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

Abstract

Focal-onset seizures and encephalopathy are prominent Background: 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.We used the modified Delphi process to harness the clinical Methods: 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.Consensus on a new definition of mitochondrial stroke-like Results: episodes was achieved and enabled the group to develop diagnostic criteria based on clinical features, neuroimaging and/or

Comprehensive Multi-omics Analysis Reveals Mitochondrial Stress as a Central Biological Hub for Spaceflight Impact

“…However, mitochondrial dysfunction attenuates platelet survival and increases the risk for thrombovascular events (Kunz et al, 2017;Melchinger et al, 2019), increasing stroke risk (Behrouzi and Punter, 2018). Mitochondrial dysfunction may cause stroke-like episodes independent of hypoxia (Ng et al, 2019). Therefore, spaceflight-induced mitochondrial dysfunction could increase cardiovascular disease risk in longterm missions caused by microgravity cardiovascular deconditioning and space radiation (Hughson et al, 2018).…”

The metabolic hypothesis is more likely than the epileptogenic hypothesis to explain stroke-like lesions

“…First, not all patients with a mitochondrial disorder (MID) who ever experienced a SLL also have an individual history positive for epilepsy 2 . Thus, we disagree with the statement that "seizures are commonly present at the outset of strokelike episodes (SLEs)" 1 . Second, the electroencephalography during a SLL does not reveal epileptogenic activity in most cases 3 .…”

“…We read with interest the consensus statement by Ng et al about the pathogenesis and treatment of stroke-like lesions (SLLs) 1 . We largely disagree with the consensus paper as it does not consider arguments for alternative pathomechanisms explaining the development of a SLL.…”

When to think about mitochondrial disease

“…Most adult patients present to general neurology clinics with slowly progressive neurological symptoms, such as chronic progressive external ophthalmoplegia, myopathy, neuropathy and ataxia. However, neurologists need to be aware that the acute presentations of mitochondrial disease, such as stroke-like episodes and refractory focal-onset seizures, 3 can mimic other commoner neurological disorders, such as ischaemic stroke, infective/immune-mediated encephalitis and CNS demyelinating/inflammatory diseases. The initial description of MELAS syndrome suggested that the stroke-like episodes predominantly affect people aged less than 40 years.…”

“…7 Currently, there is no proven effective disease-modifying therapy for the stroke-like episodes; aggressive seizure management remains the most crucial step to protect patients’ cerebral function. 3…”