Perirhinal accumulation of neuronal alpha‐synuclein in a multiple system atrophy patient with dementia

Abstract

We report the case of a 79-year-old Japanese woman who developed cerebellar ataxia followed by rigidity, dysautonomia and cognitive disorders, and was thus clinically diagnosed as having possible MSA with dementia. Neuropathological findings demonstrated not only olivopontocerebellar and striatonigral degeneration with frequent glial cytoplasmic inclusions (GCIs), but also degenerative changes in the parahippocampal region, accentuated in the anterior portion of perirhinal cortex, where neuronal cytoplasmic inclusions (NCIs) and NFTs were numerous while GCIs were limited. NCIs were frequent in the deep layer, whereas NFTs were more frequent in superficial cortical layers. Other hippocampal subregions including subiculum, dentate fascia and cornu ammonis were minimally involved. NCIs in the perirhinal cortex showed intense argyrophilia with the Campbell-Switzer silver impregnation method, but not argyrophilic with the Gallyas method. Most neuronal alpha-synuclein aggregates in dendrosomatic fraction formed globular/tadpole-like, and ultrastructurally comprised granular-coated fine fibrils 12-24 nm in diameter. To the best of our knowledge, alpha-synuclein-related neuronal pathology localized in the perirhinal region without hippocampal involvement has not been previously reported in MSA, and may provide clues to elucidate how neuronal pathology evolves in the hippocampal/parahippocampal regions in MSA, particularly in cases with dementia.

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

“…Our previous study also showed that greater burden of NCI in hippocampal dentate gyrus was associated with cognitive impairment in MSA 34. More recently, a patient with MSA-dementia who had numerous NCIs in the perirhinal region without hippocampal involvement has been reported 76. Nevertheless, a correlation between the domains or degree of cognitive impairment and respective functional neuroanatomical regions remains unclear.…”

Multiple system atrophy variant with severe hippocampal pathology

“…The SN and OPC systems are known to be vulnerable regions in MSA. However, MSA patients who display abundant neuronal inclusions in the regions other than SN or OPC system have occasionally been reported as pathologic variants ( 9 , 10 , 11 , 12 , 13 , 14 , 15 ). These patients sometimes present with cortical symptoms, including frontotemporal dementia (FTD), corticobasal syndrome (CBS), or progressive aphasia (PA), which are not presented in classical cases of MSA ( 9 ).…”