Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders.

Background and Objective: Post-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts. Methods: A total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices. Results: In the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated. Conclusion: Our research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Neuromyelitis Optica Spectrum Disorder Resembling Wernicke's Encephalopathy: A Case Report and Review of the Literature.

We describe a case of Neuromyelitis Optica Spectrum Disorder (NMOSD) mimicking Wernicke's Encephalopathy (WE) to highlight an atypical presentation of NMOSD. A 39-year-old female presented with subacute encephalopathy and progressive ophthalmoplegia. Her MRI revealed T2 hyperintensities involving the mammillary bodies, periaqueductal grey matter, medial thalami, third ventricle, and area postrema. Whole blood thiamine levels were elevated and she did not improve with IV thiamine. CSF was notable for lymphocytic pleocytosis and elevated protein. She tested positive for serum Aquaporin-4 (AQP4) antibody. Subsequent imaging revealed multilevel lesions in the cervical and thoracic spinal cord. Her CSF GFAP antibody also came back positive. She steadily and significantly improved after high-dose IV steroids and plasmapheresis. She later started on chronic rituximab therapy. This represents a unique case of NMOSD presenting with the classical clinical and imaging features of WE, as opposed to the typical presenting symptoms of NMOSD. As such, demyelinating disorders should be considered when there is concern for diencephalic and midline pathologies, particularly without classic WE risk factors. Conversely, clinicians should be aware of secondary nutritional complications arising from severe area postrema syndrome.

Recaídas del trastorno de espectro de la neuromielitis óptica e influencia estacional en una cohorte de un país ecuatorial / Neuromyelitis optica spectrum disorders relapses and seasonal influence in an equatorial country cohort

Introducción La evidencia sobre la distribución estacional de las recaídas del trastorno del espectro de la neuromielitis óptica (NMOSD), especialmente en países tropicales, es limitada y diversa. Objetivo Evaluar la influencia de las variaciones estacionales en las recaídas del NMOSD en un país localizado sobre la línea ecuatorial. Pacientes y métodos Se llevó a cabo un estudio ecológico, con información retrospectiva de una cohorte de pacientes con NMOSD atendida entre enero de 2003 y diciembre de 2020 en Medellín, Colombia. Se recolectaron datos demográficos y clínicos de los pacientes, así como información sobre variables estacionales y climáticas. Se calculó la frecuencia de recaídas por estación, mes y año, y se realizó una regresión binomial negativa para evaluar la asociación entre el número de recaídas, y las variables estacionales y climáticas. Resultados Se incluyó a 113 pacientes, de los cuales el 89,38% eran mujeres, con una edad media en el momento del diagnóstico de NMOSD de 44,97 (±13,98) años y una mediana de tres recaídas (rango intercuartílico: 1-2). Se registraron 237 recaídas, la mayoría en pacientes seropositivos para anticuerpos antiacuaporina 4 (87,76%) y con mielitis longitudinal extensa como la presentación clínica más común (53,59%). Las recaídas se presentaron con mayor frecuencia durante la segunda temporada lluviosa (28,69%; n = 68), y en los meses de noviembre y diciembre. Sin embargo, en la regresión binomial negativa no se observó una asociación significativa entre el número de recaídas y las variables climáticas y estacionales, los meses y los años. Conclusión Las variables climáticas y los patrones estacionales no muestran una asociación significativa con cambios en el número de recaídas del NMOSD en pacientes residentes en un país localizado sobre la línea ecuatorial. (AU)

INTRODUCTION Information about seasonal distribution of Neuromyelitis optica spectrum disorders (NMOSD) attacks, particularly in tropical countries, has rarely been described and the reported data are diverse. OBJECTIVE. To evaluate influence of seasonal variation in NMOSD relapses in an equatorial country. PATIENTS AND METHODS Exploratory observational, retrospective ecological study in a cohort of patients with NMOSD followed from January 2008 to December 2019. Data of demographic, clinical information, characteristics of relapses and seasonal temporal variation were recorded. Also, the annual, monthly and intra-annual seasonal variation of relapses was quantified. A negative binomial regression was used to estimate the associations between the number of relapses and climatic and temporal variables. RESULTS One hundred thirteen patients were included, most of them were female (89.38%), with a mean age at NMOSD diagnosis was 44.97 (±13.98) and the median of relapses per patient were 2 relapses (IQR 1-3). The patients presented 237 relapses, most of these in AQP4 seropositive patients (87.76%) and longitudinal extensive myelitis was the most frequent type of relapse (53.59%). According to the temporal variation, relapses were more common in the second rainy season (28.69%) during November and December. However, there weren’t significant differences in the number of relapses between seasons and climatic variables in the multivariable model. CONCLUSION. The number of NMOSD relapses in this equatorial country cohort did not exhibit any significant associations with climatic variations, including changes in rainy or dry seasons. (AU)

Clinical Research into Central Nervous System Inflammatory Demyelinating Diseases Related to COVID-19 Vaccines.

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. OBJECTIVE: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). METHODS: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. RESULTS: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33). CONCLUSION: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.

The Schwann cell-specific G-protein Gαo (Gnao1) is a cell-intrinsic controller contributing to the regulation of myelination in peripheral nerve system.

Myelin sheath abnormality is the cause of various neurodegenerative diseases (NDDs). G-proteins and their coupled receptors (GPCRs) play the important roles in myelination. Gnao1, encoding the major Gα protein (Gαo) in mammalian nerve system, is required for normal motor function. Here, we show that Gnao1 restricted to Schwann cell (SCs) lineage, but not neurons, negatively regulate SC differentiation, myelination, as well as re-myelination in peripheral nervous system (PNS). Mice lacking Gnao1 expression in SCs exhibit faster re-myelination and motor function recovery after nerve injury. Conversely, mice with Gnao1 overexpression in SCs display the insufficient myelinating capacity and delayed re-myelination. In vitro, Gnao1 deletion in SCs promotes SC differentiation. We found that Gnao1 knockdown in SCs resulting in the elevation of cAMP content and the activation of PI3K/AKT pathway, both associated with SC differentiation. The analysis of RNA sequencing data further evidenced that Gnao1 deletion cause the increased expression of myelin-related molecules and activation of regulatory pathways. Taken together, our data indicate that Gnao1 negatively regulated SC differentiation by reducing cAMP level and inhibiting PI3K-AKT cascade activation, identifying a novel drug target for the treatment of demyelinating diseases.

Síndrome de Brown-Séquard como forma de presentación de mielitis transversa idiopática / Brown-Séquard syndrome as a presentation of idiopathic transverse myelitis

El síndrome de Brown-Séquard es el conjunto de signos y síntomas causado por hemisección medular de diversos orígenes. Puede generarse por múltiples causas; las traumáticas son las más frecuentes. Las causas menos frecuentes son patología inflamatoria, isquémica, tumoral o infecciosa. Se presenta un niño de 12 años, con instauración aguda y progresiva de un síndrome de hemisección medular derecho, con parálisis hipo/arrefléctica homolateral y afectación de sensibilidad termoalgésica contralateral. En la resonancia magnética de médula espinal, se observó compromiso inflamatorio en hemimédula derecha a nivel de segunda y tercera vértebras torácicas. Con diagnóstico de mielitis transversa idiopática, inició tratamiento con corticoide intravenoso a altas dosis con evolución clínica favorable y restitución de las funciones neurológicas.

Brown-Séquard syndrome refers to a set of signs and symptoms caused by hemisection of the spinal cord from various sources. It may have multiple causes; traumatic injuries are the most frequent ones. The less common causes include inflammation, ischemia, tumors, or infections. This report is about a 12-year-old boy with an acute and progressive course of right hemisection of the spinal cord, with ipsilateral hypo/areflexic paralysis and contralateral loss of thermalgesic sensation. The MRI of the spinal cord showed inflammation in the right side of the spinal cord at the level of the second and third thoracic vertebrae. The patient was diagnosed with idiopathic transverse myelitis and was started on intravenous high-dose corticosteroids; he showed a favorable clinical course and recovered neurological functions.

Treatment refractory acute necrotizing myelitis after COVID-19 vaccine injection: a case report.

Introduction and importance: Post-vaccination myelitis is a rare and debilitating clinical situation. There are few reports of post-COVID-19 infection and vaccination neurological sequela. Case presentation: A 69-year-old lady was admitted to the emergency department due to weakness and hypoesthesia in her hands 1 week after the Sinopharm vaccine injection. MRI showed a cervicothoracic cord haemorrhagic lesion that deteriorated within 48 h. The clinical course was refractory to conservative treatments. She underwent an emergency cervical laminectomy as a salvage treatment. Intraoperative samples were in favour of acute necrotizing myelitis. Discussion: In the review of the literature, the inflammatory storm, vasculitis, and many unknown etiologies are deemed to be the possible causes of encephalopathy and myelitis after COVID-19 infection and vaccination. There are few cases of post-COVID-19 myelitis and hematomyelia, but this case was the first report of post-vaccination necrotizing myelitis. Conclusion: Post-vaccination necrotizing myelitis is a lethal medical situation requiring intensive and emergent neurosurgical vigilance. Early clinical diagnosis in the beginning and full neurosurgical-neurological treatment armamentarium options are cornerstones of treatment paradigms. Salvage treatment options such as extensive laminectomy may play a life-saving role in treatment refractory cases of acute necrotizing myelitis.

Parakinesia Brachialis Oscitans and Excessive yawning From Tumefactive Demyelination.

We present a case and video of a 31-year-old man with biopsy-confirmed tumefactive demyelination affecting the right internal capsule causing left hemiplegia, excessive yawning, and the curious but well-described phenomenon of parakinesia brachialis oscitans (PBO) with transient tonic elevation of his paralyzed arm while yawning. PBO is most commonly reported in ischemic stroke with internal capsule or pontomedullary brainstem lesions. Our case uniquely demonstrates this phenomenon in the case of tumefactive demyelination. We also highlight excessive yawning which has also been described in multiple sclerosis.

MOG-IgG testing strategies in accordance with the 2023 MOGAD criteria: a clinical-laboratory assessment.

BACKGROUND: Live cell-based assay (LCBA) is the gold standard for MOG-IgG detection, and fixed CBA (FCBA) is a widely used commercial alternative. Recent criteria attributed a diagnostic value to MOG-IgG titration with both LCBA and FCBA, with low-titre samples requiring additional supporting features for MOGAD diagnosis. However, FCBA titration is not validated. We aimed to assess the impact of the criteria-based MOG-IgG testing in MOGAD diagnosis. METHODS: Thirty-eight serum samples of LCBA MOG-IgG1-positive MOGAD patients were titred on MOG-IgG LCBA and FCBA, and the presence of supporting features for MOGAD assessed. MOGAD criteria were evaluated in four testing scenarios: (a) FCBA without titration; (b) FCBA with titration; c) LCBA without titration; (d) LCBA with titration. RESULTS: FCBA without titration failed to reach MOGAD diagnosis in 11/38 patients (28.9%, negative results in 5, lack of supporting features in 6). Patients with unconfirmed diagnosis had optic neuritis (ON, n = 8), or transverse myelitis (TM, n = 3). FCBA with titration allowed MOGAD diagnosis in 4 additional patients. Correlation between LCBA and FCBA titres was moderate (Spearman's rho 0.6, p < 0.001). CONCLUSIONS: FCBA yields high rate of misdiagnosis mainly due a lower analytical sensitivity. FCBA titration provides a moderate diagnostic advantage in FCBA positive patients.

Spectrum of various CNS inflammatory demyelination diseases following COVID-19 vaccinations.

BACKGROUND AND PURPOSE: Although rare, neurological adverse events have been reported post-COVID-19 vaccination. This study reports 16 patients diagnosed with CNS inflammatory demyelinating diseases (CNS-IDD) within 6 weeks of COVID-19 vaccine administration. METHODOLOGY: A prospective observational study was conducted from June 2021 to May 2022. All patients were diagnosed according to the latest international guidelines with CNS-IDD within 6 weeks of COVID-19 vaccine exposure. Data regarding the demographic profile, clinical features, type of COVID-19 vaccination, radiological findings and occurrence of symptoms were noted and further analysed using descriptive statistics. RESULTS: We reported 16 cases (median age 40 years) of CNS demyelination: fourteen occurred in temporal association with ChAdOx1-S vaccine and two in association with BBV152 vaccine. Median time duration of presenting symptoms after vaccination was 19 days (3-40 days). The most common presentation was myelitis (7/16 patients), followed by optic neuritis (6/16 patients). Demyelination events were reported after first and second dose in thirteen and five patients respectively, although two patients reported such events after both vaccine dosages. Myelin oligodendrocyte glycoprotein (MOG) IgG antibodies were positive in eight patients. Tumefactive demyelination was seen in four patients. Management included high-dose methylprednisolone, PLEX, IVIG or a combination of those, with a favourable outcome in the majority of cases. CONCLUSION: Although a rare event, awareness regarding potential demyelinating episodes post-COVID-19 vaccination can help in early diagnosis. The presence of increased MOG-IgG antibodies with temporal association in post-COVID vaccine patients raises a possibility of an immunogenic phenomenon leading to demyelinating disorders.

Brown-Séquard syndrome as a presentation of idiopathictransverse myelitis. / Síndrome de Brown-Séquard como forma de presentación de mielitis transversa idiopática.

Brown-Séquard syndrome refers to a set of signs and symptoms caused by hemisection of the spinal cord from various sources. It may have multiple causes; traumatic injuries are the most frequent ones. The less common causes include inflammation, ischemia, tumors, or infections. This report is about a 12-year-old boy with an acute and progressive course of right hemisection of the spinal cord, with ipsilateral hypo/areflexic paralysis and contralateral loss of thermalgesic sensation. The MRI of the spinal cord showed inflammation in the right side of the spinal cord at the level of the second and third thoracic vertebrae. The patient was diagnosed with idiopathic transverse myelitis and was started on intravenous high-dose corticosteroids; he showed a favorable clinical course and recovered neurological functions.

El síndrome de Brown-Séquard es el conjunto de signos y síntomas causado por hemisección medular de diversos orígenes. Puede generarse por múltiples causas; las traumáticas son las más frecuentes. Las causas menos frecuentes son patología inflamatoria, isquémica, tumoral o infecciosa. Se presenta un niño de 12 años, con instauración aguda y progresiva de un síndrome de hemisección medular derecho, con parálisis hipo/arrefléctica homolateral y afectación de sensibilidad termoalgésica contralateral. En la resonancia magnética de médula espinal, se observó compromiso inflamatorio en hemimédula derecha a nivel de segunda y tercera vértebras torácicas. Con diagnóstico de mielitis transversa idiopática, inició tratamiento con corticoide intravenoso a altas dosis con evolución clínica favorable y restitución de las funciones neurológicas.

Tract-wise microstructural analysis informs on current and future disability in early multiple sclerosis.

OBJECTIVES: Microstructural characterization of patients with multiple sclerosis (MS) has been shown to correlate better with disability compared to conventional radiological biomarkers. Quantitative MRI provides effective means to characterize microstructural brain tissue changes both in lesions and normal-appearing brain tissue. However, the impact of the location of microstructural alterations in terms of neuronal pathways has not been thoroughly explored so far. Here, we study the extent and the location of tissue changes probed using quantitative MRI along white matter (WM) tracts extracted from a connectivity atlas. METHODS: We quantified voxel-wise T1 tissue alterations compared to normative values in a cohort of 99 MS patients. For each WM tract, we extracted metrics reflecting tissue alterations both in lesions and normal-appearing WM and correlated these with cross-sectional disability and disability evolution after 2 years. RESULTS: In early MS patients, T1 alterations in normal-appearing WM correlated better with disability evolution compared to cross-sectional disability. Further, the presence of lesions in supratentorial tracts was more strongly associated with cross-sectional disability, while microstructural alterations in infratentorial pathways yielded higher correlations with disability evolution. In progressive patients, all major WM pathways contributed similarly to explaining disability, and correlations with disability evolution were generally poor. CONCLUSIONS: We showed that microstructural changes evaluated in specific WM pathways contribute to explaining future disability in early MS, hence highlighting the potential of tract-wise analyses in monitoring disease progression. Further, the proposed technique allows to estimate WM tract-specific microstructural characteristics in clinically compatible acquisition times, without the need for advanced diffusion imaging.

Encefalomielite aguda disseminada com provável etiologia de Bartonella henselae / Acute disseminated encephalomyelitis with probable Bartonella henselae etiology

RESUMO A encefalomielite aguda disseminada é uma doença rara, aguda, inflamatória e desmielinizante do sistema nervoso central, presumivelmente associada, em mais de três quartos dos casos, a infecções (virais, bacterianas ou inespecíficas) e imunizações ou sem qualquer antecedente indentificável. Habitualmente, apresenta um curso monofásico com início de sintomas inespecíficos na fase prodrómica, podendo evoluir com alterações neurológicas multifocais e até à perda total da acuidade visual. Descrevemos o caso de um menino de 9 anos com quadro inicial de edema de papila causado por encefalomielite aguda disseminada devido a Bartonella henselae. Apesar da gravidade da doença, o diagnóstico e o tratamento precoce proporcionaram bons desfechos.

ABSTRACT Acute disseminated encephalomyelitis is a rare, acute, inflammatory, and demyelinating disease of the central nervous system. Presumably associated in more than three quarters of cases by infections (viral, bacterial, or nonspecific) and immunizations or without any identifiable antecedent. It usually presents a monophasic course with onset of nonspecific symptoms in the prodromal phase and may evolve with multifocal neurological changes and even visual acuity loss. We describe a case of a 9-year-old boy with an initial picture of papillary edema caused by acute disseminated encephalomyelitis due to Bartonella henselae. Despite the severity of the disease, early diagnosis and treatment provided good outcomes.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) Following Adenovirus Meningitis After First Delivery: Case Report and Literature Review.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a group of central nervous system (CNS) demyelinating diseases caused by autoantibodies against myelin oligosaccharide protein (MOG), a myelin sheath component protein, and present with a variety of symptoms, including optic neuritis, myelitis, acute disseminated encephalomyelitis (ADEM), brainstem encephalitis, and corticobasal encephalitis. It is currently unknown at what point in life MOGAD can develop or how it can be triggered by autoimmune mechanisms. Here, we report a case of a mature woman who suffered from adenoviral meningitis one month after childbirth and developed MOGAD but was able to return to child rearing with high-dose methylprednisolone therapy. This case suggests that the risk of developing MOGAD early after childbirth may be increased. The case also suggested that adenoviral infection may be involved in the development of MOGAD.

Occupational outcomes of people with multiple sclerosis during the COVID-19 pandemic: a systematic review with meta-analysis.

Background: People with Multiple Sclerosis (PwMS) are vulnerable to unfavorable occupational outcomes and the COVID-19 pandemic brought major consequences on people's professional lives. In this view, we decided to investigate the occupational outcomes of PwMS during the COVID-19 pandemic. Methods: We performed a systematic review with meta-analysis searching key terms in four databases. We initially included any peer-reviewed original article that enrolled adult patients with the diagnosis of MS and assessed any occupational variable during the COVID-19 pandemic. There were no time limits and no language restrictions. The primary outcomes were the prevalence of unemployment, retirement and employment status change among people with MS during the COVID-19 pandemic. Other outcomes included the modality and characteristics of work: type of work, full-time work, part-time work and remote work. We also searched for data from studies that addressed any change in the work status due to the COVID-19 outbreak. Results: We identified 49 eligible articles comprising a total sample size of 17,364 individuals with MS. The pooled prevalence of unemployment and retirement was 0.47 (95% CI = 0.42-0.53). The pooled prevalence of PwMS who were unemployed or retired was positively associated with the progressive phenotype of the disease (p = 0.017) and the use of glatiramer acetate (p = 0.004), but negatively associated with hospitalization due to COVID-19 (p = 0.008) and the use of immunosuppressants (p = 0.032), siponimod (p < 0.001), and cladribine (p = 0.021). The pooled proportion of PwMS that reported any change of the employment status during the COVID-19 pandemic was 0.43 (95% CI = 0.36-0.50) while the pooled prevalence of PwMS who worked remotely during this period was 0.37 (95% CI = 0.15-0.58). The change in employment status was negatively associated with the duration of MS (p = 0.03) but positively associated with the progressive phenotype of the disease (p < 0.001). Conclusion: Our seminal review may serve as an example of how patients with neurological diseases or disabilities in general may have their jobs impacted in a pandemic and foster the context of global socio-economic crisis.

Incidence of Optic Neuritis among Omani Patients with Multiple Sclerosis at the Sultan Qaboos University Hospital, Muscat, Oman.

Objectives: Multiple sclerosis (MS) is a chronic, multifaceted, heterogeneous autoimmune disease, with optic neuritis (ON) being a common early manifestation among those with MS. This study aimed to estimate the incidence of ON among Omani patients with MS. Methods: This retrospective cross-sectional study included all Omani patients diagnosed with MS at the Sultan Qaboos University Hospital, Muscat, Oman, between January 1991 and December 2019. The data were collected from the neurology registry and electronic medical records and analysed descriptively using univariant and multivariant statistical techniques. Results: Out of the 185 patients diagnosed with MS during the study period, 170 were included in the analysis. The male-to-female ratio was 1:2 and the mean age was 28 years. The incidence of ON in the population was 28.8%, with 83.7% of ON patients presenting with relapse-remitting MS (RRMS). Overall, 28.6% of patients presented with O N as an initial manifestation of MS, whereas 42.8% developed ON at a later stage. Most patients (49.4%) were from higher-latitude regions of Oman such as Muscat and Al Batinah. Conclusions: The incidence of both MS and ON increased over the study period. While the overall incidence was low in comparison with Western data, it was similar to the rates reported elsewhere in the Arabian Peninsula. Overall, ON was the most common manifestation of MS in the cohort, with younger female patients more frequently presenting with both MS and ON. A significant association was found between the RRMS subtype and ON presentation.

Alucinosis peduncular en esclerosis múltiple, síntoma poco común en la expresión de enfermedad desmielinizante / Peduncular hallucinosis in multiple sclerosis, a rare symptom in demyelinating disease

Introducción: La alucinosis peduncular (AP) hace referencia a alucinaciones autodiscriminadas, cuyo origen son lesiones en el mesencéfalo y en el puente. Presentación del caso: Paciente 27 años, femenina, con alucinaciones visuales, auditivas autodiscriminadas por ella misma, sin antecedentes previos de importancia y con lesiones en resonancia magnética cerebral y cervical en el pedúnculo cerebeloso superior, tegmento pontino, y en columna cervical con bandas oligoclonales patrón 2, que cumplían criterios de Mc Donalds para esclerosis múltiple. Discusión: La alucinosis peduncular hace referencia a la presencia de alucinaciones visuales, criticadas por el paciente, con la consecuencia de lesiones de las vías inhibitorias por deaferentación y desinhibición mesencéfalotalámicas, y retinogenículo calcarina, descritas como manifestación de múltiples patologías neurológicas como trauma, afectación vascular, tumores y pocos casos de enfermedad desmielinizante, entre otras. Conclusión: La alucinosis peduncular es una forma atípica de presentación de lesiones pontomesencefálicas descritas en varias patologías; se debe tener en cuenta en la localización de la lesión neurológica; se han reportado pocos casos como síntoma de la enfermedad desmielinizante.

Introduction: Peduncular hallucinosis (PA) refers to self-discriminating hallucinations, these are caused by lesions in the midbrain and pons. Presentation of the case: 27-year-old right handed female patient with visual and auditory hallucinations self-discriminated by the patient, with no prior history of importance and with lesions in cerebral and cervical Magnetic Resonance in the superior cerebellar peduncle, pontine tegmentum, and in the cervical spine with pattern 2 oligo clonal bands, which met Mc Donald's criteria for multiple sclerosis. Discussion: Peduncular hallucinosis refers to the presence of visual hallucinations criticized by the patient, consequence of lesions in the inhibitory pathways with deafferentation and disinhibition of the midbrain-thalamic and retinogeniculus-calcarine pathways. Described as a manifestation of multiple neurological pathologies such as trauma, vascular, tumor and few cases of demyelinating among others. Conclusion: Peduncular hallucinosis is an atypical form of presentation of pontomesencephalic lesions described in several pathologies, it must be taken into account when locating the neurological lesion, few cases have been reported as symptom of the demyelinating disease.

Deletion of voltage-gated calcium channels in astrocytes decreases neuroinflammation and demyelination in a murine model of multiple sclerosis.

The experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis was used in combination with a Cav1.2 conditional knock-out mouse (Cav1.2KO) to study the role of astrocytic voltage-gated Ca++ channels in autoimmune CNS inflammation and demyelination. Cav1.2 channels were specifically ablated in Glast-1-positive astrocytes by means of the Cre-lox system before EAE induction. After immunization, motor activity was assessed daily, and a clinical score was given based on the severity of EAE symptoms. Cav1.2 deletion in astrocytes significantly reduced the severity of the disease. While no changes were found in the day of onset and peak disease severity, EAE mean clinical score was lower in Cav1.2KO animals during the chronic phase of the disease. This corresponded to better performance on the rotarod and increased motor activity in Cav1.2KO mice. Furthermore, decreased numbers of reactive astrocytes, activated microglia, and infiltrating lymphocytes were found in the lumbar section of the spinal cord of Cav1.2KO mice 40 days after immunization. The degree of myelin protein loss and size of demyelinated lesions were also attenuated in Cav1.2KO spinal cords. Similar results were found in EAE animals treated with nimodipine, a Cav1.2 Ca++ channel inhibitor with high affinity to the CNS. Mice injected with nimodipine during the acute and chronic phases of the disease exhibited lower numbers of reactive astrocytes, activated microglial, and infiltrating immune cells, as well as fewer demyelinated lesions in the spinal cord. These changes were correlated with improved clinical scores and motor performance. In summary, these data suggest that antagonizing Cav1.2 channels in astrocytes during EAE alleviates neuroinflammation and protects the spinal cord from autoimmune demyelination.