title: Myoclonus epilepsy and ragged-red fibres (MERRF). 1. A clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study.
abstract: Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.
authors.affiliation: Montreal Neurological Institute and Hospital, Québec, Canada.
authors.forename: S F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: S
authors.initials: S
authors.lastname: Carpenter
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: G
authors.initials: G
authors.lastname: Karpati
authors.forename: E A
authors.initials: EA
authors.lastname: Shoubridge
authors.forename: F
authors.initials: F
authors.lastname: Andermann
authors.forename: E
authors.initials: E
authors.lastname: Meyer
authors.forename: J L
authors.initials: JL
authors.lastname: Tyler
authors.forename: M
authors.initials: M
authors.lastname: Diksic
authors.forename: D
authors.initials: D
authors.lastname: Arnold
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002648:Child; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000648:ultrastructure; D009132:Muscles / Q000473:pathology; D009420:Nervous System / Q000473:pathology; D010375:Pedigree; D012867:Skin / Q000473:pathology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D005947:Glucose