Reversible Cerebral Vasculopathy, Transverse Myelitis, and Active Systemic Lupus Erythematosus in an Aquaporin-4 Antibody-Positive Patient
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 19, 2021 Category: Neurology Authors: Gritsch, D., Mbonde, A. A., Harahsheh, E. Y., Chong, B. W., Wingerchuk, D. M. Tags: Autoimmune diseases, Lupus, Vasculitis, Devic's syndrome, Transverse myelitis Clinical/Scientific Notes Source Type: research

Different Fumaric Acid Esters Elicit Distinct Pharmacologic Responses
Conclusions Fumaric acid esters exhibit different biodistribution and may elicit different biological responses; furthermore, pharmacodynamic effects of combinations differ unpredictably from monotherapy. The strong potential to induce lymphopenia in patients with MS may be a result of activation of apoptosis pathways by MEF compared with DMF. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 19, 2021 Category: Neurology Authors: Wipke, B. T., Hoepner, R., Strassburger-Krogias, K., Thomas, A. M., Gianni, D., Szak, S., Brennan, M. S., Pistor, M., Gold, R., Chan, A., Scannevin, R. H. Tags: All Demyelinating disease (CNS), Multiple sclerosis Article Source Type: research

Learning More About HHV-6 Encephalitis
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 12, 2021 Category: Neurology Authors: Berger, J. R. Tags: Encephalitis, Meningitis, All Epilepsy/Seizures Editorial Source Type: research

Immune Skew of Circulating Follicular Helper T Cells Associates With Myasthenia Gravis Severity
Conclusions Alternation of cTfh is a key feature in the development of MG and may become a biomarker for disease severity and therapeutic efficacy. Classification of Evidence This study provides Class II evidence that the level of cTfh is associated with disease severity in patients with MG. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 12, 2021 Category: Neurology Authors: Ashida, S., Ochi, H., Hamatani, M., Fujii, C., Kimura, K., Okada, Y., Hashi, Y., Kawamura, K., Ueno, H., Takahashi, R., Mizuno, T., Kondo, T. Tags: Autoimmune diseases, Myasthenia Article Source Type: research

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts
Objective The aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing. Methods We performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompet...
Source: Neurology Neuroimmunology and Neuroinflammation - January 12, 2021 Category: Neurology Authors: Berzero, G., Campanini, G., Vegezzi, E., Paoletti, M., Pichiecchio, A., Simoncelli, A. M., Colombo, A. A., Bernasconi, P., Borsani, O., Di Matteo, A., Rossi, V., Foiadelli, T., Savasta, S., Compagno, F., Zecca, M., Baldanti, F., Marchioni, E. Tags: Article Source Type: research

CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS
Conclusion These results point to a role of SERPINA3 as a biomarker associated with the progressive forms of MS, particularly PPMS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 12, 2021 Category: Neurology Authors: Fissolo, N., Matute-Blanch, C., Osman, M., Costa, C., Pinteac, R., Miro, B., Sanchez, A., Brito, V., Dujmovic, I., Voortman, M., Khalil, M., Borras, E., Sabido, E., Issazadeh-Navikas, S., Montalban, X., Comabella Lopez, M. Tags: Multiple sclerosis Article Source Type: research

Aryl Hydrocarbon Receptor Activation in Astrocytes by Laquinimod Ameliorates Autoimmune Inflammation in the CNS
Conclusions Taken together, these findings suggest that AHR activation by clinically relevant AHR agonists may represent a novel therapeutic approach for the treatment of MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 6, 2021 Category: Neurology Authors: Rothhammer, V., Kenison, J. E., Li, Z., Tjon, E., Takenaka, M. C., Chao, C.-C., Alves de Lima, K., Borucki, D. M., Kaye, J., Quintana, F. J. Tags: Multiple sclerosis Article Source Type: research

CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups: An Autoantigenomic Approach
Conclusions The repertoire of targeted autoantigens of patients with CIDP differs in a systematic degree from those of controls. Systematic autoantigenomic approaches can help to understand the disease and to discover novel bioinformatical tools and novel autoantigen panels to improve diagnosis, treatment, prognosis, or patient stratification. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 6, 2021 Category: Neurology Authors: Moritz, C. P., Tholance, Y., Stoevesandt, O., Ferraud, K., Camdessanche, J.-P., Antoine, J.-C. Tags: All Immunology, Autoimmune diseases, Peripheral neuropathy, Chronic inflammatory demyelinating polyneuropathy Article Source Type: research

Effect of Ocrelizumab in Blood Leukocytes of Patients With Primary Progressive MS
Objective To analyze the changes induced by ocrelizumab in blood immune cells of patients with primary progressive MS (PPMS). Methods In this multicenter prospective study including 53 patients with PPMS who initiated ocrelizumab treatment, we determined effector, memory, and regulatory cells by flow cytometry at baseline and after 6 months of therapy. Wilcoxon matched paired tests were used to assess differences between baseline and 6 months' results. p Values were corrected using the Bonferroni test. Results Ocrelizumab reduced the numbers of naive and memory B cells (p
Source: Neurology Neuroimmunology and Neuroinflammation - January 6, 2021 Category: Neurology Authors: Fernandez-Velasco, J. I., Kuhle, J., Monreal, E., Meca-Lallana, V., Meca-Lallana, J., Izquierdo, G., Gascon-Gimenez, F., Sainz de la Maza, S., Walo-Delgado, P. E., Maceski, A., Rodriguez-Martin, E., Roldan, E., Villarrubia, N., Saiz, A., Blanco, Y., Sanch Tags: All Demyelinating disease (CNS), Multiple sclerosis Article Source Type: research

Evidence for Independent Hepatitis E Virus Replication in the Brain
A 46-year-old man presented with a 5-year history of fatigue, frequent painful muscular spasms in the extremities, and tingling sensations in the hands and feet. His medical history consisted of attention-deficit/hyperactivity disorder, a cervical Mycobacterium avium lymphadenitis during childhood and lateral ligament reconstruction of both ankles after trauma. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 5, 2021 Category: Neurology Authors: den Drijver, E. P. M., Brouwer, A. E., Synhaeve, N. E., Keijer, J. P., Verweij, J. J., Murk, J.-L., Pas, S. D. Tags: Encephalitis, Viral infections, Post-infectious, Clinical neurology history Clinical/Scientific Notes Source Type: research

Unilateral Relapsing Primary Angiitis of the CNS: An Entity Suggesting Differences in the Immune Response Between the Cerebral Hemispheres
Conclusions Combining our 3 cases with others reported in the literature allows better clinical understanding about this rare and extremely puzzling disease entity. We hypothesize that a functional difference in immune responses, caused by such discrepancies as basal levels of cytokines, asymmetric distribution of microglia, and differences in modulation of the systemic immune functions, rather than a structural antigenic difference, between the right and left brain may explain this phenomenon, but this is speculative. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 5, 2021 Category: Neurology Authors: AbdelRazek, M. A., Hillis, J. M., Guo, Y., Martinez-Lage, M., Gholipour, T., Sloane, J., Cho, T., Matiello, M. Tags: All Immunology, Autoimmune diseases, Vasculitis, Infarction Article Source Type: research

TDP-43-specific Autoantibody Decline in Patients With Amyotrophic Lateral Sclerosis
Conclusions Our results may suggest TDP-43–specific immune aberrations in patients with ALS. The skewed immune profiles observed in patients with ALS could indicate a deficiency in the clearance capacity and/or blocking of TDP-43 transmission and propagation. The decrease in levels of high affinity/avidity anti-TDP-43 NAbs and IgMs correlates with disease progression and may be disease predictors. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 24, 2020 Category: Neurology Authors: Nielsen, A. K., Folke, J., Owczarek, S., Svenstrup, K., Winge, K., Pakkenberg, B., Aznar, S., Brudek, T. Tags: All Immunology, Amyotrophic lateral sclerosis Article Source Type: research

Biological Significance of Anti-SARS-CoV-2 Antibodies: Lessons Learned From Progressive Multifocal Leukoencephalopathy
Conclusion Based on pathogenic lessons learned from PML under natalizumab therapy, we suggest the incorporation of functional assays that determine neutralizing properties of SARS-CoV-2–specific antibodies. In addition, we outline the potential role of T-cell detection assays in determining herd immunity in a given population or in studying therapeutic responses to vaccines. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 24, 2020 Category: Neurology Authors: Manouchehri, N., Steinman, L., Stuve, O. Tags: All Immunology, Viral infections, COVID-19, Multiple sclerosis Article Source Type: research

Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS
Conclusions These findings suggest that serum AHR agonist levels negatively correlate with disability in RRMS and PMS and decrease longitudinally in correlation with MRI markers of disease progression. Thus, serum AHR agonistic activity may serve as novel biomarker for disability progression in MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 24, 2020 Category: Neurology Authors: Tsaktanis, T., Beyer, T., Nirschl, L., Linnerbauer, M., Grummel, V., Bussas, M., Tjon, E., Mühlau, M., Korn, T., Hemmer, B., Quintana, F. J., Rothhammer, V. Tags: All Immunology, Autoimmune diseases, Prognosis, Multiple sclerosis Article Source Type: research

N2 year in review
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 18, 2020 Category: Neurology Authors: Dalmau, J., Dalakas, M. C., Kolson, D. L., Paul, F., Zamvil, S. S. Tags: Editor ' s Corner Source Type: research

Anti-CD20 therapies and pregnancy in neuroimmunologic disorders: A cohort study from Germany
Objective To report pregnancy outcomes and disease activity (DA) in women with MS, neuromyelitis optica spectrum disorders (NMOSDs), and other neuroimmunologic diseases (ONID) after treatment with rituximab (RTX)/ocrelizumab (OCR) 12 months before or during pregnancy. Methods Data were collected in the German MS and pregnancy registry and centers from the Neuromyelitis Optica Study Group. Sixty-eight known outcomes of 88 pregnancies from 81 women (64 MS, 10 NMOSD, and 7 ONID) were included and stratified in 3 exposure groups:>6M-group = RTX/OCR>6 but ≤12 months before the last menstrual period (LMP) (n = 8);
Source: Neurology Neuroimmunology and Neuroinflammation - December 17, 2020 Category: Neurology Authors: Kümpfel, T., Thiel, S., Meinl, I., Ciplea, A. I., Bayas, A., Hoffmann, F., Hofstadt-van Oy, U., Hoshi, M., Kluge, J., Ringelstein, M., Aktas, O., Stoppe, M., Walter, A., Weber, M. S., Ayzenberg, I., Hellwig, K. Tags: Multiple sclerosis Article Source Type: research

Targeting B cells to modify MS, NMOSD, and MOGAD: Part 2
Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD) or are in advanced stages of clinical development. Currently, ocrelizumab and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This part of the review focuses on monoclonal antibody B cell–depleting strategies in NMOSD and the emerging related myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G–associ...
Source: Neurology Neuroimmunology and Neuroinflammation - December 16, 2020 Category: Neurology Authors: Graf, J., Mares, J., Barnett, M., Aktas, O., Albrecht, P., Zamvil, S. S., Hartung, H.-P. Tags: HIV Views [amp ] Reviews Source Type: research

Targeting B Cells to Modify MS, NMOSD, and MOGAD: Part 1
Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD), or are in advanced stages of clinical development. Currently, ocrelizumab, ofatumumab, and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This review focuses on the current state of knowledge about the role of B lymphocytes in immune-mediated pathophysiology and its implications for the mode of action. To understand ...
Source: Neurology Neuroimmunology and Neuroinflammation - December 16, 2020 Category: Neurology Authors: Graf, J., Mares, J., Barnett, M., Aktas, O., Albrecht, P., Zamvil, S. S., Hartung, H.-P. Tags: Views [amp ] Reviews Source Type: research

Acute disseminated encephalomyelitis after SARS-CoV-2 infection
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Tags: Correction Source Type: research

Obesity's role in MS: An intervention target with possible interactions
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Authors: Fitzgerald, K. C., Mowry, E. M. Tags: Multiple sclerosis, All epidemiology, Risk factors in epidemiology Editorial Source Type: research

Interleukin-15 enhances proinflammatory T-cell responses in patients with MS and EAE
Conclusions Our results underscore that IL-15 contributes to the amplification of T-cell inflammatory properties after disease onset in both MS and EAE. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Authors: Laurent, C., Deblois, G., Clenet, M.-L., Carmena Moratalla, A., Farzam-kia, N., Girard, M., Duquette, P., Prat, A., Larochelle, C., Arbour, N. Tags: All Immunology, Autoimmune diseases, Multiple sclerosis Article Source Type: research

Treating MS after surviving PML: Discrete strategies for rescue, remission, and recovery patient 2: From the National Multiple Sclerosis Society Case Conference Proceedings
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Authors: Cruz, R. A., Hogan, N., Sconzert, J., Sconzert, M., Major, E. O., Lisak, R. P., Melamed, E., Varkey, T. C., Meltzer, E., Goodman, A., Komogortsev, O., Parsons, M. S., Costello, K., Graves, J. S., Newsome, S., Zamvil, S. S., Frohman, E. M., Frohman, T. C. Tags: All Demyelinating disease (CNS), Multiple sclerosis Diagnostic and Treatment Challenges Source Type: research

Treating MS after surviving PML: Discrete strategies for rescue, remission, and recovery patient 1: From the National Multiple Sclerosis Society Case Conference Proceedings
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Authors: Anadani, N., Hyland, M., Cruz, R. A., Lisak, R., Costello, K., Major, E. O., Jassam, Y., Meltzer, E., Varkey, T. C., Parsons, M. S., Goodman, A. D., Graves, J. S., Newsome, S., Zamvil, S. S., Frohman, E. M., Frohman, T. C. Tags: All Immunology, Multiple sclerosis Diagnostic and Treatment Challenges Source Type: research

Overweight/obesity in young adulthood interacts with aspects of EBV infection in MS etiology
Conclusions With regard to MS risk, overweight/obesity in young adulthood acts synergistically with both aspects of EBV infection, predominantly among those with a genetic susceptibility to the disease. The obese state both induces a chronic immune-mediated inflammation and affects the cellular immune response to infections, which may contribute to explain our findings. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 15, 2020 Category: Neurology Authors: Hedström, A. K., Brenner, N., Butt, J., Hillert, J., Waterboer, T., Olsson, T., Alfredsson, L. Tags: Multiple sclerosis Article Source Type: research

Presentations and mechanisms of CNS disorders related to COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic. In addition to severe respiratory symptoms, there are a growing number of reports showing a wide range of CNS complications in patients with COVID-19. Here, we review the literature on these complications, ranging from nonspecific symptoms to necrotizing encephalopathies, encephalitis, myelitis, encephalomyelitis, endotheliitis, and stroke. We postulate that there are several different mechanisms involved in COVID-19–associated CNS dysfunction, particularly activation of inflammatory and thro...
Source: Neurology Neuroimmunology and Neuroinflammation - December 11, 2020 Category: Neurology Authors: Bodro, M., Compta, Y., Sanchez-Valle, R. Tags: Other cerebrovascular disease/ Stroke, Encephalitis, COVID-19 Views [amp ] Reviews Source Type: research

Identification of circulating MOG-specific B cells in patients with MOG antibodies
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 9, 2020 Category: Neurology Tags: Correction Source Type: research

High serum neurofilament associates with diffuse white matter damage in MS
Conclusions Our findings suggest that elevated serum NfL in MS results from neuroaxonal damage both within the NAWM and focal T2 lesions. This pathologic heterogeneity ought to be taken into account when interpreting NfL findings at the individual patient level. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 8, 2020 Category: Neurology Authors: Saraste, M., Bezukladova, S., Matilainen, M., Tuisku, J., Rissanen, E., Sucksdorff, M., Laaksonen, S., Vuorimaa, A., Kuhle, J., Leppert, D., Airas, L. Tags: DWI, Multiple sclerosis Article Source Type: research

Chitinases and chitinase-like proteins as biomarkers in neurologic disorders
Chitinases are hydrolytic enzymes widely distributed in nature. Despite their physiologic and pathophysiologic roles are not well understood, chitinases are emerging as biomarkers in a broad range of neurologic disorders, where in many cases, protein levels measured in the CSF have been shown to correlate with disease activity and progression. In this review, we will summarize the structural features of human chitinases and chitinase-like proteins and their potential physiologic and pathologic functions in the CNS. We will also review existing evidence for the role of chitinases and chitinase-like proteins as diagnostic an...
Source: Neurology Neuroimmunology and Neuroinflammation - December 8, 2020 Category: Neurology Authors: Pinteac, R., Montalban, X., Comabella, M. Tags: All Immunology, Amyotrophic lateral sclerosis, Alzheimer's disease, Multiple sclerosis Views [amp ] Reviews Source Type: research

Time course of dementia following sepsis in German health claims data
Conclusions For sepsis survivors, medium-term dementia risk remains elevated, whereas long-term risk may reach the level of those without sepsis, even after controlling for delirium. These findings encourage identifying modifiable components of hospital and rehabilitation care. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 8, 2020 Category: Neurology Authors: Fritze, T., Doblhammer, G., Widmann, C. N., Heneka, M. T. Tags: All Cognitive Disorders/Dementia, Delirium Article Source Type: research

Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study
Conclusions Safety and efficacy of repeated IT-MSC-NP treatment was sustained for 2 years; however, the degree of disability reversal was not sustained in a subset of patients. CSF biomarkers altered in response to IT-MSC-NP treatment may reflect specific immunoregulatory and trophic mechanisms of therapeutic response in MS. Classification of evidence This study provides Class IV evidence that for patients with progressive MS, IT administration of MSC-NPs is safe and effective. The study is rated Class IV because of the absence of a non–IT-MSC-NP-treated control group. Clinicaltrials.gov identifier NCT01933802. (So...
Source: Neurology Neuroimmunology and Neuroinflammation - December 4, 2020 Category: Neurology Authors: Harris, V. K., Stark, J. W., Yang, S., Zanker, S., Tuddenham, J., Sadiq, S. A. Tags: All Clinical trials, Multiple sclerosis Article Source Type: research

Combination of teriflunomide and interferon as follow-up therapy after fingolimod-associated PML
Progressive multifocal leukoencephalopathy (PML) is one of the most important adverse events in relapsing-remitting MS (RRMS) patients treated with disease-modifying therapies (DMTs). Especially natalizumab is known to increase the risk for PML, depending on the John Cunningham virus (JCV) index in serum and the number of years on therapy with natalizumab.1 Fingolimod and dimethyl fumarate are associated with a considerably lower risk of PML.2 (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 3, 2020 Category: Neurology Authors: Fischer-Barnicol, B., Oechtering, J., Kuhle, J., Lorscheider, J., Kappos, L., Derfuss, T. Tags: Viral infections, Multiple sclerosis Clinical/Scientific Notes Source Type: research

Overlapping central and peripheral nervous system syndromes in MOG antibody-associated disorders
Conclusions Myeloradiculitis, combined central and peripheral demyelination syndromes, and inflammatory neuropathies may be associated with MOGAD and may be immunotherapy responsive. We identified a subgroup who may have pathology mediated by coexistent autoantibodies. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 3, 2020 Category: Neurology Authors: Rinaldi, S., Davies, A., Fehmi, J., Beadnall, H. N., Wang, J., Hardy, T. A., Barnett, M. H., Broadley, S. A., Waters, P., Reddel, S. W., Irani, S. R., Brilot, F., Dale, R. C., Ramanathan, S., the Australian and New Zealand MOG Study Group Tags: Neuropathic pain, All Demyelinating disease (CNS) Article Source Type: research

Monitoring of radiologic disease activity by serum neurofilaments in MS
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 25, 2020 Category: Neurology Tags: Correction Source Type: research

Is MS affecting the CNS only?: Lessons from clinic to myelin pathophysiology
MS is regarded as a disease of the CNS where a combination of demyelination, inflammation, and axonal degeneration results in neurologic disability. However, various studies have also shown that the peripheral nervous system (PNS) can be involved in MS, expanding the consequences of this disorder outside the brain and spinal cord, and providing food for thought to the still unanswered questions about MS origin and treatment. Here, we review the emerging concept of PNS involvement in MS by looking at it from a clinical, molecular, and biochemical point of view. Clinical, pathologic, electrophysiologic, and imaging studies g...
Source: Neurology Neuroimmunology and Neuroinflammation - November 24, 2020 Category: Neurology Authors: Oudejans, E., Luchicchi, A., Strijbis, E. M. M., Geurts, J. J. G., van Dam, A.-M. Tags: MRI, Clinical neurology history, EMG, Multiple sclerosis Views [amp ] Reviews Source Type: research

Tumefactive inflammatory lesions in juvenile metachromatic leukodystrophy
Juvenile metachromatic leukodystrophy (MLD) is caused by autosomal recessive defects in the ARSA gene coding for arylsulfatase A. Clinically, it is characterized by slowly progressive ataxia, spasticity, cognitive decline, and behavioral disturbances starting at age 4–10 years. White matter abnormalities are often first seen in the corpus callosum subsequently extending into the periventricular regions with a diffuse symmetrical pattern. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 23, 2020 Category: Neurology Authors: Meier, K., Gärtner, J., Huppke, P. Tags: Metabolic disease (inherited), Leukodystrophies, All Pediatric, All Demyelinating disease (CNS) Clinical/Scientific Notes Source Type: research

Mendelian randomization study shows no causal effects of serum urate levels on the risk of MS
Conclusion This MR study does not support a clinically relevant causal effect of serum urate levels on the risk of MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 19, 2020 Category: Neurology Authors: Harroud, A., Richards, J. B., Baranzini, S. E. Tags: Multiple sclerosis, Risk factors in epidemiology Article Source Type: research

Laquinimod dampens IL-1{beta} signaling and Th17-polarizing capacity of monocytes in patients with MS
Conclusions Our findings suggest that inhibited NF-B signaling and downregulation of IL-1β expression in monocytes contributes to the immunomodulatory effects of laquinimod and that the impairment of Th17 polarization might mediate its disease-modifying activity in MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 17, 2020 Category: Neurology Authors: Engel, S., Jolivel, V., Kraus, S. H.- P., Zayoud, M., Rosenfeld, K., Tumani, H., Furlan, R., Kurschus, F. C., Waisman, A., Luessi, F. Tags: Multiple sclerosis Article Source Type: research

Eastern equine encephalitis and use of IV immunoglobulin therapy and high-dose steroids
Conclusions Clinicians should suspect EEE in immunocompetent patients with early subcortical neuroimaging abnormalities and CSF neutrophilic predominance. This study suggests a lower mortality than previously reported, but a high morbidity rate in EEE. IVIG as an adjunctive to standard of care may be considered early during hospitalization. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 10, 2020 Category: Neurology Authors: Wilcox, D. R., Collens, S. I., Solomon, I. H., Mateen, F. J., Mukerji, S. S. Tags: MRI, Encephalitis, Viral infections, Natural history studies (prognosis), EEG Article Source Type: research

Placental transfer of NMDAR antibodies causes reversible alterations in mice
Conclusions In this model, placental transfer of patients' NMDAR antibodies caused severe but reversible synaptic and neurodevelopmental alterations. Reversible antibody effects may contribute to the infrequent and limited number of complications described in children of patients who develop anti-NMDAR encephalitis during pregnancy. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 10, 2020 Category: Neurology Authors: Garcia-Serra, A., Radosevic, M., Pupak, A., Brito, V., Rios, J., Aguilar, E., Maudes, E., Arino, H., Spatola, M., Mannara, F., Pedreno, M., Joubert, B., Gines, S., Planaguma, J., Dalmau, J. Tags: Autoimmune diseases, Developmental disorders, Neonatal Article Source Type: research

Chitinase 3-like 1 and neurofilament light chain in CSF and CNS atrophy in MS
Conclusions NfL and CHI3L1 in CSF were differentially related to brain and spinal cord atrophy. CSF CHI3L1 was associated with spinal cord volume loss and was less affected than NfL by disease duration and age, whereas CSF NfL was associated with brain gray matter atrophy. CSF NfL and CHI3L1 measurement provides complementary information regarding brain and spinal cord volumes. Classification of evidence This study provides Class II evidence that CSF CHI3L1 is associated with spinal cord volume loss and that CSF NfL is associated with gray matter atrophy. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 10, 2020 Category: Neurology Authors: Schneider, R., Bellenberg, B., Gisevius, B., Hirschberg, S., Sankowski, R., Prinz, M., Gold, R., Lukas, C., Haghikia, A. Tags: MRI, Cerebrospinal Fluid, Multiple sclerosis Article Source Type: research

Clostridium bolteae is elevated in neuromyelitis optica spectrum disorder in India and shares sequence similarity with AQP4
Objective To understand the role of gut microbiome in influencing the pathogenesis of neuromyelitis optica spectrum disorders (NMOSDs) among patients of south Indian origin. Methods In this case-control study, stool and blood samples were collected from 39 patients with NMOSD, including 17 with aquaporin 4 IgG antibodies (AQP4+) and 36 matched controls. 16S ribosomal RNA (rRNA) sequencing was used to investigate the gut microbiome. Peripheral CD4+ T cells were sorted in 12 healthy controls, and in 12 patients with AQP4+ NMOSD, RNA was extracted and immune gene expression was analyzed using the NanoString nCounter human im...
Source: Neurology Neuroimmunology and Neuroinflammation - November 4, 2020 Category: Neurology Authors: Pandit, L., Cox, L. M., Malli, C., D'Cunha, A., Rooney, T., Lokhande, H., Willocq, V., Saxena, S., Chitnis, T. Tags: Article Source Type: research

Seizure-related 6 homolog like 2 autoimmunity: Neurologic syndrome and antibody effects
Conclusions SEZ6L2-abs associate with a subacute cerebellar syndrome with frequent extrapyramidal symptoms. The potential pathogenic effect of the antibodies is not mediated by internalization of the antigen. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 3, 2020 Category: Neurology Authors: Landa, J., Guasp, M., Petit-Pedrol, M., Martinez-Hernandez, E., Planaguma, J., Saiz, A., Ruiz-Garcia, R., Garcia-Fernandez, L., Verschuuren, J., Saunders-Pullman, R., Ramirez-Gomez, L., Geschwind, M. D., Dalmau, J., Sabater, L., Graus, F. Tags: Autoimmune diseases, All Clinical Neurology, Gait disorders/ataxia Article Source Type: research

Intermediate uveitis associated with MS: Diagnosis, clinical features, pathogenic mechanisms, and recommendations for management
Uveitis is a major cause of visual impairment and blindness among working-age adults, accounting for 10% of legal blindness in the United States. Among people with MS, the prevalence of uveitis is 10 times higher than among the general population, and because MS and uveitis share similar genetic risk factors and immunologic effector pathways, it is not clear whether uveitis is one of the manifestations of MS or a coincident disorder. This uncertainty raises several diagnostic and management issues for clinicians who look after these patients, particularly with regard to recognizing visual symptoms resulting from demyelinat...
Source: Neurology Neuroimmunology and Neuroinflammation - October 30, 2020 Category: Neurology Authors: Abraham, A., Nicholson, L., Dick, A., Rice, C., Atan, D. Tags: All Immunology, All Neuro-ophthalmology, Multiple sclerosis Views and Reviews Source Type: research

A case of neonatal onset multisystem inflammatory disease supporting a role of interleukin-1{beta} in moyamoya syndrome
Moyamoya syndrome (MMS) is a chronic progressive cerebrovascular condition characterized by bilateral stenosis/occlusion of the terminal internal carotid artery (ICA) often extending to neighboring cerebral arteries with prominent collateral circulation and increased risk of hemorrhage. Symptoms include stroke, TIA, and headache.1 MMS's etiology is unknown. However, experimental evidence from arterial smooth muscle cells (SMC) derived from patients with MMS has suggested that interleukin-1 beta (IL-1β)-dependent prostaglandin overproduction plays a crucial role in its pathogenesis.2 Neonatal onset multisystem inflamma...
Source: Neurology Neuroimmunology and Neuroinflammation - October 27, 2020 Category: Neurology Authors: Wohlrab, F., Bauknecht, C., Meisel, C., Dreier, J. P. Tags: Stroke in young adults, All Immunology, All Pediatric, Other neurocutaneous disorders Clinical/Scientific Notes Source Type: research

Disease activity in pregnancy and postpartum in women with MS who suspended rituximab and natalizumab
Conclusion Disease reactivity during the postpartum period was lower among women with MS who suspended RTX before pregnancy, relative to those who suspended NTZ and untreated women. These findings suggest that RTX may exert long-acting effects on MS disease activity that encompass pregnancy and postpartum periods. Classification of evidence This study provides Class IV evidence that in patients with MS who were on treatment before pregnancy, RTX reduces clinical disease activity compared with NTZ in the postpartum period. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 21, 2020 Category: Neurology Authors: Razaz, N., Piehl, F., Frisell, T., Langer-Gould, A. M., McKay, K. A., Fink, K. Tags: Multiple sclerosis, Cohort studies Article Source Type: research

A probable case of anti-NMDAR encephalitis from 1830
This issue of N2 highlights the diversity of autoimmune disorders that affect the nervous system. Whether you are interested in T–cell- or B–cell-mediated disorders or prefer white matter or gray matter, you will likely find an article of interest. In addition for the medical sleuths among our readers, we have the likely resolution of a 190-year-old unresolved diagnosis. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 21, 2020 Category: Neurology Authors: Dalmau, J. Tags: Editor ' s Corner Source Type: research

Laminar analysis of the cortical T1/T2-weighted ratio at 7T
Objective In this observational study, we explored cortical structure as function of cortical depth through a laminar analysis of the T1/T2-weighted (T1w/T2w) ratio, which has been related to dendrite density in ex vivo brain tissue specimens of patients with MS. Methods In 39 patients (22 relapsing-remitting, 13 female, age 41.1 ± 10.6 years; 17 progressive, 11 female, age 54.1 ± 9.9 years) and 21 healthy controls (8 female, , age 41.6 ± 10.6 years), we performed a voxel-wise analysis of T1w/T2w ratio maps from high-resolution 7T images from the subpial surface to the gray matter/white matter boundar...
Source: Neurology Neuroimmunology and Neuroinflammation - October 21, 2020 Category: Neurology Authors: Petracca, M., El Mendili, M. M., Moro, M., Cocozza, S., Podranski, K., Fleysher, L., Inglese, M. Tags: MRI, Multiple sclerosis Article Source Type: research

Childhood choreoathetosis secondary to hyper-IgM syndrome (CD40 ligand deficiency)
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 16, 2020 Category: Neurology Authors: Coulter, I. C., Yan, H., Gorodetsky, C., Akhbari, M., Breitbart, S., Kalia, S. K., Fasano, A., Ibrahim, G. M. Tags: All Immunology, Chorea, All Pediatric, Surgery/Stimulation Clinical/Scientific Notes Source Type: research

Nucleic acid oxidation is associated with biomarkers of neurodegeneration in CSF in people with HIV
Objective To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aβ-42, and elevated CSF total tau and neurofilament light (NFL). Methods This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusi...
Source: Neurology Neuroimmunology and Neuroinflammation - October 14, 2020 Category: Neurology Authors: Ellis, R. J., Moore, D. J., Sundermann, E. E., Heaton, R. K., Mehta, S., Hulgan, T., Samuels, D., Fields, J. A., Letendre, S. L. Tags: HIV Article Source Type: research

Mild progressive multifocal leukoencephalopathy after switching from natalizumab to ocrelizumab
Conclusions The clinical course of carryover PML was mild in both patients, suggesting that B-cell depletion possibly did not aggravate PML-IRIS in these 2 patients. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 13, 2020 Category: Neurology Authors: Toorop, A. A., van Lierop, Z. Y. G., Strijbis, E. E. M., Teunissen, C. E., Petzold, A., Wattjes, M. P., Barkhof, F., de Jong, B. A., van Kempen, Z. L. E., Killestein, J. Tags: Multiple sclerosis Article Source Type: research