The figure-of-eight walk test is a reliable and valid test for assessing walking skill in people with multiple sclerosis.

BACKGROUND: The ability to turn while walking is essential for people's activities of daily living. Difficulties in turning while walking are commonly shown in people with multiple sclerosis (PwMS). The figure-of-eight walk test (F8W) is a clinical test assessing walking skill in a curved pathway; however, its reliability and validity have not been systematically examined for PwMS. PURPOSES: The study is aimed to investigate: (1) the test-retest reliability of the F8W in PwMS; (2) the standard error of measurement and minimum detectable change in the F8W times; (3) the concurrent and known-groups validity of the F8W times; and (4) the cut-off times that best discriminate fallers from non-fallers with MS. METHOD: This cross-sectional study included 41 PwMS and 33 healthy people. The F8W was performed along with the Timed Up and Go Test (TUG), Berg Balance Scale (BBS), Activities-specific Balance Confidence Scale (ABC), and Expanded Disability Status Scale (EDSS). To determine the test-retest reliability, the F8W was conducted twice, 7-10 days apart. The reliability was assessed using the intraclass correlation coefficient (ICC), Bland-Altman plots, standard error of measurement (SEM), and minimal detectable change (MDC). To examine validity, the correlations between the F8W and the TUG, BBS, ABC, and EDSS were assessed using correlation coefficients, and the completion times of the F8W were compared between PwMS and healthy people, and between fallers and non-fallers with MS. The receiver operating characteristic curve was constructed to determine the optimal F8W cut-off time discriminating fallers from non-fallers with MS. RESULTS: The F8W had excellent test-retest reliability with an ICC of 0.916. Bland-Altman plots showed high agreement between sessions. The SEM and MDC were found to be 0.45 and 1.25, respectively. The F8W indicated a moderate to strong correlation with other outcome measures (correlation coefficients ranged from -0.596 to 0.839, p<0.05). On the F8W, PwMS had a longer time than healthy people while fallers had a longer time than non-fallers with MS (p<0.001, and p<0.001, respectively). The cut-off time of 8.52 s best discriminated the fallers from non-fallers with MS. CONCLUSIONS: The F8W is a reliable and clinically available measurement tool for walking skill in PwMS.

The 3-m backward walk test: reliability and validity in ambulant people with multiple sclerosis.

To investigate: (a) the interrater and test-retest reliability of the 3-m backward walk test (3MBW) in ambulant people with multiple sclerosis (PwMS); (b) minimal detectable change (MDC); (c) concurrent and known-groups validity; and (d) the cutoff time to best discriminate fallers from nonfallers with multiple sclerosis (MS). Forty-nine PwMS and 36 healthy people were included in this cross-sectional study. The 3MBW was administered with the timed up and go test, Berg Balance Scale, four square step test, Falls Efficacy Scale-International, and Expanded Disability Status Scale. The 3MBW was simultaneously performed by two independent raters to examine the interrater reliability while was repeated after 7-10 days to examine the test-retest reliability. The 3MBW showed good interrater reliability [intraclass correlation coefficient (ICC) = 0.987-0.989] and excellent test-retest reliability (ICC = 0.854-0.889). The MDC was found to be 1.69 s. The 3MBW had moderate-to-strong correlations with the other measures. For the 3MBW, PwMS had worse performance than healthy people ( P < 0.001), whereas fallers with MS had worse performance than nonfallers with MS ( P < 0.001). The 3MBW time of 7.86 s was determined to best discriminate fallers from nonfallers with MS. The 3MBW is a reliable, simple, and easy-to-administer tool for assessing backward walking among ambulant PwMS.

Association of cholesterol 7α-hydroxylase (CYP7A1) promoter polymorphism (rs3808607) and cholesterol 24S-hydroxylase (CYP46A1) intron 2 polymorphism (rs754203) with serum lipids, vitamin D levels, and multiple sclerosis risk in the Turkish population.

BACKGROUND: Patients with multiple sclerosis (MS) have significantly lower vitamin D levels. Cholesterol is known to be the precursor for vitamin D synthesis, and cholesterol removal is regulated by cholesterol 7α-hydroxylase (CYP7A1) in the liver and cholesterol 24S-hydroxylase (CYP46A1) in the brain. In this study, single nucleotide polymorphisms (SNPs) within the genes CYP7A1 (rs3808607) and CYP46A1 (rs754203) were investigated for their effects on serum lipid profiles, vitamin D levels, and the risk of developing MS. METHODS: Patients with MS (n = 191) and controls (n = 100) were tested using the PCR-RFLP method to determine their genotypes for rs3808607 and rs754203 SNPs. RESULTS: The minor (C) allele frequency for CYP7A1 rs3808607 variation was 0.380 in patients with MS and 0.305 in control subjects (P = .074). For CYP46A1 rs754203, the frequencies of the minor (C) allele were 0.272 and 0.250 in patients and control subjects, respectively (P = .563). Serum vitamin D (25(OH)D3) concentrations were significantly lower in patients than in control subjects (P = .002). The CYP46A1 rs754203 SNP was associated with total cholesterol levels in patients, whereas the CYP7A1 rs3808607 variant was not associated with serum lipid parameters or vitamin D levels in patients or control subjects. CONCLUSION: CYP7A1 rs3808607 and CYP46A1 rs754203 variations are not likely to confer an independent risk for MS development in the Turkish population. To the best of our knowledge, this is the first study to investigate the association between CYP46A1 rs754203 and MS risk.

Generation and characterization of human induced pluripotent stem cell line METUi001-A from a 25-year-old male patient with relapsing-remitting multiple sclerosis.

Multiple sclerosis is a chronic disease characterized by inflammation, demyelination, and axonal damage in the central nervous system. Here, we established an induced pluripotent stem cell (iPSC) line METUi001-A from the peripheral blood mononuclear cells of a 25-year-old male individual with clinically diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS) using the integration-free Sendai reprogramming method. We demonstrated that the iPSCs are free of exogenous Sendai reprogramming vectors, have a normal male karyotype, express pluripotency markers, and differentiate into the three germ layers. The iPSC line can serve as a valuable resource to generate cellular model systems to investigate molecular mechanisms underlying RRMS.

Association analysis of Glutathione S-transferase omega-1 and omega-2 genetic polymorphisms and ischemic stroke risk in a Turkish population.

OBJECTIVES: Oxidative stress is a known risk factor for the pathogenesis of atherosclerosis, the main cause of ischemic stroke. Glutathione S-transferase (GST) omega-1 and omega-2, members of phase II enzymes, play a role in the antioxidant system. The single nucleotide polymorphisms (SNPs), C419A and A424G in GST omega genes can cause a decrease in enzyme activity. The aim of this study was to investigate the possible association between these polymorphisms and ischemic stroke risk in a Turkish population. METHODS: The genotypes and allele frequencies for 239 patients and 130 controls were determined by the PCR/RFLP method. No significant differences were found between patients and controls in terms of genotype and allele frequencies. RESULTS: The frequency of the polymorphic 'A' allele was 0.358 in patients and 0.342 in controls for the C419A polymorphism in the GSTO1 gene. The frequency of the polymorphic 'G' allele for GSTO2 A424G SNP was 0.370 in patients and 0.404 in controls. The combined homozygous wild type genotype 'CCAG' was significantly higher in control group than in the patients. CONCLUSION: No significant difference was observed between the stroke patients and controls in terms of genotypes and allele distributions. Double combine haplotype CCAA was found to be protective against ischemic stroke when compare to other haplotypes. However, different genotypes of GSTO1 and GSTO2 were observed to have effects on stroke risk in subgroups of diabetics and smokers. In conclusion, the current study is the first to report this finding.

Validity and Reliability of the Turkish Version of the Questionnaire for the Assessment of Dysphagia in Multiple Sclerosis.

INTRODUCTION: The aim of this study was to investigate the validity and reliability of the Turkish version of the Questionnaire for the Assessment of DYsphagia in MUltiple Sclerosis (DYMUS) that has been developed for evaluating dysphagia in patients with multiple sclerosis. METHODS: This methodological study was conducted in the neurology clinic and outpatient department of a training hospital between March 15 and September 15, 2015. The study included 117 patients aged 18 years and over who had a definite diagnosis of multiple sclerosis, could communicate in Turkish, and volunteered to be included. Data were collected using a descriptive information form, the DYMUS, and the Eating Assessment Tool (EAT-10). The scale was translated and back translated to determine the language validity, and a specialist was consulted to make sure the content was valid. We used the EAT-10 and Kurtzke's Expanded Disability Status Scale (EDSS) concurrently to test the criterion-related validity. The test-retest procedure was used at 1-week intervals for 37 patients in this study. Descriptive statistics, factor analysis, Kappa analysis, reliability analysis, and correlation analysis were used to analyze the data. RESULTS: Factor analysis revealed that the scale was bifactorial, and this was consistent with its original form. There were positive and statistically significant relationships between the DYMUS and EAT-10 (r=0.90, p<0.001) and the mean EDSS scores (r=0.49, p<0.001). The internal consistency of the total scale was high (Cronbach's alpha coefficient= 0.91). The Cronbach's alpha coefficients pertaining to dysphagia for solids and liquids were determined to be 0.88 and 0.83, respectively. The total scale and subscales demonstrated a high test-retest reliability (r=0.79-0.95, p<0.001). CONCLUSION: In this study, the Turkish version of the DYMUS was found to be a valid and reliable tool for evaluating dysphagia in patients with multiple sclerosis.

Genetic polymorphisms of vitamin D3 metabolizing CYP24A1 and CYP2R1 enzymes in Turkish patients with ischemic stroke.

Objective Vitamin D deficiency is known as an important risk factor in pathogenesis of atherosclerosis, which contributes to stroke development. Genetic variations including single nucleotide polymorphisms (SNPs) in enzymes involved in vitamin D metabolism can affect susceptibility to the development of stroke. Therefore, the objective of this study was to investigate the association between polymorphisms of vitamin D metabolizing enzymes (rs927650 SNP in CYP24A1, and rs10741657 SNP in CYP2R1 genes,) and ischemic stroke risk in Turkish population. Materials and methods To test this hypothesis, we designed a case-control study which consisted of 256 ischemic stroke patients and 132 controls. Genotypes were determined by PCR-RFLP technique. Results No significant differences were found between patients and controls in terms of CYP24A1 rs927650 and CYP2R1 rs10741657 genotype frequencies. Polymorphic allele frequencies of CYP24A1 rs927650 and CYP2R1 rs10741657 were 0.414 and 0.660 in stroke patients, respectively. Conclusion This is the first study conducted regarding the association of CYP24A1 rs927650 and CYP2R1 rs10741657 genetic polymorphisms and ischemic stroke risk. The polymorphic genotypes of these polymorphisms, together with hypertension, diabetes, smoking, and obesity, were found as significant risk factors for ischemic stroke.

Clinical, Radiological and Electrophysiological Comparison of Immunomodulatory Therapies in Multiple Sclerosis.

INTRODUCTION: Although it has been shown that immunomodulatory therapies (IMTs) in multiple sclerosis (MS) can modify the course of the disease by reducing the relapse rate and delaying the progression of disability, no study comparing IMTs head-to-head in terms of clinical, radiological, and electrophysiological changes is available. We aimed to investigate the effects of interferon-beta (IFN-B) 1b, IFN-B-1a subcutaneous (sc), IFN-B-1a intramuscular (im), and glatiramer acetate (GA) therapies on clinical, electrophysiological, and radiological findings. METHODS: We studied a cohort of 85 MS patients who were followed up for at least 2 years and had complete charting, including pre-treatment and post-treatment clinical, radiological, and electrophysiological findings. We compared the IMTs' effects on these findings retrospectively. RESULTS: Annual relapse rates were 0.1 for IFN-B-1a sc, 0.2 for IFN-B-1b, 0.3 for GA, and 0.5 for IFN-B-1 a im (p=0.01). The percentages of relapse-free patients after one year were 54.5% for IFN-B-1a im and GA, 82.9% for IFN-B-1a sc, and 86.4% for IFN-B-1b, and after two years the percentages were 27.3% for IFN-B-1a im, 54.5% for GA, 72.7% for IFN-B-1b, and 78% for IFN-B-1a sc (p<0.05). Disability scores after 2 years increased for IFN-B-1a im, decreased for IFN-B-1a sc (with a 0.1-point increase compared to the first year), and did not change for IFN-B-1b or GA compared to before treatment. Within the 2-year treatment period, no significant increase in the number of magnetic resonance T2 lesions was observed. No significant differences were found for any of the therapies in terms of evoked potentials. CONCLUSION: Our results revealed that high dose and more frequent regimens were more effective in terms of reducing the relapse rate, whereas there were no differences in terms of efficacy on radiological and electrophysiological findings between groups. Additional prospective studies comparing the efficacy of IMTs on MS are needed.

Association of cytochrome P4502E1 and NAD(P)H:quinone oxidoreductase 1 genetic polymorphisms with susceptibility to large artery atherosclerotic ischemic stroke: a case-control study in the Turkish population.

Stroke, a major cause of death and disability, is described as interruption or severe reduction of blood flow in cerebral arteries. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and carotid atherosclerosis is a risk factor for stroke. Combination of multiple environmental and genetic risk factors is thought to increase stroke. Therefore, investigation of the polymorphisms of enzymes is of crucial importance to determine the molecular etiology of the disease. To test this hypothesis, we performed a case-control study in which we compared the distribution of CYP2E1 and NQO1 genotypes between 245 large artery atherosclerotic ischemic stroke patients and 145 controls, using PCR-RFLP. A significant difference was observed between stroke patients and controls with respect to the CYP2E1*5B genotype (odds ratio; OR 8.069, P = 0.011) and allele (OR 7.876, P = 0.011) distribution. However, this polymorphism was not a significant predictor of disease status in logistic regression analysis. NQO1*2 polymorphism genotype distribution was significantly different between patients and controls (P = 0.027) and heterozygote *1*2 genotype was found to be a protective factor against large artery atherosclerotic ischemic stroke in logistic regression analysis (OR 0.562, P = 0.018). This is the first study conducted regarding the association of CYP2E1 and NQO1 genetic polymorphisms and large artery atherosclerotic ischemic stroke risk in Turkish population.

Decreased cerebral vasomotor reactivity in patients with obstructive sleep apnea syndrome.

OBJECTIVE: In obstructive sleep apnea syndrome (OSAS), any of the activated neural, vascular, hemodynamic, metabolic, inflammatory, and thrombotic mechanisms may be related to increased cerebrovascular disease and risk of death; however, the possible pathophysiological process between obstructive sleep apnea syndrome and stroke has not been clearly explained. We hypothesize that alterations in vasomotor reactivity in patients may be responsible for their altered cerebral blood flow, and may contribute to the increased risk of ischemic stroke. METHODS: A total of 30 untreated patients with severe obstructive sleep apnea and 26 control subjects were included in the study. The mean blood flow velocity and breath holding index were measured in middle cerebral artery bilaterally in both patient and control groups by using transcranial Doppler ultrasound. We compared the values between two groups. RESULTS: The mean blood flow velocity and breath holding indexes were significantly decreased in the patient group when compared with the control group. There were no correlations between cerebral hemodynamic parameters and polysomnographic findings in patients. CONCLUSION: Our findings suggest that there was a deteriorated vasodilator response to hypercapnia in patients with OSAS. This deterioration may stem from chemoreceptors or endothelial damages that lead to vascular relaxation and vasodilatation in cerebrovascular circulation. This impaired cerebral vascular regulation may contribute to the increased risk of stroke in patients with OSAS.

Reduced breath holding index in patients with chronic migraine.

Migraine is a neurovascular disorder characterized by autonomic nervous system dysfunction and severe headache attacks. Studies have shown that changes in the intracranial vessels during migraine have an important role in the pathophysiology. Many studies have been conducted on the increased risk of stroke in patients with migraine, but insufficient data are available on the mechanism underlying the increase. This study aimed to evaluate basal cerebral blood flow velocity and vasomotor reactivity in patients with chronic migraine. We evaluated 38 patients with chronic migraine. Three of them were excluded because they had auras and four of them were excluded because of their use of medication that can affect cerebral blood flow velocity and breath holding index (beta or calcium channel blockers). Our study population consisted of 31 patients with chronic migraine without aura and 29 age- and gender-matched healthy individuals who were not taking any medication. The mean blood flow velocity and breath holding index were measured on both sides from the middle cerebral artery and posterior cerebral artery, with temporal window insonation. The breath holding index for middle cerebral artery and posterior cerebral artery was significantly lower in the migraine group compared to that of the control group (p < 0.05).The vasomotor reactivity indicates the dilatation potential of a vessel, and it is closely related to autoregulation. According to our results, the vasodilator response of cerebral arterioles to hypercapnia was lower in patients with chronic migraine. These findings showed the existence of impairments in the harmonic cerebral hemodynamic mechanisms in patients with chronic migraine. This finding also supports the existing idea of an increased risk of stroke in patients with chronic migraine due to impaired vasomotor reactivity.

Activities of daily living and self-care agency in patients with multiple sclerosis for the first 10 years.

PURPOSE: The aim of the study was to present the effects of the disease and analyze the relationship between activities of daily living (ADL) and self-care in multiple sclerosis (MS) patients who have had the disease for the first 10 years. DESIGN: This study was a descriptive cross-sectional study. METHODS: A total of 67 patients who fit the inclusion criteria of the study and volunteered to participate were included in the sample. Data were collected using the Exercise of Self-Care Agency Scale and the Barthel Index. FINDINGS: The mean age was 38.43±9.92. There was a statistically significant correlation between participants'educational backgrounds and self-care scores and between disease duration and Barthel index score (p<.05). CONCLUSIONS: The self-care levels of patients who have had MS for the first 10 years are medium, and they tend to be mildly dependent in performing their ADL. The duration of MS is positively correlated with level of ADL. CLINICAL RELEVANCE: In this study, it was shown that the duration of the disease in MS patients should be taken into account by rehabilitation nurses to implement effective nursing care.

The effects of topiramate therapy on cerebral metabolism in migraine with aura patients.

AIM: Topiramate is an antiepileptic drug with multiple mechanisms of action that is also used for migraine prophylaxis. This study aimed to investigate the efficacy of topiramate therapy for migraine prophylaxis, based on vasomotor reactivity ([VMR] an indicator of cerebral autoregulation), and to identify changes in cerebral hemodynamics during the treatment. MATERIAL AND METHODS: We included 20 migraine (with aura) patients (group 1) and 20 healthy controls (group 2) in the study. Transcranial Doppler monitoring was performed in both groups with patients in the supine and resting position. Using a two-sided temporal window at depths of 45-60 mm for the middle cerebral artery (MCA) and depths of 60-70 mm for the posterior cerebral artery (PCA), basal flow rates and VMR values were measured. Group 1 initially received 25 mg/d of topiramate orally, and then the dose was increased 25 mg every week. At the fourth week; the optimal dose was increased to 50 mg b.i.d. and the treatment was continued at this dose. Transcranial Doppler parameters were re-evaluated 2 months after treatment. In addition, the number of attacks per month, duration of pain, and visual analog scale (VAS) scores obtained before the treatment and 2 months after the treatment in group 1 were compared. RESULTS: Basal flow rates and VMR values recorded from the right and left MCA in group 1 were significantly higher than those in the control group (P < 0.05). Flow velocities obtained from the right and left MCA, and the VMR values in group 1 after topiramate treatment did not differ significantly from those in the control group (P > 0.05). In addition, the number of attacks, duration of pain, and VAS scores in group 1 were significantly lower after the treatment than before the treatment (P < 0.05). CONCLUSION: Topiramate is an effective prophylactic treatment in migraine with aura patients and appeared to play a positive role in the regulation of cerebrovascular autonomic control.

Importance of NOS3 genetic polymorphisms in the risk of development of ischemic stroke in the Turkish population.

In the present study, we aimed to investigate the relationship between endothelial nitric oxide synthase 3 (NOS3) G894T, T-786C, and intron 4 variable number of tandem repeat (VNTR) variants, alone or in combination, and the risk of incidence of ischemic stroke in the Turkish population. The genotypes for all polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 245 ischemic stroke patients and 145 controls. In the case-control analysis, no significant difference was observed between stroke patients and controls with respect to NOS3 G894T, T-786C, and intron 4 VNTR polymorphisms genotype and allele frequency distribution. However, the copresence of G894T and intron 4 VNTR risk-elevating genotypes in the same individual increased the risk of stroke seven times (odds ratio=7.083, 95% confidence interval=0.866-57.963, p=0.029).