Mild Hyperhomocysteinemia and Low Folate Concentrations as Risk Factors for Cervical Arterial Dissection

Araúz, Antonio; Hoyos, Leticia; Cantú, Carlos; Jara, Aurelio; Martínez, Leticia; García, I. Suárez; Fernández, María de los Ángeles; Alonso, Elisa

doi:10.1159/000104479

Cited by 52 publications

(38 citation statements)

References 37 publications

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“…Major and minor cervical trauma [13][14][15][16][17] Arterial hypertension [18][19][20] Young age 12 Current use of oral contraceptives 21 Migraine [22][23][24] Fibromuscular dysplasia 11,[25][26][27][28][29][30][31][32] Ultrastructural connective tissue abnormalities 33 Vascular subtype of Ehlers-Danlos syndrome 34 Marfan syndrome 18,35 Turner syndrome 19,36 Williams syndrome 37 Familial cases 18,38 Hereditary hemochromatosis 39 Osteogenesis imperfecta type I 40 α1-Antitrypsin deficiency 41,42 677T genotype MTHFR [43][44][45] Hyperhomocysteinemia 46 Cystic medial necrosis of intracranial vessels 47 Styloid process length 48 ICAM-1 E4690 K gene polymorphism 49 Autosomal-dominant polycystic kidney disease 50 Infections [51][52][53][54] Moyamoya disease …”

Section: Table 1 Factors Associated With CDmentioning

confidence: 99%

Cervical Arterial Dissections and Association With Cervical Manipulative Therapy

Biller¹,

Sacco²,

Albuquerque³

et al. 2014

Stroke

179

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3155Purpose-Cervical artery dissections (CDs) are among the most common causes of stroke in young and middle-aged adults.The aim of this scientific statement is to review the current state of evidence on the diagnosis and management of CDs and their statistical association with cervical manipulative therapy (CMT). In some forms of CMT, a high or low amplitude thrust is applied to the cervical spine by a healthcare professional. Methods-Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. Results-Patients with CD may present with unilateral headaches, posterior cervical pain, or cerebral or retinal ischemia (transient ischemic or strokes) attributable mainly to artery-artery embolism, CD cranial nerve palsies, oculosympathetic palsy, or pulsatile tinnitus. Diagnosis of CD depends on a thorough history, physical examination, and targeted ancillary investigations. Although the role of trivial trauma is debatable, mechanical forces can lead to intimal injuries of the vertebral arteries and internal carotid arteries and result in CD. Disability levels vary among CD patients with many having good outcomes, but serious neurological sequelae can occur. No evidence-based guidelines are currently available to endorse best management strategies for CDs. Antiplatelet and anticoagulant treatments are both used for prevention of local thrombus and secondary embolism. Case-control and other articles have suggested an epidemiologic association between CD, particularly vertebral artery dissection, and CMT. It is unclear whether this is due to lack of recognition of preexisting CD in these patients or due to trauma caused by CMT. Ultrasonography, computed tomographic angiography, and magnetic resonance imaging with magnetic resonance angiography are useful in the diagnosis of CD. Follow-up neuroimaging is preferentially done with noninvasive modalities, but we suggest that no single test should be seen as the gold standard.

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Section: Table 1 Factors Associated With CDmentioning

confidence: 99%

Cervical Arterial Dissections and Association With Cervical Manipulative Therapy

Biller¹,

Sacco²,

Albuquerque³

et al. 2014

Stroke

179

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“…51 Three studies found a positive association between the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype and CAD. 8,9,66 Three other studies did not find any significant association between MTHFR 677TT and CAD. 7,13,60 We performed a meta-analysis of 5 studies 7,9,13,60,66 (in 440 cases and 1220 control subjects); the sixth study 8 was not included in the meta-analysis because of overlapping data with a subsequent analysis from the same group.…”

Section: Genetic Association Studiesmentioning

confidence: 89%

“…Five studies reported associations with 3 different candidate genes: ICAM-1, COL3A1, and MTHFR. 8,9,12,51,66 The associations with the ICAM-1 E469K polymorphism and the COL3A1 3ЈUTR 2-bp deletion, 12,51 observed in 2 relatively small studies, have not been replicated and should therefore be interpreted with caution. The ICAM-1 E469K polymorphism could modify the affinity of ICAM-1 to its ligands, which may lead to increased activation of cytokines and proteases, thus inducing extracellular matrix degradation and weakening of the arterial wall.…”

Section: Genetic Association Studiesmentioning

confidence: 99%

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The Genetics of Cervical Artery Dissection

Debette

Markus

2009

Stroke

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Background and Purpose-The pathophysiology of cervical artery dissections (CAD), a major cause of ischemic stroke in young adults, is poorly understood. Several arguments suggest a genetic predisposition. Methods-We systematically reviewed all published data on genetic risk factors for CAD and performed a meta-analysis of association studies with the MTHFR C677T polymorphism. Results-Rarely, CAD is associated with a known monogenic connective tissue disease, mainly vascular Ehlers-Danlos syndrome. However, in the large majority of CAD cases, there is no evidence for a known monogenic disease. Several arguments, including the association of CAD with dermal connective tissue abnormalities that are inherited, suggest that genetic factors also play a role in "sporadic" CAD as part of a multifactorial predisposition. We identified 15 genetic association studies: 10 were negative and 5 reported associations of 3 genetic variants in 3 different candidate genes. Two studies reported associations with polymorphisms in ICAM-1 and COL3A1, but neither has been replicated. Three studies reported an association with the MTHFR 677TT genotype, but 3 other studies did not replicate this. A meta-analysis of these data identified an overall significant association of the MTHFR 677TT genotype with CAD (OR, 1.67; 95% CI, 1.21 to 2.31). We also identified 9 studies screening candidate genes for mutations and 4 linkage studies, yielding mostly negative results. Conclusions-Although several interesting hypotheses were generated, the majority of genetic studies in CAD have been negative until now, but they were markedly underpowered. Progress in unraveling the genetics of CAD will require the collection of DNA samples from large multicenter series. (Stroke. 2009;40:e459-e466.)

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“…There have been a number of case-control studies evaluating the association between the MTHFR/C677T and carotid dissection [20,21,22,23]. Many of these reports have provided conflicting results often hampered by the relatively small number of subjects included in each study.…”

Section: Introductionmentioning

confidence: 99%

The Genetics of Carotid Dissection: Meta-Analysis of a MTHFR/C677T Common Molecular Variant

McColgan¹,

Sharma²

2008

Cerebrovasc Dis

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Background and Purpose: Carotid dissection is a recognized cause of stroke. An association has been reported between carotid dissection and elevated homocysteine levels. Homocysteine levels are partly determined by a thermolibile form of methyltetrahydrofolate reductase (MTHFR) which has a common C677T single nucleotide polymorphism (SNP). We sought to undertake a comprehensive genetic meta-analysis of this SNP and its association with carotid dissection. Methods: All case-control studies evaluating MTHFR/C677T in carotid dissection were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) using both fixed and random effects were determined for both dominant and recessive genetic models. Analyses were also undertaken to compare the effects of the homogenous forms of MTHFR/C677T. Results: Four manuscripts analyzing a total of 420 individuals (183 cases and 237 controls) were identified. The pooled OR for the dominant MTHFR/T677 model was 1.36 (95% CI 0.89–2.08; p = 0.16) while the pooled OR for the recessive TT model was 1.07 (95% CI 0.61–1.89; p = 0.81). To ensure a subtle recessive effect was not being masked by the inclusion of the heterozygous genotype, comparison of the CC and TT genotypes in cases against controls was undertaken but no significant association was observed (OR 0.73; 95% CI 0.38–1.40; p = 0.34). Conclusions: Our data does not support an association between the MTHFR/C677T molecular variant and carotid dissection. As this SNP accounts for the majority of the genetic variance of homocysteine levels, our data suggests that homocysteine is unlikely to play a major role in this condition.

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Mild Hyperhomocysteinemia and Low Folate Concentrations as Risk Factors for Cervical Arterial Dissection

Cited by 52 publications

References 37 publications

Cervical Arterial Dissections and Association With Cervical Manipulative Therapy

Cervical Arterial Dissections and Association With Cervical Manipulative Therapy

The Genetics of Cervical Artery Dissection

The Genetics of Carotid Dissection: Meta-Analysis of a MTHFR/C677T Common Molecular Variant

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