Primary degeneration of oculomotor, motor, and somatosensory systems and auditory and visual pathways in spinocerebellar ataxia type 7: A clinicopathological study in a Japanese autopsy case.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia associated with retinal degeneration. The disease is rare in Japan, and this is the first full description of clinicopathological findings in a Japanese autopsy case of genetically confirmed SCA7 having 49 cytosine-adenine-guanine (CAG) trinucleotide repeats in the ataxin 7 gene. A 34-year-old Japanese man with no family history of clinically apparent neurodegenerative diseases presented with gait disturbance, gradually followed by truncal instability with progressive visual loss by the age of 42 years. He became wheelchair-dependent by 51 years old, neurologically exhibiting cerebellar ataxia, slow eye movement, slurred and scanning speech, lower limb spasticity, hyperreflexia, action-related slowly torsional dystonic movements in the trunk and limbs, diminished vibratory sensation in the lower limbs, auditory impairment, and macular degeneration. Brain magnetic resonance imaging revealed atrophy of the brainstem and cerebellum. He died of pneumonia at age 60 with a 26-year clinical duration of disease. Postmortem neuropathological examination revealed pronounced atrophy of the spinal cord, brainstem, cerebellum, external globus pallidus (GP), and subthalamic nucleus, microscopically showing neuronal cell loss and fibrillary astrogliosis with polyglutamine-immunoreactive neuronal nuclei and/or neuronal nuclear inclusions (NNIs). Degeneration was also accentuated in the oculomotor system, auditory and visual pathways, upper and lower motor neurons, and somatosensory system, including the spinal dorsal root ganglia. There was a weak negative correlation between the frequency of nuclear polyglutamine-positive neurons and the extent of neuronal cell loss. Clinicopathological features in the present case suggest that neurological symptoms, such as oculomotor, auditory, visual, and sensory impairments, are attributable to degeneration in their respective projection systems affected by SCA7 pathomechanisms and that dystonic movement is related to more significant degeneration in the external than internal GP.