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.
Highlights
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
Any further responses from the reviewers can be found at the end of the article Correspondence We read with interest the consensus statement by Ng et al about the pathogenesis and treatment of stroke-like lesions (SLLs)[1]
There is no animal model of a MID available in which triggering of seizures induces the development of a SLL
Summary
Any reports and responses or comments on the article can be found at the end of the article. As with increased oxygen concentrations in venous blood from MID patients, cells within the SLL are no longer capable of utilising oxygen sufficiently. They most likely change their energy metabolism to anaerobic glycolysis or produce ATP within the cytoplasm by means of glycolysis. SLLs may develop in response to stress as neurons carrying mutated mitochondria are no longer capable to meet an increased metabolic demand. Extra-cortical SLLs are no argument against the metabolic hypothesis as high energy demand may occur in the cortex and in other cerebral locations, depending on the current tasks of a network or circuit. Understanding the pathophysiology of SLLs is a prerequisite to optimally manage them
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