Investigation of the Rho-kinase 2 gene Thr431Asn polymorphism in migraine.

BACKGROUND: Migraine has a complex etiology determined by genetic and environmental factors, but the molecular mechanisms and genetics of this disease have not yet been fully clarified. AIM: This case/control study was designed to analyze the genotype distributions and allele frequencies for the Rho-kinase 2 (ROCK2) gene Thr431Asn polymorphism among the migraine patients. MATERIALS AND METHODS: A total of 155 migraine patients and 155 healthy age and sex matched controls were included in this study. Genomic deoxyribonucleic acid from migraine patients and controls was analyzed by real-time polymerase chain reaction. RESULTS: Neither genotype distributions nor the allele frequencies for the Thr431Asn polymorphism showed a significant difference between the groups. In addition, there were no marked differences in genotype and allele frequencies for the migraine without aura and migraine with aura subgroups when compared with control group. CONCLUSION: This is the first study to show that the ROCK2 gene Thr431Asn polymorphism is not a risk factor for the migraine in the Turkish population.

Lack of association between the C276T polymorphism of the neuronal nitric oxide synthase gene and migraine.

A migraine attack is a spectacularly complex brain event that can produce a wide array of neurological and systemic symptoms. The molecular mechanisms and genetics of migraine have not yet been clarified. The objective of this study was to analyze the genotype distributions and allele frequencies for the C276T polymorphism of the neuronal nitric oxide synthase (nNOS) gene among the patients with migraine. The diagnosis of migraine was made clinically based on questionnaires. One hundred and twenty patients with migraine were genotyped for the C276T polymorphism of the nNOS gene and compared with 185 age-matched healthy controls. Genomic DNA from migraine patients and controls was analyzed by polymerase chain reaction (PCR). A PCR-restriction fragment-length polymorphism analysis of nNOS gene polymorphism was performed, and the results were compared. Neither genotype distributions nor the allele frequencies for the C276T polymorphism showed a significant difference between the groups. Additionally, there was no marked differences in genotype distribution or allele frequencies for the migraine without aura and migraine with aura subgroups when compared to control group. These results suggested that migraine of the Turkish population seemed to develop without any alterations in nNOS C276T polymorphism. Our data showed that there is no marked association between the C276T polymorphism of the nNOS gene and migraine.

Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression.

BACKGROUND: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS. OBJECTIVE: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey. METHODS: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D). RESULTS: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables). CONCLUSIONS: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.

'Is RLS a harbinger and consequence of MS?: Striking results of the 'RELOMS-T' study'.

BACKGROUND: Although studies report a high prevalence rate of restless legs syndrome (RLS) among patients with multiple sclerosis (PwMS) ranging from 13.3 to 65.1%, little is known about the causes of this relationship. METHODS: To ascertain the prevalence, features and impact of RLS among PwMS a nation-wide, multicenter, prospective and a cross-sectional survey, designed to reflect all of the PwMS throughout Turkey, was conducted in 13 centers. Exploring the relationship of the two conditions could possibly contribute to the understanding of the causes of the high and wide-ranging prevalence rates and the pathophysiology of both diseases. RESULTS: Of the 1068 participants 173 (16,2%) found to have RLS [RLS(+)] and 895 (83,8%) did not [RLS(-)]. Among the RLS(+) 173, all but 8 patients (4,6%) were underdiagnosed in terms of RLS. More than half of the patients with RLS had 'severe' or 'very severe' RLS. The onset of RLS was before or synchronous with the onset of MS in about a half of our patients. CONCLUSION: We conclude that RLS should be meticulously investigated in PwMS and MS can be a direct cause of RLS at least in part of PwMS. Our data about the timing of the onset of MS and RLS, along with the high prevalence of RLS in PwMS suggest that the pathologic changes in the initial phases of MS can possibly trigger RLS symptoms.

Valproic Acid as a Cause of Transient Atrio-Ventricular Conduction Block Episodes.

Herein we share, to our knowledge for the first time, a a case of valproic acid use complicated by symptomatic atrio-ventricular conduction block episodes on Holter monitoring. Symptomatic atrio-ventricular block episodes should be considered as an unusual side effect of valproic acid despite normal blood therapeutic level. Before consideration of pacemaker implantation in such cases, valproic acid usage should be investigated, and dose reduction should be attempted.

Coexistence of restless legs syndrome and multiple sclerosis aggravates anxiety and depression / A coexistência da síndrome das pernas inquietas e esclerose múltipla agrava ansiedade e depressão

ABSTRACT Background: Among the comorbidities that accompany multiple sclerosis (MS), restless legs syndrome (RLS) is one of the most common. Anxiety and depression are common psychological comorbidities that impact the quality of life of patients with MS (PwMS), as well as patients with RLS. Objective: To investigate the psychiatric burden of MS and RLS coexistence, we conducted a nationwide, multicenter and cross-sectional survey. Methods: Participants were assessed by using demographic and clinical parameters along with the Hamilton Anxiety and Hamilton Depression Scales (HAM-A and HAM-D). Results: Out of the 1,068 participants, 173 (16.2%) were found to have RLS [RLS(+)] and 895 (83.8%) did not [RLS(-)]. The mean scores for HAM-A and HAM-D were significantly higher among RLS(+) subjects than among RLS(-) subjects (p<0.001 for all variables). Conclusions: According to our data, the presence of RLS in PwMS may increase the occurrence of both anxiety and depression symptoms. Awareness and treatment of RLS in PwMS could possibly reduce the symptoms of psychiatric comorbidities originating from RLS.

RESUMO Antecedentes: Considerando-se as comorbidades que acompanham a esclerose múltipla (EM), a síndrome das pernas inquietas (SPI) é uma das mais comuns, e ansiedade e depressão são comorbidades psicológicas comuns que afetam a qualidade de vida de pacientes com EM, bem como de pacientes com SPI. Objetivo: Investigar a carga psiquiátrica da coexistência de EM e SPI por meio de uma pesquisa nacional, multicêntrica e transversal. Métodos: Os participantes foram avaliados por parâmetros demográficos e clínicos, além da versão turca das escalas de ansiedade e depressão de Hamilton (HAM-A e HAM-D). Resultados: Dos 1.068 participantes, 173 (16,2%) apresentaram SPI [SPI (+)] e 895 (83,8%) não [SPI (-)]. As pontuações médias no HAM-A e no HAM-D foram significativamente maiores em indivíduos com SPI (+) do que naqueles com SPI (-) (p <0,001 para todas as variáveis). Conclusões: De acordo com nossos dados, a presença de SPI na EM pode aumentar a ocorrência de sintomas de ansiedade e depressão. A conscientização e o tratamento da SPI na EM podem reduzir os sintomas de comorbidades psiquiátricas originadas da SPI.

A prospective study of Willis-Ekbom disease/restless legs syndrome during and after pregnancy.

OBJECTIVES: Willis-Ekbom disease/restless legs syndrome (WED/RLS) is the most common sleep-related movement disorder in pregnancy. We designed a prospective longitudinal study to investigate the correlates of WED/RLS during and after pregnancy. DESIGN: A total of 138 pregnant women with WED/RLS and a control group of 251 age-matched pregnant women were enrolled prospectively. A questionnaire was administered during a face-to-face interview at first evaluation during pregnancy and three months after delivery. RESULTS: Among all women in the first trimester, 15.6% were diagnosed with WED/RLS, whereas 32.8% of those in the second trimester and 38.8% of those in the third trimester were diagnosed with WED/RLS (p = 0.032). In regression analysis, later gestational age [p < 0.001; odds ratio (OR) 1.054] and previous history of WED/RLS (p = 0.001; OR 2.795) were positively correlated with the presence of WED/RLS, while ferritin levels (p = 0.001; OR 0.956) were negatively correlated with the presence of WED/RLS. Ferritin levels were also negatively correlated with the International RLS Study Group severity index (p = 0.041). Forty-eight patients (34.8%) experienced WED/RLS symptomatology after delivery. The ferritin levels were lower, and the mean number of pregnancies was higher, in women with residual WED/RLS (p = 0.008). CONCLUSION: Our survey showed that WED/RLS was more common in the second and third trimesters. Emergence of WED/RLS during the second trimester was strongly associated with residual WED/RLS. Lower ferritin levels were associated with both WED/RLS in pregnancy and residual WED/RLS after delivery. A higher number of pregnancies were also associated with a greater likelihood of having residual WED/RLS after delivery.

Plasma nitrite levels, total antioxidant status, total oxidant status, and oxidative stress index in patients with tension-type headache and fibromyalgia.

OBJECTIVES: Tension-type headache (TTH) and fibromyalgia syndrome (FM) are worldwide seen chronic pain syndromes of unknown etiology. Despite the growing body of data on pathophysiology and generation mechanisms of pain; our knowledge on pain mechanisms in both FM and TTH is yet to be limited. PATIENTS AND METHODS: We investigated the plasma nitrite levels, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) in 35 TTH, 33 FM patients and 31 healthy controls. RESULTS: The mean plasma nitrite levels and TAS levels were significantly low and OSI was found to be significantly high in TTH and FM groups compared to the control group (p=0.001, p=0.001, p=0.001 and p=0.001, respectively). The mean serum TOS levels were also significantly higher in FM group according to the control group (p=0.034), but there was not a significant difference between TTH and control groups (p=0.066). CONCLUSION: These results indicated that; FM and TTH patients revealed higher oxidative stress index and lower total nitrite levels than healthy controls. We conclude that oxidative stress may have a role in the pathophysiological mechanisms of TTH and FM, although, whether it is the cause or the consequence, is not clear.

Is increased red cell distribution width (RDW) indicating the inflammation in Alzheimer's disease (AD)?

Increasing evidence indicates that inflammation has a substantial role in the pathogenesis and progression of AD. RDW, a measure of heterogeneity in the size of circulating erythrocytes, is associated with inflammatory markers in many numerous diseases. Present study was undertaken to assess the interrelationships between RDW and AD. A total of 197 patients with AD (male/female: 96/101, mean age 76.2 ± 6.9) and 133 patients as controls with normal cognitive function (male/female: 72/61, mean age 71.68 ± 5.3) were enrolled in this cross-sectional study. RDW values of all participants were measured. Mini-Mental State Examination (MMSE) and clock drawing tests were performed for cognitive assessment. DSM-IV and NINCDS-ADRDA criteria were used for diagnosis of AD. The mean RDW values were significantly higher in AD group (13.93 ± 1.1 vs. 13.24 ± 1.2; p<0.001) and also a negative moderate correlation between RDW and MMSE was identified (r: -0.453; p<0.001). After adjusting for confounders, RDW has the strongest association with AD (odd ratio (OR) 1.51, CI=1.10-2.07). In present study RDW levels were significantly increased in patients with AD. Whereas elevated RDW value is usually considered as a novel biomarker of inflammation, the results of our study may support the role of inflammation in pathophysiology of AD. Furthermore the correlation of RDW with poorer cognition status suggests that it may be used as a marker of AD severity.

Economic impact of primary headaches in Turkey: a university hospital based study: part II.

This study was planned to investigate the economic impact of headache on Turkish headache sufferers attending a tertiary care outpatient headache clinic.A total of 937 headache patients were included in this study and questioned using a questionnaire for the profile of patients and headache, quality of life of patients and economic impact of headache. The median total direct cost was found to be 88.0 USD and the median total cost was 160.7 USD. The drug treatment cost was the highest item followed by the specialist outpatient care cost. The average lost and inefficient work/school days was 1.5 (0-45) and 8.4 (0-100) days for one year. It was shown that loss of productivity was higher for migraine without aura group when compared with the episodic and chronic tension-type headache groups. The results of this nationwide university hospital based study methshowed that headache, especially migraine, has considerable economic impact on patients.

Validity and reliability of the Turkish Migraine Disability Assessment (MIDAS) questionnaire.

OBJECTIVES: The aim of this study is to assess the comprehensibility, internal consistency, patient-physician reliability, test-retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache. BACKGROUND: MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine. DESIGN AND METHODS: This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test-retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test-retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to +/-3 days difference in the number of days with headache between visits 1 and 2). RESULTS: A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that "they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001). Internal consistency of MIDAS was assessed using Cronbach's alpha and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test-retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache-related disability over a 3-month period similar to MIDAS questionnaire. CONCLUSION: These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test-retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self-administered report by migraine patients themselves.