Disconnection of cerebellar Purkinje cells in Kearns-Sayre syndrome.

Kearns-Sayre syndrome (KSS) is a sporadic multisystem disorder due to rearrangements in mitochondrial DNA (mtDNA). To gain further insight into the pathogenesis of cerebellar dysfunction in KSS, antibodies against synaptophysin (SY) were used to identify presynaptic terminals and antibodies to calbindin D (CB) to identify Purkinje cells in the cerebellar cortex and in the dentate nucleus from two autopsied cases of KSS. By conventional neuropathology we found marked spongiform degeneration and by immunohistochemistry a disruption of presynaptic terminals and of the terminal arborizations of Purkinje cell axons on multipolar neurons of the dentate nucleus in the KSS patients. We suggest that a disconnection of Purkinje cells at the dentate nucleus may play a role in the pathogenesis of cerebellar ataxia in KSS.