Spasticity and Dystonia: A Brief Review

Spasticity and dystonia are two neurological conditions with a broad range of clinical manifestations that can emerge at any age. Although the spasticity and dystonia symptoms are caused by different pathophysiological mechanisms, both of them may cause functional impairment that contributes to a poor quality of life. Spasticity is characterised by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex. It mostly occurs in disorders of the central nervous system (CNS) affecting the upper motor neurons, such as multiple sclerosis, amyotrophic lateral sclerosis, cerebrovascular diseases, cerebral palsy, traumatic brain injury, stroke, and spinal cord injury. Therapeutic options may combine, in various proportions, physical therapy, occupational therapy, self-rehabilitation, the use of orthoses and assistive devices, drug treatment, orthopaedic surgery, and neurosurgery. Dystonia is defined as a syndrome of involuntary movement that manifests as excessive muscle contractions that frequently cause twisting and repetitive movements or abnormal postures. It is often intensified or exacerbated by physical activity, and symptoms may progress into adjacent muscles. Dystonia has many different manifestations and causes, and many different treatment options are available. These options include physical and occupational therapy, oral medications, intramuscular injection of botulinum toxins, and neurosurgical interventions

Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis

Introduction Natalizumab (NTZ) is one of the most effective treatment options for multiple sclerosis (MS) treatment. Our study aimed to evaluate the effectiveness of NTZ when administered according to the extended dosing strategy compared with standard 4-weekly administration in a large Italian MS population. Materials and methods This retrospective multicentre study included patients with relapsing-remitting MS (RR-MS) who received NTZ administrations between the 1 June 2012 and the 15 May 2018 and were followed by the ’Italian MS Register’. All patients with MS were stratified into two groups based on NTZ administration schedule: standard interval dosing (SID) patients who received infusions on average from 28 to 32 days (median 30) and extended interval dosing (EID) including patients who have been infused with interval between 33 and 49 days (median 43). Clinical data were assessed at baseline (before starting NTZ), after 12 (T1) and 24 months (T2) of treatment. Results Out of 5231 patients with RR-MS screened, 2092 (mean age 43.2±12.0, 60.6% women) were enrolled. A total of 1254 (59.9%) received NTZ according to SID, and 838 (40.1%) according to EID. At 12 and 24 months, no differences in terms of annualised relapse rate and disability status were found between the two groups. Progression index and confirmed disability worsening were similar between the two groups. Discussion The use of NTZ with an extended interval schedule showed similar effectiveness compared with SID. Unchanged clinical efficacy of EID schedule may raise the question of a possible advantage in terms of tolerability and safety

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Changes in Anti-JCV Antibody Status in a Large Population of Multiple Sclerosis Patients Treated with Natalizumab

Natalizumab (NTZ) can be associated with an opportunistic infection, progressive multifocal leukoencephalopathy (PML), caused by John Cunningham virus (JCV). High titer of anti-JCV antibody (JCV index) in patients treated with NTZ for over 2 years limit it use, leading to treatment discontinuation

A evaluation of the shift in spasticity category in individuals with multiple sclerosis-related spasticity treated with nabiximols

Background: Over 80% of individuals with multiple sclerosis (MS) experience MS-associated spasticity (MSS). In many European countries, after failure of first-line treatments, moderate or severe MSS can be treated with nabiximols, a cannabis-based add-on treatment. Objective: This post hoc analysis assessed the shift of participants treated with nabiximols from higher (severe or moderate) to lower (moderate or mild/none) spasticity. Methods: Previously published data from two randomised controlled trials (RCTs), GWSP0604 (NCT00681538) and SAVANT (EudraCT2015-004451-40), and one large real-world study (consistent with EU label), all enriched for responders, were re-analysed. Spasticity severity, measured using the 0–10 numerical rating scale (spasticity NRS), was categorised as none/mild (score <4), moderate (score ⩾4–7), or severe (score ⩾7). Results: In the two RCTs, the shift of participants with severe MSS into a lower category was significantly greater at week 12 for those receiving nabiximols versus placebo [GWSP0604: OR (95% CI), 4.4 (1.4, 14.2), p  = 0.0125; SAVANT: 5.2 (1.2, 22.3), p  = 0.0267]. In all three studies, over 80% of assessed patients with severe spasticity at baseline reported a shift into a lower category of spasticity after 12 weeks. Conclusions: A meaningful proportion of MSS patients treated with nabiximols shifted to a lower category of spasticity severity, typically maintained to the end of the 12-week study period