Transcutaneous spinal direct current stimulation increases corticospinal transmission and enhances voluntary motor output in humans

Optimization of motor performance is of importance in daily life, in relation to recovery following injury as well as for elite sports performance. The present study investigated whether transcutaneous spinal direct current stimulation (tsDCS) may enhance voluntary ballistic activation of ankle muscles and descending activation of spinal motor neurons in able‐bodied adults. Forty‐one adults (21 men; 24.0 ± 3.2 years) participated in the study. The effect of tsDCS on ballistic motor performance and plantar flexor muscle activation was assessed in a double‐blinded sham‐controlled cross‐over experiment. In separate experiments, the underlying changes in excitability of corticospinal and spinal pathways were probed by evaluating soleus (SOL) motor evoked potentials (MEPs) following single‐pulse transcranial magnetic stimulation (TMS) over the primary motor cortex, SOL H‐reflexes elicited by tibial nerve stimulation and TMS‐conditioning of SOL H‐reflexes. Measures were obtained before and after cathodal tsDCS over the thoracic spine (T11‐T12) for 10 min at 2.5 mA. We found that cathodal tsDCS transiently facilitated peak acceleration in the ballistic motor task compared to sham tsDCS. Following tsDCS, SOL MEPs were increased without changes in H‐reflex amplitudes. The short‐latency facilitation of the H‐reflex by subthreshold TMS, which is assumed to be mediated by the fast conducting monosynaptic corticomotoneuronal pathway, was also enhanced by tsDCS. We argue that tsDCS briefly facilitates voluntary motor output by increasing descending drive from corticospinal neurones to spinal plantar flexor motor neurons. tsDCS can thus transiently promote within‐session CNS function and voluntary motor output and holds potential as a technique in the rehabilitation of motor function following central nervous lesions

Spinal inhibition of descending command to soleus motoneurons is removed prior to dorsiflexion

Non-technical summary: The coordination of antagonistic muscle activity starts well in advance of the onset of voluntary movement. We recently demonstrated that antagonist muscle responses evoked by stimulation of the brain were increased prior to voluntary contraction at the ankle. Although our data indicated that this was explained by activation of a subcortical motor program, the neural pathways involved are unknown. Here we probe the transmission in the underlying neuronal networks by peripheral nerve stimulation in order to investigate the neural pathways responsible for this facilitation of antagonist muscle responses. We demonstrate that this stimulation produces a spinal inhibition of the antagonist muscle responses, which is removed prior to voluntary contraction. We propose that the removal of this inhibition might explain the increased antagonist muscle responses prior to voluntary contraction at the ankle. This mechanism might enable the direction of movement to be changed quickly during functional motor tasks such as dribbling

In vitro evaluation of the activity of teriflunomide against SARS-CoV-2 and the human coronaviruses 229E and OC43

Previous data have suggested an antiviral effect of teriflunomide, including against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the agent underlying the ongoing COVID-19 pandemic. We undertook an in vitro investigation to evaluate the inhibitory activity of teriflunomide against SARS-CoV-2 in a cell-based assay. Teriflunomide was added to Vero (kidney epithelial) cells that had been infected with SARS-CoV-2. A nucleocapsid immunofluorescence assay was performed to examine viral inhibition with teriflunomide and any potential cytotoxic effect. The 50% effective concentration (EC50) for teriflunomide against SARS-CoV-2 was 15.22 μM. No cytotoxicity was evident for teriflunomide in the Vero cells (i.e., the 50% cytotoxic concentration [CC50] was greater than the highest test concentration of 100 μM). The data were supported by additional experiments using other coronaviruses and human cell lines. In the SARS-CoV-2-infected Vero cells, the prodrug leflunomide had an EC50 of 16.49 μM and a CC50 of 54.80 μM. Our finding of teriflunomide-mediated inhibition of SARS-CoV-2 infection at double-digit micromolar potency adds to a growing body of evidence for a broad-ranging antiviral effect of teriflunomide

Assessment of a portable device for the quantitative measurement of ankle joint stiffness in spastic individuals

OBJECTIVE: Spasticity is a common complication with neurological diseases and CNS lesions. Instrumented systems to evaluate spasticity often cannot provide an immediate result, thus limiting their clinical usefulness. In this study we investigated the accuracy and reliability of the portable Neurokinetics RA1 Ridgidity Analyzer to measure stiffness of the ankle joint in 46 controls, 14 spinal cord injured (SCI) and 23 multiple sclerosis (MS) participants.  METHODS: Ankle stiffness measures were made twice by two raters, at speeds above and below the expected stretch reflex threshold. Ankle torque was measured with the portable device and a stationary torque motor. Inter- and intra-rater reliability was assessed with the intra-class correlation coefficient (ICC).  RESULTS: Stiffness measures with the portable and stationary devices were significantly correlated for controls and MS participants (p < 0.01). Intra-rater reliability for the portable device ranged from 0.60-0.89 (SCI) and 0.63-0.67 (control) and inter-rater reliability ranged from 0.70-0.73 (SCI) and 0.61-0.77 (control). Ankle stiffness measures in SCI and MS participants were significantly larger than in controls for both slow (p < 0.05) and fast movements (p < 0.01), with stiffness being larger for fast compared to slow movements in SCI and MS participants (p < 0.05), but not in controls (p = 0.5).  CONCLUSION: The portable device correlated well with measures obtained by a torque motor in both controls and MS participants, showed high intra- and inter-rater reliability for the SCI participants, and could easily distinguish between stiff and control ankle joints. However, the device, in its current form, may be less accurate during rapid movements when inertia contributes to stiffness and the shape of the air-filled pads did not provide a good interface with the foot.  SIGNIFICANCE: This study demonstrates that a portable device can potentially be a useful diagnostic tool to obtain reliable information of stiffness for the ankle joint

Persistence, Adherence, and Switching to Higher-Cost Therapy in Patients with Multiple Sclerosis Initiating Oral Disease-Modifying Therapies: A Retrospective Real-World Study

Article full text The article associated with this page has been accepted for online publication and is in the final stages of production. The link to the full text will be made available on this page in the next few days. The above graphical abstract represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online (see “read the peer-reviewed publication” opposite).  © The authors, CC-BY-NC 2022.  </p

Descriptive data of study participants (group mean ± SD).

<p>Descriptive data of study participants (group mean ± SD).</p

Exercise Data.

<p>Exercise Data.</p