Management of mitochondrial stroke‐like‐episodes

Abstract

Aim of this review is to discuss recent findings concerning the management of stroke-like episodes (SLEs) in patients with mitochondrial disorders (MIDs). Various databases were searched for appropriate literature. SLEs are a dominant feature of MIDs and occur most frequently in MELAS-syndrome, less frequently in MERRF-syndrome, Kearns-Sayre-syndrome, or Leigh-syndrome. SLEs occur at all ages and are frequently accompanied by other cerebral abnormalities. Clinically, SLEs mimic ischemic stroke but not on imaging studies and concerning the management. The morphological equivalent on MRI is the stroke-like-lesion, representing a vasogenic edema (hyperintensity on T2, diffusion-weighted imaging and apparent diffusion coefficient in the acute and subacute or chronic stage, most frequently in the parieto-occipital region, surpassing vascular territories). For diagnostic and therapeutic reasons SLEs need to be clearly delineated from ischemic stroke and cerebral bleeding. Though there is no causal therapy available, symptomatic and general measures can help to resolve the clinical manifestations. In conclusion this review shows that SLEs are a dominant feature of some syndromic or non-syndromic MIDs. The most effective strategy for the treatment of SLEs appears to be the application of L-arginine, coenzyme-Q, steroids, edaravone, creatine-monohydrate, or dichloracetate.

Prognosis of symptomatic patients with the A3243G mutation of mitochondrial DNA

“…15 The effect of antiplatelet agents remains uncertain. In our investigation, all of our 12 patients with stroke showed large or cortical infarctions.…”

Carotid dissection in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

“…The etiology of the stroke-like episodes in MELAS has been debated with several proposed mechanisms: a global failure in mitochondrial energy metabolism, neuronal hyperexcitability, or an underlying mitochondrial angiopathy [2]. Evidence supporting a vascular etiology includes both the accumulation of abnormal mitochondria and the accumulation of mutant mtDNA in small cerebral arteries [3][4][5].…”

“…The most commonly associated genetic mutation is an adenine to guanine transition at nucleotide 3243 in the mitochondrial genome [1]. The pathogenesis of stroke-like episodes is not fully understood, but is believed to be due to mitochondrial angiopathy, metabolic defects, or neuronal hyperexcitability [2]. Mitochondrial angiopathy has largely been attributed to small vessel disease.…”

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population

“…Mitochondrial diseases are a rare, but well-recognized cause of ischemic stroke (IS)-like episodes at various ages [2,4]. While MELAS is the most common cause, other mitochondrial diseases such as myoclonic epilepsy with ragged red fibers (MERRF), Kearns-Sayre syndrome, Leigh syndrome, mitochondrial recessive ataxia syndrome (MIRAS), and hyperornithinemia-hyperammonemia-homocitrullinuria (triple-H syndrome) have also rarely been reported to be associated with IS-like lesions [4,5].…”

“…While MELAS is the most common cause, other mitochondrial diseases such as myoclonic epilepsy with ragged red fibers (MERRF), Kearns-Sayre syndrome, Leigh syndrome, mitochondrial recessive ataxia syndrome (MIRAS), and hyperornithinemia-hyperammonemia-homocitrullinuria (triple-H syndrome) have also rarely been reported to be associated with IS-like lesions [4,5]. The pathophysiology and course of stroke-like episodes in patients with mitochondrial diseases are distinct from IS and are probably underlied by a number of mechanismsalone or in combination-discussed in detail elsewhere [4]. We previously reported only two MELAS patients among 1008 young patients with first-ever IS at their age of 15-49 years [6].…”