Investigation of cerebrospinal fluid (CSF) in the diagnostic work-up in suspected multiple sclerosis (MS) patients has regained attention in the latest version of the diagnostic criteria due to its ...good diagnostic accuracy and increasing issues with misdiagnosis of MS based on over interpretation of neuroimaging results. The hallmark of MS-specific changes in CSF is the detection of oligoclonal bands (OCB) which occur in the vast majority of MS patients. Lack of OCB has a very high negative predictive value indicating a red flag during the diagnostic work-up, and alternative diagnoses should be considered in such patients. Additional molecules of CSF can help to support the diagnosis of MS, improve the differential diagnosis of MS subtypes and predict the course of the disease, thus selecting the optimal therapy for each patient.
Inflammasomes are protein complexes that respond to a wide range of pathogens and cellular damage signals. Their activation prompts the caspase-1-mediated cleavage of the proinflammatory cytokines ...IL-1β and IL-18. Inflammasome dysregulation has been demonstrated to play a role in a range of diseases involving the adaptive immune system like multiple sclerosis, rheumatic diseases, and type 1 diabetes. Priming and activation of inflammasomes can be modulated by microRNAs (miRNAs), small noncoding RNAs that regulate gene expression posttranscriptionally. miRNAs, such as miR-223-3p, have been demonstrated to directly target the inflammasome components NLRP3, caspase-1, and caspase-8. Other miRNAs like miR-155-5p modulate TLR-, IL-1R-, TNFR-, and IFNAR-mediated signaling pathways upstream of the inflammasomes. In this study, we discuss how a more detailed elucidation of miRNA-driven inflammasome regulation helps in understanding the molecular processes underlying immune-mediated human diseases, holds potential for the identification of biomarkers and may offer novel targets for the development of future therapeutics.
In contrast to other diseases that go along with spasticity (e.g. spinal cord injury), spasticity in chronic autoimmune diseases involving the CNS is complicated by the ongoing damage of neuronal ...networks that leads to permanent changes in the clinical picture of spasticity.
Multiple sclerosis (MS) is the most frequent autoimmune disease of the central nervous system (CNS) and spasticity is one of the most disabling symptoms. It occurs in more than 80% MS patients at some point of the disease and is associated with impaired ambulation, pain and the development of contractures.
Besides causing cumulative structural damage, neuroinflammation occurring in MS leads to dynamic changes in motor circuit function and muscle tone that are caused by cytokines, prostaglandins, reactive oxygen species and stress hormones that affect neuronal circuits and thereby spasticity.
The situation is complicated further by the fact that therapeutics used for the immunotherapy of MS may worsen spasticity and drugs used for the symptomatic treatment of spasticity have been shown to have the potential to alter immune cell function and CNS autoimmunity itself. This review summarizes the current knowledge on the immunologic pathways that are involved in the development, maintenance, dynamic changes and pharmacological modulation of spasticity in MS.
The aim of this study was to report the basic cerebrospinal fluid (CSF) profile in patients with primary progressive multiple sclerosis (PPMS).
The results of CSF analysis from 254 patients with PPMS ...were collected at four university hospitals in Germany. Routine CSF parameters and different indices of intrathecal immunoglobulin synthesis were evaluated. We assessed possible correlations between the various CSF parameters and the expanded disability status scale (EDSS) both at the time of lumbar puncture and during the course of the disease.
The median cell count and albumin concentration in the CSF did not deviate from normal values. The CSF-serum albumin-quotient (QALB) was elevated in 29.6% of the patients, while intrathecal immunoglobulin G (IgG) oligoclonal bands (OCBs) were detected in 91.1% of the patients. CSF-lactate levels as well as local IgM- and IgA-synthesis were correlated with the yearly disease progression rate, as assessed by EDSS.
We present the results of the hitherto largest and most detailed CSF biomarker profile in a cohort of 254 patients with PPMS. As reported previously, OCBs are the most sensitive marker for intrathecal IgG synthesis. CSF-lactate concentrations are positively correlated with the progression rate, which might suggest that mitochondrial dysfunction plays a relevant role in PPMS. The negative correlation between intrathecally produced IgM and IgA and disease progression may indicate their hitherto unexplored protective role.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Nabiximols (Sativex®), a cannabinoid-based oromucosal spray, is an add-on therapy for patients with moderate to severe multiple sclerosis spasticity (MSS) resistant to other medications. The primary ...objective was to provide real-life observational data of clinical experience of nabiximols in contrast to formal clinical trials of effectiveness.
This was an observational, prospective, multicenter, non-interventional study with a follow-up period of 3-4 months, conducted in routine care setting in Germany. Patients with moderate to severe MSS were included at nabiximols' initiation. Structured documentation forms, questionnaires and validated instruments were used for data collection at inclusion, 1 and 3 months after inclusion.
Overall, 335 patients were assessed of whom 276 fitted the criteria and were included in the effectiveness analysis. After 1 month, nabiximols provided relief of resistant MSS in 74.6% of patients according to specialist assessment; mean spasticity 0-10 numerical rating scale (NRS) score decreased from 6.1 ± 1.8 to 5.2 ± 2.0 points; in patients with NRS improvement ≥20% mean NRS score decreased by 40%. After 3 months, 55.3% of patients had continued to use nabiximols and the mean NRS score had decreased by 25% from baseline. 17% of patients reported adverse events.
Real-life data confirm nabiximols as an effective and well-tolerated treatment option for resistant MSS in clinical practice.
There are few diseases where as much therapeutic progress has been made in recent years as in multiple sclerosis. Nine different drug classes with more than a dozen approved therapies are now ...available. Similarly, there have been unimaginable advances in understanding neuromyelitis optica (now neuromyelitis optica spectrum disorder NMOSD) over the past 15 years. Building on the knowledge gained, the first therapies have been approved in recent years. In this review, we aim to present all therapies approved for the treatment of MS or NMOSD. The different forms of application, different approval criteria and most important side effects will be presented. This work is intended for physicians who are interested in MS and NMOSD therapies and want to get a first overview and does not replace the respective guidelines of the regulatory authorities.
Recent studies on Multiple Sclerosis (MS) pathology mention the involvement of "tertiary B cell follicles" in MS pathogenesis. This inflammatory process, which occurs with interindividually great ...variance, might be a link between MS pathology and headaches. The aim of this study was to detect the prevalence of headaches and of subtypes of headaches (migraine, cluster, tension-type headache TTH) in an unselected MS collective and to compile possibly influencing factors. Unselected MS patients (n = 180) with and without headache were examined by a semi-structured interview using a questionnaire about headache, depression and the health status. Additionally clinical MS data (expanded disability state score EDSS, MS course, medication, disease duration) were gathered. N = 98 MS patients (55.4%) reported headaches in the previous 4 weeks. We subsequently grouped headache patients according to the IHS criteria and detected 16 (16.3%) MS patients suffering from migraine (migraine with aura: 2 2%; migraine without aura: 14 14.3%), 23 (23.5%) suffering from TTH and none with a cluster headache. Thus, headaches of 59 (60.2%) MS patients remained unclassified. When comparing MS patients with and without headaches significant differences in age, gender, MS course, physical functioning, pain and social functioning occurred. MS patients with headaches were significantly younger of age (p = 0.001), female (p = 0.001) and reported more often of a clinically isolated syndrome (CIS) and relapsing/remitting MS (RRMS) instead of secondary chronic progressive MS (SCP). EDSS was significantly lower in MS patients suffering from headaches compared to the MS patients without headaches (p = 0.001). In conclusion headache in MS patients is a relevant symptom, especially in early stages of the MS disease. Especially unclassified headache seems to represent an important symptom in MS course and requires increased attention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuroimmunological diseases and their treatment compromise the immune system, thereby increasing the risk of infections and serious illness. Consequently, vaccinations to protect against infections ...are an important part of the clinical management of these diseases. However, the wide variety of immunotherapies that are currently used to treat neuroimmunological disease - particularly multiple sclerosis and neuromyelitis optica spectrum disorders - can also impair immunological responses to vaccinations. In this Review, we discuss what is known about the effects of various immunotherapies on immunological responses to vaccines and what these effects mean for the safe and effective use of vaccines in patients with a neuroimmunological disease. The success of vaccination in patients receiving immunotherapy largely depends on the specific mode of action of the immunotherapy. To minimize the risk of infection when using immunotherapy, assessment of immune status and exclusion of underlying chronic infections before initiation of therapy are essential. Selection of the required vaccinations and leaving appropriate time intervals between vaccination and administration of immunotherapy can help to safeguard patients. We also discuss the rapidly evolving knowledge of how immunotherapies affect responses to SARS-CoV-2 vaccines and how these effects should influence the management of patients on these therapies during the COVID-19 pandemic.
Immunomodulatory and immunosuppressive treatments for multiple sclerosis (MS) are associated with an increased risk of infection, which makes treatment of this condition challenging in daily clinical ...practice. Use of the expanding range of available drugs to treat MS requires extensive knowledge of treatment-associated infections, risk-minimizing strategies and approaches to monitoring and treatment of such adverse events. An interdisciplinary approach to evaluate the infectious events associated with available MS treatments has become increasingly relevant. In addition, individual stratification of treatment-related infectious risks is necessary when choosing therapies for patients with MS, as well as during and after therapy. Determination of the individual risk of infection following serial administration of different immunotherapies is also crucial. Here, we review the modes of action of the available MS drugs, and relate this information to the current knowledge of drug-specific infectious risks and risk-minimizing strategies.
Multiple Sclerosis (MS) is a heterogeneous immune mediated disease of the central nervous system (CNS). Fatigue is one of the most common and disabling symptom of MS. It interferes with daily ...activities on the level of cognition and motor endurance. Motor fatigue can either result from lesions in cortical networks or motor pathways (“primary fatigue”) or it may be a consequence of detraining with subsequent adaptions of muscle and autonomic function. Programmed exercise interventions are used frequently to increase physical fitness in MS-patients. Studies investigating the effects of training on aerobic capacity, objective endurance and perceived fatigability have yielded heterogenous results, most likely due to the heterogeneity of interventions and patients, but probably also due to the non-uniform pathophysiology of fatigability among MS-patients. The aim of this review is to summarize the current knowledge on the pathophysiology of motor fatigability with special reference to the basic exercise physiology that underlies our understanding of both pathogenesis and treatment interventions.
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