•Cladribine is a highly effective, recently available treatment in multiple sclerosis.•This case report describes a patient with a mild COVID-19 infection during second year treatment with ...cladribine.•Normal immune response with detectable antibodies to SARS-CoV2 three months after the infection.
Cladribine is a highly effective, recently available treatment in multiple sclerosis. This case report describes a patient with COVID-19 infection during second year treatment with cladribine. The infection was mild and she was able to mount an adequate immune response with detectable antibodies three months later.
Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small ...cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values<0.0001). Walking speed as measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All patients were aware of the nature of the treatment agent, and of the study outcomes.
Natalizumab, as used in a real-life setting, might improve MS-related fatigue based on the results from this one-armed un-controlled stud. Also other parameters related to patients' quality of life seemed to improve with natalizumab treatment.
ClinicalTrials.gov NCT00884481.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. ...Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the ...susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and others have previously established a protective effect of HLA-A*02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB1*15 and A*02, in particular DRB1*01 (OR = 0.82, p = 0.034) and B*12 (including B*44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB1*15 and DRB1*01 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4 × 10(-06)), DRB1*15 and C*12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 × 10(-05)), indicating that the effect size of these allele groups varies when taking DRB1*15 into account. Analysis of inferred haplotypes showed that almost all DRB1*15 bearing haplotypes were risk haplotypes, and that all A*02 bearing haplotypes were protective as long as they did not carry DRB1*15. In contrast, we found one class I haplotype, carrying A*02-C*05-B*12, which abolished the risk of DRB1*15. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB1*15 and A*02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB1*15 and several alleles of DRB1 and class I genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
New treatment options may make "no evidence of disease activity" (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to "evidence of disease activity" (EDA) with ...at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8-2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0-1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Driving ability is a key function for the majority of patients with multiple sclerosis (MS) to help maintain daily interactions. Both physical and cognitive disability, as well as ...treatments, may affect the ability to drive. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. In this article, we review the evidence relating the antispasticity medicine, Δ9‐tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®), and its potential impact on driving performance.
Methods
Articles were identified by searching PubMed from 1/1/2000 to 30/6/2017 using a specified list of search terms. The articles identified using these search terms were augmented with relevant references from these papers and other articles known to the authors.
Results
The results from THC:CBD oromucosal spray driving studies and real‐world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray. The majority of patients reported an improvement in driving ability after starting THC:CBD oromucosal spray, and it was speculated that this may be related to reduced spasticity and/or better cognitive function. It should be noted that THC blood levels are significantly lower than the levels associated with recreational use of herbal cannabis.
Conclusions
THC:CBD oromucosal spray was shown not to impair driving performance. However, periodic assessment of patients with MS driving ability is recommended, especially after relapses and changes in treatment. Blood THC measurements might be above authorized thresholds for some countries following administration of THC:CBD oromucosal spray, thus specific knowledge of each country's driving regulations and a medical certificate are recommended.
Multiple sclerosis (MS) is a chronic neurological disease associated with a multitude of symptoms that may cause physical and cognitive disability and reduce well‐being and quality of life (QoL). Driving ability is a key function which the majority of patients want to retain to maintain family/friend, social, and work‐related interactions. Spasticity is a common symptom associated with MS, and it may affect driving performance either directly or via the medications used to treat it. Δ9‐tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is approved across the EU for the management of moderate‐to‐severe MS‐related spasticity in adult patients resistant to other antispasticity therapies. Cannabinoid‐based medicines require special consideration due to the legal complexities surrounding THC. The results from THC:CBD oromucosal spray driving studies and real‐world registries did not show any evidence of an increase in motor vehicle accidents associated with THC:CBD oromucosal spray.
•Chronic fatigue and major depression (MDD)-like symptoms are common manifestations of multiple sclerosis (MS), both with huge impact on quality of life.•It seems likely that proinflammatory ...cytokines, tryptophan catabolites (the KYN pathway) and the gut-brain axis are involved in the mechanisms causing chronic fatigue and MDD-like symptoms in MS.•In future research, MS-related fatigue and depression should be examined using a longitudinal design and both immune-inflammatory and KYN pathway biomarkers should be measured, relevant clinical characteristics judiciously registered, and self-report instruments for both fatigue and depression should be used.
Chronic fatigue and major depression (MDD)-like symptoms are common manifestations of multiple sclerosis (MS), both with huge impact on quality of life. Depression can manifest itself as fatigue, and depressive symptoms are often mistaken for fatigue, and vice versa. The two conditions are sometimes difficult to differentiate, and their relationship is unclear. Whether chronic fatigue and depression occur primarily, secondarily or coincidentally with activated immune-inflammatory pathways in MS is still under debate. We have carried out a descriptive review aiming to gain a deeper understanding of the relationship between chronic fatigue and depression in MS, and the shared pathways that underpin both conditions. This review focuses on immune-inflammatory pathways, the kynurenine pathway and the gut-brain axis. It seems likely that proinflammatory cytokines, tryptophan catabolites (the KYN pathway) and the gut-brain axis are involved in the mechanisms causing chronic fatigue and MDD-like symptoms in MS. However, the evidence base is weak, and more research is needed. In order to advance our understanding of the underlying pathological mechanisms, MS-related fatigue and depression should be examined using a longitudinal design and both immune-inflammatory and KYN pathway biomarkers should be measured, relevant clinical characteristics judiciously registered, and self-report instruments for both fatigue and depression should be used.
Multiple sclerosis is a chronic, often disabling, disease of the central nervous system affecting more than 1 in 1,000 people in most western countries. The inflammatory lesions typical of multiple ...sclerosis show autoimmune features and depend partly on genetic factors. Of these genetic factors, only the HLA gene complex has been repeatedly confirmed to be associated with multiple sclerosis, despite considerable efforts. Polymorphisms in a number of non-HLA genes have been reported to be associated with multiple sclerosis, but so far confirmation has been difficult. Here, we report compelling evidence that polymorphisms in IL7R, which encodes the interleukin 7 receptor α chain (IL7Rα), indeed contribute to the non-HLA genetic risk in multiple sclerosis, demonstrating a role for this pathway in the pathophysiology of this disease. In addition, we report altered expression of the genes encoding IL7Rα and its ligand, IL7, in the cerebrospinal fluid compartment of individuals with multiple sclerosis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development.
A nationwide, prospective cohort study based on ...participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999-2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators.
In this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67).
Childhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose-response relationship. Further studies are needed to identify underlying mechanisms.
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