scholarly journals Therapeutic Benefits of Short-Arm Human Centrifugation in Multiple Sclerosis–A New Approach

2022 ◽  
Vol 12 ◽  
Author(s):  
Chrysoula Kourtidou-Papadeli ◽  
Christos A. Frantzidis ◽  
Christos Bakirtzis ◽  
Anatoli Petridou ◽  
Sotiria Gilou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Training Programme ◽  
Progressive Multiple Sclerosis ◽  
Artificial Gravity ◽  
Muscle Oxygen ◽  
Therapeutic Benefits ◽  
Before And After ◽  
Degree Of Disability ◽  
Brain Reorganization

Short-arm human centrifugation (SAHC) is proposed as a robust countermeasure to treat deconditioning and prevent progressive disability in a case of secondary progressive multiple sclerosis. Based on long-term physiological knowledge derived from space medicine and missions, artificial gravity training seems to be a promising physical rehabilitation approach toward the prevention of musculoskeletal decrement due to confinement and inactivity. So, the present study proposes a novel infrastructure based on SAHC to investigate the hypothesis that artificial gravity ameliorates the degree of disability. The patient was submitted to a 4-week training programme including three weekly sessions of 30 min of intermittent centrifugation at 1.5–2 g. During sessions, cardiovascular, muscle oxygen saturation (SmO2) and electroencephalographic (EEG) responses were monitored, whereas neurological and physical performance tests were carried out before and after the intervention. Cardiovascular parameters improved in a way reminiscent of adaptations to aerobic exercise. SmO2 decreased during sessions concomitant with increased g load, and, as training progressed, SmO2 of the suffering limb dropped, both effects suggesting increased oxygen use, similar to that seen during hard exercise. EEG showed increased slow and decreased fast brain waves, with brain reorganization/plasticity evidenced through functional connectivity alterations. Multiple-sclerosis-related disability and balance capacity also improved. Overall, this study provides novel evidence supporting SAHC as a promising therapeutic strategy in multiple sclerosis, based on mechanical loading, thereby setting the basis for future randomized controlled trials.

scholarly journals Laquinimod Supports Remyelination in Non-Supportive Environments

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1363 ◽  
Author(s):  
Stella Nyamoya ◽  
Julia Steinle ◽  
Uta Chrzanowski ◽  
Joel Kaye ◽  
Christoph Schmitz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Oligodendrocyte Progenitor Cells ◽  
Protective Effects ◽  
Oligodendrocyte Progenitor ◽  
Functional Deficits ◽  
Supportive Environments ◽  
Multiple Sclerosis Patients ◽  
Active Multiple Sclerosis

Inflammatory demyelination, which is a characteristic of multiple sclerosis lesions, leads to acute functional deficits and, in the long term, to progressive axonal degeneration. While remyelination is believed to protect axons, the endogenous-regenerative processes are often incomplete or even completely fail in many multiple sclerosis patients. Although it is currently unknown why remyelination fails, recurrent demyelination of previously demyelinated white matter areas is one contributing factor. In this study, we investigated whether laquinimod, which has demonstrated protective effects in active multiple sclerosis patients, protects against recurrent demyelination. To address this, male mice were intoxicated with cuprizone for up to eight weeks and treated with either a vehicle solution or laquinimod at the beginning of week 5, where remyelination was ongoing. The brains were harvested and analyzed by immunohistochemistry. At the time-point of laquinimod treatment initiation, oligodendrocyte progenitor cells proliferated and maturated despite ongoing demyelination activity. In the following weeks, myelination recovered in the laquinimod- but not vehicle-treated mice, despite continued cuprizone intoxication. Myelin recovery was paralleled by less severe microgliosis and acute axonal injury. In this study, we were able to demonstrate that laquinimod, which has previously been shown to protect against cuprizone-induced oligodendrocyte degeneration, exerts protective effects during oligodendrocyte progenitor differentiation as well. By this mechanism, laquinimod allows remyelination in non-supportive environments. These results should encourage further clinical studies in progressive multiple sclerosis patients.

Oral D-Aspartate enhances synaptic plasticity reserve in progressive multiple sclerosis

2019 ◽  
Vol 26 (3) ◽  
pp. 304-311 ◽  
Author(s):  
Carolina G Nicoletti ◽  
Fabrizia Monteleone ◽  
Girolama A Marfia ◽  
Alessandro Usiello ◽  
Fabio Buttari ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Synaptic Plasticity ◽  
Cortical Excitability ◽  
Short Interval ◽  
Oral Intake ◽  
Long Term Potentiation ◽  
Progressive Multiple Sclerosis ◽  
Clinical Effects ◽  
Term Potentiation ◽  
Before And After

Background: Synaptic plasticity reserve correlates with clinical recovery after a relapse in relapsing–remitting forms of multiple sclerosis (MS) and is significantly compromised in patients with progressive forms of MS. These findings suggest that progression of disability in MS is linked to reduced synaptic plasticity reserve. D-Aspartate, an endogenous aminoacid approved for the use in humans as a dietary supplement, enhances synaptic plasticity in mice. Objective: To test whether D-Aspartate oral intake increases synaptic plasticity reserve in progressive MS patients. Methods: A total of 31 patients affected by a progressive form of MS received either single oral daily doses of D-Aspartate 2660 mg or placebo for 4 weeks. Synaptic plasticity reserve and trans-synaptic cortical excitability were measured through transcranial magnetic stimulation (TMS) protocols before and after D-Aspartate. Results: Both TMS-induced long-term potentiation (LTP), intracortical facilitation (ICF) and short-interval ICF increased after 2 and 4 weeks of D-Aspartate but not after placebo, suggesting an enhancement of synaptic plasticity reserve and increased trans-synaptic glutamatergic transmission. Conclusion: Daily oral D-Aspartate 2660 mg for 4 weeks enhances synaptic plasticity reserve in patients with progressive MS, opening the path to further studies assessing its clinical effects on disability progression.

scholarly journals Effects of 4-Week Creatine Supplementation Combined with Complex Training on Muscle Damage and Sport Performance

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1640 ◽  
Author(s):  
Chia-Chi Wang ◽  
Chu-Chun Fang ◽  
Ying-Hsian Lee ◽  
Ming-Ta Yang ◽  
Kuei-Hui Chan
Keyword(s):  
Placebo Group ◽  
Muscle Damage ◽  
Muscular Strength ◽  
Creatine Supplementation ◽  
Training Programme ◽  
Sport Performance ◽  
Repetition Maximum ◽  
Before And After ◽  
Complex Training

Creatine supplementation has an ergogenic effect in an acute complex training bout, but the benefits of chronic creatine supplementation during long-term complex training remain unknown. The study aimed to evaluate the effects of 4-week complex training combined with creatine supplementation on sport performances and muscle damage biomarkers. Thirty explosive athletes were assigned to the creatine or placebo group, which consumed 20 g of creatine or carboxymethyl cellulose, respectively, per day for 6 days followed by 2 g of the supplements until the end of the study. After 6 days of supplementation, subjects performed tests of one repetition maximum (1-RM) strength of half squat and complex training bouts to determine the optimal individual post-activation potentiation time. Thereafter, all subjects performed a complex training programme consisting of six sets of 5-RM half squats and plyometric jumps 3 times per week for 4 weeks. Body composition, 30-m sprint and jump performances were assessed before and after the training period. Moreover, blood creatine kinase (CK) activity was analysed at the first and the last training bout. After the training, the 1-RM strength in the creatine group was significantly greater than in the placebo group (p < 0.05). CK activity after the complex training bout in the creatine group was significantly reduced compared with the placebo group (p < 0.05). No differences were noted for other variables. This study concluded that creatine supplementation combined with complex training improved maximal muscular strength and reduced muscle damage during training.

One-year cyclophosphamide treatment combined with methylprednisolone improves cognitive dysfunction in progressive forms of multiple sclerosis

2005 ◽  
Vol 11 (3) ◽  
pp. 360-363 ◽  
Author(s):  
H Zéphir ◽  
J de Seze ◽  
K Dujardin ◽  
G Dubois ◽  
M Cabaret ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Executive Functions ◽  
Progressive Multiple Sclerosis ◽  
Mechanisms Of Action ◽  
Cognitive Efficiency ◽  
Secondary Progressive ◽  
Before And After ◽  
Cyclophosphamide Treatment ◽  
One Year ◽  
Positive Effect

We conducted an evaluation of changes in cognition in progressive multiple sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide (700 mg/m2) with methylprednisolone (1 g). Twenty-eight consecutive progressive MS patients (10 primary progressive, 18 secondary progressive MS) were evaluated before and after six and 12 months of treatment. The WAIS-R score, memory and executive functions were evaluated. Under treatment we found a significant improvement in global cognitive efficiency, encoding abilities, planning abilities and inhibition after six and 12 months. However, mechanisms of action of the positive effect of these anti-inflammatory and immunosuppressive treatments on cognition remain unclear.

Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease

2015 ◽  
Vol 22 (6) ◽  
pp. 817-821 ◽  
Author(s):  
Richard Gonsette ◽  
Marc Debouverie ◽  
Christian Sindic ◽  
Jean-Christophe Ferré ◽  
Gilles Edan
Keyword(s):  
Multiple Sclerosis ◽  
Lymphocyte Subsets ◽  
Progressive Multiple Sclerosis ◽  
Left Ventricular ◽  
Open Label ◽  
Annual Relapse Rate ◽  
Cerebral Mri ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients

Background: Mitoxantrone has been approved for patients with worsening relapsing–remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. Objectives: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd+) lesions, and its safety. Methods: Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd+ lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. Results: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 ( p = 0.01). The annual relapse rate was reduced by 87% ( p < 10−4). Two patients experienced a transient reduction in left ventricular fraction. Conclusion: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.

Detecting clinically-relevant changes in progressive multiple sclerosis

2014 ◽  
Vol 21 (2) ◽  
pp. 171-179 ◽  
Author(s):  
LVAE Bosma ◽  
JM Sonder ◽  
JJ Kragt ◽  
CH Polman ◽  
BMJ Uitdehaag
Keyword(s):  
Multiple Sclerosis ◽  
Outcome Measurement ◽  
Progressive Multiple Sclerosis ◽  
Meaningful Change ◽  
Disability Scale ◽  
Impact Scale ◽  
Disability Status ◽  
Disease Impact

Objective: To investigate which changes in different clinical outcome measures contribute most to increased disease impact, as reported by the patient, in progressive multiple sclerosis (MS). Methods: From a cohort of prospectively-followed MS patients, we selected progressive patients with two visits, 4–6 years apart. We assessed long-term changes on the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT) and Guy’s Neurological Disability Scale (GNDS). We defined the presence or absence of clinically meaningful change by using the Multiple Sclerosis Impact Scale (MSIS-29) as an anchor measure. We also studied change on recently identified sub-scales of GNDS. Results: Change on GNDS (especially the spinal-plus subscale) contributed most to increased disease impact. Also change on the T25FW contributed largely. Specific profiles of change in T25FW and MSIS seemed to exist (generally, a lower increase in disease impact in patients with longer disease duration and higher baseline impact/disability). In some patients a dissociation existed between increased impact, according to the MSIS-29, and objective physical worsening of the T25FW. Conclusion: These results support using GNDS (particularly the spinal-plus domain) and T25FW in outcome measurement in progressive MS. We suggest there is a relation between baseline clinical characteristics and an increased impact at follow-up. This may have implications for patient selection in trials for progressive MS.

Sick leave and disability pension before and after diagnosis of multiple sclerosis

2016 ◽  
Vol 22 (14) ◽  
pp. 1859-1866 ◽  
Author(s):  
Erik Landfeldt ◽  
Anna Castelo-Branco ◽  
Axel Svedbom ◽  
Emil Löfroth ◽  
Andrius Kavaliunas ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sick Leave ◽  
Disability Pension ◽  
Disease Diagnosis ◽  
First Year ◽  
Final Sample ◽  
Before And After ◽  
Considerable Morbidity ◽  
Long Term Impact

Background: Multiple sclerosis (MS) is associated with considerable morbidity and serious disability, but little is known of the long-term impact of the disease on work ability. Objectives: To assess sick leave (short-term absence) and disability pension (long-term absence) before and after diagnosis of MS. Methods: Patients with MS in Sweden were identified in a nationwide disease-specific register and matched with general population controls. Sick leave and disability pension were measured before and after index (i.e. the MS diagnosis date). Results: The final sample comprised 6092 patients and 60,345 controls (mean age 39 years; 70% female). The mean annual prevalence of sick leave ranged from 12% the first year after index to 23% after 11 years among patients and from 13% to 13% among controls. Corresponding estimates for disability pension were 12% and 55% for patients and 7% and 9% for controls. Significant differences in sick leave were observed up to 15 years before index and 3 years for disability pension. Conclusion: Patients with MS in Sweden have elevated levels of sick leave and disability pension up to 15 years before disease diagnosis. Our results highlight the burden of disease on affected patients and society and underscore the substantial unmet medical need.

scholarly journals Gaining First Insights on Secondary Progressive Multiple Sclerosis Patients Treated With Siponimod in Clinical Routine: Protocol of the Noninterventional Study AMASIA (Preprint)

2020 ◽  
Author(s):  
Tjalf Ziemssen ◽  
Olaf Hoffmann ◽  
Luisa Klotz ◽  
Herbert Schreiber ◽  
Martin S Weber ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Socioeconomic Conditions ◽  
Clinical Routine ◽  
Relapsing Remitting ◽  
Noninterventional Study ◽  
Relapsing Remitting Multiple Sclerosis

BACKGROUND A high proportion of patients with relapsing remitting multiple sclerosis convert to secondary progressive multiple sclerosis (SPMS) characterized by irreversibly progressing disability and cognitive decline. Siponimod (Mayzent), a selective sphingosine-1-phosphate receptor modulator, was recently approved by the European Medicines Agency for the treatment of adult SPMS patients with active disease, as evidenced by relapses or magnetic resonance imaging features of ongoing inflammatory activity. Approval by the Food and Drug Administration covers a broader range of indications, comprising clinically isolated syndrome, relapsing remitting multiple sclerosis, and active SPMS. However, treatment effects of siponimod have not been assessed in a structured setting in clinical routine so far. OBJECTIVE The objectives of AMASIA (imp<strong>A</strong>ct of <strong>M</strong>ayzent [siponimod] on second<strong>A</strong>ry progressive multiple <strong>S</strong>clerosis patients in a long-term non-<strong>I</strong>nterventional study in Germ<strong>A</strong>ny), a prospective noninterventional study, are to assess the long-term effectiveness and safety of siponimod in clinical routine and to evaluate the impact of disease burden on quality of life and socioeconomic conditions. Here, we report the study design of AMASIA. METHODS Treatment effects of siponimod will be evaluated in 1500 SPMS patients during a 3-year observational phase. According to the genetic polymorphism of CYP2C9, the initial dose will be titrated to the maintenance dose of 1 mg (CYP2C9*1*3 and *2*3) or 2 mg (all other polymorphisms of CYP2C9 except *3*3, which is contraindicated) taken orally once daily. Primary endpoint is the 6-month confirmed disability progression, as assessed by a functional composite endpoint comprising the Expanded Disability Status Scale and symbol digit modalities test to take appropriate account of cognitive changes and increase sensitivity. Further measures including multiple sclerosis activity data; assessments of functional domains; questionnaires addressing the patients’, physicians’, and relatives’ perspectives of disability progression; cognitive worsening; quality of life; and socioeconomic aspects will be documented using the multiple sclerosis documentation system MSDS3D. RESULTS AMASIA is being conducted between February 2020 and February 2025 in up to 250 neurological centers in Germany. CONCLUSIONS AMASIA will complement the pivotal phase III–derived efficacy and safety profile of siponimod with real-world data and will further evaluate several individual treatment aspects such as quality of life and socioeconomic conditions of patients and caregivers. It might help to establish siponimod as a promising option for the treatment of SPMS patients in clinical routine. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/19598

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