Clinicopathological findings of a mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes/Leigh syndrome overlap patient with a novel m.3482A>G mutation in MT‐ND1

Abstract

We report clinicopathological findings of a patient with mitochondrial encephalopathy, lactic acidosis, and stroke‐like episodes/Leigh syndrome (MELAS/LS) associated with a novel m.3482A>G mutation in MT‐ND1. A 41‐year‐old woman had experienced multiple stroke‐like episodes since age 16. She developed akinetic mutism two months before admission to our hospital. Neurological examination revealed akinetic mutism, bilateral deafness, and muscular atrophy. Cerebrospinal fluid tests revealed elevated pyruvate and lactate levels. Fluid‐attenuated inversion recovery images on magnetic resonance imaging showed hyperintense areas in the right frontal and both sides of temporal and occipital lobes, both sides of the striatum, and the midbrain. Muscle biopsy revealed strongly succinate dehydrogenase‐reactive blood vessels. L‐arginine therapy improved her consciousness and prevented further stroke‐like episodes. However, she died from aspiration pneumonia. Postmortem autopsy revealed scattered infarct‐like lesions with cavitation in the cerebral cortex and necrotic lesions in the striatum and midbrain. The patient was pathologically confirmed as having MELAS/LS based on two characteristic clinicopathological findings: presenting MELAS/LS overlap phenotype and effectiveness of L‐arginine treatment.

The variant m.3482A>G in MT‐ND1 is benign and not responsible for MELAS/Leigh overlap syndrome

“…1 Postmortem investigations revealed postischemic changes of the cerebral cortex, bilateral necrosis of the striatum and the midbrain, and calcification of the basal ganglia. 1 We have the following comments and concerns.…”

“…The variant m.3482A>G in MT-ND1 is benign and not responsible for MELAS/Leigh overlap syndrome With interest we read the article by Hayashi et al about a 41-year-old woman diagnosed upon clinical presentation with mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS)/Leigh overlap syndrome and the variant m.3482A>G in MT-ND1, described as novel and considered to be pathogenic. 1 MELAS manifested phenotypically with recurrent stroke-like episodes (SLEs) from the age of 16 years, akinetic mutism, impaired hearing, and myopathy. 1 Postmortem investigations revealed postischemic changes of the cerebral cortex, bilateral necrosis of the striatum and the midbrain, and calcification of the basal ganglia.…”

“…1 MELAS manifested phenotypically with recurrent stroke-like episodes (SLEs) from the age of 16 years, akinetic mutism, impaired hearing, and myopathy. 1 Postmortem investigations revealed postischemic changes of the cerebral cortex, bilateral necrosis of the striatum and the midbrain, and calcification of the basal ganglia. 1 We have the following comments and concerns.…”

“…The cause of ischemic stroke at age 25 years remains unclear. 1 We should be told whether this stroke was truly ischemic in nature or another SLE, how the stroke was classified using the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification (e.g. macroangiopathy, embolism, or microangiopathy), 3 how the stroke manifested on multimodal magnetic resonance imaging (MRI), and whether the patient had any classical cardiovascular risk factors.…”

l -Arginine in Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

“…Positive: N = 15 (54%); n = 18 (55%) Within 24 h (N = 5; n = 6) 20,24,41,43 ; few days (N = 1; n = 1) 44 ; 1 wk (N = 1; n = 1) 39 ; 3-4 wk (N = 2; n = 3), 37,40 ; 6 wk (N = 2; n = 2) 22,25 Improved; timing N/R (N = 3; n = 4) 26,38,42 Partial improvement (N = 1; n = 3 over 27 mo) 23 Positive: Within 24 h of treatment, improvement (episode or patient): headache 31/39 (79%); disability 25/31 (81%); nausea/vomiting 32/36 (89%); positive visual symptoms 20/31 (65%) 10,11 Positive: N = 1; n = 1, improved consciousness within 4 wk of treatment 21 Positive: N = 5 (56%); n = 8 (47%) within 24 h of end of treatment. All treatment immediately on hospital presentation 9…”