Familial Cavernous Hemangioma

A 30-year-old woman presented with diplopia after resection of an intracranial cavernous malformation. Fundus examination showed an asymptomatic intraocular cavernous hemangioma of the retina. Clinicians should be aware of the potential coexistence of intraocular and intracranial cavernous malformations; the presence of both should suggest familial etiology. As with other intracranial and intraocular vascular lesions (e.g., arteriovenous malformation in Wyburn-Mason syndrome, retinal hemangioblastoma in von Hippel Lindau disease, and choroidal hemangioma in Sturge-Weber syndrome), the presence of a vascular lesion in either location should prompt evaluation for additional pathology.

Photo Essay Section Editors: Melissa W. Ko, MD Dean M. Cestari, MD Peter Quiros, MD Familial Cavernous Hemangioma Guadalupe Torres, BS, Ashwini T. Kini, MD, Bayan Al Othman, MD, Andrew G. Lee, MD FIG. 1. Left eye fundus periphery demonstrating multiple superficial grape-like hemorrhagic clusters in the superonasal quadrant, suggestive for cavernous hemangioma of retina. Abstract: A 30-year-old woman presented with diplopia after resection of an intracranial cavernous malformation. Fundus examination showed an asymptomatic intraocular cavernous hemangioma of the retina. Clinicians should be aware of the potential coexistence of intraocular and intracranial cavernous malformations; the presence of both should suggest familial etiology. As with other intracranial Baylor College of Medicine (GT), Houston, Texas; Department of Ophthalmology (ATK, BAO, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; The Houston Methodist Research Institute (AGL), Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas Medical Branch, Galveston, Texas; University of Texas MD Anderson Cancer Center (AGL), Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Suite Scurlock 450, Houston, TX 77030; E-mail: [e-mail] 262 and intraocular vascular lesions (e.g., arteriovenous malformation in Wyburn-Mason syndrome, retinal hemangioblastoma in von Hippel Lindau disease, and choroidal hemangioma in Sturge-Weber syndrome), the presence of a vascular lesion in either location should prompt evaluation for additional pathology. Journal of Neuro-Ophthalmology 2020;40:262-264 doi: 10.1097/WNO.0000000000000778 © 2019 by North American Neuro-Ophthalmology Society A 30-year-old woman was evaluated for diplopia after a left craniotomy for removal of a temporal cavernoma. Neuro-ophthalmologic examination revealed a fourth nerve palsy. Dilated fundus examination showed multiple superficial grape-like hemorrhagic clusters in the superonasal quadrant of her left fundus, suggestive of cavernous hemangioma of the retina (Fig. 1). She had initially presented to the emergency department 4 years before the craniotomy after a witnessed Torres et al: J Neuro-Ophthalmol 2020; 40: 262-264 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay FIG. 2. Preoperative MRI. A. T1 axial image demonstrating acute hemorrhage in the left temporal lobe. B and C. Axial MRI with gradient-echo sequence demonstrating multiple bilateral and diffuse focal regions of susceptibility induced signal loss of variable size, consistent with cavernous malformations. tonic-clonic seizure. At that time, the patient was found to have a hemorrhage over her left parietal cortex on computed tomography. This was confirmed by MRI, which revealed multiple foci of both acute and chronic hemorrhage, concerning for cerebral cavernomas (Fig. 2). Pathology of the resected specimen showed thin-walled vessels with collagenous adventitia and no intervening brain parenchyma; the elastin stain confirmed lack of uniform elastic lamina. All findings were thus consistent with a cavernous malformation (Fig. 3A, B). The patient was followed by the neurology service for control of her seizures; she had serial MRIs to monitor the intraparenchymal lesions, which remained stable. DISCUSSION The prevalence of familial cerebral cavernous malformation (FCCM) is approximately 0.5% of the population (1). It has an autosomal dominant inheritance pattern and most commonly manifests in the brain, skin, and eyes (1,2). Patients usually present with seizures or focal neurologic deficits due to cerebral hemorrhages (1). The ocular man- ifestation of FCCM is usually retinal cavernous hemangiomas, with an estimated incidence of approximately 5% (1,3). However, central nervous system involvement has been found in approximately 14% of patients with retinal cavernous hemangiomas (4). In order to diagnose FCCM in a proband, either or both of the following conditions must be met: 1) multiple cerebral cavernous malformations (CCMs) or one CCM and at least one other family member with one or more CCMs; 2) a heterozygous pathogenic variant in the genes KRIT1 (CCM1), CCM2, or PDCD10 (CCM3) (5). If FCCM is diagnosed in a patient, it is appropriate to evaluate both asymptomatic and symptomatic at-risk relatives in order to identify those who would benefit from screening and preventative measures (6). As is the case for any patient with an intracranial or intraocular vascular lesion, evaluation should be undertaken for lesions in other locations and for evidence of known syndromes (i.e., arteriovenous malformation in WyburnMason syndrome, retinal hemangioblastoma in von Hippel Lindau disease, and choroidal hemangioma in Sturge- Weber syndrome). FIG. 3. Temporal lobectomy specimen, 10· objective (·100 magnification). A. Hematoxylin and eosin stained section showing dilated thin-walled vessels with collagenous adventitia and no intervening brain parenchyma. Focal hemosiderin deposition is present within the vascular adventitia and adjacent brain parenchyma. B. Elastic stain demonstrates a uniform lack of internal elastic lamina within vascular channels. Torres et al: J Neuro-Ophthalmol 2020; 40: 262-264 263 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo Essay STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. T. Kini; b. Acquisition of data: B. Al Othman; c. Analysis and interpretation of data: A. T. Kini. Category 2: a. Drafting the manuscript: G. Torres; b. Revising it for intellectual content: A. G. Lee. Category 3: a. Final approval of the completed manuscript: A. G. Lee. REFERENCES 1. Labauge P, Krivosic V, Denier C, Tournier-Lasserve E, Gaudric A. Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study. Arch Ophthalmol. 2006;124:885-886. 264 2. Wood MW, White RJ, Kernohan JW. Cavernous hemangiomatosis involving the brain, spinal cord, heart, skin and kidney. Mayo Clin Proc. 1957;32:249-254. 3. Sarraf D, Payne AM, Kitchen ND, Sehmi KS, Downes SM, Bird AC. Familial cavernous hemangioma. Arch Ophthalmol. 2000;118: 969- 973. 4. Wang W, Chen L. Cavernous hemangioma of the retina: a comprehensive review of the literature (1934-2015). Retina 2017;37:611-621. 5. Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol. 2007;6:237-244. 6. Morrison L, Akers A. Cerebral cavernous malformation, familial. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, eds. GeneReviews [Internet]. Seattle, WA: University of Washington, Seattle, 2003:1993-2017. Updated August 4, 2016. Torres et al: J Neuro-Ophthalmol 2020; 40: 262-264 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.