Be Cool: A Holistic and Innovative Approach to Rehabilitation in Multiple Sclerosis: Study Protocol for a Randomized Controlled Trial.

(1) Background: Individuals with multiple sclerosis (MS) have to deal with numerous symptoms that adversely impact their quality of life. While pharmaceutical treatments offer some relief, they often fall short of addressing the full spectrum of MS symptoms. To bridge this gap, we introduce the Be Cool rehabilitation program, a comprehensive protocol designed to enhance the well-being and life quality of MS individuals. (2) Methods: The Be Cool program is a multifaceted approach that combines exercise training, nutritional guidance, psychological support, and cooling strategies. Adapted to meet the unique needs of MS individuals, this program aims to mitigate symptoms, promote physical and mental health, and improve overall quality of life. The integration of these strategies addresses the complex challenges faced by MS individuals, offering a holistic solution beyond conventional medication. (3) Conclusions: The Be Cool rehabilitation protocol is designed to offer individuals with MS a comprehensive approach to symptom management, fostering improvements in their quality of life. By addressing the multifaceted nature of MS through an integrated strategy, the program holds promise for more effective management of the condition.

A Prospective, Observational Study Assessing Effectiveness, Safety, and QoL of Greek Patients with Multiple Sclerosis Under Treatment with Fingolimod.

INTRODUCTION: Fingolimod is the first approved oral therapy for relapsing-remitting multiple sclerosis (RRMS). The present study aimed to further characterize fingolimod's safety profile, and to assess the patient-reported treatment satisfaction and impact of fingolimod on the quality of life (QoL) of patients with multiple sclerosis (MS) treated in routine care in Greece. METHODS: This was a multicenter, prospective, observational, 24-month study conducted in Greece by hospital-based and private practice neurologists who specialize in MS. Eligible patients had initiated fingolimod within 15 days in accordance with the locally approved label. Safety outcomes included any adverse event (AE) observed during the study period and efficacy outcomes included both objective (disability progression and 2-year annualized relapse rate) and patient-reported assessments (Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 and the EuroQol (EQ)-5-dimension (5D) 3-level instruments). RESULTS: A total of 489 eligible patients (age 41.2 ± 9.8 years; 63.7% female; 4.2% treatment-naive) were exposed to fingolimod for a median of 23.7 months. During the observation period, 20.5% of the participants experienced 233 AEs. Lymphopenia (8.8%), leukopenia (4.2%), hepatic enzyme increased (3.4%), and infections (3.0%) were the most common. Most patients (89.3%) did not experience disability progression; the 2-year annualized relapse rate decreased by 94.7% compared to baseline. The median EQ-visual analogue scale (VAS) was 74.5 at month 24 vs. 65.0 at enrollment (p < 0.001) and the EQ-5D index score was 0.80 vs. 0.78, respectively. Significant improvements were noted in the TSQM global satisfaction and effectiveness domain scores between 6 and 24 months post enrollment (median scores at month 24, 71.4 and 66.7, respectively) (p < 0.001). Significant increases from enrollment to the 24th month were also noted in the patients' global satisfaction and effectiveness domain scores [mean change of 7.4 ± 17.7 (p = 0.005) and mean increase of 5.4 ± 16.2) (p = 0.043), respectively]. CONCLUSION: In the real-world setting of Greece, fingolimod demonstrates a clinical benefit and a predictable and manageable safety profile, which contribute towards high patient-reported treatment satisfaction and improvements in the QoL of patients with MS.

Deciphering anti-MOG IgG antibodies: Clinical and radiological spectrum, and comparison of antibody detection assays.

IgG antibodies to myelin oligodendrocyte glycoprotein (MOG) detected by cell based assays (CBA) have been identified in a constantly expanding spectrum of CNS demyelinating disorders. However, a universally accepted CBA has not been adopted yet. We aimed to analyze the clinical and radiological features of patients with anti-MOG IgG1-antibodies detected with a live-cell CBA and to compare the three most popular MOG-CBAs. We screened sera from 1300 Greek patients (including 426 patients referred by our 8 clinics) suspected for anti-MOG syndrome, and 120 controls with the live-cell MOG-CBA for IgG1-antibodies. 41 patients, versus 0 controls were seropositive. Clinical, serological and radiological data were available and analyzed for the 21 seropositive patients out of the 426 patients of our clinics. Their phenotypes were: 8 optic neuritis, 3 myelitis, 3 neuromyelitis optica, 2 encephalomyelitis, 2 autoimmune encephalitis and 3 atypical MS. We then retested all sera of our 426 patients with the other two most popular MOG-CBAs for total IgG (a live-cell and a commercial fixed-cell CBAs). Seven IgG1-seropositive patients were seronegative for one or both IgG-CBAs. Yet, all 21 patients had clinical and radiological findings previously described in MOG-antibody associated demyelination disease supporting the high specificity of the IgG1-CBA. In addition, all IgG1-CBA-negative sera were also negative by the IgG-CBAs. Also, all controls were negative by all three assays, except one serum found positive by the live IgG-CBA. Overall, our findings support the wide spectrum of anti-MOG associated demyelinating disorders and the superiority of the MOG-IgG1 CBA over other MOG-CBAs.

Switching from fingolimod to alemtuzumab in patients with highly active relapsing-remitting multiple sclerosis: Α case series.

BACKGROUND: The management of "aggressive" and "highly-active" relapsing-remitting multiple sclerosis remains problematic. Although a number of highly efficacious agents are currently available, the optimal timing of their use and the balancing between efficacy and immediate and long-term consequences are still a matter of conjecture. METHODS: We describe the clinical, radiological and immunological profile of three multiple sclerosis patients with persistent clinical and radiological disease activity under fingolimod treatment. After fingolimod cessation patients demonstrated severe disease exacerbation and were successfully treated with alemtuzumab. RESULTS: All patients experienced significant improvement after the administration of alemtuzumab and achieved no evidence of disease activity status that persisted after a median of 19 months of follow-up (range: 17-25 months). Confirmed disability improvement was achieved in all cases. Quantitative MRI data demonstrated a reduction of the T2 lesion load in 2 out of 3 patients and complete abrogation of inflammatory activity in all patients after the administration of alemtuzumab. Α patient presented a previously unreported, persistent lymphocytosis after alemtuzumab administration, that was not associated with infectious, lymphoproliferative or autoimmune diseases and had no apparent clinical implications. CONCLUSIONS: Alemtuzumab appears to be an effective and safe short-term therapeutic option both as a rescue therapy for the disease flare-up associated with fingolimod withdrawal, as well as for the reversal of the deteriorating course observed in patients who fail treatment with fingolimod.

Cognitive and brain reserve in multiple sclerosis--A cross-sectional study.

BACKGROUND: Cognitive impairment (CI) is detected in 40-70% of multiple sclerosis (MS) patients, but only 33-50% of the CI variance is explained by the disease burden assessed by MRI. The cognitive reserve (CR) hypothesis has been postulated to account for this discrepancy. So far, most previous studies have confirmed the CR hypothesis in MS but failed to examine CR indices collectively or use clinically relevant neuropsychological assessments. The aim of this study was to replicate previous findings for the effect of CR (and its counterpart; brain reserve-BR) in MS by considering these caveats. METHODS: 128 RRMS and 13 SPMS patients were recruited in this cross-sectional study (mean age 43.5 ±â€¯10.4 years old, 73% females, mean disease duration 153.7 ±â€¯89.4). CR was assessed by the Cognitive Reserve Index questionnaire (CRIq) and BR by the intracranial volume. Neuropsychological assessment was made by using the recommended for clinicians Brief International Cognitive Assessment for MS (BICAMS) tool. Other measurements included clinical characteristics, psychological status, fatigue, and MRI volumetric imaging parameters. Multiple linear regression models were implemented to ascertain the putative moderating role (i.e. interaction terms) of CR and BR in cognition. RESULTS: Exploratory univariate analyses revealed significant negative correlations between both disability and depression with cognitive scores (rho = -0.382, p < 0.001, rho = -0.278, p = 0.001, respectively), only. After controlling for gender, disability and depression, a significant moderating protective effect of CR on the associations between both grey and peripheral grey matter volumes with verbal memory was found (beta = 1.834, p = 0.045, beta = 1.936, p = 0.04 for the interaction terms, respectively). Also, BR moderated the effect of the total brain volume on verbal memory (beta = 1.516, p = 0.043). CONCLUSION: This study showed that by using composite measures of CR and simple, clinically-orientated neuropsychological assessments, the protective role of CR and BR is mostly restricted to memory function. Future research should embark on investigating interventions that will aim to enhance CR for the prevention of CI in MS.

Multiple Sclerosis Patients Valuing Their Own Health Status: Valuation and Psychometric Properties of the 15D.

An ongoing debate on decision and cost-utility analyses is whether to use preferences of general public or patients. The aim of this study was to replicate the valuation procedure of the multi-attribute utility generic measure, 15D, using a sample of multiple sclerosis (MS) patients and to assess its psychometric properties. Consecutive outpatient MS patients were recruited from two MS centers in Greece. The three-stage valuation procedure was applied and, with the use of elicited preference weights, an MS patients' algorithm was developed. The original Finnish value set derived from healthy individuals was also used to calculate scores and a comparison between the two algorithms was made. A total of 64 MS patients were evaluated. The 15D scores obtained with the MS patients' valuation algorithm were higher than the original one. The derived utilities differed significantly with respect to age, depressive symptoms, Expanded Disability Status Scale score and clinical form. MS patients indicated as most important domains mobility, mental functioning and vitality. Cronbach's alpha was estimated 0.876 and correlations between relevant dimensions of the instruments were moderate to high. The 15D was generally feasible and reliable in patients with MS and the valuation system yielded acceptable psychometric properties.

Cognitive impairment as a central cholinergic deficit in patients with Myasthenia Gravis.

BACKGROUND: The purpose of this study was to investigate with neurophysiological and neuropsychological methods such as pupillometry, cognitive test and Hamilton Depression Rating Scale (HAM-D) the hypothesis of Central Nervous System (CNS) cholinergic involvement in patients with Myasthenia Gravis (MG). METHODS: Thirty-two patients (32) with MG and a mean age of 51.1 ± 17.2 volunteered to participate in this investigation, while thirty-three (33) healthy subjects with a mean age of 50.2 ± 14.8 served as controls. All subjects underwent pupillometric measurements and performed the Wechsler Memory Scale (WMS) and HAM-D. The pupillometric indices studied were: 1) latency for the onset of constriction (T1), 2) maximum constriction velocity (VCmax) and 3) maximum constriction acceleration (ACmax). RESULTS: T1 was found significantly increased by 21.7% (p < 0.05) in MG patients as compared to healthy subjects. Conversely, VCmax and ACmax were significantly decreased in MG patients by 33.3% (p < 0.05) and 43.5% (p < 0.05) respectively, as opposed to healthy subjects. Additionally, MG patients showed significantly decreased score in WMS by 41.6% (p < 0.05) as compared to healthy controls. No significant difference was found for HAM-D between the two groups. CONCLUSIONS: VCmax and ACmax are governed mainly by the action of the Parasympathetic Nervous System, through acetylcholine. The results of this study demonstrate that the CNS may be affected in MG and support the hypothesis that MG has central cholinergic effects manifested by cognitive dysfunction.

Multiple sclerosis registries in Europe - results of a systematic survey.

BACKGROUND: Identification of MS registries and databases that are currently in use in Europe as well as a detailed knowledge of their content and structure is important in order to facilitate comprehensive analysis and comparison of data. METHODS: National MS registries or databases were identified by literature search, from the results of the MS Barometer 2011 and by asking 33 national MS societies. A standardized questionnaire was developed and sent to the registries' leaders, followed by telephone interviews with them. RESULTS: Twenty registries were identified, with 13 completing the questionnaire and seven being interviewed by telephone. These registries differed widely for objectives, structure, collected data, and for patients and centres included. Despite this heterogeneity, common objectives of the registries were epidemiology (n=10), long-term therapy outcome (n=8), healthcare research (n=9) and support/basis for clinical trials (n=8). While physician-based outcome measures (EDSS) are used in all registries, data from patients' perspectives were only collected in six registries. CONCLUSIONS: The detailed information on a large number of national MS registries in Europe is a prerequisite to facilitating harmonized integration of existing data from MS registries and databases, as well as comprehensive analyses and comparison across European populations.

Learning of a novel visuo-postural co-ordination task in adults with multiple sclerosis.

OBJECTIVE: A behavioural study was conducted to investigate how cerebellar dysfunction associated with multiple sclerosis affects the ability to learn a novel visuo-postural co-ordination task. DESIGN: A prospective design, 2 group by 1 treatment (4 practice blocks). SUBJECTS: Ten patients with multiple sclerosis diagnosed with cerebellar ataxia and 10 age-matched healthy controls. METHODS: Participants stood over a dual force platform (ERBE Balance System) and performed visually guided lateral weight-shifting movements. The task required subjects to gradually transfer weight between sides while maintaining each foot's force vector within visually specified force constraints ranging from 0% to 100% of bodyweight with maximum allowed variation set to +/-20%. The time required to complete the task and the number of spatial errors (noted each time the foot's vector exceeded the +/-20% force constraint) were recorded. Training consisted of 3 blocks of 5 trials separated by 1-minute intervals and followed by 5 retention trials. RESULTS AND CONCLUSION: Statistics revealed a significant decrease in movement time and spatial errors across trial blocks in both groups; however, the group with multiple sclerosis showed a limited and slower rate of performance improvement characterized by increased within- and between-subject variability. These findings may have important implications in the design of rehabilitation protocols for improving motor skill performance in adults with multiple sclerosis.

Animal models of central nervous system immune-mediated diseases: therapeutic interventions with bioactive peptides and mimetics.

Experimental allergic encephalomyelitis (EAE) is a T helper 1 (Th1) mediated autoimmune disease and the principal animal model for multiple sclerosis (MS). Like MS, EAE is characterized by a coordinated inflammatory attack on the myelin sheath in the central nervous system (CNS), with damage to axons. No matter whether the ideal animal model is not yet available, much knowledge concerning the pathogenesis of MS has been achieved through studies on EAE. Dissecting the underlying immune mechanisms provided recognition of several myelin antigens that are vulnerable in autoimmune attack. The beneficial effect and the mechanism of action of a number of the currently used immunomodulating agents in MS therapy were first indicated in EAE. Altered peptide ligands (APL) can modulate T-cell responses to native peptide antigens implicated in the pathogenesis of autoimmune diseases such as MS and EAE. However, peptide therapy is hindered due to the sensitivity of peptides to proteolytic enzymes as well as due to some immune-mediated side effects. A number of cyclic myelin peptide analogs seem to be potential candidates in maintaining the biological function of the original peptide and effective in controlling inflammation in EAE. Additional data regarding the immunomodulating and neuroprotective effect of these much promising agents is required. Based on the data from studies on EAE models, clinical trials should also be designed in order to elucidate the impact of such APL-induced immune responses in MS disease activity. These clinical trials should carefully incorporate monitoring of both clinical, neuroimaging and immunological parameters.