Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome Presenting With Neurotrophic Keratopathy

Clinical Correspondence Cerebellar Ataxia With Neuropathy and Vestibular Areflexia Syndrome Presenting With Neurotrophic Keratopathy Grace L. Paley, MD, PhD, Nathan H. Kung, MD, Robert C. Bucelli, MD, PhD, Todd P. Margolis, MD, PhD, Gregory P. Van Stavern, MD C erebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is an inherited, progressive ataxic disorder affecting cerebellar, vestibular, and somatic sensory function (1). The causative gene(s) is still unknown. The clinical diagnosis requires evidence of combined vestibular and sensory ganglionopathy with exclusion of several known genetic ataxias. Our patient with CANVAS developed bilateral neurotrophic keratopathy, an association, to the best of our knowledge, not previously reported. A woman in her 60s experienced intermittent binocular diplopia, oscillopsia while in motion, persistent foreign body sensation in both eyes, and several years of progressive ataxia. Her medical history was significant for a recent diagnosis of CANVAS. There was no family history of ataxia or neuromuscular disorders. She had a previous diagnosis of dry eye syndrome treated with artificial tears and courses of topical steroids with incomplete relief. On examination, visual acuity was 20/80 in the right eye and 20/40 in the left eye. Pupillary testing was normal. Ocular motility showed full versions and ductions but markedly impaired smooth pursuit and hypermetric saccades. The patient displayed frequent square wave jerks but no nystagmus. Alternate cover testing revealed orthophoria Department of Ophthalmology and Visual Sciences (GLP, NHK, TPM, GPVS), Washington University in St. Louis, St. Louis, Missouri; and Department of Neurology (RCB, GPVS), Washington University in St. Louis, St. Louis, Missouri. Supported by DOVS Core Grant 5 P30 EY02687, Institute for Clinical and Translational Sciences grant RR023496, Biostat Core Grant U54 RR023496, NIH Core Vision Grant P30 EY02687, and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences. The funding organizations had no role in the design or conduct of this research. The authors report no conflicts of interest. Address correspondence to Gregory P. Van Stavern, MD, Departments of Ophthalmology and Visual Sciences and Neurology, School of Medicine, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO 63110; E-mail: [e-mail]. 342 at distance and 8 prism diopters of exotropia at near. Impaired vestibulo-ocular reflex (VOR) gain was observed on head impulse and visually enhanced VOR testing bilaterally. Slit-lamp examination revealed diffuse corneal epithelial microcysts with punctate erosions and moderate conjunctival inflammation in both eyes (Fig. 1). Corneal sensation was absent or severely reduced without blink reflex bilaterally, but Schirmer testing without anesthesia revealed normal tear production in each eye. There was mild lagophthalmos of the right eye. Ophthalmoscopy was normal in each eye. Vestibular testing demonstrated absent vestibuloocular reflex to ice-water caloric irrigation and poor optokinetic responses. Electromyography and nerve conduction studies showed a peripheral polyneuropathy with diffusely absent sensory nerve action potentials and normal compound muscle action potential amplitudes in the arms and legs. The patient was diagnosed with neurotrophic keratopathy and follicular conjunctivitis, the latter possibly caused by preserved artificial tears. She was instructed to stop artificial tears, start topical prednisolone sodium phosphate 1% drops in each eye, and at bedtime use preservative-free ointment with taping the right eye closed. She was prescribed 4 diopters basein-prism over the right eye to minimize diplopia from her convergence insufficiency during reading. At a 2-month followup, visual acuity improved to 20/30 in the right eye and 20/40 in the left eye with resolution of the follicular conjunctivitis and decrease in corneal microcyst density. She remained symptomatically and clinically stable at 6-month follow-up. CANVAS is characterized by slowly progressive balance and sensory impairment leading to disability and diminished quality of life. The heterogeneous presentation from variable neuronal involvement may delay diagnosis (2). In addition, CANVAS should be differentiated from several genetic and metabolic disorders including multiple system Paley et al: J Neuro-Ophthalmol 2018; 38: 342-343 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Neurotrophic keratopathy. After instillation of fluorescein dye, there are areas of corneal staining seen on slit-lamp examination (A) and with cobalt blue light (B). atrophy, Friedreich ataxia, multiple subtypes of spinocerebellar ataxia, thiamine deficiency, neurosarcoidosis, paraneoplastic disease, and other autoimmune neuropathies. Unfortunately, as genetic testing was not covered by her insurance provider, our patient was unable to undergo definitive testing to exclude important disease mimics. Beyond this limitation, our patient otherwise fulfilled all other diagnostic criteria for clinically definite CANVAS. Although CANVAS has been described as sparing the afferent visual pathways (1), patients typically report oscillopsia and display eye movement abnormalities from cerebellar and bilateral vestibular dysfunction (2,3). In addition to her ocular motility findings, our patient had ocular surface disease in the setting of decreased corneal sensation, which contributed to her visual symptoms. Abnormalities of the blink reflex have been reported in patients with CANVAS (4); however, to the best of our knowledge, this is the first report of neurotrophic keratopathy in association with CANVAS. Neurotrophic keratopathy may be underrecognized in CANVAS and other sensory neuropathies and, as in our patient, mis- Paley et al: J Neuro-Ophthalmol 2018; 38: 342-343 diagnosed as dry eye syndrome. Accurate diagnosis is essential so these patients may receive appropriate treatment to optimize vision, particularly when they are at increased risk of falls from their underlying neurological disorder. REFERENCES 1. Szmulewicz DJ, Roberts L, McLean CA, MacDougall HG, Halmagyi GM, Storey E. Proposed diagnostic criteria for cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Neurol Clin Pract. 2016;6:61-68. 2. Cazzato D, Dalla Bella E, Dacci P, Mariotti C, Lauria G. Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome: a slowly progressive disorder with stereotypical presentation. J Neurol. 2016;263:245-249. 3. Szmulewicz DJ, McLean CA, MacDougall HG, Roberts L, Storey E, Halmagyi GM. CANVAS an update: clinical presentation, investigation and management. J Vestib Res. 2014;24:465-474. 4. Szmulewicz DJ, Seiderer L, Halmagyi GM, Storey E, Roberts L. Neurophysiological evidence for generalized sensory neuronopathy in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome. Muscle Nerve. 2015;51:600-603. 343 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.