Mitochondrial Strokes: Diagnostic Challenges and Chameleons.

Chiara Pizzamiglio,William L Macken,Cathy E Woodward,Michael G Hanna,Robert D S Pitceathly,Enrico Bugiardini

doi:10.3390/genes12101643

Abstract

Mitochondrial stroke-like episodes (SLEs) are a hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). They should be suspected in anyone with an acute/subacute onset of focal neurological symptoms at any age and are usually driven by seizures. Suggestive features of an underlying mitochondrial pathology include evolving MRI lesions, often originating within the posterior brain regions, the presence of multisystemic involvement, including diabetes, deafness, or cardiomyopathy, and a positive family history. The diagnosis of MELAS has important implications for those affected and their relatives, given it enables early initiation of appropriate treatment and genetic counselling. However, the diagnosis is frequently challenging, particularly during the acute phase of an event. We describe four cases of mitochondrial strokes to highlight the considerable overlap that exists with other neurological disorders, including viral and autoimmune encephalitis, ischemic stroke, and central nervous system (CNS) vasculitis, and discuss the clinical, laboratory, and imaging features that can help distinguish MELAS from these differential diagnoses.

Highlights

Academic Editors: Monika Olahova and Robert W
The diagnosis can be extremely challenging during the acute phase of an stroke-like episode (SLE), when the patient is presenting with MELAS for the first time
A follow up brain MRI performed after seven days showed extension of the lesion into the left occipital lobe (Figure 3), compatible with a mitochondrial stroke-like lesion

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Mitochondrial stroke-like episodes (SLEs) are defined as acute/subacute, evolving, focal neurologic deficits, usually driven by seizure activity, in primary mitochondrial diseases (PMDs) [1], and are the hallmark of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). According to the diagnostic criteria of MELAS [7], a combination of clinical findings of SLE plus evidence of mitochondrial dysfunction (i.e., definitive gene mutation related to MELAS, mitochondrial abnormalities in muscle biopsy, high lactate levels in plasma and/or in cerebral spinal fluid, or deficiency of mitochondrial enzyme activities) are necessary for a definite diagnosis. The diagnosis can be extremely challenging during the acute phase of an SLE, when the patient is presenting with MELAS for the first time. We describe four patients with MELAS presenting with an SLE that initially masqueraded as other acute/subacute acquired neurologic disorders, and highlight the importance of early diagnosis and appropriate management of SLEs to improve outcomes in MELAS

Materials and Methods

Findings

Case 1

Case 2

Discussion

Conclusions