Effects of brain-computer interface with functional electrical stimulation for gait rehabilitation in multiple sclerosis patients: preliminary findings in gait speed and event-related desynchronization onset latency.

Objective.Brain-computer Interfaces (BCI) with functional electrical stimulation (FES) as a feedback device might promote neuroplasticity and hence improve motor function. Novel findings suggested that neuroplasticity could be possible in people with multiple sclerosis (pwMS). This preliminary study explores the effects of using a BCI-FES in therapeutic intervention, as an emerging methodology for gait rehabilitation in pwMS.Approach.People with relapsing-remitting, primary progressive or secondary progressive MS were evaluated with the inclusion criteria to enroll the nine participants required by the statistically computed sample size. Each patient trained with a BCI-FES during 24 sessions distributed in eight weeks. The effects were evaluated on gait speed (Timed 25 Foot Walk), walking ability (12-item Multiple Sclerosis Walking Scale), quality of life measures, the true positive rate as the BCI-FES performance metric and the event-related desynchronization (ERD) onset latency of the sensorimotor rhythms.Main results.Seven patients completed the therapeutic intervention. A statistically and clinically significant post-treatment improvement was observed in gait speed, as a result of a reduction in the time to walk 25 feet (-1.99 s,p= 0.018), and walking ability (-31.25 score points,p= 0.028). The true positive rate showed a statistically significant improvement (+15.87 score points,p= 0.018). An earlier ERD onset latency (-180 ms) after treatment was found.Significance.This is the first study that explored gait rehabilitation using BCI-FES in pwMS. The results showed improvement in gait which might have been promoted by changes in functional brain connections involved in sensorimotor rhythm modulation. Although more studies with a larger sample size and control group are required to validate the efficacy of this approach, these results suggest that BCI-FES technology could have a positive effect on MS gait rehabilitation.

Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina / Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis

INTRODUCCIÓN: Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. OBJETIVO: Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. DESARROLLO: Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. CONCLUSIÓN: Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of formal consensus-RAND/UCLA method was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial.

Objective: To assess masitinib in the treatment of ALS. Methods: Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 mg/kg/d. Following a blinded transition from phase 2 to phase 2/3, a prospectively defined two-tiered design was implemented based on ALSFRS-R progression rate from disease-onset to baseline (ΔFS). This approach selects a more homogeneous primary efficacy population ("Normal Progressors", ΔFS < 1.1 points/month) while concurrently permitting secondary assessment of the broader population. Primary endpoint was decline in ALSFRS-R at week-48 (ΔALSFRS-R), with the high-dose "Normal Progressor" cohort being the prospectively declared primary efficacy population. Missing data were imputed via last observation carried forward (LOCF) methodology with sensitivity analyses performed to test robustness. Results: For the primary efficacy population, masitinib (n = 99) showed significant benefit over placebo (n = 102) with a ΔALSFRS-R between-group difference (ΔLSM) of 3.4 (95% CI 0.65-6.13; p = 0.016), corresponding to a 27% slowing in rate of functional decline (LOCF methodology). Sensitivity analyses were all convergent, including the conservative multiple imputation technique of FCS-REGPMM with a ΔLSM of 3.4 (95% CI 0.53-6.33; p = 0.020). Secondary endpoints (ALSAQ-40, FVC, and time-to-event analysis) were also significant. Conversely, no significant treatment-effect according to ΔALSFRS-R was seen for the broader "Normal and Fast Progressor" masitinib 4.5 mg/kg/d cohort, or either of the low-dose (masitinib 3.0 mg/kg/d) cohorts. Rates of treatment-emergent adverse events (AEs) (regardless of causality or post-onset ΔFS) were 88% with masitinib 4.5 mg/kg/d, 85% with 3.0 mg/kg/d, and 79% with placebo. Likewise, rates of serious AE were 31, 23, and 18%, respectively. No distinct event contributed to the higher rate observed for masitinib and no deaths were related to masitinib. Conclusions: Results show that masitinib at 4.5 mg/kg/d can benefit patients with ALS. A confirmatory phase 3 study will be initiated to substantiate these data.

Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients.

One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina. METHODS: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients. CONCLUSIONS: The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina.

Neurorehabilitation therapy of patients with severe stroke based on functional electrical stimulation commanded by a brain computer interface.

INTRODUCTION: Brain computer interface is an emerging technology to treat the sequelae of stroke. The purpose of this study was to explore the motor imagery related desynchronization of sensorimotor rhythms of stroke patients and to assess the efficacy of an upper limb neurorehabilitation therapy based on functional electrical stimulation controlled by a brain computer interface. METHODS: Eight severe chronic stroke patients were recruited. The study consisted of two stages: screening and therapy. During screening, the ability of patients to desynchronize the contralateral oscillatory sensorimotor rhythms by motor imagery of the most affected hand was assessed. In the second stage, a therapeutic intervention was performed. It involved 20 sessions where an electrical stimulator was activated when the patient's cerebral activity related to motor imagery was detected. The upper limb was assessed, before and after the intervention, by the Fugl-Meyer score (primary outcome). Spasticity, motor activity, range of movement and quality of life were also evaluated (secondary outcomes). RESULTS: Desynchronization was identified in all screened patients. Significant post-treatment improvement (p < 0.05) was detected in the primary outcome measure and in the majority of secondary outcome scores. CONCLUSIONS: The results suggest that the proposed therapy could be beneficial in the neurorehabilitation of stroke individuals.

Clinical manifestations of peripheral nervous system involvement in human chronic Chagas disease

We conducted a clinical and electromyographical study in patients with Chagas' disease indeterminiate or chronic stages of the illness. Altogether 841 patients were examined. Only 511 Were admitted within the protocol; the remainder patients were rejected because they showed other causes able to danage the nervous system. Fifty two (1O. 17 per cent) out of the 511 patients showed signs and symptoms of peripheral nervous system involvement in the form of sensory impairiment and diminished tendon jerks suggesting the presence neuropathy. Forty five of them were submitted to a conventional electromygraphical examination. Fifthem of the showed normal results, while the remainder 30 disclosed a rcduced interference pattern, being most of the remainig motor unit potentials fragmented or poliphasic, reduced sensory and motor conduction velocities and diminished amplitude of the sensory action potential. 'The findings suggest that some chagasic paties in the determinate or chronic stages of the disease may develop a clinical mild sensory-motor peripheral neuropathy.