Time matters: Early-phase multiple sclerosis is accompanied by considerable impairments across multiple domains.

Impairments across multiple domains are a disabling consequence of multiple sclerosis (MS). Originating from preventive medical strategies, the "time matters"-perspective has become a focal point when treating MS. In particular, early detection of physical and cognitive deficits, along with deficits in patient-reported outcomes seems crucial to further optimize both pharmacological and non-pharmacological MS treatment strategies. Therefore, this topical review investigates the level of impairments across multiple domains (physical function, cognitive function, and patient-reported outcomes) in the early stage of MS (⩽5 years since diagnosis, including clinically isolated syndrome (CIS)), when compared to matched healthy controls. Even at early disease stages, studies show impairments corresponding to 8%-34% and small-to-large numerical effect sizes (0.35-2.85) in MS/CIS patients across domains. This evidence call for early screening programs along with early interventions targeting the multiple impaired domains. This further highlights the importance of preventive initiatives preserving and/or restoring physical and cognitive reserve capacity if possible.

The association between heart diseases and suicide: a nationwide cohort study.

OBJECTIVE: To assess the association between specific heart diseases and suicide. DESIGN: Nationwide retrospective cohort study. PARTICIPANTS: A total of 7 298 002 individuals (3 640 632 males and 3 657 370 females) aged ≥15 years and living in Denmark during 1980-2016. MAIN OUTCOME MEASURES: Incidence rate ratios (IRR) with 95% confidence intervals. In multivariate analysis, we adjust for sex, period, age group, living status, income level, Charlson Comorbidity Index, psychiatric disorders prior to heart disease and self-harm prior to heart disease. RESULTS: Excess suicide rate ratios were found for following disorders: heart failure (IRR: 1.48; 95% CI: 1.38-1.58); cardiomyopathy (IRR: 1.41; 95% CI: 1.16-1.70); acute myocardial infarction (IRR: 1.28; 95% CI: 1.21-1.36); cardiac arrest with successful resuscitation (IRR: 4.75; 95% CI: 3.57-6.33); atrial fibrillation and flutter (IRR: 1.42; 95% CI: 1.32-1.52); angina pectoris (IRR: 1.19; 95% CI: 1.12-1.26); and ventricular tachycardia (IRR: 1.53; 95% CI: 1.20-1.94). A higher rate of suicide was noted during the first 6 months after the diagnosis of heart failure (IRR: 2.38; 95% CI: 2.04-2.79); acute myocardial infarction (IRR: 2.24; 95% CI: 1.89-2.66); atrial fibrillation and flutter (IRR: 2.70; 95% CI: 2.30-3.18); and angina pectoris (IRR: 1.83; 95% CI: 1.53-2.19) when compared to later. CONCLUSION: Several specific disorders were found to be associated with elevated rates of suicide. Additionally, we found temporal associations with higher suicide rates in the first time after diagnosis. Our results underscore the importance of being attentive towards psychological distress in individuals with heart disease.

Hospital ethics reflection groups: a learning and development resource for clinical practice.

BACKGROUND: An ethics reflection group (ERG) is one of a number of ethics support services developed to better handle ethical challenges in healthcare. The aim of this article is to evaluate the significance of ERGs in psychiatric and general hospital departments in Denmark. METHODS: This is a qualitative action research study, including systematic text condensation of 28 individual interviews and 4 focus groups with clinicians, ethics facilitators and ward managers. Short written descriptions of the ethical challenges presented in the ERGs also informed the analysis of significance. RESULTS: A recurring ethical challenge for clinicians, in a total of 63 cases described and assessed in 3 ethical reflection groups, is to strike a balance between respect for patient autonomy, paternalistic responsibility, professional responsibilities and institutional values. Both in psychiatric and general hospital departments, the study participants report a positive impact of ERG, which can be divided into three categories: 1) Significance for patients, 2) Significance for clinicians, and 3) Significance for ward managers. In wards characterized by short-time patient admissions, the cases assessed were retrospective and the beneficiaries of improved dialogue mainly future patients rather than the patients discussed in the specific ethical challenge presented. In wards with longer admissions, the patients concerned also benefitted from the dialogue in the ERG. CONCLUSION: This study indicates a positive significance and impact of ERGs; constituting an interdisciplinary learning resource for clinicians, creating significance for themselves, the ward managers and the organization. By introducing specific examples, this study indicates that ERGs have significance for the patients discussed in the specific ethical challenge, but mostly indirectly through learning among clinicians and development of clinical practice. More research is needed to further investigate the impact of ERGs seen from the perspectives of patients and relatives.

Risk factors of major infections in schizophrenia. A nationwide Danish register study.

BACKGROUND: Risk of infections is elevated in patients with schizophrenia. Predicting their occurrence is essential, as infections in this group of patients are associated with prolonged hospital admission and increased mortality. The objective of the current investigation was to identify the potential risk factors of major infection after diagnosis with schizophrenia. METHODS: This national prospective observational cohort study included 7788 people with schizophrenia born in Denmark between 1975 and 1990. Socio-demographic, psychiatric and health related data were obtained from Danish national registers. The Cox regression model was used for data analyses. Crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95%CIs) are presented. RESULTS: The most significant risk factors associated with the development of major infections included young age, female gender, medical comorbidity and substance abuse. A history of treatment with antipsychotics preceding the diagnosis was negatively associated with such morbidity. CONCLUSION: This study reports several factors that might increase the risk of infections in individuals with schizophrenia. Early intervention towards infections should be considered in the subpopulation of schizophrenia patients who are at increased risk of infections.

Prevalence of depressive disorder among patients with fibromyalgia: Systematic review and meta-analysis.

BACKGROUND: It is acknowledged that fibromyalgia (FM) as a medical (rheumatological) disorder and major depressive disorder (MDD) as a mental disorder often co-occurs, but the inconsistency is prevailing at study-level and no overall estimate of the co-occurrence exist. AIMS: This systematic review and meta-analysis aimed to estimate the overall point- and life-time prevalence of MDD among FM patients based on structured clinical interviews (SCI); and to estimate the point-prevalence of MDD among FM patients based on screening symptom scales (SSS). METHOD: The electronical databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO were searched for papers that reported on prevalence of MDD among FM patients. Eligible studies were included in a random effects meta-analysis pooling the prevalence of depression. RESULTS: The literature search identified 11 eligible studies for the meta-analysis. For SCI, the overall pooled point-prevalence (PP) was 25% (95% CI 19 to 31%), and life-time prevalence (LP) was 65% (95% CI 59 to 71%). When estimating the PP with self-administered SSS the overall pooled PP was 45% (95% CI 32 to 59%), and a single clinician-administered SSS yielded a PP of 23% (95% CI 10 to 41%). There was low inconsistency for the SCI and high inconsistency for the SSS. CONCLUSION: One fourth of all FM patients had MDD, and more than half experienced MDD during their life-time according to clinician-administered instruments. Prevalence of MDD was almost twice as high when using self-administered symptom scales and may be likely to overestimate the co-occurrence.

Ethical challenges assessed in the clinical ethics Committee of Psychiatry in the region of Southern Denmark in 2010-2015: a qualitative content analyses.

BACKGROUND: The aim of this article is to give more insight into what ethical challenges clinicians in mental healthcare experience and discuss with a Clinical Ethics Committee in psychiatry in the Region of Southern Denmark. Ethical considerations are an important part of the daily decision-making processes and thereby for the quality of care in mental healthcare. However, such ethical challenges have been given little systematic attention - both in research and in practices. METHODS: A qualitative content analysis of 55 written case-reports from the Clinical Ethics Committee. The Committee offers clinicians in mental healthcare structured ethical analyses of ethical challenges and makes a thorough written case-report. RESULTS: The ethical challenges are grouped into three overarching topics: 1. Clinicians and their relation to patients and relatives. 2. Clinicians and institutional aspects of mental healthcare 3. Clinicians and mental healthcare in a wider social context. Through presentation of illustrative examples the complexity of daily clinical life in mental healthcare becomes evident, as well as typical interests, values and arguments. CONCLUSIONS: This qualitative study indicates that difficult ethical challenges are an inherent part of mental healthcare that requires time, space and competence to be dealt with adequately.

Ten-year prevalence of mental disorders in patients presenting with chronic pain in secondary care: A register linkage cohort study.

BACKGROUND: Prevalence rates of mental disorders in patients with chronic pain vary and may be overestimated when assessed by screening instruments only. Objectives were to estimate the 10-year prevalence of different mental disorders diagnosed by psychiatrists in patients with chronic pain compared with the Danish general population. METHODS: Patients (n = 7197) consulted in the interdisciplinary Pain Clinic South at Odense University Hospital, Denmark, from 2005 to 2015 were included. Data from the Pain Clinic were linked to the Danish National Patient Register-Psychiatry and the Danish Civil Registration System. Age and gender standardized prevalence ratios (SPR) were calculated. RESULTS: In all, 17.8% of patients with chronic pain had been diagnosed with a mental disorder. The most frequent diagnoses were adjustment disorders (subcategory of anxiety disorders) (8.9%), depression (6.1%), personality disorders (3.8%), and substance abuse disorders (3.5%). Women and men with chronic pain had higher rates of anxiety disorders (SPR 3.1; 95% CI 2.9-3.4) and depression (SPR 2.5; 95% CI 2.3-2.8), whereas men had higher rates of substance abuse disorders (SPR 1.6; 95% CI 1.3-1.9) than found for the general population. CONCLUSIONS: Although depression and anxiety were noted more frequently among patients with chronic pain than the general population, prevalence rates were lower than previously reported. The most frequent diagnoses were adjustment disorders. SIGNIFICANCE: Prevalence rates of anxiety and depression diagnosed by psychiatrists in patients with chronic pain were found to be lower than previous findings using screening instruments. Adjustment disorders were the most frequent disorders diagnosed, as this study is the first to investigate.

Performed and perceived walking ability in relation to the Expanded Disability Status Scale in persons with multiple sclerosis.

BACKGROUND: The severity of walking impairment in persons with multiple sclerosis (pwMS) at different levels on the expanded disability status scale (EDSS) is unclear. Furthermore, it is unclear if the EDSS is differently related to performed- and perceived walking capacity tests. AIMS: To quantify walking impairment and perceived impact of MS on walking according to EDSS scores and to examine the relations between these parameters in pwMS. METHODS: EDSS was collected by neurologists and walking was assessed by the timed 25ft walk test (T25FWT), two minute walk test (2MWT), six minute walk test (6MWT) and the 12-item MS walking scale (MSWS-12) in 474 PwMS with mild (EDSS 1-4: n=200) to moderate (EDSS 4.5-6.5: n=274) MS. Magnitude of walking impairment was calculated and related to EDSS. RESULTS: Compared to predicted values in healthy controls, walking speed was reduced by 41.5±25.8% in the 6MWT for the total MS group and by 21.8±20.2% and 55.8±19.1% in the mild and moderate MS subgroups, respectively. The EDSS score showed the strongest relationship to the 2MWT and the 6MWT in the total MS group (r=-0.76, p<0.0001), to the MSWS-12 score in the mild MS group (r=0.56, p<0.0001), and to the 2MWT in the moderate MS group (r=-0.50, p<0.0001). CONCLUSION: In pwMS (EDSS scores 1-6.5), walking speed is on average reduced by ~40% when compared to predicted values in healthy controls, and impairments are already present at early disease stages, suggesting early initiation of rehabilitation. The 2MWT and 6MWT show the strongest relationship to EDSS, but the MSWS-12 identify impairments more gradually at low EDSS scores.

Cerebrospinal fluid biomarkers for Parkinson's disease - a systematic review.

Diagnosis of Parkinson's disease (PD) relies on clinical history and physical examination, but misdiagnosis is common in early stages. Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments. Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid, associated with the pathophysiology or pathogenesis of PD. This systematic review includes cerebrospinal fluid biomarker studies focusing on different disease pathways: oxidative stress, neuroinflammation, lysosomal dysfunction and proteins involved in PD and other neurodegenerative disorders, focusing on four clinical domains: their ability to (1) distinguish PD from healthy subjects and other neurodegenerative disorders as well as their relation to (2) disease duration after initial diagnosis, (3) severity of disease (motor symptoms) and (4) cognitive dysfunction. Oligomeric alpha-synuclein might be helpful in the separation of PD from controls. Through metabolomics, changes in purine and tryptophan metabolism have been discovered in patients with PD. Neurofilament light chain (NfL) has a significant role in distinguishing PD from other neurodegenerative diseases. Several oxidative stress markers are related to disease severity, with the antioxidant urate also having a prognostic value in terms of disease severity. Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD. In the future, larger longitudinal studies, corroborating previous research on viable biomarker candidates or using metabolomics identifying a vast amount of potential biomarkers, could be a good approach.

Effect of slow release-Fampridine on muscle strength, rate of force development, functional capacity and cognitive function in an enriched population of MS patients. A randomized, double blind, placebo controlled study.

DESIGN: This study was conducted as a randomized, double blind, placebo-controlled parallel group trial preceded by open label enrichment phase. OBJECTIVES: The objectives of this study were 1) to examine the effect of SR-Fampridine treatment on muscle strength in terms of maximal voluntary contraction (MVC) and rate of force development (RFD) of the lower extremities and 2) to replicate previously published data on the effect of slow release-Fampridine (SR-Fampridine) on the functional capacity of the lower limbs, the upper limb and cognitive function, in persons with multiple sclerosis (pwMS). METHODS: Previously identified responders to SR-Fampridine were randomized to SR- Fampridine or placebo treatment for four weeks. On days 0 and 26-28 participants underwent testing by isokinetic dynamometry, Nine Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Six Spot Step Test (SSST), Timed 25 Foot Walk Test (T25FW) and 5-Times Sit-to-Stand (5-STS). RESULTS: A statistical significant effect of SR-Fampridine on MVC was demonstrated during knee extension, knee flexion and hip flexion of the weakest leg, as well as on RFD during knee extension and knee flexion of the weakest leg. Furthermore, a significant effect of SR-Fampridine on T25FW, SSST and 5-STS was demonstrated. CONCLUSION: Gold standard dynamometry assessment of muscle strength showed improved MVC and RFD in persons with MS treated with SR-Fampridine compared to placebo. Furthermore, previous findings on the effects of SR-Fampridine on functional capacity of the lower limbs were replicated. ClinicalTrials.gov identifier: NCT01656148.

Psychosocial therapy and causes of death after deliberate self-harm: a register-based, nationwide multicentre study using propensity score matching.

BACKGROUND: Psychosocial therapy after deliberate self-harm might be associated with reduced risk of specific causes of death. METHOD: In this matched cohort study, we included patients, who after an episode of deliberate self-harm received psychosocial therapy at a Suicide Prevention Clinic in Denmark between 1992 and 2010. We used propensity score matching in a 1:3 ratio to select a comparison group from 59 046 individuals who received standard care. National Danish registers supplied data on specific causes of death over a 20-year follow-up period. RESULTS: At the end of follow-up, 391 (6.9%) of 5678 patients in the psychosocial therapy group had died, compared with 1736 (10.2%) of 17 034 patients in the matched comparison group. Lower odds ratios of dying by mental or behavioural disorders [0.54, 95% confidence interval (CI) 0.37-0.79], alcohol-related causes (0.63, 95% CI 0.50-0.80) and other diseases and medical conditions (0.61, 95% CI 0.49-0.77) were noted in the psychosocial therapy group. Also, we found a reduced risk of dying by suicide as well as other external causes, however, not by neoplasms and circulatory system diseases. Numbers needed to treat were 212.9 (95% CI 139.5-448.4) for mental or behavioural disorders as a cause of death, 111.1 (95% CI 79.2-210.5) for alcohol-related causes and 96.8 (95% CI 69.1-161.8) for other diseases and medical conditions. CONCLUSIONS: Our findings indicate that psychosocial therapy after deliberate self-harm might reduce long-term risk of death from select medical conditions and external causes. These promising results should be tested in a randomized design.

Distribution-based estimates of minimum clinically important difference in cognition, arm function and lower body function after slow release-fampridine treatment of patients with multiple sclerosis.

OBJECTIVE: To provide distribution-based estimates of the minimal clinical important difference (MCID) after slow release fampridine treatment on cognition and functional capacity in people with MS (PwMS). METHOD: MCID values were determined after SR-Fampridine treatment in 105 PwMS. Testing included the Timed 25 Foot Walk (T25FW), the Symbol Digit Modalities Test (SDMT), the Six Spot Step Test (SSST), the 9-Hole-Peg-Test (9-HPT), and the 5-Time-Sit-To-Stand test (5-STS). RESULTS: MCID values: T25FW 17.8% (9.1-17.8), SDMT 17.1% (9.2-17.1), SSST 16.7% (8.5-16.7), 9-HPT 15.3% (0-15.3), and 5-STS 34.6% (16.9-34.6). CONCLUSION: This study presents distribution-based estimates of MCID values for the SSST, the 9-HPT, and the 5-STS and confirms MCID estimates for the T25FW and the SDMT.

Minocycline added to subcutaneous interferon ß-1a in multiple sclerosis: randomized RECYCLINE study.

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) ß-1a therapy. METHODS: This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN ß-1a 44 µg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN ß-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN ß-1a therapy.

Genetic analysis of the isolated Faroe Islands reveals SORCS3 as a potential multiple sclerosis risk gene.

BACKGROUND: In search of the missing heritability in multiple sclerosis (MS), additional approaches adding to the genetic discoveries of large genome-wide association studies are warranted. OBJECTIVE: The objective of this research paper is to search for rare genetic MS risk variants in the genetically homogenous population of the isolated Faroe Islands. METHODS: Twenty-nine Faroese MS cases and 28 controls were genotyped with the HumanOmniExpressExome-chip. The individuals make up 1596 pair-combinations in which we searched for identical-by-descent shared segments using the PLINK-program. RESULTS: A segment spanning 63 SNPs with excess case-case-pair sharing was identified (0.00173 < p > 0.00212). A haplotype consisting of 42 of the 63 identified SNPs which spanned the entire the Sortilin-related vacuolar protein sorting 10 domain containing receptor 3 (SORCS3) gene had a carrier frequency of 0.34 in cases but was not present in any controls (p = 0.0008). CONCLUSION: This study revealed an oversharing in case-case-pairs of a segment spanning 63 SNPs and the entire SORCS3. While not previously associated with MS, SORCS3 appears to be important in neuronal plasticity through its binding of neurotrophin factors and involvement in glutamate homeostasis. Although additional work is needed to scrutinise the genetic effect of the SORCS3-covering haplotype, this study suggests that SORCS3 may also be important in MS pathogenesis.

Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis.

Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying attention to the medical treatments of the patient. At present, PwMS are routinely enrolled in immunosuppressive medication, but exercise-induced immunomodulatory effects have not been investigated under these circumstances. The objective of this study was to investigate the acute and chronic cytokines responses to resistance exercise training in medicated PwMS. Thirty-five people with relapsing-remitting multiple sclerosis (MS) treated with interferon (IFN)-ß, were randomized to a 24-week progressive resistance training (PRT) or control group. Plasma interleukin (IL)-1ß, IL-4, IL-10, IL-17F, IL-23, tumor necrosis factor-α and IFN-γ were measured before and after 24 weeks of PRT. The acute effect was evaluated following standardized single-bout resistance exercise in the untrained and the trained state. No changes were observed in resting cytokine levels after PRT. However, an indication of reduced IL-17F secretion following resistance exercise was observed in the trained compared with the untrained state. This study suggests little acute and chronic effect of PRT on cytokine levels in IFN-treated PwMS.

The effect of exercise on depressive symptoms in multiple sclerosis based on a meta-analysis and critical review of the literature.

BACKGROUND AND PURPOSE: The purpose of this study was to perform a systematic review of the literature on the effects of exercise on depressive symptoms in patients with multiple sclerosis (MS), as well as to apply meta-analytical procedures to the results. METHODS: A systematic search covering eight databases was conducted. The included studies were randomized controlled trials applied to people with definite MS who completed a structured exercise intervention which were compared to any comparator, including other forms of exercise. The outcomes included a primary measure of depression/depressive symptoms or an instrument with a clearly defined depression subscale. RESULTS: Fifteen randomized controlled trial studies were identified including a total of 331 exercising subjects and 260 controls. The average Physiotherapy Evidence Database (PEDro) score was 5.6 ± 1.3 points. Only one study applied depressive symptoms as the primary outcome. Four studies showed positive effects of exercise on depressive symptoms. An in-depth analysis of the studies revealed that the baseline level of depressive symptoms, patient disability level, choice of depression instrument and exercise intensity may influence the results. The meta-analysis included 12 studies reflecting a total of 476 subjects. The standardized mean difference across studies was g = -0.37, 95% confidence interval (-0.56; -0.17), and the null hypothesis of homogeneity within the sample could not be rejected (Q = 12.05, df = 11, P = 0.36). DISCUSSION: Exercise may be a potential treatment to prevent or reduce depressive symptoms in individuals with MS, but existing studies do not allow solid conclusions. Future well-designed studies evaluating the effects of exercise on depressive symptoms and major depression disorder in MS are highly warranted.

High inbreeding in the Faroe Islands does not appear to constitute a risk factor for multiple sclerosis.

BACKGROUND: Large population-based genome-wide association studies have identified several multiple sclerosis (MS) genetic risk variants, but the existing missing heritability warrants different strategies. Isolated populations offer an alternative way of searching for rare genetic variants and evaluating the possible role of consanguinity in the development of MS. Studies of consanguinity and MS risk have yielded conflicting results. OBJECTIVES: In this study we investigated the role of consanguinity on MS risk in the relatively isolated Faroe Islands, which have a presumed high level of inbreeding. METHODS: A total of 29 cases and 28 matched controls were genotyped and assessed for inbreeding coefficients, number of runs of homozygosity (ROH) at different lengths and observed number of homozygotes as measures of relatedness. Parametric and non-parametric statistical models were applied. RESULTS: Both cases and controls exhibited considerable relatedness demonstrated by very high inbreeding coefficients, large number of observed homozygotes and many long ROH. However, apart from the number of ROH ≥ 2.5 mega base pairs, no significant differences between the two groups were observed. CONCLUSIONS: Overall, no significant difference between cases and controls were found, indicating that consanguinity in itself does not appear to be an important risk factor for MS in the population of the Faroe Islands.

Changes in cognition, arm function and lower body function after slow-release Fampridine treatment.

OBJECTIVE: We aimed to evaluate the effect of slow-release (SR) Fampridine on multiple outcome measures reflecting different domains, and to compare the responsiveness of the Six Spot Step Test (SSST) and the Timed 25 Foot Walk (T25FW). METHODS: For this study 108 participants were included. On day 0 they were tested with the T25FW, the SSST, the 9-Hole Peg Test (9-HPT), the 5 Times Sit-To-Stand test (5-STS) and the Symbol Digit Modalities Test (SDMT). Four weeks of treatment with SR Fampridine 10 mg BID was commenced. Participants were tested again after 26-28 days of treatment. RESULTS: Mean changes observed were: SSST -3.4±6.4 s (p<0.001), T25FW -1.2±3.7 s (p<0.001), 9-HPT -1.2±6.0 s (p<0.001), 5- STS -3.4±7.2 s (p<0.001) and SDMT 1.4±4.8 a.u. (p=0.003). Change on the SSST differed significantly from T25FW (SSST 17.0±19.6% vs. T25FW 11.2±17.1%, p=0.0013). Some 48.6% were found to have a meaningful change on the SSST compared with 25.7% on the T25FW. The response to treatment with SR Fampridine did not correlate with age, sex, Expanded Disability Status Scale and disease duration. CONCLUSION: SR Fampridine treatment has significant effects on different domains including upper and lower body and cognition. Furthermore, the SSST is more responsive to the effect of SR Fampridine than is the T25FW. ClinicalTrials.gov identifier: NCT01656148.