Mitochondrial DNA in Stroke and Migraine with Aura

Ojaimi, Joseline; Katsabanis, Sophie; Bower, Simon; Quigley, Anita; Byrne, Edward

doi:10.1159/000015826

Cited by 30 publications

(26 citation statements)

References 14 publications

(15 reference statements)

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“…17 With regard to stroke, a correlation to secondary LHON mutations has been reported. 18 The results of this study demonstrated a significantly higher risk of stroke among LHON patients, suggesting that there might be an association with primary LHON mutations.…”

Section: Discussionmentioning

confidence: 57%

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

Vestergaard

Rosenberg

Torp‐Pedersen

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients.METHODS. This study, based on Danish nationwide health registries, included 141 patients diagnosed with LHON and 297 unaffected family members in the maternal line. The incidence of comorbidities and mortality for patients with LHON and unaffected family members was compared with that in the general population.RESULTS. Having LHON was associated with an almost 2-fold risk of mortality with a rate ratio (RR) of 1.95 (95% confidence interval [CI]: 1.47-2.59; P < 0.001). The incidence of several diseases was increased for LHON patients, but not for family members. The incidence of stroke was 5.73 per 1000 patient-years for LHON patients compared to 2.33 for the general population, and the RR was 2.38 (95% CI: 1.58-3.58; P < 0.001). The incidence of demyelinating disorders was 2.24 compared to 0.21 for the general population; RR was 12.89 (95% CI: 6.70-24.77; P < 0.001). A 4-fold risk of dementia was seen for LHON patients (RR: 4.26, 95% CI: 1.91-9.48; P < 0.001), incidence 1.45 for LHON and 0.37 for the general population. Moreover, LHON patients had an increased risk of epilepsy, atherosclerosis, nerve symptoms, neuropathy, and alcohol-related disorders.CONCLUSIONS. The manifestation of LHON was associated with increased mortality and increased incidence of several disorders including stroke, demyelinating disorder, dementia, and epilepsy.

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Section: Discussionmentioning

confidence: 57%

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

Vestergaard

Rosenberg

Torp‐Pedersen

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Homoplasmic mtDNA sequence changes are known to increase the risk for the development of some multi-factorial conditions, including deafness and Alzheimer and Parkinson dementias [Shoffner and Wallace, 1995;Guan et al, 2001]. Homoplasmic mtDNA sequence variants reported to be associated with migraine or its variants include A11084G [Shimomura et al, 1995], T4216C, G13708A [Ojaimi et al, 1998], G1606A [Sacconi et al, 2002], and the U5 mtDNA haplogroup [Finnila et al, 2001].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Wang

Ito

Adams

et al. 2004

American J of Med Genetics Pt A

106

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Migraine headache is a very common condition affecting about 10% of the population that results in substantial morbidity and economic loss. The two most common variants are migraine with (MA) and without (MO) aura. Often considered to be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately childhood condition characterized by severe, discrete episodes of nausea, vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested in common migraine and CVS based upon a strong bias towards the maternal inheritance of disease, and several other factors. Temporal temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and RFLP was used to screen almost 90% of the mtDNA, including the control region (CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVS+) and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence variants were found in six CVS+ and in zero control subjects (P = 0.003). These variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2 (HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the nt 16040-16188 segment of HV1 that includes the termination associated sequence (TAS), a functional location important in the regulation of mtDNA replication. Based upon our findings, sequencing and statistical analysis looking for homoplasmic nucleotide changes was performed in HV1 among 30 CVS+, 30 randomly-ascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases. Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold more common relative to control subjects in both CVS groups (P = 0.01 combined data) and in MO (P = 0.02), but not in MA (P = 0.5 vs. control subjects and 0.02 vs. MO). No group differences were noted in the remainder of HV1. We conclude that sequence variation in this small "peri-TAS" segment is associated with CVS and MO, but not MA. These variants likely constitute risk factors for disease development. Our findings are consistent with previous data demonstrating progression of CVS into MO in many cases, and the co-segregation in a maternal inheritance pattern of CVS and MO within families. A mitochondrial component in the pathogenesis of migraine and CVS has therapeutic implications, especially concerning the avoidance of fasting.

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“…12 This mutation is also frequently found in patients with stroke and migraine with aura. 13 Young patients with mild vascular risk factors for ischemic stroke should not necessarily be excluded from studies of mitochondrial disease. In fact, diabetes mellitus is a usual component of the mitochondrial diseases, 14 and patients having hypertriglyceridemia have also been described 15 Case 5 showed mild arterial hypertension, and case 6 suffered from dyslipidemia.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Disease and Stroke

Martínez-Fernández

Gil-Peralta²,

R³

et al. 2001

Stroke

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Background and Purpose-It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. Methods-Patients aged Յ50 years, admitted to the Stroke Unit from January 1999 to May 2000 with a diagnosis of ischemic stroke of unknown origin, were included in the study. All of them had full biochemical and hematologic tests, neuroimaging studies, transesophageal echocardiography, and extracranial and transcranial Doppler sonography. Patent foramen ovale was ruled out. Lactic acid concentrations were measured after anaerobic exercise of the forearm, and a morphological, biochemical, and molecular study after biceps muscle biopsy was performed. Results-Of the 18 patients so far included, 3 (17%) presented lactic acid hyperproduction after physical exercise, and 6 (33%) showed deficit of the mitochondrial respiratory chain complexes.

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Mitochondrial DNA in Stroke and Migraine with Aura

Cited by 30 publications

References 14 publications

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy: A Nationwide Cohort Study

Mitochondrial DNA control region sequence variation in migraine headache and cyclic vomiting syndrome

Mitochondrial Disease and Stroke

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