Mitochondrial stroke-like episodes: The search for new therapies

Orsucci, Daniele; Ienco, Elena Caldarazzo; Montano, Vincenzo; Siciliano, Gabriele; Mancuso, Michelangelo

doi:10.1016/j.phrs.2022.106228

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…In view of the spread of lesions beyond the arterial region, SLEs are more likely to be caused by neuronal hyperexcitability rather than from mitochondrial angiopathy. Recently, more and more researches proposed that neuronal hyperexcitability can better explain the stroke-like lesions than mitochondrial angiopathy (Ng et al, 2019;Orsucci et al, 2022). In short, changes in cerebral blood flow, oxygen metabolism and neuronal excitability occur during SLEs, resulting in abnormal changes in characteristic distribution patterns and evolution regularity.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

et al. 2023

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ObjectiveMitochondrial encephalomyopathy with lactic acidosis and stroke−like episodes (MELAS) is one of the most common inherited mitochondrial disorders. Due to the high clinical and genetic heterogeneity of MELAS, it is still a major challenge for clinicians to accurately diagnose the disease at an early stage. Herein, we evaluated the neuroimaging findings of MELAS with an m.3243A>G mutation in MT−TL1 and analyzed the possible underlying pathogenesis of stroke-like episodes.Materials and methodsFifty-nine imaging studies in 24 patients who had a confirmed genetic diagnosis of m.3243A>G (MT-TL1; tRNALeu) associated with MELAS were reviewed in our case series. The anatomic location, morphological features, signal/intensity characteristics and temporal evolution of lesions were analyzed on magnetic resonance imaging (MRI), and computed tomography (CT) images. The supplying vessels and metabolite content of the lesions were also evaluated by using MR angiography (MRA)/CT angiography (CTA), and MR spectroscopy (MRS), respectively.ResultsThe lesions were most commonly located in the posterior brain, with 37 (37/59, 63%) in the occipital lobe, 32 (32/59, 54%) in the parietal lobe, and 30 (30/59, 51%) in the temporal lobe. The signal characteristics of the lesions varied and evolved over time. Bilateral basal ganglia calcifications were found in 6 of 9 (67%) patients who underwent CT. Cerebral and cerebellar atrophy were found in 38/59 (64%) and 40/59 (68%) patients, respectively. Lesion polymorphism was found in 37/59 (63%) studies. MRS showed elevated lactate doublet peaks in 9/10 (90%) cases. MRA or CTA revealed that the lesion-related arteries were slightly dilated compared with those of the contralateral side in 4 of 6 (67%) cases.ConclusionThe imaging features of MELAS vary depending on the disease stage. Polymorphic lesions in a single imaging examination should be considered a diagnostic clue for MELAS. Stroke-like episodes may be involved in a complex pathogenetic process, including mitochondrial angiopathy, mitochondrial cytopathy, and neuronal excitotoxicity.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

et al. 2023

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“…A less mitochondria-toxic AED is pregabalin. In case AEDs are ineffective, a cocktail of vitamins, cofactors and antioxidants may be implemented [ 22 , 23 , 24 , 25 , 26 , 29 , 30 , 31 , 32 , 33 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

Stroke-like Episodes in Inherited Neurometabolic Disorders

2022

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Stroke-like episodes (SLEs) are significant clinical manifestations of metabolic disorders affecting the central nervous system. Morphological equivalents presented in neuroimaging procedures are described as stroke-like lesions (SLLs). It is crucial to distinguish SLEs from cerebral infarction or intracerebral hemorrhage, mainly due to the variety in management. Another significant issue to underline is the meaning of the main pathogenetic hypotheses in the development of SLEs. The diagnostic process is based on the patient’s medical history, physical and neurological examination, neuroimaging techniques and laboratory and genetic testing. Implementation of treatment is generally symptomatic and includes L-arginine supplementation and adequate antiepileptic management. The main aim of the current review was to summarize the basic and actual knowledge about the occurrence of SLEs in various inherited neurometabolic disorders, discuss the possible pathomechanism of their development, underline the role of neuroimaging in the detection of SLLs and identification of the electroencephalographic patterns as well as histological abnormalities in inherited disorders of metabolism.

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Mitochondrial stroke-like episodes: The search for new therapies

Cited by 2 publications

References 39 publications

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes with an MT-TL1 m.3243A>G point mutation: Neuroradiological features and their implications for underlying pathogenesis

Stroke-like Episodes in Inherited Neurometabolic Disorders

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