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.

Spectrum of Serious Neurological and Psychiatric Adverse Events in Indian COVID-19 Vaccine Recipients: A Systematic Review of Case Reports and Case Series.

Indian data regarding serious neurological and psychiatric adverse events, following coronavirus disease 2019 (COVID-19) vaccination, are lacking. We, therefore, systematically evaluated cases of post-vaccinal serious neurological and psychiatric adverse reactions published from India. A systematic review of cases published from India, which were archived in PubMed, Scopus, and Google Scholar databases, was performed; pre-print databases along with ahead-of-print contents were searched in addition. Retrieved articles, as on June 27, 2022, were evaluated following PRISMA guidelines. EndNote 20 web tool was used to make a PRISMA flow chart. Individual patients' data were compiled in a tabular form. The protocol of the systematic review was registered with PROSPERO (CRD42022324183). A total of 64 records describing 136 instances of serious neurological and psychiatric adverse events were identified. More than 50% (36/64) reports were from the following four states, namely, Kerala, Uttar Pradesh, New Delhi, and West Bengal. The mean age of persons developing these complications was 44.89 ± 15.77 years. In the majority, adverse events occurred within 2 weeks of administration of the first dose of COVISHIELD vaccine. Immune-mediated central nervous system (CNS) disorders were identified in 54 instances. Guillain-Barre syndrome and other immune-mediated peripheral neuropathies were reported in 21 cases. Post-vaccinal herpes zoster was recorded in 31 vaccine recipients. Psychiatric adverse events were recorded in six patients. In Indian recipients of COVID-19 vaccine, a variety of serious neurological complications were reported. The overall risk appears minuscule. Immune-mediated central and peripheral neuronal demyelinations were the most frequently reported post-vaccinal adverse events. A large number of cases of herpes zoster have also been reported. Immune-mediated disorders responded well to immunotherapy.

Neurological sequelae of vaccines.

IMPORTANCE: Vaccines are a safe and efficacious way to prevent a variety of infectious diseases. Over the course of their existence, vaccines have prevented immeasurable morbidity and mortality in humans. Typical symptoms of systemic immune activation are common after vaccines and may include local soreness, myalgias, nausea, and malaise. In the vast majority of cases, the severity of the infectious disease outweighs the risk of mild adverse reactions to vaccines. Rarely, vaccines may be associated with neurological sequela that ranges in severity from headache to transverse myelitis, acute disseminated encephalomyelitis, and Guillain-Barre syndrome (GBS). Often, a causal link cannot be confirmed, and it remains unclear if disease onset is directly related to a recent vaccination. OBSERVATIONS: This review serves to summarize reported neurologic sequelae of commonly used vaccines. It will also serve to discuss potential pathogenesis. It is important to note that many adverse events or reactions to vaccines are self-reported into databases, and causal proof cannot be obtained. CONCLUSIONS AND RELEVANCE: Recognition of reported adverse effects of vaccines plays an important role in public health and education. Early identification of these symptoms can allow for rapid diagnosis and potential treatment. Vaccines are a safe option for prevention of infectious diseases.

Transcriptome Profiling in Autoimmune Diseases

Autoimmune diseases are a group of different inflammatory disorders characterized by systemic or localized inflammation, affecting approximately 0.1–1% of the general population. Several studies suggest that genetic risk loci are shared between different autoimmune diseases and pathogenic mechanisms may also be shared. The strategy of performing differential gene expression profiles in autoimmune disorders has unveiled new transcripts that may be shared among these disorders. Microarray technology and bioinformatics offer the most comprehensive molecular evaluations and it is widely used to understand the changes in gene expression in specific organs or in peripheral blood cells. The major goal of transcriptome studies is the identification of specific biomarkers for different diseases. It is believed that such knowledge will contribute to the development of new drugs, new strategies for early diagnosis, avoiding tissue autoimmune destruction, or even preventing the development of autoimmune disease. In this review, we primarily focused on the transcription profiles of three typical autoimmune disorders, including type 1 diabetes mellitus (destruction of pancreatic islet beta cells), systemic lupus erythematosus (immune complex systemic disorder affecting several organs and tissues), and multiple sclerosis (inflammatory and demyelinating disease of the nervous system). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Combined peripheral and central nervous system demyelination post-COVID-19 vaccination: A case report

Background: During the era of the Coronavirus disease 2019 (COVID-19) pandemic, various neurological syndromes were reported during or after the infection. Fortunately, efforts were made to successfully develop various vaccines with high efficacy and safety. Despite the promising results of those vaccines, they are too novel to be fully understood. Here we are shedding light on a neurological case presentation that may be attributed to one of the COVID-19 vaccines. Case presentation: A 23-year-old male patient with no prior comorbidities presented with quadriparesis and numbness that were clinically and electrophysiologically consistent with Guillain-Barre Syndrome (GBS). The condition started 10 days after the first dose of the AstraZeneca vaccine. Moreover, MRI of the brain and spinal cord has shown evidence of non-specific central demyelination. Despite the radiological finding, the patient is not fulfilling the diagnosis of a known demyelination disorder and the lesions regressed on follow-up. Since no better explanation or trigger could be found, a post-vaccination immune-mediated reaction was considered. Conclusion(s): We still cannot assume the certainty of the causality association between the vaccine and the neurological presentation. Meanwhile, we suggest vigilance for cases of GBS or myelitis following vaccination for Covid-19 and that post-vaccination surveillance programs ensure a statistically significant tool to prove or dispsrove the causality.Copyright © 2022 The Authors

Social and Environmental Triggers of Multiple Sclerosis onset: A Retrospective Study from Iran

Introduction: Multiple sclerosis (MS) is an often-disabling disease of the central nervous system (CNS). The possible triggers of its first presentation such as stressful events, viral infections, vaccinations, and labor are still a matter of debate among scientists. Considering the possible role of infections in MS onset and the reported cases of CNS demyelination following COVID-19 infection and variety of COVID-19 vaccines, this study was conducted to investigate and compare the possible social, environmental, and physical triggers of MS onset before and during the COVID-19 pandemic. Material(s) and Method(s): A cross-sectional study was conducted from 28 February 2022 to 9 June 2022. A researcher-made questionnaire was designed in MS research center of Iran and distributed as an online google form on social media among 1340 Iranian MS patients. Demographic information, MS disease-related data, possible MS triggers (stressful life events, COVID-19 and other infections, COVID-19 and other vaccines, pregnancy or labor, head trauma, surgery, weight loss) were recorded. Patients were divided into two groups regarding the time of MS diagnosis (before and during the COVID-19 pandemic). Binary logistic regression method was used to determine the possible association between patient-reported triggers and diagnosis time (before and during the pandemic) adjusting for possible confounders. Result(s): Of 920 participants, 670 (72.8 %) were female, and the mean age (SD) was 35.63 (+/-8.1). The majority of participants 637 (69.2%) had non-progressive forms of MS, and only 70 (7.6 %) needed assistance for ambulation. The time of MS diagnosis was before the start of the COVID-19 pandemic in 635 (69 %) participants. The differences between the most common first symptoms which led to MS diagnosis, visual type (n: 317 (49.9 %)) before the pandemic and sensory type (n: 170 (59.6 %)) after the pandemic were significant (p-values: 0.008 and <0.01 respectively). A stressful life event was the most common patient-reported MS trigger in both groups, (n: 356 (56.1%)) in patients who were diagnosed before the COVID-19 pandemic, and (n: 156 (54.7%)) in the latter group. Comparing two groups (MS diagnosed before and during the pandemic), economic problems (AOR: 1.81;95%ACI: 1.23-2.65) and job loss (AOR: 2.89;95%ACI: 1.37-6.08) were significantly more frequent stressful life event which trigger MS onset in the latter group while, the stress of occupational or educational exams (AOR: 0.52;95%ACI: 0.34-0.79) was more prevalent in the first group. Conclusion(s): Social triggers such as stressful life events are closely associated with MS onset that had been increased in some categories after the COVID-19 pandemic. If truly recognized, they could be used to prevent the development and exacerbation of the disease.Copyright © 2022

CNS Complications Following COVID-19 Vaccines: an Egyptian Case Series

Background: Despite the perceived safety and efficacy of COVID-19 vaccines, many reports worldwide highlighted the development of many complications involving CNS. Ischemia, new onset demyelination, and exacerbation of preexisting demyelinating conditions were among the most reported ones. The aim of this study is to report a series of Egyptian patients who developed either first episode of CNS ischemia, demyelination, or exacerbation of a preexisting demyelinating condition after receiving one of the approved COVID-19 vaccines. Material(s) and Method(s): Prospective collection of cases presenting with different CNS complications in temporal association with receiving one of the approved COVID vaccines in the period between December 2021 and March 2022. All patients presented for consultation at Alexandria University Neuroimmunology unit. Result(s): We identified 8 cases with post- vaccine CNS complications. There were 5 females and 3 males, and their ages ranged from 24-60 years. Their symptoms developed after an interval ranging from 3 days up to 4 weeks after the first (n= 3) or second dose of vaccine (n=5). All except one patient were diagnosed as either new onset MS or exacerbation of a preexisting MS. The last case was diagnosed as spinal cord infarction. Conclusion(s): This series adds to the growing literature of the possible association between COVID-19 vaccines and development/ exacerbation of CNS demyelination or ischemia. More data with long-term follow up is needed to establish or refute the causal relationship but meanwhile counseling patients without discouraging vaccination is advised.Copyright © 2022

A Rare Case of Miller Fisher Syndrome in a 45-Year-Old Female.

Miller Fisher syndrome (MFS) is an uncommon form of Guillain-Barré syndrome (GBS), a neurological condition that is acquired, degenerative, demyelinating, and frequently characterized by gradual, symmetrical ascending paralysis. Ophthalmoplegia, ataxia, and areflexia are common symptoms that follow a bacterial or viral infection. Here, we want to draw attention to a rare case of MFS in a 45-year-old Indian female who had dysphagia, dysphasia, ataxia, and dyskinesia while moving around. Unusually, she had no past medical history of Campylobacter jejuni infection, recent vaccinations, upper respiratory tract infections, or any sexually transmitted diseases. Since this disorder has excellent prognosis, early diagnosis and effective treatment are crucial to minimizing unnecessary medical intervention and psychological suffering.

Triggers of Guillain-Barré Syndrome: Campylobacter jejuni Predominates.

Guillain-Barré syndrome (GBS) is a rare immune-mediated acute polyradiculo-neuropathy that typically develops after a previous gastrointestinal or respiratory infection. This narrative overview aims to summarise and discuss current knowledge and previous evidence regarding triggers and pathophysiology of GBS. A systematic search of the literature was carried out using suitable search terms. The most common subtypes of GBS are acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The most common triggers of GBS, in three quarters of cases, are previous infections. The most common infectious agents that cause GBS include Campylobacter jejuni (C. jejuni), Mycoplasma pneumoniae, and cytomegalovirus. C. jejuni is responsible for about a third of GBS cases. GBS due to C. jejuni is usually more severe than that due to other causes. Clinical presentation of GBS is highly dependent on the structure of pathogenic lipo-oligosaccharides (LOS) that trigger the innate immune system via Toll-like-receptor (TLR)-4 signalling. AIDP is due to demyelination, whereas in AMAN, structures of the axolemma are affected in the nodal or inter-nodal space. In conclusion, GBS is a neuro-immunological disorder caused by autoantibodies against components of the myelin sheath or axolemma. Molecular mimicry between surface structures of pathogens and components of myelin or the axon is one scenario that may explain the pathophysiology of GBS.

An unusually fulminant case of encephalomyelitis in an 80 year old

Background: There have been reports of demyelinating syndromes in association with COVID-19 and to a much lesser extent COVID 19 vaccines. The association between demyelination and vaccines, in general, remains controversial. We review a presentation of fulminant demyelination, and discuss antecedent COVID-19 vaccination, the formulation of a broader differential diagnosis and ultimately the pathologic diagnosis. Case presentation: An 80-year-old woman presented with seizure, encephalopathy, quadriparesis and ultimately expired. She received a SARS-CoV-2 vaccine one day prior. Imaging revealed contrast enhancing cerebral lesions, longitudinally extensive transverse myelitis. CSF was markedly inflammatory. Pathologic examination of the CNS lesions revealed demyelination and inflammation beyond white matter, not restricted to a perivenular distribution. Conclusion(s): This case depicts a seemingly fulminant course of a diffuse demyelinating syndrome characterized clinicopathologically as Marburg's variant of multiple sclerosis. There are several unique aspects of this case including the extremely rapid course, the unusual evolution of CSF abnormalities, with hypoglycorrhachia and markedly elevated protein. The proximity to vaccination is a pertinent association to document, though we cannot unequivocally prove causation.Copyright © 2022 The Authors

MOTOR CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN A CHILD.

Motor chronic inflammatory demyelinating polyneuropathy (M-CIDP) is a form of atypical CIDP. This article presents a clinical observation of M-CIDP in a 15-year-old boy, as well as a description of laboratory and instrumental diagnostic data. The boy had a chronic development (> 2 months) of flaccid tetraparesis, predominantly of the proximal muscles of the limbs, without sensory disorders. According to electroneuromyography, there were signs of demyelinating lesions of the proximal parts of the peripheral nerves. There was an increase in the thickness of the nerves of the upper limbs according to ultrasound. In the liquor protein-cell dissociation, as well as in the blood, IgG antibodies to the surface glycoprotein S of the SARS-CoV-2 coronavirus were found. The clinical and neurophysiological picture corresponded to the reliable criteria for CIDP. The therapy with intravenous immunoglobulins had a significant positive effect in the form of an increase in the strength of the limb muscles.Copyright © Russian Neurological Journal. All rights reserved.

MOTOR CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN A CHILD.

Motor chronic inflammatory demyelinating polyneuropathy (M-CIDP) is a form of atypical CIDP. This article presents a clinical observation of M-CIDP in a 15-year-old boy, as well as a description of laboratory and instrumental diagnostic data. The boy had a chronic development (> 2 months) of flaccid tetraparesis, predominantly of the proximal muscles of the limbs, without sensory disorders. According to electroneuromyography, there were signs of demyelinating lesions of the proximal parts of the peripheral nerves. There was an increase in the thickness of the nerves of the upper limbs according to ultrasound. In the liquor protein-cell dissociation, as well as in the blood, IgG antibodies to the surface glycoprotein S of the SARS-CoV-2 coronavirus were found. The clinical and neurophysiological picture corresponded to the reliable criteria for CIDP. The therapy with intravenous immunoglobulins had a significant positive effect in the form of an increase in the strength of the limb muscles.Copyright © Russian Neurological Journal. All rights reserved.

MOTOR CHRONIC INFLAMMATORY DEMYELINATING POLYNEUROPATHY IN A CHILD.

Motor chronic inflammatory demyelinating polyneuropathy (M-CIDP) is a form of atypical CIDP. This article presents a clinical observation of M-CIDP in a 15-year-old boy, as well as a description of laboratory and instrumental diagnostic data. The boy had a chronic development (> 2 months) of flaccid tetraparesis, predominantly of the proximal muscles of the limbs, without sensory disorders. According to electroneuromyography, there were signs of demyelinating lesions of the proximal parts of the peripheral nerves. There was an increase in the thickness of the nerves of the upper limbs according to ultrasound. In the liquor protein-cell dissociation, as well as in the blood, IgG antibodies to the surface glycoprotein S of the SARS-CoV-2 coronavirus were found. The clinical and neurophysiological picture corresponded to the reliable criteria for CIDP. The therapy with intravenous immunoglobulins had a significant positive effect in the form of an increase in the strength of the limb muscles.Copyright © Russian Neurological Journal. All rights reserved.

COVID-19 associated acute demyelination masquerading as stroke: a case report

BackgroundDuring the recent outbreak of COVID-19, various atypical extrapulmonary manifestations are being seen, including neurological ones. Reported cases mainly include encephalopathy, myelitis, and cranial nerve involvement. This case describes uncommon neuroradiological finding in the context of COVID-19.Case presentationWe report an atypical case of COVID-19 presenting with stroke-like episode, with MRI brain showing isolated bilateral posterior internal capsule involvement. This has rarely been reported in literature.ConclusionAs the numbers of COVID-19 cases are increasing, such atypical presentations should be kept in mind.

Guillain-Barre Syndrome and COVID-19 Vaccine: A Report of Nine Patients

Introduction: Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.Methods: In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.Results: The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.Conclusion: The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental;therefore, more studies are needed to investigate a causal relationship.

34th Annual Meeting of the Japanese Society for Neuroimmunology (JSNI)

The proceedings contain 14 papers. The topics discussed include: MOG-positive anti-NMDA receptor encephalitis with no demyelinating lesions: two case reports;safety and tolerability of rozanolixizumab in the randomized phase 3 MycarinG study;Outcomes from RAISE: A randomized, phase 3 trial of zilucoplan in generalized myasthenia gravis;efficacy and safety of zilucoplan in myasthenia gravis: responder analysis from the randomized Phase 3 RAISE trial;distinct effects among calcium-binding proteins for microglia to produce chemokines associated with the clinical severity of ALS;astroglial connexin 43 is a novel therapeutic target for a chronic multiple sclerosis model;targeting lymphocytes in SPMS: Th cell populations as a biomarker to predict the efficacy of Siponimod;CSF lysophospholipids as a novel biomarker in relapsing-remitting multiple sclerosis;the immune response to SARS-COV-2 MRNA vaccines in siponimod-treated patients with secondary progressive multiple sclerosis;patient characteristics of siponimod-treated SPMS patients in Japan: interim results from post-marketing surveillance;and efficacy of ravulizumab across sex and age subgroups of patients with generalized myasthenia gravis: a post hoc analysis of the CHAMPION MG study.

Progressive multifocal leukoencephalopathy, neuroradiology-neuropathology

Introduction: Progressive multifocal leukoencepha-lopathy (PmL) is an unfavorable demyelinating disease of the CNS caused by reactivation of JC virus (JCV). JCV is a double-stranded DNA human polyomavirus predominatingly acquired in childhood. Blood samples taken from healthy persons indicate that 50-90% of adults have been exposed to this virus. JCV is an opportunistic pathogen, with PmL manifesting primarily in patients with immunodefciency or taking immunomodulatory treatments or with lymphoproliferative diseases. We report a patient who developed PmL shortly after diagnosis of follicular lymphomma. Case presentation: A 70-year-old-woman admitted to the neurological departament with hemiparesis, psy-chomotor slowing down, balance problems, dizziness and in depressed mood. the patient underwent aorto-femoral transplant 12 years ago and for 10 years was under constant observation of a hematologist due to enlarged lymph nodes. Five years ago, the patient had planoepithelial cell carcinoma removed. the patient also sufered from COViD-19 infection and sufered from depression. elevated leukocytosis and D dimers, were the only abnormal results obtained in laboratory tests. However, pulmonary embolism was excluded in Ct angio. Cytometry of blood showed follicular lymphoma. Radiological fndings: mRi and Ct scans showed multiple asymmetrical pathological areas of hyperin-tense signal in t2-dependent images, hypointense in t1-dependent ones and Ct-hypodense regions which extended continuously in control examinations. they were located in the white matter of multiple lobes of both brain hemispheres subcortically and periventric-ullary. the subcortical U-fbers were involed. they did not show contrast enhancement and mass efect. they showed peripheral ring and patchy difusion restriction particularly at their leading edge. in spite of the used steroid therapy the patient's health deteriorated rapidly. the patient died of symptoms of cardio-respiratory failure 1 month after admission to hospital. Neuropathological features: the neuropathological examination revealed numerous foci of demyelination in the white matter of the frontal lobe, the parietal lobe in the pons and in the cerebellum. myelin losses were accompanied by damage to oligodendrocytes and proliferation of macrophages. the nuclei of the damaged oligodendrocytes were enlarged and hyperchromatic, and some had a "ground-glass" appearance typical of viral infection. the astrocytes were bizarre with lobulat-ed, hiperchromatic or hypochromatic nuclei and damage of cytoplasmic procesesses (clasmatodendrosis). Conclusion(s): the triad of neuropathological injuries: destruction of oligodendrocytes with intranuclear viral inclusions ("ground-glass" appearance), multifocal demyelination and bizarre astrocytes allowed for the diagnosis of late form of classical progressive multifo-cal leukoencephalopathy (cPmL), despite the short time since diagnosis of follicular lymphoma, but with many years of enlargement of the lymph nodes.