Association between stroke-like episodes and neuronal hyperexcitability in MELAS with m.3243A&gt;G: A case report

Sakaï, Shota; Osaki, Masato; Hidaka, Masaoki; Kimura, Satoshi; Ohya, Yuichiro; Ago, Tetsuro; Kitazono, Takanari; Arakawa, Shuji

doi:10.1016/j.ensci.2018.08.003

Cited by 6 publications

(12 citation statements)

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“…The pathomechanism of SLEs remains still unclear; however, there are some hypotheses that may propose an explanation for the most probable ways of SLL development [ 1 , 5 , 6 ]. In general, the SLE’s pathogenesis is associated with the dysfunction of mitochondria [ 1 , 5 , 17 , 23 ]. Morphological equivalents of SLEs are described as SLLs and could be detected via neuroimaging techniques, especially magnetic resonance imaging (MRI).…”

Section: Introductionmentioning

confidence: 99%

“…We also considered the main neurometabolic disorders associated with SLEs occurrence, specific neuroimaging changes and the electroencephalographic (EEG) patterns coexisting with various metabolic errors of metabolism. Performing a continuous EEG could especially improve the accuracy of diagnostic management in patients with inborn errors of metabolisms and reveal epileptic discharges secondary to increased specific metabolites due to the epileptogenic hypothesis [ 1 , 4 , 5 , 6 , 10 , 12 , 17 , 23 ]. It seems to be crucial to differentiate SLEs mainly from ischemic stroke due to distinct necessary treatment procedures.…”

Section: Introductionmentioning

confidence: 99%

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Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

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Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial to distinguish SLEs from cerebral infarction or intracerebral hemorrhage, mainly due to the variety in management. Another significant issue to underline is the meaning of the main pathogenetic hypotheses in the development of SLEs. The diagnostic process is based on the patient’s medical history, physical and neurological examination, neuroimaging techniques and laboratory and genetic testing. Implementation of treatment is generally symptomatic and includes L-arginine supplementation and adequate antiepileptic management. The main aim of the current review was to summarize the basic and actual knowledge about the occurrence of SLEs in various inherited neurometabolic disorders, discuss the possible pathomechanism of their development, underline the role of neuroimaging in the detection of SLLs and identification of the electroencephalographic patterns as well as histological abnormalities in inherited disorders of metabolism.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

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“…,45 NA Unclear (N = 1; n = 1)23 Unclear: N = 2; n = 2 N/R: N = 2; n = 235 NA N/R: N = 1; n = 134 NANeuroimagingPositive: N = 5; n = 5 Lactate and ↑ NAA/Cho at 3 d (MRS) and ↓ FLAIR signal (MRI) 8 d (N = 1; n = 1)44 ;↓ lactate at 36 h (N = 1; n = 1)43 MRI high-intensity signal normalized at 1 wk (N = 2; n = 2)41 Improvements in MRS, timing not clear (N = 1; n = 1)12 Positive: At 30 min, uptake in the decreased rCBF in the ischemic region improved (SPECT)10 NA MRI was not used in the evaluation of response to IV L-arginine Some improvements: N = 5; n = 6 Partial resolution after 3 d (N = 1; n = 1, 1st episode N/R)24 ; 1 mo (N = 1; n = 1)15 ; timing unclear (N = 1; n = 1)22 ; most of the abnormal MRI signals disappeared at 38 d (N = 1; n = 1, 1st episode N/R)26 No change in lesion but ↓ peak lactate (N = 1; n = 2)37 NA NANegative: N = 3; n = 3 3 mo after discharge, new episode (MRI); ↑ atrophy (FLAIR) (N = 1; n = 1)13 6 d, lesions further expanded (DWI) (N = 1; n = 1)17 MRI at 4 mo after admission: diffuse brain atrophy (N = 1; n = 1)36 NA NA Unclear: N = 2; n = 2 MRS (lactate and NAA signal) improved compared with previous episode27 ↓Blood vessel dilation and hyperperfusion (MRI, CT) 13 d (N = 1; n = 1)38 …”

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

Stefanetti

Errington

et al. 2022

Neurology

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Objective:Stroke management in the context of primary mitochondrial disease is clinically challenging and the best treatment options for patients with stroke-like episodes remain uncertain. We sought to perform a systematic review on the safety and efficacy of L-arginine use in the acute and prophylactic management of stroke-like episodes in patients with mitochondrial disease.Methods:The systematic review was registered in PROSPERO (CRD42020181230). We searched six databases from inception − 15/01/2021: MEDLINE, Embase, Scopus, Web of Science, CINAHL and ClinicalTrials.gov. Original articles and registered trials available, in English, reporting L-arginine use in the acute or prophylactic management of stroke-like episodes in patients with genetically confirmed mitochondrial disease were eligible for inclusion.Data on safety and treatment response were extracted and summarized by multiple observers. Risk of bias was assessed by the methodological quality of case reports, case series and a risk-of-bias checklist for non-randomized studies. Quality of evidence was synthesized using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and Grade of Recommendations. The predetermined main outcome measures were clinical response to L-arginine treatment, adverse events, withdrawals, and deaths (on treatment and/or during follow up), as defined by the author.Results:Thirty-seven articles met inclusion [0=randomised controlled trials (RCTs); 3 open-label; 1 retrospective cohort; 33 case reports/case series] (N = 91 patients; 86% m.3243A>G). In the case reports, 54% of patients reported a positive clinical response to acute L-arginine, of which 40% were concomitantly treated with AEDs. Improved headache at 24-hours was the greatest reported benefit in response to IV L-arginine in the open-label trials (31/39, 79%). Of 15/48 patients (31%) who positively responded to prophylactic L-arginine, AEDs were either used (7/15) or unreported (8/15). Moderate adverse events were reported in the follow-up of both IV and oral L-arginine treatment and 11 patients (12%) died during follow up or while on prophylactic treatment.Conclusion:The available evidence is of poor methodological quality and classified as Level 5. IV and/or oral L-arginine confers no demonstrable clinical benefit in either the acute or prophylactic treatment of MELAS, with more robust controlled trials required to assess its efficacy and safety profile.

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“…With interest we read the article by Sakai et al about a 53 years-old female with MELAS syndrome due to the variant m.3243A>G in the tRNA /( Leu ) gene [1]. The patient was admitted for a first stroke-like episode (SLE), which did not resolve upon administration of L-arginine alone but only after addition of levetirazetam [1]. We have the following comments and concerns.…”

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confidence: 99%

“…The patient was obviously underweighted with 32 kg and a body height of 149 cm [1]. Was the low body weight attributable to a gastrointestinal abnormality, to a specific diet the patient was taking regularly, to a hormonal problem, or to the drugs she was regularly taking?…”

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confidence: 99%

Antiepileptics and NO-precursors may be beneficial for stroke-like episodes

Finsterer

2019

eNeurologicalSci

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Pathogenesis and management of stroke-like episodes in mitochondrial disorders is under debate and no consensus has been reached thus far how this phenomenon should be managed. Frequently applied are nitric oxide (NO) precursors but a well-designed study confirming the effectiveness of such an approach is lacking. Administration of antiepileptic drugs can be meaningful if there is paroxysmal activity on EEG or if a patient presents with seizures. The case reported by Sakai et al. suggests that administration of antiepileptic drugs for a stroke-like episode may be beneficial even in the absence of seizures or paroxysmal EEG activity.

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Association between stroke-like episodes and neuronal hyperexcitability in MELAS with m.3243A>G: A case report

Abstract: HighlightsThe pathophysiology of the stroke-like episodes of MELAS has not completely been elucidated.Here we report a case of stroke-like episodes, successfully treated with levetiracetam.Neuronal hyperexcitability can be the underlying mechanism of stroke-like episodes in MELAS.

Cited by 6 publications

References 12 publications

Stroke-like Episodes in Inherited Neurometabolic Disorders

Stroke-like Episodes in Inherited Neurometabolic Disorders

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

Antiepileptics and NO-precursors may be beneficial for stroke-like episodes

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