Validity and reliability of the 3-meter backward walk test in patients with multiple sclerosis.

BACKGROUND: The 3-meter backward walk test (3MBWT) evaluates neuromuscular control, proprioception, protective reflexes, fall risk, and balance. This study aimed to examine the reliability, validity, and minimal detectable change (MDC) of the 3MBWT in patients with Multiple Sclerosis (pwMS). METHODS: 40 pwMS (8 male, 32 female) were included in the study. The Intraclass Correlation Coefficient (ICC) was used for the reliability of the 3MBWT. MDC estimates were calculated using baseline data. The validity of the 3MBWT was evaluated by the correlation between The Timed Up and Go test (TUG), The 12-item Multiple Sclerosis Walking Scale (MSWS-12), The 2 Min Walk Test (2MWT), The Timed 25-Foot Walk Test (T25FW), and The Four Square Step Test (FSST) RESULTS: The intra-rater (ICC 0.944-0.945) and inter-rater (ICC 0.932-0.935) reliability of the 3MBWT was determined to be excellent. MDC values for intra-rater were 1.13-1.30 sec, and MDC values for inter-rater were 1.10-1.24 sec. The correlation with 3MBWT, TUG, MSWS-12, and 2MWT was found to be statistically significant. CONCLUSION: The 3MBWT was found to be valid and reliable in pwMS. It is a short and easily applied test in outpatient and inpatient clinics without any need for equipment. According to the MDC results, small differences in pwMS can be adequately detected with 3MBWT. Therefore, it may be a clinically suitable test for detecting subtle changes in synergistic motor functions related to prorioception in relapsing or remitting periods. It, also may add some more information on to EDSS data for following the disease progression as well as treatment responses.

Muscle architecture and its relationship with lower extremity muscle strength in multiple sclerosis.

This study was planned to determine the muscle architecture (pennation angle, muscle fiber length, and muscle thickness) and its relationship to lower extremity muscle strength in patients with Multiple Sclerosis (pwMS). The muscle architecture (pennation angle, muscle fiber length, and muscle thickness) and lower extremity muscle strength were assessed in 33 pwMS [13 Relapsing-Remitting MS (RRMS), 5 Primary Progressive MS (PPMS), 5 Secondary Progressive MS (SPMS), and 11 matched healthy controls (HC)]. Muscle architecture features were assessed with ultrasonography and muscle strength were assessed with a digital hand-held dynamometer. The rectus femoris muscle thickness and pennation angle, gastrocnemius muscle thickness, and the tibialis anterior pennation angle were significantly lower in pwMS compared to HC (p < 0.05). The strength of hip flexors, hip extensors, knee extensors, foot plantar, and foot dorsi flexors were lower in pwMS. In PPMS group, muscle strength of hip flexors was lower than RRMS and SPMS groups, and muscle strength of foot dorsi flexors was lower than RRMS (p < 0.05). In pwMS, positive correlations were found, between knee flexor strength and biceps femoris pennation angle. Also knee extensor strength and rectus femoris fiber length and muscle thickness were correlated positively (p < 0.05). According to our results the muscle architecture is affected in MS. The determination of architectural changes of lower extremity muscles may guide the arrangement of optimal strength exercises in functional rehabilitation programs.ClinicalTrials: NCT03766698.

Hypothesis: Do miRNAs Targeting the Leucine-Rich Repeat Kinase 2 Gene (LRRK2) Influence Parkinson's Disease Susceptibility?

Parkinson's disease (PD) is a frequently occurring neurodegenerative motor disorder adversely impacting global health. There is a paucity of biomarkers and diagnostics that can forecast susceptibility to PD. A new research frontier for PD pathophysiology is the study of variations in microRNA (miRNA) expression whereby miRNAs serve as "upstream regulators" of gene expression in relation to functioning of the dopamine neuronal pathways. Leucine-Rich Repeat Kinase 2 (LRRK2) is a frequently studied gene in PD. Little is known about the ways in which expression of miRNAs targeting LRKK2 impact PD susceptibility. In a sample of 204 unrelated subjects (102 persons with PD and 102 healthy controls), we report here candidate miRNA expression in whole blood samples as measured by real-time PCR (hsa-miR-4671-3p, hsa-miR-335-3p, hsa-miR-561-3p, hsa-miR-579-3p, and hsa-miR-3143) that target LRRK2. Using step-wise logistic regression, and controlling for covariates such as age, gender, PD disease severity, concomitant medications, and co-morbidity, we found that the combination of has-miR-335-3p, has-miR-561-3p, and has-miR-579-3p account for 50% of the variation in regards to PD susceptibility (p<0.0001). Notably, the hsa-miR-561-3p expression was the most robust predictor of PD in both univariate and multivariate analyses (p<0.001). Moreover, the biological direction (polarity) of the association was plausible in that the candidate miRNAs displayed a diminished expression in patients. This is consistent with the hypothesis that decreased levels of miRNAs targeting LRRK2 might result in a gain of function for LRRK2, and by extension, loss of neuronal viability. To the best of our knowledge, this is the first clinical association study of the above candidate miRNAs' expression in PD using peripheral samples. These observations may guide future clinical diagnostics research on PD.

Plasma urotensin-2 level and Thr21Met but not Ser89Asn polymorphisms of the urotensin-2 gene are associated with migraines.

BACKGROUND: Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). METHODS: One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. RESULTS: Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (ß = 0.508, p = 0.001). CONCLUSION: Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.

Oxidative stress and DNA damage in patients with migraine.

BACKGROUND: Oxidative stress is implicated in the pathogenesis of migraine, but no published studies have examined both oxidative stress levels and oxidative DNA damage on the same patient group. METHODS: In this study, total oxidant status (TOS); total antioxidant status (TAS); oxidative stress index (OSI); and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is an indicator of oxidative DNA damage, were measured in the plasma samples of 50 prophylactic unmediated migraineurs (11 with aura and 39 without aura) and 30 matched healthy volunteers. RESULTS: No significant differences in TAS, TOS, and OSI values were observed between patients and controls. However, plasma 8-OHdG levels were found to be significantly higher in migraine patients than in the control group (p = 0.001); this increase in plasma 8-OHdG levels was more prominent in cases with migraine without aura than with aura (p = 0.001). Our results suggested an evidence of oxidative stress-related DNA damage in migraine. CONCLUSION: DNA damage reflected by plasma 8-OHdG did not studied in migraine before. Therefore, further research on oxidative stress-related DNA damage and the extent of its clinical manifestations in migraine may provide additional data to our current knowledge.

Investigation of the Plasma Nitrite Levels and Oxidant-Antioxidant Status in Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Obstructive sleep apnea (OSA) is one of the most prevalent sleep disorders. In the present study, we assessed the nitrite level, which is an indirect indicator of nitric oxide (NO), total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI), which may be associated with endotel dysfunction. We investigated the difference between the groups and the relationship among the severity of comorbid conditions. METHODS: This study was conducted in 39 OSA patients confirmed by polysomnography and 40 healthy subjects (controls). The OSA group consisted of 10 women and 29 men and the control group consisted of 20 women and 20 men. Polysomnographic revealed mild OSA in two, moderate in 7 and severe in 30 cases. We measured plasma TAS, TOS and nitrite levels from venous blood. The OSI value was obtained by dividing the TOS and TAS values. Values were compared with the control group and between patient groups. RESULTS: A high body mass index (BMI), cardiovasculer diseases (CVD) and the use of medication for co-morbid diseases were more prevalent in the OSA group (p=.001, p=.029 and p=.006, respectively). The median plasma TOS level and OSI in the obstructive sleep apnea syndrome (OUA) group were significantly higher than those in the control group (p=.001 and p=.001, respectively). The plasma median nitrite level and TAS did not show any significant difference between the OSA and the control groups. None of the parameters revealed a significant difference between severe and moderate OSA cases. CONCLUSION: Our findings in the present study revealed that the oxidant-antioxidant balance shifted toward the oxidant side in OSA cases; however, the NO level did not change. These findings together may point out that some molecules other than NO may have a role in the pathophysiology of endothelial dysfunction and also in the disturbed oxidant-antioxidant balance in OSA.