Multiple Sclerosis Journal - Experimental, Translational and Clinical最新文献

Introduction: Fatigue is a highly prevalent symptom in people with multiple sclerosis. It demands careful assessment and prompt intervention to improve their quality of life and overall burden of disease. This scoping review aims to provide a comprehensive synthesis and update of the existing evidence on the effectiveness of different pharmacological and nonpharmacological interventions for multiple sclerosis (MS)-related fatigue.

Methods: To ensure the transparency and quality of the articles chosen for this scoping review, the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for Scoping Reviews was used. Exclusively randomized controlled trials published between 2016 and 2023 were included.

Results: Twenty-eight articles were analyzed. We found that pharmacological interventions are few and have included the use of Amantadine, Ondansetron, Methylphenidate, and Modafinil, with little effects on fatigue. Nonpharmacological interventions are diverse and include cognitive behavioral therapy, guided imagery, phototherapy, exercise, brain stimulation, and lavender administration with evidence of a statistically significant decrease in fatigue.

Conclusions and discussion: Current evidence on the effectiveness of pharmacological and nonpharmacological interventions is inconclusive. Lack of knowledge of the pathophysiology of fatigue limits its prevention, control, and management recommendations. A comprehensive and interdisciplinary approach is required to manage this symptom in patients with MS.

Background: Comorbidities in people with multiple sclerosis (PwMS) can affect disease course and quality of life.

Objectives: To investigate comorbidities in the five years after diagnosis, timing of comorbidity occurrence, age and sex effects, and differences between multiple sclerosis (MS) and other chronic autoimmune diseases (AIDs).

Methods: In this retrospective cohort study, we systematically assessed differences in diagnosis frequencies in newly diagnosed PwMS (n = 9,880) compared to matched controls (noAID, n = 29,640) and individuals with other AIDs (psoriasis, n = 29,640; Crohn's disease, n = 9,880).

Results: Some comorbidities of PwMS are similarly frequent in other AIDs, while others, such as depression, are more prevalent in PwMS (odds ratio (OR) vs noAID = 2.03(1.94-2.13)). We found that personality disorders are more frequently recorded in PwMS before (OR  = 1.34(1.21-1.49)) and after MS diagnosis (OR  = 1.32(1.16-1.5)), especially in women (OR  = 1.39(1.2-1.6)). PwMS are more frequently diagnosed with Lyme disease (OR  = 1.98(1.69-2.33)), which was predominantly recorded by general practitioners after presentation with neurological symptoms. We observed lower acute tonsillitis frequencies in PwMS (OR  = 0.8(0.75-0.85)).

Conclusions: Our results suggest that PwMS might have a generally increased risk for specific personality disorders. More frequent Lyme disease recordings for PwMS suggest misdiagnoses of MS symptoms. Lower tonsillitis frequencies suggest a link between MS and protection from specific infections.

Few controlled trials of disease-modifying therapies (DMTs) have been conducted on the pediatric-onset multiple sclerosis (PoMS) population, leading to extensive off-label use of therapies approved only for adults. This highlights the need for real-world evidence to guide clinical practice. Clinical registries can offer high-quality data, but limitations such as missing and erroneous information must be considered. This validation study compared Swedish Multiple Sclerosis registry data from 122 PoMS patients to medical records. Generally (≥89%), data were confirmed. However, missing data exceeded 30% for rituximab infusions, magnetic resonance imaging, and relapses. Overall, the registry provides valid, real-world data on DMT use in PoMS.

Background: Diffusion tensor imaging (DTI) in adults with multiple sclerosis (MS) has identified marked volume and diffusion abnormalities of the fornix, the main white matter (WM) output tract of the hippocampus.

Objective: To determine if the fornix is affected in pediatric-onset MS (POMS) using the same DTI protocols used in adult-onset MS (AOMS), which would suggest its early involvement in the disease course.

Methods: High-resolution, fluid-suppressed diffusion tractography was used to identify the fornix in 11 POMS patients (13-19 years old) and 26 controls. Fornix volume and diffusion metrics were compared between groups and with other total/regional brain volumes, and then correlated with cognitive/clinical scores.

Results: POMS showed lower fornix volumes (-26%) compared to controls, which was greater than proportional losses in total and other regional brain volumes. Notably, the hippocampus volume was not lower in POMS. DTI yielded lower fractional anisotropy (-7%) and higher mean (+12%), axial (+7%), and radial (+16%) diffusivities in POMS. There were no significant correlations between fornix volume/diffusion metrics and cognitive/clinical scores.

Conclusion: Diffusion tractography showed marked injury to the fornix in POMS that precedes injury to connected gray matter such as hippocampus, implicating the fornix as an early brain region affected in MS.

Background: SLIPPERS (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids) is a rare variant of a syndrome called CLIPPERS (Chronic Lymphocytic Inflammation with Ponsine Perivascular Enhancement Responsive to Steroids). SLIPPERS is characterized by distinct supratentorial lesions that share radiological and pathological characteristics with CLIPPERS. The ongoing issue is whether these syndromes should be considered as a distinct disease entity or simply a form for a variety of underlying conditions such as granulomatosis, vasculitis, and infectious diseases.

Case: We present a unique case of SLIPPERS observed in a 26-year-old woman with no notable medical or familial background. Laboratory findings ruled out certain diseases from the list of differentials and cranial MRI showed T2 hyperintense areas with linear-patchy enhancements, a pattern consistent with SLIPPERS syndrome. Consequently, patient was diagnosed with SLIPPERS syndrome and received methylprednisolone therapy.

Conclusion: Both SLIPPERS and CLIPPERS are complicated syndromes posing diagnostic challenges and requiring careful investigation to avoid misdiagnosis. Following a thorough differential diagnosis, appropriate treatment can be initiated, and follow-up is required.

Background: Work ability index (WAI) is an instrument that measures work ability in workplace surveys and health examinations in occupational health and research. It has been used in different population groups. But research is limited among people with multiple sclerosis (PwMS).

Objective: To determine the factors associated with work ability among PwMS in Sweden.

Methods: A total of 4103 PwMS who answered a web-based survey were included in the analysis. Work ability was assessed using the work ability score (WAS) component of WAI. Univariable and multivariable linear regression analyses were performed to assess the association of sociodemographic, clinical, and self-reported health variables with WAS.

Results: Just over half of the PwMS reported good (37.0%) or excellent (16.3%) WAS. The overall mean WAS was 6.9 (standard deviation = 2.8). Health-related quality of life (R-squared = 31.6%), fatigue (28.3%), occupation (22.6%), and expanded disability status scale (EDSS) score (18.1%), explained the highest proportions of variation in WAS, individually. In the adjusted model, occupation, EDSS score, and fatigue had the strongest associations with WAS with significantly lower scores in those with no occupation, higher EDSS score, and severe fatigue levels.

Conclusion: Work ability among PwMS was lower than in the general population in Sweden. Occupation, EDSS score and fatigue were among the most important factors associated with work ability.

The prodromal features of multiple sclerosis (MS) are non-specific and are prevalent in the general population. Several studies indicate an increased use of healthcare resources by individuals with MS in the years preceding their diagnosis, suggesting a trend of deteriorating health prior to the clinical manifestation of MS. This study aimed to capture the possible associations of sick leave with the timing of the diagnosis of MS. Our findings suggest that sick leave with neurological diagnoses - excluding MS, and other diagnoses during the year before MS onset is associated with a shorter time to MS diagnosis.

Background: In Denmark, specialized multiple sclerosis (MS) clinics offer free-of-charge treatment to people with MS. However, not all people with MS attend regular clinical follow-up.

Objective: To identify people with MS who do not attend Danish MS clinics and identify barriers to treatment.

Methods: The Danish Multiple Sclerosis Registry was linked to other national Danish registries with follow-up from 2000-2020. We used a time-dependent Cox regression to rank factors associated with low attendance to clinical follow-up visits based on the magnitude of hazard ratios (HRs).

Results: We included 10,175 adults with MS, of which 3862 (38%) had less than one visit annually. The five top-ranked factors that reduced the risk of visits occurring included never having received diseases modifying treatment (HR: 0.48; 95%CI: 0.46-0.49), been diagnosed with MS before 2009 (0.79; 0.78-0.81), association with MS center in an outer region of Denmark (0.82; 0.80-0.84), having progressive MS type (0.88; 0.86-0.91) and not having received symptomatic treatment at diagnosis (0.91; 0.89-0.93).

Conclusion: Our results highlight disease-specific and geographic inequalities in the management of people with MS in Denmark. Strategies to prevent this inequality, especially for people with progressive phenotypes and those who need supportive and non-medical treatment and care, should be implemented.

Background: Cognitive dysfunction in multiple sclerosis (MS) occurs early. Locally adapted neuropsychological data from India in MS is scarce.

Objectives: We aimed to identify the pattern of cognitive impairment in relapsing MS (RMS) with mild disability using a regionally-adapted MS-specific cognitive battery.

Methodology: The study included 59 persons with MS (pwMS) with expanded disability status scale (EDSS)≤ 4 and 62 controls. The battery had 8 neuropsychological tests (Paced Auditory Serial Addition Test [PASAT], Symbol Digit Modalities Test [SDMT], Rey Auditory Verbal Learning Test [RAVLT], Brief Visuospatial Memory Test-Revised [BVMT-R], verbal fluency [VF], Judgement of Line Orientation Test [JOLOT], Wisconsin Card Sorting Test [WCST] and Trail Making Test-B [TMT-B]) with 11 measures. The scores were compared between the groups for pattern and associations of cognitive impairment.

Results: The pwMS cohort had 39 (66.1%) females; mean age of 32.56 (±8.17) years. Scores were significantly worse for pwMS in 10 of 11 tests (except JOLOT). Cohen's-d test showed the largest effect sizes for PASAT, SDMT, VF and TMT-B. Cognitive impairment (defined as ≥2 abnormal tests) were noted in 41 (69.5%) pwMS. Male sex was associated with cognitive impairment (p = 0.002).

Conclusions: In pwMS with mild disability, nearly two-thirds had cognitive abnormalities, predominantly involving processing speed, working memory, executive function, and VF.

Intermediate uveitis (IU) may be associated with multiple sclerosis (MS), with both conditions possibly sharing pathogenic mechanisms. Two patients presented with bilateral IU. Despite targeted uveitis treatment with corticosteroids and methotrexate, both had ongoing disease activity with symptoms, and fluorescein angiographic abnormalities. Both were subsequently identified to have radiologically isolated MS in the absence of clinical demyelination. Treatment with natalizumab in isolation, led to rapid and sustained resolution of uveitis, enabling discontinuation of other immunosuppression. This case series adds evidence supporting use of alpha-4 integrins in the treatment of MS-associated uveitis, in addition to its known high-efficacy in MS.