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The latest articles on Neuroscience and Neuroimmunology

Published on: 26 May 2022 Viewed: 262

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles are related to Neuroscience and Neuroimmunology.

Title: Feedback from neurology residents and neuroimmunology fellows about the practical training in multiple sclerosis
Authors: Guilherme Diogo Silva
Type: Original Article
Abstract:
Objective
To obtain feedback from Neurology residents and Neuroimmunology fellows about the practical training in multiple sclerosis (MS).

Methods
A survey was developed and administered electronically to Neurology residents or Neuroimmunology fellows that received training in eight large MS outpatient clinics in Brazil, from 2018 to 2021. We evaluated their beliefs on: (1) the optimal number of MS patients evaluated in a 4-hour outpatient clinic session, (2) the quality of dedicated MS medical records, (3) the training of the neurological exam in MS patients, (4) the teaching discussion with the attending neuroimmunologist and (5) the prescription of MS disease-modifying drugs (DMDs).

Results
The response rate was 57% (43/76). We found that 4 or 5 MS patients would be optimal during a 4-hour outpatient clinic session. Optimal MS medical records were considered structured and presented in a timeline of disease activity and the history of DMDs. 18 in 43 (42%) respondents felt insecure in performing clinical scales used in MS patients. Discussion with the attending neurologist specialized in Neuroimmunology was considered adequate in only half of the respondents, suggesting a need for improvement in teaching strategies. Almost a quarter of the respondents (11/43, 26%) felt that the prescription of DMDs was complex and challenging. Some respondents suggested that readymade templates could be helpful.

Conclusion
The number of patients, medical records, use of MS clinical scales, discussion with attending neurologist specialized in MS care, and the prescription of DMDs present room for improvement in MS training for Neurology residents and Neuroimmunology fellows.
Access this article: https://doi.org/10.1016/j.msard.2022.103821


Title: SARS-CoV-2 infection in patients with neuroimmunological disorders in a tertiary referral centre from the north of Portugal
Authors: João Moura, Henrique Nascimento, Inês Ferreira, Raquel Samões, Catarina Teixeira, Dina Lopes, Daniela Boleixa, Ana Paula Sousa, Ernestina Santos, Ana Martins Silva
Type: Research Article
Highlights:
●Older age appears to be the most implicated factor in COVID-19 severity in patients with neuroimmunological disorders.
●We found no association between disease modifying therapy and outcome.
●COVID-19 mortality rate appears to be greater in patients with neuroimmunological disorders compared to the general population.
●Recognizing the risk factors for severe COVID-19 in patients with neuroimmunological disorders could help to improve treatment decision making and appropriate monitoring strategies.
Abstract:
Introduction
The impact of COVID-19 in patients with neuroimmunological disorders is not fully established. There is some evidence suggesting an increased risk of more severe infection associated with the use of immunosuppressors in this population. Objective
To characterize SARS-CoV-2 infection in patients followed in the neuroimmunology outpatient clinic of a tertiary centre from the north of Portugal.

Methods
Retrospective analysis of neuroimmunological patients with PCR-proven SARS-CoV-2 infection during the observational period of 20 months.

Results
Ninety-one patients were infected, 68.1% female, with a mean age of 48.9±16.7 years. The median disease duration was 11.0 (IQR 6.0-19.0) years. Sixty-one patients (67.0%) had Multiple Sclerosis, of which 50 with relapsing-remitting course, 12 (13.2%) Myasthenia Gravis (MG), 6 (6.6%) Autoimmune Encephalitis and 6 (6.6%) Chronic Inflammatory Demyelinating Polyneuropathy. Seventy-six patients (83.5%) were taking disease-modifying therapy, 77.6% of which were on immunosuppressants, including anti-CD20 in 12 (13.2%). Most patients had mild COVID-19 (84.6%), with 3 cases (3.3%) of severe disease and, 7 cases (7.7%) of critical disease being reported. In total, 13 patients were hospitalized and 4 died. Patients with severe to critical disease were significantly older than patients with milder forms (69.4±21.0 versus 46.5±14.4 years, p<0.01). MG was also associated with more severe disease (p=0.02). There was no association between comorbidities or use of immunosuppressors (including anti-CD20) and COVID-19 severity.

Conclusions
Greater age and MG were associated with severe or critical COVID-19. We found no association between a specific DMT, including anti-CD20, and outcome. Clinical recovery was achieved by 93.4%.
Access this article: https://doi.org/10.1016/j.msard.2022.103893


Title: Parkinsonism in multiple sclerosis patients: A prospective observational study
Authors: Shlok Sarin, Alexander Wang, Mohamed Elkasaby, Hesham Abboud
Type: Original Article
Abstract:
Background
Rare cases of coexisting multiple sclerosis and parkinsonism have been reported in the literature. However, the true prevalence, clinical characteristics, and causal relation between the two entities have not been systematically evaluated.

Objective
To evaluate the prevalence of parkinsonism in patients with multiple sclerosis and examine the causal relationship, if any.

Methods
Consecutive patients referred to the multiple sclerosis clinic were evaluated by a neurologist with double training in both neuroimmunology and movement disorders. All patients were specifically screened for movement disorders via a movement disorder survey and a focused exam. Video samples were independently rated by two blinded movement disorder raters. Pre-specified criteria were developed for five potential clinical scenarios: incidental idiopathic Parkinson's disease, incidental Parkinson-plus syndrome, drug-induced parkinsonism, acute symptomatic parkinsonism, and chronic symptomatic parkinsonism.

Results
From 2016 to 2021, 336 patients were evaluated. Of those, 12 patients (3.6%) had clinical parkinsonism (average age 68 years, 66% females). Nine patients (75%) were deemed to have incidental Parkinson's disease, 2 (17%) had drug-induced parkinsonism, and 1 (8.3%) was deemed to have demyelination-related chronic symptomatic parkinsonism. The latter presented with gradual and progressive parkinsonism without prodromal symptoms. Both blinded raters agreed with the parkinsonism phenomenology. In addition to typical enhancing and non-enhancing demyelinating lesions, the patient had lesions bilaterally in the basal ganglia. She had positive oligoclonal bands in the cerebrospinal fluid. DAT scan was normal. She was diagnosed with PPMS with activity and progression manifesting solely with secondary parkinsonism. Her disease stabilized with ocrelizumab. There were no cases of acute symptomatic parkinsonism or co-existing Parkinson-plus syndrome over the five-year duration of the study. Three of the incidental idiopathic Parkinson's disease cases had radiologically isolated syndrome.

Conclusion
Parkinsonism in MS is rare and most cases are incidental. However, clinicians need to recognize the entity of demyelination-related chronic symptomatic parkinsonism in patients with progressive MS phenotypes and demyelinating lesions in the basal ganglia and/or upper midbrain. Parkinsonism may be the sole clinical presentation of progressive MS and the only indication for DMT initiation or escalation. There is an over-representation of radiologically isolated syndrome in patients with presumptive incidental demyelination and idiopathic Parkinson's disease. Prospective studies utilizing high-field MRI and longitudinal DAT scans are needed to better characterize the complex relationship between demyelination and parkinsonism.
Access this article: https://doi.org/10.1016/j.msard.2022.103796


Title: Neuroimmune communication regulating pruritus in atopic dermatitis
Authors: Martin Steinhoff, Fareed Ahmad, Atul Pandey, Angeliki Datsi, Ayda AlHammadi, Sara Al-Khawaga, Aysha Al-Malki, Jianghui Meng, Majid Alam, Joerg Buddenkotte
Type: Research Article

Atopic dermatitis (AD) is a common, chronic-relapsing inflammatory skin disease with significant disease burden. Genetic and environmental trigger factors contribute to AD, activating 2 of our largest organs, the nervous system and the immune system. Dysregulation of neuroimmune circuits plays a key role in the pathophysiology of AD, causing inflammation, pruritus, pain, and barrier dysfunction. Sensory nerves can be activated by environmental or endogenous trigger factors, transmitting itch stimuli to the brain. On stimulation, sensory nerve endings also release neuromediators into the skin, contributing again to inflammation, barrier dysfunction, and itch. In addition, dysfunctional peripheral and central neuronal structures contribute to neuroinflammation, sensitization, nerve elongation, and neuropathic itch, thus chronification and therapy resistance. Consequently, neuroimmune circuits in skin and central nervous system may be targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids, and ions excite/sensitize sensory nerve endings, which not only induces itch but further aggravates/perpetuates inflammation, skin barrier disruption, and pruritus as well. Thus, targeted therapies for neuroimmune circuits as well as pathway inhibitors (eg, kinase inhibitors) may be beneficial to control pruritus in AD either in systemic and/or in topical form. Understanding neuroimmune circuits and neuronal signaling will optimize our approach to control all pathological mechanisms in AD, inflammation, barrier dysfunction, and pruritus.
Access this article: https://doi.org/10.1016/j.jaci.2022.03.010


Title: Single-cell multiomics in neuroinflammation
Authors: Florian Ingelfinger, Eduardo Beltrán, Lisa A Gerdes, Burkhard Becher
Type: Research Article
Highlights:
●Advances in multiomics expand the modalities that can be detected in single cells.
●Single-cell omics truly unravel the complexity of the immune system.
●Transitioning into clinical application will pave the way to personalised medicine.
●Tools will determine the future of precise screening, diagnosis and treatment.

The central nervous system (CNS) is, more than other organs, particularly vulnerable to inflammation and immune responses must be tightly controlled in order to maintain host protection. Accordingly, neuroinflammation is an orchestrated process involving various cell types that may dramatically change their phenotypic and functional properties upon entering the CNS. Recent advances in single-cell multiomics offer the unique opportunity to resolve this cellular heterogeneity in a holistic fashion and reshape our understanding of the molecular and cellular processes during neuroinflammation. Here, we provide an overview of technical advances in single-cell multiomics and the tremendous impact on our basic understanding of neuroinflammation. We discuss insights obtained in neuroinflammatory diseases and elaborate to which extent these tool sets could be applied in a clinical setting.
Access this article: https://doi.org/10.1016/j.coi.2022.102180

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