Summary Multiple sclerosis (MS) is a common, complex neurological disease. The precise aetiology of MS is not yet known, although epidemiological data indicate that both genetic and environmental ...factors are important. The evidence that the environment acts long before MS becomes clinically evident is well established and suggests the existence of a prodromal phase for the disease. The increasing incidence of MS emphasises the need for strategies to prevent this chronic disorder, and the possibility of a prodrome indicates a window of opportunity to potentially reverse early disease processes before clinical disease becomes evident. Studying a prodrome requires techniques other than clinical observation such as monitoring endophenotypes that result from associated risk factors. However, our current knowledge of causal pathways and endophenotypes in MS is limited. Identifying and studying individuals with a high risk of developing the disease provides a powerful opportunity to understand the MS causal cascade and is highly relevant to strategies that are aimed at preventing this debilitating disease.
The use of high-efficacy disease-modifying therapies (DMTs) early in the course of multiple sclerosis (MS) has been shown to improve clinical outcomes and is becoming an increasingly popular ...treatment strategy. As a result, monoclonal antibodies, including natalizumab, alemtuzumab, ocrelizumab, ofatumumab, and ublituximab, are frequently used for the treatment of MS in women of childbearing age. To date, only limited evidence is available on the use of these DMTs in pregnancy. We aim to provide an updated overview of the mechanisms of action, risks of exposure and treatment withdrawal, and pre-conception counseling and management during pregnancy and post-partum of monoclonal antibodies in women with MS. Discussing treatment options and family planning with women of childbearing age is essential before commencing a DMT in order to make the most suitable choice for each individual patient.
Clinical syndromes associated with antibodies against myelin oligodendrocyte glycoprotein (MOG) are now recognized as a distinct neurological disease entity, and are gaining increasing attention. The ...pathogenic mechanisms underlying MOG-antibody disease (MOGAD) remain incompletely understood. Case series, facilitated by registries, and observational studies over the past few years have shed increasing light on the clinical aspects and therapeutic approaches of MOGAD. MOGAD may manifest with a variety of clinical syndromes, including acute disseminated encephalomyelitis (ADEM), autoimmune encephalitis, optic neuritis (ON) and transverse myelitis (TM). MOGAD can be either monophasic or relapsing. This review aims to provide a comprehensive updated description of the clinical spectrum, paraclinical features, and prognosis of MOG-antibody disease, as well as summarize its therapeutic considerations. Randomized clinical trials, standardized diagnostic criteria and treatment guidelines are the steps forward.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is more common in women than men and is most commonly diagnosed in early adulthood; thus, many patients will not have completed their families at the time of diagnosis. There ...is increasing awareness of the importance of early treatment in preventing long-term disability in MS. Delaying treatment until women with MS have completed their families can lead to the development of irreversible disability in at least some cases. It is therefore important to discuss family planning and pregnancy proactively. However, to date there is limited evidence to inform such discussions. We set out to develop consensus guidelines for the treatment of MS in pregnancy to encourage and facilitate discussions in this important area. The guidelines draw on available evidence from drug-specific pregnancy registers and published literature and have been scored by a panel of experts from a variety of disciplines using modified Delphi criteria. They cover prepregnancy counselling, management during pregnancy, delivery and anaesthetic options, postpartum advice and specific advice regarding currently licensed disease-modifying drugs. As the complexity and range of available disease-modifying drugs increase, further data gathering via a UK-wide MS pregnancy register is recommended.
Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are cytoskeletal proteins of neurons and their release into cerebrospinal fluid has shown ...encouraging results as a biomarker for neurodegeneration. This study aimed to validate the quantification of the Nf light chain (NfL) in blood samples, as a biofluid source easily accessible for longitudinal studies.
We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF.
Patients with Alzheimer's disease (AD) (30.8 pg/ml, n=20), Guillain-Barré-syndrome (GBS) (79.4 pg/ml, n=19) or amyotrophic lateral sclerosis (ALS) (95.4 pg/ml, n=46) had higher serum NfL values than a control group of neurological patients without evidence of structural CNS damage (control patients, CP) (4.4 pg/ml, n=68, p<0.0001 for each comparison, p=0.002 for AD patients) and healthy controls (HC) (3.3 pg/ml, n=67, p<0.0001). Similar differences were seen in corresponding CSF samples. CSF and serum levels correlated in AD (r=0.48, p=0.033), GBS (r=0.79, p<0.0001) and ALS (r=0.70, p<0.0001), but not in CP (r=0.11, p=0.3739). The sensitivity and specificity of serum NfL for separating ALS from healthy controls was 91.3% and 91.0%.
We developed and validated a novel ECL based sandwich immunoassay for the NfL protein in serum (NfL(Umea47:3)); levels in ALS were more than 20-fold higher than in controls. Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson's disease (PD) and osteoporosis are chronic diseases associated with increasing age. Single studies have reported associations between them and the major consequence, namely, increased risk ...of fractures. The aim of this systematic review and meta-analysis was to evaluate the relationship of PD with osteoporosis, bone mineral density (BMD) and fracture risk.
A literature search was undertaken on 4 September 2012 using multiple indexing databases and relevant search terms. Articles were screened for suitability and data extracted where studies met inclusion criteria and were of sufficient quality. Data were combined using standard meta-analysis methods.
23 studies were used in the final analysis. PD patients were at higher risk of osteoporosis (OR 2.61; 95% CI 1.69 to 4.03) compared with healthy controls. Male patients had a lower risk for osteoporosis and osteopenia than female patients (OR 0.45; 95% CI 0.29 to 0.68). PD patients had lower hip, lumbar spine and femoral neck BMD levels compared with healthy controls; mean difference, -0.08, 95% CI -0.13 to -0.02 for femoral neck; -0.09, 95% CI -0.15 to -0.03 for lumbar spine; and -0.05, 95% CI -0.07 to -0.03 for total hip. PD patients were also at increased risk of fractures (OR 2.28; 95% CI 1.83 to 2.83).
This systematic review and meta-analysis demonstrate that PD patients are at higher risk for both osteoporosis and osteopenia compared with healthy controls, and that female patients are at greater risk than male patients. Patients with PD also have lower BMD and are at increased risk of fractures.
Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence COVID-19 severity. There is concern about the use of ...anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor-seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6-monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment-onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B cell monitoring until (1-3%) B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small molecule anti-viral treatment to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.
Concerns regarding infection with the novel coronavirus SARS-CoV-2 leading to COVID-19 are particularly marked for pregnant women with autoimmune diseases such as multiple sclerosis (MS). There is ...currently a relative paucity of information to guide advice given to and the clinical management of these individuals. Much of the limited available data around COVID-19 and pregnancy derives from the obstetric literature, and as such, neurologists may not be familiar with the general principles underlying current advice. In this article, we discuss the impact of potential infection on the pregnant woman, the impact on her baby, the impact of the current pandemic on antenatal care, and the interaction between COVID-19, MS and pregnancy. This review provides a framework for neurologists to use to guide the individualised advice given to both pregnant women with MS, and those women with MS who are considering pregnancy. This includes evidence derived from previous novel coronavirus infections, and emerging evidence from the current pandemic.
Multiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous ...meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.
We performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35-1.63, p < 10⁻¹⁵; non-conservative: RR 1.52, 95% CI 1.39-1.66, p < 10⁻¹⁹). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98-3.61, p = 0.06).
Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
