Mitochondrial metabolic stroke: Phenotype and genetics of stroke-like episodes

Stroke-like episodes (SLEs) are the hallmark of mitochondrial encephalopathy with lactic acidosis and stroke-like episode (MELAS) syndrome but rarely occur also in other specific or nonspecific mitochondrial disorders. Pathophysiologically, SLLs are most likely due to a regional disruption of the blood-brain barrier triggered by the underlying metabolic defect, epileptic activity, drugs, or other factors. SLEs manifest clinically with a plethora of cerebral manifestations, which not only include features typically seen in ischemic stroke, but also headache, epilepsy, ataxia, visual impairment, vomiting, and psychiatric abnormalities. The morphological correlate of a SLE is the stroke-like lesion (SLL), best visualised on multimodal MRI. In the acute stages, a SLL presents as vasogenic edema but may be mixed up with cytotoxic components. Additionally, SLLs are characterized by hyperperfusion on perfusion studies. In the chronic stage, SLLs present with a colorful picture before they completely disappear, or end up as white matter lesion, cyst, laminar cortical necrosis, focal atrophy, or as toenail sign. Treatment of SLLs is symptomatic and relies on recommendations by experts. Beneficial effects have been reported with nitric-oxide precursors, antiepileptic drugs, antioxidants, the ketogenic diet, and steroids. Lot of research is still needed to uncover the enigma SLE/SLL.