Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neuropathol Exp Neurol. 2012 Feb;71(2):148-61. doi: 10.1097/NEN.0b013e318244477d.

Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study.

Author information

1
Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.

Abstract

Cerebellar ataxia is a prominent clinical symptom in patients with mitochondrial DNA (mtDNA) disease. This is often progressive with onset in young adulthood. We performed a detailed neuropathologic investigation of the olivary-cerebellum in 14 genetically and clinically well-defined patients with mtDNA disease. Quantitative neuropathologic investigation showed varying levels of loss of Purkinje cells and neurons of the dentate nucleus and inferior olivary nuclei. Typically, focal Purkinje cell loss was present in patients with the m.3243A>G mutation caused by the presence of microinfarcts, with relative preservation of neuronal cell populations in the olivary and dentate nuclei. In contrast, patients with the m.8344A>G mutation or recessive POLG mutations showed extensive and global neuronal cell loss in all 3 olivary-cerebellum areas examined. Molecular analysis of mutated mtDNA heteroplasmy levels revealed that neuronal cell loss occurred independently of the level of mutated mtDNA present within surviving neurons. High levels of neuronal respiratory chain deficiency, particularly of complex I, were detected in surviving cells; levels of deficiency were greater in regions with extensive cell loss. We found a relationship between respiratory deficiency and neuronal cell density, indicating that neuronal cell death correlates with respiratory deficiency. These findings highlight the vulnerability of the olivary-cerebellum to mtDNA defects.

PMID:
22249460
PMCID:
PMC3272439
DOI:
10.1097/NEN.0b013e318244477d
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Silverchair Information Systems Icon for PubMed Central
    Loading ...
    Support Center