Abstract Gait, coordination, and balance may be severely compromised in patients with multiple sclerosis (MS), with considerable consequences on the patient's daily living activities, psychological ...status and quality of life. For this reason, MS patients may benefit from robotic-rehabilitation and virtual reality training sessions. Aim of the present study was to assess the efficacy of robot-assisted gait training (RAGT) equipped with virtual reality (VR) system in MS patients with walking disabilities (EDSS 4.0 to 5.5) as compared to RAGT without VR. We enrolled 40 patients (randomized into two groups) undergoing forty RAGT ± VR sessions over eight weeks. All the patients were assessed at baseline and at the end of the treatment by using specific scales. Effect sizes were very small and non-significant between the groups for Berg Balance Scale (− 0.019, CI95% − 2.403 to 2.365) and TUG (− 0.064, 95%CI − 0.408 to 0.536) favoring RAGT + VR. Effects were moderate-to-large and significant for positive attitude (− 0.505, 95%CI − 3.615 to 2.604) and problem-solving (− 0.905, 95%CI − 2.113 to 0.302) sub-items of Coping Orientation to Problem Experienced, thus largely favoring RAGT + VR. Our findings show that RAGT combined with VR is an effective therapeutic option in MS patients with walking disability as compared to RAGT without VR. We may hypothesize that VR may strengthen RAGT thanks to the entrainment of different brain areas involved in motor panning and learning.
Background:
In the general population, maternal COVID-19 is associated with worse maternal and fetal outcomes. Two previous studies have assessed COVID-19 clinical outcomes in pregnant women with ...multiple sclerosis (MS), but there are no data about maternal and fetal outcomes.
Objectives:
In this multicenter study, we aimed to assess maternal and fetal outcomes in pregnant women with MS and COVID-19 infection.
Methods:
We recruited pregnant patients with MS who contracted COVID-19 and were followed up in Italian and Turkish Centers, during 2020–2022. A control group was extracted from a previous Italian cohort. Associations between group (COVID-19 or healthy patients) and clinical outcomes (maternal complications, fetal malformations, and spontaneous abortion) were investigated with a weighted logistic regression where propensity score–based inverse probability of treatment weighting (IPTW) approach was applied for adjusting for difference in baseline confounders.
Results:
In the multivariable analysis, COVID-19 during pregnancy was associated with a higher risk of maternal complications (odd ratio (OR) = 2.12; 95% confidence interval (CI) = 1.32–3.48; p = 0.002), while it was not associated with higher risk of spontaneous abortion and fetal malformations.
Conclusion:
Our data indicate that COVID-19 during pregnancy increases the risk of maternal complications, while it seems to have no significant impact on fetal outcomes.
Background
Natalizumab (NTZ) is an effective treatment for relapsing–remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or ...efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients.
Materials and methods
The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as “lack of efficacy”, “progressive multifocal leukoencephalopathy (PML) risk” or “other”.
Results
Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1 years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy 1682 (32.7% of 5151) vs 221 (4.3%),
p
< 0.001; other reasons were identified for 99 (1.9%) patients. Patients discontinuing treatment were older, had longer disease duration and worse EDSS at the time of NTZ initiation and at last follow-up on NTZ treatment. The JCV index and EDSS at baseline were predictors for stopping therapy (HR 2.94, 95% CI 1.22–4.75;
p
= 0.02; HR 1.36, 95% CI 1.18–5.41;
p
= 0.04).
Conclusions
Roughly 60% of MS patients stayed on NTZ treatment during the observation period. For those patients in whom NTZ discontinuation was required, it was mainly due to PML concerns.
Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe ...immune-related (ir) adverse events (AEs). Here, we report the clinical and immune–biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting.
To prospectively investigate whether T1 changes in normal-appearing white matter (WM) and normal-appearing gray matter (GM) in multiple sclerosis (MS) are global or regional and their relationship to ...disease type.
The institutional ethics review board approved study; written informed consent was obtained. Whole-brain T1 maps were obtained in 67 patients with MS and 24 healthy control subjects with three-dimensional fast low-angle shot flip angle-array method, with correction for B(1) imperfections. Analysis of variance was performed on T1 histogram parameters of global normal-appearing WM and GM. Regional mean T1 values were analyzed with a multilevel approach. Multiple linear regression analysis was performed to investigate associations with clinical disability and overall atrophy. For patients, T2 lesion load was determined.
T1 histograms of normal-appearing WM had significantly higher peak positions for patients with MS (792 msec +/- 36 in secondary progressive SP MS) than for control subjects (746 msec +/- 23) and were significantly broader and lower (all P < .001). Histograms for cortical normal-appearing GM were significantly shifted (peak positions, 1263 msec +/- 44 in control subjects and 1355 msec +/- 62 in patients with SP MS) (P < .001). Histogram peak positions were significantly higher in SP MS than in relapsing-remitting (RR) and primary progressive MS (P < .05). In SP disease, at least 31% of normal-appearing WM and 20% of cortical normal-appearing GM were affected. In MS, T1 was significantly elevated in all normal-appearing WM and cortical normal-appearing GM regions (all P < .01) but was elevated only in the thalamus in deep GM (P < .05). Cortical T1 histogram peak position was associated with clinical disability; T2 lesion load was not.
Results suggest that a global disease process affects large parts of both normal-appearing WM and GM in MS and effects are worse for SP MS than for RR MS.
Objective
This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID‐19) in people with multiple sclerosis ...(PwMS).
Methods
We retrospectively collected data of PwMS with suspected or confirmed COVID‐19. All the patients had complete follow‐up to death or recovery. Severe COVID‐19 was defined by a 3‐level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID‐19 by multivariate and propensity score (PS)‐weighted ordinal logistic models. Sensitivity analyses were run to confirm the results.
Results
Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID‐19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty‐eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized.
After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti‐CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio OR = 2.37, 95% confidence interval CI = 1.18–4.74, p = 0.015) with increased risk of severe COVID‐19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS‐weighted analysis and by all the sensitivity analyses.
Interpretation
This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID‐19 pandemic persists. ANN NEUROL 2021;89:780–789
•Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS).•Venous thrombosis is a rare complication.•We describe a man who developed cerebral sinus thrombosis after ...alemtuzumab.•The etiology remains unknown.
Alemtuzumab is a highly effective treatment for relapsing-remitting multiple sclerosis (MS). Its molecular target is CD 52, a GPI-anchored protein. Herein, we describe the case of a 40-year-old man with MS treated with alemtuzumab, who developed cerebral sinus thrombosis. In the literature, alemtuzumab was associated with venous thrombosis, attributed to a paroxysmal nocturnal hemoglobinuria (PNH)-like mechanism. In our case, no PNH clones were detected. Other common causes of cerebral venous thrombosis, like infections and thrombophilia, were excluded, thus the pathogenic mechanism remains obscure.
Low‐frequency median nerve stimulation, paired with suprathreshold transcranial magnetic stimulation (TMS) over the optimal site for activation of the abductor pollicis brevis (APB) muscle induces a ...long‐lasting increase in the excitability of corticospinal output neurons, if median nerve stimulation is given 25 ms before TMS. Here we employed this protocol of stimulation to assess associative plasticity of the primary motor hand area in 10 patients with writer’s cramp and 10 age‐matched controls. Motor evoked potentials (MEPs) were recorded from right APB muscle and right first dorsal interosseus (FDI) muscle. Resting and active motor threshold, mean MEP amplitude at rest, short‐latency intracortical inhibition (SICI) at an interstimulus interval of 2 ms and the duration of the cortical silent period (CSP) were assessed immediately before and after associative stimulation. In both groups, associative stimulation led to an increase in resting MEP amplitudes which was more pronounced in the right APB muscle. Compared with healthy controls, stimulation‐induced facilitation of MEP amplitudes was stronger in patients with writer’s cramp. In addition, only patients showed a slight decrease of resting and active motor thresholds after conditioning stimulation. In both groups, associative stimulation induced a prolongation of CSP in the APB and FDI muscles, which was significant only in the APB muscle in healthy controls. Associative stimulation had no effects on SICI in patients and healthy controls. Taken together, in patients with writer’s cramp, the motor system exhibited an abnormal increase in corticospinal excitability and an attenuated reinforcement of intracortical inhibitory circuits that generate the CSP in response to associative stimulation. This altered pattern of sensorimotor plasticity may favour maladaptive plasticity during repetitive skilled hand movements and, thus, may be of relevance for the pathophysiology of writer’s cramp and other task‐specific dystonias.
We tested the hypothesis that fatigue in MS is related to a dysfunction in cortical areas involved in movement preparation. Thirty-three patients with clinically definite MS (16 with fatigue MS-F, 17 ...without fatigue MS-NF) and a relapsing-remitting course, matched for disease severity and duration, disability scores and level of depression were enrolled. They underwent a combined assessment with magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS) and, for the electrophysiological study, were compared with 12 healthy controls. MRI was used to assess regional and total lesion-load volume (LL) on T1- and T2-weighted sequences and total brain volume on T1-weighted sequences. With TMS we tested central motor conduction time, short intracortical inhibition (SICI) and facilitation (ICF), pre-movement facilitation related to a simple reaction time paradigm and the effect of short trains of 5-Hz repetitive TMS (rTMS). No significant differences were found in total and regional LL between MS-F and MS-NF, except for a significant increase in frontal lobe LL in MS-F. Neurophysiological assessment did not disclose any difference of SICI and ICF among the three groups. The significant increase of MEP size produced by 5 Hz rTMS in controls was absent in both MS-NF and MS-F. MS-F lacked pre-movement facilitation compared with MS-NF and controls. The lack of pre-movement facilitation and the increased frontal lobe lesion load were significantly correlated to the FSS score, suggesting that central fatigue in MS is probably due to a dysfunction of cortical motor areas involved in movement preparation.
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