Background:
Neural plasticity represents the substrate by which the damaged central nervous system (CNS) re-learns lost behaviors in response to rehabilitation. In persons with multiple sclerosis ...(MS), rehabilitation can therefore exploit the potential of neural plasticity to restore CNS functions beyond the spontaneous mechanisms of recovery from MS-related damage.
Methods:
Here, we reviewed the currently available evidence on the occurrence of mechanisms of structural and functional plasticity following rehabilitation, motor, and/or cognitive training. We presented both data gained from basic laboratory research on animal models and data on persons with MS obtained by advanced magnetic resonance imaging (MRI) techniques.
Results:
Studies on physical and environmental enrichment in experimental MS models showed beneficial effects mediated by both immune modulation and activity-dependent plasticity, lowering tissue destruction and restoring of CNS network function. Translational researches in MS people demonstrated structural and/or functional MRI changes after various interventions, but their heterogeneity and small sample sizes (5–42 patients) raise concerns about the interpretation and generalization of the obtained results.
Discussion:
We highlighted the limitations of published studies, focusing on the knowledge gaps to be filled in terms of neuropathological correlations between changes detected in animal models and changes detected in vivo by neuroimaging.
Objective:
To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different ...mechanisms of action.
Methods:
We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms.
Results:
A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age.
Discussion:
Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
Objective
To identify risk factors for an increased lethality of COVID-19 in patients with multiple sclerosis (MS).
Methods
We searched scientific databases to identify cohort studies with the number ...of deaths in patients with MS. We fitted inverse-variance weighted meta-regressions with random-effects models to identify potential moderators (determinants) of COVID-19-related lethality (outcome).
Results
After an independent screening, 18 articles satisfied the eligibility criteria; all data were collected before anti-SARS-COV-2 vaccination was available. Out of 5,634 patients, 111 died, yielding a pooled death rate of 1.97% (95% confidence intervals 1.61–2.33). There was a substantial heterogeneity between the included studies (
Q
17
= 66.9,
p
< 0.001;
I
2
= 77.5%), but no relevant publication bias (
p
= 0.085). Higher lethality was observed in studies including older patients (
β
= 0.80,
p
= 0.025) and in studies with higher proportions of patients with comorbidity (
β
= 0.17,
p
= 0.046), progressive disease course (
β
= 0.15,
p
= 0.027), and current treatment with anti-CD20 agents (
β
= 0.18,
p
< 0.001). Otherwise, higher proportions of patients treated with interferon beta (
β
= – 0.16,
p
< 0.001) and teriflunomide (
β
= – 0.11,
p
= 0.035) were associated with lower lethality. These estimates did not change even in both multivariable meta-regressions including adjustment variables and leave-one-out sensitivity analyses.
Conclusion
Except for age and comorbidities, risk factors in common with the general population, we identified MS-specific determinants influencing the lethality of COVID-19. Our findings suggest the implementation of a risk mitigation plan for patients with progressive MS and for those treated with anti-CD20 agents.
Background:
Natalizumab (NTZ) is sometimes discontinued in patients with multiple sclerosis, mainly due to concerns about the risk of progressive multifocal leukoencephalopathy. However, NTZ ...interruption may result in recrudescence of disease activity.
Objective:
The objective of this study was to summarize the available evidence about NTZ discontinuation and to identify which patients will experience post-NTZ disease reactivation through meta-analysis of existing literature data.
Methods:
PubMed was searched for articles reporting the effects of NTZ withdrawal in adult patients (⩾18 years) with relapsing–remitting multiple sclerosis (RRMS). Definition of disease activity following NTZ discontinuation, proportion of patients who experienced post-NTZ disease reactivation, and timing to NTZ discontinuation to disease reactivation were systematically reviewed. A generic inverse variance with random effect was used to calculate the weighted effect of patients’ clinical characteristics on the risk of post-NTZ disease reactivation, defined as the occurrence of at least one relapse.
Results:
The original search identified 205 publications. Thirty-five articles were included in the systematic review. We found a high level of heterogeneity across studies in terms of sample size (10 to 1866 patients), baseline patient characteristics, follow up (1–24 months), outcome measures (clinical and/or radiological), and definition of post-NTZ disease reactivation or rebound. Clinical relapses were observed in 9–80% of patients and peaked at 4–7 months, whereas radiological disease activity was observed in 7–87% of patients starting at 6 weeks following NTZ discontinuation. The meta-analysis of six articles, yielding a total of 1183 patients, revealed that younger age, higher number of relapses and gadolinium-enhanced lesions before treatment start, and fewer NTZ infusions were associated with increased risk for post-NTZ disease reactivation (p ⩽ 0.05).
Conclusions:
Results from the present review and meta-analysis can help to profile patients who are at greater risk of post-NTZ disease reactivation. However, potential reporting bias and variability in selected studies should be taken into account when interpreting our data.
Objective
To estimate whether the risk of death from COVID-19 in patients with multiple sclerosis (MS) exceeds that of the general population.
Methods
We conducted a pooled analysis of cohort studies ...on COVID-19 in patients with MS published until July 31, 2021. We calculated the pooled crude death rate (CDR) and estimated the indirectly-adjusted age-standardized lethality ratio (SLR) to assess the risk of death from COVID-19 in patients with MS as compared to general population.
Results
Out of 520 articles, 18 fulfilled criteria for pooled analysis, with a total of 5634 patients (28.6% males, mean age 41.8 years). Of them, 111 died, yielding a CDR of 1.97% (95% confidence intervals CIs 1.61–2.33). The estimated SLR was 1.24 (95% CIs 1.01–1.48) after indirect age-standardization using case-fatality rates obtained from the detailed surveillance data available at the World Health Organization (WHO) website. A leave-one-out sensitivity analysis and the analysis of temporal trends of SLR from March 2020 to July 2021 provided consistent findings.
Conclusions
Our pooled analysis suggests a 24%-increased risk of death from COVID-19 in patients with MS. These findings must be interpreted with caution, mainly because of the difficulties in COVID-19 case detection (especially in the first pandemic wave) and heterogeneity of the analyzed cohorts. Confirmation in larger population-based studies is warranted.
Objective
To evaluate systematically the efficacy of exergames for balance dysfunction in neurological conditions and to identify factors of exergaming protocols that may influence their effects.
...Methods
We searched electronic databases for randomized clinical trials investigating the effect of commercial exergames versus alternative interventions on balance dysfunction as assessed by standard clinical scales in adults with acquired neurological disabilities. Standardized mean differences (Hedge’s
g
) were calculated with random-effects models. Subgroup analyses and meta-regression were run to explore potential modifiers of effect size.
Results
Out of 106 screened articles, 41 fulfilled criteria for meta-analysis, with a total of 1223 patients included. Diseases under investigation were stroke, Parkinson’s disease, multiple sclerosis, mild cognitive impairment or early Alzheimer’s disease, traumatic brain injury, and myelopathy. The pooled effect size of exergames on balance was moderate (
g
= 0.43,
p
< 0.001), with higher frequency (number of sessions per week) associated with larger effect (
β
= 0.24,
p
= 0.01). There was no effect mediated by the overall duration of the intervention and intensity of a single session. The beneficial effect of exergames could be maintained for at least 4 weeks after discontinuation, but their retention effect was specifically explored in only 11 studies, thus requiring future investigation. Mild to moderate adverse events were reported in a minority of studies. We estimated a low risk of bias, mainly attributable to the lack of double-blindness and not reporting intention-to-treat analysis.
Conclusions
The pooled evidence suggests that exergames improve balance dysfunction and are safe in several neurological conditions. The findings of high-frequency interventions associated with larger effect size, together with a possible sustained effect of exergaming, may guide treatment decisions and inform future research.
Exergames represent a way to perform physical activity through active video games, serving as potentially useful tool in the field of neurorehabilitation. However, little is known regarding the ...possible role of exergames in improving cognitive functions in persons suffering from neurological disabilities.
A search for relevant articles was carried out on PubMed/Medline, Scopus, PEDro, and Google Scholar. Only randomized controlled studies and non-randomized but controlled studies were retained. The following additional inclusion criteria were applied: studies focused on physical activity interventions carried out by means of exergames; populations targeted were affected by neurological disabilities; and reported results were related to cognitive outcomes. We calculated standardized mean differences (SMD) and pooled results using a random effects meta-analysis.
Of 520 abstracts screened, thirteen studies met the criteria to be included yielding a total of 465 participants, 233 randomized to exergames, and 232 allocated to the alternative or no intervention. The included studies varied in terms of studied populations (e.g., multiple sclerosis, post-stroke hemiparesis, Parkinson's disease, dementia, dyslexia, Down syndrome), type and duration of interventions, and cognitive outcome measures. Exergames significantly improved executive functions (SMD=0.53, P=0.005; 8 studies, N.=380) and visuo-spatial perception (SMD=0.65, P<0.0001; 5 studies, N.=209) when compared to the alternative or no intervention. There were no significant differences for attention (SMD=0.57, P=0.07; 7 studies, N.=250) and global cognition (SMD=0.05, P=0.80; 6 studies, N.=161).
Exergames are a highly-flexible tool for rehabilitation of both cognitive and motor functions in adult populations suffering from various neurological disabilities and developmental neurological disorders. Additional high-quality clinical trials with larger samples and more specific cognitive outcomes are needed to corroborate these preliminary findings.
Exergames could be considered either as a supplemental treatment to conventional rehabilitation, or as strategy to extend benefits of conventional programs at home.
Background:
Patients with multiple sclerosis (MS) are at increased risk of infection. Vaccination can mitigate these risks but only if safe and effective in MS patients, including those taking ...disease-modifying drugs.
Methods:
A modified Delphi consensus process (October 2017–June 2018) was used to develop clinically relevant recommendations for making decisions about vaccinations in patients with MS. A series of statements and recommendations regarding the efficacy, safety and timing of vaccine administration in patients with MS were generated in April 2018 by a panel of experts based on a review of the published literature performed in October 2017.
Results:
Recommendations include the need for an ‘infectious diseases card’ of each patient’s infectious and immunisation history at diagnosis in order to exclude and eventually treat latent infections. We suggest the implementation of the locally recommended vaccinations, if possible at MS diagnosis, otherwise with vaccination timing tailored to the planned/current MS treatment, and yearly administration of the seasonal influenza vaccine regardless of the treatment received.
Conclusion:
Patients with MS should be vaccinated with careful consideration of risks and benefits. However, there is an urgent need for more research into vaccinations in patients with MS to guide evidence-based decision making.
We performed a dual-task experiment to explore the effect of nabiximols on postural control in 22 patients with multiple sclerosis. They were assessed with static posturography and Stroop test in ...single- and dual-task conditions at treatment start and after 1, 3 and 12 months. At follow-up, we found more impaired postural control in single-task (F = 3.07, p = 0.044) and dual-task (F = 4.90, p = 0.005) conditions in patients who continued treatment (continuers, n = 11) compared with those who discontinued (quitters, n = 11). Continuers were more impaired at Stroop test only in dual-task condition (F = 3.17, p = 0.038). Our findings suggest that nabiximols had a detrimental effect on postural control, especially in multi-tasking conditions.
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