Unusual sensory-motor neuropathies in post-COVID-19 patients admitted in rehabilitation hospitals: a case-series.

BACKGROUND: Several neurological complications occurred in SARS-CoV-2 disease (COVID-19), mainly related to inflammatory and vascular disorders. The involvement of the peripheral nervous system (PNS) has been mostly reported as Guillain-Barré Syndrome, while focal peripheral neuropathies have been rarely described. CASE REPORT: We report the cases of ten patients hospitalized in Rehabilitation Units after COVID-19, who presented severe focal motor involvement. Electrophysiological investigations revealed focal sensory-motor neuropathies, atypical for many aspects: bilaterality, location and contemporary involvement of different nervous districts. We speculate that their pathogenesis is possibly related to prolonged abnormal postures maintained during hospitalization in Intensive Care Unit, virus neurotropism and thrombotic vascular damage involving vasa nervorum. CLINICAL REHABILITATION IMPACT: Motor neuropathies could induce severe disability and their early recognition in post COVID-19 patients is of primary importance for a specific rehabilitation treatment.

The Dysphagia in Multiple Sclerosis Questionnaire Correlates with Fiber-Optic Endoscopic Examination for Detecting Swallowing Deficits in MS.

Multiple sclerosis (MS) refers to chronic inflammation of the central nervous system including the brain and spinal cord. Assessing for the presence of dysphagia in subjects with MS represents a challenge for neurologists in clinical practice. The aim of the present study was to verify the relationship between DYMUS scores, a patient-reported scale, and objective symptoms using the Dysphagia Outcome Severity Score (DOSS), based on fiber-optic endoscopy. Data were collected in a multicenter study. Two hundred and fifteen MS patients were enrolled, irrespective of self-reported dysphagia. DOSS revealed dysphagia in 122 subjects (56.7%). Compared with non-dysphagic subjects, the presence of dysphagia was related to more severe disability, longer disease duration, and a progressive form of the disease. A DYMUS score of 0 strongly correlated with a DOSS of 6 (sensitivity 100%) while DYMUS score of > 2 correlated with a DOSS < 7 (specificity 82%) of the self-reported scale. The DYMUS questionnaire can be a useful clinical tool for red-flagging patients who should undergo objective testing and referral to a otorhinolaryngologist.

Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study.

INTRODUCTION: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. MATERIALS AND METHODS: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. RESULTS: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. CONCLUSION: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients.

OnabotulinumtoxinA Reduces Temporal Pain Processing at Spinal Level in Patients with Lower Limb Spasticity.

Spasticity is a muscle tone disorder associated with different neurological conditions. Spasticity could be associated with pain, high disability, poor functional recovery, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) is considered a first-line treatment for spasticity and, more recently, it also represents a therapeutic option for various chronic pain conditions. In this open label study, we aim to evaluate the effect of the BoNT-A on the spinal nociception in patients affected by spasticity of the lower limbs with associated pain with predominantly neuropathic features. Ten patients with stroke, 10 with multiple sclerosis and 5 with spinal cord injury were enrolled in the study. They were tested with clinical scales (neuropathic pain scale inventory (NPSI), numerical rating scale (NRS), modified Ashworth scale (MAS) and with the nociceptive withdrawal reflex at lower limbs to explore the spinal temporal summation threshold at baseline and 30 day after BoNT-A injection. OnabotulinumtoxinA (50 to 200 units per site) was injected in the lower limb muscles according to the distribution of spasticity. No significant differences were found at baseline for neurophysiological features across groups. After the BoNT-A injection, we recorded a significant reduction in MAS and NRS scores. Regarding the neurophysiological parameters, we described a significant increase in the temporal summation threshold after the BoNT-A injection. Our data supports the hypothesis that peripherally injected OnabotulinumtoxinA modulates the excitability of spinal cord nociceptive pathways. This activity may take place irrespective of the effect of the drug on spasticity.

The Effects of Transcutaneous Spinal Direct Current Stimulation on Neuropathic Pain in Multiple Sclerosis: Clinical and Neurophysiological Assessment.

Background: Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. Methods: Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group (n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group (n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS (n = 12) and sham ts-DCS (n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. Results: Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. Conclusions: Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT02331654.

Body Weight Support Combined With Treadmill in the Rehabilitation of Parkinsonian Gait: A Review of Literature and New Data From a Controlled Study.

Background: Gait disorders represent disabling symptoms in Parkinson's Disease (PD). The effectiveness of rehabilitation treatment with Body Weight Support Treadmill Training (BWSTT) has been demonstrated in patients with stroke and spinal cord injuries, but limited data is available in PD. Aims: The aim of the study is to investigate the efficacy of BWSTT in the rehabilitation of gait in PD patients. Methods: Thirty-six PD inpatients were enrolled and performed rehabilitation treatment for 4-weeks, with daily sessions. Subjects were randomly divided into two groups: both groups underwent daily 40-min sessions of traditional physiokinesitherapy followed by 20-min sessions of overground gait training (Control group) or BWSTT (BWSTT group). The efficacy of BWSTT was evaluated with clinical scales and Computerized Gait Analysis (CGA). Patients were tested at baseline (T0) and at the end of the 4-weeks rehabilitation period (T1). Results: Both BWSTT and Control groups experienced a significant improvement in clinical scales as FIM and UPDRS and in gait parameters for both interventions. Even if we failed to detect any statistically significant differences between groups in the different clinical and gait parameters, the intragroup analysis captured a specific pattern of qualitative improvement associated to cadence and stride duration for the BWSTT group and to the swing/stance ratio for the Control group. Four patients with chronic pain or anxious symptoms did not tolerate BWSTT. Conclusions: BWSTT and traditional rehabilitation treatment are both effective in improving clinical motor functions and kinematic gait parameters. BWSTT may represent an option in PD patients with specific symptoms that limit traditional overground gait training, e.g., severe postural instability, balance disorder, orthostatic hypotension. BWSTT is generally well-tolerated, though caution is needed in subjects with chronic pain or with anxious symptoms. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03815409.

Assessing and treating pain associated with stroke, multiple sclerosis, cerebral palsy, spinal cord injury and spasticity. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.

Pain is a common and disabling symptom in patients with stroke, multiple sclerosis (MS), cerebral palsy (CP), spinal cord injury (SCI) and other conditions associated with spasticity, but data on its prevalence, and natural history, as well as guidelines on its assessment and treatment in the field of neurorehabilitation, are largely lacking. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) searched and evaluated current evidence on the frequency, evolution, predictors, assessment, and pharmacological and non-pharmacological treatment of pain in patients with stroke, MS, CP, SCI and other conditions associated with spasticity. Patients with stroke, MS, CP, and SCI may suffer from pain related to spasticity, as well as nociceptive and neuropathic pain (NP), whose prevalence, natural history, impact on functional outcome, and predictors are only partially known. Diagnosis and assessment of the different types of pain in these patients is important, because their treatment may differ. Botulinum neurotoxin is the first choice treatment for spasticity, while some antidepressant and antiepileptic drugs may be effective on NP, but pharmacological treatment varies according to the underlying disease. In most cases, a single therapy is not sufficient to treat pain, and a multidisciplinary approach, which include pharmacological and non-pharmacological treatments is needed. Further studies, and in particular randomized controlled trials, are needed on these topics.

Acute and Chronic Effect of Acoustic and Visual Cues on Gait Training in Parkinson's Disease: A Randomized, Controlled Study.

In this randomized controlled study we analyse and compare the acute and chronic effects of visual and acoustic cues on gait performance in Parkinson's Disease (PD). We enrolled 46 patients with idiopathic PD who were assigned to 3 different modalities of gait training: (1) use of acoustic cues, (2) use of visual cues, or (3) overground training without cues. All patients were tested with kinematic analysis of gait at baseline (T0), at the end of the 4-week rehabilitation programme (T1), and 3 months later (T2). Regarding the acute effect, acoustic cues increased stride length and stride duration, while visual cues reduced the number of strides and normalized the stride/stance distribution but also reduced gait speed. As regards the chronic effect of cues, we recorded an improvement in some gait parameters in all 3 groups of patients: all 3 types of training improved gait speed; visual cues also normalized the stance/swing ratio, acoustic cues reduced the number of strides and increased stride length, and overground training improved stride length. The changes were not retained at T2 in any of the experimental groups. Our findings support and characterize the usefulness of cueing strategies in the rehabilitation of gait in PD.

Behavioral and neuroplastic effects of low-frequency rTMS of the unaffected hemisphere in a chronic stroke patient: a concomitant TMS and fMRI study.

Repetitive Transcranial Magnetic Stimulation (rTMS) ameliorates motor and neuropsychological deficits following stroke, but little is known about the underlying neuroplasticity. We investigated neuroplastic changes following 5 days of low-frequency rTMS on the intact motor cortex to promote motor recovery in a chronic patient with subcortical stroke. The feasibility of administering multiple treatments was also assessed 6 months later by applying the same protocol over the patient's parietal cortex to improve visuospatial disorders. Behavioral improvements and no adverse events were observed. Neuroimaging findings indicated that motor symptoms amelioration was associated with downregulation and cortical reorganization of hyperactive contralesional hemisphere.

A methodological reappraisal of non invasive high voltage electrical stimulation of lumbosacral nerve roots.

OBJECTIVE: To describe a neurophysiological method to locate the optimal stimulation site (OSS) over the vertebral column, customized to the individual subject, to achieve maximal activation of lumbosacral roots by means of non-invasive high voltage electrical stimulation (HVES). METHODS: OSS was located in 30 volunteers by testing different stimulation points of a surface multi-electrode array placed over the dorso-lumbar junction of the vertebral column. The dorso-ventral stimulating montage was used (Troni et al., 1996). Motor responses to root stimulation (rCMAPs) were bilaterally recorded from Vastus Medialis (VM), Tibialis Anterior (TA), Soleus (SL) and Flexor Hallucis Brevis (FHB) muscles. The direct nature of rCMAPs was tested by delivering two maximal stimuli 50 ms apart. RESULTS: Except for a few subjects with large girth, maximal rCMAPs could be obtained from all muscles with a stimulating current intensity up to 550 V (1050 mA). Maximal double HVES excluded any reflex component in the recorded rCMAPs. The procedure was well tolerated and no side effects were observed. CONCLUSIONS: A single maximal electric shock delivered at the proper vertebral level by means of the dorso-ventral montage is able to safely achieve synchronous, bilateral maximal activation of several roots, from L3 to S1. SIGNIFICANCE: Maximal activation of lumbosacral roots at their origin, unattainable with magnetic stimulation, is the essential requirement for direct detection of proximal nerve conduction slowing and block in lower limbs.