This chapter focuses on disorders due to mitochondrial respiratory chain (MRC) dysfunction and use the collective term mitochondrial cytopathy. It discusses two mtDNA disorders, myoclonus epilepsy with ragged red fibers (MERRF) and mitochondrial myopathy encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Epilepsy occurs primarily in the group of patients that develop stroke-like lesions (SLL) and seizures are often preceded by or associated with migraine-like headache. Magnetic resonance spectroscopy can demonstrate elevated lactate in regions of the brain, while positron emission tomography (PET) scanning can provide metabolic information suggesting lowered ATP production. Convulsive status epilepticus (CSE) is treated aggressively using traditional protocols. Benzodiazepine infusion is evaluated as a first line together with phosphenytoin and occasionally phenobarbital. The epilepsies in mitochondrial cytopathies often reveal both focal and generalized features. Treatment of mitochondrial cytopathies comprises awareness of the potential complications and early and aggressive control of seizures.

Stroke-like episodes have most frequently been reported in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), a multisystemic syndrome associated with mutations of mitochondrial DNA (mtDNA). Blood lactate levels are increased because of a dysfunction in the respiratory chain, with resulting inhibition of the citric acid cycle and accumulation of pyruvate and lactate. Stroke-like episodes have been reported to be associated with other mtDNA mutations. These mutations are point mutations lying within tRNA-encoding genes or within proteinencoding genes, or are deletions encompassing several genes, showing that all these different genetic anomalies can cause a similar dysfunction of the mitochondrion resulting in stroke. Brain imaging can show calcifications of the basal ganglia and focal lesions in the occipital and parietal lobes that are not usually restricted to a vascular territory. NMR spectroscopy detects increased lactate levels. Published therapies include coenzyme Q10, nicotinamide and coadministration of cytochrome c, vitamin B1, and B2.

This chapter, reviews mitochondrial and other selective metabolic causes of stroke. In MELAS, despite the microangiopathic findings in the brain and muscles, the stroke-like episodes are more likely attributed to mitochondrial and metabolic dysfunction in neural tissue and glia rather than to ischemic vascular pathology. Kearns Sayre syndrome (KSS) is a mitochondrial disorder caused by large heteroplasmic deletions in mtDNA. Brain infarction, presumably secondary to cardioembolic sources, may occur. Hyperhomocysteinemia is a clinical syndrome caused by several enzyme deficiencies in methionine metabolism. Patients with homocystinuria have markedly elevated plasma homocysteine concentrations. Most patients present with peripheral venous thrombosis, including pulmonary embolism. Stroke, peripheral arterial occlusions, or myocardial infarction can be the initial presentation. The increased tendency for thrombosis usually presents as an ischemic stroke. Metabolic stroke due to hypoxemia and vascular insufficiency may occur in methylmalonic acidemia. Metabolic causes of stroke are quite heterogeneous.