Bilateral retinal pathology following a first-ever clinical episode of autoimmune optic neuritis
Conclusions Retinal structural damage develops rapidly following acute ON and is associated with subsequent functional visual deficits. Our results also suggest bilateral retinal pathology following unilateral ON, possibly caused by subclinical involvement of the contralateral NON eyes. Moreover, our data may assist in clinical trial planning in studies targeting tissue damage in acute ON. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 22, 2020 Category: Neurology Authors: Wicki, C. A., Manogaran, P., Simic, T., Hanson, J. V. M., Schippling, S. Tags: Retina, Visual loss, Multiple sclerosis, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Article Source Type: research

Understanding neurodegenerative changes of the afferent visual pathway in MS
The chronic involvement of the afferent visual system in multiple sclerosis (MS) is a powerful model to understand the temporal course and functional relevance of neurodegeneration because it is very well distinguishable from neighboring structures and offers quantifiable structural and functional metrics. Optical coherence tomography (OCT) of the retina and diffusion tensor imaging (DTI)-based tractography of the optic radiation have proven to provide sensitive markers for neurodegeneration of the visual pathway in MS.1,2 OCT-derived neuroaxonal retinal damage, represented by thinning of the retinal nerve fiber layer (RNF...
Source: Neurology Neuroimmunology and Neuroinflammation - January 22, 2020 Category: Neurology Authors: Zimmermann, H. G., Oertel, F. C. Tags: MRI, DWI, Evoked Potentials/Visual, Multiple sclerosis, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Editorial Source Type: research

MS optic neuritis-induced long-term structural changes within the visual pathway
Conclusion A single history of ON induces long-term structural damage within the retina and OR suggestive of both retrograde and anterograde neuroaxonal degeneration. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 22, 2020 Category: Neurology Authors: Pawlitzki, M., Horbrügger, M., Loewe, K., Kaufmann, J., Opfer, R., Wagner, M., Al-Nosairy, K. O., Meuth, S. G., Hoffmann, M. B., Schippling, S. Tags: MRI, DWI, Evoked Potentials/Visual, Multiple sclerosis, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Article Source Type: research

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient
Conclusions Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 17, 2020 Category: Neurology Authors: Cellucci, T., Van Mater, H., Graus, F., Muscal, E., Gallentine, W., Klein-Gitelman, M. S., Benseler, S. M., Frankovich, J., Gorman, M. P., Van Haren, K., Dalmau, J., Dale, R. C. Tags: Autoimmune diseases, Encephalitis, All Pediatric Article Source Type: research

Clinical significance of Kelch-like protein 11 antibodies
Conclusions KLHL11-abs associate with a spectrum of syndromes and tumors wider than those previously reported; 44% of patients have concurrent neuronal antibodies, some of them (anti-NMDAR) pathogenically relevant. Brain immunostaining is not useful for routine screening of KLHL11-abs. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 17, 2020 Category: Neurology Authors: Maudes, E., Landa, J., Munoz-Lopetegi, A., Armangue, T., Alba, M., Saiz, A., Graus, F., Dalmau, J., Sabater, L. Tags: Autoimmune diseases, All Clinical Neurology, Paraneoplastic syndrome Article Source Type: research

Pregnancy outcomes in anti-NMDA receptor encephalitis: Case series
Conclusions Patients who develop anti-NMDAR encephalitis during pregnancy or become pregnant during recovery often have obstetrical complications, but most of the newborns are healthy and appear to have normal development. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 16, 2020 Category: Neurology Authors: Joubert, B., Garcia-Serra, A., Planaguma, J., Martinez-Hernandez, E., Kraft, A., Palm, F., Iizuka, T., Honnorat, J., Leypoldt, F., Graus, F., Dalmau, J. Tags: Autoimmune diseases, Developmental disorders, Neonatal Article Source Type: research

BMI and low vitamin D are causal factors for multiple sclerosis: A Mendelian Randomization study
Conclusions We provide novel evidence that BMI before the age of 10 is an independent causal risk factor for MS and strengthen evidence for the causal role of vitamin D in the pathogenesis of MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 14, 2020 Category: Neurology Authors: Jacobs, B. M., Noyce, A. J., Giovannoni, G., Dobson, R. Tags: Multiple sclerosis, All epidemiology Article Source Type: research

Dimethyl fumarate vs fingolimod following different pretreatments: A retrospective study
Conclusions DMF treatment was associated with higher clinical disease activity compared with FTY treatment. A subgroup analysis suggested beneficial effects of FTY in treatment-naive and patients pretreated with natalizumab. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 14, 2020 Category: Neurology Authors: Diem, L., Daponte, A., Findling, O., Miclea, A., Briner, M., Salmen, A., Gold, R., Kilidireas, C., Chan, A., Evangelopoulos, M. E., Hoepner, R. Tags: Multiple sclerosis Article Source Type: research

Tick-borne encephalitis vaccination in multiple sclerosis: A prospective, multicenter study
Conclusion TBE vaccination showed good tolerability and was safe in patients with MS. MS disease activity was not increased, and annualized relapse rates decreased after vaccination. Vaccine response differs according to the underlying DMT. Trial registration ClinicalTrials.gov, clinicaltrials.gov, Identifier: NCT02275741. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - January 9, 2020 Category: Neurology Authors: Winkelmann, A., Metze, C., Frimmel, S., Reisinger, E. C., Zettl, U. K., Loebermann, M. Tags: Viral infections, All Clinical trials, Multiple sclerosis Article Source Type: research

Refractory chronic spontaneous urticaria after the use of alemtuzumab in multiple sclerosis
A 40-year-old woman developed erythematous, raised and pruritic, migratory lesions on a daily basis affecting her whole body for the past 3 months; the appearance of the rash was consistent with urticaria. There was associated angioedema affecting her lips and face. Her medical history was significant for MS, diagnosed 9 years before, manifesting clinically with mobility, speech, and cognitive impairment. Initial treatment was with β-interferon and glatiramer acetate; however, disease relapse prompted switching to alemtuzumab, with 2 standard courses given 12 months apart (60 and 36 mg, respectively, the last dose giv...
Source: Neurology Neuroimmunology and Neuroinflammation - January 8, 2020 Category: Neurology Authors: Hu, H., Reddell, S., Riminton, S., Chan, C., Urriola, N. Tags: All Immunology, Autoimmune diseases, All Clinical Neurology, Multiple sclerosis Clinical/Scientific Notes Source Type: research

Clinical features of seronegative, but CSF antibody-positive, anti-NMDA receptor encephalitis
Objective To determine the frequency of anti-NMDA receptor encephalitis without detectable serum NMDAR antibodies and to compare the clinical features of these patients with those with NMDAR antibodies in serum and CSF. Methods This is a retrospective assessment of serum antibody status and clinical features of 489 patients with anti-NMDAR encephalitis, defined by the presence of NMDAR antibodies in the CSF, and available paired serum/CSF samples examined at Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi I Sunyer, Barcelona, between January 2007 and December 2017. NMDAR antibodies were...
Source: Neurology Neuroimmunology and Neuroinflammation - January 3, 2020 Category: Neurology Authors: Guasp, M., Modena, Y., Armangue, T., Dalmau, J., Graus, F. Tags: Autoimmune diseases, Encephalitis, All Clinical Neurology Article Source Type: research

Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15
Conclusions Our data indicate that increased HLA-DRB1 and -DRB5 expression in the brain of patients with MS may be an important factor in how the HLA-DR15 haplotype contributes to MS pathomechanisms in the target organ. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 27, 2019 Category: Neurology Authors: Enz, L. S., Zeis, T., Schmid, D., Geier, F., van der Meer, F., Steiner, G., Certa, U., Binder, T. M. C., Stadelmann, C., Martin, R., Schaeren-Wiemers, N. Tags: Autoimmune diseases, Gene expression studies, Multiple sclerosis Article Source Type: research

Diffusion basis spectrum imaging provides insights into MS pathology
Conclusions DBSI fiber fraction and nonrestricted isotropic fraction were the most useful markers of injury in the NAWM CC. These 2 DBSI measures reflect axon loss in animal models. Because of its ability to reveal axonal loss, as well as demyelination, DBSI may be a useful outcome measure for trials of CNS reparative treatments. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 23, 2019 Category: Neurology Authors: Sun, P., George, A., Perantie, D. C., Trinkaus, K., Ye, Z., Naismith, R. T., Song, S.-K., Cross, A. H. Tags: MRI, DWI, Clinical neurology examination, All Demyelinating disease (CNS), Multiple sclerosis Article Source Type: research

Relapse recovery: The forgotten variable in multiple sclerosis clinical trials
Conclusions In patients with MS presenting without good recovery after the initial relapse, immediate DMT initiation favorably influences the likelihood of more ambulatory-benign disease akin to patients with good recovery after the initial relapse. Classification of evidence This study provides Class III evidence that for patients with MS without good recovery after the initial relapse, immediate DMT initiation increases the likelihood of a benign disease course. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 17, 2019 Category: Neurology Authors: Kantarci, O. H., Zeydan, B., Atkinson, E. J., Conway, B. L., Castrillo-Viguera, C., Rodriguez, M. Tags: Quality of life, Class III, Burden of disease, Multiple sclerosis Article Source Type: research

Telemedicine assessment of long-term cognitive and functional status in anti-leucine-rich, glioma-inactivated 1 encephalitis
Conclusions Telemedicine is a feasible tool to assess the cognitive and functional outcome in patients with anti-LGI1 encephalitis. Cognitive impairment is often missed if only functional scales are used. Premorbid cognitive reserve and MRI with bilateral hippocampal hyperintensity were predictors for long-term cognitive impairment. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 17, 2019 Category: Neurology Authors: Sola-Valls, N., Arino, H., Escudero, D., Solana, E., Llado, A., Sanchez-Valle, R., Blanco, Y., Saiz, A., Dalmau, J., Graus, F. Tags: Autoimmune diseases, Encephalitis, All Clinical Neurology, Neuropsychological assessment, Assessment of cognitive disorders/dementia Article Source Type: research

Frequency of myelin oligodendrocyte glycoprotein antibody in multiple sclerosis: A multicenter cross-sectional study
Conclusion Our findings indicate that MOG-Ab are exceptional in MS phenotype, suggesting that the MOG-Ab testing should not be performed in typical MS presentation. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 13, 2019 Category: Neurology Authors: Cobo-Calvo, A., d'Indy, H., Ruiz, A., Collongues, N., Kremer, L., Durand-Dubief, F., Rollot, F., Casey, R., Vukusic, S., De Seze, J., Marignier, R. Tags: Multiple sclerosis, Devic's syndrome Article Source Type: research

Treating muscle-specific kinase myasthenia gravis from the inside out
Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is an autoimmune disease of the neuromuscular junction with some remarkable characteristics. Although MuSK is expressed in all skeletal muscles, patients with this disease present with particularly cranial, bulbar, and respiratory muscle weakness, leading to a relatively high frequency of respiratory crises.1 Despite several available immunosuppressive or immunomodulatory treatments, patients with MuSK MG often retain residual muscle weakness and experience more often severe muscle atrophy than patients with the more frequent MG with acetylcholine rece...
Source: Neurology Neuroimmunology and Neuroinflammation - December 12, 2019 Category: Neurology Authors: Huijbers, M. G., Verschuuren, J. J. G. M. Tags: Myasthenia Editorial Source Type: research

SHP2 inhibitor protects AChRs from effects of myasthenia gravis MuSK antibody
Conclusions Stimulating the agrin-LRP4-MuSK-DOK7 AChR clustering pathway with NSC-87877, or other drugs, could represent a novel therapeutic approach for MuSK-MG and could potentially improve other NMJ disorders with reduced AChR numbers or disrupted NMJs. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 12, 2019 Category: Neurology Authors: Huda, S., Cao, M., De Rosa, A., Woodhall, M., Rodriguez Cruz, P. M., Cossins, J., Maestri, M., Ricciardi, R., Evoli, A., Beeson, D., Vincent, A. Tags: Myasthenia Article Source Type: research

N2 year in review
2019 has been a very good year for our journal. N2 was included in MEDLINE and in June received its first impact factor, a competitive 7.353. We have been fortunate to recruit Dr. Marinos Dalakas to our team of International Associate Editors. Dr. Dalakas is Professor of Neurology at the University of Athens (Greece) and Jefferson University (Philadelphia, PA). His remarkable knowledge on inflammatory and autoimmune neuromuscular diseases will be a great asset to the journal. These accomplishments and successes would not have been possible without the growing number of readers, the increasing number of manuscript submissio...
Source: Neurology Neuroimmunology and Neuroinflammation - December 12, 2019 Category: Neurology Authors: Dalmau, J., Dalakas, M. C., Kolson, D. L., Paul, F., Zamvil, S. S. Tags: Editor ' s Corner Source Type: research

Paraneoplastic cerebellar ataxia and antibodies to metabotropic glutamate receptor 2
Conclusions mGluR2-Abs are a novel biomarker of paraneoplastic cerebellar ataxia. The potential pathogenic effect of the antibodies is not mediated by downregulation or internalization of neuronal surface mGluR2. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 11, 2019 Category: Neurology Authors: Ruiz-Garcia, R., Martinez-Hernandez, E., Joubert, B., Petit-Pedrol, M., Pajaron-Boix, E., Fernandez, V., Salais, L., del Pozo, M., Armangue, T., Sabater, L., Dalmau, J., Graus, F. Tags: Diagnostic test assessment, Autoimmune diseases, Clinical neurology examination, Gait disorders/ataxia, Paraneoplastic syndrome Article Source Type: research

Alemtuzumab therapy changes immunoglobulin levels in peripheral blood and CSF
Conclusions Our results suggest to monitor IgG levels for safety reasons in patients treated with alemtuzumab—in particular when additional treatment courses are required—and to consider preventive action in critical cases. Classification of evidence This study provides Class IV evidence that for patients with RRMS alemtuzumab reduces immunoglobulin levels. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 11, 2019 Category: Neurology Authors: Möhn, N., Pfeuffer, S., Ruck, T., Gross, C. C., Skripuletz, T., Klotz, L., Wiendl, H., Stangel, M., Meuth, S. G. Tags: Class IV, Multiple sclerosis Article Source Type: research

Anti-IGLON5 disease: A new case without neuropathologic evidence of brainstem tauopathy
Conclusion The absence of pTau deposits in the brainstem of the present patient suggests that the tauopathy of patients with anti-IgLON5 disease may be a late, secondary event. The anti-IgLON5 brainstem tauopathy has a specific molecular signature different from primary tauopathies. pTau deposits restricted to the hippocampus/limbic regions of patients with anti-IgLON5 may represent an age-related comorbidity. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 11, 2019 Category: Neurology Authors: Erro, M. E., Sabater, L., Martinez, L., Herrera, M., Ostolaza, A., Garcia de Gurtubay, I., Tunon, T., Graus, F., Gelpi, E. Tags: All Immunology, Myoclonus, All Sleep Disorders Article Source Type: research

A case of idiopathic multicentric Castleman disease in an alemtuzumab-treated patient with MS
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 5, 2019 Category: Neurology Tags: Correction Source Type: research

IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 5, 2019 Category: Neurology Tags: Correction Source Type: research

Neurologic complications of acute hepatitis E virus infection
Conclusions Neurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - December 5, 2019 Category: Neurology Authors: Ripellino, P., Pasi, E., Melli, G., Staedler, C., Fraga, M., Moradpour, D., Sahli, R., Aubert, V., Martinetti, G., Bihl, F., Bernasconi, E., Terziroli Beretta-Piccoli, B., Cerny, A., Dalton, H. R., Zehnder, C., Mathis, B., Zecca, C., Disanto, G., Kaelin-L Tags: Peripheral neuropathy Article Source Type: research

An inflammatory milieu: Optic perineuritis, retroperitoneal fibrosis, and giant cell arteritis
We present a patient initially diagnosed with idiopathic RPF treated with immunosuppression, who subsequently developed optic perineuritis followed by GCA. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 26, 2019 Category: Neurology Authors: Gold, D. M., Galetta, S. L. Tags: Secondary headache disorders, MRI, Autoimmune diseases, Vasculitis, Visual loss Clinical/Scientific Notes Source Type: research

West Nile virus-associated vasculitis and intracranial hemorrhage
West Nile virus (WNV) is a neurotropic flavivirus and the leading cause of mosquito-borne diseases in North America. In approximately 20% of cases, infection leads to a self-limited febrile illness and, in less than 1%, to a neuroinvasive disease often manifesting as meningoencephalitis with or without acute flaccid paralysis.1 Herein, we report the first case of WNV-associated CNS vasculitis and intracranial hemorrhage, thus expanding the spectrum of WNV infection. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 22, 2019 Category: Neurology Authors: Harroud, A., Almutlaq, A., Pellerin, D., Paz, D., Linnell, G. J., Gendron, D. Tags: Vasculitis, Encephalitis, Viral infections, Intracerebral hemorrhage, Subarachnoid hemorrhage Clinical/Scientific Notes Source Type: research

Neuromyelitis optica spectrum disorders with unevenly clustered attack occurrence
Conclusions Patients with NMOSD showed mixed periods of "clustered" occurrence with frequent attacks presenting with similar manifestations and "nonclustered" intermittent periods with sparse relapses. Approximately half of the relapses occurred during the "clustered" period within 12 months of the last clinical attack. Clinicians should pay special attention to whether the patients are presently in the "clustered" or "nonclustered" period to decide optimal relapse-preventive strategies. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 22, 2019 Category: Neurology Authors: Akaishi, T., Nakashima, I., Takahashi, T., Abe, M., Ishii, T., Aoki, M. Tags: Article Source Type: research

An argument for broad use of high efficacy treatments in early multiple sclerosis
Two different treatment paradigms are most often used in multiple sclerosis (MS). An escalation or induction approach is considered when treating a patient early in the disease course. An escalator prioritizes safety, whereas an inducer would favor efficacy. Our understanding of MS pathophysiology has evolved with novel in vivo and in vitro observations. The treatment landscape has also shifted significantly with the approval of over 10 new medications over the past decade alone. Here, we re-examine the treatment approach in light of these recent developments. We believe that recent work suggests that early prediction of t...
Source: Neurology Neuroimmunology and Neuroinflammation - November 22, 2019 Category: Neurology Authors: Stankiewicz, J. M., Weiner, H. L. Tags: Multiple sclerosis Views [amp ] Reviews Source Type: research

Antibodies to neurofascin, contactin-1, and contactin-associated protein 1 in CIDP: Clinical relevance of IgG isotype
Conclusions Our findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment. Classification of evidence This study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%). (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 21, 2019 Category: Neurology Authors: Cortese, A., Lombardi, R., Briani, C., Callegari, I., Benedetti, L., Manganelli, F., Luigetti, M., Ferrari, S., Clerici, A. M., Marfia, G. A., Rigamonti, A., Carpo, M., Fazio, R., Corbo, M., Mazzeo, A., Giannini, F., Cosentino, G., Zardini, E., Curro, R., Tags: Autoimmune diseases, All Neuromuscular Disease, Peripheral neuropathy, Chronic inflammatory demyelinating polyneuropathy Article Source Type: research

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE)
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 15, 2019 Category: Neurology Tags: All Immunology, All Clinical Neurology, All Neuro-ophthalmology, Multiple sclerosis, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Correction 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 - November 15, 2019 Category: Neurology Tags: All Immunology, All Clinical Neurology, All Neuro-ophthalmology, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Correction Source Type: research

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions
Conclusions We determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - November 12, 2019 Category: Neurology Authors: Krysko, K. M., LaHue, S. C., Anderson, A., Rutatangwa, A., Rowles, W., Schubert, R. D., Marcus, J., Riley, C. S., Bevan, C., Hale, T. W., Bove, R. Tags: Autoimmune diseases, Multiple sclerosis Article Source Type: research

A case of idiopathic multicentric Castleman disease in an alemtuzumab-treated patient with MS
Alemtuzumab is an efficacious therapy for active relapsing-remitting MS (RRMS), but its use is complicated by the potential development of secondary autoimmunity.1 Recent data from phase 3 extension studies confirm thyroid autoimmunity as the most abundant entity of secondary autoimmunity found in up to 30%–40% of treated patients, with most events mild or moderate in severity. Data also show low rates of previously known autoimmune phenomena, such as immune thrombocytopenia and nephropathy.2 However, further entities including sarcoidosis, vitiligo, and hemophagocytic lymphohistiocytosis (HLH) have been described in...
Source: Neurology Neuroimmunology and Neuroinflammation - November 8, 2019 Category: Neurology Authors: Rolfes, L., Pfeuffer, S., Ruck, T., Windhagen, S., Oschlies, I., Pavenstädt, H.-J., Angenendt, L., Wiendl, H., Krämer, J., Meuth, S. G. Tags: Autoimmune diseases, Multiple sclerosis Clinical/Scientific Notes Source Type: research

Black African and Latino/a identity correlates with increased plasmablasts in MS
Conclusion The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 31, 2019 Category: Neurology Authors: Telesford, K. M., Kaunzner, U. W., Perumal, J., Gauthier, S. A., Wu, X., Diaz, I., Kruse-Hoyer, M., Engel, C., Marcille, M., Vartanian, T. Tags: Autoimmune diseases, Underserved populations, Multiple sclerosis Article Source Type: research

Lymphocyte pharmacodynamics are not associated with autoimmunity or efficacy after alemtuzumab
Conclusions Repopulation kinetics of the evaluated peripheral lymphocyte subsets did not predict autoimmune AE occurrence or disease activity, including return of disease activity after 2 alemtuzumab courses. Further study is needed to investigate potential antigen-level markers of treatment response. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 29, 2019 Category: Neurology Authors: Wiendl, H., Carraro, M., Comi, G., Izquierdo, G., Kim, H. J., Sharrack, B., Tornatore, C., Daizadeh, N., Chung, L., Jacobs, A. K., Hogan, R. J., Wychowski, L. V., Van Wijmeersch, B., On behalf of the CARE-MS I, CARE-MS II, and CAMMS03409 Investigators Tags: MRI, Autoimmune diseases, Clinical trials Randomized controlled (CONSORT agreement), Multiple sclerosis Article Source Type: research

Learning from adverse treatment effects
The diagnosis and treatment of patients with adverse side effects of therapy can be challenging. Part of this challenge is staying up to date on the potential adverse effects associated with the increasingly numerous and complex treatments available. Among the excellent studies in the November issue of N2, there are several that address this issue. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 28, 2019 Category: Neurology Authors: Dalmau, J. Tags: Editor ' s Corner Source Type: research

Classifying the antibody-negative NMO syndromes: Clinical, imaging, and metabolomic modeling
Conclusions PCA identifies 3 phenotypic subgroups within antibody-negative patients and that the metabolite discriminators of RRMS and Ab-NMOSD suggest that these groupings have some pathogenic meaning. Thus, the identified clinico-radiologic discriminators may provide useful diagnostic clues when seeing antibody-negative patients in the clinic. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 28, 2019 Category: Neurology Authors: Yeo, T., Probert, F., Jurynczyk, M., Sealey, M., Cavey, A., Claridge, T. D. W., Woodhall, M., Waters, P., Leite, M. I., Anthony, D. C., Palace, J. Tags: Multiple sclerosis, Devic's syndrome Article Source Type: research

Normal gut microbiome in NMDA receptor encephalitis
Conclusion Patients with NMDAR encephalitis and controls both had a normal gut microbiome. The lack of overabundance of certain bacterial species in patients suggests that microbiome changes are no major contributors to the pathogenesis, disease course, or prognosis in NMDAR encephalitis. Despite the small sample size and heterogeneous groups, findings indicate differences to other neuroimmunologic diseases. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 17, 2019 Category: Neurology Authors: Herken, J., Bang, C., Rühlemann, M. C., Finke, C., Klag, J., Franke, A., Prüss, H. Tags: Autoimmune diseases, Encephalitis, All Clinical Neurology Article Source Type: research

Anti-NMDAR encephalitis: A single-center, longitudinal study in China
Conclusions Patients in China present with psychosis and seizure frequently but have a low percentage of underlying neoplasms. Re-enforced first-line immunotherapy is effective in managing anti-NMDAR encephalitis in the acute phase. Although relapse is relatively common, with combined first-line and long-term immunotherapy, most patients reached favorable outcomes. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 16, 2019 Category: Neurology Authors: Xu, X., Lu, Q., Huang, Y., Fan, S., Zhou, L., Yuan, J., Yang, X., Ren, H., Sun, D., Dai, Y., Zhu, H., Jiang, Y., Zhu, Y., Peng, B., Cui, L., Guan, H. Tags: Autoimmune diseases, All Clinical Neurology Article Source Type: research

IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis
Objective To test the hypothesis that patients with amyotrophic lateral sclerosis (ALS) inheriting the common interleukin 6 receptor (IL6R) coding variant (Asp358Ala, rs2228145, C allele) have associated increases in interleukin 6 (IL6) and IL6R levels in serum and CSF and faster disease progression than noncarriers. Methods An observational, case-control study of paired serum and CSF of 47 patients with ALS, 46 healthy, and 23 neurologic disease controls from the Northeastern ALS Consortium Biofluid Repository (cohort 1) was performed to determine serum levels of IL6, sIL6R, and soluble glycoprotein 130 and compared acro...
Source: Neurology Neuroimmunology and Neuroinflammation - October 14, 2019 Category: Neurology Authors: Wosiski-Kuhn, M., Robinson, M., Strupe, J., Arounleut, P., Martin, M., Caress, J., Cartwright, M., Bowser, R., Cudkowicz, M., Langefeld, C., Hawkins, G. A., Milligan, C. Tags: All Immunology, All Clinical Neurology, Amyotrophic lateral sclerosis, All Genetics Article Source Type: research

Identification of circulating MOG-specific B cells in patients with MOG antibodies
Conclusions This study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell–directed therapy. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 14, 2019 Category: Neurology Authors: Winklmeier, S., Schlüter, M., Spadaro, M., Thaler, F. S., Vural, A., Gerhards, R., Macrini, C., Mader, S., Kurne, A., Inan, B., Karabudak, R., Özbay, F. G., Esendagli, G., Hohlfeld, R., Kümpfel, T., Meinl, E. Tags: All Immunology, Autoimmune diseases, All Demyelinating disease (CNS), Devic's syndrome, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Article Source Type: research

Pembrolizumab as a treatment for PML?: Waiting for Godot
Progressive multifocal leukoencephalopathy (PML) is an infrequent but severe disease of the brain. In the setting of immunosuppression, the polyomavirus JC (JCV) may reactivate, migrate to the brain, infect oligodendrocytes, and to a lesser extent astrocytes, and cause demyelinating lesions. As there are currently no available anti-JCV therapy, the only treatment consists of restoring immunity. Whereas restoring immunity is feasible in patients with AIDS-PML (by giving antiretroviral therapy) or in natalizumab-treated patients with MS (by stopping administration of natalizumab), achieving this in patients with hemopat...
Source: Neurology Neuroimmunology and Neuroinflammation - October 9, 2019 Category: Neurology Authors: Du Pasquier, R. A. Tags: Autoimmune diseases, Viral infections Editorial Source Type: research

Pembrolizumab for progressive multifocal leukoencephalopathy due to primary immunodeficiency
Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease of the CNS, which develops almost exclusively in immunocompromised patients and is caused by JC virus (JCV), a common polyomavirus.1 So far, treatment efficacy is only modest if the compromised immune system cannot be restored.2–4 A potential treatment target is the programmed cell death protein 1 (PD-1) whose expression on CD4+ and CD8+ T lymphocytes has been shown to be elevated in patients with PML. Moreover, blocking of the PD-1 receptor resulted in increased JCV-specific T-cell immune response in a subgroup of patients w...
Source: Neurology Neuroimmunology and Neuroinflammation - October 9, 2019 Category: Neurology Authors: Küpper, C., Heinrich, J., Kamm, K., Bücklein, V., Rothenfusser, S., Straube, A. Tags: Clinical/Scientific Notes Source Type: research

Ineffective treatment of PML with pembrolizumab: Exhausted memory T-cell subsets as a clue?
Progressive multifocal leukoencephalopathy (PML) is a rare pathologic CNS condition caused by JC polyomavirus (JCPyV) in immunodeficient patients. Immune checkpoint inhibition was previously reported to potentially facilitate the antiviral response.1 (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 9, 2019 Category: Neurology Authors: Pawlitzki, M., Schneider-Hohendorf, T., Rolfes, L., Meuth, S. G., Wiendl, H., Schwab, N., Grauer, O. M. Tags: Autoimmune diseases, Viral infections Clinical/Scientific Notes Source Type: research

Vitamin D enhances responses to interferon-{beta} in MS
Conclusion Vitamin D enhances IFN-β induction of multiple proteins and also reverses the Th1/Th2 bias in MS seen with IFN-β alone. The combination of vitamin D and IFN-β has potential benefit in ameliorating MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - October 3, 2019 Category: Neurology Authors: Feng, X., Wang, Z., Howlett-Prieto, Q., Einhorn, N., Causevic, S., Reder, A. T. Tags: Autoimmune diseases, Endocrine, Nutritional, All Demyelinating disease (CNS), Multiple sclerosis Article Source Type: research

Elevated levels of miR-181c and miR-633 in the CSF of patients with MS: A validation study
Objective To validate a previously discovered microRNA (miRNA) panel in the CSF of patients with MS, we now tested the diagnostic value of CSF-derived candidate miRNAs in a case-control study in a larger MS cohort. Methods The levels of miR-181c, miR-633, and miR-922 were analyzed in the CSF of 218 patients with MS and 211 patients with other neurologic diseases (OND) by real-time quantitative reverse transcriptase PCR. Results CSF levels of both miR-181c (p
Source: Neurology Neuroimmunology and Neuroinflammation - October 1, 2019 Category: Neurology Authors: Kramer, S., Haghikia, A., Bang, C., Scherf, K., Pfanne, A., Duscha, A., Kaisler, J., Gisevius, B., Gold, R., Thum, T., Haghikia, A. Tags: Autoimmune diseases, Clinical neurology examination, Multiple sclerosis Article Source Type: research

Fatal PCR-negative herpes simplex virus-1 encephalitis with GABAA receptor antibodies
We report an unusual case of a patient with refractory status epilepticus due to HSVE with antibodies against GABAA receptors (GABAAR). (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 25, 2019 Category: Neurology Authors: Schuster, S., Abrante, L., Matschke, J., Lütgehetmann, M., Holst, B., Gelderblom, M., Braass, H., Leypoldt, F., Magnus, T. Tags: Autoimmune diseases, Encephalitis, Viral infections, Post-infectious, Status epilepticus Clinical/Scientific Notes Source Type: research

Effects of natalizumab therapy on intrathecal antiviral antibody responses in MS
Conclusions These data indicate that JCV-specific antibodies are produced intrathecally in a minority of patients with MS, and NAT treatment affects the intrathecal humoral immune response against JCV relatively specifically compared with other neurotropic viruses. Further studies are needed to determine whether this effect translates to higher risk of progressive multifocal leukoencephalopathy development. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 25, 2019 Category: Neurology Authors: Largey, F., Jelcic, I., Sospedra, M., Heesen, C., Martin, R., Jelcic, I. Tags: Cerebrospinal Fluid, Multiple sclerosis Article Source Type: research

Overnight loss of pigmented hair in autoimmune autonomic neuropathy treated with IVIg
Autoimmune autonomic neuropathy is an immune-mediated disease, which can be associated with high titers of pathogenic antibodies to the nicotinic ganglionic acetylcholine receptor (gAChR).1–3 IV immunoglobulin (IVIg) is a commonly used treatment in autoimmune autonomic neuropathy associated with gAChR antibodies. Herein, we report a patient with an autonomic neuropathy associated with high-titer gAChR antibodies who developed selective pigmented hair loss while being treated with IVIg. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 25, 2019 Category: Neurology Authors: Turner, L. E., Pittock, S. J., McEvoy, M. T., Flanagan, E. P. Tags: Clinical/Scientific Notes Source Type: research