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Show Journal ofN'euro- Ophthalmology 20( 4): 248- 249, 2000. © 2000 Lippincott Williams & Wilkins, Inc., Philadelphia Unilateral Adie Pupil as Sole Ophthalmic Sign of Anti- Hu Paraneoplastic Syndrome Michiko Kimura Bruno, MD, Jacqueline M. S. Winterkom, PhD, MD, Mark A. Edgar, MD, Ayeesha Kamal, MD, and J. Patrick Stiibgen, MD Unilateral Adie pupil is usually a benign finding. The authors report the case of a 73- year- old man in whom pupillary abnormality was accompanied by areflexia, generalized sensorimotor neuropathy, and autonomic dysfunction. Anti- Hu antibody associated with small cell lung cancer was found in the serum and cerebrospinal fluid. Unilateral Adie pupil was the sole ophthalmic manifestation of anti- Hu syndrome. A variety of ophthalmic signs can signal paraneoplastic syndromes, most commonly ophthalmopareses, opsoclonus- myoclonus syndrome, cancer- associated retinopathy, or optic neuropathy. The authors present a case in which a unilateral Adie pupil was the sole ophthalmic manifestation of anti- Hu syndrome. CASE REPORT A 73- year- old man noticed blurry vision OD while reading. When he looked in a mirror, he saw that his right pupil was dilated. During the following weeks, he was bothered by bright lights. About 3 months earlier, he had developed generalized malaise and a dry cough. Shortly thereafter, he noticed discomfort and numbness in both feet, as if he were walking on a " cushion of air." As the numbness ascended to his ankles, he developed difficulty walking. He then started to experience pins- and- needles sensations and numbness in his fingers. He complained of dry mouth and noted dizziness when he stood up. Family members described that the patient sweated profusely while eating hot food. He was a heavy smoker and a social drinker. His medical history was significant for a myocardial infarction and bypass surgery. Visual acuity was 20/ 30 OU, visual fields were full, and eye movements were intact, with smooth pursuit, brisk saccades, and no ptosis or nystagmus. The fundus appeared normal. The right pupil was mydriatic, 8 mm in diameter, and showed neither direct nor consensual constriction to light. The right pupil did not constrict on attempted accommodation. The left pupil was 4.5 mm in Manuscript received May 4, 2000; accepted September 12, 2000. From the Departments of Neurology and Neuroscience, Ophthalmology, and Pathology, Weill Medical College of Cornell University, New York, New York. Address correspondence and reprint requests to Jacqueline M. S. Winterkom, 900 Northern Boulevard, Suite # 210, Great Neck, NY 11021. diameter and constricted to near and to light shown in either eye, without afferent pupillary defect. Forty minutes after instillation of a drop of dilute pilocarpine 0.1 % OU, the right pupil had constricted to 1.0 mm, whereas the left pupil diameter remained 4.5 mm. The patient's general examination was remarkable only for orthostatic hypotension, with blood pressure dropping from 170/ 100 mm Hg supine to 100/ 60 mm Hg sitting, without change in pulse rate. On neurologic examination, his cognitive function was normal. He had loss of all modalities of somatic sensation distally in all four extremities. His coordination was impaired. He was areflexic and distally weak, and he had flexor response of the toes. Gait was wide- based and unsteady. Magnetic resonance imaging ( MRI) of the head, cervical spine, and lumbar spine was within normal limits. Results of blood tests were normal, including complete blood count, chemistries, vitamin B12, folate, angio-tensin- converting enzyme, thyroid function tests, and acetylcholine receptor antibodies. Serum Lambert- Eaton Myasthenic syndrome ( LEMS) antibody was negative. Nerve conduction studies showed an axonal sensorimotor polyneuropathy. There was no incremental response to repetitive stimulation. Biopsy of the sural nerve showed no significant changes with hematoxylin and eosin ( H& E) staining, but electron microscopy showed changes consistent with severe axonopathy ( Fig. 1). Cerebrospinal fluid contained protein of 105 mg/ dl and glucose of 69 mg/ dl. Anti- Hu antibody titers were positive in both cerebrospinal fluid and serum. Computed tomography ( CT) of the chest showed a 0.8- cm nodule in the left upper lobe of the lung, and biopsy of a mediastinal lymph node confirmed small cell lung carcinoma. DISCUSSION Anti- Hu antibodies in serum or CSF have been associated with a wide spectrum of neurologic disorders, including brainstem and limbic encephalomyelitis, cerebellar degeneration, sensory and motor neuropathies, autonomic dysfunction, and visual loss. Neuro- ophthal-mologic presentations of anti- Hu antibody syndrome can be prominent ( 1) and include ophthalmopareses, nystagmus, and opsoclonus- myoclonus, which is usually asso- 248 UNILATERAL ADIE PUPIL AS SOLE OPHTHALMIC SIGN OF ANTI- HU PARANEOPLASTIC SYNDROME 249 FIG. 1. Electron micrograph of sural nerve shows severe axon-opathy. Small and large myelinated and unmyelinated fibers are depleted. No regenerative sprouts or onion bulbs are seen. Numerous stacks of denervated Schwann cell cytoplasm are identified ( uranyl acetate- lead citrate, original magnification x7,200). ciated with anti- Ri syndrome ( 2). Multifocal involvement of the nervous system is common in anti- Hu antibody syndrome. In D. almau et al.' s series ( 3), autonomic nervous system involvement, most frequently orthostatic hypotension, was found in 28% of their cases. According to Dalmau et al., 11% of patients had abnormal pupillary responses, either " slowly reactive" or " pinpoint" pupils." One patient with brainstem signs including nystagmus and a right VI nerve palsy was reported to have a " left afferent pupillary defect." Tonic pupils have been reported in association with cancer. In 1965, Beallo ( 4) reported a patient, eventually diagnosed with oat cell carcinoma, who presented with bilateral tonic pupils, ptosis, and a myasthenic syndrome. The case had features of Lambert- Eaton myasthenic syndrome ( LEMS), which subsequently has been associated with autonomic insufficiency and pupil abnormality ( 5). Several other cases of Adie pupil in the literature predating identification of serum anti- Hu antibodies were associated with presumed paraneoplastic sensory neuropathy with autonomic involvement ( 6- 9). Our patient presented with unilateral mydriasis as his sole ophthalmic sign. Testing with dilute pilocarpine showed cholinergic supersensitivity of the OD, consistent with Adie pupil. The patient's persistent symptoms and the absence of any pupillary response to accommodation or light indicate that the regeneration typically seen 2 months after onset of Adie pupil had not yet occurred. Orthostasis and temperature dysregulation suggested generalized autonomic dysfunction, in which bilateral pupillary involvement would be expected ( 10). However, in our case, widespread neuropathy was associated with only unilateral pupillary involvement, a more typical presentation for idiopathic Adie syndrome. In our patient, peripheral neuropathy was associated with areflexia. Adie syndrome comprises areflexia and tonic pupil, raising the possibility that tonic pupil is underdiagnosed in other cases of peripheral neuropathy with areflexia. The pathologic condition common to peripheral neuropathy and Adie pupil has not been elucidated. Loss of ganglion cells in parasympathetic ciliary ganglia was seen in a patient with Adie syndrome reported by Har-riman and Garland ( 11), who speculated that concurrent loss of dorsal root ganglion cells might be responsible for the areflexia. Loss of dorsal root ganglion cells with inflammation has been shown in anti- Hu antibody sensory neuropathy, suggesting neuronopathy ( 2). Histologic features seen in electron micrographs of this patient's sural nerve were consistent with the axonal degeneration seen in peripheral nerves with paraneoplastic sensorimotor neuropathy ( 2,8). Although we do not have histologic confirmation of a lesion in the parasympathetic nerves innervating the pupil; we can speculate that a similar degenerative process occurred. Although unilateral Adie pupil usually is a benign finding, development of a unilateral Adie pupil even without any other neuro- ophthalmic signs in an elderly patient may herald anti- Hu paraneoplastic syndrome. 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