Letter To The Editor Open Access
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 6, 2020; 8(1): 242-244
Published online Jan 6, 2020. doi: 10.12998/wjcc.v8.i1.242
Cluster headache as a manifestation of a stroke-like episode in a carrier of the MT-ND3 variant m.10158T>C
Josef Finsterer, Neurological Department, Messerli Institute, Vienna 1180, Austria
ORCID number: Josef Finsterer (0000-0003-2839-7305).
Author contributions: Finsterer J performed research, literature search, discussion, first draft, critical comments.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Josef Finsterer, MD, PhD, Attending Doctor, Neurological Department, Messerli Institute, Danube Univ Krems, Postfach 20, Vienna 1180, Austria. fifigs1@yahoo.de
Received: August 30, 2019
Peer-review started: August 30, 2019
First decision: December 12, 2019
Revised: December 19, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: January 6, 2020
Processing time: 129 Days and 2 Hours

Abstract

In a recent article Fu et al reported about a 52 years old female with a mitochondrial disorder due to the variant m.10158T>C in the mtDNA located gene MT-ND3. The study has a number of shortcomings. The study would particularly profit from providing more data about multisystem disease, from providing the current medication, the cerebro-spinal fluid findings, the detailed phenotypic presentation, and the genotype of first-degree relatives. Since the index patient had experienced recurrent seizures it is crucial to know the current and previous anti-seizure medication as it may strongly determine the outcome. Some of them are mitochondrion-toxic and particularly valproic acid may exhibit fatal side effects. The outcome may also depend on the degree of multisystem involvement why it is crucial to prospectively investigate the patient for subclinical involvement of organs not obviously affected. Additionally, the outcome of the stroke-like lesions on imaging would be interesting to see. Stroke-like lesions may completely disappear or may end up as white matter lesion, laminar cortical necrosis, focal atrophy, cyst, or as the so-called toenail sign. There is also a need of discussing more profoundly the imaging findings and their diagnostic significance and to investigate first degree relatives of the index patient clinically and genetically. Though highly interesting, the presentation of this case of a mitochondrial disorder lacks clinical and genetic data of the patient and his relatives. Outcome parameters, such as severity of disease, degree of progression, drugs, pathogenicity of the mutation, and multisystem involvement require a profound discussion.

Key Words: Heteroplasmy; mtDNA; Oxidative phosphorylation; Stroke-like episode

Core tip: The recent report about a 52 years old female with a mitochondrial disorder due to the variant m.10158T>C in MT-ND3 may profit from a more thorough investigation of the index case and his relatives. Outcome parameters, such as severity of disease, degree of progression, drugs, pathogenicity of the mutation, and multisystem involvement need to be assessed to guide treatment and genetic counselling.



TO THE EDITOR

In a recent article, Fu et al[1] reported about a 52 years female with a mitochondrial disorder (MID) due to the variant m.10158T>C in MT-ND3. The patient manifested phenotypically with recurrent stroke-like episodes, cluster headache, and epilepsy. We have the following comments and concerns.

We do not agree with the statement that the m.10158T>C variant in ND3 is a common mutation[1]. When searching PubMed for this particular mtDNA variant only five hits could be achieved. Thus, the variant m.101157T>C has to be classified as a rare variant.

Since the index patient had undergone a spinal tap, we should know if cerebrospinal fluid (CSF) lactate was elevated or not upon investigations of the CSF.

Since up to 75% of the mtDNA variants are transmitted via a maternal line of inheritance[2], we should know if the mother or any other first degree elative was clinically affected and if the mtDNA variant m.10158T>C was detected in any of the other first degree relatives.

Stroke-like lesions (SLLs) in the acute/expanding stage typically manifest with hyperperfusion on single-photon emission computed tomography or perfusion weighted imaging. Thus, we should know if perfusion weighted imaging was applied and if hyperperfusion could be detected. It is also crucial to demonstrate reduced oxygen extraction within the SLL by means of oxygen extraction fraction-MRI. Was this technique applied and was there reduced oxygen extraction?

Since SLLs may disappear without any remnants on MRI, or may end up as white matter lesion, laminar cortical necrosis, cysts, or the toenail-sign[3], we should know the outcome of the various SLLs in this patient. Which were the results of the long-term follow-up on MRI?

The index patient obviously did not only manifest in the cerebrum (SLLs, seizures, cognitive impairment) but also in the endocrine system (short stature), and the heart (atrial fibrillation). Since patients with a MID most frequently manifest with multisystem disease[4], we should know if the index patient was prospectively investigated for manifestations of the genotype in organs other than the brain and the endocrine organs. We also should be informed why the patient received oral anticoagulation with a vitamin-K antagonist. Was this due to atrial fibrillation, heart failure, or valve replacement therapy?

Missing is the current medication of the patient. Since the patient had experienced recurrent seizures, it is crucial to know the antiepileptic drug (AED) regimen. Since some of the AEDs are potentially mitochondrion-toxic[5] we should know if recurrence of seizures and SLLs could be attributed at least in part to the application of mitochondrion-toxic AEDs or to in-effectivity of the AEDs.

Cluster headache had been occasionally reported as a manifestation of a MID[6,7]. Did cluster headache in the index patient resolve upon application of widely agreed therapies for cluster headache?

Overall, this interesting case could be more meaningful by providing more data about multisystem disease, the current medication, the CSF findings, the phenotype and genotype of other first-degree relatives, outcome of the SLLs on imaging, and by discussing more profoundly the imaging findings and their significance.

Footnotes

Manuscript source: Unsolicited manuscript

Specialty type: Medicine, Research and Experimental

Country of origin: Austria

Peer-review report classification

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P-Reviewer: Kvolik S S-Editor: Zhang L L-Editor: A E-Editor: Xing YX

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