Involvement of spinal motor neurons in parkin-positive autosomal recessive juvenile parkinsonism.
We intensively examined the spinal cord of an autosomal recessive juvenile parkinsonism (ARJP) female patient with a homozygous exon 3 deletion in the parkin gene, anticipating a possible involvement of anterior horn neurons. Although the clinical features of the patient were consistent with parkinsonism as a result of parkin mutation, her tendon reflex was abolished in the lower limbs. This feature was in contrast with hyperreflexia, usually found in previous reports of ARJP. Histologically, on the level of the cervical, thoracic, and sacral spinal cord, anterior horn neurons were well preserved and normal. However, the lumbar spinal cord exhibited many swellings of proximal axons (spheroids) and degenerative changes in the somata of the large anterior horn neurons such as central chromatolysis, cystatin C-negative small eosinophilic inclusions, and eosinophilic Lewy body-like inclusions. Ultrastructurally, accumulations of neurofilaments and abnormal structures, such as inclusion bodies similar to skein-like inclusions and disorganized rough endoplasmic reticulum, were observed in the somata and neuronal processes. Lewy body-like inclusions in this study were positively immunostained for both alpha-synuclein and ubiquitin that closely resemble Lewy bodies, but are different from Lewy body-like inclusions negatively immunostained for alpha-synuclein in amyotrophic lateral sclerosis. These findings suggest that eosinophilic inclusions that closely resemble Lewy bodies may be formed in the spinal motor neurons of ARJP patients with parkin mutations and the motor neurons of these patients may be vulnerable to neurodegeneration.
Sasaki
Shoichi
S
Department of Neurology, Neurological Institute, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. ssasaki@nij.twmu.ac.jp
Shirata
Akiko
A
Yamane
Kiyomi
K
Iwata
Makoto
M
D000328:Adult; D000368:Aged; D000870:Anterior Horn Cells / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein