Headache and migraine in mitochondrial disease and its impact on life—results from a cross-sectional, questionnaire-based study

Abstract

Headache is frequent in patients with mitochondrial disorders. Previous studies point to a higher prevalence of headache in these patients than in the general population. As mitochondrial disorders often present a variety of other symptoms, the question arises how much the presence of headache really influences daily life. We performed a cross-sectional, questionnaire-based study investigation with 61 patients with a genetically proved mitochondrial disease mainly composed of CPEO phenotype. Headache was examined using a standardized questionnaire, and classified according to ICHD-2. Headache-related disability was evaluated by the Headache-Impact-Test-6 (HIT-6). Additionally, depression and anxiety were examined using the Hospital Anxiety and Depression Scale (HADS) and Short-Form-Health Survey (SF-12) was used to investigate the health-related quality of life. Headache was reported by 43/61 (70.5%) of the patients. 35/61 patients (57.4%) described a Tension-type headache (TTH) and 26 patients (42.6%) a migraine. Patients reporting headache had a significantly higher HIT-6 score than those without (mean: 54.47 vs. 38.47, p < 0.001). The HIT-6 score was significantly higher in patients reporting a migraine compared to those with a tension-type headache (mean: 62.13 vs. 46.18, p < 0.001). In the HADS score and in the SF-12 were not significantly influenced by the occurrence of headache. This study confirms the previously reported frequent occurrence of headache in a large cohort of patients with a confirmed mitochondrial disease. Migraine had the greatest impact on daily living, which appeared not to be confounded by depression and anxiety. Thus, we conclude that Migraine may be a substantial contributor for burden of disease in patients with mitochondrial diseases.

Case report: Monoclonal CGRP-antibody treatment in a migraine patient with a mutation in the mitochondrial single-strand binding protein (SSBP1)

“…Headaches account for one of the five most debilitating symptoms of mitochondrial diseases ( 6 ). Headaches, especially migraine, have a substantial impact on social functioning and everyday life in patients with mitochondriopathies ( 5 ). However, both, acute as well as a preventive treatment for migraine in patients with mitochondrial disease are challenging—data on the use and efficacy of medication are scarce.…”

“…involvement as well as neurological symptoms, such as epileptic seizures, ataxia, and headache (1). The presence of migraine with and without aura and other headache disorders, such as tension-type headaches, is well described in mitochondrial diseases, such as chronic progressive external ophthalmoplegia (CPEO), myoclonic epilepsy with ragged-red fibers (MERRF) and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (2)(3)(4)(5). Headache prevalence in this patient group seems to be higher than in the general population (3).…”

“…Headache prevalence in this patient group seems to be higher than in the general population ( 3 ). In MELAS, between 50 and 90% of the patients report headaches ( 3 , 5 , 6 ), however, headache frequency and headache presentation can vary widely in this respective patient population. Although headache is associated with several mitochondriopathies, only one of them is currently listed in the latest International Classification of Headache Disorders, 3rd edition (ICHD-3) ( 7 ).…”

The Mitochondrial Biomarkers FGF-21 and GDF-15 in Patients with Episodic and Chronic Migraine

“…Previous studies have identified different cut-off values of the two biomarkers for mitochondrial disease in children, young adults, and adults [ 14 , 15 , 16 ]. Even considering the different kits for the determination of the biomarkers, the values especially for GDF-15 in this study were markedly below the cut-off values.…”

“…From the epidemiologic point of view, several studies show a higher prevalence of migraine than expected in patients with a genetically proved mitochondrial disorder such as MELAS, MERRF (myoclonic epilepsy with ragged red fibers) and LHON (Leber’s hereditary optic neuropathy) [ 11 , 12 , 13 , 14 ]. Migraine is a substantial contributor for burden of disease in patients with mitochondrial diseases [ 15 ]. However, in genetic analyses, none of the frequent point mutations of the mitochondrial DNA, e.g., m.3243 A > G associated with the MELAS-syndrome, in patients with migraine with aura were detected [ 16 ].…”