Quantification of upper limb dysfunction in the activities of the daily living in persons with multiple sclerosis.

BACKGROUND: Dysfunction in upper limb (UL) function has been reported as an important indicator for disease progression in persons with multiple sclerosis (PwMS), thus a relevant outcome in clinical trials. However, standard assessment of UL function is limited to Nine-Hole Peg Test (NHPT) which assesses fine dexterity. This study aimed to deeply endophenotype UL involvement in PwMS and identify the most accurate set of measures needed to capture the complexity of UL dysfunction in the activities of daily living (ADL). METHODS: 257 PwMS underwent an extensive UL assessment using standardized measures of grip strength and endurance, coordination, vibratory and tactile sensation, dexterity, capacity and functionality. Limitation in ADL was defined from an objective perspective using a timed test (Test d'Evaluation de la performance des Membres Supérieurs des Personnes Âgées: TEMPA) and from a subjective perspective using a questionnaire (Disabilities of the Arm, Shoulder and Hand: DASH). Disease severity subgroups were compared utilizing the Kruskal-Wallis test and frequencies determined the prevalence of abnormal UL for each measure. The Jonckheere-Terpstra test compared tested variables with disease severity. Then Receiver operating characteristic (ROC) curve analysis was used to test the accuracy of each tested variable in defining abnormality in the TEMPA and DASH. Cut-off scores were calculated using the Youden index. The predictive value of various tests over TEMPA and DASH were tested using a linear regression analysis. RESULTS: UL dysfunction was highly prevalent in all the modalities tested, even in participants with no/mild disability. Box and Block Test (BBT), finger-nose test (FNT), and NHPT were independently selected with ROC analyses as the most accurate measures in detecting abnormalities in TEMPA and DASH. In multivariate regression models, BBT and FNT, and NHPT all contributed to predicting TEMPA (adj. R2 0.795, P < 0.001), while only BBT and FNT predicted DASH. CONCLUSIONS: UL dysfunction is highly prevalent in PwMS, even when global disability is mild. BBT and FNT are time-efficient and cost-effective measures that complement the NHPT for more precise monitoring of PwMS at all disease stages.

Quantification characteristics of digital spiral analysis for understanding the relationship among tremor and clinical measures in persons with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a degenerative neurological condition causing demyelination and neuronal loss. Tremor, a symptom of MS, is prevalent in 45.0-46.8% NARCOMS registrants. Although several tools to measure tremor exist, few outcomes are quantitative or regularly utilized clinically. NEW METHOD: Introduction of a novel adaptation of the digital spiral drawing to find a quick, sensitive, and clinically useful technique, to predict tremor in persons with MS (pwMS). Digital spiral measures included: Segment Rate (SEGRT), Standard Deviation (SD) of Radial Velocity (VSD-R), SD of Tangential Velocity (VSD-T), SD of Overall Velocity (VSD-O), Mean Drawing Velocity (MNV-O) and Mean Pen Pressure Acceleration (MNA-P). Digital spiral measures were compared with the manual Archimedes Spiral (AS) drawing and the following clinical measures: Finger-Nose Test (FNT), presence of visually observed intention tremor (VOT), Nine-Hole Peg Test (NHPT), and Box and Block Test (BBT). RESULTS: All clinical measures utilized demonstrated significant relationships with all digital variables, except VSD-R. The forward-stepwise regression revealed BBT accounted for the most variance, followed by SEGRT. Comparison with Existing Methods: SEGRT is more sensitive in detecting VOT and better for quantifying tremor than AS. BBT and SEGRT are optimal predictive measures for tremor. CONCLUSIONS: SEGRT has stronger sensitivity and negative predictive value than AS in detecting VOT. All clinical measures (NHPT, FNT, BBT, and AS) were significantly associated with the digital variables (SEGRT, VSD-T, VSD-O, MNV-O, and MNA-P) except for VSD-R. After controlling for Patient Determined Disease Steps (PDDS), BBT and SEGRT are the best predictive measures for tremor.

Changes in Cognitive Processing Speed, Mood, and Fatigue in an Observational Study of Persons With Multiple Sclerosis Treated With Dalfampridine-ER.

OBJECTIVE: Multiple sclerosis (MS) is a degenerative neurological condition that results in impairments in multiple domains including cognition, fatigue, and mood. Dalfampridine-extended release (D-ER) has been approved to improve walking in persons with MS. It is plausible that D-ER could improve cognition, fatigue, and mood through the same mechanisms. We aim to examine effects of D-ER on cognition, depression, mood, and fatigue and to describe how these associations differ among those with and without D-ER related improvements in walking speed. METHODS: Patients with MS at the Mandell Center who were newly prescribed D-ER as part of their standard MS care were invited to participate in this observational pre-post study. Thirty-nine participants with MS were observed for 14 weeks; 31 remained on D-ER for 14 weeks or longer. Of these, 28 were then subdivided based on walk responder status. Cognition was assessed using the SDMT; depression was measured with the CESD. Self-reported cognition, mood, and fatigue were also measured using subscales of the Performance Scales (PS). RESULTS: Among those on drug through 14 weeks, there was significant improvement in the SDMT (P < 0.001) and the PS Fatigue score (P = 0.04). Among those who discontinued drug before 14 weeks, PS Cognition and PS Mood scores significantly improved (P = 0.02). Timed walk responders had significant improvements in SDMT (P < 0.001) and PS Fatigue (P = 0.046) from baseline to week 14. Among timed walk nonresponders, none of the measures significantly changed. CONCLUSIONS: Dalfampridine-extended release may improve cognition and fatigue in persons with MS, especially among timed walk responders.

Reproducibility of ambulatory blood pressure changes from the initial values on two different days

OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: The subjects comprised 88 men and 57 women (mean age±SE 22.4±0.3 years) with normal BP (118.3±0.9/69.7±0.6 mmHg). For the total sample, the correlation between the ambulatory BP change on day 1 vs. day 2 over 24, waking, and sleeping hours ranged from 0.37-0.61; among women, the correlation was 0.38-0.71, and among men, it was 0.24-0.52. Among women, the ambulatory systolic/diastolic BP change was greater by 3.1±1.0/2.4±0.8 mmHg over 24 hours and by 3.0±1.1/2.4±0.8 mmHg over waking hours on day 1 than on day 2. The diastolic ambulatory BP change during sleeping hours was greater by 2.2±0.9 mmHg on day 1 than on day 2, but the systolic ambulatory BP change during sleeping hours on days 1 and 2 did not differ. Among men, the ambulatory BP change on days 1 and 2 did not differ. CONCLUSION: Our primary findings were that the ambulatory BP change from the initial values was moderately reproducible; however, it was more reproducible in men than in women. These results suggest that women, but not men, may experience an alerting reaction to initially wearing the ambulatory BP monitor. .

Reproducibility of ambulatory blood pressure changes from the initial values on two different days.

OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: The subjects comprised 88 men and 57 women (mean age±SE 22.4±0.3 years) with normal BP (118.3±0.9/69.7±0.6 mmHg). For the total sample, the correlation between the ambulatory BP change on day 1 vs. day 2 over 24, waking, and sleeping hours ranged from 0.37-0.61; among women, the correlation was 0.38-0.71, and among men, it was 0.24-0.52. Among women, the ambulatory systolic/diastolic BP change was greater by 3.1±1.0/2.4±0.8 mmHg over 24 hours and by 3.0±1.1/2.4±0.8 mmHg over waking hours on day 1 than on day 2. The diastolic ambulatory BP change during sleeping hours was greater by 2.2±0.9 mmHg on day 1 than on day 2, but the systolic ambulatory BP change during sleeping hours on days 1 and 2 did not differ. Among men, the ambulatory BP change on days 1 and 2 did not differ. CONCLUSION: Our primary findings were that the ambulatory BP change from the initial values was moderately reproducible; however, it was more reproducible in men than in women. These results suggest that women, but not men, may experience an alerting reaction to initially wearing the ambulatory BP monitor.

Correlates of endothelial function and the peak systolic blood pressure response to a graded maximal exercise test.

PURPOSE: An elevated systolic blood pressure (SBP) response to a graded maximal exercise stress test (GEST) may be a predictor of endothelial dysfunction and hypertension. We examined relationships among the GEST peak SBP response and indicators of endothelial function. METHODS: Men (n=48, 43.7±1.4 yr) with high BP (145.1±1.5/85.5±1.1 mmHg) completed a GEST. Peak SBP was the highest SBP achieved during the GEST. Blood samples were taken for fasting glucose and insulin, nitric oxide (NO), and DNA. Endothelial nitric oxide synthase (NOS3, rs2070744) -786 T>C genotyping was determined by PCR. NOS3 genotypes were combined using a dominant model [TT (n=24); TC/CC (n=24)]. Brachial artery reactivity (BAR) was determined via ultrasound before, 1 min, and 3 min post occlusion and calculated as % change. Analysis of variance (ANOVA) tested changes in the peak SBP GEST response by NOS3 genotype. Multiple variable regression analyses examined relationships among the GEST peak SBP response and measures of endothelial function. RESULTS: %BAR change at 1 min (r(2)=0.093, p=0.020), glucose (r(2)=0.062, p=0.014), NOS3 -786 T>C (r(2)=0.040, p=0.024), NO (r(2)=0.037, p=0.064), and age (r(2)=0.009, p=0.014) explained 24.1% of the GEST peak SBP response (p=0.043). The GEST peak SBP change from baseline was 11.1±5.0 mmHg higher among those with the NOS3 C allele (92.4 mmHg+3.8) than the NOS3 TT genotype (81.3 mmHg+3.2) (p=0.03). CONCLUSION: Indicators of endothelial function appear to explain a clinically significant portion of the GEST peak SBP response. Further investigation is needed to unravel the mechanisms by which endothelial function influences the GEST peak SBP response.