Consensus-based statements for the management of mitochondrial stroke-like episodes

Abstract

Background: Focal-onset seizures and encephalopathy are prominent features of a stroke-like episode, which is a severe neurological manifestation associated with subtypes of mitochondrial disease. Despite more than 30 years of research, the acute treatment of stroke-like episodes remains controversial. Methods: We used the modified Delphi process to harness the clinical expertise of a group of mitochondrial disease specialists from five European countries to produce consensus guidance for the acute management of stroke-like episodes and commonly associated complications. Results: Consensus on a new definition of mitochondrial stroke-like episodes was achieved and enabled the group to develop diagnostic criteria based on clinical features, neuroimaging and/or electroencephalogram findings. Guidelines for the management of strokelike episodes were agreed with aggressive seizure management strongly recommended at the outset of stroke-like episodes. Conclusions: Our consensus statement defines stroke-like episodes in terms of an epileptic encephalopathy and we have used this to revise both diagnostic criteria and guidelines for management. A prospective, multi-centre, randomised controlled trial is required for evaluating the efficacy of any compound on modifying the trajectory of stroke-like episodes.

Keywords: MELAS; POLG; antiepileptic drugs; encephalopathies; epilepsy; m.3243A>G; neurodegenerative disorders (other than dementia); status epilepticus; stroke.

Figure 1.. Definition, clinical features and diagnostic criteria of stroke-like episodes.

( A) Consensus-based definition of mitochondrial stroke-like episode and diagnostic criteria. ( B) A list of neurological signs and symptoms associated with stroke-like episodes. ( C) MRI head FLAIR-sequence (i) shows typical stroke-like lesions (confluent cortical and subcortical hyperintensities) involving bilateral parietal lobes with restricted diffusion demonstrated in the right parietal lobe (ii). This patient who has the m.3243A>G-related MELAS syndrome presented with subacute-onset intermittent speech arrest, confusion and focal motor seizures affecting left arm and leg. ( D) The electroencephalogram (EEG) of the same patient shows a well-formed and symmetrical 8–9Hz alpha rhythm intermixed with a large amount of diffuse theta wave in the temporal areas. A persistent sharp/spike and slow wave focus is seen over the right central electrodes (dotted-line red boxes), corresponding with the stroke-like lesion in the right parietal area identified on the MRI scan.