Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort.

OBJECTIVE: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. METHODS: Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. RESULTS: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). SIGNIFICANCE: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Electroclinical patterns in patients with nonconvulsive status epilepticus: Etiology, treatment, and outcome.

INTRODUCTION: This study investigated the clinical and electroencephalography (EEG) features and prognostic factors of patients with nonconvulsive status epilepticus (NCSE). MATERIALS AND METHODS: We retrospectively reviewed the clinical files and EEG data of 45 (28 females, mean age 54 ±â€¯22.6 years) consecutive patients with NCSE over a five-year period. An EEG interpreter who was blinded to the clinical findings evaluated the EEGs according to the Salzburg Consensus Criteria (SCC) for NCSE. Patient demographics, etiology, neuroimaging and laboratory data, EEG features, treatment, and outcome measures were analyzed. RESULTS: The most common etiology for NCSE was acute symptomatic etiologies (57.8%) and cerebrovascular disease (48.9%). The majority (68.9%) of the patients presented with new-onset status epilepticus (SE). NCSE was refractory to treatment in 31.1% of patients. The most common status pattern consisted of rhythmic delta/theta activity in 62.3% of EEGs. Twenty-five status patterns on the EEGs were classified as definite, 30 as possible, and six as no NCSE according to the SCC. The in-hospital mortality rate was high (33.3%) showing an association with potentially fatal etiology, refractory SE, treatment with continuous I.V. anesthetics and also the presence of multiple status patterns and nonreactivity in EEGs (p < 0.05). CONCLUSIONS: The SCC for NCSE have high diagnostic accuracy but do not affect prognosis. Potentially fatal etiology, multiple status patterns on EEG and non-reactive EEGs may carry significantly greater risk for short-term mortality.

Calcitonin gene related peptide gene polymorphism in migraine patients.

OBJECTIVE: Calcitonin gene related peptide (CGRP), which has a vasodilator effect, is held responsible for neurogenic inflammation and vasodilatation of the cranial vessels in migraine pathophysiology. In this study, we investigated the association between alpha CGRP gene polymorphism (CALCA T-692C) and migraine. MATERIAL AND METHODS: One hundred and thirty-four female migraineurs and 96 healthy female cases were enrolled in the study. The patient group was further subdivided into migraine with and without aura groups. The CALCA T-692C gene polymorphism was identified using polymerase chain reaction (PCR) technique and restriction fragment length polymorphism (RFLP). RESULTS: The genotype and allele frequencies of CALCA T-692C gene polymorphism did not differ between the migraine and control groups. Between the migraine with and without aura subgroups, there was no difference. No association was seen between the CALCA T-692C gene polymorphisms and migraine attack severity and frequency. CONCLUSION: Our study did not show any association between CALCA T-692C gene polymorphism and migraine.

Latency of epileptic and psychogenic nonepileptic seizures.

BACKGROUND: Due to their semiological similarities, psychogenic nonepileptic seizures (PNESs) can occasionally hardly be differentiated from epileptic seizures (ESs), and long-term video-electroencephalographic monitoring (VEM) is needed for the differential diagnosis. OBJECTIVE: To investigate the time of the first clinical event and its distribution on the days of VEM in ES and PNES patients. METHODS: In total, a consecutive series of 48 PNES and 51 ES patients matched for gender and age were retrospectively and consecutively evaluated. The time distribution of the seizures during the day was noted. Seizure latency was determined as the time in hours from the start of the video-electroencephalographic recording to the first clinical event. RESULTS: The seizure latency was significantly shorter in PNES patients compared to ES patients (p < 0.001). Seventy-two percent of PNES patients and 49.1% of ES patients had their first seizure in the 24 hours of video-EEG recording (p = 0.023). Recording longer than 48 hours was required for 12.5% of PNES patients and 37.3% of ES patients (p = 0.006). While ESs were almost evenly distributed throughout the day, most PNESs occurred during the evening hours (p = 0.011). CONCLUSION: We observed that the PNESs appeared earlier than the ESs in the VEM and were concentrated during daylight hours. Although not strictly reliable, seizure latency can contribute to the differential diagnosis of ES and PNES.

ANTECEDENTES: Debido a sus similitudes semiológicas, las crisis no epilépticas psicógenas (CNEP) en ocasiones apenas se pueden diferenciar de las crisis epilépticas (CE), y se necesita una monitorización video-electroencefalográfica (EEG) prolongada para el diagnóstico diferencial. OBJECTIVO: Investigar el momento del primer evento clínico y su distribución en los días de monitorización video-EEG en pacientes con CE y CNEP. MéTODOS: Se evaluó retrospectivamente a una serie consecutiva de 48 pacientes con CNEP y 51 con ES emparejados por sexo y edad. Se anotó la distribución temporal de las incautaciones durante el día. La latencia de las crisis se determinó como el tiempo en horas desde el inicio de la grabación del video-EEG hasta el primer evento clínico. RESULTADOS: La latencia de las crisis fue significativamente menor en los pacientes con CNEP en comparación con los pacientes con CE (p < 0,001). El 72% de los pacientes con CNEP y el 49,1% de los pacientes con CE tuvieron su primera crisis en las 24 horas de registro del video-EEG (p = 0,023). Se requirió un registro de más de 48 horas para el 12,5% de los pacientes con CNEP y el 37,3% de los pacientes con CE (p = 0,006). Mientras que las CE se distribuyeron casi uniformemente a lo largo del día, la mayoría de las CNEP ocurrieron durante las horas después del anochecer (p = 0,011). CONCLUSIóN: Observamos que las CNEPs aparecieron antes que las CEs en la monitorización video-EEG, y se agruparon durante las horas del día. Aunque no es estrictamente confiable, la latencia de las crisis puede contribuir al diagnóstico diferencial de ES y CNEP.

Investigation of the Genetic Etiology in Idiopathic Generalized Epileptic Disorders by Targeted Next-generation Sequencing Technique

Background: Idiopathic generalized epilepsy is the most common group of epilepsy disorders in children and adolescents. Various types of genetic abnormality were identified among the hereditary factors that explain epilepsy. Aims: To determine the variations in the etiopathogenesis, treatment protocol planning, and prognosis of idiopathic generalized epilepsy using the next-generation sequencing method. Study Design: A cross-sectional study. Methods: This study included 32 patients with idiopathic generalized epilepsy. Genomic DNA was obtained from peripheral venous blood samples taken from the patients. A total of 18 genes encoding ion channel subunits that are involved in monogenic disorders and are associated with idiopathic generalized epilepsy were included. The targeted custom next-generation sequencing panel was designed to cover all coding exons and all exon/intron splice site regions of 18 genes. Results: We detected 9 (28%) variations, including 1 likely pathogenic (a variant in the SCN1A gene) and 8 of unknown clinical significance (2 in the CLCN2 genes, GABBR2, SCN1B, SLC2A1, SLC4A10 genes, and 2 in the TBC1D24 gene). Conclusion: Study results should be supported by functional advanced studies, with increased existing knowledge in the relevant variations.

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period.

The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients (p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels.

Migraine in metabolic syndrome.

OBJECTIVES: Recent studies suggest that insulin resistance is more common in patients with migraine. Insulin resistance underlies the pathogenesis of obesity, diabetes, and hypertension that are components of metabolic syndrome. As migraine is associated with an increased risk of vascular disorders, such as stroke, and migraine patients have higher diastolic blood pressure than healthy individuals, we aimed to investigate the 1-year prevalence of migraine in metabolic syndrome. METHODS: Two hundred ten patients with metabolic syndrome were enrolled in the study. Migraine was diagnosed according to International Classification of Headache Disorders-II criteria. RESULTS: Migraine prevalence was estimated as 11.9% in men and 22.5% in women with metabolic syndrome. Of the metabolic syndrome components, diabetes, increased waist circumference, and body mass index were significantly more frequent in patients with migraine in contrast to those without migraine (P<0.05). Hypertension and dyslipidemia frequencies showed no difference between 2 groups. CONCLUSIONS: Our results demonstrate that migraine prevalence in metabolic syndrome was higher than in the general population.

Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in Turkish patients with ischemic stroke.

The low plasma nitric oxide concentrations and reduced vascular reactivity are considered major proatherogenic mechanisms in cardiovascular diseases. The present study aimed to assess the allelic frequency and the genotypic distribution of the Glu298Asp gene polymorphism at exon 7 of endothelial nitric oxide synthase (eNOS) gene in Turkish ischemic stroke patients compared to appropriate healthy controls, and to correlate the genetic findings with stroke subtypes. The study population included 146 (75 males, 71 females) patients with ischemic stroke which were categorized according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) and 133 (34 males, 99 females) healthy subjects. The eNOS polymorphism was identified with a PCR followed by RFLP with the restriction enzyme BanII. Genotypes were defined as GG, GT, and TT according to the presence of the G and T alleles. In this case-control study, we did not find any significant difference in either the genotypic distribution or allelic frequency of Glu298Asp gene polymorphism between the patients and the controls. In addition, there was also no significant difference for the genotype distribution and the allelic frequency among the stroke subtypes. The results suggested the lack of the association between the Glu298Asp gene polymorphism and ischemic stroke or subtypes of ischemic stroke in the Turkish population.

An epidemiologic investigation of amyotrophic lateral sclerosis in Thrace, Turkey, 2006-2010.

OBJECTIVE: The aim of the study was to investigate the incidence and prevalence of amyotrophic lateral sclerosis (ALS) in Thrace, Turkey in a five-year time period (2006-2010). METHODS: Study population included residents of three provinces (Edirne, Tekirdag, Kirklareli) in the Thrace region. Cases were ascertained from all of the neurologic centers and hospitals of these provinces. Demographic and clinical information was collected for each patient. Newly diagnosed ALS patients who are fulfilling the El Escorial revised diagnostic criteria were enrolled into the study. RESULTS: We identified a total of 145 patients (93 males, 52 females). The mean age at diagnosis was 57.0 ± 13.6. According to El Escorial criteria, 60.0% of the cases were definite ALS, 24.8% were probable, and 15.2% were possible ALS. Thirty-two cases were bulbar (22.1%), 113 cases (77.9%) were spinal onset. Mean time delay from onset to diagnosis was 12.0 ± 11.2 months. Age-gender standardized incidence rates with reference to Turkey, USA 2008 census were 1.9 (95% confidence interval (CI), 1.8-2.1), 1.9 (95%CI, 1.8-2.2) for overall. There were 112 living ALS patients at the end of the study. Crude point prevalence was calculated as 7.3 per 100,000 population (95%CI, 5.9-8.7). CONCLUSIONS: This is the first study to provide fundamental data about demographic and clinical characteristics about ALS in Thrace region of Turkey. Incidence and prevalence of ALS in Thrace region of Turkey appear to be comparable with European countries.

Low leptin levels in migraine: a case control study.

BACKGROUND: Obesity has been shown to be a risk factor for transformation of episodic migraine to chronic form, and adipocytokines have been implicated to modulate some of the cytokins such as interleukin-6 and tumor necrosis factor, which also act in the neurogenic inflammation in migraine. The aim of the study was to assess leptin levels, one of the adipocytokines, in headache-free period of migraine patients and investigate its relation to vascular risk factors. MATERIAL AND METHODS: Sixty-one patients with episodic migraine headaches and 64 control subjects were enrolled in the study. Demographic data and anthropometric measurements were obtained from all participants; body mass index and fat mass values were calculated. Glucose and lipid parameters were measured by oxidase technique and cholesterol esterase enzymatic assays, and leptin levels were measured by ELISA in serum samples obtained after an overnight fasting. RESULTS: Leptin levels were found significantly lower in migraineurs than controls (40.1 +/- 21.2 ng/mL, 48.5 +/- 24.5 ng/mL; P < .05). Although body mass index did not differ between 2 groups, fat mass, and fat percentages were significantly lower in migraine patients (19.4 +/- 8.8 kg, 26.0 +/- 8.7 kg; P < .001 and 28 +/- 9%, 34 +/- 5%; P < .001, respectively). CONCLUSION: Migraine patients have low leptin levels and fat mass which may be related to the pathogenesis of migraine. The importance and impact of our findings on the prevalence, characteristics, and treatment of migraine needs to be investigated in further detailed studies.

Insulin resistance and high sensitivity C-reactive protein in migraine.

BACKGROUND: A relationship between migraine and vascular disorders such as hypertension, stroke, and coronary ischemia has been recently reported. Insulin resistance and endothelial dysfunction, which commonly underlies these disorders, have not been widely investigated in migraine patients. In this study, we aimed to investigate the existence of insulin resistance and endothelial dysfunction, and their relationship to vascular risk factors in patients with migraine. METHODS: We evaluated insulin resistance and high-sensitivity C-reactive protein (hs-CRP), a marker of endothelial dysfunction, in 60 migraine patients and 25 healthy control subjects. Multiple analysis of covariance test was used to adjust for known confounding factors that can influence insulin metabolism and endothelial function, such as obesity, blood pressure, and lipid parameters. RESULTS: Insulin resistance, as measured homeostasis model assessment (HOMA)-R levels, was significantly higher in the migraine group (p<0.001). After adjustment for confounding variables, the relationship between migraine and the HOMA-R levels remained significant (p<0.001). The hs-CRP levels did not differ between the migraine and control groups. CONCLUSIONS: Our data show that insulin resistance is present in migraine patients. Endothelial dysfunction is not found during the headache-free period. Further studies are needed to explain the role of insulin resistance in migraine pathogenesis.

Subclinical Cushing's syndrome is a potential cause of metabolic dementia and rapidly progressive Alzheimer-type dementia.

Excess of glucocorticoid hormones are found to exert deleterious effects on the structure and function of central nervous system, especially the hippocampus. This is manifested as mental and mood changes in Cushing syndrome. Subclinical Cushing's syndrome (SCS) is much more prevalent than Cushing's syndrome, and presents with increased plasma cortisol levels, but lack of the cardinal manifestations of Cushing's syndrome. In dementia, the impairment of hypothalamic-pituitary-adrenal axis has been shown, and hypercortisolism has been accused for rapidly progressive cognitive decline in Alzheimer disease. We hypothesized that SCS may cause metabolic dementia, and should be searched in case of rapidly progressive dementia of Alzheimer type.

The roles of oxidized low-density lipoprotein and interleukin-6 levels in acute atherothrombotic and lacunar ischemic stroke.

The role of circulating, oxidized low-density lipoprotein and interleukin-6 levels in acute ischemic stroke considering the primary-vessel disease was investigated. The study consisted of 28 patients with acute ischemic stroke and 23 control subjects. Patients were subdivided into large-vessel (n = 12) and small-vessel (n =16) disease stroke groups according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The means of oxidized low-density lipoprotein and interleukin-6 levels of patients with acute ischemic stroke were higher than controls (P < .01, P < .05). Mean oxidized low-density lipoprotein level was higher in the large-vessel disease group than in the small-vessel disease group (P < .01). The mean of inteleukin-6 levels was higher in the small-vessel disease group (P < .01). The results of the present study showed that oxidative stress promotes large-vessel disease rather than small-vessel disease stroke, and inflammation may play important an role in the development of small-vessel disease stroke.

Latency of epileptic and psychogenic nonepileptic seizures / Latencia de las crisis epilépticas y psicógenas no epilépticas

Abstract Background Due to their semiological similarities, psychogenic nonepileptic seizures (PNESs) can occasionally hardly be differentiated from epileptic seizures (ESs), and long-term video-electroencephalographic monitoring (VEM) is needed for the differential diagnosis. Objective To investigate the time of the first clinical event and its distribution on the days of VEM in ES and PNES patients. Methods In total, a consecutive series of 48 PNES and 51 ES patients matched for gender and age were retrospectively and consecutively evaluated. The time distribution of the seizures during the day was noted. Seizure latency was determined as the time in hours from the start of the video-electroencephalographic recording to the first clinical event. Results The seizure latency was significantly shorter in PNES patients compared to ES patients (p < 0.001). Seventy-two percent of PNES patients and 49.1% of ES patients had their first seizure in the 24 hours of video-EEG recording (p = 0.023). Recording longer than 48 hours was required for 12.5% of PNES patients and 37.3% of ES patients (p = 0.006). While ESs were almost evenly distributed throughout the day, most PNESs occurred during the evening hours (p = 0.011). Conclusion We observed that the PNESs appeared earlier than the ESs in the VEM and were concentrated during daylight hours. Although not strictly reliable, seizure latency can contribute to the differential diagnosis of ES and PNES.

Resumen Antecedentes Debido a sus similitudes semiológicas, las crisis no epilépticas psicógenas (CNEP) en ocasiones apenas se pueden diferenciar de las crisis epilépticas (CE), y se necesita una monitorización video-electroencefalográfica (EEG) prolongada para el diagnóstico diferencial. Objectivo Investigar el momento del primer evento clínico y su distribución en los días de monitorización video-EEG en pacientes con CE y CNEP. Métodos Se evaluó retrospectivamente a una serie consecutiva de 48 pacientes con CNEP y 51 con ES emparejados por sexo y edad. Se anotó la distribución temporal de las incautaciones durante el día. La latencia de las crisis se determinó como el tiempo en horas desde el inicio de la grabación del video-EEG hasta el primer evento clínico. Resultados La latencia de las crisis fue significativamente menor en los pacientes con CNEP en comparación con los pacientes con CE (p < 0,001). El 72% de los pacientes con CNEP y el 49,1% de los pacientes con CE tuvieron su primera crisis en las 24 horas de registro del video-EEG (p = 0,023). Se requirió un registro de más de 48 horas para el 12,5% de los pacientes con CNEP y el 37,3% de los pacientes con CE (p = 0,006). Mientras que las CE se distribuyeron casi uniformemente a lo largo del día, la mayoría de las CNEP ocurrieron durante las horas después del anochecer (p = 0,011). Conclusión Observamos que las CNEPs aparecieron antes que las CEs en la monitorización video-EEG, y se agruparon durante las horas del día. Aunque no es estrictamente confiable, la latencia de las crisis puede contribuir al diagnóstico diferencial de ES y CNEP.

Serum osteoprotegerin levels in patients with acute atherothrombotic stroke and lacunar infarct.

BACKGROUND: Arterial calcification is associated with increased risk of cardiovascular events. Osteoprotegerin (OPG) is a cytokine involved in the bone metabolism and vascular calcification. Recent data support a relationship between high serum levels of OPG and increased risk for cardiovascular disease in human. The aim of this study was to evaluate the OPG serum levels in acute ischemic stroke. Our study was further designed to detect differences in serum OPG levels between subtypes of ischemic stroke. MATERIALS AND METHODS: The study consisted of 51 patients with acute ischemic stroke and 28 control subjects. Stroke subtypes were defined by the TOAST classifications. Serum OPG levels were measured with the ELISA method. RESULTS: OPG serum levels were significantly higher in patients with ischemic stroke than in control subjects (p<0.001). OPG serum levels were significantly higher in large-vessel disease (LVD) subtype compared with small-vessel disease (SVD) subtype and controls (p<0.001, p<0.001). There was no significant difference in OPG serum levels between SVD group and control subjects. Serum OPG levels were correlated with age (r=0.407, p=0.005) and fasting glucose levels (r=0.542, p=0.001) in ischemic stroke group. Logistic regression analysis showed that plasma OPG levels (OR 2.1, 95% CI, 1.16 to 3.4, p=0.01) associated with presence of stroke independently of the other risk factors. CONCLUSIONS: High serum OPG levels were associated with the LVD stroke subtype, suggesting that OPG levels may play role in pathogenesis of atherothrombotic stroke. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

Factors affecting the quality of life in drug-resistant epilepsy patients.

Epilepsy patients whose seizures cannot be controlled by treatment have a lower quality of life (QoL). The aim of the present study was to compare the potential factors affecting the QoL in patients who were seizure-free with medication or who had drug-resistant epilepsy. The study included 46 drug-resistant and 42 seizure-free epilepsy patients. The demographic and clinical features of the patients were investigated for their effects on patient QoL. The QoL was assessed by the QoL in Epilepsy Inventory-89 and depression was detected by the Beck Depression Inventory. The QoL was significantly lower in the drug-resistant patients than in the seizure-free epilepsy patients (p < 0.001). Depression, lower education level, and unemployment were associated with lower QoL scores (p < 0.001, p < 0.01, p < 0.001, respectively). After adjusting for lower education level and unemployment, depression remained as an independent factor affecting QoL (p < 0.05). In addition to their efforts to control and stop seizures, clinicians should remain aware of depression and treat it effectively to improve the QoL of drug-resistant epilepsy patients.

Ictal asystole mimicking seizure deterioration in temporal lobe epilepsy.

We report on a patient with temporal lobe epilepsy, secondary to a left lateral temporal cavernoma, in whom the change in seizure semiology suggested recurrence of secondary generalized seizures. Anticonvulsive medication previously controlled secondary generalized seizures over a period of years but focal seizures continued at a lower rate. Continuous video-EEG monitoring revealed ictal asystole associated with myoclonic syncope and falls during focal seizures arising from the left temporal lobe. After implantation of a cardiac pacemaker, no more falls occurred during the focal seizures. In conclusion, recurrence of seizure-associated falls is typically attributed to recurrence of secondary generalized seizures, however, ictal asystole should be considered in selected epilepsy patients as a differential diagnosis of falls. [Published with video sequence].

Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients.

INTRODUCTION: In this study, we investigated the association of migraine with the Variable Number of Tandem Repeats (VNTR), repeated as 27 base pair, gene polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) and the insertion/deletion of angiotensin converting enzyme (ACE) gene polymorphisms. METHODS: One hundred and five migraine and ninety seven healthy female control subjects were enrolled in the study. The patients were subdivided as migraine with aura and without aura, and the frequency and severity of migraine headaches were recorded. The eNOS VNTR (eNOS 4 a/b) and ACE insertion/deletion gene polymorphisms (ACE I/D) were assessed by polymerase chain reactions. RESULT: The allele and genotype frequencies of eNOS 4 a/b gene polymorphism showed no difference between the migraine and control groups. The genotypic distribution of the ACE I/D gene polymorphism in the migraine group significantly differed from that in the control group. The DD and ID genotype increased the risk of migraine as much as 2.571 (95% CI-1.138-5.811) and 4.453 (95% CI-2.006-9.883) compared to the II genotype. The same increased risk sustained for both genotypes in the migraine with aura subgroup, but only the ID genotype remained as the risk factor in the migraine without aura subgroup (OR-3.750, 95% CI-1.493-9.420). No association of gene polymorphisms with migraine frequency and severity was observed. CONCLUSION: Our findings support the relationship between migraine and the ACE I/D gene polymorphism. However, no association was found between migraine and the eNOS 4 a/b gene polymorphism.