MTHFR Gene Polymorphisms and Cardiovascular Risk Factors, Clinical-Imagistic Features and Outcome in Cerebral Venous Sinus Thrombosis

Abstract

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012–February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A—Leiden, prothrombin G20210A, PAI-1 675 4G/5G; Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases; 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p < 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p < 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.

Diagnosis and Management of Mixed Transcortical Aphasia Due to Multiple Predisposing Factors, including Postpartum and Severe Inherited Thrombophilia, Affecting Multiple Cerebral Venous and Dural Sinus Thrombosis: Case Report and Literature Review

“…The predominant genetic mutations linked to CVT are inherited thrombophilias. The three most frequent mutations associated with CVT include factor V Leiden, factor II prothrombin variant (PT 20210A), and the homozygosity for MTHFR C677T [11][12][13]. Women are more predisposed to CVT than men because of hormonal factors, while the highest incidence rate in adults is around 30 years [14][15][16].…”

“…Various neuroimaging investigation techniques can detect cerebral veins and dural sinus thrombosis. Cerebral edema and venous infarction may be apparent with any modality, although for the detection of the thrombus itself, the most commonly used imaging techniques are computed tomography (CT) and magnetic resonance imaging (MRI), both of which use various types of radiocontrast to perform a venogram and visualize the veins around the brain [13]. Thrombi can be identified using CT or MRI by means of the "dense triangle sign", the "cord sign", or the "empty delta sign [3,18,36].…”

Case report: cerebral sinus vein thrombosis in two patients with AstraZeneca SARS-CoV-2 vaccination

“…Genetic thrombophilia factor testing revealed an MTHFR mutation in both patients with an additional heterozygous PAI-1 gene polymorphism in patient B, but no evidence of a factor V ARG506 mutation or prothrombin G20210A mutation could be found. Gogu et al recently demonstrated that in 114 cases of CSVT 52.6% had MTHFR gene polymorphism (45.6% homozygous mutation) for C677T or A1298C, partially associated with other evidence of thrombophilia such as hyperhomocysteinemia [ 4 ].…”

Clinical Spectrum and Neuroimagistic Features in Hospitalized Patients with Neurological Disorders and Concomitant Coronavirus-19 Infection

“…We reviewed the medical records of all patients admitted with neurological disorders and concomitant SARS-CoV-2 RNA infection detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). Demographic (sex and age), clinical, radiologic examination (head CT, brain MRI, and chest CT), laboratory parameters (leucocyte, lymphocyte, and thrombocyte count; blood glucose, lactate dehydrogenase (LDH), highly sensitive C-reactive protein (hsCRP); erythrocyte sedimentation rate (ESR); D-dimer; fibrinogen; activated partial thromboplastin time (APTT); prothrombin time (PT); and international normalized ratio (INR)); and lumbar puncture and neurophysiologic test (EEG and EMG) data, if indicated, were all considered [ 10 ].…”