Background/Aims: To measure the Timed Up and Go (TUG), imagined TUG (iTUG), and the difference of time between these two tests (delta time) in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and 20 healthy age-matched controls and to examine whether an association with cognitive functions, motor impairment, and behavioral changes can be determined. Methods: The mean ± SD of TUG, iTUG and delta time were used as outcomes. Spatiotemporal gait parameters were recorded by a 12-camera optoelectronic system during straight walking at usual self-selected speed. Cognitive functions were assessed by a standardized neuropsychological examination. Results: Patients performed the TUG slower than the controls (10.00 ± 1.70 s vs. 8.71 ± 1.04 s, p = 0.01, respectively). The TUG was correlated with gait parameters, cognitive functions, and behavior, whereas delta time was correlated only with cognitive functions. Conclusion: TUG represents an interesting test to reveal subtle deficits in RRMS patients with low disability and is related to motor, cognitive, and behavioral functioning. Combining with the TUG, delta time could easily give additional information on specific cognitive functions in the assessment of patients with RRMS.

Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent. They can be the immediate cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. Autoantibodies are often considered useful biomarkers for the improvement of diagnostic accuracy, for the staging of disease progression or for the follow up of a biological response to a therapeutic intervention. The purpose of this article is to review the autoantibodies that are available to investigate immune-mediated neurological conditions. The detection of some of these autoantibodies may help the clinician to establish a definite diagnosis which may further facilitate the therapeutic decision.

Mulltiple sclerosis and pregnancy Multiple sclerosis (MS) is diagnosed between the second and fourth decade. More than 2/3 of patients are women and are often in childbearing age. We may ask two main questions: Which implication of pregnancy on the evolution of MS has to be considered ? Which influence of MS on the pregnancy is expected? In other words could the pregnancy worsen MS and could MS represent specific risks for the pregnancy?

Neuromyelitis optica (NMO) or Devic's syndrome is a severe demyelinating disease of the central nervous system involving preferentially the optic nerves and the spinal cord. Until recently, NMO was described as an atypical multiple sclerosis IMS), characterized by an unusual clinical presentation, a severe relapsing progression, and a poor response to usual MS treatments. The recent discovery of the so-called NMO-IgG, a highly NMO-specific antibody directed against the blood brain barrier and the aquaporine-4, allowed to refine diagnostic criteria and to classify this disease as an autoimmune channelopathy. According to this recent advance, early diagnostic and specific treatment targeting the humoral response should be considered.

We investigated whether glatiramer acetate (GA) treatment may affect Th1 differentiation at various T-cell maturation stages. Specifically, we analyzed the effect of in vivo GA treatment on intracellular synthesis of IL-2 and TNF-α by naive, memory and effector CD4+ and CD8+ T cells by five-colour flow cytometry. Our data indicate that GA treatment downregulates/normalizes an accelerated Th1 differentiation of CD4+ T cells in RRMS patients at all stages of T-cell maturation. Most notably, we conclude that, by altering naive, unprimed CD4+ T cells, GA treatment appears to affect T-cell differentiation, at least in part, in an antigen-independent manner.

An International Working Group for Treatment Optimization in MS met to recommend evidence‐based therapeutic options for the management of suboptimal responses or intolerable side‐effects in patients treated with disease‐modifying drugs (DMDs) for multiple sclerosis (MS). Several DMDs are now available for the treatment of MS that have been shown to alter the clinical course of the disease by decreasing disease activity and delaying the progression of disability. Nevertheless, many patients continue to experience disease activity whilst on treatment, and recommendations have been made on how the success of therapy in an individual patient can be assessed. However, even after having identified criteria for a suboptimal response to current treatments, clinicians require guidance on how to improve the outcomes. This report summarizes the conclusions from a workshop at which this issue was addressed. We suggest treatment pathways for optimizing therapy for those patients with suboptimal responses to DMDs, and therapeutic options for patients with unacceptable side‐effects on their current therapy.

The updated recommendations presented here reflect new developments in the diagnostic work-up and immunotherapy of multiple sclerosis (MS) as well as optimization of medical care for MS patients. Monoclonal antibodies provide considerable improvement of treatment, but their use in basic therapy is restricted by their side effect profile. Thus, for the time being, natalizumab is only approved for monotherapy after basic treatment has failed or for rapidly progressive relapsing-remitting MS. In contrast, long-term data on recombinant beta-interferons and glatiramer acetate (Copaxone((R))) show that even after several years no unexpected side effects occur and that a prolonged therapeutic effect can be assumed which correlates with the dose or frequency of treatment. Recently IFN-beta 1b (Betaferon((R))) was approved for prophylactic treatment after the first attack (clinically isolated syndrome, CIS). During treatment with beta-interferons, neutralizing antibodies can emerge with possible loss of effectivity. In contrast, antibodies play no role in treatment with glatiramer acetate. During or after therapy with mitoxantrone, serious side effects (cardiomyopathy, acute myeloid leukemia) appeared in 0.2-0.4% of cases. Plasmapheresis is limited to individual curative attempts in escalating therapy of a severe attack. According to the revised McDonald criteria, the diagnosis of MS can be made as early as the occurrence of the first attack (CIS). Recommendations for optimized care of MS patients are also new, thus implementing a resolution of the European Parliament.

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system that leads to a progressive deterioration of the neurological functions. The concept of primary myelin and oligodendrocyte damage with axon sparing (axon-myelin dissociation) has been recently reconsidered with the demonstration that neuro-axonal lesions are an early phenomenon, linked to the inflammatory process, observed outside demyelinated areas, and correlated with the progression of the disease. Neurodegeneration in MS, long considered as a late process following recurrent episodes of demyelination, is now accepted as an early and major trigger of MS pathogenesis on which research should focus in the