Multiple Sclerosis Journal最新文献

The pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.

Background: Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk.

Objective: To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis.

Methods: Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture.

Results: In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS.

Conclusion: We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights.

Background: Rapidly reversible weakness with neck flexion (McArdle sign) is common in patients with multiple sclerosis (MS). The pathophysiology is unknown.

Objective: To evaluate changes in central motor conduction time (CMCT) in patients with and without McArdle sign.

Methods: We measured McArdle sign with a torque cell and CMCT with neck flexed and extended in patients with MS, other causes of myelopathy, and healthy controls.

Results: CMCT was prolonged with neck flexion disproportionately in those with MS-associated myelopathy (MSAM) with prominent McArdle sign compared to MS patients with lesser degrees of McArdle sign, and to controls.

Conclusion: McArdle sign may result from stretch-induced slowing of conduction due to demyelination.

Background: Information on symptomatic therapy (ST) use in women of childbearing age with multiple sclerosis is sparse, and data on the impact of ST pregnancy exposure on pregnancy outcome are lacking.

Objective: To investigate (1) ST use patterns pre-conception, during pregnancy and postpartum and (2) pregnancy outcomes.

Methods: Pregnancy data from the German Multiple Sclerosis and Pregnancy Registry were analyzed for the ST use from pre-conception to postpartum. Pregnancy outcomes were compared between ST-exposed (n = 282) and matched (disease modifying therapy and age) ST-naive (n = 536) pregnancies.

Results: Of 2,449 pregnancies, 1,053 (43.0%) received ST anytime between pre-conception and postpartum, 282 (11.5%) at pre-conception and during pregnancy. The most commonly used drug classes were antidepressants (24.8%), analgetics (31.0%), and anticonvulsives (8.7%). Exposure to ST during pregnancy did not result in an increased incidence of adverse pregnancy outcomes, major congenital abnormalities, or pregnancy complications.

Conclusion: Nearly 50% of women used ST between pre-conception and postpartum, but only 12% pre-conception and during pregnancy. ST use during pregnancy did not adversely affect pregnancy outcomes in our cohort. More data are needed to analyze the effect of ST on pregnancy and fetal outcomes stratified by drug to improve recommendations for ST use in family planning.

Recognizing neuromyelitis optica spectrum disorder (NMOSD) and differentiating NMOSD from multiple sclerosis (MS) and other disorders can be challenging yet it is extremely important to prevent misdiagnosis, defined in this review as the incorrect diagnosis of patients who truly have NMOSD, particularly in aquaporin-4-IgG (AQP4-IgG)-seronegative cases. The heterogeneity of clinical presentations and wide range of differential diagnoses often lead to missed diagnoses of NMOSD. Misapplication of the 2015 NMOSD criteria and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis in clinical practice. Despite the presence of a specific biomarker for NMOSD (AQP4-IgG), misdiagnosis rates have been reported as high as 35%. Studies indicate that misdiagnosed patients often undergo unnecessary prolonged immunotherapy, leading to health risks and increased morbidity. Accurate definitive diagnosis is crucial as long-term outcomes and treatment approaches differ based on the correct diagnosis, and inappropriate immunotherapy can lead to disability in NMOSD patients. This review outlines factors linked to NMOSD misdiagnosis and briefly discusses strategies to reduce misdiagnosis.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

Results: A total of 364 participants were included. In total, 55.5% presented with WoS and 44.5% without WoS during natalizumab treatment. Longitudinal analyses showed no association between sNfL and sGFAP levels and WoS at any timepoint. Biomarker levels at baseline did not predict first-time WoS occurrence.

Conclusion: Acute and chronic neuronal and axonal damage are most likely not the underlying cause of WoS.

Background: The MSIS-29 measures the physical and psychological impact of MS.

Objective: The associations between MSIS-29 domains and demographic/clinical aspects were examined and trajectories analysed over time.

Methods: Data were collected in the Trajectories of Outcome in Neurological Conditions study for a diverse population of people with MS, with follow-up for up to 5 years. Following Rasch analysis, minimal important change (MIC) was computed for ensuing total, physical and psychological domains.

Results: Fit to the Rasch model using data from 5921 participants validated physical, psychological and total domains, and the conversion table transforms raw scores to interval-level metric equivalents. These domains showed significant differences across demographic (age, gender, employment, education, and marital status) and clinical (subtype, treatment, and duration) factors with large effect sizes. The MIC scores were physical: 9.1, total: 14.1, which were both above measurement error, and psychological: 5.5 which was not, so 1.6% of participants reported psychological change which was clinically important but not statistically significant. Trajectory analysis showed three groups, one stable and two with significant slopes, improving and deteriorating.

Conclusion: The MSIS-29 has shown adequate fit to the Rasch model after accommodating problems with local item dependency, through a bi-factor solution. The domains showed good discrimination across key factors.

Myelin oligodendrocyte glycoprotein (MOG)-associated disorders are inflammatory demyelinating diseases of the CNS. Cerebral cortical encephalitis (CCE) is characterized by cortical fluid-attenuated inversion recovery hyperintensity with seizures and headaches. We report two cases of MOG antibody-associated CCE (MOG-CCE) evaluated using serial MRI sequences, including arterial spin labeling (ASL), pre- and posttreatment. In both patients, ASL demonstrated hyperperfusion correlating with disease activity, which normalized following steroid therapy. Our cases highlight the usefulness of ASL in early detection, monitoring, and assessment of treatment response in MOG-CCE.

Background: ¹¹C-PBR28 positron emission tomography (PET), targeting the translocator protein, and paramagnetic rim lesions (PRL) have emerged as promising imaging markers of MS chronic inflammation. No consensus on which is the optimal marker exists.

Objectives: To investigate the ability of ¹¹C-PBR28 PET and PRL assessment to identify chronic inflammation in white matter (WM) MS lesions and their relation to neurological impairment.

Methods: Based on ¹¹C-PBR28 uptake, brain WM lesions from 30 MS patients were classified as PET active or inactive. The PRL presence was assessed on 7T phase reconstructions, T1/T2 ratio was calculated to measure WM microstructural integrity.

Results: Less than half (44%) of non-PRL WM lesions were active on ¹¹C-PBR28 imaging either throughout the lesion (whole active) or at its periphery. PET peripherally active lesions and PRL did not differ in T1/T2 ratio and ¹¹C-PBR28 uptake. A positive correlation was observed between PRL and active PET lesion count. Whole active PET lesion volume was the strongest predictor (β = 0.97, p < 0.001) of increased Expanded Disability Status Scale scores.

Conclusion: ¹¹C-PBR28 imaging reveals more active WM lesions than 7T PRL assessment. Although PRL and PET active lesion counts are related, neurological disability is better explained by PET whole active lesion volume.