Metabolic stroke in childhood: Diagnostic approach and suggestions for therapy

Abstract

The central nervous system is particularly vulnerable to certain metabolic abnormalities that may result in energy failure and subsequent neuronal cell death with clinical presentation as strokelike episodes. The mitochondrion and its electron transport chain machinery provide the main source of ATP for neurons and the most frequent causes of metabolic stroke are associated with the disorders of mitochondria. Mitochondrial diseases are a heterogeneous group of conditions affecting different organs of the body with variable severity. Both inborn errors (e.g. organic acidurias) and mitochondrial cytopathies can lead to stroke by vascular or cytotoxic mechanisms, thereby making a differential diagnosis complicated when using standard clinical investigations or neuroimaging. This article will provide an overview of various metabolic strokes in childhood with a special emphasis on the most frequent mitochondrial diseases.

Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management

“…Inherited metabolic and genetic defects increase the risk of a stroke (3)(4)(5). The physiopathology of a metabolic stroke in patients with inherited metabolic diseases are overlapping (2).…”

“…Patients with mitochondrial disorders are at risk of developing metabolic stroke (6,7). SLEs are the hallmark of mitochondrial encephalopathy with lactic acidosis and strokelike episode (MELAS) syndrome, and they appear less frequently in other specific or non-specific mitochondrial disorders (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(28)(29)(30)(31)(32)(33)(34)(35). Although the pathophysiology of SLEs is not entirely clear, it may involve mitochondrial dysfunction in the neurons and capillary endothelial cells (2,7).…”

“…The most relevant risk factors and causes of a pediatric stroke are vasculopathies, infections, cardiac anomalies, or coagulopathies (1). Although strokes are rarely caused by metabolic disorders, they are increasingly recognized as inherited causes of pediatric strokes (2)(3)(4)(5)(6)(7). Metabolic disorders may cause classical ischemic strokes, such as those occurring in patients with cystathionine β-synthase deficiency, or more commonly "metabolic strokes, " such as those occurring in patients with mitochondrial disorders (3)(4)(5).…”

“…Although strokes are rarely caused by metabolic disorders, they are increasingly recognized as inherited causes of pediatric strokes (2)(3)(4)(5)(6)(7). Metabolic disorders may cause classical ischemic strokes, such as those occurring in patients with cystathionine β-synthase deficiency, or more commonly "metabolic strokes, " such as those occurring in patients with mitochondrial disorders (3)(4)(5). Metabolic strokes begin with metabolic dysfunctions that lead to the rapid onset of central neurological deficits in the absence of vessel occlusion or rupture (3)(4)(5)7).…”

“…Metabolic disorders may cause classical ischemic strokes, such as those occurring in patients with cystathionine β-synthase deficiency, or more commonly "metabolic strokes, " such as those occurring in patients with mitochondrial disorders (3)(4)(5). Metabolic strokes begin with metabolic dysfunctions that lead to the rapid onset of central neurological deficits in the absence of vessel occlusion or rupture (3)(4)(5)7). Early recognition of these metabolic disorders and prompt initiation of appropriate treatment may improve the prognosis.…”