臨床神経学

第49回日本神経学会総会

<シンポジウム10-1>ミトコンドリア病治療の現状と将来
MELASの脳卒中様発作の病態と治療

飯塚 高浩

北里大学医学部神経内科学〔〒228-8555 相模原市北里1-15-1〕

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a distinct clinical syndrome caused by mutations in mitochondrial DNA. Crucial molecular mechanism includes a lack of taurine modification at the wobble uridine of the mutant tRNALeu (UUR), causing UUG condon-specific translational defect and mitochondrial protein synthesis failure. However, the pathogenesis of stroke-like episodes remains unknown.
We previously reported that stroke-like episodes were more likely non-ischemic events, characterized by increased capillary permeability, hyperperfusion, neuronal vulnerability and neuronal hyperexcitability, in which neuronal hyperexcitability plays an important role in initiation of the cascades of stroke-like events by increasing energy demand. We also emphasized a role of prolonged epileptic activities in progressive spread of stroke-like lesions, and then proposed a non-ischemic neurovascular cellular mechanism. Once neuronal hyperexcitability developed in a localized region as a result from either mitochondrial dysfunction in capillary endothelial cells, or in neurons or astrocytes, epileptic activities depolarize adjacent neurons, leading to propagation of epileptic activities in surrounding cortex. Increased capillary permeability in the presence of mitochondrial capillary angiopathy may cause unique edematous lesions predominantly involving the cortex. As a consequence, most susceptible layers of the cortex may result in neuronal loss. Therapeutic targets include each ongoing process of the disease.
Full Text of this Article in Japanese PDF (269K)

(臨床神経, 48:1006−1009, 2008)
key words:MELAS, 脳卒中様発作, けいれん, 頭痛, 病態

(受付日:2008年5月17日)