MELAS-Syndrom als Differenzialdiagnose des juvenilen ischämischen Insultes

Zusammenfassung

Die mitochondriale Enzephalomyopathie, Laktazidose und schlaganfallähnliche Episoden (MELAS)-Syndrom ist eine phäno- und genotypisch heterogene mitochondriale Erkrankung mit klinischem Beginn zwischen der ersten und dritten Dekade. Das klinische Hauptmerkmal der Erkrankung ist die schlaganfallähnliche Episode, die einen ischämischen Schlaganfall imitiert, aber meist nur transient auftritt und ohne längerfristige Behinderung einhergeht. Das morphologische Äquivalent im MRI ist eine T2-Hyperintensität, vorwiegend über der temporo-parieto-occipitalen Region, nicht beschränkt auf ein bestimmtes Gefäßterritorium, die in der Diffusions- und ADC-gewichteten Sequenz ebenfalls hyperintens imponiert (vasogenes Ödem, schlaganfallähnliche Läsion). Als weitere klinische Manifestationen können epileptische Anfälle, kognitiver Abbau, psychotische Episoden, Laktazidose, Migräne, Visusstörung, Hörstörung, Kleinwuchs, Diabetes oder eine Myopathie auftreten. Die Muskelbiopsie zeigt typischerweise „ragged-red fibers”, COX-negative Fasern, SDH-Überreaktivität, und abnorm geformte Mitochondrien mit parakristallinen Einschlüssen. Die Diagnose beruht auf dem Nachweis eines biochemischen Defektes der Atmungskette oder einer der krankheitsauslösenden Mutationen, von denen 80 % das mitochondriale tRNALeu-Gen betreffen.

Abstract

Mitochondrial encephalomyopathy, lactacidosis and stroke-like episode (MELAS) syndrome is a phenotypically and genetically heterogenous mitochondrial disorder with a clinical onset between the first and third decade. The clinical hallmark is the stroke-like-episode, which mimicks ischemic stroke but is usually transient and non-disabling in nature. The morphological equivalent on MRI is a T2-hyperintensity, predominantly over the temporo-parieto-occipital region, not confined to a vascular territory, which is also hyperintense on diffusion weighted imaging and on apparent diffusion coefficient sequences (vasogenic edema, stroke-like lesion). Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes, or myopathy. Muscle biopsy typically shows ragged-red fibers, COX-negative fibers, SDH hyperreactivity, and abnormally shaped mitochondria with paracristalline inclusions. The diagnosis is confirmed by demonstration of a biochemical respiratory chain defect or one of the disease-causing mutations, of which 80 % affect the mitochondrial tRNALeu gene.

Schlüsselwörter

Schlaganfall - mitochondriale Funktionsstörung - Enzephalomyopathie - metabolische Erkrankung - Zentralnervensystem

Key words

Stroke - mitochondrial disorder - encephalomyopathy - metabolic disorder - central nervous system

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