Patient reported outcomes in a secondary progressive MS cohort related to cognition, MRI and physical outcomes.

Background: Patient-reported outcomes (PROs) are increasingly being used as outcomes in secondary progressive multiple sclerosis (SPMS) trials. We examined how PROs reflect disease burden in SPMS.

Methods: In this observational prospective study, 65 SPMS patients were examined by five different PROs (Fatigue Scale Motor Cognition (FSMC), Multiple Sclerosis Impact Scale version 2 (MSIS-29v2), 36-Item Short Form Health Survey version 2 (SF-36v2), EQ-5D-5L and Work Productivity and Activity Impairment Questionnaire: Multiple Sclerosis version 2.

Dimethyl fumarate decreases neurofilament light chain in CSF and blood of treatment naïve relapsing MS patients.

Objectives: In a prospective phase IV trial of the first-line oral treatment dimethyl fumarate (DMF), we examined dynamics of neurofilament light (NFL) chain in serum, plasma and cerebrospinal fluid (CSF) samples collected over 12 months from relapsing-remitting multiple sclerosis (RRMS) patients. NFL changes were related to disease activity.

Methods: We examined NFL levels by single-molecule array in 88 CSF, 348 plasma and 131 sera from treatment-naïve RRMS patients (n=52), healthy controls (n=23) and a placebo group matched by age, sex and NFL (n=52).

Predictors of treatment outcome in patients with paediatric onset multiple sclerosis.

Background: Disease-modifying therapies (DMT) are increasingly used for children with multiple sclerosis (MS) even though most double-blinded randomized controlled trials evaluating efficacy, safety and dosing strategy of a specific drug have included adults.

Objective: To investigate predictors of treatment outcomes in patients with paediatric onset MS treated with DMTs.

Methods: Prospective cohort study from the nationwide Danish Multiple Sclerosis Registry including all patients with a MS diagnosis who initiated treatment with an approved DMT before the age of 18 ( = 137) and followed until their 25th birthday.

Reliability and Validity of a Danish Version of the Multiple Sclerosis Neuropsychological Screening Questionnaire.

Background: More than half of all patients with multiple sclerosis (MS) acquire cognitive impairment as part of their disease progression. Because cognitive dysfunction adds substantially to disability and coping strategies, a cost-effective screening tool is needed for cognitive impairment. The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) has previously shown good validity in American, Argentinean, and Dutch MS cohorts.

The six-spot-step test - a new method for monitoring walking ability in patients with chronic inflammatory polyneuropathy.

The aim of this study was to evaluate whether the six-spot-step test (SSST) is more suitable for monitoring walking ability in patients with chronic inflammatory polyneuropathy than the timed 25-foot-walking test (T25FW). In the SSST, participants have to walk as quickly as possible across a field measuring 1 × 5 m, while kicking blocks out of five circles on the floor. Sixty-two patients and 61 controls performed the SSST and T25FW.

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.

[Diagnosis and treatment of neuromyelitis optica].

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease characterized by antibodies against aquaporin-4 in up to 80% of the cases and even less in the NMO spectrum disorders, which may be difficult to distinguish from early multiple sclerosis. While immunosuppressive therapy should be introduced in definite NMO, treatment strategies of NMO spectrum disorders are less clearly defined. Here, we review the current guidelines for treatment of NMO and NMO spectrum disorders in the light of two cases, and suggest a practical approach to the management of these disorders.

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).

Recurrence or rebound of clinical relapses after discontinuation of natalizumab therapy in highly active MS patients.

A number of studies have reported flare-up of multiple sclerosis (MS) disease activity after cessation of natalizumab, increasing to a level beyond the pre-natalizumab treatment level. Our aim was to describe the development in clinical disease activity following cessation of natalizumab therapy in a large unselected cohort of highly active patients. We studied 375 highly active patients who had suffered at least two significant relapses within 1 year or three relapses within 2 years, or had been treated with mitoxantrone for highly active disease.

4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review.

This systematic review summarizes the existing evidence on the effect of 4-aminopyridine (4-AP) as a symptomatic treatment of decreased walking capacity in patients with multiple sclerosis (MS) when administered as an immediate release compound and a slow release compound. It summarizes existing evidence on the basic mechanisms of 4-AP from experimental studies and evidence on the clinical use of the compound. A systematic literature search was conducted of the following databases: PubMed and EMBASE.

Effects of early treatment with glatiramer acetate in patients with clinically isolated syndrome.

Background: The placebo-controlled phase of the PreCISe study showed that glatiramer acetate delayed onset of clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndrome and brain lesions on MRI.

Objective: To compare the effects of early versus delayed glatiramer acetate treatment in the open-label phase of PreCISe.

Methods: Patients with a clinically isolated syndrome suggestive of MS with unifocal manifestation and ≥2 T2-weighted brain lesions were randomized to receive glatiramer acetate 20 mg/d (early-treatment, n=198) or placebo (delayed-treatment, n=211) for 36 months or until conversion to CDMS, followed by open-label glatiramer acetate treatment for two years.

Progression and CSF Inflammation after Eradication of Oligoclonal Bands in an MS Patient Treated with Allogeneic Hematopoietic Cell Transplantation for Follicular Lymphoma.

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) has been proposed as treatment for multiple sclerosis (MS) and other autoimmune diseases.

Aims: To describe the effects of allo-HCT on the course of MS in a 49-year-old woman with longstanding progressive MS who was treated with allo-HCT for follicular lymphoma.

Methods: Non-myeloablative conditioning allo-HCT, examination for IgG oligoclonal bands and measurement of CXCL13 and matrix metalloproteinase-9 (MMP-9) concentration in the cerebrospinal fluid (CSF).

[Aminopyridines for symptomatic treatment of multiple sclerosis].

3,4-diaminopyridine (DAP) and 4-aminopyridine (AP) block potassium channels and can improve action potentials in demyelinated nerve fibres. We identified ten randomised placebo-controlled trials investigating AP/DAP as symptomatic treatment in multiple sclerosis. There is evidence that AP and DAP improve muscle strength in the lower extremities and that AP increases walking speed, and it might improve Expanded Disability Status Scale scores, spasticity and fatigue.

Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring.

Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy.

Methylprednisolone in combination with interferon beta-1a for relapsing-remitting multiple sclerosis (MECOMBIN study): a multicentre, double-blind, randomised, placebo-controlled, parallel-group trial.

Background: Interferon beta is commonly used to treat patients with relapsing-remitting multiple sclerosis; however, the treatment is only partially effective in reducing relapses and progression of disability. Corticosteroids are used to treat relapses in patients with multiple sclerosis. We therefore aimed to investigate the combination of cyclic methylprednisolone and interferon beta for the treatment of relapsing-remitting multiple sclerosis.

Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.

Background: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis.

Methods: In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis.

Methylprednisolone does not restore biological response in multiple sclerosis patients with neutralizing antibodies against interferon-β.

Background And Purpose: Neutralizing antibodies (NAbs) appearing during treatment with Interferon-beta (IFN-beta) reduce or abolish bioactivity and therapeutic efficacy. Initial combination therapy with methylprednisolone (MP) may reduce the frequency of NAb positive patients. We hypothesized that MP treatment might also reduce NAb levels and re-establish IFN-beta bioactivity in patients already NAb+, who discontinue IFN-beta therapy.

Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis.

Background: It is unknown whether immunosuppression of patients who have developed interferon-beta (IFN-beta) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood.

Objective: We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-beta bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-beta.

Methods: We included 13 patients with MS with NAbs and a low IFN-beta bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial.

[Magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis].

The use of MRI in MS diagnosis and follow-up is reviewed. The acquirements to the MRI protocol given by the revised McDonald diagnostic criteria are discussed.

[Is "quality of life" a relevant goal in clinical studies of rehabilitation?].

By consensus and in accordance with the WHO, the relevant outcomes of rehabilitation are "function" and "social participation". Nevertheless, most physicians will agree that improved Quality of Life (QoL) is the ultimate goal of medicine. Although many well-validated health-related QoL instruments are available, these are generally flawed due to considerable redundancy and lack of consistent responsiveness.

[Diagnosis of multiple sclerosis: revision of the McDonald criteria].

The 2005 revision of the McDonald diagnostic criteria for multiple sclerosis is reviewed. A standard clinical approach to the diagnosis of multiple sclerosis, including the use of a standard MRI protocol, VEP, CSF evaluation and other paraclinical tests is suggested.