NEURORADIOLOGICAL FEATURES OF 6 KINDREDS WITH MELAS TRNA(LEU) A3243G POINT MUTATION - IMPLICATIONS FOR PATHOGENESIS

Objective-To determine the neuroradiological abnormalities associated with subjects carrying the mitochondrial myopathy, encephalopathy, lac tic acidosis, and strokelike episodes (MELAS) tRNA(Leu(UUR)) A3243G po int mutation Methods-Mitochondrial genetic analysis was performed on 2 4 subjects from six kindreds with the MELAS tRNA(Leu(UUR)) A3243G poin t mutation. Cerebral CT and MRI were performed on 24 patients and 15 p atients respectively. Previous neuroradiological investigations includ ing cerebral CT from four deceased members of the families were also r eviewed. Histological examination of postmortem specimens of two patie nts within the kindreds was performed. Results-The commonest radiologi cal finding was basal ganglia calcification. Other abnormalities inclu ded focal lesions and cerebellar and cerebral atrophy. Basal ganglia c alcification was progressive, symmetric, and asymptomatic. Histologica lly, basal ganglia calcification in one patient was found to be in the pericapillary regions of the globus pallidus, with no neuronal involv ement. Focal lesions most commonly involved the grey matter of the par ietal and occipital lobes and cerebellum. Histopathological examinatio n suggested that these were due to cellular rather than vascular dysfu nction. Enlargement of the fourth ventricle was the first sign of cere bellar atrophy. Cerebral and cerebellar atrophy were only present with severe disease. Conclusions-These radiological findings, when conside red in the context of the clinical and pathological findings, seem to reflect two major disease processes: an intermittent abrupt loss of fu nction associated with cell injury from which there is at least partia l recovery and a slowly progressive degenerative process causing basal ganglia calcification, and cerebral and cerebellar atrophy. The clini cal and radiological features resulting from these processes are disti nctive and provide insight into the consequences of mitochondrial dysf unction on the brain.