Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving ...axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex ...condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits.
To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments.
This observational cross-sectional study involved 41 PwMS with severe hand dexterity impairment stratified according to the Expanded Disability Status Scale (EDSS) into mild-moderate (
= 17; EDSS, 1-5.5), severe ambulant (
= 15; EDSS, 6-6.5), and severe nonambulant (
= 9; EDSS, 7-9.5). Behavioral outcome measures exploring body function, activity, and participation were administered. The sEMG activity of six upper limb muscles of the most affected side was measured during a reaching task.
The most severe group was significantly older and more affected by secondary progressive MS than the other two groups. Positive significant associations between UL deterioration and impairments at different International Classification of Functioning, Disability, and Health domains were noted in the most severe group. The progressive decline in manual dexterity was moderately to strongly associated with the deterioration of the overall UL activity (ρ = 0.72;
< 0.001) and disuse (amount of use ρ = 0.71;
< 0.001; quality of movement ρ = 0.77;
< 0.001). There was a low correlation between manual dexterity and UL function (ρ = 0.33;
= 0.03). The muscle activation pattern investigated by sEMG was characterized by a decrease in modularity and timing delay in the wrist extensor muscles activation in the severe ambulant patients (EDSS, 6-6.5). Similar impairments were observed in the proximal muscles (anterior deltoid) in the more advanced stages (EDSS ≥ 7).
Behavioral assessment, together with measures of muscle activation patterns, allows investigating the pathophysiology of UL impairments in PwMS across progressive neurological disability severity to implement task-specific rehabilitation interventions.
IntroductionMultiple sclerosis (MS), the most common neurological disease causing disability in young adults, is widely recognised as a major stress factor. Studies have shown that the first years ...after the diagnosis are distressing in terms of adjustment to the disease and that MS negatively affects patients’ psychological well-being, quality of life (QoL) and social functioning. However, the links between disease-specific variables at diagnosis, resilience and psychological adjustment of patients with MS remain largely unexplored, especially in adolescents and young adults. This observational study aims to fill the gap of knowledge on biopsychosocial characteristics and resilience of young adults with MS to evaluate the relationship among these variables and to develop a biopsychosocial model of resilience.Methods and analysisBiological and clinical characteristics of young adults newly diagnosed with MS will be investigated by collecting clinical information, performing neurological examinations, MRI and analysing cerebrospinal fluid and blood biomarkers (eg, measures of inflammation), body composition, gut microbiota and movement/perceptual markers. Psychosocial characteristics (eg, psychological distress, coping strategies), QoL, psychological well-being and resilience will be assessed by self-report questionnaires. Comparative statistics (ie, analysis of variance or unpaired samples t-test, correlation and regression analyses) will be applied to evaluate the relationship among biological, psychological and social factors. The results are expected to allow a comprehensive understanding of the determinants of resilience in young patients with MS and to inform resilience interventions, tailored to young patients’ specific needs, aiming to reduce the risk of maladaptive reactions to the disease and to improve psychological well-being and QoL.Ethics and disseminationThe study has been approved by the Verona University Hospital Ethics Committee (approval number: 2029CESC). The findings will be disseminated through scientific publications in peer-reviewed journals, conference presentations, social media and specific websites.Trial registration numberClinicalTrials.gov (NCT03825055).
Integration of robotics and upper limb rehabilitation in people with multiple sclerosis (PwMS) has rarely been investigated.
To compare the effects of robot-assisted hand training against non-robotic ...hand training on upper limb activity in PwMS. To compare the training effects on hand dexterity, muscle activity, and upper limb dysfunction as measured with the International Classification of Functioning.
This single-blind, randomized, controlled trial involved 44 PwMS (Expanded Disability Status Scale:1.5-8) and hand dexterity deficits. The experimental group (
= 23) received robot-assisted hand training; the control group (
= 21) received non-robotic hand training. Training protocols lasted for 5 weeks (50 min/session, 2 sessions/week). Before (T0), after (T1), and at 1 month follow-up (T2), a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Action Research Arm Test. Secondary outcomes: Nine Holes Peg Test; Fugl-Meyer Assessment Scale-upper extremity section; Motricity Index; Motor Activity Log; Multiple Sclerosis (MS) Quality of Life-54; Life Habits assessment-general short form and surface electromyography.
There were no significant between-group differences in primary and secondary outcomes. Electromyography showed relevant changes providing evidence increased activity in the extensor carpi at T1 and T2.
The training effects on upper limb activity and function were comparable between the two groups. However, robot-assisted training demonstrated remarkable effects on upper limb use and muscle activity. https://clinicaltrials.gov NCT03561155.
Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in ...patients with breakthrough disease is unknown.
This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch non-switchers). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch.
In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p = 0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004).
Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct ...phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated(181) tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most sensitive indicators of sCJD, the highest sensitivity, specificity and positive predictive value were obtained when all the above markers were combined. The latter approach also allowed a reliable differential diagnosis with other neurodegenerative dementias.
Introduction: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with an immune mediated pathogenesis. Several therapies that suppress or modulate diverse immune ...system functions have been used for decades with the aim of modifying the disease course. However, these treatments have either limited efficacy or potentially serious adverse events that prevent first-line use on large scale.
Areas covered: The aim of the present article is to review ongoing or recently completed clinical trials investigating immunosuppressive drugs for MS. The websites clinicaltrials.gov, clinicaltrialsregister.eu, and pubmed.gov were searched for phase 1, phase 2, and phase 3 trials starting from 2012. Twelve drugs were identified, including seven monoclonal antibodies and five small molecules.
Expert opinion: Current or recently completed trials of immunosuppressants for MS are mainly proof-of-concept studies enrolling patients with relapsing disease and using efficacy endpoints based on magnetic resonance imaging measures of inflammatory activity. Sphingosine 1-phosphate receptor modulators and B-cell depleting therapies represent the most commonly investigated drugs, suggesting that mechanisms of action that have already shown promise for MS treatment are being exploited to find new therapies with improved safety, tolerability, and convenience of dosing. Clinical trials of immunosuppressants for progressive MS are largely lacking.
Multiple sclerosis (MS) is the prototypical inflammatory demyelinating disorder of the central nervous system (CNS). Although many advances have been made in the comprehension of its pathogenesis, ...the etiology is still unknown. The complexity of MS reflects in the extreme variability of the clinical manifestations and clinical course both between and within patients, in addition to immunopathological mechanisms and response to treatment. Several prognostic factors have been suggested in large scale studies, but predictions in individual cases are difficult to make. Cerebrospinal fluid (CSF) biomarkers, such as 14-3-3, tau, and cystatin C are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, none has shown sufficient reproducibility to be applied in clinical practice. Here we review the current literature addressing the above mentioned biomarkers as MS severity predictors at an early stage.
Background
A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not ...been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD).
Objective
The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS.
Methods
Serum samples were collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control individuals (HCs). An indirect ELISA was set up to detect specific Abs against HERV-W env-su peptides.
Results
Our data showed that two antigenic peptides, particularly HERV-Wenv93–108 and HERV-Wenv248–262, were statistically significantly present only in serum of MS compared to NMOSD and HCs. Thus, the specific humoral immune response against HERV-W env-su glycoprotein antigens found in MS is widely missing in NMOSD.
Conclusion
Increased circulating serum levels of these HERV-W Abs may be suitable as additional biomarkers to better differentiate MS from NMOSD.
Abstract Introduction Nabiximols is a cannabinoid compound approved for the treatment of multiple sclerosis (MS)-related spasticity. However, additional symptoms, such as pain, urinary urgency and ...sleep disturbance, may benefit from treatment. Case report The present report describes a patient with secondary progressive MS and severe lower limbs spasticity who was started on treatment with nabiximols. The patient also suffered from trigeminal neuralgia, which he was not treating due to inefficacy or side effects of all previously tried medications. After nabiximols initiation the patient experienced a marked benefit on trigeminal neuralgia, which completely resolved, while spasticity responded only partially to treatment. Conclusion Nabiximols mechanism of action is based on the interaction with CB1 and CB2 receptors, which are expressed by central nervous system neurons and are known to modulate pain among other effects. The present case indicates that nabiximols and other cannabinoids need to be further tested for the treatment of trigeminal neuralgia.
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