Type 1 diabetes and environment . . . and other stories

A linked ecological analysis of environmental and demographic variables identified several factors, including poor air quality, outdoor light at night, and higher population density that were negatively associated with the incidence of diabetes (Diabetologia doi:10.1007/s00125-020-05087-7). A case-control study using a database of people known to have autoimmune disease raises anxiety about central nervous system inflammatory events (JAMA Neurol doi:10.1001/jamaneurol.2020.1162). A history of exposure to TNF inhibitors carried a threefold increase in risk both of demyelinating diseases, such as multiple sclerosis and optic neuritis, and of non-demyelinating conditions, such as encephalitis, neurosarcoidosis, and vasculitis.

Acute central nervous system inflammation following COVID-19 vaccination: An observational cohort study.

BACKGROUND: Reports suggest a potential association between coronavirus disease 2019 (COVID-19) vaccines and acute central nervous system (CNS) inflammation. OBJECTIVE: The main objective of this study is to describe features of acute CNS inflammation following COVID-19 vaccination. METHODS: A retrospective observational cohort study was performed at the BARLO MS Centre in Toronto, Canada. Clinicians reported acute CNS inflammatory events within 60 days after a COVID-19 vaccine from March 2021 to August 2022. Clinical characteristics were evaluated. RESULTS: Thirty-eight patients (median age 39 (range: 20-82) years; 60.5% female) presented within 0-55 (median 15) days of a receiving a COVID-19 vaccine and were diagnosed with relapsing remitting multiple sclerosis (MS) (n = 16), post-vaccine transverse myelitis (n = 7), clinically isolated syndrome (n = 5), MS relapse (n = 4), tumefactive demyelination (n = 2), myelin oligodendrocyte glycoprotein antibody disease (n = 1), neuromyelitis optica spectrum disorder (n = 1), chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (n = 1) and primary autoimmune cerebellar ataxia (n = 1). Twenty-two received acute treatment and 21 started disease-modifying therapy. Sixteen received subsequent COVID-19 vaccination, of which 87.5% had no new or worsening neurological symptoms. CONCLUSION: To our knowledge, this is the largest study describing acute CNS inflammation after COVID-19 vaccination. We could not determine whether the number of inflammatory events was higher than expected.

The epidemiology and burden of neuromyelitis optica spectrum disorder, multiple sclerosis, and MOG antibody-associated disease in a province in Thailand: A population-based study.

BACKGROUND: Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown. OBJECTIVES: To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon. METHODS: Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated. RESULTS: Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well. CONCLUSION: CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases.

COVID-19 vaccination in patients with multiple sclerosis receiving disease-modifying therapies: pragmatic issues.

The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies. Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.

Signs and symptoms of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation. METHOD: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number. RESULTS: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p < 0.001). All cases should be referred to variants up to Delta. CONCLUSION: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms.

Acute disseminated encephalomyelitis (ADEM) Following SARS-CoV-2 Infection: A Case Report from Iran

The new coronavirus disease 2019 (COVID-19) outbreak has rapidly spread throughout the world, becoming a serious public health problem. COVID-19, in addition to respiratory symptoms, has neurotropic characteristics that can impact the nervous system. We present a 22-year-old female who developed diplopia and numbness of her limbs eight days after affecting by COVID-19 and she showed a left-sided outward gaze palsy without any history of previous a specific illness or medication. Supratentorial, infratentorial, and cervical cord enhancing plaques confirmed an acute demyelinating process in favor of Acute disseminated encephalomyelitis (ADEM). Her oligoclonal bands (OCB) were positive as well. As a result, a provisional diagnosis of ADEM was made. Her condition improved dramatically after starting corticosteroids and rituximab. Resumen El nuevo brote de coronavirus de 2019 (COVID-19) se ha propagado rápidamente a nivel mundial, convirtiéndose en un serio problema de salud pública. La COVID-19, además de síntomas respiratorios, tiene características neurotrópicas que pueden repercutir en el sistema nervioso. Presentamos el caso de una mujer de 22 años, que desarrolló diplopía y entumecimiento de las extremidades inferiores ocho días después de verse afectada por la COVID-19, mostrando parálisis de la mirada excéntrica en el lado izquierdo sin antecedentes de enfermedades o medicaciones específicas previas. La intensidad de las placas supratentoriales, infratentoriales y de la columna cervical confirmó un proceso desmielinizante agudo que favorecía encefalomielitis diseminada aguda (ADEM). Asimismo, sus bandas oligoclonales (OCB) fueron positivas. En consecuencia, se diagnosticó provisionalmente ADEM. Su situación mejoró considerablemente tras iniciar tratamiento con corticosteroides y rituximab.

Potential biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating diseases screened by tandem mass spectrometry technology

Objective To screen the potential biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating diseases by tandem mass tags (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology. Methods Twenty patients with demyelinating diseases (demyelinating group) and 10 patients with noninflammatory neurological diseases (NND group) from Beijing Tiantan Hospital affiliated to Capital Medical University from January 2020 to January 2021 were enrolled in this study. The demyelinating group included 10 patients with Guillain-Barre syndrome (GBS subgroup) and 10 patients with multiple sclerosis (MS subgroup). TMT proteomics was used to screen out the different protein expression patterns between the demyelinating group and the NND group and between the GBS subgroup and the MS subgroup (difference>2 or<0.5 and with statistical significance), and String database was used to perform gene ontology (GO) analysis and Kyoto encyclopedia of gene and genomes (KEGG) analysis on the pathways involved in the differently expressed proteins between the groups. In addition, 80 demyelinating patients (demyelinating diseases validation group) and 40 healthy subjects (healthy control group) were selected for retrospective analysis of general lipid indexes. The demyelinating diseases validation group included 40 GBS patients (GBS validation group) and 40 MS patients (MS validation group). Receiver operating characteristic (ROC) curve was obtained to evaluate the value of general lipid indexes for the diagnosis of demyelinating diseases and the differential diagnosis between GBS and MS groups. Results A total of 362 proteins were detected by TMT proteomics. There were 101 differentially expressed proteins between the demyelinating group and the NND group, and 45 differentially expressed proteins between the GBS group and the MS group. Compared with the NND group, GO enrichment analysis showed that the top five enrichment pathways in the demyelinating group were macrophage colony stimulating factor and receptor complex, negative regulation of cholesterol input, negative regulation of very low density lipoprotein particle clearance, triglyceride-rich lipoprotein particle remodeling, and cholesterol reverse transport. Compared with MS group, the top five enriched pathways in GBS group were high-density lipoprotein particle receptor binding, negative regulation of very low density lipoprotein particle remodeling, negative regulation of cholesterol input, negative regulation of very low density lipoprotein particle clearance, and medium density lipoprotein particle. KEGG enrichment analysis results showed that differentially expressed proteins in the demyelinating group and the NND group were enriched in 8 pathways, including phosphatidylinositide 3-kinases-protein kinase B signaling pathway, complement and coagulation cascade reaction, extracellular matrix and its receptor interaction, Staphylococcus aureus infection, cholesterol metabolism, RAS signaling pathway, phagosome, and mitogen-activated protein kinase signaling pathway. Differentially expressed proteins in GBS group and MS group were enriched in 9 pathways: cholesterol metabolism, complement and coagulation cascade, platelet activation, peroxisome proliferators-activated receptors signaling pathway, vitamin digestion and absorption, novel coronavirus infection, fat digestion and absorption, axon guidance, and neutrophil extracellular trap formation pathway. The levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) were significantly higher, while high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels were significantly lower in the demyelinating disease validation group than in the healthy control group (all P<0.05 or 0.01). Area under the curve (AUC) of TG, TC, HDL-C, LDL-C, apoA1 and apoB alone or in combination for the diagnosis of immune-mediated demyelinating diseases was 0.746, 0.643, 0.798, 0.703, 0.806, 0.708 and 0.868, respectively. The AUC of HDL-C, apoA1, LDL-C and apoB for differential diagnosis between GBS and MS was 0.692, 0.653, 0.632, 0.695 and 0.718, respectively. Conclusions There are differences in cerebrospinal fluid proteomics between patients with immune-mediated demyelinating disease and patients with NND, GBS and MS, and the differentially expressed protein patterns mainly exist in the pathways related to lipid metabolism. Lipid related indicators may be used as biomarkers for the diagnosis and differential diagnosis of immune-mediated demyelinating disease. © 2022 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

Central Nervous System Demyelination Following COVID-19 mRNA-Based Vaccination: Two Case Reports and Literature Review.

As the world embarks on mass vaccination against SARS-CoV2 to alleviate the spread of this highly contagious novel coronavirus, there are growing anecdotal reports on immune-related neurological complications following immunisation. Similarly, we encountered 2 cases of central nervous system demyelination at our centre with Comirnaty (BNT162b2), a mRNA-based COVID-19 vaccine. Our first patient had typical clinical-radiological manifestations of acute disseminated encephalomyelitis (ADEM) after his COVID-19 vaccination. This was the sixth reported case to date. Our second patient presented with an unusual complaint of trigeminal neuralgia, with an identifiable demyelinating lesion observed in the pons on neuroimaging. Both cases responded well to immunotherapy. However, larger prospective controlled studies and formal registries are much needed to ascertain a possible relationship between COVID-19 vaccines and acute central nervous system demyelination.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease and Transverse Myelitis Probably Associated With SARS-CoV-2 mRNA Vaccines: Two Case Reports.

Post-vaccination CNS demyelinating syndromes have been reported with a variety of vaccines including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. We report a case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) probably associated with the mRNA-1273 (by Moderna) SARS-CoV-2 mRNA vaccine, and a case of acute transverse myelitis (ATM) probably associated with the BNT162b2 (by Pfizer-BioNTech) SARS-CoV-2 mRNA vaccine. A 38-year-old man developed left blurry vision, lower extremity weakness/paresthesia, and bowel/bladder dysfunction three days after receiving the Moderna vaccine. He was diagnosed with left optic neuritis and longitudinally extensive transverse myelitis; he tested positive for the myelin oligodendrocyte glycoprotein antibody. A 39-year-old woman presented with progressive lower extremity weakness/numbness 7 days after receiving the Pfizer vaccine. She was diagnosed with ATM. Both patients improved with intravenous corticosteroids. The association between CNS demyelinating syndromes and vaccination has been reported for many years. We describe two cases of acute CNS demyelinating events probably associated with both mRNA variations of the SARS-CoV-2 vaccines. While the risk of CNS demyelinating events is non-negligible, the incidence is very low and the overall benefits of vaccination outweigh the marginal risk. However, providers should be aware of this potential neurological complication of the SARS-CoV-2 mRNA vaccines.

Neurological and neuropsychological adverse effects of SARS-CoV-2 vaccines - where do we stand?

The devastating characteristic of COVID-19 pandemic calls for immediate and effective solutions to tackle it. Vaccines seem to be the only promising and effective way to fight against the novel coronavirus - even against new mutated variants. Because of the rapid development and distribution of numerous COVID-19 vaccines in different platforms, meticulous evaluation of vaccines' safety is more critical than ever - especially given the fact that most of the candidates have not completed the clinical phase. Therefore, to optimize the vaccines' safety and efficacy, it is highly important to carefully report and scientifically discuss the serious adverse effects following vaccination. In this respect, we discuss different neurological and neuropsychological adverse effects of COVID-19 vaccines including demyelinating diseases, Bell's palsy (BP), cerebrovascular complications, seizures, functional neurological disorders (FNDs), and some other rare adverse events, and hypothetical mechanisms which can lead to the reported side effects. Given the fact that the incidence of such events are rare and most of them are treatable, the current review aims to shed light on how much the relationship between COVID-19 vaccines and these complications can be reliable and provide an insight for future studies with much more meticulous methodologies to discuss the possible correlational or causal relationship between these complications and COVID-19 vaccines and elucidate whether or not the neurological side effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines can count as a considerable threat to public health.

Does COVID-19 increase the long-term relapsing-remitting multiple sclerosis clinical activity? A cohort study.

BACKGROUND: Some current evidence is pointing towards an association between COVID-19 and worsening of multiple sclerosis (MS), stressing the importance of preventing COVID-19 among people with MS (pwMS). However, population-based evidence regarding the long-term post-COVID-19 course of relapsing-remitting multiple sclerosis (RRMS) was limited when this study was initiated. OBJECTIVE: To detect possible changes in MS clinical disease activity after COVID-19. METHODS: We conducted an observational study from July 2020 until July 2021 in the Isfahan MS clinic, comparing the trends of probable disability progression (PDP) - defined as a three-month sustained increase in expanded disability status scale (EDSS) score - and relapses before and after probable/definitive COVID-19 diagnosis in a cohort of people with RRMS (pwRRMS). RESULTS: Ninety pwRRMS were identified with definitive COVID-19, 53 of which were included in the final analysis. The PDP rate was significantly (0.06 vs 0.19, P = 0.04), and the relapse rate was insignificantly (0.21 vs 0.30, P = 0.30) lower post-COVID-19, compared to the pre-COVID-19 period. The results were maintained after offsetting by follow-up period in the matched binary logistic model. Survival analysis did not indicate significant difference in PDP-free (Hazard Ratio [HR] [95% CI]: 0.46 [0.12, 1.73], P = 0.25) and relapse-free (HR [95% CI]: 0.69 [0.31, 1.53], P = 0.36) survivals between the pre- and post-COVID-19 periods. Sensitivity analysis resulted similar measurements, although statistical significance was not achieved. CONCLUSION: While subject to replication in future research settings, our results did not confirm any increase in the long-term clinical disease activity measures after COVID-19 contraction among pwRRMS.

Multiple Sclerosis Following SARS-CoV-2 Infection: A Case Report and Literature Review.

Coronavirus disease 19 (COVID-19) is caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Apart from respiratory manifestations, COVID-19 can affect the nervous system due to its neurotropic features. Neurological manifestations and complications include headache, polyneuropathies, cerebrovascular accidents, seizures, encephalopathy, and demyelinating disease. We describe a case of multiple sclerosis, a demyelinating disease following COVID-19 infection, rarely reported in the literature. A 47-year-old female presented with fatigue, blurry vision, numbness, and signs of upper motor neuron lesions that had occurred three weeks after COVID-19 infection. Magnetic resonance imaging of the brain revealed demyelinating lesions in the periventricular area of both hemispheres, suggesting a demyelinating disease. A provisional diagnosis of multiple sclerosis was made. Her condition improved after the commencement of methylprednisolone.

Evidence of Post-COVID-19 Transverse Myelitis Demyelination.

The COVID-19 infection is associated with neurological complications involving both the central and peripheral nervous systems. We present a case of a healthy 36-year-old woman who developed symptoms of transverse myelitis (TM) four weeks following a positive COVID-19 infection. She presented with severe fatigue, bilateral lower extremity ascending tingling, progressive muscle weakness, diminished sensation to pain, temperature and vibration, hyperreflexia, and neurogenic bladder. MRI showed extensive demyelination of the cervical and thoracic spine, and cerebrospinal fluid (CSF) analysis showed mildly elevated protein with normal cell count and no evidence of infection, including negative COVID-19 PCR. The patient was treated with intravenous methylprednisolone dosed daily for five days, and markedly improved and continued to be followed up closely at the office.

Characterization of humoral response to COVID mRNA vaccines in multiple sclerosis patients on disease modifying therapies.

Little is known about COVID-19 mRNA vaccine humoral immune responses in patients with central nervous system autoimmune demyelinating diseases, multiple sclerosis (MS) and neuromyelitis optica (NMO), who are on B-cell depleting therapies (BCDT) and other disease modifying therapies (DMTs). We conducted a single center prospective study to identify the clinical and immunological features associated with vaccine-induced antibody response in 53 participants before and after COVID-19 mRNA vaccination. This is the first report on the anti-spike RBD and anti-nucleocapsid antibody response, along with pre- and post-vaccine absolute lymphocyte counts (ALC) and flow cytometry analysis of CD19 and CD20 lymphocytes in patients with MS and NMO. We tested the hypothesis that patients on BCDT may have impaired COVID-19 vaccine humoral responses. Among patients on BCDT, 36.4% demonstrated a positive antibody response to spike RBD, in comparison to 100% in all other groups such as healthy controls, untreated MS, and patients on non-B cell depleting DMTs (p < 0.0001). Immunological data revealed lower baseline (pre-vaccination) levels of IgM in patients on BCDT (p = 0.003). Low CD19 and CD20 counts and a shorter interval from the last B cell depleting therapy infusion to the first vaccine dose were associated with a negative spike RBD antibody response (non-seroconverter) in patients on BCDT. Age, body mass index (BMI) and total treatment duration did not differ between seroconverters and non-seroconverters.

Relation between COVID-19 and Guillain-Barré syndrome in adults. Systematic review. / Relación entre COVID-19 y síndrome de Guillain-Barré en adultos. Revisión sistemática.

INTRODUCTION: Numerous cases have been reported of patients with symptoms of Guillain-Barré syndrome associated with COVID-19, but much information is still lacking on this association and its implications. The objective of this review is to analyse the available evidence on this topic in the adult population. MATERIAL AND METHODS: A systematic review was conducted of studies published on scientific databases: PubMed, Cochrane, Science Direct, Medline, and WHO COVID-19 database. RESULTS: We identified 47 studies, which were analysed and completed using the Covidence platform; the final analysis included 24 articles, with a total of 30 patients. CONCLUSIONS: We found a strong association between both conditions; furthermore, the studies analysed highlight differences in the presentation of the disease, with greater severity of symptoms in Guillain-Barre syndrome associated with COVID-19.