review on this topic. Thus, the aim of this study was to report on a rare case of brain metastasis from laryngeal SCC and to carry out a survival analysis of cases reported in the literature.

CASE REPORT

A 65-year-old male was admitted to our department with a right hemiparesis. Three years ago, the patient had undergone total laryngectomy with bilateral neck dissection. He had been a smoker for 40 years before that operation. On histopathology a diagnosis of a poor differentiated SCC (T4a, N2c, M0; G3) had been made. The patient had then been submitted to adjuvant radiation therapy. One year later, a total body computed tomography (CT) scan detected multiple pulmonary lesions with mediastinal lymph node enlargement, which were treated with chemotherapy (carboplatin and fluorouracil, but the treatment was interrupted after only two sessions for drug toxicity). Radiological follow-up showed stability of pulmonary lesions for 18 months when a disease progression was evidenced by a lung CT scan. Thus, the patient underwent a second cycle of chemotherapy with paclitaxel (interrupted after three sessions for the onset of fatigue and hand–foot syndrome) with stability of pulmonary lesions. Due to the onset of the right hemiparesis, the patient was submitted to brain magnetic resonance imaging, which showed a large left occipital mass with contrast enhancement and perilesional edema [ Figure 1 ]. The patient was then submitted to occipital craniotomy and total removal of the tumor. The postoperative course was uneventful with improvement of hemiparesis. On histopathological examination, the tumor was poorly differentiated although foci of squamous differentiation were present, as highlighted by immunohistochemistry for CK5/6 and p40. A diagnosis of a brain metastasis from laryngeal SCC was made [ Figure 2 ]. The patient was then submitted to adjuvant radiation therapy. One month later, he started a new cycle of chemotherapy with methotrexate. He is in good clinical conditions at 7-month follow-up with a still ongoing chemotherapy.

Figure 1

Brain magnetic resonance imaging showing a polylobate lesion in the left occipital lobe isohypointense on (a) axial T2-weighted images and (b) fluid attenuation inversion recovery sequences. Perilesional edema is evident with compression of the occipital horn of the lateral ventricle and mass effect. On (c) T1-weighted sequences after gadolinium administration, the tumor showed a dishomogeneous contrast enhancement

Figure 2

Histopathological examination revealed a metastasis of a poorly differentiated carcinoma composed of nests of cell with hyperchromic and irregular nuclei (a and b). The tumor showed strong immunoreactivity for pan-cytokeratins (AE1/AE3) and focal positivity for CK5/6 and p40, showing areas of squamous differentiation (c and d)

DISCUSSION

SCC represents more than 90% of the tumors arising from the larynx, and smoking habit and alcohol consumption are reported as the most important risk factors for its development.[ 8 11 ] Locoregional spreading by contiguous structures and lymphatic invasion is the most common growing pattern for laryngeal SCC. Distant spreading is rare and is sustained by hematogenous dissemination or perineural invasion.[ 6 ] The incidence of clinical distant metastases from laryngeal SCC ranges from 1% to 4%[ 1 ] and the lung is the most frequent site, followed by bone and liver.[ 4 ] Intracranial metastases from laryngeal SCC are extremely rare. In fact, looking at the literature, we were able to find only 18 reported cases [ Table 1 ]. To our knowledge, this is the first literature review on these cases. Moreover, by plotting Kaplan–Meier curves we carried out a survival analysis to provide an estimate of overall survival (OS) and to find possible prognostic factors associated with better OS. P values 4 ] The intracranial location was in the brain parenchyma in 10 cases, in the cavernous sinus in 6 (1 with pituitary gland involvement), and in the pituitary gland in 1 case. In one patient, there were multiple brain metastases and a concomitant meningeal metastasis.[ 10 ] In another patient, a brain metastasis and a lesion in the cavernous sinus with involvement of pituitary gland and orbit were reported.[ 15 ] Thus, 42.10% (8/19 cases) of patients with a brain metastasis from laryngeal SCC had a lesion involving the sellar and parasellar regions showing an incidence that seems to be higher compared with how reported for all intracranial metastases in this region (incidence ranging between 0.14% and 28%).[ 3 ] From a therapeutic point of view, three cases received no therapy. In the remaining ones, radiotherapy or chemotherapy or a combination of them was performed. Only three cases and the present one underwent an operation. In all previous operated cases, only a surgical biopsy was made.[ 4 13 15 ] Thus, this is the first reported case of an intracranial metastasis from laryngeal SCC submitted to a total removal of the lesion. From Kaplan–Meier analysis, we found a statistically significant difference in the OS between the treated and untreated groups (P = 0.045) with a median OS of 2.3 months in the untreated groups and 8.77 months in the treated group [ Figure 3a ]. Moreover, we found a statistically significant better OS in patients with a Karnofsky performance status (KPS) ≥70 (P = 0.0132; median OS in KPS ≥70 group: 11.37 months; median OS in KPS Figure 3b ]) and a better OS in recursive partitioning analysis (RPA) classes I and II compared with RPA class III (P = 0.0194; median OS in RPA class I group: 12.6 months; median OS in RPA class II group: 5 months; median OS in RPA class III group: 2.8 months; [ Figure 3c ]). Overall, the 6-month OS was 43.75% and the 1-year OS was 21.42%.

Table 1

Clinical and outcome data of patients with brain metastasis from laryngeal squamous cell carcinoma

Figure 3

Kaplan–Meier survival curve of patients with intracranial metastasis from laryngeal squamous cell carcinoma stratified by treatment. (a) There was a statistically significant difference in the overall survival between the treated and untreated groups. (b) KPS score ≥70 and (c) RPA classes I and II were associated with better overall survival

It should be evidenced that our study has some limitations such as the limited number of cases included in the analysis and the heterogeneity of considered studies. All these factors should be considered as potential bias in survival analysis. Nonetheless, in our opinion, this study has the merit of providing indications about the survival and prognosis of patients with a brain metastasis from laryngeal SCC. In summary, the prognosis of an untreated brain metastasis from laryngeal SCC is very poor. Surgery and/or radiochemotherapy increase the survival of these patients. KPS score and RPA class are confirmed as prognosticators in these patients.

CONCLUSION

Brain metastases from laryngeal SCC are rare. No standardized treatments are available in the literature. This is the first study that, carrying out a survival analysis of previous cases, has provided indications about the survival and prognosis of these patients. Surgery and/or radiochemotherapy increase the survival of these patients compared with untreated cases. Moreover, KPS score and RPA class affect the outcome of these patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand, that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Abramson AL, Parisier SC, Zamansky MJ, Sulka M. Distant metastases from carcinoma of the larynx. Laryngoscope. 1971. 81: 1503-11

2. Ahmad K, Kim YH, Post MJ, Byun Y, Fayos JV. Hematogenous neoplastic spread to the cavernous sinus: Report of a case. Int J Radiat Oncol Biol Phys. 1984. 10: 321-

3. Altay T, Krisht KM, Couldwell WT. Sellar and parasellar metastatic tumors. Int J Surg Oncol 2012. 2012. p.

4. de Bree R, Mehta DM, Snow GB, Quak JJ. Intracranial metastases in patients with squamous cell carcinoma of the head and neck. Otolaryngol Head Neck Surg. 2001. 124: 217-21

5. Dimri K, Rastogi N, Lal P. Intracranial metastasis in carcinoma of the glottis. Lancet Oncol. 2003. 4: 515-6

6. Ghosh-Laskar S, Agarwal JP, Yathiraj PH, Tanawade P, Panday R, Gupta T. Brain metastasis from nonnasopharyngeal head and neck squamous cell carcinoma: A case series and review of literature. J Cancer Res Ther. 2016. 12: 1160-3

7. Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer. 1993. 71: 452-6

8. Marur S, Forastiere AA. Head and neck squamous cell carcinoma: Update on epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2016. 91: 386-96

9. Merino OR, Lindberg RD, Fletcher GH. An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1977. 40: 145-51

10. Pan Z, Yang G, Qu L, Yuan T, Pang X, Wang Y. Leptomeningeal metastasis from early glottic laryngeal cancer: A case report. Oncol Lett. 2015. 10: 2915-8

11. Raitiola H, Pukander J, Laippala P. Glottic and supraglottic laryngeal carcinoma: Differences in epidemiology, clinical characteristics and prognosis. Acta Otolaryngol. 1999. 119: 847-51

12. Traserra J, Comas J, Conde C, Cuchi A, Cardesa A. Metastatic involvement of the cavernous sinus from primary pharyngolaryngeal tumors. Head Neck. 1990. 12: 426-9

13. Uzal MC, Kocak Z, Doganay L, Tokatli F, Caloglu M, Kilincer C. Pituitary metastasis mimicking a macroadenoma from carcinoma of the larynx: A case report. Tumori. 2001. 87: 451-4

14. Warwick-Brown NP, Cheesman AD. Intracranial metastases from a supraglottic carcinoma (a case report). J Laryngol Otol. 1987. 101: 624-6

15. Weiss R, Myssiorek D, Kahn L, Patel M. Laryngeal squamous cell carcinoma metastatic to the pituitary gland: A case study. Otolaryngol Head Neck Surg. 1994. 111: 816-9

16. Zahra M, Tewfik HH, McCabe BF. Metastases to the cavernous sinus from primary carcinoma of the larynx. J Surg Oncol. 1986. 31: 69-70

Abstract

Background:Segmental arterial mediolysis (SAM) is an uncommon vascular disease, which manifests as catastrophic intraabdominal hemorrhage caused by rupture of visceral dissecting aneurysms in most cases. The etiology of SAM is still unclear, but SAM may be a vasospastic disorder and the responsible pressor agent is norepinephrine. Recently, abdominal SAM coexisting with intracranial dissecting aneurysms has been reported, but the relationship between intraabdominal and intracranial aneurysms in SAM remains unclear, as no cases of concomitant abdominal SAM and ruptured intracranial saccular aneurysm have been reported.

Case Description:A 49-year-old woman underwent emergent clipping for a ruptured saccular aneurysm at the left C1 portion of the internal carotid artery. Intraoperatively, norepinephrine was continuously administered intravenously under general anesthesia. Four days after the subarachnoid hemorrhage (SAH), the patient suddenly developed shock due to massive hematoma in the abdominal cavity. Imaging showed multiple aneurysms involving the splenic artery, gastroduodenal artery, common hepatic artery, and superior mesenteric artery. Coil embolization of the splenic artery was performed immediately to prevent bleeding. Subsequent treatment for cerebral vasospasm following SAH was performed with prevention of hypertension, and the patient recovered with left temporal lobe infarction. The diagnosis was abdominal SAM based on the clinical, imaging, and laboratory findings.

Conclusion:Norepinephrine release induced by SAH and/or iatrogenic administration of norepinephrine may have promoted abdominal SAM in this case. Abdominal SAM may occur subsequent to rupture of ordinary saccular aneurysm, and may provoke catastrophic abdominal hemorrhage in the spasm stage after SAH.

Keywords: Internal carotid artery, intraabdominal aneurysm, norepinephrine, segmental arterial mediolysis, subarachnoid hemorrhage

INTRODUCTION

Segmental arterial mediolysis (SAM) is an uncommon nonatherosclerotic, noninflammatory vascular disease.[ 18 ] SAM is characterized by vacuolization and lysis of the outer arterial media, severing of the adventitia from the outer media, and formation of arterial gaps, which result in dissecting aneurysm.[ 18 ] SAM manifests as catastrophic intraabdominal hemorrhage caused by rupture of visceral aneurysms in most cases, but any vessel may be involved, including the intracranial and coronary arteries.[ 18 ] SAM is characterized by multiple lesions occurring at different times.[ 5 7 ] The etiology of SAM is still unclear, but SAM may be a vasospastic disorder and the responsible pressor agent may be norepinephrine.[ 17 18 19 ] Recently, abdominal SAM coexisting with intracranial dissecting aneurysms has been reported in a few cases, [ 2 4 8 10 12 14 ] but the relationship between intraabdominal and intracranial aneurysms in SAM remains unclear. Moreover, concomitant abdominal SAM and ruptured intracranial saccular aneurysm have not been reported previously. We describe a rare case of abdominal SAM in which massive intraabdominal hemorrhage occurred during the acute stage of subarachnoid hemorrhage (SAH) caused by the sequential rupture of both visceral and intracranial saccular aneurysms. In this case, the etiologies of the intraabdominal and intracranial aneurysms were thought to be different, but the occurrence of the intraabdominal aneurysms was suspected to be related to SAH. The possibility of abdominal hemorrhage due to SAM should be considered during the period following SAH caused by rupture of typical saccular aneurysm.

CASE REPORT

A 49-year-old woman consulted our hospital because of sudden onset of headache and vomiting. Physical examination found the World Federation of Neurosurgical Societies grade II with systolic blood pressure of 152 mm Hg. No morphological features were identified suggesting congenital structural vascular disease such as Ehlers–Danlos syndrome or Marfan's syndrome. Her past history and family history were unremarkable, and systemic evaluation demonstrated no abnormality. Most laboratory data on admission were unremarkable including white blood cell count of 11.3 × 10³/mm³, C-reactive protein level of 0.3 mg/dL, and negative findings for human immunodeficiency virus and syphilis. She smoked 10 cigarettes per day and occasionally consumed alcohol. Computed tomography (CT) of the head revealed SAH [ Figure 1a ] and cerebral angiography showed a saccular aneurysm at the C1 portion of the left internal carotid artery (ICA) [ Figure 1b ].

Figure 1

(a) Computed tomography scan of the head demonstrating subarachnoid hemorrhage mainly in the left sylvian fissure. (b) Left carotid angiogram showing a saccular aneurysm (arrow) at the C1 portion of the left internal carotid artery without the typical angiographic appearance of dissecting aneurysm such as focal irregularity of the vessel wall and fusiform dilatation

The patient underwent emergent clipping of the typical saccular aneurysm which had no features of dissection [ Figure 2 ]. Norepinephrine was continuously administered intravenously between 1.8 to 4.8 μg/min during the operation under general anesthesia to prevent any decrease in blood pressure caused by increased remifentanil hydrochloride dose. The postoperative course was uneventful without neurological deficits. Postoperative natural hypertension was permitted and systolic blood pressure was controlled between 130 to 160 mm Hg without continuous intravenous administration of norepinephrine. However, 4 days after the SAH, the patient suddenly developed shock after severe abdominal pain. CT of the abdomen revealed massive hematoma in the abdominal cavity around a splenic artery aneurysm, suggestive of the origin of bleeding [ Figure 3a ]. In addition to this lesion, three-dimensional CT angiography of the abdomen showed multiple aneurysms involving the gastroduodenal artery, common hepatic artery, and superior mesenteric artery [ Figure 3b ]. Blood transfusion for shock and coil embolization of the splenic artery to prevent bleeding were performed immediately. Extensive laboratory analysis was performed with negative myeloperoxidase-anti-neutrophil cytoplasmic antibody, proteinase 3-anti-neutrophil cytoplasmic antibody, and anti-nuclear antibody. The diagnosis of abdominal lesions was compatible with SAM based on the combination of clinical and imaging findings and absence of laboratory findings indicating infection or inflammatory etiology.

Figure 2

Intraoperative photograph showing a saccular aneurysm (arrow) in the left internal carotid artery without the features of dissecting aneurysm

Figure 3

(a) Oblique coronal maximum intensity projection image of the abdomen demonstrating intraabdominal hematoma (white arrow) around the splenic artery aneurysm (black arrow) and common hepatic artery aneurysm (dotted arrow). (b) Three-dimensional computed tomography angiogram of the abdomen showing multiple aneurysms with the characteristics of dissection of the splenic artery (large arrow), gastroduodenal artery (arrowhead), common hepatic artery (dotted arrow), and superior mesenteric artery (small arrow)

Treatment for cerebral vasospasm following SAH was performed with prevention of hypertension, which might be contraindicated in the presence of abdominal lesions. She was given oral and continuous intravenous administration of calcium antagonist to maintain a systolic blood pressure of 100–140 mm Hg. Left temporal lobe infarction was detected, but the patient was discharged after 1 month hospitalization with mild aphasia which recovered completely afterward. The patient remained asymptomatic for 34 months after SAH and CT angiography of the head and abdomen demonstrated no recurrence of the aneurysms in both visceral and intracranial arteries.

DISCUSSION

The differential diagnosis of SAM includes atherosclerosis, fibromuscular dysplasia (FMD), Behçet's disease, polyarteritis nodosa, neurofibromatosis, Ehlers–Danlos syndrome type IV, Marfan's syndrome, and mycotic aneurysms.[ 1 18 ] Dissections and aneurysms are common in Ehlers–Danlos syndrome and Marfan's syndrome, but involvement of the splanchnic vasculature is less common.[ 1 7 ] The absence of physical signs and symptoms, and laboratory indicators of systemic inflammation are helpful to distinguish SAM from inflammatory vasculitides.[ 1 ] SAM typically involves the medium and large abdominal muscular arteries, and the natural history of the arterial lesions can be divided into the injurious phase followed by the reparative phase. In the injurious stage, arterial gaps are created by transmedial mediolysis and loss of the internal elastica and intima putatively caused by disruption and loss of musculostromal connection.[ 18 ] In the reparative phase, proliferation of granulation tissue repairs medial defects and so obliterates small gaps and fortifies arterial aneurysms. SAM may be the precursor of FMD based on the morphological appearance of SAM in the reparative phase.[ 18 ] However, FMD is not caused only by SAM but also represents a group of arterial disorders with diverse etiologies.[ 18 ] The clinical presentations of these two disorders differ, as SAM manifests as profuse bleeding from the abdominal intestinal arteries whereas FMD manifests as ischemic changes causing hypertension or strokes derived from renal artery alterations in the former and ICA changes in the latter.[ 18 ] Definitive diagnosis of SAM requires histopathological evaluation of the arterial lesions, but endovascular treatment of abdominal aneurysms in SAM has been reported recently.[ 13 ] The clinical non-pathological guidelines for the diagnosis of abdominal SAM consist of absence of congenital predisposition for dissections, absence of more plausible diagnosis such as FMD or arteritis, abdominal or flank pain, vascular lesions such as dissection of the mesenteric or renal arteries, and absence of inflammatory markers.[ 7 ] Our case satisfied these criteria for abdominal lesions, so abdominal SAM was indicated despite the absence of pathological findings.

SAM was first described as a distinct pathological entity in 1976, [ 15 ] and initially named segmental mediolytic arteritis since SAM was suspected to represent an immune-mediated arteritis.[ 15 18 ] However, this hypothesis was negated by the findings of inconstant inflammatory changes and absence of laboratory evidence of immunological or infectious assault.[ 16 18 19 ] Subsequently, SAM was suspected to be the result of an inappropriate vasospastic response expressed in a splanchnic vascular bed undergoing vasoconstriction as a response to shock or severe hypoxemia.[ 16 ] The etiology of SAM is still unclear. However, similar pathological findings were induced in an experimental model by administering ractopamine, a beta-2 adrenergic agonist, which suggested that SAM is a vasospastic disorder and that the responsible pressor agent is norepinephrine.[ 17 18 19 ] Moreover, SAM may be a disorder principally caused by iatrogenic or accidental exposure to alpha-1 adrenergic receptor agonists or beta-2 agonists which can induce release of norepinephrine from the peripheral nervous system.[ 17 18 ] The release of norepinephrine from varicosities of the efferent nerves of the splanchnic arteries stimulates the alpha-1 receptor on the cell membrane of the medial smooth muscle to cause either transient intense vasoconstriction followed by apoptosis or direct initiation of apoptosis caused by shearing separation of the adventitia from the media.[ 17 19 ] The quantity of released norepinephrine is important in determining the extent of mediolysis.[ 19 ] SAM develops very rapidly after exposure to such agents, within 1–4 days, and results in the formation of apoptotic lesions.[ 17 ]

Recently, abdominal SAM coexisting with intracranial dissecting aneurysms has been reported. Locations of the intracranial aneurysm included the ICA, basilar artery, vertebral artery (VA), and anterior cerebral artery.[ 2 4 8 10 12 14 ] An autopsy case of SAM with both intraabdominal and intracranial VA dissections indicated that medial defects, which resemble the vascular lesions found in patients with SAM, are very important in the occurrence of intracranial VA dissections.[ 10 11 ] However, pathological findings of intracranial aneurysm are difficult to obtain except for autopsy cases, so the relationship between intraabdominal and intracranial lesions in SAM is unclear, especially whether the intracranial aneurysm is caused by SAM or not. Moreover, in our case, the cause of sequential rupture of the intracranial and intraabdominal aneurysms was also unclear, but patients with SAH show approximately 3-fold increase in total body norepinephrine spillover into the plasma within 48 h after insult, compared with healthy subjects.[ 9 ] This sympathetic activation persists for 7–10 days. Such marked elevation in norepinephrine spillover shows no association with the Hunt and Hess score, Fisher score, or location of the aneurysm.[ 9 ] Therefore, whether the intracranial aneurysm is caused by SAM or not, norepinephrine release induced by SAH and/or iatrogenic administration of norepinephrine may have promoted the occurrence of abdominal SAM and rupture of visceral aneurysm in the acute stage of SAH.

The intracranial aneurysm of our patient seemed not to be related to SAM in contrast to the abdominal lesions because of the absence of dissection, but occurred as a typical saccular aneurysm. The limitation of this case is the absence of histopathological evidence of abdominal SAM, but it is important to be aware of the possibility that abdominal SAM may occur subsequent to rupture of ordinary saccular aneurysm, and may provoke catastrophic abdominal hemorrhage in the spasm stage after SAH. The different etiologies of the intracranial and intraabdominal aneurysms in this case may indicate that intracranial dissecting aneurysms coexisting with abdominal SAM are not necessarily caused by SAM and the concomitance of abdominal SAM and SAH is not rare.

Ten cases of coexisting SAH and visceral aneurysm have been reported.[ 2 3 4 6 8 12 14 20 21 22 ] Table 1 presents the characteristics of the patients, of whom only six also suffered from abdominal bleeding caused by rupture of visceral aneurysm, as in our patient.[ 3 4 6 14 21 22 ] Only three of the six cases were diagnosed as abdominal SAM, [ 4 14 22 ] but all resembled our case in clinical features, that is, the abdominal bleeding occurred within several days in most cases to 1 month in one case of the onset of SAH, and the intracranial aneurysms were not all dissections but also included saccular types. Abdominal SAM could not be excluded in the abdominal lesions of three cases with saccular intracranial aneurysms.[ 3 6 21 ] The occurrence of abdominal SAM may be underestimated and more common than suggested by the few reported cases.

Table 1

Reported cases of subarachnoid hemorrhage concomitant with visceral aneurysm

The postoperative hypertensive state to counteract cerebral vasospasm following SAH may have also influenced the abdominal bleeding of SAM in this case, but the ideal management strategies for vasospasm in the presence of abdominal SAM have not yet been established because of the rarity of SAM following SAH. The catastrophic abdominal bleeding due to SAM during the acute stage of SAH prevents safe treatment for vasospasm following SAH, so blood transfusion and hemostasis of abdominal bleeding should be ensured immediately as the first step for such hemorrhagic shock. Moreover, it is important to recognize the causative abdominal lesions as SAM, because the resultant shock should not be treated by adrenergic agents which could intensify SAM and generate additional lesions.[ 18 ] Surgical treatment for abdominal SAM generally consists of surgical ligation or resection of the aneurysm, but advanced endovascular techniques are increasingly used to manage SAM without the need for major surgery.[ 13 ] Endovascular treatment of the visceral aneurysms is a suitable and less invasive treatment modality, especially for patients in the vasospasm stage after SAH.

CONCLUSION

Norepinephrine release induced by SAH and/or iatrogenic administration of norepinephrine may have promoted abdominal SAM in this case. Little is known about the association of increased levels of norepinephrine with SAM after SAH, in spite of the risk that SAM may induce sudden visceral hemorrhage in the unstable cerebral circulation stage of vasospasm, which is likely to result in death and needs prompt diagnosis and treatment. Neurosurgeons should be aware of the possibility of unexpected abdominal hemorrhage caused by SAM within several days following SAH. Early recognition of SAM and management can lead to significant reduction in subsequent complications and mortality. The different etiologies of the intracranial and intraabdominal aneurysms in this case may indicate that intracranial dissecting aneurysms coexisting with abdominal SAM are not necessarily caused by SAM and the concomitance of abdominal SAM and SAH is not rare. The natural history of SAM is poorly understood, so we continue to follow up our patients regularly.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. The form specifies that the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Baker-LePain JC, Stone DH, Mattis AN, Nakamura MC, Fye KH. Clinical diagnosis of segmental arterial mediolysis: Differentiation from vasculitis and other mimics. Arthritis Care Res (Hoboken). 2010. 62: 1655-60

2. Cooke DL, Meisel KM, Kim WT, Stout CE, Halbach VV, Dowd CF. Serial angiographic appearance of segmental arterial mediolysis manifesting as vertebral, internal mammary and intra-abdominal visceral artery aneurysms in a patient presenting with subarachnoid hemorrhage and review of the literature. J Neurointerv Surg. 2013. 5: 478-82

3. Fuse T, Takagi T, Yamada K, Fukushima T. Systemic multiple aneurysms of the intracranial arteries and visceral arteries: Case report. Surg Neurol. 1996. 46: 258-61

4. Hellstern V, Aguilar Pérez M, Kohlhof-Meinecke P, Bäzner H, Ganslandt O, Henkes H. Concomitant retroperitoneal and subarachnoid hemorrhage due to segmental arterial mediolysis: Case report and review of the literature. Clin Neuroradiol. 2018. 28: 445-50

5. Inada K, Maeda M, Ikeda T. Segmental arterial mediolysis: Unrecognized cases culled from cases of ruptured aneurysm of abdominal visceral arteries reported in the Japanese literature. Pathol Res Pract. 2007. 203: 771-8

6. Isla A, Roda JM, Alvarez F, Blázquez MG. Concurrent intracranial and intraabdominal aneurysms. J Neurosurg Sci. 1988. 32: 121-2

7. Kalva SP, Somarouthu B, Jaff MR, Wicky S. Segmental arterial mediolysis: Clinical and imaging features at presentation and during follow-up. J Vasc Interv Radiol. 2011. 22: 1380-7

8. Matsuda R, Hironaka Y, Takeshima Y, Park YS, Nakase H. Subarachnoid hemorrhage in a case of segmental arterial mediolysis with coexisting intracranial and intraabdominal aneurysms. J Neurosurg. 2012. 116: 948-51

9. Naredi S, Lambert G, Edén E, Zäll S, Runnerstam M, Rydenhag B. Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage. Stroke. 2000. 31: 901-6

10. Ro A, Kageyama N, Takatsu A, Fukunaga T. Segmental arterial mediolysis of varying phases affecting both the intra-abdominal and intracranial vertebral arteries: An autopsy case report. Cardiovasc Pathol. 2010. 19: 248-51

11. Ro A, Kageyama N. Pathomorphometry of ruptured intracranial vertebral arterial dissection: Adventitial rupture, dilated lesion, intimal tear, and medial defect. J Neurosurg. 2013. 119: 221-7

12. Sakata N, Takebayashi S, Shimizu K, Kojima M, Masawa N, Suzuki K. A case of segmental mediolytic arteriopathy involving both intracranial and intraabdominal arteries. Pathol Res Pract. 2002. 198: 493-7

13. Shenouda M, Riga C, Naji Y, Renton S. Segmental arterial mediolysis: A systematic review of 85 cases. Ann Vasc Surg. 2014. 28: 269-77

14. Shinoda N, Hirai O, Mikami K, Bando T, Shimo D, Kuroyama T. Segmental arterial mediolysis involving both vertebral and middle colic arteries leading to subarachnoid and intraperitoneal hemorrhage. World Neurosurg. 2016. 88: 694e5-10

15. Slavin RE, Gonzalez-Vitale JC. Segmental mediolytic arteritis: A clinical pathologic study. Lab Invest. 1976. 35: 23-9

16. Slavin RE, Cafferty L, Cartwright J. Segmental mediolytic arteritis. A clinicopathologic and ultrastructural study of two cases. Am J Surg Pathol. 1989. 13: 558-68

17. Slavin RE, Yaeger MJ. Segmental arterial mediolysis – An iatrogenic vascular disorder induced by ractopamine. Cardiovasc Pathol. 2012. 21: 334-8

18. Slavin RE. Segmental arterial mediolysis: A clinical-pathologic review, its role in fibromuscular dysplasia and description and differential diagnosis of the masquerader-muscular artery cystic necrosis. World J Cardiovasc Dis. 2013. 3: 64-81

19. Slavin RE. Segmental arterial mediolysis: A review of a proposed vascular disease of the peripheral sympathetic nervous system – A density disorder of the alpha-1 adrenergic receptor?. J Cardiovasc Dis Diagn. 2015. 3: 190-

20. Soga Y, Nose M, Arita N, Komori H, Miyazaki T, Maeda T. Aneurysms of the renal arteries associated with segmental arterial mediolysis in a case of polyarteritis nodosa. Pathol Int. 2009. 59: 197-200

21. Stetler WR, Pandey AS, Mashour GA. Intracranial aneurysm with concomitant rupture of an undiagnosed visceral artery aneurysm. Neurocrit Care. 2012. 16: 154-7

22. Welch BT, Brinjikji W, Stockland AH, Lanzino G. Subarachnoid and intraperitoneal hemorrhage secondary to segmental arterial mediolysis: A case report and review of the literature. Interv Neuroradiol. 2017. 23: 378-81

Abstract

Background:The effectiveness of microvascular decompression in treating hemifacial spasm is widely accepted. However, some experience recurrence of hemifacial spasm after successful decompression surgery. Especially, delayed recurrence more than 5 years after surgery is rare and the cause of this phenomenon is unknown.

Case Description:A female underwent microvascular decompression to treat her hemifacial spasm 6 years ago. Six years later, her hemifacial spasm recurred and she underwent a second surgery. The second surgery revealed that the sponge had become fragile, losing the ability to absorb the impact of pulsatile compression of the offending artery on the root exit zone of her facial nerve.

Conclusion:We report a case in which degeneration of material, a sponge (polyurethane), used in decompression surgery caused delayed recurrence of hemifacial spasm. The selection of appropriate prosthetic materials is essential in such functional surgeries.

Keywords: Hemifacial spasm, microvascular decompression, prosthesis

INTRODUCTION

One of the standard treatments for hemifacial spasm is microvascular decompression. However, few reports have addressed the mechanism of recurrence after successful decompression surgery. Chang et al. concluded that recurrence after more than 5 years of surgery is rare.[ 2 ] Furthermore, the cause of delayed recurrence is unclear.

We encountered a case showing recurrence of hemifacial spasm 6 years after successful decompression surgery. Our surgical findings indicated prosthetic material degeneration over time resulting in loss of prosthetic function. We caution that a similar choice of prosthetic material for decompression may cause delayed recurrence of hemifacial spasm after initial success in decompression surgery.

CASE DESCRIPTION

A 48-year-old female had a 2-year history of right hemifacial spasm. She had been treated with clonazepam and other alternative therapies with limited effect. She was admitted to our hospital for microvascular decompression surgery for her hemifacial spasm. Preoperative magnetic resonance imaging (MRI) with T2-based cisternography revealed attachment of her right posterior inferior cerebellar artery (PICA) to her facial nerve exit zone. We carried out microvascular decompression surgery with a lateral suboccipital approach and placed a sponge (polyurethane) between the PICA and the brainstem, fixing them with fibrin glue [ Figure 1a ]. Her postoperative course was uneventful. Her hemifacial spasm disappeared completely 3 days after the decompression surgery. Postoperative MRI showed a PICA running course without attachment to the brainstem [ Figure 2a ].

Figure 1

(a) Operative view of the first surgery. The sponge was flexible and the bubbles in the sponge were large. (b) Operative view of the second surgery. The sponge was fragile and the honeycomb structure was not preserved

Figure 2

(a) T2-based cisternography immediately after the first surgery. The PICA was located far from the brainstem. (b) T2-based cisternography at the time of recurrence. The distance from the brainstem of PICA was narrowed when compared with that in Figure 2a

Six years after her surgery, she noticed a mild spasm in her superior orbicularis oculi muscle which spread to her prioral muscles and occasionally sustained a tonic state. She visited our department and underwent a MRI scan. T2-based cisternography showed a closed PICA running course compared with the MRI immediately after her initial surgery [ Figure 2b ]. At this point, she was eager to undergo decompression surgery again, even if it was only for inspection. We carried out the second surgery with her informed consent.

Using a lateral suboccipital approach through the previous incision and craniotomy, we dissected the arachnoid adhesion and confirmed that the sponge placed in the first surgery between the offending artery and the brainstem was not dislocated. However, the sponge was degenerated. The structure of the sponge was fragile and easy to collapse. The honeycomb structure or bubbles in the sponge were not preserved [ Figure 1b ]. We attempted to remove the sponge, but its adhesion to the lower cranial nerves was strong. We inserted Teflon between the sponge and the brainstem and moved the distal portion of the PICA to the dura of the petrous surface with Teflon strings. Her facial spasm disappeared immediately after the surgery and she experienced no complications. She has experienced no spasmatic movements on her face during the year after the second surgery.

DISCUSSION

Microvascular decompression as a treatment for hemifacial spasm has been very safe due to the progress in intraoperative monitoring including auditory brainstem response and surgical techniques.[ 1 2 3 9 ] However, a wide variety of materials can be used for decompression, depending on facility standards and surgeon preference. There is no material commonly used worldwide, and treatment results cannot be compared even in cases with identical descriptions of materials such as Teflon or Teflon sponge. In fact, even in our facilities, we have a history of using several materials including sponge, Teflon, polyester fibers, Gore-Tex, and Teflon Paget, preventing analysis of correlations between the materials and long-term results of microvascular decompression. Furthermore, proper amount of material to be used for decompression is still a subject of controversy.[ 5 ] As an alternative, the transposition technique, in which the offending artery is moved away from the facial nerve exit zone, has been recommended; however, it is not possible to accomplish this completely.[ 6 ] In the present case, we used the transposition technique to achieve permanent decompression, but the presence of short perforators and limited cisternal space for movement may have prevented completion. The interpostion technique, involving the insertion of materials between offending arteries and the root exit zone of facial nerves, is also widely used.[ 11 ] For this technique, materials that can be used as permanent prostheses are required.

Contrarily, the cause of delayed recurrence after initially successful decompression surgery has remained unclear. The major reasons proposed for delayed recurrence in previous reports included shift of prosthesis, vascular rerouting due to atherosclerosis, and incomplete decompression procedures.[ 2 3 9 10 ] Transient facial palsy, a major complication, is a specific reason for delayed recurrence.[ 8 ] In our case, because spasm was absent for 6 years, it was clear that decompression of the root exit zone was successful. Our surgical findings showed that there was no other offending artery, that the previous offending artery had moved, and that the sponge was clearly inserted between the offending artery and the root exit zone. However, because the sponge was found to have lost its elasticity, we concluded that material degeneration over time may have been the main reason for recurrence. Unfortunately, the sponge could not be removed because its adhesion to the lower cranial nerves was too strong, and we could not perform histopathological or other analysis of the degeneration of this material.

Sponge can be a good material to use in microvascular decompression.[ 4 ] This material can slide over the offending artery and attain its full size during surgery, while delivery is easy because it can be folded and moved in a compressed state. However, this material may not be suitable as a permanent prosthesis, based on our observation that its elasticity deteriorates over time, preventing it from absorbing the impact of arterial pulsations on the facial nerve root exit zone. This was the cause for recurrence of facial spasm in our patient. Our report thus indicates a risk of recurrence due to material degeneration.

Because delayed recurrence of facial spasm is rare, it is challenging to detect and study. A recent report showed that fluoroscope-guided facial nerve block and pulsed radiofrequency treatment might be effective for patients with recurrent facial spasm.[ 7 ] Further studies addressing the selection of appropriate prosthetic materials in microvascular decompression are needed, involving multiple centers and long-term observation of patients after initially successful decompression surgeries.

We report a case of delayed recurrence of hemifacial spasm after initial successful decompression surgery due to prosthetic material degeneration over time. Our report indicates that the use of similar materials may cause such delayed spasm recurrence after microvascular decompression surgery and highlights the need for use of appropriate prosthetic materials.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgments

The authors are thankful to the patient for her co-operation. This study was supported by the Juntendo University Research Institute for Diseases of Old Age (Tokyo, Japan).

References

1. Barker FG, Jannetta PJ, Bissonette DJ, Shields PT, Larkins MV, Jho HD. Microvascular decompression for hemifacial spasm. J Neurosurg. 1995. 82: 201-10

2. Chang WS, Chung JC, Kim JP, Chung SS, Chang JW. Delayed recurrence of hemifacial spasm after successful microvascular decompression: Follow-up results at least 5 years after surgery. Acta Neurochir (Wien). 2012. 154: 1613-9

3. Dou NN, Zhong J, Liu MX, Xia L, Sun H, Li B. Teflon might be a factor accounting for a failed microvascular decompression in hemifacial spasm: A technical note. Stereotact Funct Neurosurg. 2016. 94: 154-8

4. Fargen KM, Blackburn S. Surgical decompression for optic neuropathy from carotid artery ectasia: Case report with technical considerations. World Neurosurg. 2014. 82: 239.e9-12

5. Jiang C, Xu W, Dai Y, Lu T, Jin W, Liang W. Failed microvascular decompression surgery for hemifacial spasm: A retrospective clinical study of reoperations. Acta Neurochir (Wien). 2017. 159: 259-63

6. Lin CF, Chen HH, Hernesniemi J, Lee CC, Liao CH, Chen SC. An easy adjustable method of ectatic vertebrobasilar artery transposition for microvascular decompression. Clin Neurol Neurosurg. 2012. 114: 951-6

7. Park HL, Lim SM, Kim TH, Kang KH, Kang H, Jung YH. Intractable hemifacial spasm treated by pulsed radiofrequency treatment. Korean J Pain. 2013. 26: 62-4

8. Rhee DJ, Kong DS, Park K, Lee JA. Frequency and prognosis of delayed facial palsy after microvascular decompression for hemifacial spasm. Acta Neurochir (Wien). 2006. 148: 839-43

9. Sindou MP. Microvascular decompression for primary hemifacial spasm. Importance of intraoperative neurophysiological monitoring. Acta Neurochir (Wien). 2005. 147: 1019-26

10. Xu XL, Zhen XK, Yuan Y, Liu HJ, Liu J, Xu J. Long-term outcome of repeat microvascular decompression for hemifacial spasm. World Neurosurg. 2018. 110: e989-97

11. Zhao H, Zhang X, Tang YD, Zhang Y, Ying TT, Zhu J. Operative complications of microvascular decompression for hemifacial spasm: Experience of 1548 cases. World Neurosurg. 2017. 107: 559-64

Abstract

Background:Pneumocephalus is a common finding following intracranial procedures, typically asymptomatic and resolves within several days. However, in some cases, pneumocephalus presents with headache, encephalopathy, or symptoms of elevated intracranial pressure. Here, we present a case of iatrogenic tension pneumocephalus following endoscopic sinus surgery, presenting as abnormal involuntary movements resembling a movement disorder with choreiform movements.

Case Description:A 67-year-old previously healthy male presented with new onset chorea and dystonia associated with headache, encephalopathy, and postural instability 4 days after undergoing endoscopic sinus surgery for chronic sinusitis and nasal polyps. Computed tomography showed prominent intraventricular pneumocephalus causing enlargement of the anterior horns of both lateral ventricles with lateral displacement of the basal ganglia nuclei and a bony defect in the skull base. Neurosurgical correction of the cranial defect provided complete symptomatic resolution. Pneumocephalus as a result of an iatrogenic injury of the skull base manifesting as an acute movement disorder is a rare complication of a nasal sinus procedure. We speculate that compression of the caudate nucleus and striatum resulted in decreased pallidothalamic inhibition and thalamocortical disinhibition leading to the development of a hyperkinetic movement disorder.

Conclusion:This unusual presentation of a common procedure illustrates a neurological emergency that requires prompt recognition and timely correction.

Keywords: All movement disorders, clinical neurological examination, dystonia

INTRODUCTION

Tension pneumocephalus resulting in caudate compression is a unique etiology of choreiform movements.

CASE DESCRIPTION

A 67-yeal-old man with no significant medical history presented to the emergency department (ED) with a one-day course of new onset headache, chorea, postural instability, and disorientation. Four days before presentation, he underwent endoscopic sinus surgery for chronic sinusitis and nasal polyps at an outpatient sinus surgery center. The operation was reported as uneventful and he was discharged home neurologically intact. No medications were prescribed nor used without prescription by the patient. Three days after surgery, the patient developed bilateral frontal headache associated with poor movement control, inability to ambulate or operate his automobile. At arrival to the ED, he was afebrile, hemodynamically stable, and in no acute distress. On neurological examination, he was awake, but inattentive, oriented to self and place but not time. There was no nuchal rigidity and cranial nerves were intact. He was noted to have involuntary chorea-like movements of the neck and shoulders as well as dystonic posturing of his right arm and neck. His muscle strength was preserved and tone was increased in the lower extremities. Right patellar hyperreflexia, right ankle clonus, and right extensor plantar response were present. Sensory examination was unremarkable. He was unable to stand due to significant postural instability. Clear fluid rhinorrhea was noted during the exam. Computed tomography on presentation showed prominent pneumocephalus with intraventricular air causing enlargement of the anterior horns of both lateral ventricles with lateral displacement of the basal ganglia nuclei bilaterally [ Figure 1a ] and a bony defect at the lateral lamella and fovea ethmoidalis with formation of an encephalocele [Figure 1b and c ]. Emergent endoscopy confirmed an anterior skull base defect of approximately 1.5 cm with associated encephalocele [ Figure 2 ]. A multilayer repair was completed using synthetic inlay, an inferior turbinate-free mucosal graft onlay, and DuraSeal (Integra Life Science). His postoperative course was characterized by gradual improvement in neurological symptoms. On postoperative day 3, the patient was noted to have a normal neurological examination with radiographic resolution of the pneumocephalus and he was discharged home.

Figure 1

Nonenhanced computerized tomography scans showing in the (a) axial and (b) coronal planes, extra-axial, subarachnoid, and intraventricular air (arrows in b shows depression of the ventricular wall causing distortion of the bilateral caudate nuclei). (c) Coronal computerized tomography scan with arrow depicting bony defect caused by iatrogenic transgression of the fovea ethmoidalis

Figure 2

Endoscopic endonasal view via the right nare with arrows showing bony defect edge with dural violation and encephalocephele. Insert shows perspective (The Rhoton collection)

DISCUSSION

Pneumocephalus as a result of an iatrogenic injury of the skull base presenting as an acute movement disorder is a rare complication of a nasal sinus procedure. This complication resulted from the violation of the subdural and subarachnoid compartments resulting in CSF drainage and intraventricular accumulation of air under pressure. The intraventricular air caused lateral ventricle distortion that compressed and displaced the bilateral basal ganglia nuclei inferolaterally.

Pneumocephalus is a routine radiographic finding after intracranial procedures, usually asymptomatic and resolves within days. Infrequently, iatrogenic violation of the dura with subsequent CSF loss results in a “valve” phenomenon with intracranial accumulation of air that can cause mass effect on surrounding structures. A dramatic example is the “Mt Fuji sign” with bilateral frontal lobe compression. Further communication to the ventricular system and subarachnoid space can lead to intraventricular accumulation of air and progressive neurological deterioration.[ 1 5 6 ] While headache and encephalopathy are common presentations of tension pneumocephalus, abnormal involuntary movements have not been associated with intraventricular tension pneumocephalus and to our knowledge have not been previously reported.[ 7 ]

Historically, isolated intraventricular air was most commonly encountered after pneumoencephalography. Neurological complications of this air procedure lack a particular pattern and include headaches, alteration of consciousness, and seizures as well as abnormal pyramidal and extrapyramidal system involvement.[ 8 ] However, with this diagnostic modality falling out of use in modern medicine, intraventricular pneumocephalus is rarely seen.

Lutjens and colleagues reported a single case of akinetic mutism and Parkinsonism associated with tension pneumocephalus after decompression of a subdural hygroma where downward pressure distorted the frontal hemispheres and deep nuclei.[ 4 ] Our case demonstrates development of focal chorea and dystonia associated with upper motor neuron signs and encephalopathy due to compression and displacement of basal ganglia nuclei by intraventricular tension pneumocephalus. We speculate that bilateral compression of the caudate nucleus and striatum by intraventricular air in the anterior horns of the lateral ventricles resulted in decreased pallidothalamic inhibition and thalamocortical disinhibition leading to the development of reversible abnormal movements. Similarly, bilateral basal ganglia injury caused by autoimmune disorders, drugs, hypoxia, metabolic disorders, or infection has been reported to present as acute chorea.[ 2 3 ]

This presentation illustrates a neurosurgical emergency that requires prompt recognition and intervention.[ 5 6 ] Timely correction of the anatomical defect in this individual resulted in complete recovery of neurological function. Surgeons performing endonasal procedures and physicians evaluating patients in the ED for acute onset of movement disorders should be aware of this uncommon presentation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Gönül E, Izci Y, Sali A, Baysefer A, Timurkaynak E. Subdural and intraventricular traumatic tension pneumocephalus: Case report. Minim Invasive Neurosurg. 2000. 43: 98-101

2. Hantraye P, Riche D, Maziere M, Isacson O. A primate model of Huntington's disease: Behavioral and anatomical studies of unilateral excitotoxic lesions of the caudate-putamen in the baboon. Exp Neurol. 1990. 108: 91-104

3. Lin JJ. Generalized chorea in the syndrome of acute bilateral basal ganglia lesions in patients with diabetic uremia. J Clin Neurosci. 2011. 18: 1266-8

4. Lütjens G, Capelle HH, Krauss JK. Akinetic mutism and parkinsonism due to subdural and intraventricular tension pneumocephalus. J Neurol Surg A Cent Eur Neurosurg. 2013. 74: e116-8

5. Mammis A, Agarwal N, Eloy JA, Liu JK. Intraventricular tension pneumocephalus after endoscopic skull base surgery. J Neurol Surg A Cent Eur Neurosurg. 2013. 74: e96-9

6. Martínez-Capoccioni G, Serramito-García R, Cabanas-Rodríguez E, García-Allut A, Martín-Martín C. Tension pneumocephalus as a result of endonasal surgery: An uncommon intracranial complication. Eur Arch Otorhinolaryngol. 2014. 271: 1043-9

7. Pillai P, Sharma R, MacKenzie L, Reilly EF, Beery PR, Papadimos TJ. Traumatic tension pneumocephalus – Two cases and comprehensive review of literature. Int J Crit Illn Inj Sci. 2017. 7: 58-64

8. White YS, Bell DS, Mellick R. Sequelae to pneumoencephalography. J Neurol Neurosurg Psychiatry. 1973. 36: 146-51

Abstract

Background:Langerhans cell histiocytosis (LCH) is a rare disease that may affect the central nervous system; it is caused by dendritic cell proliferation, and typically occurs in children. LCH frequently appears in the pituitary stalk and rarely results in multiple enhanced lesions in the brain parenchyma.

Case Description:We present a case of a 40-year-old woman who deveolped panhypopituitarism and central diabetes insipidus in the postpartum period requiring hormone replacement therapy. At first, magnetic resonance imaging only revealed thickening of the pituitary stalk; while 6 months later, a single enhanced mass lesion was detected in the hypothalamus. Another 5 months later, the lesion had enlarged with appearance of multiple, enhanced satellite lesions in the basal ganglia and white matter. The patient underwent successful craniotomy to obtain a biopsy sample; LCH of the hypothalamus was definitively diagnosis by histopathological examination. Steroids were administrated and resulted in significant reduction of all lesions.

Conclusions:Definitive histopathological diagnosis and subsequent appropriate therapy, such as steroid administration, are required when LCH lesions in the hypothalamus become progressively enlarged and new lesions appear in the brain parenchyma.

Keywords: Brain parenchyma, hypothalamus, Langerhans cell histiocytosis, multiple enhanced lesions, steroid

INTRODUCTION

Langerhans cell histiocytosis (LCH) is a rare disease that may affect the central nervous system (CNS); It is caused by dendritic cell proliferation, and typically occurs in children.[ 5 ] The clinical presentation of LCH varies from single to multiple lesions, and the clinical outcome depends on the affected systemic organs. Some patients with LCH only require radiological observation, while others have a poor prognosis despite aggressive multimodal treatment.[ 5 ] Although LCH in the CNS frequently occurs in the hypothalamus, intraparenchymal satellite lesions have been reported in previous case reports.[ 6 9 ] However, the clinical features of LCH with satellite parenchymal lesions remain unknown. We experienced a rare case of LCH of the hypothalamus resulting in multiple satellite lesions in the basal ganglia and white matter. The patient was successfully treated with steroids after histological confirmation.

CASE DESCRIPTION

A 40-year-old Japanese woman visited our hospital with complaints of thirst, polydipsia, and polyuria. She had delivered her first baby without any perinatal difficulties 6 months earlier. From her symptoms, she was diagnosed with central diabetes insipidus (DI) by an endocrinologist, and the DI was controlled by desmopressin. Subsequently, the patient developed symptoms of fatigue, galactorrhoea, and amenorrhea, leading to the diagnosis of panhypopituitarism. T1-weighted magnetic resonance imaging (MRI) showed thickening of the pituitary stalk and disappearance of hyperintensity in the posterior lobe of the pituitary gland [ Figure 1a ]. Whole-body computed tomography revealed no other abnormalities. After 6 months, the mass lesion in the hypothalamus had clearly enlarged; she was referred to our department for biopsy of the lesion for definitive diagnosis [ Figure 1b ]. No procedure for cerebrospinal fluid sampling, such as lumbar puncture, was performed before the biopsy.

Figure 1

T1-weighted sagittal magnetic resonance imaging images with contrast enhancement. (a) The image was obtained at the time of diagnosis of panhypopituitarism, showing the pituitary stalk thickening (white arrowhead). (b) Image after 6 months showed that the lesion at the hypothalamus was enlarged (white arrowhead)

She was alert, and no neurological abnormalities were found. After another 5 months, follow-up MRI revealed that the lesion in the hypothalamus had further enlarged and new, multiple enhanced lesions were detected in the basal ganglia and white matter [Figure 2a and b ]. Biopsy of the hypothalamic lesion was performed using bifrontal craniotomy. Using the interhemispheric approach with opening of the lamina terminalis, we detected a white, solid lesion in the hypothalamus. Although the lesion was solid and bled easily, sufficient samples were obtained for histological examination. Her postoperative course was uneventful.

Figure 2

T1-weighted magnetic resonance imaging images with contrast enhancement. (a) Axial image showed that new multiple enhanced lesions were present at the basal ganglia (white arrowhead) and deep white matter in the frontal lobe (white arrow). (b) Coronal image showed that the lesion at the hypothalamus had progressed (black arrowhead), and there were some enhanced lesions surrounding the hypothalamus (white arrowhead)

Histopathological examination of the surgical specimens showed remarkable invasion of several types of inflammatory cells with fibrosis [ Figure 3a ]. Some of the inflammatory cells were immunoreactive for CD1a, which is a definitive marker of dendritic cells [ Figure 3b ], and others were immunoreactive for CD68, CD8, and CD20, which are markers for macrophages, T lymphocytes, and B lymphocytes, respectively [Figure 3c - e ]. There was also immunoreactivity for glial fibrillary acidic protein, which marks a response for reactive astrocytes [ Figure 3f ].

Figure 3

Histopathological findings of surgical specimen. (a) Hematoxylin and eosin staining showed highly present fibrosis and inflammatory cells invasion. (b) Immunoreactivity for CD1a, which is definitive marker of dendritic cell, was found. Positivity for CD68 (c), CD8 (d), and CD20 (e) was indicative of the presence of macrophages, T lymphocytes and B lymphocytes, respectively. (f) Immunoreactivity for glial fibrillary acidic protein, a marker for nerve fibers was strongly positive

Finally, we diagnosed the lesion as LCH in the CNS. After steroids were started (60 mg/day of prednisone) for 1 month, all lesions in the hypothalamus, basal ganglia, and white matter were clearly reduced in size, as detected on MRI. Steroid treatment was gradually decreased, and no recurrence has been observed 18 months postoperatively [Figure 4a and b ].

Figure 4

T1-weighted coronal magnetic resonance imaging images with contrast enhancement. (a) Before steroid administration, there were enhanced lesions at the hypothalamus (white arrow) and the cerebral parenchyma (white arrowheads). (b) Eighteen months after administration of steroid, the enhanced lesion at the hypothalamus was reduced (white arrow), and the lesions at the brain parenchyma were completely diminished

DISCUSSION

In this present report, we described the case of a woman who developed LCH manifesting as panhypopituitarism and DI in the postpartum period. At first, the lesion only involved the pituitary stalk and spread to the hypothalamus 6 months later. In addition, the lesion became further enlarged and, after another 5 months, multiple new lesions emerged in the basal ganglia and white matter. Therefore, biopsy was performed to determine the therapeutic strategy. Finally, LCH was diagnosed by histology. This is an extremely rare case, which revealed sequential changes of hypothalamic LCH with multiple satellite lesions in the basal ganglia and white matter, and these lesions were reduced in size directly after steroid administration.

Although monoclonal proliferation of dendritic cells has been considered the cause of LCH, the exact mechanisms remain unknown. Definitive diagnosis of LCH was obtained by immunohistological examination of surgical specimens. The specimens showed invasion of aggressive inflammatory cells that immunoreacted with CD1a. It is reported that the annual incidence of LCH is 0.5 cases per 100,000 children younger than 15 years, but the incidence in adults remains unknown.[ 9 ] There is organic predominance in the lung among adult patients with LCH and an etiological relationship between smoking and LCH in the lungs.[ 4 11 ] The clinical presentations and outcomes of LCH vary, and treatment depends on whether there are single or multiple lesions and on whether high-risk organs, such as the bone marrow, liver, spleen, and lungs, are involved.[ 5 ] Most isolated skin lesions are self-limited and disappear without treatment, and single bone lesions treated with surgical resection or radiation therapy have excellent prognoses.[ 5 ] Previous reports have described that some patients with LCH had good outcomes with steroid administration.[ 1 ] However, LCH occasionally has a poor prognosis when it affects multiple systemic organs, even if aggressive chemotherapy is administered.[ 8 ] In some cases, malignancy or immune reactivation might appear during the clinical course.[ 2 5 ] Although no genetic examination was performed in our case, genetic examinations, such as BRAF V600E and MAP2K1 mutations, are recommended to make a prognosis.[ 5 ]

The hypothalamus, one of the most common regions where LCH appears, is involved in approximately 40% of LCH cases in the CNS and is well-known as a clinical landmark of DI.[ 10 ] In contrast, diverse forms of LCH originating from other CNS lesions exist, but they are rare.[ 9 ] Few reports have found LCH in the CNS associated with multiple enhanced lesions in the brain parenchyma, similar to our present case.[ 6 7 9 ] However, an adult LCH case with progressively enhanced CNS lesions affecting the hypothalamus and brain parenchyma is extremely rare. In one of the reported cases, whole-brain autopsy was performed and revealed particular histopathological features, including diffuse inflammation, mainly composed of CD8+ T lymphocytes present in the whole brain and CD20+ B lymphocytes only at the perivascular lesions. These autopsy findings led to the notion that the multiple enhanced lesions in the brain parenchyma detected on MRI might have been inflammatory active perivascular lesions, composed of lymphocytes as determined by histopathological examination.[ 7 ] LCH lesions consist of different types of inflammatory cells; the level of invasion and percentage of these cells differ for each organ.[ 3 ] Notably, the cerebral LCH parenchymal lesions in the CNS in our case mainly consisted of lymphocytes.

Because of its low incidence, the treatment of LCH in the CNS has not been established. Previous reports have described some treatment strategies, such as surgery, radiation, anti-inflammatory medications, anti-angiogenic medications, and chemotherapy. These treatments are administered depending on the clinical presentation in the CNS.[ 6 ] In the present case, steroid administration induced remarkable size reduction of the enhanced LCH lesions in the hypothalamus and brain parenchyma. In addition, no recurrence or neurological deterioration has been noticed. This clinical course confirmed that the enhanced lesions in both the hypothalamus and brain parenchyma were mainly provoked by local aggressive inflammatory responses. In our case, steroid administration effectively induced anti-inflammatory actions that affected all lesions. It can, therefore, be speculated that decreased enhancement of cerebral parenchymal lesions is caused by inflammatory active responses by lymphocytes and dendritic cells.

We experienced an extremely rare case of LCH of the hypothalamus leading to multiple enhanced lesions in the basal ganglia and white matter. Definitive diagnosis was made by biopsy, and steroid administration reduced these lesions without recurrence over 1 year. When a patient has a lesion in the hypothalamus and multiple other lesions in the brain parenchyma suggestive of LCH, early biopsy for definitive diagnosis and steroid administration are strongly recommended. The present case suggests that the enhanced lesions of LCH in the CNS, mainly composed of lymphocytes, can spread to the brain parenchyma but can be promptly reduced after steroid administration.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

This work was supported by Hemragul Sabit and Erika Komura, who prepared slides and performed immunohistochemistry.

References

1. Akçay S, Eyüboglu FO, Arícan A, Demírhan B. Effect of pulse steroid therapy in a patient with Langerhans’ cell histiocytosis. Respirology. 2001. 6: 357-60

2. Bechan GI, Egeler RM, Arceci RJ. Biology of Langerhans cells and Langerhans cell histiocytosis. Int Rev Cytol. 2006. 254: 1-43

3. Favara BE, Jaffe R. The histopathology of Langerhans cell histiocytosis. Br J Cancer Suppl. 1994. 23: S17-23

4. Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J. Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-net. Orphanet J Rare Dis. 2013. 8: 72-

5. Grana N. Langerhans cell histiocytosis. Cancer Control. 2014. 21: 328-34

6. Grois N, Fahrner B, Arceci RJ, Henter JI, McClain K, Lassmann H. Central nervous system disease in Langerhans cell histiocytosis. J Pediatr. 2010. 156: 873-810

7. Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain. 2005. 128: 829-38

8. Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H. Response to initial treatment of multisystem Langerhans cell histiocytosis: An important prognostic indicator. Med Pediatr Oncol. 2002. 39: 581-5

9. Prayer D, Grois N, Prosch H, Gadner H, Barkovich AJ. MR imaging presentation of intracranial disease associated with Langerhans cell histiocytosis. AJNR Am J Neuroradiol. 2004. 25: 880-91

10. Prosch H, Grois N, Prayer D, Waldhauser F, Steiner M, Minkov M. Central diabetes insipidus as presenting symptom of Langerhans cell histiocytosis. Pediatr Blood Cancer. 2004. 43: 594-9

11. Vassallo R, Ryu JH, Colby TV, Hartman T, Limper AH. Pulmonary Langerhans’-cell histiocytosis. N Engl J Med. 2000. 342: 1969-78

Abstract

Background:We present one of the first documented cases in the literature of an adult with Klippel-Trenaunay syndrome (KTS) with a large frontal osseous hemangioma.

Case Description:A 30-year-old male presented with a rapidly enlarging frontal skull lesion that had developed in only 3 months. Radiological investigation revealed a highly vascular lesion attached to the frontal bone. The lesion was surgically resected with the patient making complete recovery. Histopathology was consistent with an osseous hemangioma.

Conclusion:We report the clinical presentation and surgical management of a rare presentation of osseous hemangioma in a patient with KTS.

Keywords: Hemangioma, Klippel-Trenaunay syndrome, Neuropathology

INTRODUCTION

Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder characterized by the classic triad of capillary malformation, venous malformation, and limb overgrowth.[ 6 ] The eponymous syndrome was first described by French physicians Maurice Klippel and Paul Trenaunay in the early 20^th century.[ 1 ] A well described entity of KTS is the development of peripheral vascular hemangioma, however, hemangioma arising from the skull is rare and to our knowledge, not described in the literature prior. We present the unique case of a 30-year-old male who presented with a rapidly expansile hemangioma arising from the frontal bone of the skull. Clinical presentation and surgical resection are described.

CASE REPORT

A 30-year-old male with a known history of KTS presented with a rapidly enlarging subcutaneous central frontal mass, measuring 41 × 47 × 54 mm since its formation just 3 months earlier causing pain and an obvious cosmetic defect. The patient had no demonstrable neurological signs on examination with normal pre-operative laboratory studies, however, had previous episodes of significant hemorrhage arising from the lesion as a result of minor trauma.

Clinically, the patient was dysmorphic, most notably severe soft tissue overgrowth, bilateral lower limb lymphoedema, and cellulitis. Despite this, he had no history of other complications arising as a result of his KTS such as malignancy or peripheral hemangioma.

Radiological findings initially began with computed tomography angiogram, which revealed a destructive expansile arterially-enhancing lesion arising from the frontal bone. Heterogenous contrast enhancement on magnetic resonance imaging [ Figure 1 ] further defined the lesional dural involvement and invasion into the superior sagittal sinus sparring cerebral parenchyma.

Figure 1

T1 weighted post contrast magnetic resonance imaging depicting the destructive nature and invasion of the vascular lesion; although it is closely associated with dura and superior saggital sinus, there is no evidence of parenchymal invasion. Digital Subtraction Cerebral Angiogram (right sided image) further characterizing the vascular lesion; arterial supply with fistulization from the ophthalmic artery and also some lesser arterial supply from the superficial temporal arteries bilaterally

Gross total resection consisted of a T-shaped incision followed by bilateral frontal craniectomies [ Figure 2 ]. The vascular lesion was identified arising from frontal bone and within the superior saggital sinus. The lesion was resected en bloc from calvaria. A custom-made titanium implant was used for cranioplasty [ Figure 3 ].

Figure 2

These images detailing of the preparation and incisional marking. The lesion's sheer size can be appreciated

Figure 3

From Left to Right; Saggital and axial postoperative magnetic resonance imaging sections; H and E stains showing the mixed cavernous and capillary portions of the highly vascular lesion with invasion into bone

Postoperatively, the patient had a full recovery. Histopathological hemotoxylin and eosin stains revealed the lesion extending through bone, with a small foci of extramedullary hemopoiesis, consistent with hemangioma. There has been no evidence of recurrence 6 months post resection.

DISCUSSION

Since its description in the early 20^th century, prevalence has remained uncommon.

To our knowledge, vascular lesions arising from the skull in patients with KTS have not been previously described in the literature. Previous reports do highlight the increased prevalence and wide variability of malignancy in patients with KTS peripherally and in the spine.[ 5 7 ]

Hemangioma are benign vascular tumors, most commonly seen in pediatric age groups.[ 4 ] Rapid growth and sinus involvement both increase hemorrhagic risk.

Intraoperatively, the tumor was seen to locally invade into calvaria with evidence of skull remodeling and destruction which is scarcely discussed as a characteristic of vascular hemangioma in past literature. Gross total resection is the gold standard of therapy and recommended by the authors. This minimizes recurrence and allows for tissue histopathological diagnosis in a syndrome known for predisposition to malignancy. The role for non-operative management in hemangioma including radiotherapy still exists.[ 2 ] The ambiguity of the lesion usually necessitates histopathological tissue diagnosis, with previous reports detailing the close resemblance to meningiomas and hemangiopericytoma.[ 3 ]

Postoperatively, the patient received regular follow-up with radiological screening for tumor recurrence.

We, as the authors would like to highlight this unique case of an intracranial osseous hemangioma with frontal skull based origin in a patient with KTS, a rare syndrome with a predisposition to malignancy. There are associated dangers and complexities for the surgeon involved in resection of these uncommon lesions.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Kihiczak GG, Meine JG, Schwartz RA, Janniger CK. Klippel-Trenaunay syndrome: A multisystem disorder possibly resulting from a pathogenic gene for vascular and tissue overgrowth. Int J Dermatol. 2006. 45: 883-90

2. Morace R, Marongiu A, Vangelista T, Galasso V, Colonnese C, Giangaspero F. Intracranial capillary hemangioma: A description of four cases. World Neurosurg. 2012. 78: 191.E15-21

3. Phi JH, Kim SK, Cho A, Kim DG, Paek SH, Park SH. Intracranial capillary hemangioma: Extra-axial tumorous lesions closely mimicking meningioma. J Neurooncol. 2012. 109: 177-85

4. Simon SL, Moonis G, Judkins AR, Scobie J, Burnett MG, Riina HA. Intracranial capillary hemangioma: Case report and review of the literature. Surg Neurol. 2005. 64: 154-9

5. Spallone A, Tcherekayev VA. Simultaneous occurrence of aneurysm and multiple meningioma in Klippel-Trenaunay patients: Case report. Surg Neurol. 1996. 45: 241-4

6. Uller W, Fishman SJ, Alomari AI. Overgrowth syndromes with complex vascular anomalies. Semin Pediatr Surg. 2014. 23: 208-15

7. Yilmaz T, Cikla U, Kirst A, Baskaya MK. Glioblastoma multiforme in Klippel-Trenaunay-weber syndrome: A case report. J Med Case Rep. 2015. 9: 83-

Abstract

Background:Multiple sclerosis (MS) is a chronic central nervous system inflammatory demyelinating disease characterized by multiple lesions disseminated in time and space. The lesions often have characteristic imaging findings on magnetic resonance (MR) imaging and cerebrospinal fluid findings that lead to their diagnosis. At times, these lesions may resemble tumors due to their large size (>2 cm), significant vasogenic edema, and ring-enhancing MR imaging findings. Such lesions are described as tumefactive demyelinating lesions or tumefactive MS, and they are generally seen in aggressive forms of MS associated with rapid progression.

Case Description:We report an uncommon but clinically significant case of transtentorial brain herniation secondary to malignant cerebral edema from tumefactive MS in a 50-year-old woman. After the initial diagnosis of MS, the patient continued to have progression of her white matter lesions suggesting evolution of her MS despite treatment with intravenous (IV) steroids, IV immunoglobulin, and plasmapheresis. She was admitted to the hospital with a new, large, ring-enhancing lesion that displayed significant mass effect from vasogenic edema and progressed, necessitating a decompressive hemicraniectomy.

Conclusion:Tumefactive MS presents a unique pathology that can often mimic primary brain tumors. Although these lesions affect white matter and infrequently cause a significant amount of mass effect, they can act like a tumor, causing edema that generates sufficient intracranial pressure to cause transtentorial herniation.

Keywords: Decompressive hemicraniectomy, transtentorial herniation, tumefactive demyelinating lesion, tumefactive multiple sclerosis

INTRODUCTION

Primary demyelinating disease of the central nervous system presents in many different forms such as multiple sclerosis (MS), myelinoclastic diffuse sclerosis, and acute demyelinating encephalomyelitis. MS is a chronic inflammatory demyelinating disease of the central nervous system that is characterized by multiple lesions disseminated in time and space. Typical MS-associated lesions have a predilection for the periventricular areas, cerebellum, brainstem, spinal cord, and optic nerves and are visualized on T1 contrast-enhanced sequences as partially ring-enhancing on the basis of their acuteness.[ 2 9 11 ]

The term “tumefactive demyelinating lesion” in conjunction with MS was first introduced by Kepes in 1993.[ 10 ] These lesions occur more frequently in women, especially during the second or third decade of life. They are often misdiagnosed on neuroimaging due to their ill-defined margins, variable degree of perilesional edema, mass effect, central zones of necrosis, and cystic degeneration. The characteristic histopathological features of these lesions are the presence of foamy macrophages, reactive gliosis, and perivascular lymphocytic infiltrate.

Malignant edema from tumefactive MS lesions has been described in previous case reports. Most tumors and demyelinating lesions show considerable fluid-attenuated inversion recovery signal changes on magnetic resonance (MR) imaging that denote clinically significant vasogenic edema.[ 9 ] Most case reports describe lesions leading to subfalcine herniation.[ 14 18 22 ] Only two cases have been described in which MS presented with transtentorial brain herniation. The first case was described in 2001 of a cystic ring-enhancing frontal lesion that showed moderate mass effect on the lateral ventricles.[ 2 ] The second case involved a 22-year-old woman who presented with a 3-day course of headache and quickly worsened neurologically within the first 24 h of admission.[ 19 ] The patient had tumefactive demyelination with transtenorial herniation. Such a rapid decline in mentation and progression to a stuporous state is a rare circumstance that has not been reported in the literature.

We describe an uncommon case of confirmed tumefactive MS that mimicked a brain tumor in which the development of malignant edema led to transtentorial herniation.

CASE DESCRIPTION

This is a 50-year-old woman with an established diagnosis of MS manifested by transverse myelitis. She had been treated with intravenous (IV) steroids and glatiramer acetate with excellent results in the past for episodes of left-sided weakness after MR imaging of the brain done 1 year before this presentation revealed a deep white matter lesion with an incomplete ring-enhancing pattern without midline shift or edema [ Figure 1 ].

Figure 1

Axial T1-weighted contrast-enhanced magnetic resonance image demonstrating a right temporoparietal, partial ring-enhancing lesion in the white matter

On the current admission, she presented with nausea, vomiting, and lethargy. A computed tomographic (CT) scan of the head demonstrated subfalcine herniation [ Figure 2 ] secondary to extensive vasogenic edema, which explained her obtundation. She was admitted to the intensive care unit and placed on 1000 mg of IV methylprednisone on a daily basis. Considerable improvement in her mentation was noted over the next day.

Figure 2

Axial computed tomographic image obtained at the time of admission, before high-dose steroid therapy was started, showing subfalcine herniation

On the third day of her stay in the intensive care unit, she developed a nonreactive dilated right pupil and was found to be somnolent. A repeat CT scan revealed worsening edema, causing transtentorial herniation [ Figure 3 ]. She was taken immediately to the operating room for a right decompressive hemicraniectomy.

Figure 3

Axial computed tomographic image showing aggressive development of edema causing transtentorial herniation

Intraoperatively, after removal of the bone flap, the right cerebral hemisphere herniated through the bony defect. Underlying the dura, there was a significant amount of abnormal brain tissue that was grayish in color. A biopsy of the tissue was performed, and the skin edges were closed. The patient was continued on the high-dose steroid therapy and remained under close observation in the intensive care unit. Over the next 3 days, she became more alert and her right pupil returned to normal size and reactivity. She regained her previous baseline neurologic status with a left hemiparesis and was able to communicate easily.

The results of the pathologic examination were consistent with demyelinating disease. Due to the enhancing nature of the lesion as well as the extensive edema, there was a concern for an underlying pathology that was not obvious. It was decided to continue treatment with immunosuppressive therapies and repeat neuroimaging in a few weeks after interval resolution of the edema. After 5 weeks, the patient's skin flap had become sunken; however, given her ongoing immunotherapy, a cranioplasty was not performed. She was transferred to a rehabilitation facility.

DISCUSSION

Tumefactive MS lesions present as large intracranial lesions that may resemble brain tumors. The incidence is thought to be 0.3 cases per 100,000 patients per year.[ 16 ] There is no clear gender predilection for tumefactive lesions. Patients in their 20s and 30s are most likely to be affected, although cases involving pediatric and older patients have also been described.[ 15 ] These lesions are typically larger than 2 cm in diameter and usually cause considerable edema and mass effect.[ 1 6 18 20 ] They are commonly seen as ring-enhancing lesion[ 3 6 ] which makes their diagnosis challenging because tumors and infections have a similar appearance on MR imaging. An open ring-enhancing lesion is almost pathognomonic for MS and affected patients can frequently present with localized neurological deficits, such as hemiparesis, aphasia, ataxia, headaches, and seizures. The ring enhancement is thought to be an advancing area of active inflammation away from a central and more chronic nonenhancing core.[ 8 ] Histologically active lesions consist of areas of demyelination with hypercellularity and reactive astrocytes that may contain multiple nuclei (Creutzfeldt cells) closely intermingled with myelin-containing foamy macrophages.[ 15 ]

Cerebrospinal fluid testing may be normal or demonstrate elevation of the immunoglobulin G index and oligoclonal bands. These findings have been demonstrated in 11–33% of the cases of tumefactive MS.[ 16 ] Biopsy often helps differentiate these demyelinating lesions from other pathologies. It is also worth noting that biopsy results can be misleading if not interpreted by an experienced neuropathologist. Initial biopsy results may be interpreted incorrectly in as many as 31% of the cases; most frequently, the lesion is misdiagnosed as a low-grade astrocytoma.[ 16 ]

Treatment of tumefactive lesions is generally challenging and recovery is often incomplete. Treatment choices include IV methylprednisolone, β-interferons, plasma exchange, rituximab, and natalizumab (monoclonal antibody). IV steroid therapy is generally initiated for any acute, symptomatic tumefactive lesion. Plasmapheresis should be tried in the event of a relapse or no response to steroid therapy.[ 17 21 ] Available data suggest that disease-modifying therapies like interferon-β and glatiramer acetate may be tried.[ 5 12 ] There are no data to suggest superiority of one over the other. There are certain case reports where patients with relapsing-remitting MS undergoing treatment with fingolimod (sphingosine-1-phosphate receptor modulator) have developed tumefactive lesions on discontinuation of therapy.[ 5 ] This observation needs further study. Rituximab and cyclophosphamide have shown benefit in tumefactive lesions.[ 4 7 ] Series consisting of cases of biopsy-confirmed tumefactive MS suggest that lesions without significant mass effect may help differentiate MS lesions from other space-occupying lesions.[ 13 14 18 22 ]

To our knowledge, our case represents the second reported case[ 19 ] of cerebral herniation from tumefactive MS. This case illustrates the importance of recognizing the catastrophic complications that may arise as a result of mass effect from vasogenic edema if this condition is not diagnosed and treated early and aggressively.

CONCLUSION

Tumefactive MS presents a unique pathology that can often mimic primary brain tumors. Although these lesions affect white matter and infrequently cause a significant amount of mass effect, there are now two cases that show these lesions can act like tumors causing edema that generates sufficient intracranial pressure to cause transtentorial herniation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

The authors thank Paul H. Dressel BFA for the preparation of the illustrations and Debra J. Zimmer for editorial assistance.

References

1. Almalki DM, Mudhafar OY, Alsaman AS, Mahmoud AA. Diagnostic uncertainty of tumefactive cystic demyelinating lesions. Neurosciences (Riyadh). 2013. 18: 176-7

2. Censori B, Agostinis C, Partziguian T, Gazzaniga G, Biroli F, Mamoli A. Large demyelinating brain lesion mimicking a herniating tumor. Neurol Sci. 2001. 22: 325-9

3. Dagher AP, Smirniotopoulos J. Tumefactive demyelinating lesions. Neuroradiology. 1996. 38: 560-5

4. Dastgir J, DiMario FJ. Acute tumefactive demyelinating lesions in a pediatric patient with known diagnosis of multiple sclerosis: Review of the literature and treatment proposal. J Child Neurol. 2009. 24: 431-7

5. Faissner S, Hoepner R, Lukas C, Chan A, Gold R, Ellrichmann G. Tumefactive multiple sclerosis lesions in two patients after cessation of fingolimod treatment. Ther Adv Neurol Disord. 2015. 8: 233-8

6. Given CA, Stevens BS, Lee C. The MRI appearance of tumefactive demyelinating lesions. AJR Am J Roentgenol. 2004. 182: 195-9

7. Haupts MR, Schimrigk SK, Brune N, Chan A, Ahle G, Hellwig K. Fulminant tumefactive multiple sclerosis: Therapeutic implications of histopathology. J Neurol. 2008. 255: 1272-3

8. He J, Grossman RI, Ge Y, Mannon LJ. Enhancing patterns in multiple sclerosis: Evolution and persistence. AJNR Am J Neuroradiol. 2001. 22: 664-9

9. Kaeser MA, Scali F, Lanzisera FP, Bub GA, Kettner NW. Tumefactive multiple sclerosis: An uncommon diagnostic challenge. J Chiropr Med. 2011. 10: 29-35

10. Kepes JJ.editors. Large focal tumor-like demyelinating lesions of the brain: Intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients. Ann Neurol. 1993. 33: 18-27

11. Kobayashi M, Shimizu Y, Shibata N, Uchiyama S. Gadolinium enhancement patterns of tumefactive demyelinating lesions: Correlations with brain biopsy findings and pathophysiology. J Neurol. 2014. 261: 1902-10

12. La Mantia L, Di Pietrantonj C, Rovaris M, Rigon G, Frau S, Berardo F. Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis. Cochrane Database Syst Rev. 2016. 11: CD009333-

13. La Puma D, Llufriu S, Sepúlveda M, Blanco Y, Ribalta T, Graus F. Long-term follow-up of immunotherapy-unresponsive recurrent tumefactive demyelination. J Neurol Sci. 2015. 352: 127-8

14. Liao PY, Chen CY. Regarding tumefactive demyelinating lesion, its image diagnosis, and discussion. Am J Emerg Med. 2015. 33: 290-1

15. Lucchinetti CF, Gavrilova RH, Metz I, Parisi JE, Scheithauer BW, Weigand S. Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain. 2008. 131: 1759-75

16. Masdeu JC, Moreira J, Trasi S, Visintainer P, Cavaliere R, Grundman M. The open ring. A new imaging sign in demyelinating disease. J Neuroimaging. 1996. 6: 104-7

17. Meca-Lallana JE, Hernández-Clares R, León-Hernández A, Genovés Aleixandre A, Cacho Pérez M, Martín-Fernández JJ. Plasma exchange for steroid-refractory relapses in multiple sclerosis: An observational, MRI pilot study. Clin Ther. 2013. 35: 474-85

18. Ninomiya S, Hara M, Morita A, Teramoto H, Momose M, Takahashi T. Tumefactive demyelinating lesion differentiated from a brain tumor using a combination of magnetic resonance imaging and (11) C-methionine positron emission tomography. Intern Med. 2015. 54: 1411-4

19. Ragel BT, Fassett DR, Baringer JR, Browd SR, Dailey AT. Decompressive hemicraniectomy for tumefactive demyelination with transtentorial herniation: Observation. Surg Neurol. 2006. 65: 582-3

20. Sinha MK, Garg RK, Bhatt ML, Chandra A. Tumefactive demyelinating lesion: Experience with two unusual patients. J Postgrad Med. 2010. 56: 146-9

21. Weiner HL, Dau PC, Khatri BO, Petajan JH, Birnbaum G, McQuillen MP. Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis. Neurology. 1989. 39: 1143-9

22. Yamashita S, Kimura E, Hirano T, Uchino M. Tumefactive multiple sclerosis. Intern Med. 2009. 48: 1113-4

Abstract

Background:Gliosarcoma (GS) is a primary rare malignant brain tumor that accounts 4% of all high-grade glial tumor of the brain.

Case Description:We present a 45-year-old female admitted to our center with progressive headache since 1 month ago concomitant with nausea and emesis and generalized weakness. Imaging revealed a large solid mass with well-defined margin and some cystic portions that enhanced brightly with contrast. We decided to operate the patient via right parietal craniotomy and we totally resected all visible portions of the mass, as en bloc resection. The histopathological report of the mass was GS. We are following the patient up to now, for about 50 months, and she is good without any compliant or neurologic deficit. All follow-up magnetic resonance imaging (MRI) did not show any tumor recurrence.

Conclusion:Aiming to achieve longer progression-free survival in cases of GS, we recommend resecting all portions of the mass as much as possible, so named en bloc resection, and then refer the patients for appropriate and timely chemoradiotherapy.

Keywords: En bloc resection, gliosarcoma, overall survival, progression-free survival

BACKGROUND

Gliosarcoma (GS) is a primary rare malignant brain tumor that contains both gliomatous and sarcomatous (mesenchymal) components and accounts 4% of all high-grade glial tumor of the brain.[ 6 ] Based on the 2007 World Health Organization (WHO) classification, GS is a Grade 4 tumor same as glioblastoma multiform (GBM).[ 8 ] In the literature, mean overall survival (OS) of GS in untreated patients is 4 months and with multidisciplinary tri-modal therapy, the mean OS is about 15 months.[ 10 ] We present a patient with GS that we treated her and she has 50 months disease-free survival up to now.

CASE DESCRIPTION

We present a 45-year-old female admitted to our center with progressive headache since 1 month ago concomitant with nausea, emesis, and generalized weakness. She had minimal headache since 2 years ago and, on admission clinical examination, we did not find any neurologic deficits. Also, the patient had bilateral pupillary edema on fundoscopy. She had bilateral positive Hoffmann's sign. On first brain computed tomography (CT), we saw a large heterogeneous mass with some vasogenic edema at right parieto-occipital region with 0.5 cm midline shift that compressed right occipital horn of lateral ventricle [ Figure 1a ]. The brain magnetic resonance imaging (MRI) with and without gadolinium (Gd) revealed a large solid mass with well-defined margin and some cystic portions that enhanced brightly with Gd [Figure 1b and c ]. The vasogenic edema was less than our expectation.

Figure 1

Preoperative brain computed tomography scan (a) of the patient revealed a large heterogeneous mass at right parieto-occipital region with some vasogenic edema that produces a 0.5 cm midline shift of the brain. On the brain magnetic resonance imaging, we found a solid-cystic hyper-intense mass on T2 sequences (b) that it is brightly enhanced after injection of gadolinium (c). Follow-up brain magnetic resonance imaging with gadolinium revealed no remnant of tumor (d)

According to very large mass effect, we decided to operate the patient via right parietal craniotomy. The tumor had a more firm consistency compared with adjacent normal brain tissue and it was well demarcated and we totally resected all visible portions of the mass, as en bloc resection. The histopathological report of the mass was GS [Figure 2a – d ]. After surgical treatment, the patient's treatment continued by chemotherapy with temozolamide and a course of radiotherapy. We are following the patient up to now, for about 50 months, and she is good without any compliant or neurologic deficit. All follow-up MRI did not show any tumor recurrence [ Figure 1d ].

Figure 2

Histopathologic finding revealed a biphasic tumor with alternating between glial and mesenchymal differentiation (a, H and E × 400). Immunohistochemically (IHC), we see G-FAP positive portions (negative for reticulin, b × 100) and in concomitant with reticulin-riched portions (negative for G-FAP, c × 400) in other sites. Also, we can see positive staining for Ki-67 (d × 400)

DISCUSSION

The GS, as known Feigin tumor, is a rare and malignant glioma.[ 3 ] With best existing tri-modal therapy, contained surgical gross total resection and then chemoradiotherapy, this tumor has very poor prognosis.[ 10 ] For GS, histopathological exam shows both gliomatous and sarcomatous components. At the surgery compared with GBM, the borders of tumor are more distinct because of presence of sarcomatous component, but on the other hand, the patients have less response to adjuvant treatment contained chemotherapy and radiotherapy during postoperative period.

In the literature, we found only eight reports of GS with OS >2 years [ Table 1 ]. Considering the term of survival, we have to pay attention to this subject that the “overall survival” is different with “progression-free survival” (PFS). The patients with longer OS have not necessarily longer PFS and they may have multiple recurrence period needed complete treatment courses that patients suffered from them. Longer PSF can predict more excellent quality of life (QOL). Compared with our case, only four reports of GS had a longer OS concomitant with long PFS.[ 1 4 9 10 ]

Table 1

A literature review for all reported cases with GS and longer OS

Although in almost all cases, infiltrative nature of gliomatous tumors hinder to remove all portions of them, because of sarcomatous components of GS, differences in consistency of tumoral tissue compared with brain tissue assist to define a relatively well-demarcated plane between them during surgery. In addition, en bloc resection with preservation of tissue planes during dissection prevents missing any tumor component intermingled with brain parenchyma at the time of dissection. Finally, location of the lesion in non-eloquent area of brain lets intraoperative manipulations and more feasible en bloc tumor removal. We think all these factors together in association with appropriate and timely adjuvant therapy helps surgeon to give the most chance of PFS to the patient with GS.

CONCLUSION

We present a patient with GS that has a long PFS after surgical treatment. Aiming to achieve longer PFS in cases of GS and regarding to more distinct consistency, we recommend resecting all portions of the mass, as much as possible, to reach en bloc resection and then refer the patients for appropriate and timely chemoradiotherapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Burzynski SR, Janicki TJ, Burzynski GS, Marszalek A. Long-term survival (>13 years) in a child with recurrent diffuse pontine gliosarcoma: A case report. J Pediatr Hematol Oncol. 2014. 36: e433-9

2. Chen L, Xiao H, Xu L, Zou Y, Zhang Y, Xu M. A case study of a patient with gliosarcoma with an extended survival and spinal cord metastases. Cell Biochem Biophys. 2012. 62: 391-5

3. Feigin IH, Gross SW. Sarcoma arising in glioblastoma of the brain. Am J Pathol. 1955. 31: 633-53

4. Huo Z, Yang D, Shen J, Li Y, Wu H, Meng Y. Primary gliosarcoma with long-survival: Report of two cases and review of literature. Int J Clin Exp Pathol. 2014. 7: 6323-32

5. Kalita O, Zlevorova M, Megova M, Vaverka M, Trojanec R, Tuckova L. A patient with primary intraventricular gliosarcoma and long-term survival-A case report. Klin Onkol. 2016. 29: 454-9

6. Karsy M, Gelbman M, Shah P, Balumbu O, Moy F, Arslan E. Established and emerging variants of glioblastoma multiforme: Review of morphological and molecular features. Folia Neuropathol. 2012. 50: 301-21

7. Linhares P, Martinho O, Carvalho B, Castro L, Lopes JM, Vaz R. Analysis of a synchronous gliosarcoma and meningioma with long survival: A case report and review of the literature. Surg Neurol Int. 2013. 4: 151-

8. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007. 114: 97-109

9. Wang Z, Kong QT, Wu XH, Zhu XX. Long-term survival in gliosarcoma with radiation-induced meningeal sarcomas: Case report and molecular features. J Cancer Res Ther. 2015. 11: 651-

10. Winkler PA, Buttner A, Tomezzoli A, Weis S. Histologically repeatedly confirmed gliosarcoma with long survival: Review of the literature and report of a case. Acta Neurochir (Wien). 2000. 142: 91-5

Abstract

Background:The thalamus is normally supplied by each posterior cerebral artery (PCA). The artery of percheron is a variant of this anatomy as it arises as a single trunk unilaterally from the PCA to supply the thalamus bilaterally. Occlusion of this artery is rare, and the diagnosis is usually missed without obtaining an MRI.

Case Description:We illustrate the case of a 68-year-old male who presented with coma, ocular gaze palsy, and severe bradycardia from bilateral thalamic nuclei and midbrain infarction, as described as an artery of Percheron infarction. The patient recovered neurologically under conservative treatment with a residual vertical diplopia from downward gaze palsy. He underwent cardiac pacer implantation for severe bradycardia at the end of his admission. The thalamic pathway associated with cardiac rhythm, especially the zona inserta, is discussed. Publications related to the artery of Percheron are reviewed.

Conclusion:Coma and ocular gaze palsy are the most common presentations following thalamic and midbrain ischemia from artery of Percheron infarction. To our knowledge, only a single case of artery of Percheron infarction with severe bradycardia has been reported in the past. Our case attested the role of thalamic nuclei controlling cardiac rhythm.

Keywords: Artery of Percheron, coma, severe bradycardia, thalamic infarct, Zonainserta

INTRODUCTION

The artery of Percheron arises as a single common trunk from one of the posterior cerebral arteries (PCA), and provides a bilateral arterial blood supply to the paramedian thalamic and rostral midbrain.[ 6 14 ] Artery of Percheron variance is rare, with an incidence of 11.7% from cadaveric study.[ 6 ] The most common clinical presentations are coma and ocular movement disorders.[ 1 2 3 ] There are four patterns of magnetic resonance imaging (MRI) diffusion study, (1) bilateral paramedian thalamic with midbrain infarction (43%), (2) bilateral paramedian thalamic without midbrain infarction (38%), (3) bilateral paramedian thalamic with anterior thalamic and midbrain infarction (14%), and (4) bilateral paramedian thalamic with anterior thalamus without midbrain infarction (5%).[ 7 ] From a neurophysiology stand point, the thalamus is the part of Reticular Activating System (RAS) that mediates consciousness by connecting the brainstem, thalamus, and cerebral cortex.[ 6 ] The thalamus not only functions to maintain consciousness through the RAS but it also controls the cardiovascular response center at the zona incerta area.[ 12 ] Regarding the cardiovascular connection, zona inserta receives afferent fibers from the anterior insular cortex before sending efferent fibers to the cardiovascular center in medulla.

Alterations of consciousness from a bilateral thalamic infarction is prevalent in the literature,[ 13 14 ] whereas only one case has been reported having severe bradycardia.[ 12 ] We demonstrate a case with coma, ocular gaze palsy, and severe bradycardia following infarction of the artery of Percheron.

CASE

A 68-year-old, right-handed Native American male with a past medical history of hypertension and Gleason grade 3 prostate cancer presented to the emergency room with alterations of consciousness and severe bradycardia. His past surgical history included prostate cancer surgery and degenerative lumbar spine surgery. He is thin, athletic build with a BMI of 18.8. He is a non-smoker and has a baseline heart rate of 50 beats per minute. On the day of admission, he suddenly became unconscious while talking to his wife and fell from the chair. Less than five minutes later, he woke up and was confused. He was found incoherent upon arrival of the emergency medical team. His vitals were normal, and he was able to maintain his airway en route to the hospital. At the emergency room, his heart rate was 30–40 beats/min, blood pressure 120/78 mmHg, respiratory rate 16 breaths/min, and temperature 36.8° C. His oxygen saturation was above 92% on room air. Neurologically, his eyes were closed but opened in response to painful stimuli (E2, Glassgow Coma Score). He made noises and spoke incoherent words sporadically (V3, Glassgow Coma Score). He was not able to follow commands but was able to localize painful stimuli to his extremities equally bilaterally (M5, Glassgow Coma Score). His pupils were 3 mm in diameter and reactive to light. He was not alert enough to follow the extraocular muscle testing. His face was symmetric, and his reflexes were normal. Neither Babinski nor clonus sign were present. Given his initial Glasgow coma score of 10, he was intubated in the emergency room for airway protection. Code stroke was activated at the same time as a computer tomography (CT) head was obtained [ Figure 1 ]. Subsequently, a stroke was ruled out after a normal head CT. This misled to an initial diagnosis of a coma from metabolic causes. Emergency blood chemistry was sent which resulted normal. A spot electroencephalogram was negative for seizure activity or any post ictal changes. He received respiratory support in the intensive care unit. At 24 hours after admission, an MRI was obtained which showed bilateral thalamic and midbrain infarction [ Figure 2 ]. Considering the etiology of this cerebral infarction, a Computed tomography angiography (CTA) of the brain and neck was obtained. This showed patency of all intra and extra cranial vasculature without evidence of stenosis [ Figure 3 ]. Given these MRI findings and his extensive negative laboratory workup, his diagnosis was changed to an infarction of the artery of Percheron. His heart rate was 30–40 beats/min with a systolic blood pressure ranging from 100–110 mmHg. His condition continued to improve, and he was successfully extubated the next day. At 48 h after admission, his heart rate ranged from 30–40 bpm with a systolic blood pressure ranging from 100–110 mmHg. He did not receive any inotropic or chronotropic medications during this admission. The continuous electrocardiography monitoring demonstrated sinus bradycardia. There were no cardiac wall motion abnormalities demonstrated by echocardiography, and the patient had an ejection fraction of 55%. His neurological examination was positive for dysarthria and downward gaze palsy. He was then transferred to the regular nursing floor where he received both physical and speech therapy with improvement. He did not suffer from any syncopal episodes nor did he have symptoms of cerebral hypo-perfusion for the duration of his admission. He stayed in the hospital for 10 days, and later underwent cardiac pacer placement [ Figure 4 ] before he was discharged to home. His home medications included aspirin, atorvastatin, diltiazem, seroquel, and asotalol. Follow-up appointment at 3 months revealed that his only complaint pertaining to a neurological deficit was vertical diplopia from slight downward gaze palsy.

Figure 1

Normal non-contrast head CT during initial work up upon arrival to the emergency room

Figure 2

Diffusion weighted image 48 h after admission demonstrating a bilateral thalamic (left) and midbrain (right) infarction

Figure 3

Follow-up CTA demonstrating patency of the basilar artery, the right-sided dominance of the vertebral artery, and patency of both posterior cerebral arteries

Figure 4

AP CXR status post pacemaker placement

DISCUSSION

Although myocardial contraction is mainly controlled by the intrinsic sinoatrium and atrioventricular nodes, it also receives extrinsic neural input from anterior insula, posterior hypothalamus, rostral ventrolateral medulla, and the zona incerta.[ 17 12 ] Episodes of cardiovascular changes after neural triggers are well known in medicine. For example, the vasovagal response has been described as a known cause of syncope or fainting. Stimulation of the Herring nerve, a branch of the Vagus nerve that innervates the carotid bulb, produces bradycardia. This is known as the carotid reflex. Myocardial damage following ischemia, as known as Takotsubo syndrome results from sympathetic hyperactivity.[ 11 16 18 ] Moreover, psychological stressors upregulate sympathetic neural input with resultant cardiac arrhythmia generation.[ 13 ] The above evidence supports the rich and complex interplay among the nervous and cardiac systems. Unlike the sympathetic system, the knowledge of thalamic visceral pathway is still limited. Thalamic nuclei, specifically the zona incerta is the center of the diencephalon that controls visceral response and receives input from multiple areas of the neural axis.[ 12 ] The zona incerta is initially described as zone of uncertainty.[ 10 ] Stimulation of the zona incerta and ventrolateral diencephalon lower blood pressure and heart rate in rats.[ 17 ] The proposed mechanism is interrupting the sympathetic efferent from posterior thalamus, which received an afferent from anterior insular cortex.[ 13 19 ] The zona incerta is part of the thalamic nuclei that normally receives its vascular supply from independent arteries, the left and right PCA. In certain instance, both thalamic nuclei are supplied by a single end perforator called artery of Percheron.[ 14 ] We confidently diagnose this case with an artery of Percheron infarction as a cause of severe bradycardia and coma for a number of reasons. One, the MRI pattern of bilateral paramedian thalamic and midbrain infarction is the most common finding in this type of infarction.[ 7 ] Two, the simultaneous onset of coma and bradycardia resulted from bilateral thalamic infarction. Three, we could not find another cause of bradycardia such as myocardial ischemia, thyroid disease, or atrial fibrillation.[ 15 ] To be specific and better clarify our hypothesis, the RAS system along with the zona incerta pathway inside thalamic nuclei were both disrupted from ischemia. From the literature search, a single case of severe bradycardia after bilateral thalamic infarction has been previously reported.[ 12 ] More research is needed to explore the pathway that connects the thalamic nuclei to the cardiovascular system. With a rapid growing knowledge in neuromodulation, such as deep brain stimulation for Parkinson disease and depression,[ 8 ] thalamic nuclei could potentially be the next target for cardiovascular disease.

Consciousness is mediated by the RAS. Its nuclei are spread throughout the thalamus and brainstem, sending reciprocal fibers bilaterally to multiple areas of the cerebral cortex.[ 21 ] The thalamic and brain stem RAS nuclei receive blood supply from the vertebral, basilar, and proximal posterior cerebellar artery. Disruption of the vascular supply to the RAS can alter consciousness ranging from dizziness, syncope, and coma.[ 5 ] Bilateral thalamic nuclei along with midbrain infarction are typical for the artery of Percheron.[ 7 ] The artery of Percheron is rarely visualized on magnetic resonance angiography, with a reported incidence of 0.4% of all strokes.[ 13 ] No literature has reported the sensitivity of CTA to detect the artery of Percheron. Coma and ophthalmoplegia are the most common presentations. An infarction in this location results in a supranuclear vertical gaze palsy, which is related to the rostral interstitial and Edinger-Westphal nuclei.[ 20 ] Considering the fact that CT can easily miss an early thalamic infarct, basilar artery occlusion, and venous sinus thrombosis,[ 20 ] it is important to not immediately rule these pathologies out as evidenced by us missing the thalamic infarction on initial head CT. At that time, code stroke was subsequently deactivated, and we shifted our approach toward other causes of coma. We followed the algorithmic approach to the comatose patient that targeted metabolic causes, seizure, central nervous system infection, and poisoning in most cases.[ 4 ] In our case, we did not find any common etiology of his coma within the first 24 h, hence why we pursued a brain MRI and a CTA of the head and neck to rule out any pathology that could have been missed. Besides a bilateral thalamic nuclei and midbrain infarction on brain MRI, there was no other pathology observed. Neither head CTA nor neck CTA revealed any vascular pathology. To optimize treatment for the patient, we searched extensively for the etiology of a bilateral thalamic nuclei and midbrain infarction. Thromboembolism, vascular dissection, and vascular steal phenomenon were ruled out given a normal appearing of intra and extracranial CTA. Cardiac embolism was ruled out given a normal echocardiography and emboli monitoring. Global cerebral hypoperfusion was ruled out given the infarction is outside the watershed area. In addition, considering the fact that small artery atherosclerosis and cardioembolism are the most frequent stroke mechanisms,[ 3 ] this further supported the conclusion that our patient was having an artery of Percheron infarction from atherosclerosis. Other rare reports including an artery of Percheron infarction following transpheniod pituitary surgery[ 2 ] and cardiac catheterization.[ 9 ] Given the rarity of this case, physicians must be aware of bilateral thalamic infarctions and the artery of Percheron variant when approaching the comatose patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Arauz A, Patino-Rodriguez HM, Vargas-Gonzalez JC, Arguelles-Morales N, Silos H, Ruiz-Franco A. Clinical spectrum of artery of Percheron infarct: Clinical-radiological correlations. J Stroke Cerebrovasc Dis. 2014. 23: 1083-8

2. Aryan S, Thakar S, Hegde AS. Artery of Percheron infarction after endoscopic pituitary surgery. Acta Neurochir (Wien). 2016. 158: 1973-5

3. Bjornstad B, Goodman SH, Sirven JI, Dodick DW. Paroxysmal sleep as a presenting symptom of bilateral paramedian thalamic infarctions. Mayo Clin Proc. 2003. 78: 347-9

4. Edlow JA, Rabinstein A, Traub SJ, Wijdicks EFM. Diagnosis of reversible causes of coma. Lancet. 2014. 384: 2064-76

5. Jumean K, Arqoub AA, Al Hadidi MA, Hawatmeh A, Shaaban H. Bilateral thalamic stroke due to occlusion of the artery of Percheron in a patient with a patent foramen ovale. J Nat Sci Biol Med. 2016. 7: 109-12

6. Kocaeli H, Yilmazlar S, Kuytu T, Korfali E. The artery of Percheron revisited: Acadaveric anatomical study. Acta Neurochir (Wien). 2013. 155: 533-9

7. Lazzaro NA, Wright B, Castillo M, Fischbein NJ, Glastonbury CM, Hildenbrand PG. Artery of percheron infarction: Imaging patterns and clinical spectrum. AJNR Am J Neuroradiol. 2010. 31: 1283-9

8. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C. Deep brain stimulation for treatment-resistant depression. Neuron. 2005. 45: 651-60

9. Mazek H, Sherif K, Suarez J, Wischmeyer J. The artery of Percheron infarction after coronary angiography. Case Rep Cardiol 2016. 2016. p.

10. Mitrofanis J. Some certainty for the “zone of uncertainty”. Exploring the function of the zona incerta?. Neuroscience. 2005. 130: 1-15

11. Oppenheimer S. Cerebrogenic cardiac arrhythmias: Cortical lateralization and clinical significance. Clin Auton Res. 2006. 16: 6-11

12. Peruzzotti-Jametti L, Bacigaluppi M, Giacalone G, Strambo D, Comi G, Sessa M. Life-threatening bradycardia after bilateral paramedian thalamic and midbrain infarction. J Neurol. 2011. 258: 1895-7

13. Pitts-Tucker T, Small J. Artery of Percheron: An unusual stroke presentation. BMJ Case Rep. 2018. p.

14. Qian J, Wu C, Peng J, Liu H. Bilateral paramedian thalamic and midbrain infarction due to occlusion of the artery of percheron in an elderly male: Acase report. Neurol Sci. 2017. 38: 1123-6

15. Richardson L. Sick sinus syndrome. JAAPA. 2017. 30: 50-1

16. S Y-H. Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo syndrome: Asystematic review of the literature to date. Cardiovasc Revasc Med. 2014. 15: 35-42

17. Spencer SE, SawyerWB , LoewyAD . L-glutamate stimulation of the zonaincerta in the rat decreases heart rate and blood pressure. Brain Res. 1988. 458: 72-81

18. Thayer JF, Lane RD. Claude Bernard and the heart-brain connection: Further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev. 2009. 33: 81-8

19. Thurtell MJ, Halmagyi GM. Complete ophthalmoplegia: An unusual sign of bilateral paramedian midbrain-thalamic infarction. Stroke. 2008. 39: 1355-7

20. Wong ML, Edlow JA. Artery of Percheron stroke. J Emerg Med. 2018. 55: 114-7

21. Yeo SS, Chang PH, Jang SH. The ascending reticular activating system from pontine reticular formation to the thalamus in the human brain. Front Hum Neurosci. 2013. 7: 416-

Keywords: Clear cell meningioma, dural attachment, fourth ventricle

A 35-year-old female patient was admitted with complaints of intermittent headache for 9 months and progressive gait disturbance for 6 months. She also complained of swaying while walking and disabling vertigo. Neurological examination on admission revealed ataxic dysarthria and ataxia of gait along with deranged cerebellar functions. Fundoscopy revealed papilledema.

Computed tomography (CT) showed a homogeneous hyperdense lesion occupying the whole fourth ventricle, with proximal enlargement of ventricular horns and heterogeneous enhancement on contrast administration. There were neither intralesional calcifications nor cyst formations. Magnetic resonance imaging [Figure 1a – f ] confirmed the intraventricular location of the tumor that appeared isointense to the surrounding gray matter on T1 and hyperintense on T2-weighted sequences, with very intense and homogenous enhancement after intravenous injection of gadolinium- diethlenetriamine penta-acetic acid. The lesion had smooth margins with extension through the foramina of Luschka and inferiorly to the cervical canal up to C2 vertebrae and filling the entire cisterna magna without any dural attachment, thus prompting us to label it preoperatively as being an ependymoma.

Figure 1

Contrast-enhanced MRI of brain showing fourth ventricle occupying mass lesion extending into bilateral foramen of Luschka and into cervical cord which is hypointense on T1W axial (a); heterogenous hyperintense on T2W axial (b) and sagittal (c); and heterogeneously enhancing on contrast administration on axial (d), sagittal (e), and coronal (f) images

Surgery was done in prone position via suboccipital craniotomy and C1 posterior arch excision. Tumor was encountered on opening dura. It was firm, well-vascularized, grayish, encapsulated, and extending into cervical canal compressing the spinal cord. No attachment to dura or choroid plexus was encountered. Gross total excision was achieved and postoperative contrast-enhanced CT showed no residual [Figure 2a – d ]. Postoperative course was uneventful and the patient was discharged home 12 days later.

Figure 2

Postoperative contrast enhanced computed tomography. (CECT) imaging showing complete excision of mass lesion on axial (a–c) and sagittal (d) images. Histopathological photographs of hematoxylin–eosin stain section (20× magnification) (e) showing patternless arrangement of tumor cells with interspersed collagen fibrils and clear cytoplasm. Periodic acid–Schiff–diastase staining (f) showing breakdown of glycogen and clear cytoplasm suggestive of clear-cell meningioma

Histopathological evaluation [Figure 2e and f ] revealed a meningeal neoplasm with diffuse architecture and patternless arrangement of tumor cells with interspersed collagen fibrils. Tumor cells appear clear with fine chromatin and inconspicuous nuclei. MIB-1-labeling index was reported to below 1%. Final diagnosis was clear-cell meningioma, World Health Organization grade II.

Meningiomas occurring primarily in fourth ventricle are rare entities and are believed to be originating from choroid plexus or tela choroidae.[ 1 3 ] Clear-cell meningiomas occur most commonly within cerebellopontine angle and spine. Other unusual locations reported are brainstem and fourth ventricle.[ 2 ] Clear-cell meningiomas behave aggressively and are associated with poor prognosis and high recurrence rates. Long-term follow-up is thus recommended in such patients.[ 2 ]

Preoperative diagnosis of meningioma is difficult but should be kept in mind as differential as they differ in terms of surgical challenge and clinical outcome as compared to other tumors in this location.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Alver I, Abuzayed B, Kafadar AM, Muhammedrezai S, Sanus GZ, Akar Z. Primary fourth ventricular meningioma: Case report and review of the literature. Turk Neurosurg. 2011. 21: 249-53

2. Burgan O, Bahl A, Critcher V, Zaki H, McMullan P, Sinha S. Clear cell meningioma of the fourth ventricle in a child: A case report and literature review. Pediatr Neurosurg. 2010. 46: 462-5

3. Shrestha R, Yue-Kang Z, Chao Y. Fourth ventricular meningioma in an adult: Case report and review of the literature. Indian J Neurosurg. 2012. 01: 161-4

Abstract

Background:Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are clinically rare, nonneoplastic, noninflammatory-calcified lesions of the central nervous system. Resection of a lesion usually indicates good prognosis without recurrence. However, we experienced a unique case of CAPNON that repeatedly recurred after resection.

Case Description:A 52-year-old woman with recurrence of an undiagnosed brain tumor, which was resected 12 years ago, was admitted to our institution. Three calcifying lesions along with perifocal edema were detected in the frontal interhemispheric fissure. We performed the second surgery for total removal of the lesions. The patient was diagnosed with CAPNON on the basis of the clinical features of the lesions and medical examination results. However, 14 months after the second surgery, recurrence occurred, and the patient has been followed up conservatively thereafter.

Conclusion:CAPNONs may indicate healing process associated with an unidentified agent. Maximum resection, including an unidentified agent, is necessary to prevent recurrence.

Keywords: Brain tumor, calcification, Calcifying pseudoneoplasms of the neuraxis, recurrence

INTRODUCTION

Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are rare, heavily calcified lesions of the central nervous system. These lesions are nonneoplastic and noninflammatory. To the best of our knowledge, only 62 cases of CAPNON have been reported, including the present case (intracranial: 44; spinal: 18), since it was first identified in 1978.[ 5 ] The natural course and precise etiology of these lesions remain unknown. CAPNONs cause a variety of symptoms that depend on their anatomical location, although seizures have often been reported. Previous case studies have indicated that total resection of the lesions is typically associated with good prognosis without recurrence. Herein, we describe the unique clinical course of CAPNON in a patient who required a second surgical resection 12 years after the initial procedure.

CASE HISTORY

Clinical course

A 40-year-old woman presented to our institution with excessive somnolence. She was diagnosed with brain tumor in the right frontal lobe parenchyma following computed tomography (CT) scan of the head. The primary lesion was a high-density mass of approximately 11 mm in diameter. The mass had signs of calcification, and it was surrounded by low-density lipomas [ Figure 1a ]. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) revealed a rim-enhanced mass. Moreover, edema was observed in the right frontal lobe parenchyma [ Figure 2 ].

Figure 1

(a) Head computed tomography (CT) scan prior to the first surgery. A high-density calcification associated with a lipoma is seen in the frontal interhemispheric fissure. Swelling is also observed in the brain parenchyma surrounding the lesion. (b) Head CT-scan after the first surgery. The calcification and perifocal edema have resolved

Figure 2

Initial magnetic resonance imaging. (a–c) A low-intensity area is seen on T1- and T2-weighted and fluid-attenuated inversion recovery images. (d) Gadolinium-enhanced T1-weighted images reveal a high-intensity area around the rim of the mass and edema in the right frontal lobe parenchyma

We performed the first surgery to confirm the tumor diagnosis. Only the largest mass was removed. After surgery, CT scan revealed that the edema in the right frontal lobe had resolved [ Figure 1b ]. No malignant histopathological changes were observed, although a definitive diagnosis was not established. The patient did not experience recurrence for 3 years after the first surgery; however, she did not undergo any medical examinations thereafter.

After 12 years, the patient was admitted to our institution because of tumor recurrence. Head CT-scan revealed three highly dense mass lesions in the frontal interhemispheric fissure [ Figure 3a ]. On MRI, low-intensity masses were observed on T1- and T2-weighted images. Further analysis revealed the presence of edema surrounding the lesions in the right frontal lobe parenchyma and corpus callosum. CT angiography indicated that the lesions surrounded the anterior cerebral artery (ACA) [ Figure 3b ]. Conventional cerebral angiography revealed no vascular lesions or blood supply associated with the masses. The lesions were diagnosed as the progression of a residual tumor. She underwent surgery again to excise the lesion to make an accurate diagnosis and reduce perifocal edema.

Figure 3

(a) Head computed tomography (CT) scan prior to the second surgery. Three high-density mass lesions are observed in the frontal interhemispheric fissure. Swelling is also observed in the brain parenchyma around the lesions. (b) 3D CT angiography reveals an area of calcification surrounding the anterior cerebral artery

Second surgery

We performed bifrontal re-craniotomy and approached the lesion by tracing the right ACA from distal to proximal in the interhemispheric fissure and identified a calcifying mass lesion surrounding the ACA [ Figure 4 ]. A lipoma was found near the lesion. However, no association was observed between the two. The calcifying mass was hard to remove using a suction tube. Therefore, the lesion was broken using forceps, and the pieces were gradually removed. Total resection of all three lesions from the artery surface was possible. Postoperative head CT-scan confirmed the absence of all calcifying masses as well as reduced brain edema around the lesion [ Figure 5a ]. The patient showed partial improvement.

Figure 4

Intraoperative photographs obtained during the second surgery. White calcified mass surrounding the artery in the interhemispheric fissure. *Branch of anterior cerebral artery

Figure 5

(a) Head computed tomography (CT) scan after the second surgery. Three high-density masses are removed without residual calcification. Edema around the lesions is reduced. (b–d) Head CT-scan 14, 18, and 24 months after the second surgery. A small high-density mass observed in the frontal interhemispheric cistern again. The mass lesion has grown to approximately 3.5 mm in diameter, and the size remains the same

Histopathological examination revealed a hypocellular nodule with calcium deposition. The lymphocyte or plasma cells infiltrated into the margin of the mass. No malignant change occurred [Figure 6a and b ]. The patient was diagnosed with CAPNON on the basis of clinical course and imaging histopathological examination results. Follow-up CT-scan was performed 14 months after the second surgery, and it revealed a small, high-density mass at the same location. The lesion was approximately 3.5 mm in diameter, and the size remained the same for 2 years [Figure 5b – d ]. Because the patient's neurological condition did not change, we continued to follow-up conservatively.

Figure 6

(a) Specimens obtained during the second surgery. A strong nodular calcification observed in small vessels. Epithelioid or spindle cells are also observed at the margin of the nodule [hematoxylin–eosin (HE) staining ×40]. (b) Specimens obtained during the first surgery. Multiple calcifications are observed in the brain parenchyma (HE staining ×40)

DISCUSSION

CAPNONs are rare, calcified lesions of the central nervous system; they can occur in extra-axial, intra-axial, and intraosseous locations. Moreover, these lesions have been referred to as fibro-osseous lesions, cerebral calculi, brain stones, and calcifying pseudo-tumors. By exerting pressure on adjacent structures, they may cause various symptoms according to their anatomical location.

Typically, CT scan shows a CAPNON as a well-demarcated, densely calcified mass, whereas MRI shows uniform low-intensity signals on both T1- and T2-weighted images. Rim enhancement may also be observed on Gd-MRI. Shrier et al. have reported that gadolinium enhancement occurs when a lesion is associated with a highly vascular fibrous stroma.[ 7 ] Few cases are associated with perifocal edema in the brain parenchyma. Aiken et al. have described these findings as typical radiological features of CAPNON that may help in differentiating it from other diseases.[ 1 ]

Considering the lack of mass effect, the presence of high-intensity areas around the lesions on T2-weighted images represents gliosis. However, in the present case, a high-intensity area was observed in the adjacent frontal lobe parenchyma prior to the first and second surgeries, which diminished after resection. High-intensity signal on T2-weighted images may indicate areas of edema. So far, six cases of perifocal edema associated with CAPNON have been identified, including the present case. Of them, two included extra-axial lesions that severely compressed the spinal cord and brain stem. Edema in these cases may be a result of the strong mass effect. However, in the present case, prior to the first surgery, no significant compression of the brain parenchyma had occurred. Therefore, an unidentified agent may have contributed to the lesion formation.

Histopathologically, CAPNON is typically characterized by hypocellular chondromyxoid matrix and variable amounts of fibrovascular stroma, which are often surrounded by palisading spindles or epithelioid cells and occasionally surrounded by multinucleate giant cells. Various states of calcification in the form of osseous metaplasia, scattered psammoma bodies, or calcium deposits have been observed in some cases; however, cellular proliferation and mitosis have not been reported. These features may be associated with the healing process that occurs in damaged tissues. Previous reports have indicated that epithelioid cells surrounding the lesion are positive for vimentin, possibly because of the presence of macrophages and lymphocytes and that most cells are positive for epithelial membrane antigen (EMA) and negative for glial fibrillary acidic protein and S-100. In the present case, epithelioid cells were only positive for vimentin.[ 9 ] Epithelial-derived EMA-positive cells may not be important for lesion formation. Multiple calcifications were observed in the brain parenchyma after the first surgery, although calcified masses after the second surgery were primarily located in the subarachnoid space surrounding the ACA.

In the present case, CAPNONs were accompanied by lipomas. Salim et al. reported a similar case with agenesis of the corpus callosum, and other cases of lipomas were observed in the interhemispheric cistern.[ 6 8 ] Intracranial lipomas are considered as congenital malformations, and they frequently occur in the interhemispheric cistern. Research has indicated that the abnormal differentiation of the meninx primitiva during subarachnoid cistern development causes the formation of intracranial lipomas, and they are frequently accompanied by other anomalies.[ 10 ]

Calcifications are usually observed in the collagenous capsule or parenchyma surrounding the lipoma.[ 11 ] However, in this case, lipomas and CAPNONs were not associated. Although their simultaneous occurrence may be coincidental, these meningeal abnormalities may indicate healing process and the progressive nature of CAPNONs.

Several authors have reported that CAPNONs progressed for 3–11 years.[ 2 3 9 ] In the present study, the lesion that remained after the first surgery had progressed for over 12 years and recurred 14 months after the second surgery. According to a previous report, the recurrence rate of CAPNON is 9 ]

After the second surgery, we considered that the residual lesions may regrow in the future, and these lesions should be removed along with the affected tissue as much as possible. Although total resection was performed, regrowth occurred after the second surgery. Therefore, removing the tissues surrounding the calcifications may also be necessary in reducing the effect of the unknown agents that may cause regrowth. However, health-care professionals must be cautious during aggressive resection to avoid injury in the adjacent structures.

Stienen et al. have analyzed the association between residual tumors and recurrence based on previous cases. However, they have observed no significant difference in terms of recurrence between the patients who underwent complete resection and the patient who underwent incomplete resection.[ 9 ] Total resection is not always required, particularly when lesions are associated with important neurological structures. In cases where total resection is not possible, medical treatment may control the lesion progression. Kwan et al.[ 4 ] have reported a case of symptomatic spinal CAPNON that resolved after indomethacin administration. However, the case may have been representative of a different disease because the lesion was not diagnosed using histological methods. Nevertheless, both medical treatment and surgery should be considered in CAPNON management.

CONCLUSIONS

This study presented the case of a patient who required a second surgery to remove a CAPNON 12 years after the initial surgery. CAPNONs may be indicative of the healing process associated with an unidentified agent. Although surgery is typically associated with good prognosis, residual lesions may regrow. Thus, maximum resection must be performed, particularly in younger patients. Due to possible recurrence, patients should undergo periodic follow-ups. Moreover, further accumulation of cases is required to elucidate the underlying pathophysiology of CAPNON.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

No funding was received for this research.

Conflicts of interest

There are no conflicts of interest.

References

1. Aiken AH, Akgun H, Tihan T, Barbaro N, Glastonbury C. Calcifying pseudoneoplasms of the neuraxis: CT, MR imaging, and histologic features. AJNR Am J Neuroradiol. 2009. 30: 1256-60

2. Jun C, Burdick B. An unusual fibro-osseous lesion of the brain. Case report. J Neurosurg. 1984. 60: 1308-11

3. Kerr EE, Borys E, Bobinski M, Shahlaie K. Posterior fossa calcifying pseudoneoplasm of the central nervous system. J Neurosurg. 2013. 118: 896-902

4. Kwan MK, Abdelhai AM, Beng Saw L, Wei Chan CY. Symptomatic calcifying pseudotumor of the thoracic spine that resolved with the indomethacin treatment: A case report. Spine (Phila Pa 1976). 2012. 37: E1676-9

5. Rhodes RH, Davis RL. An unusual fibro-osseous component in intracranial lesions. Hum Pathol. 1978. 9: 309-19

6. Salim AA, Wilson PJ, Cherukuri RK, McKenzie S, Buckland ME. An unusual association of calcifying pseudoneoplasm of the neuraxis with interhemispheric lipoma and agenesis of corpus callosum. Pathology. 2012. 44: 657-9

7. Shrier DA, Melville D, Millet D, Qian J, Millet D, Nelson C. Fibro-osseous lesions involving the brain: MRI. Neuroradiology. 1999. 41: 18-21

8. Smith DM, Berry AD. Unusual fibro-osseous lesion of the spinal cord with positive staining for glial fibrillary acidic protein and radiological progression: A case report. Hum Pathol. 1994. 25: 835-8

9. Stienen MN, Abdulazim A, Gautschi OP, Schneiderhan TM, Hildebrandt G, Lucke S. Calcifying pseudoneoplasms of the neuraxis (CAPNON): Clinical features and therapeutic options. Acta Neurochir. 2013. 155: 9-17

10. Truwit CL, Barkovich AJ. Pathogenesis of intracranial lipoma: An MR study in 42 patients. AJR Am J Roentgenol. 1990. 155: 855-64

11. Yilmaz N, Unal O, Kiymaz N, Yilmaz C, Etlik O. Intracranial lipomas–a clinical study. Clin Neurol Neurosurg. 2006. 108: 363-8

Abstract

Background:Schizencephaly is a rare defect which is identified as clefts that are lined with grey matter extending from the ependyma of the cerebral ventricles to the pia mater. An encephalocele occurs due to failure of neural tube closure resulting in a gap through which cerebrospinal fluid and meninges can bulge into a pouch. There have been rare instances when these two defects have presented simultaneously.

Case Description:We report a case of a 17-year-old child who was brought by his parents with complaint of swelling over his nose and forehead and aggressive behavior since birth. Magnetic resonance imaging findings were consistent with frontoethmoidal meningoencephalocele with schizencephaly. Lumbar drain was inserted and kept in place for 1 week followed by surgical correction of the defect. Our case is interesting because of delayed presentation as it is a rare entity and its association with schizencephaly.

Conclusion:Encephalocele association with schizencephaly is rare.

Keywords: Frontoethmoidal, hypertelorism, meningoencephalocele, schizencephaly

INTRODUCTION

Meningoencephalocele results from failure of rostral neuropore closure during the fourth week of development or primary defect of mesoderm or ectoderm and involves overlying tissues such as meninges and calvarias. The causative factors are genetic, drugs, nutritional, and environmental factors.[ 1 3 6 7 10 11 12 13 14 ] Schizencephaly is a rare disorder of neuronal migration which is characterized by a cerebrospinal fluid (CSF)-filled cleft extending from the surface of the cerebral hemispheres (pial) to the ventricular surface (ependyma). Schizencephaly results from abnormal neuronal migration during the first few weeks after gestation.[ 1 ] Collagen type IV alpha 1 chain (COL4A1) is an important gene associated with schizencephaly, and hedgehog signaling pathway and ectoderm differentiation are among its related pathways/super pathways. Brain, spinal cord, and cortex and growth/size/body region and mortality aging are the related phenotypes.[ 14 ]

CLINICAL PRESENTATION

A 17-year-old male child was brought by his parents with complaints of swelling over his forehead and nasal bridge since birth. He underwent primary closure of the swelling at the age of 35 days. Postoperatively, he presented with discharge of clear fluid from the site of incision and discharge was resolved with daily dressing. He remained well for 2 months but swelling gradually started to reappear. The size of the swelling has remained unchanged since then and he had not sought further medical care for this swelling. He was delivered full term at a local hospital. There was no significant antenatal history of intrauterine infections or teratogenic drug use.

On examination, we found a well-behaved child with hypertelorism and a fluctuant swelling over his forehead and nasal bridge approximately 6 × 4.8 cm. The swelling had positive transillumination test and positive cough impulse. There were no other associated anomalies. Milestones were up-to-date. He never went to school because of cosmetic deformity, and as per the parents, the child was extremely aggressive. Neurological examination revealed the extraocular movements to be normal and cranial nerves were grossly intact. There was no pronator drift or distal extremity weakness. He had memory impairment and reduced IQ.

Magnetic resonance imaging (MRI) was consistent with frontoethmoidal meningoencephalocele with schizencephaly [Figures 1 and 2 ]. The patient was planned for surgery to resect the redundant protruding tissue and close the defect with help from the plastic surgery team. Intraoperatively, the patient was found to have an atrophied left cerebral hemisphere. No histopathology was sent. Dura was reconstructed by fascia taken from the pericranium and fat taken from the abdomen, reconstruction of the nasal bridge was done from bone graft from calvaria which was fixed with plate, redundant skin was excised, and medial canthus was repositioned to correct hypertelorism. Lumbar drain was placed for a week postoperatively to prevent chances of postoperative leak following dural closure. It was planned to perform a rhinoplasty at a later date for him.

Figure 1

(a and b) Midline frontal cranial defect, more to the left with herniation of the meninges and brain tissue, representing frontoethmoidal encephalocele. The herniated brain tissue has hypotense T1 signals suggestive of gliosis. (c) The defect in coronal section

Figure 2

There is a grey matter lined cleft extending through the frontal region on the left down to the lateral ventricles, representing schizencephaly

DISCUSSION

The incidence of encephalocele globally is 1 per 35,000 births, but it is six times more common with 1 in every 6,000 births in South-East Asia.[ 7 ] The classification is based on the location – frontal, parietal, and occipital – and herniated contents such as meninges (meningeal) or meninges and parenchyma (meningoencephaloceles).[ 3 ] The most common cause is congenital defects secondary to improper closure of neural tube and it occurs in the midline; the cause can also be acquired or spontaneous occurring most commonly in cranial sutures.[ 3 10 ] Recent studies have shown a direct role for collagen IV in rare genetic conditions such as cerebral hemorrhage and porencephaly in infants.[ 8 ] In our case, the congenital meningoencephalocele is hypothesized considering the midline position of the lesion, although no clear documentation of such is found.

The case presented is more interesting due to its association with schizencephaly, a rare birth defect with incidence in the United States estimated at 1.54/100,000 births per year.[ 13 ] Morphologically, schizencephaly can be divided into two types. Type I (“closed lips”) is established when cerebral mantle has fused clefts with no relation to the ventricular system. Type II (“open lips”) is established when there is connection of lateral ventricle with subarachnoid space filled with CSF.[ 13 ] A patient with schizencephaly clinically presents with epilepsy, hydrocephalus, hemiparesis, delayed milestones, and psychomotor retardation.[ 6 ] Depending on the extent of cerebral cortex involvement, the outcome is variable. In the case presented, the patient had nonprogressive swelling with absence of any other findings such as mental retardation, epilepsy, or hemiparesis.

A recently reported study showed relationship between schizencephaly and mutation of the procollagen alpha-1 (IV) (COL4A1) gene.[ 5 ] In mice, COL4A1 mutation leads to ocular dysgenesis, cortical dysplasia, porencephaly, and myopathy;[ 4 9 ] approximately 20% of patients with schizencephaly have a COL4A1 mutation.[ 5 ] Patients with the COL4A1 mutation have shown to have an increased risk of cerebrovascular disease and intracerebral hemorrhage.[ 2 ] Studies have shown that meningoencephalocele has many contributing factors; in addition to genetic, environmental factor plays an important role.[ 9 ] However, there are two reported cases of familial recurrence of schizencephaly and meningoencephalocele, indicating that genetic factors are important to disease etiologies.[ 11 ]

Imaging studies help diagnosis of encephaloceles and schizencephaly. T1-weighted images reveal herniated parenchyma as hypotense and hyperintense on T2-weighted images.[ 3 ] Schizencephaly can be differentiated from porencephaly on imaging by the presence of gray matter lined cleft on MRI.[ 10 ] The clinical, radiographic, and pathologic findings of the patients confirm meningoencephalocele with schizencephaly. In fact, many of the findings such as patient's age, symptoms, and clinical course are very similar to a case reported in 2014.[ 11 ] However, two distinctions make this case notable. First, the patient's history of surgical correction of mass at age 35 days, and second the meningoencephalocele involvement of the frontal location. Management depends on the size and severity of the lesion leading to surgical correction by bone draft, and VP shunt is needed in cases where they are complicated by hydrocephalus.

CONCLUSION

Encephalocele association with schizencephaly is rare. While correcting large frontoethmoidal encephalocele, few important points should be considered such as slow decompression of CSF from the lesion and preservation of major veins.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. Alexander RC, Patkar AA, Lapointe JS, Flynn SW. Schizencephaly associated with psychosis. J Neurol Neurosurg Psychiatry. 1997. 63: 373-5

2. de Vries LS, Mancini GM. Intracerebral hemorrhage and COL4A1 and COL4A2 mutations, from fetal life into adulthood. Ann Neurol. 2012. 71: 439-41

3. Dobrin N, Mihaela B, Cost B, Tudorache C, Chiriac A, Poeat I. Acquired parietal intradiploic encephalocele. Case report and review of the literature. Romanian Neurosurg. 2011. p. 18-

4. Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005. 308: 1167-71

5. Harada T, Uegaki T, Arata K, Tsunetou T, Taniguchi F. Schizencephaly and porencephaly due to fetal intracranial hemorrhage: A report of two cases. Yonago Acta Med. 2018. 60: 241-5

6. Hung PC, Wang HS, Chou ML. Schizencephaly in children: A single medical center retrospective study. Pediatr Neonatol. 2018. 59: 1-8

7. Junaid M, Sobani ZA, Shamim AA, Kazi M, Khan MJ. Nasal encephaloceles presenting at later ages: Experience of Otorhinolaryngology Department at a tertiary care center in Karachi, Pakistan. J Pak Med Assoc. 2012. 62: 74-6

8. Khoshnoodi J, Pedchenko V, Hudson BG. Mammalian collagen IV. Microsc Res Tech. 2008. 71: 357-70

9. Labelle-Dumais C, Dilworth DJ, Harrington EP, de Leau M, Lyons D, Kabaeva Z. COL4A1 mutations cause ocular dysgenesis, neuronal localization defects, and myopathy in mice and Walker-Warburg syndrome in humans. PLoS Genet. 2011. 7: e1002062-

10. Lotfinia I, Mahdkhah A. Intradiploic meningoencephalocele, case report and review of literature. J Clin Exp Neurosci. 2013. 1: 10-

11. Mishra SS, Senapati SB, Das S, Deo RC. Large vertex meningoencephalocele with schizencephaly: An interesting case with neurosurgical challenge. J Pediatr Neurosci. 2014. 9: 136-8

12. Pitkin , Roy M. Folate and neural tube defect. Am J Clin Nutr. 2007. 85: 285S-8S

13. Stopa J, Kucharska-Miąsik I, Dziurzyńska-Białek E, Kostkiewicz A, Solińska A, Zając-Mnich M. Diagnostic imaging and problems of schizencephaly. Pol J Radiol. 2014. 79: 444-9

14. Yoneda Y, Haginoya K, Kato M, Osaka H, Yokochi K, Arai H. Phenotypic spectrum of COL4A1 mutations: Porencephaly to schizencephaly. Ann Neurol. 2013. 73: 48-57

Abstract

Background:Intraventricular and extraventricular central neurocytomas (CN) are equally frequent among 20–40-year-old men and women. However, sellar and suprasellar extraventricular CN are extremely rare, with only 12 reported cases.

Case Description:The authors report the case of a Brazilian 27-year-old man who presented with progressive vision loss during the last 4 years and serious bilateral keratoconus. We also review the epidemiological, clinical, radiological, pathological, and treatment features of the 12 reported cases. The patient developed left amaurosis and right temporal hemianopsia after undergoing bilateral corneal transplantation, which was detected during campimetry testing, and subsequently underwent magnetic resonance imaging, which revealed a huge hypophyseal tumor. Endocrinological evaluation revealed complete loss of pituitary function. The patient was referred to our department and underwent a two-step surgery (using transsphenoidal approach and cranio-orbital zygomatic approach) based on the diagnosis of an extraventricular central nervous system neurocytoma. Tumor removal was successful, and the patient was discharged at 3 weeks after admission to our department.

Conclusion:Although extraventricular neurocytomas of the brain are rare, careful preoperative consideration of its anatomy, pathophysiological features, and radiological features can enhance the treatment outcomes.

Keywords: Central nervous system, central nervous system neoplasms, central neurocytomas, neurocytoma

INTRODUCTION

Central neurocytomas (CN) are neuronal neoplasms with little aggressive behavior, which were initially described by Hassoun et al. in 1982 as an intraventricular tumor exhibiting histological similarities to oligodendrogliomas.[ 6 ] In 2000, the World Health Organization recognized the existence of extraventricular neurocytomas which received their own classification in 2007, although the intraventricular and extraventricular forms have strong cellular similarity and are both considered grade II tumors.[ 19 ] Approximately 0.1–1.0% of central nervous system neoplasms are CN, and approximately 10% of CN are considered extraventricular at presentation,[ 1 ] although there are 15 ] Thus, we report our experience with an extraventricular central nervous system neurocytoma, which occupied the sellar and suprasellar compartments in a young man and review the related literature.

CASE REPORT

History

A Brazilian 27-year-old man presented with a 4-year history of progressive bilateral vision loss caused by serious keratoconus. A neuro-ophthalmological evaluation revealed near-total left-eye amaurosis and moderate right-eye vision loss. The patient subsequently underwent bilateral corneal transplantation, although his condition progressed to left amaurosis and right temporal hemianopsia during the following 2 months. Thus, he underwent magnetic resonance imaging (MRI), which revealed a 79-cm³ bulky solid expansive lesion that involved the sellar and suprasellar compartments. The lesion had well-defined lobulated margins and a heterogeneous appearance without cystic or calcified components. There was no edema in the adjacent brain parenchyma. The imaging also revealed invasion of the sellar floor, lateral displacement of both internal carotid arteries, medial obliteration of the cavernous sinus, and extrinsic compression of the optic chiasm, hypothalamus, and third ventricle [ Figure 1 ]. Injection of a paramagnetic agent revealed diffuse and heterogeneous enhancement in the lesion. The preliminary diagnosis was a pituitary adenoma, and endocrinological evaluation revealed complete loss of pituitary function. Thus, the patient was referred to our department for evaluation and treatment.

Figure 1

Sagittal (left) and coronal (right) results from gadolinium-enhanced T1-weighted magnetic resonance imaging

Surgery

We initially selected the endoscopic endonasal approach, which revealed that the tumor was unexpectedly firm. We then sent a specimen for intraoperative pathological analysis. The results were inconclusive for macroadenoma, and we chose to stop the surgery until we received a conclusive result (approximately 60% of the tumor had been removed at that point). The patient did not experience any postoperative deficits during the 8 days until we received conclusive pathological diagnosis of CN without signs of malignancy. Immunohistochemical analysis revealed positive synaptophysin expression, a Ki-67 index of 0.8%, and negative AE1/AE3 expression [ Figure 2 ]. Based on these results, we performed a second surgery through the right cranio-orbital zygomatic approach, which resulted in successful microsurgical total resection of the tumor.

Figure 2

Histological sections show solid neoplastic cell proliferation, as well as noncohesive monomorphic small cells with round nuclei, fine chromatin, and well-distributed micronucleoli. The cytoplasm is poorly defined and a fine smooth granular vascular network is observed in the absence of necrosis or mitotic figures. Left: Hematoxylin and eosin staining (×400). Right: Immunohistochemical analysis revealed positive synaptophysin expression, a Ki-67 index of 0.8%, and negative AE1/AE3 expression (×400). Color versions are available as an online supplementary resource

Postoperative course

The patient was successfully treated for postoperative insipidus diabetes during a 1-week stay in the intensive care unit. He was subsequently discharged at 3 weeks after his admission to our department without any new neurological deficits and with improvement of the right-eye hemianopsia. Computed tomography (CT) at 1 week after the surgery revealed gross total resection of the tumor and mild ventricular dilation, without any manifestations of hypertensive hydrocephalus that required further treatment [ Figure 3 ]. Close outpatient follow-up was performed for 18 months, and the endocrinological workup revealed no improvement of pituitary function, although the patient did not experience any motor, sensory, or autonomic deficits. He continues to receive hormone replacement using testosterone, thyroid hormones, cortisol (prednisone), and exogenous vasopressin (desmopressin). The MRI scans from the 4-month and 18-month follow-ups revealed a hyperintense central sellar mass, which was compatible with an autologous fat graft that was used during the surgery to prevent fistula. These scans also revealed sellar contrast enhancement in both approaches, which was probably related to fibrosis [ Figure 4 ]. Thus, if any residual tumor was present, it did not grow during the last year of follow-up.

Figure 3

Gross total resection of the tumor was confirmed based on the sagital (a), coronal (b), and axial results (c) from the postoperative computed tomography

Figure 4

Four-month follow-up axial (a) and sagittal results (b) from T1-weighted magnetic resonance imaging revealed a hyperintense sellar mass, which was compatible with an autologous fat graft that was used to prevent nasal fistula. Findings from T1-weighted gadolinium-enhanced magnetic resonance imaging after 4 months (c) and 18 months (d)

DISCUSSION

Intraventricular and extraventricular CN are equally frequent in 20–40-year-old men and women.[ 4 6 15 ] The symptoms of extraventricular CN are generally nonspecific, including headache, dizziness, nausea, vision changes, and symptoms related to focal compression or intracranial hypertension.[ 4 6 7 13 15 ] The most common sites of extraventricular CN are the frontal lobe (30–46%), parietal lobe (11–23%), temporal lobe (13–20%), occipital lobe (2–11%), and cerebellum (6–9%).[ 2 7 11 13 15 ] Other less common locations include the thalamus, corpus callosum, sella, hypothalamus, pineal region, pons, spinal cord, and sphenoid wing.[ 1 4 15 19 ] Extraventricular CN usually appear as large solitary solid formations and may contain cystic components (40–71%), small calcifications (10–46%), or hemorrhagic foci (20–33%),[ 2 7 11 13 ] whereas CT usually reveals discreetly hyperdense solid portions, compared to the gray matter.[ 8 15 ] The preferred diagnostic modality is MRI as extraventricular CN can have discrete iso/hyperintense signals in both the T1- and T2-weighted images, and signs of restricted water diffusion may also be present. An intense and often heterogeneous enhancement is observed when using intravenous contrast agents, although 5–10% of cases do not exhibit enhancement. Spectroscopy reveals elevated levels of choline and reduced levels of N-acetyl-aspartate.[ 5 8 11 13 14 15 19 ]

The CN lesions can be grade III malignant variants (20–27%), which occur more often in older patients and typically exhibit greater infiltrative behavior, metastatic behavior, and unresectability. These lesions also frequently exhibit atypical cells, marked mitosis, vascular proliferation, necrosis, an MIB1 index of >2%, and a Ki-67 index of >2%.[ 1 2 5 7 8 9 11 13 15 ] The treatment of choice for extraventricular CN is total tumor excision, with adjuvant radiotherapy in cases of incomplete or questionable resection. However, there is lack of evidence regarding the ability of adjuvant radiotherapy to prevent recurrence or mortality in these cases.[ 2 5 7 9 11 13 15 ] The typical recurrence rates are 28% for intraventricular CN and 36% for extraventricular CN, with combined mortality rates of 4–6%. However, the atypical variants of intraventricular and extraventricular CN have a two-fold higher rate of unresectability, compared to typical CN, with mortality rates of 20–30% for intraventricular CN and 44% for extraventricular CN.[ 2 5 7 9 15 ]

Sellar and suprasellar extraventricular CN are extremely rare, and only 12 reported cases[ 4 5 10 11 12 14 16 17 18 19 ] were identified during our review of the PubMed and Bireme databases using the following keywords: neurocytoma, central, extraventricular, sellar, suprasellar, pituitary, and hypophysis. The clinical, radiological, pathological, and treatment features of these cases are shown in Table 1 . The overall age range was 23–64 years, with a higher incidence at the ages of 40–60 years (mean: 49.75 years, median: 50 years), although no sex-specific tendency was observed. Reduced visual acuity was the original complaint in 91.7% of the cases (the symptoms at presentation were not described in one case), with bitemporal or asymmetrical hemianopsia. Half of the reported cases had an interval of 2–12 months between their symptom development and diagnosis, although only six reports described the patient's hormonal status and only 66% of those patients had a slight increase in prolactin levels.

The reported cases were assessed using CT (66.7%) and/or MRI (100%), which revealed that the tumors were generally solid, bulky (a major axis of ≥3.0 cm), homogeneous, well-defined, and with limited or no swelling in the adjacent parenchyma. Two cases involved small-scattered calcifications, and four cases involved cystic components. All 10 patients with published imaging findings had invasion of the cavernous sinus. The CT scans commonly revealed discreetly iso/hyperdense tumors, and discrete iso/hyperintense findings were observed on approximately 58% of the T1- and T2-weighted images. All reported cases exhibited enhancement after the administration of an iodinated or paramagnetic intravenous contrast agent, with one-half of the results being prominent and nine cases exhibiting heterogeneous enhancement. Ten cases had detailed histological and immunohistochemical data, with generally positive results for synaptophysin expression (9/10 cases) and generally negative results for GFAP expression (8/10 cases). Two patients exhibited signs of malignancy (48 years and 64 years old), with MIB1 indexes of 3% and 4–10%, respectively. Only two patients had gross total tumor resection and eight patients had only partial resection, with 75% of those patients undergoing postoperative radiotherapy. Two patients with atypical extraventricular CN developed distant dural metastases or local recurrences. The main differential diagnosis was pituitary adenoma, especially the nonfunctioning type, which is usually isodense during CT, rarely contains calcification (5–7%) or hemorrhagic foci, and usually exhibits variable hypo/isointense signals during T1- and T2-weighted MRI. Furthermore, pituitary adenoma usually exhibits intense enhancement, but this is slightly slower than the rest of the pituitary gland.[ 3 20 ] Other diagnostic hypotheses include craniopharyngioma (more common in children, heterogeneous lesions, usually contains calcifications)[ 3 19 20 ] and meningiomas (more common in adults, homogeneous lesions, generally isodense during CT and isointense during T1-/T2-weighted MRI, can be calcified).[ 3 19 20 ] In all reported cases, an extraventricular neurocytoma was not suspected based on the preoperative imaging, which strongly indicated a giant pituitary tumor, as in the present case. Therefore, we believe that cases with a suspected huge pituitary lesion should always be screened based on the possibility that it is a sellar/suprasellar neurocytoma. We believe that total tumor resection should be the goal of surgical treatment, and that this goal is achievable using both craniotomy and endoscopic approaches.

In conclusion, we encountered a rare case of an extraventricular CN in the sellar/suprasellar region. Given the unusual nature of this case, we examined the 12 other reported cases and attempted to identify the features and signs that may help facilitate the diagnosis of these tumors in this region. Furthermore, we reported common histopathological characteristics and surgical approaches from those cases. We strongly believe that total tumor resection must be the primary goal of the surgery, and that combined surgical approaches can help facilitate this outcome.

Availability of data and materials

Not applicable.

Authors’ contributions

BN, LCTP, RAFC, RMQ, LGA, EQ, LHC, ISTP, CHM, and FBF contributed to conception and design as well as the acquisition, analysis, and interpretation of data. RMQ, LGA, ISTP, and CHM contributed to acquisition and interpretation of imaging data. BN, LCTP, RAFC, RMQ, LGA, EQ, LHC, ISTP, CHM, and FBF documented the patient's status and contributed to analysis and interpretation of data. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Acknowledgements

Not applicable.

References

1. Agarwal S, Sharma MC, Sarkar C, Suri V, Jain A, Sharma MS. Extraventricular neurocytomas: A morphological and histogenetic consideration. A study of six cases. Pathology. 2011. 43: 327-34

2. Brat DJ, Scheithauer BW, Eberhart CG, Burger PC. Extraventricular neurocytomas: Pathologic features and clinical outcome. Am J Surg Pathol. 2001. 25: 1252-60

3. Bresson D, Herman P, Polivka M, Froelich S. Sellar lesions/pathology. Otolaryngol Clin North Am. 2016. 49: 63-93

4. Chen H, Zhou R, Liu J, Tang J. Central neurocytoma. J Clin Neurosci. 2012. 19: 849-53

5. Choudhri O, Razavi SM, Vogel H, Li G. Atypical and rare variants of central neurocytomas. Neurosurg Clin N Am-. 2015. 26: 91-8

6. Donoho D, Zada G. Imaging of central neurocytomas. Neurosurg Clin N Am. 2015. 26: 11-9

7. Han L, Niu H, Wang J, Wan F, Shu K, Ke C. Extraventricular neurocytoma in pediatric populations: A case report and review of the literature. Oncol Lett. 2013. 6: 1397-405

8. Huang WY, Zhang BY, Geng DY, Zhang J. Computed tomography and magnetic resonance features of extraventricular neurocytoma: A study of eight cases. Clin Radiol. 2013. 68: e206-12

9. Kane AJ, Sughrue ME, Rutkowski MJ, Aranda D, Mills SA, Lehil M. Atypia predicting prognosis for intracranial extraventricular neurocytomas. J Neurosurg. 2012. 116: 349-54

10. Kawaji H, Saito O, Amano S, Kasahara M, Baba S, Namba H. Extraventricular neurocytoma of the sellar region with spinal dissemination. Brain Tumor Pathol. 2014. 31: 51-6

11. Liu K, Wen G, Lv XF, Deng YJ, Deng YJ, Hou GQ. MR imaging of cerebral extraventricular neurocytoma: A report of 9 cases. AJNR Am J Neuroradiol. 2013. 34: 541-6

12. Makis W, McCann K, McEwan AJ. Extraventricular neurocytoma treated with 177Lu DOTATATE PRRT induction and maintenance therapies. Clin Nucl Med Mar. 2015. 40: 234-6

13. Patil AS, Menon G, Easwer HV, Nair S. Extraventricular neurocytoma, a comprehensive review. Acta Neurochir (Wien). 2014. 156: 349-54

14. Peng P, Chen F, Zhou D, Liu H, Li J. Neurocytoma of the pituitary gland: A case report and literature review. Biomed Rep. 2015. 3: 301-3

15. Sweiss FB, Lee M, Sherman JH. Extraventricular neurocytomas. Neurosurg Clin N Am. 2015. 26: 99-104

16. Wang J, Song DL, Deng L, Sun SY, Liu C, Gong DS. Extraventricular neurocytoma of the sellar region: Case report and literature review. Springerplus. 2016. 5: 987-

17. Wang Y, Tao R, Liu B. Response to: Extraventricular neurocytoma of the sellar region. Br J Neurosurg. 2013. 27: 551-2

18. Xiong Z, Zhang J, Li Z, Jiang J, Han Q, Sun S. Acomparative study of intraventricular central neurocytomas and extraventricular neurocytomas. J Neurooncol. 2015. 121: 521-9

19. Yang GF, Wu SY, Zhang LJ, Lu GM, Tian W, Shah K. Imaging findings of extraventricular neurocytoma: Report of 3 cases and review of the literature. AJNR Am J Neuroradiol. 2009. 30: 581-5

20. Zee CS, Go JL, Kim PE, Mitchell D, Ahmadi J. Imaging of the pituitary and parasellar region. Neurosurg Clin N Am. 2003. 14: 55-80