[Diagnostic criteria in classical infantile subacute necrotizing encephalomyelopathy (Leigh's disease)]

Abstract

Subacute necrotizing encephalomyelopathy (SNE; Leigh's disease), though a defined entity in neuropathological and morphological terms, is characterized by high clinical heterogenity. SNE of infancy can be defined and diagnosed on the basis of clinical symptoms more readily than juvenile and adult forms. Four patients with SNE displayed combinations of recurrent vomiting, difficulty in swallowing, failure to thrive, impairment of ocular innervation, muscle tone regulation and central regulation of respiration. These symptoms, particularly in combination, point to a disorder of the brainstem and basal ganglia. In addition, all four patients were suffering from lactic acidosis. Other possible indicators, but not in all 4 patients, were abnormal CT brain scans, impaired nerve conduction velocity, elevated CSF protein levels and enlarged mitochondria in muscle cells. Abnormal brainstem auditory evoked potentials have proved to be one of the best criteria for early diagnosis of brainstem lesions. Enzyme assays of pyruvate degradation in cultured skin fibroblasts revealed diminished activity of the pyruvate dehydrogenase complex in one patient (52 pmol/mg protein x min; median range 313, 82-917, n: 58). This paper summarizes the findings and proposes primary and secondary criteria of assistance in establishing an initial clinical diagnosis of infantile SNE. As no common pathogenetic mechanisms have yet been recognized and no uniform diagnostic markers are yet available, the diagnosis still requires confirmation by histological examination of brain and brainstem, as was the case with all four patients presented.