Open AccessPurkinje Cell Pathology and Loss in Multiple Sclerosis Cerebellum
Author(s) -
Redondo Juliana,
Kemp Kevin,
Hares Kelly,
Rice Claire,
Scolding Neil,
Wilkins Alastair
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12230
Subject(s) - cerebellum , purkinje cell , cerebellar cortex , ataxia , multiple sclerosis , neuroscience , cerebellar ataxia , pathology , white matter , neurofilament , biology , medicine , immunology , magnetic resonance imaging , immunohistochemistry , radiology
Cerebellar ataxia commonly occurs in multiple sclerosis, particularly in chronic progressive disease. Previous reports have highlighted both white matter and grey matter pathological changes within the cerebellum; and demyelination and inflammatory cell infiltrates appear commonly. As P urkinje cell axons are the sole output of the cerebellar cortex, understanding pathologic processes within these cells is crucial to develop strategies to prevent their loss and thus reduce ataxia. We studied pathologic changes occurring within P urkinje cells of the cerebellum. Using immunohistochemic techniques, we found changes in neurofilament phosphorylation states within P urkinje cells, including loss of dephosphorylated neurofilament and increased phosphorylated and hyperphosphorylated neurofilament. We also found P urkinje axonal spheroids and P urkinje cell loss, both of which occurred predominantly within areas of leucocortical demyelination within the cerebellar cortex. These changes have important implications for the study of cerebellar involvement in multiple sclerosis and may help design therapies to reduce the burden of ataxia in the condition.