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The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

ABSTRACT: Stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome but occur in other mitochondrial disorders (MIDs) as well. The morphological equivalent of the SLE is the stroke-like lesion (SLL) on magnetic resonance imaging (MRI). The pathophysiology of SLLs is under debate, but several hypotheses have been raised to explain the phenomenon. Of these, the metabolic, epileptogenic, and vascular hypotheses are the most frequently discussed. There are several arguments for and against these hypotheses, but a consensus has not been reached which of them provides the correct explanation. A recent consensus statement generated by a panel of experts applying the Delphi method, favoured the epileptogenic hypothesis and recommended treatment of SLEs with antiepileptic drugs, irrespective if the patient presented with a seizure or epileptiform discharges on electroencephalography (EEG) or not. We disagree with this general procedure and provide the following arguments against the epileptogenic hypothesis: 1. not each SLE is associated with seizures. 2. epileptiform discharges may be absent on EEG during a SLE. 3. SLLs are not restricted to the cortex. 4. antiseizure-drugs (ASDs) may not prevent the progression or recurrence of a SLL. 5. ASDs may terminate seizures but no other phenotypic feature of a SLE. 6. patients already under ASDs are not immune from developing a SLL. 7. SLLs usually last longer than seizures. 8. no animal model supports the epileptogenic hypothesis. The strongest arguments for the metabolic hypothesis are that SLLs are not confined to a vascular territory, that the oxygen-extraction fraction within a SLL is reduced, and that there is hypometabolism within a SLL on FDG-PET. SLLs may respond to antioxidants, NO-precursors, steroids, or the ketogenic diet. ASDs should be applied only if there is clinical or electrophysiological evidence of seizure-activity.

SUBMITTER: Finsterer J

PROVIDER: S-EPMC7324943 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

Finsterer Josef J

Wellcome open research 20200624

Stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome but occur in other mitochondrial disorders (MIDs) as well. The morphological equivalent of the SLE is the stroke-like lesion (SLL) on magnetic resonance imaging (MRI). The pathophysiology of SLLs is under debate, but several hypotheses have been raised to explain the phenomenon. Of these, the metabolic, epileptogenic, and vascular hypotheses are the most frequentl ...[more]

PMID: 32647751

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Project description:BackgroundTo prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists.MethodsWe assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy. At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners' specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated.ResultsFourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions.ConclusionsEpileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

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The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

Publications

The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions.

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