LETTER TO EDITOR
|Ahead of print
Stroke-like episode mimicking episodic migraine
Neurology and Neurophysiology Center, Vienna, Austria
|Date of Submission||31-Jul-2021|
|Date of Acceptance||27-Mar-2022|
|Date of Web Publication||30-Jan-2023|
Neurology and Neurophysiology Center, Postfach 20, 1180 Vienna
Source of Support: None, Conflict of Interest: None
To the Editor
With interest we read the article by Panda et al. about an 8-year-old male with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to the variant m.3243A>G, manifesting clinically with episodic migrainous headache with or without visual impairment. The case report is appealing but raises comments and concerns.
The first limitation of the case report is that no imaging studies during the episodes of migraine-like headache, which were in fact stroke-like episodes (SLEs), the clinical hallmark of MELAS, were provided. SLEs are the clinical manifestation of a stroke-like lesion (SLL) on imaging. SLLs present with distinct features on multimodal magnetic resonance imaging (MRI). They are hyperintense on diffusion-weighted imaging and perfusion-weighted imaging, and hypointense on oxygen extraction fraction-MRI. Fluor-deoxy-glucose positron emission tomography shows hypometabolism in the area of the SLL, which does not comply with a vascular territory. Missing SLEs and stroke in general, which is more frequently the case in pediatric patients than in adults, can be prevented by the application of multi-modal MRI.
As one of the pathophysiological explanations of SLLs is seizure activity (epileptogenic hypothesis), it would be interesting to know the results of electroencephalography.
A third limitation is that first-degree relatives were neither investigated clinically nor genetically. As mtDNA variants are inherited from the mother’s side in 75% of the cases, it is crucial for genetic counselling to know if the parents manifested clinically and if the variant was inherited or occurred sporadically. A strong argument in favor of maternal inheritance is that the mother of the index patient presented with similar episodes as her son. Unfortunately, it remained unclear if she succumbed from a true stroke (ischemic or bleeding) or an SLE.
A fourth limitation is that the heteroplasmy rate was not provided. Knowing the heteroplasmy rates is crucial for interpreting the phenotype, for explaining the intra- and interfamilial phenotypic heterogeneity, for genetic counselling, and for predicting the outcome.
A fifth limitation is that the patient had not been prospectively investigated for multisystem disease. MELAS is usually a multisystem disorder either already at onset or develops into a multisystem disease during the disease course. As affection of organs other than the brain in MELAS can be subclinical (e.g. liver) and as multisystem involvement may strongly determine the outcome, we should be informed about the result of these investigations.
Overall, the study has several limitations that challenge the results and their interpretation. The points raised above should be addressed to further strengthen the conclusions.
Statement of ethics
This study was in accordance with ethical guidelines and was approved by the institutional review board.
JF contributed to design, literature search, discussion, first draft, critical comments, and final approval.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Panda PK, Sharawat IK, Singh A, Sherwani P. A young child with recurrent episodes of headaches and vision loss: diagnostic clues? J Pediatr Neurosci 2021;16:82-4. [Full text]
Finsterer J, Aliyev R. Metabolic stroke or stroke-like lesion: peculiarities of a phenomenon. J Neurol Sci 2020;412:116726.
Poulton J, Finsterer J, Yu-Wai-Man P. Genetic counselling for maternally inherited mitochondrial disorders. Mol Diagn Ther 2017;21:419-29.
El-Hattab AW, Adesina AM, Jones J, Scaglia F. MELAS syndrome: clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab 2015;116:4-12.