Uncovering diagnostic clues, insights in pediatric neurodegenerative cases

Reviewed by Gena Heidary, MD, PhD Awareness of the neuro-ophthalmic findings in pediatric neurodegenerative diseases might yield insight into the diagnosis of these diseases, and the ophthalmic clues should not be overlooked, according to Gena Heidary, MD, PhD. When evaluating patients with pediatric neurodegenerative diseases, a common classification scheme stratifies the diseases by the areas within the brain which are predominantly affected-i.e., diseases of the gray matter, such as neuronal ceroid lipofuscinosis, or of the white matter, such as Pelizaeus–Merzbacher disease, or diseases that overlap, she said. These diseases can be difficult to diagnose and therefore clinicians need to be aware of the ophthalmic manifestations of these diseases to aid in diagnosis, said Dr. Heidary, assistant professor of ophthalmology, Harvard Medical School, Boston. Children with neurodegenerative diseases might experience afferent findings of vision and visual field loss, retinal degeneration, and optic atrophy, and efferent findings of strabismus, nystagmus, and sensorimotor dysfunction, she noted. Case reports Case reports Case 1 5-year-old boy presented with new-onset seizures refractory to treatment. The parents believed he was sitting closer to objects to view them, and a recent eye exam revealed vision in the legally blind range. The child was prescribed glasses for mild myopia, but they did not improve his vision, which was markedly subnormal for his age, Dr. Heidary noted. Visual fields were full, and sensorimotor evaluation was unremarkable. However, retinal evaluation showed a bull’s-eye maculopathy. Neuroimaging was remarkable for cerebral and cerebellar atrophy. The patient underwent a skin biopsy with findings diagnostic of neuronal ceroid lipofuscinosis. In this case, the retinal findings guided the workup, which led the multidisciplinary team to the diagnosis. “In cases of pediatric neurodegenerative disease that affect the retina, we want to think of the diseases that affect the inner retinal layers, especially storage disorders, such as Tay-Sachs disease that often causes a cherry-red spot because of accumulation of a substance in the inner retinal layers,” Dr. Heidary said. There are diseases that affect the outer retinal layers and cause degeneration of the photoreceptors with a finding of pigmentary retinopathy on examination. Examples of these diseases include mitochondrial disorders, such as Kearns-Sayre syndrome or spinocerebellar ataxia type 7. Case 2 A male infant had been diagnosed with nystagmus and optic atrophy at 2 years of age, at which time neuroimaging showed small-caliber optic nerves but an otherwise healthy MRI of the brain. At 7 years of age, the child presented with new esotropia. The sensorimotor exam was consistent with a new sixth-nerve palsy. Fundus examination showed optic atrophy in both eyes, a health fovea, and no pigmentary changes in the midperipheral or peripheral retina, according to Dr. Heidary. Repeat neuroimaging revealed symmetric, T2 hyperintense lesions throughout the brainstem. These findings are highly characteristic for Leigh disease, she noted. Genetic testing confirmed a mutation that caused the Leigh-like encephalopathy. Neurodegenerative diseases that present with optic atrophy include the leukodystrophies, i.e., white matter diseases, such as Pelizaeus–Merzbacher disease and adrenoleukodystrophy; mitochondrial disorders often are accompanied by optic atrophy; and some diseases, such as spinocerebellar ataxia type 7, have pigmentary retinal changes and optic atrophy, Dr. Heidary explained. Case 3, conclusions Case 3 A 21-year-old woman had acquired bilateral blepharotosis and acquired progressive external ophthalmoplegia that began when she was in her mid-teens. She also had hearing loss, which might be a clue to possible mitochondrial dysfunction, Dr. Heidary noted. The afferent examination was normal. The sensorimotor exam showed slow eye movements in all fields of gaze. The retinal periphery had pigmentary changes with a salt-and-pepper appearance. A muscle biopsy showed ragged red fibers. The diagnosis was Kearns-Sayre syndrome. “The efferent findings in neurodegenerative disease may include new-onset strabismus often with a localizing value, ophthalmoparesis or ophthalmoplegia, and/or saccadic dysfunction,” Dr. Heidary said. “Our role as consultants for these patients is to document any of these findings discussed, that is, afferent and efferent findings that might help narrow the diagnostic workup,” she said. “If we are the first to examine these patients, we should initiate a multidisciplinary team workup that includes neurology, genetics, and metabolism colleagues,” Dr. Heidary concluded. “We also might be called upon to monitor these patients for disease progression and treatment efficacy.” Gena Heidary, MD, PhD E: Gena.Heidary@childrens.harvard.edu This article was adapted from Dr. Heidary’s presentation at the 2016 meeting of the American Academy of Ophthalmology. Dr. Heidary has no financial interest in the subject. The complete review article by Dr. Heidary will be published in a special edition on pediatric neuro-ophthalmology in the Journal of Neuro-Ophthalmology this fall.