Jun 29, 2013 - 2Department of Neurology, China-Japan Friendship. Hospital, Beijing, China. 3Department of Neuroscience, School of Medicine,. UTMB ...
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PostScript is the first neuropathological description of an SCA10 patient.
RESULTS
Purkinje cell loss is the major brain pathology of spinocerebellar ataxia type 10 Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar degenerative disorder, variably associated with epilepsy.1 The mutation responsible for SCA10 is an expansion of an ATTCT repeat in intron 9 of the ATXN10 gene on chromosome 22q13.3.2 Although brain MRI of SCA10 patients show isolated cerebellar atrophy, histopathological changes in the brain of SCA10 patients remain unknown. Here, we report the postmortem neuropathological findings of an SCA10 patient and compare these with a normal age and gender-matched control subject.
SUBJECT AND METHODS The patient was a 42-year-old MexicanAmerican man with the diagnosis of SCA10 based on the presence of 2350 ATTCT repeats. Gait ataxia started at 26 years of age followed by the development of complex partial seizures with occasional secondary generalisation. An examination at age 30 showed normal mental status and typical symptoms and signs of cerebellar ataxia with MRI findings showing cerebellar atrophy without other abnormalities. Ataxia progressed and his seizures were poorly controlled even with multiple anticonvulsants and a vagal nerve stimulator. Shortly before his death, he was wheelchair bound. He developed aspiration pneumonia, which was subsequently complicated by multiple organ failure, and died after staying in the ICU for 7 days. With family’s consent for autopsy, the brain was removed 3 h postmortem. Samples were taken from cerebral cortex, hippocampus, brainstem and cerebellum. A normal postmortem control brain was obtained from a 38-year-old male who died from pulmonary emboli. We performed gross and microscopic examinations, immunohistochemistry/immunofluorescence for calbindin, neurofilament-H, NeuN, glutamic acid decarboxylase (GAD) and compared with the normal control. This J Neurol Neurosurg Psychiatry December 2013 Vol 84 No 12
We found that Purkinje cell (PC) loss is the primary pathology in SCA10 cerebellum. The cerebellum showed marked, symmetrical atrophy of the hemispheres with the vermis being less affected. H&E staining of the cerebellum revealed striking PC loss with a corresponding reduction in the molecular layer volume (figure 1 A,B). Bergmann gliosis was present in areas of PC loss. The internal granular layer was also affected but not as extensively as PC cells. PC cell linear density (PC number per centimetre of PC layer) and molecular layer thickness (the distance from the PCs to the cerebellar surface in micrometres) were significantly reduced compared with normal control (16.9±7.1 vs 58.6±9.4, p
