Normally, a part of the immune system (called complement) is activated to help fight bacteria and other threats.
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Lupus is a chronic (long-term) disease that can cause inflammation and pain in any part of your body. It’s an autoimmune disease, which means that your immune system — the body system that usually fights infections — attacks healthy tissue instead.
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Background: Cognitive impairment frequently affects multiple sclerosis (MS) patients. However, its neuroanatomical correlates still need to be fully explored. We investigated the contribution of structural and functional magnetic resonance imaging (MRI) abnormalities in explaining cognitive impairment in MS.
Methods: Brain dual-echo, diffusion tensor, 3D T1-weighted and resting-state (RS) MRI sequences were acquired from 276 MS patients and 102 healthy controls. Using random forest analysis, the contribution of regional white matter (WM) lesions, WM fractional anisotropy (FA) abnormalities, gray matter (GM) atrophy and RS functional connectivity (FC) alterations to cognitive impairment in MS patients was investigated.
Results: Eighty-four MS patients (30.4%) were cognitively impaired. The best MRI predictors of cognitive impairment (relative importance [%]) (out-of-bag area under the curve [AUC] = 0.795) were (a) WM lesions in the right superior longitudinal fasciculus (100%), left anterior thalamic radiation (93.4%), left posterior corona radiata (78.5%), left medial lemniscus (74.2%), left inferior longitudinal fasciculus (70.4%), left optic radiation (68.7%), right middle cerebellar peduncle (60.6%) and right optic radiation (53.5%); (b) decreased FA in the splenium of the corpus callosum (64.3%), left optic radiation (61.0%), body of the corpus callosum (51.9%) and fornix (50.9%); and (c) atrophy of the left precuneus (91.4%), right cerebellum crus I (84.4%), right caudate nucleus (78.6%), left thalamus (76.2%) and left supplementary motor area (59.8%). The relevance of these MRI measures in explaining cognitive impairment was confirmed in a cross-validation analysis (AUC =0.765).
Conclusion: Structural damage in strategic WM and GM regions explains cognitive impairment in MS patients more than RS FC abnormalities.
Keywords: MRI; cognitive impairment; gray matter atrophy; multiple sclerosis; resting state functional connectivity.
© 2021 European Academy of Neurology.
Knowing what MS can do to people and seeing these results who wouldn’t want to be treated with, or at least offered the option of being treated with, alemtuzumab or another IRT when they are diagnosed?
Giovannoni et al. Early treatment with alemtuzumab maintains its efficacy on clinical and MRI disease activity outcomes, including slowing of brain volume loss, over 10 years in RRMS patients: CARE-MS II follow-up (TOPAZ Study). ECTRIMS 2021, P722.
Introduction: In CARE-MS II (NCT00548405), alemtuzumab (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved clinical/MRI outcomes versus SC IFNB-1a over 2 years (y) in RRMS patients with inadequate response to prior therapy and further minimised disease in a 4-y extension study (NCT00930553). Further follow-up was available in an additional 5-y extension, TOPAZ (NCT02255656).
Aims: Evaluate the efficacy and safety of alemtuzumab in CARE-MS II patients over 10 y.
Methods: At investigator discretion, patients in TOPAZ can receive additional alemtuzumab as needed for disease activity (≥12 months apart) or other disease-modifying therapy (DMT) at any time.
Results: Proportions of patients remaining on study after 10 y were 62% (271/435) among those treated initially with alemtuzumab in the core study and 73% (107/146) among those treated with SC IFNB-1a for 2 y before switching to alemtuzumab in the extensions. In the extension studies, 39% of the alemtuzumab group did not receive further treatment (alemtuzumab or other DMT). Among the alemtuzumab group over the combined core and extension studies, 71% of patients had stable/improved EDSS scores, the mean change in EDSS score was +0.34, 58% of patients were free of 6-month confirmed disability worsening, and 49% achieved 6-month confirmed disability improvement. In Y10, the annualised relapse rate was 0.11, 71% of patients were free of MRI disease activity, 92% were free of new gadolinium-enhancing lesions, and 72% were free of new/enlarging T2 hyperintense lesions. The median annual brain volume loss was ≤0.19% each year over Y3–10. Alemtuzumab had a consistent safety profile over 10 y, with the incidence of overall adverse events (AEs) and infections declining through Y10. Cumulative incidence of thyroid AEs was 44% and immune thrombocytopaenia was 4%. Efficacy and safety in SC IFNB-1a–treated patients from the core study who switched to alemtuzumab in the extension were consistent with those treated with alemtuzumab in both the core and extension.
Conclusions: Early treatment efficacy with alemtuzumab on clinical, MRI lesion, and brain volume outcomes was maintained over 10 y in CARE-MS II patients, with 62% remaining on study and 39% receiving no additional courses or other DMTs through Y10. Safety remained consistent and manageable over 10 y, with declining AE incidences over time, including a consistent reduction in autoimmune AE occurrence after Y3.
The authors analyzed responses from 1,100 people with MS over the course of one month at nine MS centers in Italy. They used the 10-question Neurogenic Bowel Dysfunction (NBD) score, which asked participants to evaluate their NBD symptoms, including those related to both incontinence and constipation.
The researchers found that 14 percent of participants had moderate to severe bowel dysfunction. Bowel dysfunction was more likely among people with more severe levels of disability, progressive phenotypes, older age, and longer disease duration. The study authors said the severity of participants’ bowel dysfunction was predicted by such factors as bladder symptoms, difficulty walking, and female sex.
The authors noted that the rate of bowel dysfunction in participants was lower in this study as compared to other studies. However, the researchers added that this current analysis was performed on people who were classified as having a relatively low level of disability.
The study authors suggested that health care providers should proactively screen people with MS for symptoms of NBD so these symptoms can be addressed before they reach moderate to severe levels of bowel dysfunction.
Living with multiple sclerosis can lead to a wide variety of symptoms. Among those that could impact quality of life are communication issues, according to a new study.
A team of scientists from Australia’s University of Sydney reviewed online questionnaires from 260 people with MS to evaluate whether they experienced any changes that affected their ability to communicate. The study authors found that the majority of participants — 75.8 percent — said they had experienced communication changes, such as:
Stress, heat, and fatigue were among the factors that influenced communication changes, the study participants reported. Although the majority of study participants did indicate that they were affected by communication problems, just 11.2 percent had accessed services provided by speech-language pathologists, the researchers said.
Communication issues can have an impact far beyond simply being another MS symptom. In daily life, problems with communicating were found to affect participants’ interpersonal relationships, psychological well-being, career pathways, workforce identity, and social lives.
The study authors concluded that the health care community should work harder to raise awareness of how speech-language pathology services can help those with MS manage changes in communication. Helping people with MS navigate these issues when they arise could reduce the impact of communication changes on other areas of life.
September 28, 2021
Individuals with migraine had much poorer subjective sleep quality and altered sleep architecture vs. healthy individuals, according to results of a meta-analysis published in Neurology.
“Despite its association, there remains a paucity of research into sleep in migraine, and there is no consensus on whether patients exhibit objective changes in sleep architecture,” Emily Charlotte Stanyer, MPsych, of the Wolfson Centre for Age-Related Diseases at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience in the U.K., and colleagues wrote. “This is partly due to the small sample sizes of polysomnographic (PSG) studies which measure sleep.
“The current meta-analysis aims to overcome this by aggregating data from multiple studies investigating differences in subjective sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) and objective sleep architecture measured using PSG between patients with migraine and healthy controls,” they added.
The investigators sought to assess whether differences existed in subjective sleep quality measured via the PSQI and objective sleep architecture measured via polysomnography for adult and pediatric patients and healthy controls. They systematically searched five databases for case-controlled studies that measured polysomnography and/or PSQI among patients with migraine, excluding participants who were pregnant or who had other headache disorders. They entered effect sizes into a random effects model meta-analysis. They included 21 studies measuring PSQI and Migraine Disability Assessment Test scores among adults, as well as six studies and five studies measuring polysomnography among adults and children, respectively.
Results showed an overall mean study quality score of 5/9. The researchers observed no moderating effect of this score on any of the results, nor did they report any risk for publication bias. Adults with migraine had higher PSQI scores compared with health controls, with a larger effect among those with chronic vs. episodic condition. In polysomnographic studies, adults and children with migraine vs. controls had a lower percentage of rapid eye movement sleep. Pediatric patients vs. controls had less total sleep time, more wake and shorter sleep onset latency.