Serial brain imaging analysis of stroke-like episodes in MELAS

Ito, Hiromichi; Mori, Koichi; Harada, Masafumi; Minato, M.; Naito, Etsuo; Takeuchi, Mayumi; Kuroda, Yasuhiro; Kubo, Shoji

doi:10.1016/j.braindev.2008.01.003

Cited by 64 publications

(57 citation statements)

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“…Also consistent with prior studies, 7,9 we found NAA reductions in patients with MELAS compared with all other groups. Because it is found almost exclusively in neurons and synthesized in neuronal mitochondria, NAA reductions generally reflect neuronal injury, dysfunction, or loss, and/or impaired mitochondrial function.…”

Section: -101217-19supporting

confidence: 93%

“…Therefore, upon conversion to the full MELAS syndrome, the postulated hypermetabolic state would likely not be sustained and levels of NAA, tCr, and tCho would decrease, in agreement with the results of this and prior studies in MELAS. 7,9,17,38,39 Logistic regression analyses identified ventricular lactate and gray matter tCho as predictors of conversion to the MELAS phenotype. The other metabolites and clinical indices were not predictors.…”

Section: -101217-19mentioning

confidence: 99%

“…Previously, we 5 and others [6][7][8][9][10] had reported elevated cerebral lactate levels in patients with MELAS and their mutation carrier relatives.…”

mentioning

confidence: 99%

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Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers

et al. 2014

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Objective: To establish cerebral metabolic features associated with the A3243G mitochondrial DNA mutation with proton magnetic resonance spectroscopic imaging ( 1 H MRSI) and to assess their potential as prognostic biomarkers.Methods: In this prospective cohort study, we investigated 135 clinically heterogeneous A3243G mutation carriers and 30 healthy volunteers (HVs) with 1 H MRSI. Mutation carriers included 45 patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS); 11 participants who would develop the MELAS syndrome during follow-up (converters); and 79 participants who would not develop the MELAS syndrome during follow-up (nonconverters). The groups were compared with respect to MRSI metabolic indices of 1) anaerobic energy metabolism (lactate), 2) neuronal integrity (N-acetyl-L-aspartate [NAA]), 3) mitochondrial function (NAA; lactate), 4) cell energetics (total creatine), and 5) membrane biosynthesis and turnover (total choline [tCho]).Results: Consistent with prior studies, the patients with MELAS had higher lactate (p , 0.001) and lower NAA levels (p 5 0.01) than HVs. Unexpectedly, converters showed higher NAA (p 5 0.042), tCho (p 5 0.004), and total creatine (p 5 0.002), in addition to higher lactate levels (p 5 0.032), compared with HVs. Compared with nonconverters, converters had higher tCho (p 5 0.015). Clinically, converters and nonconverters did not differ at baseline. Lactate and tCho levels were reliable biomarkers for predicting the risk of individual mutation carriers to develop the MELAS phenotype. Conclusions:1 H MRSI assessment of cerebral metabolism in A3243G mutation carriers shows promise in identifying disease biomarkers as well as individuals at risk of developing the MELAS phenotype. Neurology ® 2014;82:798-805 GLOSSARY CNS 5 Columbia Neurological Score; GNP 5 Global Neuropsychological; 1 H MRSI 5 proton magnetic resonance spectroscopic imaging; HV 5 healthy volunteer; MELAS 5 mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; MRS 5 magnetic resonance spectroscopy; NAA 5 N-acetyl-L-aspartate; tCho 5 total choline; tCr 5 total creatine.

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Section: -101217-19supporting

confidence: 93%

Section: -101217-19mentioning

confidence: 99%

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Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers

et al. 2014

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“…Concerning the possible role of seizures and/or SLE treatment in the arterial abnormalities reported, in our opinion, this seems unlikely, since two of the three patients lacked clinical and EEG abnormalities in favor of epilepsy, and arterial abnormalities were restricted to the brain areas involved by the SLE. One might suspect a more diffuse cerebral artery dilatation in treatment-induced perfusion abnormalities, although an interaction between SLE treatment therapies and cerebral arteries only involved in the SLE cannot be excluded.The variability of signal changes on ADC map in SLE in our three patients corresponded well to the earlier reports analyzing ADC in SLE showing cortical hypo-, iso-, or hyperintensities during SLE, probably also depending on the timing of MRI performance (and the stage of SLE) [1,2]. …”

supporting

confidence: 90%

“…The variability of signal changes on ADC map in SLE in our three patients corresponded well to the earlier reports analyzing ADC in SLE showing cortical hypo-, iso-, or hyperintensities during SLE, probably also depending on the timing of MRI performance (and the stage of SLE) [1,2].…”

supporting

confidence: 90%

Response of the authors to the comments of Josef Josef Finsterer and Sinda Zarrouk-Mahjoub on NeuroImage “Cerebral arterial and venous MRI abnormalities in MELAS”

Renard

Ion

2018

Acta Neurol Belg

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We would like to thank Josef Josef Finsterer and Sinda Zarrouk-Mahjoub for their excellent comments on our NeuroImage "Cerebral arterial and venous MRI abnormalities in MELAS".Hereby, we will give some more clinical and radiological details on the three MELAS patients reported. All three patients had the classical m.3243A>G mutation. The first patient was a 32-year-old man with a history of seizures treated by topiramate 75 mg/day presenting with a strokelike episode (SLE) in the absence of clinical or EEG abnormalities in favor of epilepsy. ADC map showed cortical hypointensity in the involved brain region in the absence of subcortical signal abnormalities. The SLE was treated by high-dose L-arginine in the acute phase. The second patient was a 20-year-old man presenting with involuntary unilateral lower limb movements evoking partial motor seizures. ADC map showed isointensity in the cortex associated with hyperintensity in the underlying subcortical involved brain regions. The patient refused EEG and left the hospital with levetiracetam 1000 mg/day antiepileptic therapy without other specific SLE treatment. The third patient was a 54-year-old woman with a history of epilepsy treated with lacosamide 200 mg/day presenting with SLE in the absence of clinical or EEG abnormalities in favor of epilepsy. ADC map showed mixed hyper/hypointensities in the cortex and hyperintensities in the underlying subcortical brain regions. The SLE was treated by high-dose L-arginine in the acute phase.We agree with the comments of the author that the arterial abnormalities reported were probably not causative but rather a phenomenon secondary to the primary metabolic defect. Concerning the possible role of seizures and/or SLE treatment in the arterial abnormalities reported, in our opinion, this seems unlikely, since two of the three patients lacked clinical and EEG abnormalities in favor of epilepsy, and arterial abnormalities were restricted to the brain areas involved by the SLE. One might suspect a more diffuse cerebral artery dilatation in treatment-induced perfusion abnormalities, although an interaction between SLE treatment therapies and cerebral arteries only involved in the SLE cannot be excluded.The variability of signal changes on ADC map in SLE in our three patients corresponded well to the earlier reports analyzing ADC in SLE showing cortical hypo-, iso-, or hyperintensities during SLE, probably also depending on the timing of MRI performance (and the stage of SLE) [1,2].

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Inherited Metabolic Disorders and Stroke Part 1

Testai

Gorelick

2010

Arch Neurol

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nherited metabolic disorders are single-gene genetic diseases associated with multiorgan damage. Some of these conditions increase the risk of stroke through a variety of mechanisms, and there is evidence that early recognition and initiation of appropriate treatment may improve prognosis. In this 2-part review we provide an update of the genetics, stroke pathophysiology, clinical manifestations, diagnosis, and treatment of metabolic disorders associated with stroke. In part 1, we concentrate on Fabry disease and mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. In part 2 we will review homocystinuria, organic acidurias, and urea cycle disorders.

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Serial brain imaging analysis of stroke-like episodes in MELAS

Cited by 64 publications

References 17 publications

Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers

Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers

Response of the authors to the comments of Josef Josef Finsterer and Sinda Zarrouk-Mahjoub on NeuroImage “Cerebral arterial and venous MRI abnormalities in MELAS”

Inherited Metabolic Disorders and Stroke Part 1

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