Central motor conduction time may predict response to fampridine in patients with multiple sclerosis.
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ABSTRACT:
SUBMITTER: Zeller D
PROVIDER: S-EPMC4033025 | biostudies-literature | 2014 Jun
REPOSITORIES: biostudies-literature
Publications
Central motor conduction time may predict response to fampridine in patients with multiple sclerosis.
Zeller D D Reiners K K Bräuninger S S Buttmann M M
Journal of neurology, neurosurgery, and psychiatry 20131219 6
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Project description:ObjectiveThe aim of this study was to determine the efficacy of sustained-release fampridine (4-aminopyridine) in veterans with multiple sclerosis (MS) with limited ambulatory ability, and its impact on motor function in an outpatient setting.DesignRetrospective.SettingTertiary referral center [Veterans Affairs (VA) Medical Center].ParticipantsVeterans; 20 MS patients were prescribed dalfampridine (10 mg twice daily) due to their difficulty with walking based on patient and caregiver report and clinician impression of change in the ability to ambulate based on prior 10-meter (10M) and 2-minute walk tests (2MWTs).InterventionNot applicable.Main outcome measuresThe primary outcome measures were mean changes in walking speed (10M walk test), walking distance (2MWT), and Total Functional Independence Measure (TFIM). Improvement of >20% in walking speed was indicated as a clinically meaningful change.ResultsTreatment with dalfampridine resulted in significant improvement in walking speed and endurance (p < 0.05). Walking speed increased by 33% and walking endurance by 31%, representing clinically meaningful improvement. This change was not influenced by change in muscle tone. This improvement in mobility was associated with a clinically significant change in motor function. Adverse effects, including insomnia, dizziness, and headache, were experienced by five patients who discontinued the medication after a minimum of 4 weeks.ConclusionTreatment with dalfampridine resulted in clinically relevant improvements in walking speed and endurance in MS patients with limited ambulation and helped improve their motor function.
| S-EPMC3784065 | biostudies-literature
Project description:The dominantly inherited spinocerebellar ataxias (SCAs) are a large class of neurodegenerative diseases. Transcranial magnetic stimulation has been used to evaluate the function of the pyramidal tract, and central motor conduction time (CMCT) is one index used to detect pyramidal tract dysfunction. We conducted a comprehensive search of PubMed, Embase and Web of Science. Eight eligible studies were included in the meta-analysis. For upper limb CMCT, the mean difference (95% confidence interval (CI)) between the combined SCA group and the control group was 2.24 [1.76-2.72], while the mean differences (95% CIs) between the subtypes and the control group were as follows: 4.43 [3.58-5.28] for SCA1, 0.25 [-0.15,0.65] for SCA2, 1.04 [-0.37,2.46] for SCA3 and 0.49 [-0.29,1.28] for SCA6. Additionally, SCA1 significantly differed from SCA2 and SCA3 in terms of CMCT (P=0.0006 and P=0.010, respectively). We also compared lower limb CMCT between the SCA2 and control groups. The mean difference (95% CI) was 6.58 [4.49-8.67], which was clearly statistically significant. The differences in CMCT values among different subtypes suggests diverse pathological mechanisms. In general, CMCT is a promising objective index to judge the severity of disease deserving further investigation.
| S-EPMC7803510 | biostudies-literature
Project description:The effects of age, height, and gender on magnetic central and peripheral motor conduction times (CMCT, PMCT) were analyzed using a multiple regression model.Motor evoked potentials were recorded in 91 healthy volunteers. Magnetic stimulation was performed over the primary motor cortex (cortical latency) and over the cervical and lumbar spines (spinal latency). The spinal latency was taken as an estimate of PMCT and was subtracted from cortical latency to yield CMCT.Lower limb CMCT correlated significantly with height only; there were no significant predictors for upper limb CMCT. Upper and lower limb PMCT correlated with both age and height.This is among the largest studies of CMCT in normal subjects. The multiple regression model unifies previously reported simple regression analyses, reconciles past discrepancies, and allows normal ranges to be individualized.
| S-EPMC4858813 | biostudies-other
Project description:BACKGROUND:Evoked potentials (EPs) are a measure of the conductivity of the central nervous system. They are used to monitor disease progression of multiple sclerosis patients. Previous studies only extracted a few variables from the EPs, which are often further condensed into a single variable: the EP score. We perform a machine learning analysis of motor EP that uses the whole time series, instead of a few variables, to predict disability progression after two years. Obtaining realistic performance estimates of this task has been difficult because of small data set sizes. We recently extracted a dataset of EPs from the Rehabiliation & MS Center in Overpelt, Belgium. Our data set is large enough to obtain, for the first time, a performance estimate on an independent test set containing different patients. METHODS:We extracted a large number of time series features from the motor EPs with the highly comparative time series analysis software package. Mutual information with the target and the Boruta method are used to find features which contain information not included in the features studied in the literature. We use random forests (RF) and logistic regression (LR) classifiers to predict disability progression after two years. Statistical significance of the performance increase when adding extra features is checked. RESULTS:Including extra time series features in motor EPs leads to a statistically significant improvement compared to using only the known features, although the effect is limited in magnitude (ΔAUC = 0.02 for RF and ΔAUC = 0.05 for LR). RF with extra time series features obtains the best performance (AUC = 0.75±0.07 (mean and standard deviation)), which is good considering the limited number of biomarkers in the model. RF (a nonlinear classifier) outperforms LR (a linear classifier). CONCLUSIONS:Using machine learning methods on EPs shows promising predictive performance. Using additional EP time series features beyond those already in use leads to a modest increase in performance. Larger datasets, preferably multi-center, are needed for further research. Given a large enough dataset, these models may be used to support clinicians in their decision making process regarding future treatment.
| S-EPMC7085864 | biostudies-literature
Project description:Multiple sclerosis (MS) patients often suffer from gait impairment and fampridine is indicated to medically improve walking ability in this population. Patient characteristics, healthcare resource use, and costs of MS patients on fampridine treatment for 12 months in Germany were analyzed.A retrospective claims database analysis was conducted including MS patients who initiated fampridine treatment (index date) between July 2011 and December 2013. Continuous insurance enrollment during 12 months pre- and post-index date was required, as was at least 1 additional fampridine prescription in the fourth quarter after the index date. Patient characteristics were evaluated and pre- vs post-index MS-related healthcare utilization and costs were compared.A total of 562 patients were included in this study. The mean (standard deviation [SD]) age was 50.5 (9.8) years and 63% were female. In the treatment period, almost every patient had at least 1 MS-related outpatient visit, 24% were hospitalized due to MS, and 79% utilized MS-specific physical therapy in addition to the fampridine treatment. Total MS-related healthcare costs were significantly higher in the fampridine treatment period than in the period prior to fampridine initiation (€17,392 vs €10,960, P?<?0.001). While this difference was driven primarily by prescription costs, MS-related inpatient costs were lower during fampridine treatment (€1,333 vs €1,565, P?<?0.001).Physical therapy is mainly used concomitant to fampridine treatment. While healthcare costs were higher during fampridine treatment compared to the pre-treatment period, inpatient costs were lower. Further research is necessary to better understand the fampridine influence.
| S-EPMC5369011 | biostudies-literature
Project description:Objective: Persons with multiple sclerosis (PwMS), already established as responders or non-responders to Fampridine treatment, were compared in terms of disability measures, physical and cognitive performance tests, neurophysiology, and magnetic resonance imaging (MRI) outcomes in a 1-year explorative longitudinal study. Materials and Methods: Data from a 1-year longitudinal study were analyzed. Examinations consisted of the timed 25-foot walk test (T25FW), six spot step test (SSST), nine-hole peg test (9-HPT), five times sit-to-stand test (5-STS), symbol digit modalities test (SDMT), transcranial magnetic stimulation (TMS) elicited motor evoked potentials (MEP) examining central motor conduction times (CMCT), peripheral motor conduction times (PMCT) and their amplitudes, electroneuronography (ENG) of the lower extremities, and brain structural MRI measures. Results: Forty-one responders and eight non-responders to Fampridine treatment were examined. There were no intergroup differences except for the PMCT, where non-responders had prolonged conduction times compared to responders to Fampridine. Six spot step test was associated with CMCT throughout the study. After 1 year, CMCT was further prolonged and cortical MEP amplitudes decreased in both groups, while PMCT and ENG did not change. Throughout the study, CMCT was associated with the expanded disability status scale (EDSS) and 12-item multiple sclerosis walking scale (MSWS-12), while SDMT was associated with number of T2-weighted lesions, lesion load, and lesion load normalized to brain volume. Conclusions: Peripheral motor conduction time is prolonged in non-responders to Fampridine when compared to responders. Transcranial magnetic stimulation-elicited MEPs and SDMT can be used as markers of disability progression and lesion activity visualized by MRI, respectively. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03401307.
| S-EPMC8576138 | biostudies-literature
Project description:Peripheral cytokine levels may serve as biomarkers for treatment response and disease monitoring in patients with multiple sclerosis (pwMS). The objectives were to assess changes in plasma biomarkers in PwMS after 14 days of fampridine treatment and to explore correlations between changes in performance measures and plasma biomarkers. We included 27 PwMS, 14 women and 13 men, aged 52.0 ± 11.6 years, with a disease duration of 17 ± 8.5 years, and an Expanded Disability Status Scale of 6 [IQR 5.0/6.5]. Gait and hand function were assessed using performance tests completed prior to fampridine and after 14 days of treatment. Venous blood was obtained, and chemiluminescence analysis conducted to assess plasma cytokines and neurodegenerative markers. All performance measures demonstrated improvements. Biomarkers showed decreased tumor necrosis factor (TNF) receptor-2 levels. Associations were found between change scores in (i) Six Spot Step Test and Interleukin (IL)-2, IL-8, and IL-17 levels; (ii) timed 25-foot walk and interferon-γ, IL-2, IL-8, TNF-α, and neurofilament light levels, and (iii) 12-Item Multiple Sclerosis Walking Scale and IL-17 levels. The associations may reflect increased MS-related inflammatory activity rather than a fampridine-induced response or that a higher level of inflammation induces a better response to fampridine.
| S-EPMC10855557 | biostudies-literature
Project description:Several studies have demonstrated benefits of rehabilitation in multiple sclerosis (MS). However, the neuroscientific foundations for rehabilitation in MS are poorly established.As rehabilitation and motor learning share similar mechanisms of brain plasticity, we test whether the dynamics of skill learning are preserved in MS patients relative to controls.MS patients and controls learned a repeating sequence of hand movements and were assessed for short-term learning. Long-term learning was tested in another cohort of patients and controls practising the same sequence daily for two weeks.Despite differences in baseline performance, the dynamics and extent of improvements were comparable between MS and control groups for both the short- and long-term learning. Even the most severely damaged patients were capable of performance improvements of similar magnitude to that seen in controls. After one week of training patients performed as well as the controls at baseline.Mechanisms for short- and long-term plasticity may compensate for impaired functional connectivity in MS to mediate behavioural improvements. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which mechanisms of plasticity in patients may be distinct from those used for motor learning in controls.
| S-EPMC3671324 | biostudies-literature
Project description:The ovarian hormones fluctuate during the menstrual cycle in women. Such fluctuation of sex hormones, in particular estrogen, is believed to affect the central conduction time in auditory function as well as the language lateralization in cognitive function. However, findings are inconsistent. The underlying mechanisms are also unclear. This paper examined if there was any relation between the central conduction time and the language lateralization at different times during the menstrual cycle. Twenty young women with normal menstrual cycle were tested four times (5 to 7 days apart) across the menstrual cycle. The test battery included the electrophysiological measurement of auditory evoked response in brainstem and the speech performance in dichotic listening with monosyllables as stimulus pairs. The dichotic listening task was conducted under the non-forced, forced-right and forced-left attention. The central conduction time was defined by the time elapsed between two auditory elicited responses along the auditory pathway. The language lateralization in dichotic listening was expressed in ear advantage, which was the right-ear score minus the left-ear score. The results showed that the effects of test time were significant on both the central conduction time and the ear advantage under the forced-left attention. Overall, the interaural difference in the central conduction time correlates with the ear advantage (non-forced attention) at the beginning of the menstrual cycle. The change in central conduction time between two test times correlates significantly with the change in ear advantage under the non-forced and forced-left attention. Conclusively, the central conduction time depends on the time during the menstrual cycle, which in turn may affect the performance in dichotic listening.
| S-EPMC5679549 | biostudies-literature
Project description:The effects of motor imagery (MI) on functional recovery of patients with neurological pathologies, such as stroke, has been recently proven. The aim of this study is to evaluate the effectiveness of MI on motor recovery and quality of life (QOL) in patients with multiple sclerosis (pwMS). A search was carried out in the following scientific databases: PubMed, CINAHL, PEDro, Scopus, Cochrane and Web of Science, up to November 2020. The grey literature and reference lists of potentially relevant articles were also searched. The Checklist for Measuring Quality and The Cochrane collaboration's tool were used to assess the methodological quality and risk of bias of the studies. Five studies were included in the systematic review. Findings showed that pwMS using MI had significant improvements in walking speed and distance, fatigue and QOL. In addition, several benefits were also found in dynamic balance and perceived walking ability. Although the evidence is limited, rehabilitation using MI with the application of musical and verbal guides (compared to non-intervention or other interventions), can produce benefits on gait, fatigue and QOL in pwMS with a low score in the Expanded Disability Status Scale.
| S-EPMC7827037 | biostudies-literature