Assessing hand motor function in chronic immune-mediated neuropathies: a proof-of-concept study using a data glove.

Background: Chronic immune-mediated neuropathies are clinically heterogeneous and require regular, objective, and multidimensional monitoring to individualize treatment. However, established outcome measures are insufficient regarding measurement quality criteria (e.g.

No evidence of disease activity status over 3 years in a real-world cohort of relapsing remitting MS patients in Germany.

Background: Over the last decade, therapy of relapsing remitting multiple sclerosis (RRMS) has evolved with the approval of several new treatment concepts. Thus, treatment goals have become more ambitious aiming at "no evidence of disease activity" (NEDA). As NEDA-3, this concept comprises freedom of clinical disease progression and relapses as well as inflammatory MRI activity.

The NRF2 pathway as potential biomarker for dimethyl fumarate treatment in multiple sclerosis.

Objective: Immunological studies have demonstrated a plethora of beneficial effects of dimethyl fumarate (DMF) on various cell types. However, the cellular and molecular targets are incompletely understood and response markers are scarce. Here, we focus on the relation between nuclear factor (erythroid-derived 2)-like 2 (NRF2) pathway induction under DMF therapy and the composition of the blood immune cell compartment and clinical efficacy in relapsing-remitting multiple sclerosis (MS) patients.

Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells.

To date, the intracellular signaling pathways involved in dendritic cell (DC) function are poorly understood. The antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been shown to affect maturation, function, and subsequent DC-mediated T cell responses of murine and human DCs. In experimental autoimmune encephalomyelitis (EAE), as prototype animal model for a T helper cell-mediated autoimmune disease, antigen presentation, cytokine production, and costimulation by DCs play a major role.

Fingolimod effects in neuroinflammation: Regulation of astroglial glutamate transporters?

Fingolimod is an oral sphingosine-1-phosphate-receptor modulator which reduces the recirculation of immune cells and may also directly target glial cells. Here we investigate effects of fingolimod on expression of astroglial glutamate transporters under pro-inflammatory conditions. In astrocyte cell culture, the addition of pro-inflammatory cytokines led to a significant downregulation of glutamate transporters glutamate transporter-1 (slc1a2/SLC1A2) and glutamate aspartate transporter (slc1a3/SLC1A3) expression on the mRNA or protein level.

Retinal imaging and axonal degeneration in later onset multiple sclerosis.

Background: Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS typically affecting younger adults and resulting in neuro-axonal degeneration already at early stages of the disease. Less is known about the effects of a later disease onset (LOMS, onset >50years of age). Analysis of retinal layers by optical coherence tomography (OCT) is a non-invasive method to investigate retinal and neuro-axonal degeneration.

Cognitive functions over the course of 1 year in multiple sclerosis patients treated with disease modifying therapies.

Objectives: Disease-modifying therapies (DMTs) are applied to delay or prevent disease progression in multiple sclerosis (MS). While this has mostly been proven for physical symptoms, available studies regarding long-term effects of DMTs on cognitive functions are rare and sometimes inconsistent due to methodological shortcomings. Particularly in the case of fingolimod, comprehensive data on cognitive functions are not yet available.

Pivotal Role for CD16+ Monocytes in Immune Surveillance of the Central Nervous System.

Monocytes represent a heterogeneous population of primary immune effector cells. At least three different subsets can be distinguished based on expression of the low-affinity FcγRIII: CD14(++)CD16 -: classical monocytes, CD14(++)CD16(+) intermediate monocytes, and CD14(+)CD16 ++: non-classical monocytes. Whereas CD16 -: classical monocytes are considered key players in multiple sclerosis (MS), little is known on CD16(+) monocytes and how they contribute to the disease.

Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.

Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway.

Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life.

Baseline magnetic resonance imaging of the optic nerve provides limited predictive information on short-term recovery after acute optic neuritis.

Background: In acute optic neuritis, magnetic resonance imaging (MRI) may help to confirm the diagnosis as well as to exclude alternative diagnoses. Yet, little is known on the value of optic nerve imaging for predicting clinical symptoms or therapeutic outcome.

Purpose: To evaluate the benefit of optic nerve MRI for predicting response to appropriate therapy and recovery of visual acuity.

Interferon beta and vitamin D synergize to induce immunoregulatory receptors on peripheral blood monocytes of multiple sclerosis patients.

Immunoglobulin-like transcript (ILT) 3 and 4 are inhibitory receptors that modulate immune responses. Their expression has been reported to be affected by interferon, offering a possible mechanism by which this cytokine exerts its therapeutic effect in multiple sclerosis, a condition thought to involve excessive immune activity. To investigate this possibility, we measured expression of ILT3 and ILT4 on immune cells from multiple sclerosis patients, and in post-mortem brain tissue.

Demyelinating disease and anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies: a case report.

Background: Anti-N-methyl-D-aspartate receptor immunoglobulin G antibodies directed against the GluN1 subunit are considered highly specific for anti-N-methyl-D-aspartate receptor encephalitis, a severe clinical syndrome characterized by seizures, psychiatric symptoms, orofacial dyskinesia and autonomic dysfunction.

Case Presentation: Here we report a 33 year old Caucasian male patient with clinically definite multiple sclerosis who was found to be positive for anti-N-methyl-D-aspartate receptor antibodies. Rituximab therapy was initiated.

Increase of angiotensin II type 1 receptor auto-antibodies in Huntington's disease.

Background: In the recent years, a role of the immune system in Huntington's disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease.

Results: As compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease.

Patient preferences for disease-modifying drugs in multiple sclerosis therapy: a choice-based conjoint analysis.

Objectives: With an increasing number of disease-modifying treatments (DMTs) for multiple sclerosis (MS), patient preferences will gain importance in the decision-making process. We assessed patients' implicit preferences for oral versus parenteral DMTs and identified factors influencing patients' treatment preference.

Methods: Patients with relapsing-remitting MS (n = 156) completed a questionnaire assessing treatment preferences, whereby they had to decide between pairs of hypothetical treatment scenarios.

Neuromyelitis optica presenting with relapses under treatment with natalizumab: a case report.

Introduction: Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system. To date, optimal therapeutic approaches for neuromyelitis optica have yet to be defined. Natalizumab is highly effective in relapsing-remitting multiple sclerosis and might be considered as an option.

Visual search as a tool for a quick and reliable assessment of cognitive functions in patients with multiple sclerosis.

Background: Despite the high frequency of cognitive impairment in multiple sclerosis, its assessment has not gained entrance into clinical routine yet, due to lack of time-saving and suitable tests for patients with multiple sclerosis.

Objective: The aim of the study was to compare the paradigm of visual search with neuropsychological standard tests, in order to identify the test that discriminates best between patients with multiple sclerosis and healthy individuals concerning cognitive functions, without being susceptible to practice effects.

Methods: Patients with relapsing remitting multiple sclerosis (n = 38) and age-and gender-matched healthy individuals (n = 40) were tested with common neuropsychological tests and a computer-based visual search task, whereby a target stimulus has to be detected amongst distracting stimuli on a touch screen.

Immunological and clinical consequences of splenectomy in a multiple sclerosis patient treated with natalizumab.

Objective: Here we report a case of a splenectomized white woman with natalizumab-associated progressive multifocal leukoencephalopathy (PML), occurring as early as after 11 infusions and provide blood fluorescence-activated cell sorting (FACS) analyses before and after natalizumab treatment.

Design: This is a report of a single case with immunological studies.

Methods: Methods comprised neurologic examination, magnetic resonance imaging, and cerebrospinal fluid (CSF) studies as well as immune cell FACS analyses from blood.

T-cell response against varicella-zoster virus in fingolimod-treated MS patients.

Objective: To study the immune response against varicella-zoster virus (VZV) in patients with multiple sclerosis before and during fingolimod therapy.

Methods: The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in patients before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β-treated (n = 25) patients with multiple sclerosis, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.

Levetiracetam but not valproate inhibits function of CD8+ T lymphocytes.

Purpose: To further elucidate possible immune-modulatory effects of valproate (VPA) or levetiracetam (LEV), we investigated their influence on apoptosis and cytotoxic function of CD8+ T lymphocytes in humans.

Methods: In 15 healthy subjects (9 female (60%), 35.7±12.

Glatiramer acetate treatment normalizes deregulated microRNA expression in relapsing remitting multiple sclerosis.

The expression of selected microRNAs (miRNAs) known to be involved in the regulation of immune responses was analyzed in 74 patients with relapsing remitting multiple sclerosis (RRMS) and 32 healthy controls. Four miRNAs (miR-326, miR-155, miR-146a, miR-142-3p) were aberrantly expressed in peripheral blood mononuclear cells from RRMS patients compared to controls. Although expression of these selected miRNAs did not differ between treatment-naïve (n = 36) and interferon-beta treated RRMS patients (n = 18), expression of miR-146a and miR-142-3p was significantly lower in glatiramer acetate (GA) treated RRMS patients (n = 20) suggesting that GA, at least in part, restores the expression of deregulated miRNAs in MS.

Vascular pathology in multiple sclerosis: mind boosting or myth busting?

The investigation of central nervous system vascular changes in the pathophysiology of multiple sclerosis (MS) is a time-honored concept. Yet, recent reports on changes in venous cerebrospinal outflow, the advent of new magnetic resonance imaging techniques and the investigation of immunomodulatory properties of several vascular mediators on the molecular level have added new excitement to hypotheses centering around vascular pathology as determining factor in the pathophysiology of MS. Here we critically review the concept of chronic cerebrospinal venous insufficiency in MS patients and describe new imaging techniques including perfusion weighted imaging, susceptibility weighted imaging and diffusion weighted imaging which reveal central nervous system hypoperfusion, perivascular iron deposition and diffuse structural changes in the MS brain.

Primary diagnosis of Wolfram syndrome in an adult patient--case report and description of a novel pathogenic mutation.

Wolfram syndrome is a rare, autosomal recessive, neurodegenerative disorder presenting with the main clinical symptoms of childhood-onset diabetes mellitus, optic atrophy, diabetes insipidus and deafness (DIDMOAD). Later stages of the disease are dominated by neurological complications and death occurs early in life with a median life expectancy of 30 years. Here we present a 44 year old patient who presented to our hospital with central respiratory failure, cognitive impairment, ataxia and parkinsonism and was first diagnosed with Wolfram syndrome.