Journal of Neuro-Ophthalmology, June 2010, Volume 30, Issue 2

Cavernous Malformation of the Optic Nerve Mimicking Optic Neuritis

A 30-year-old woman developed acute visual loss and optic disc elevation in the left eye after breastfeeding her second son. The initial diagnosis was optic neuritis. However, MRI showed a lesion in left intraorbital and intracanalicular optic nerve and several cerebral lesions with imaging features of cerebral cavernous malformations (CCMs). Genetic testing was positive for abnormalities known to predispose to CCMs in the patient and her father, who also showed MRI evidence of CCMs. During a 44-month follow-up period in which no intervention took place, the patient's vision in the affected eye fluctuated but eventually became extinguished. Serial MRIs did not always show lesion changes that explained the visual deterioration. In familial CCM, pregnancy might be a ""second hit"" to genetically predisposed tissue.

Cavernous Malformation of the Optic Nerve Mimicking Optic Neuritis Alfonso Cerase, MD, Rossella Franceschini, MD, Stefania Battistini, MD, PhD, Ignazio Maria Vallone, MD, Silvana Penco, MSc, PhD, Carlo Venturi, MD Abstract: A 30-year-old woman developed acute visual loss and optic disc elevation in the left eye after breast-feeding her second son. The initial diagnosis was optic neuritis. However, MRI showed a lesion in left intraorbital and intracanalicular optic nerve and several cerebral lesions with imaging features of cerebral cavernous malformations (CCMs). Genetic testing was positive for abnormalities known to predispose to CCMs in the patient and her father, who also showed MRI evidence of CCMs. During a 44-month follow-up period in which no inter-vention took place, the patient's vision in the affected eye fluctuated but eventually became extinguished. Serial MRIs did not always show lesion changes that explained the visual deterioration. In familial CCM, pregnancy might be a ‘‘second hit'' to genetically predisposed tissue. Journal of Neuro-Ophthalmology 2010;30:126-131 doi: 10.1097/WNO.0b013e3181ceb428 2010 by North American Neuro-Ophthalmology Society The distribution of cerebral cavernous malformations (CCMs) follows the volume of the neuraxis, such that 80% are supratentorial, 15% are infratentorial, and 3%-5% are within the spinal cord (1,2). Cranial nerve CCMs constitute a distinctly rare subset, accounting for no more than 1% (3-10). The optic chiasm is most frequently affected (4,7,8) but the prechiasmatic optic nerve extremely rarely (11). We report a young woman presenting with left optic neuropathy that mimicked optic neuritis, but in whom neuroimaging showed multiple cerebral CCMs with familial features. CASE REPORT One week after an 8-month period of breastfeeding her second son, a 30-year-old woman awoke with visual im-pairment of the left eye. A diagnosis of optic neuritis was made elsewhere. When vision did not improve after 4 retrobulbar corticosteroid injections, she was admitted to our institution for an evaluation. Our examination disclosed a visual acuity of 20/20 in the right eye and 20/200 in the left eye. There was a left afferent pupillary defect. Ophthalmoscopy showed no abnormalities in the right eye and optic disc edema in the left eye (Fig. 1A). Visual field testing showed no abnormalities in the right eye and blind spot enlargement in the left eye. Orbital ultrasound showed only elevation of the left optic nerve head. Fluorescein angiography showed no leakage (Fig. 1B). Visual evoked potentials showed no abnormalities upon stimulating the right eye, and increased latency and a reduced P100 amplitude upon stimulating the left eye. These findings were considered suspicious for left optic neuritis. However, brain and orbit MRI (Fig. 2) showed 2 lesions consistent with CCMs, 1 type III in the left temporal lobe and 1 type II in the right frontal lobe (12), as well as thickening and abnormal signal intensity of the deep in-traorbital and intracanalicular portions of the left optic nerve The optic nerve lesion was considered consistent with a type I CCM. CT did not show calcification in any of the lesions. Treatment included a 3-day intravenous bolus of prednisone (1 g/day), followed by a month of oral Unit of Neuroimaging and Neurointervention, Department of Neurosciences, and Interdepartmental Center of Magnetic Reso-nance (AC, IMV, CV), Azienda Ospedaliera Universitaria Senese, Department of Ophthalmology and Neurosurgery, Section of Ophthalmology (RF), and Department of Neurosciences, Section of Neurology (SB), University of Siena, ‘‘Santa Maria alle Scotte'' General Hospital, Siena, Italy; and Laboratory of Clinical Chemistry and Clinical Pathology, Medical Genetics (SP), Niguarda Ca'Granda Hospital, Milano, Italy. This work was presented in part at the XXXVIII Congress of the Italian Society of Neurology, Firenze, Italy, October 13-17, 2007. Address correspondence to Alfonso Cerase, MD, Unit of Neuro-imaging and Neurointervention, Department of Neurosciences, Azienda Ospedaliera Universitaria Senese, Policlinico ‘‘Santa Maria alle Scotte,'' Viale Mario Bracci, 16, 53100 Siena, Italy; E-mail: [e-mail] 126 Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 Original Contribution Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. administration of prednisolone (50 mg/day), which was then gradually tapered. This treatment resulted in slow improvement in visual acuity of the left eye. The patient had 2 children, 1 aged 7 years and 1 aged 9 months, as well as a sister aged 25 years, all of whom were apparently healthy. The patient's father, aged 57 years, had purple-black, round, raised, nontender, angioma-like cu-taneous lesions in his right leg noted from birth. With age, these lesions had increased in size and easily bled if trau-matized. Biopsy of a right leg lesion showed cavernous hemangioma and MRI (Fig. 3) showed multiple type III and IV CCMs (12) in the brain. Genetic analysis of the proband and her father showed a novel pathogenic G235R mutation in the KRIT1 gene (13). The genetic test results were negative in the proband's sister. A repeat MRI of the proband 4 months later showed reduction in size and signal intensity of the left optic nerve lesion. Four months later, ophthalmologic examina-tion disclosed further improvement of visual acuity in the affected eye to 20/25 with reduction in blind spot enlargement. However, 5 months later visual acuity in the left eye had regressed to 20/40, and ophthalmoscopy showed increased left optic disc swelling and visual fields showed enlargement of the blind spot. MRI (Fig. 4A) disclosed more left optic nerve thickening and abnormal signal intensity. Oral administration of acetazolamide (250 mg/day) and some days later oral administration of prednisolone (50 mg/ day) for 1 month with subsequent tapering resulted in complete visual recovery. Yet 5 months later, the visual acuity of the left eye regressed again, this time to finger counting. MRI (Fig. 4B) did not show acute or subacute changes. Treatment included a 3-day intravenous bolus of prednisone (1 g/day) and oral administration of acetazol-amide (250 mg/day), followed by oral administration of 50 mg/day prednisolone for 1 month with subsequent tapering. However, 1 month after treatment had been started, visual acuity had declined to hand movements in the left eye. MRI (Fig. 4C) now showed an increase in the size and signal of the intraorbital left optic nerve CCM. Seven months later, visual acuity was no light perception in the left eye. At this stage, MRI showed regression of the optic nerve CCM. Eight and 20 months later, MRIs were unchanged. DISCUSSION We have described a patient who had sudden visual loss in 1 eye with optic disc elevation but no fluorescein leakage that mimicked optic neuritis but proved to be a presumed CCM in conjunction with multiple cerebral CCMs. No intervention occurred, and over several months of fluctuations, visual function was eventually extinguished in that eye. For CCMs in any location in the neuraxis, MRI is the method of choice for diagnosis, classification, and follow-up (1,2,12). T2* MRI provides the definitive evaluation of the total number of CCMs because of the susceptibility artifacts from microscopic deposits of hemosiderin in chronic phases of hemorrhage. On the other hand, the combination of T1 and T2 images is best to show the acute and subacute hemorrhages. A major limitation of T2* images is the severe signal loss induced by macroscopic field inhomogeneity and diamagnetic susceptibility artifacts at interfaces, which are FIG. 1. A. Red-free fundus photography of the proband at diagnosis shows blurred left optic disc margins (black arrows) compared with the normal right optic disc (white arrows). B. Fluorescein angiography in the early (0.16 second) phase (left) and late (4.37 minutes) phase (right) shows pooling of the left optic disc margins without leakage. Original Contribution Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 127 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. more common at the skull base. Type I CCMs appear homogeneously hyperintense on T1 images due to met-hemoglobin predominance in subacute hemorrhage. Type II CCMs are heterogeneous on both T1 and T2 sequences, showing a reticulated mixed signal core (‘‘popcorn''). Type III CCMs are hypointense to isointense on T1 images, hypointense on T2 images, and markedly hypointense on T2* images due to hemosiderin predominance. Type IV CCMs show tiny, punctate foci that are hypointense on T1 and T2 images, often multiple, and best seen on T2* images (2,12). Type IV CCMs rarely enhance, simulating capillary telangiectasias (14,15). None of these 4 MRI appearances is immune from changes into another MRI appearance, and the evolution is not predictable on the basis of the original morphology (1,15,16). Several authors have noted that patients with type I and type II CCMs are more commonly symptomatic com-pared with patients who have type III and type IV CCMs (12,16-18). This seems consistent with the history of our patient, but other authors did not find any significant correlation between symptoms and serial MRI changes (15). Perilesional edema and mass effect may correlate with the patient's clinical manifestations. Although our patient was originally believed to have optic neuritis, the MRI signal characteristics of the lesion FIG. 2. Brain MRI of the proband at diagnosis. Precontrast fat-suppressed axial FLAIR MRI (A), T2 coronal MRI (B), and T1 coronal MRI (C) show enlargement and high signal intensity of the deep intraorbital and intracanalicular left optic nerve (white arrows). Postcontrast fat-suppressed T1 coronal MRI (D) shows that the lesion does not enhance. T2* (gradient echo) coronal MRI (E) shows a cavernoma in the right frontal lobe (black arrow). FIG. 3. T2* (gradient echo) axial MRI of the proband's father shows multiple cavernous malformations. Original Contribution 128 Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. were not consistent with that diagnosis. In optic neuritis, the optic nerve shows abnormal signal intensity including low or normal signal intensity on T1 images, high signal intensity on T2 images, and enhancement (19,20). The optic nerve is swollen in the acute phase and may undergo atrophy in the chronic phase (21). In the acute phase, optic neuritis may also present with optic nerve sheath dilatation, probably due to interruption of the communication between the subarachnoid space of the diseased optic nerve and the chiasmal cistern. Optic nerve sheath enhancement suggests meningeal inflammation, as observed in pathologic studies (22). The MRI findings were also not consistent with a tumor of the optic nerve or optic nerve sheath (23-28), including hemangioblastoma, a benign vascular tumor commonly associated with von Hippel-Lindau disease. Most heman-gioblastomas that occur within the orbit are located in the retina, although locations within the optic nerve have been reported. Hemangioblastomas generally show an enhancing portion (23-26). Cerebral CCMs, which account for 5%-20% of all cerebral vascular malformations, are reported in 0.3% of large autopsy studies, and 0.4%-0.9% of large prospective cohort studies of the general population. Most (50%-80%) CCMs are apparently sporadic. A single CCM may be found in roughly 70% of patients with sporadic CCMs and in 8%-19% of patients with familial disease. Multiple CCMs, indicative of familial forms (1,2,12,13,18,29), are genetically heterogeneous, exhibiting an autosomal domi-nant inheritance with different preliminary estimates of disease penetrance at 3 loci: KRIT1/CCM1, CCM2, and PDCD10/CCM3, mapped to 7q, 7p, and 3q, respectively. These loci account for approximately 40%, 20%, and 40% of non-Hispanic familial cases, respectively. Familial CCMs have been shown to have a 0.2%-0.4% incidence per patient per year of de novo lesion formation (1,2,12,18). For this phenomenon, 2 possible develop-mental mechanisms have been postulated: a Knudson 2-hit mechanism and a haploinsufficiency mode (30-33). De novo formation has been associated with previous irradia-tion, viruses, hormonal influences in pregnancy, endothelial proliferation, and angiogenesis (2,34-36). Notably, CCMs have the capacity for endothelial proliferation and neo-angiogenesis, which may also explain the development of new CCMs along a biopsy tract (35). A small amount of cavernous tissue transplanted to any point along the biopsy tract may induce the transformation of normal capillaries or the growth of new, fragile vessels or recanalization by nearby parenchymal vessels (36). In the patient reported here, the visual loss started 8 days after the end of breast-feeding. Some authors suggested that pregnancy is a risk factor for growth of intraorbital tumors (37), hemorrhage from cerebral vascular malformations (38) or CCMs (17,39-43), or onset of CCM-related seiz-ures (44), resulting in an aggressive clinical course, especially in the first trimester of pregnancy. However, another series (45) did not find an increase in the risk of CCM hemor-rhage in pregnant women, and the paucity of cases in the literature would argue against this hypothesis. Although the biologic effects on CCMs of hormonal and hemodynamic alterations experienced during pregnancy are unknown, in the patient reported here they might have represented a ‘‘second hit'' to genetically predisposed tissue. Symptoms of CCMs are thought to result from recurrent episodes of hemorrhage and CCM growth. However, these changes need not cause clinical manifestations. Hemorrhage is characteristically confined within the lesion and may not result in neurologic deficits unless it creates a mass effect. Asymptomatic episodes of small hemorrhage may thus occur (46). On the other hand, clinical deterioration may also occur without any evidence of lesion change on MRI (47). This phenomenon seems consistent with the fact that in anterior visual pathway CCMs, the rise and fall of visual acuity is not necessarily associated with neuroimaging documentation of recurrent tissue hemorrhage (48), as exemplified by our patient. Surgery may be indicated in symptomatic and accessible CCMs in noneloquent parenchyma. Symptomatic patients with inaccessible lesions are usually observed, despite the often poor natural history. The role of stereotactic radio-surgery in the treatment of CCMs is still debated (2,4). In our patient, the involvement of the proximal intraorbital and intracanalicular segments of the optic nerve precluded surgery or irradiation. FIG. 4. Brain MRI follow-up in the proband. T2* (gradient echo) axial images show swelling and high signal intensity of the left optic nerve (arrows) 9 months after diagnosis (A), thinning and normal signal intensity 15 months after diagnosis (B), and relapse of swelling and high signal intensity 16 months after diagnosis (C). Open arrowheads indicate a cav-ernous malformation in the left temporal lobe. Original Contribution Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 129 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. ACKNOWLEDGMENTS We thank Roberto Faleri from the Central Library, School of Medicine, University of Siena, Policlinico ‘‘Santa Maria alle Scotte,'' Siena, Italy, for providing important references for the preparation of this scientific article and Tiziana Caselli from the Unit of Neuroimaging and Neuro-intervention, Department of Neurosciences, Azienda Ospedaliera Universitaria Senese, ‘‘Santa Maria alle Scotte'' General Hospital, Siena, Italy, for her technical help in preparing the figures. REFERENCES 1. Rivera PP, Willinsky RA, Porter PJ. Intracranial cavernous malformations. Neuroimag Clin N Am. 2003;13:27-40. 2. Raychaudhuri R, Batjer HH, Awad IA. Intracranial cavernous angioma: a practical review of clinical and biological aspects. Surg Neurol. 2005;63:319-328. 3. Matias-Guiu X, AlejoM, Sole T, Ferrer I, Noboa R, Bartumeus F. Cavernous angiomas of the cranial nerves. Report of two cases. J Neurosurg. 1990;73:620-622. 4. Deshmukh VR, Albuquerque FC, Zabramski JM, Spetzler RF. Surgical management of cavernous malformation involving the cranial nerves. Neurosurgery. 2003;53: 352-357. 5. Patro S, Kesavadas C, Kapilamoorthy TR. Right third nerve cranial palsy caused by extra-axial cavernoma in a patient with multiple intracranial cavernomas. NRJ Neuroradiol J. 2008;21:192-195. 6. Surucu O, Sure U, Mittelbronn M, Meyermann R, Becker R. Cavernoma of the trochlear nerve. Clin Neurol Neurosurg. 2007;109:791-793. 7. Hassler W, Zentner J, Wilhelm H. Cavernous angiomas of the anterior visual pathways. J Clin Neuroophthalmol. 1989; 9:160-164. 8. Hempelmann RG, Mater E, Schro¨der F, Scho¨n R. Complete resection of a cavernous haemangioma of the optic nerve, the chiasm, and the optic tract. Acta Neurochir (Wien). 2007;149:699-703. 9. Mouillon M, Romanet JP, Hermann M, Pasquier B, Hemangiome caverneux du nerf optique intra-canalaire. Bull Soc Opht France. 1984;84:875-879. 10. Patikulsila D, Visaetsilpanonta S, Sinclair SH, Shields JA. Cavernous hemangioma of the optic disk. Retina. 2007;27: 391-392. 11. Leibovitch I, Pakrou D, Selva D, Crompton J. Neuro-ophthalmic manifestations of intracranial cavernous hemangiomas. Eur J Ophthalmol. 2006;16:148-152. 12. Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, Brown B, Rigamonti D, Brown G. The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg. 1994;80: 422-432. 13. Battistini S, Ricci C, Ratti R, Cerase A, Franceschini R, Vallone IM, Patrosso MC, Miracco C, Marocchi A Penco S. A new Krit1 gene mutation in a family with cerebral cavernous malformation (CCM) associated with intraorbital optic nerve and cutaneous cavernous angiomas. Neurol Sci. 2007;28(Suppl):S336. 14. Barker FG, 2nd Amin-Hanjani S, Butler WE, Lyons S, Ojemann RG, Chapman PH, Ogilvy CS. Temporal clustering of hemorrhages from untreated cavernous malformations of the central nervous system. Neurosurgery. 2001;49: 15-22. 15. Willinsky RA, Harper W, Wallace MC, Kucharczyk W, Montanera W, Mikulis D, terBrugge K. Follow-up MR of intracranial cavernomas: the relationship between haemorrhagic events and morphology. INR Intervent Neuroradiol. 1996;2:127-135. 16. Clatterbuck RE, Elmaci I, Rigamonti D. The nature and fate of punctate (type IV) cavernous malformations. Neurosurgery. 2001;49:26-32. 17. Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg. 1991;75:709-714. 18. Labauge P, Brunereau L, Levy C, Laberge S, Houtteville JP. The natural history of familial cerebral cavernomas: a retrospective MRI study of 40 patients. Neuroradiology. 2000;42:327-332. 19. Jackson A, Sheppard S, Laitt RD, Kassner A, Moriarty D. Optic neuritis: MR imaging with combined fat- and water-suppression techniques. Radiology. 1998;206:57-63. 20. Boretius S, Gadjanski I, Demmer I, Ba¨hr M, Diem R, Michaelis T, Frahm J. MRI of optic neuritis in a rat model. Neuroimage. 2008;41:323-334. 21. Hickman SJ, Toosy AT, Jones SJ, Altmann DR, Miszkiel KA, MacManus DG, Barker GJ, Plant GT, Thompson AJ, Miller DH. A serial MRI study following optic nerve mean area in acute optic neuritis. Brain. 2004;127:2498-2505. 22. Hickman SJ, Miszkiel KA, Plant GT, Miller DH. The optic nerve sheath on MRI in acute optic neuritis. Neuroradiology. 2005;47:51-55. 23. Miller NR. Primary tumors of the optic nerve and its sheath. Eye. 2004;18:1026-1037. 24. Ohtsuka K, Hashimoto M, Suzuki Y. Review of 244 orbital tumors in Japanese patients during a 21-year period: origins and locations. Jpn J Ophthalmol. 2005;49:49-55. 25. Chung EM, Specht CS, Schroeder JW. From the archives of the AFIP: Pediatric orbit tumors and tumorlike lesions: neuroepithelial lesions of the ocular globe and optic nerve. Radiographics. 2007;27:1159-1186. 26. Smoker WR, Gentry LR, Yee NK, Nerad JA. Vascular lesions of the orbit: more than meets the eye. Radiographics. 2008; 28:185-204. 27. Sawaya RA, Sidani C, Farah N, Hourani-Risk R. Presumed bilateral optic nerve sheath meningiomas presenting as optic neuritis. J Neuroophthalmol. 2008;28:55-57. 28. Taylor T, Jaspan T,Milano G, Gregson R, Parker T, Ritzmann T, Benson C, Walker D. Radiological classification of optic pathway gliomas: experience of a modified functional classification system. Br J Radiol. 2008;81:761-766. 29. Battistini S, Rocchi R, Cerase A, Citterio A, Tassi L, Lando G, Patrosso MC, Galli R, Brunori P, Sgro` DL, Pitillo G, Lo Russo G, Marocchi A, Penco S. Clinical, magnetic resonance imaging, and genetic study of 5 Italian families with cerebral cavernous malformation. Arch Neurol. 2007; 64:843-848. 30. Knudson AG. Hereditary cancer: two hits revisited. J Cancer Res Clin Oncol. 1996;122:135-140. 31. Laurans MS, DiLuna ML, Shin D, Niazi F, Voorhees JR, Nelson-Williams C, Johnson EW, Siegel AM, Steinberg GK, Berg MJ, Scott RM, Tedeschi G, Enevoldson TP, Anson J, Rouleau GA, Ogilvy C, Awad IA, Lifton RP, Gunel M. Mutational analysis of 206 families with cavernous malformations. J Neurosurg. 2003;99:38-43. 32. Plummer NW, Zawistowski JS, Marchuk DA. Genetics of cerebral cavernous malformations. Curr Neurol Neurosci Rep. 2005;5:391-396. 33. Pagenstecher A, Stahl S, Sure U, Felbor U. A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. Hum Mol Genet. 2009;18:911-918. 34. Pozzati E, Acciarri N, Tognetti F, Marliani F, Giangaspero F. Growth, subsequent bleeding, and de novo appearance of cerebral cavernous angiomas. Neurosurgery. 1996;38: 662-669. 35. Ogilvy CS, Moayeri N, Golden JN. Appearance of a cavernous hemangioma in the cerebral cortex after biopsy of a deeper lesion. Neurosurgery. 1993;33:307-309. 36. Sure U, Freman S, Bozinov O, Benes L, Siegel AM, Bertalanffy H. Biological activity of adult cavernous malformations: a study of 56 patients. J Neurosurg. 2005; 102:342-347. Original Contribution 130 Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited. 37. Sugo N, Yokota K, Nemoto M, Hatori T, Kano T, Goto S, Seiki Y. Accelerated growth of an orbital schwannoma during pregnancy. J Neuroophthalmol. 2007;27:45-47. 38. Marcos Toledano MM, Portilla Cuenca JC, Porras Estrada LF, Go´mez Perals L. Pseudo-emesis gravidarum caused by complicated cerebral venous angioma [in Spanish]. Neurologia. 2006;21:92-95. 39. Brown RD Jr. Epidemiology and natural history of vascular malformations of the CNS. In: Awad IA, Jafar JJ, Rosenwasser RH, eds. Vascular Malformations of the Central Nervous System. Philadelphia: Lippincott Williams & Wilkins; 1999:129-148. 40. Flemming KD, Goodman BP, Meyer FB. Successful brainstem cavernous malformation resection after repeated hemorrhages during pregnancy. Surg Neurol. 2003;60: 545-548. 41. Van Lindert EJ, Tan TC, Groetenhuis JA, Wesseling P. Giant cavernous hemangiomas: report of three cases. Neurosurg Rev. 2007;30:83-92. 42. Pe´rez Lo´pez-Fraile I, Tapiador Sanjua´n MJ, Eiras Ajuria J, Gime´nez Mas JA. Cerebral cavernous angiomas in pregnancy. Two cases and a review of literature [in Spanish]. Neurologia. 1995;10:242-245. 43. Warner JE, Rizzo JF, 3rd, Brown EW, Ogilvy CS. Recurrent chiasmal apoplexy due to cavernous malformation. J Neuroophthalmol. 1996;16:99-106. 44. Aladdin Y, Gross DW. Refractory status epilepticus during pregnancy secondary to cavernous angioma. Epilepsia. 2008;49:1627-1629. 45. Maraire JN, Awad IA. Intracranial cavernous malformations: lesion behavior and management strategies. Neurosurgery. 1995;37:591-605. 46. Tung H, Giannotta SL, Chandrasoma PT, Zee CS. Recurrent intraparenchymal hemorrhages from angiographically occult vascular malformations. J Neurosurg. 1990;73:174-180. 47. Porter PJ, Willinsky RA, Harper W, Wallace MC. Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg. 1997;87:190-197. 48. Lehner M, Fellner FA, Wurm G. Cavernous haemangiomas of the anterior visual pathways. Short review on occasion of an exceptional case. Acta Neurochir (Wien). 2006;148:571-578. Original Contribution Cerase et al: J Neuro-Ophthalmol 2010; 30: 126-131 131 Copyright © North American Neuro-ophthalmology Society.Unauthorized reproduction of this article is prohibited.