<%server.execute "isdev.asp"%> More than it meets the eye! Vision loss as a presenting symptom of von Hippel–Lindau disease Nair AV, Vijayaraghavan A, Alexander PT, Mani AM, Giridhar D, Mathew V - J Pediatr Neurosci
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Year : 2020  |  Volume : 15  |  Issue : 3  |  Page : 314-316

More than it meets the eye! Vision loss as a presenting symptom of von Hippel–Lindau disease

1 Department of Neurological Sciences, Christian Medical College Vellore, Vellore, Tamil Nadu, India
2 Department of Ophthalmology, Christian Medical College Vellore, Vellore, Tamil Nadu, India

Date of Submission10-Feb-2020
Date of Decision06-Jul-2020
Date of Acceptance07-Jul-2020
Date of Web Publication06-Nov-2020

Correspondence Address:
Dr. Aditya V Nair
Department of Neurosciences, Christian Medical College Vellore, Vellore, Tamil Nadu.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_24_20

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Optic neuritis has many mimics. Careful history and fundus examination are paramount in making the correct diagnosis. Here we present a case of bilateral vision loss in a 15-year-old male who subsequently developed hypertensive crises. Subsequent evaluation showed pheochromocytoma and genetic screening confirmed Von Hippel–Lindau disease.

Keywords: Hypertensive retinopathy, pheochromocytoma, von Hippel–Lindau

How to cite this article:
Nair AV, Vijayaraghavan A, Alexander PT, Mani AM, Giridhar D, Mathew V. More than it meets the eye! Vision loss as a presenting symptom of von Hippel–Lindau disease. J Pediatr Neurosci 2020;15:314-6

How to cite this URL:
Nair AV, Vijayaraghavan A, Alexander PT, Mani AM, Giridhar D, Mathew V. More than it meets the eye! Vision loss as a presenting symptom of von Hippel–Lindau disease. J Pediatr Neurosci [serial online] 2020 [cited 2022 Dec 6];15:314-6. Available from: https://www.pediatricneurosciences.com/text.asp?2020/15/3/314/300054

   Introduction Top

Von Hippel–Lindau (VHL) is a multisystem disorder presenting as hemangioblastomas of the brain, spinal cord, and retina; renal cysts and renal cell carcinoma; pheochromocytoma and paraganglioma; pancreatic cysts and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts.[1] Pheochromocytoma as a presenting symptom of VHL is a difficult diagnosis to make considering the varied clinical manifestation overlapping with many systems.

We report an adolescent male with bilateral hypertensive papillopathy as the presenting feature of pheochromocytoma related to VHL disease, which to our knowledge has not been previously reported in India.

   Case Report Top

An apparently well 15-year-old male from northern part of India presented in August 2017, with a history of acute-onset bilateral painless vision loss of BE. Onset to nadir was within 3 days. There was no history of pain around the eyes or on eye movement. He also gave intermittent history of headache, which was not severe before the onset of vision loss for about 3 months. According to the ophthalmological findings outside, he had bilateral disc edema with a visual acuity of 6/36 bilaterally. He was managed as a case of optic neuritis with pulse methylprednisolone and subsequently on oral prednisolone taper. He reported no significant change in acuity with the same.

He presented to our emergency department 2 months after the index event with intermittent episodes of headache, palpitation, chest pain, and persisting low visual acuity with an admission blood pressure of 240/120 mm Hg and heart rate of 160 beats per minute. There was no asymmetry in upper limb blood pressure, no renal bruit, or radio-femoral delay. Neurological examination revealed normal sensorium, visual acuity of 6/36 both eyes (BE). Fundoscopic examination revealed bilateral disc edema with hard exudates, suggestive of stage 4 Keith and Wagner hypertensive retinopathy, and fields showed centrocecal scotoma in BE [Figure 1]. He had other features of end-organ damage in the form of renal failure with subnephrotic rage proteinuria and left ventricular hypertrophy. Magnetic resonance imaging (MRI) of brain contrast showed subcortical white matter T2 hyperintensities and prior right lenticular hemorrhage with normal appearing optic nerves. Cerebrospinal fluid (CSF) analysis was normal with normal opening pressure [Figure 2].
Figure 1: Fundus photographs before and after surgery showing resolution of hard exudates and disc edema

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Figure 2: (A) T2-weighted (T2W) fluid-attenuated inversion recovery sequence brain showing white matter changes and right lenticular hemorrhage. (B) Normal optic nerves and T2W axial sequence. (C) Contrast-enhanced CT abdomen arterial phase showing (red asterisk) suprarenal masses with heterogeneous enhancement

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He required intravenous antihypertensive medications to control blood pressure, and he was shifted to neuro intensive care unit (ICU) for further management. Vasculitic and connective tissue disease workup was negative, and renal artery Doppler did not reveal any stenosis. He was evaluated for endocrine causes of hypertension and was detected to have elevated urinary metanephrine levels. Computed tomography (CT) of abdomen revealed bilateral pheochromocytoma [Figure 2]. He was subsequently managed under the department of endocrinology. His antihypertensive medications were optimized and taken up for adrenalectomy, following which his blood pressure stabilized. On follow-up after 1 year, his visual acuity has improved to 6/12 BE with residual disc pallor, and resolution of hard exudates and metanephrine levels [Figure 1]. In view of bilateral pheochromocytoma, he was evaluated for genetic causes and was detected to have 3p25-26 (c.482 G > A) VHL gene chromosomal mutation consistent with VHL disease. Further follow-up has not shown any new tumors/retinal hemangioblastomas. There was no positive family history elicited. His relatives have been advised to get screened for the mutation.

   Discussion Top

Typical optic neuritis is a clinical diagnosis. In a recent study, 10% of cases referred as optic neuritis had a different final diagnosis.[2] Our patient had several red flags for optic neuritis-bilateral involvement, headache predating vision loss, atypical fundoscopic findings, and grossly elevated blood pressure, which made us consider an alternative diagnosis. Considering his young age with episodic headache, paroxysmal episodes of hypertension, and tachycardia, a diagnosis of pheochromocytoma was considered to be more likely.

Retinal arteries are histologically similar to arterioles with 100-µm caliber and no internal elastic lamina. Changes in the luminal diameter of the arterioles are the most important component in regulating systemic arterial blood pressure. They show autoregulatory mechanisms and tight junctions to maintain the blood–ocular barrier. Choroidal arterioles and capillaries have fenestrations (i.e., no blood–ocular barrier) and do not show autoregulation. Optic nerve head vessels on the other hand show intermediate characteristics with incomplete autoregulation owing to incompetent blood-ocular barrier as a result of peripapillary choroidal vessels. Because of the vascular differences between the retina, the choroid, and the optic nerve, each of these anatomic regions responds differently to hypertension.[3] Hypertensive retinopathy is a term used to describe all the ocular findings secondary to systemic arterial hypertension. Although the term implies only retinal involvement, usually there are concurrent findings in both the choroid and the optic disc, depending on the severity and chronicity of the hypertension. Our patient had features of both acute and chronic hypertension. Pheochromocytoma is a great masquerade of variety of diseases. It can mimic variety of diseases, and it needs to be considered in view of its potential cardiovascular or cerebrovascular disease complications. Pheochromocytoma is often not familial, arising from a germ line mutation. However, pheochromocytoma is associated with several familial syndromes, including multiple endocrine neoplasia 2A and multiple endocrine neoplasia 2B, VHL disease, von Recklinghausen disease, tuberous sclerosis, and Sturge– Weber syndrome More Details. Further workup should include RET proto-oncogene testing, bone scan, dermatologic examination, and genetic testing to rule out these disorders.

Vision loss presentation as a presenting symptom in pheochromocytoma has been well documented in literature.[4],[5] However, to the author’s best knowledge, this is the second case report in literature of VHL syndrome, presenting as vision loss due to hypertensive retinopathy due to pheochromocytoma, and the first from India.[6]

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Conflicts of interest

There are no conflicts of interest.

   References Top

van Leeuwaarde RS, Ahmad S, Links TP, Giles RH von Hippel–Lindau syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE. GeneReviews® NCBI Bookshelf [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2020.  Back to cited text no. 1
Weerasinghe D, Lueck C Mimics and chameleons of optic neuritis. Pract Neurol 2016;16:96-110.  Back to cited text no. 2
Hayreh SS, Servais GE, Virdi PS Fundus lesions in malignant hypertension. VI. Hypertensive choroidopathy. Ophthalmology 1986;93:1383-400.  Back to cited text no. 3
Pushpakumari P, Nampoory MR, Vaidyanathan S, Vijayalakshmi A, Visweswaran RK Bilateral pheochromocytoma with papilloedema. J Assoc Physicians India 1988;36:738-9.  Back to cited text no. 4
Petkou D, Petropoulos IK, Kordelou A, Katsimpris JM Severe bilateral hypertensive retinopathy and optic neuropathy in a patient with pheochromocytoma. Klin Monbl Augenheilkd 2008;225:500-3.  Back to cited text no. 5
Shah V, Zlotcavitch L, Herro AM, Dubovy SR, Yehoshua Z, Lam BL Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel–Lindau disease. Clin Ophthalmol 2014;8:623-8.  Back to cited text no. 6


  [Figure 1], [Figure 2]


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