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1.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200249, 2024 Jul.
Article En | MEDLINE | ID: mdl-38696737

OBJECTIVES: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disease rarely associated with malignancy. We report the clinical, MRI, immunopathology, and treatment response in a person with MOGAD and melanoma. METHODS: This is a case report of a person with a multidisciplinary evaluation at a tertiary referral center. RESULTS: A 52-year-old man presented with progressive encephalomyelitis that led to identification of metastatic melanoma. Investigations revealed positive MOG-IgG at high titers in serum (1:1,000; normal, <1:20) and CSF (1:4,096; normal, <1:2). MRI demonstrated multifocal T2 lesions with enhancement in the brain and spine. Brain biopsy showed demyelination and inflammation. MOG immunostaining was not present in the tumor tissue. He initially improved with methylprednisolone, plasmapheresis, prolonged oral steroid taper, and cancer-directed treatment with BRAF and MEK 1/2 inhibitors, but then developed bilateral optic neuritis. IV immunoglobulin (IVIG) was initiated. Five months later, he developed metastases and immune checkpoint inhibitor (ICI) treatment was started, which precipitated optic neuritis and myelitis despite IVIG and prednisone. Tocilizumab, an interleukin-6 receptor blocker, was started with excellent and sustained clinical and radiologic response. DISCUSSION: This case revealed a presentation of MOGAD concurrent with melanoma without tumor MOG immunostaining. We highlight tocilizumab as a dual-purpose treatment of MOGAD and the neurologic immune-related adverse effect of ICI.


Immune Checkpoint Inhibitors , Melanoma , Myelin-Oligodendrocyte Glycoprotein , Humans , Male , Melanoma/drug therapy , Middle Aged , Myelin-Oligodendrocyte Glycoprotein/immunology , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/administration & dosage , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/chemically induced
2.
Front Immunol ; 13: 953993, 2022.
Article En | MEDLINE | ID: mdl-35958613

Background: Immunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear. Aim: To identify the efficacy and tolerability of different treatments for MOG-AD. Methods: Systematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI). Results: Twelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=-0.85, 95% CrI: -1.7 to -0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies. Conclusions: Whilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives.


Demyelinating Autoimmune Diseases, CNS , Immunoglobulins, Intravenous , Azathioprine/adverse effects , Bayes Theorem , Demyelinating Autoimmune Diseases, CNS/drug therapy , Humans , Immunoglobulins, Intravenous/adverse effects , Mycophenolic Acid/adverse effects , Network Meta-Analysis , Recurrence , Rituximab/adverse effects
3.
J Neuroimmunol ; 364: 577812, 2022 03 15.
Article En | MEDLINE | ID: mdl-35063726

INTRODUCTION: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic neuritis, transverse myelitis, brainstem encephalitis, and other CNS manifestations and notably, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Current treatment strategy is high-dose intravenous methylprednisolone followed by maintenance immunotherapy for relapse prevention. The purpose of this study is to systematically create compelling evidence addressing the role of rituximab in relapse prevention among patient with MOGAD. METHODS: This study follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. We searched PubMed, Embase, and Google Scholar for English language papers published between 2010 and 2021. Individual study proportions were meta-analyzed to yield the pooled relapse-free patient proportion. Individual studies' mean pre- and post-treatment annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) were used to calculate the overall mean difference. RESULTS: Our meta-analysis includes 13 studies with 238 subjects. After rituximab treatment, 55% (95% CI: 0.49-0.61) of MOGAD patients remained relapse-free. Our study found that after rituximab therapy, ARR was lowered by 1.36 (95% CI 1.02-1.71, p < 0.001). Similarly, we detected a 0.52 (95% CI: 0.08 to 0.96, p = 0.02) difference in EDSS score after starting rituximab medication. Because only a handful of the included studies documented adverse events, the safety profile of rituximab for the treatment of MOGAD could not be effectively determined. CONCLUSION: Our meta-analysis shows that rituximab effectively prevents relapses in MOGAD patients.


Demyelinating Autoimmune Diseases, CNS/drug therapy , Immunologic Factors/therapeutic use , Rituximab/therapeutic use , Autoantibodies/immunology , Autoantigens/immunology , Demyelinating Autoimmune Diseases, CNS/immunology , Humans , Immunoglobulin G/immunology , Myelin-Oligodendrocyte Glycoprotein/immunology , Recurrence
4.
Article En | MEDLINE | ID: mdl-34785575

BACKGROUND AND OBJECTIVES: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. RESULTS: Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. DISCUSSION: This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD.


Antibodies, Monoclonal, Humanized/pharmacology , Aquaporin 4/immunology , Demyelinating Autoimmune Diseases, CNS/drug therapy , Myelin-Oligodendrocyte Glycoprotein/immunology , Neuromyelitis Optica/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Demyelinating Autoimmune Diseases, CNS/immunology , Female , Humans , Male , Middle Aged , Neuromyelitis Optica/immunology , Outcome Assessment, Health Care , Secondary Prevention , Young Adult
6.
Article En | MEDLINE | ID: mdl-34341094

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.


COVID-19 , Demyelinating Autoimmune Diseases, CNS , Hospitalization/statistics & numerical data , Immunologic Factors/therapeutic use , Registries/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Adult , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/therapy , Cohort Studies , Comorbidity , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/epidemiology , Female , Humans , Immunologic Factors/adverse effects , Male , Middle Aged , Mortality , New England/epidemiology , Pilot Projects , Risk Factors , Severity of Illness Index
8.
Am J Med Sci ; 360(4): 410-413, 2020 10.
Article En | MEDLINE | ID: mdl-32631578

Immunoglobulin G4 related disease (IgG4-RD) is a recently recognized immune-mediated disease which is far from understanding. A case of inflammatory demyelinating pseudotumor had been confirmed as IgG4-RD according to pathology features and clinical context. Combined with liver dysfunction, IgG4 related sclerotic cholangitis was suspected. However, primary biliary cholangitis was finally diagnosed by immune marks and histopathological findings. This is the first report in which mass lesions in the brain parenchyma were caused by IgG4-RD while liver dysfunction was due to primary biliary cholangitis. The clinical features of IgG4-RD are miscellaneous, and the accumulation of case reports might enrich clinicians experience and broaden their horizons about this condition.


Demyelinating Autoimmune Diseases, CNS/complications , Granuloma, Plasma Cell/complications , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G/immunology , Liver Cirrhosis, Biliary/complications , Adult , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/pathology , Diagnosis, Differential , Granuloma, Plasma Cell/drug therapy , Granuloma, Plasma Cell/pathology , Humans , Immunoglobulin G4-Related Disease/drug therapy , Immunoglobulin G4-Related Disease/pathology , Liver Cirrhosis, Biliary/diagnosis , Liver Cirrhosis, Biliary/drug therapy , Liver Function Tests , Magnetic Resonance Imaging , Male , Treatment Outcome
9.
Mult Scler Relat Disord ; 42: 102108, 2020 Jul.
Article En | MEDLINE | ID: mdl-32339987

Immunoglobulin G (IgG) antibodies against myelin oligodendrocyte glycoprotein in serum denote an emerging autoimmune disorder of the central nervous system. Treatment trials have not been performed so far and anecdotal reports suggest that immunotherapies approved for multiple sclerosis (MS) may not be effective. We report favorable disease control with alemtuzumab, a CD52 depleting antibody approved for active MS, in a 34-year-old woman with the rarer condition of MOG-IgG disease with MS-phenotype. MOG-IgG in serum persisted over the entire observation period of almost five years. This case emphasizes that treatment responses may be distinct for different phenotypes of MOG-IgG associated disease.


Alemtuzumab/administration & dosage , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Immunologic Factors/administration & dosage , Myelin-Oligodendrocyte Glycoprotein/immunology , Adult , Demyelinating Autoimmune Diseases, CNS/diagnosis , Female , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Phenotype
10.
Article En | MEDLINE | ID: mdl-32170045

OBJECTIVE: To investigate whether the use of mycophenolate mofetil (MMF) could reduce the relapse risk in patients with myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G (IgG)-associated disorders (MOGADs). METHODS: This prospective observational cohort study included patients with MOGAD at Peking Union Medical College Hospital between January 1, 2017, and April 30, 2019. The patients were divided into 2 groups: those with (MMF+) or without (MMF-) MMF therapy. The primary outcome was relapse at follow-up. We used Cox proportional hazards models to calculate hazard ratios (HRs) for relapse. RESULTS: Seventy-nine patients were included in our MOG cohort. Fifty (63.3%) were adults at index date, and 47 (59.5%) were women. Fifty-four (68.4%) were in the MMF+ group, and 25 (31.6%) were in the MMF- group. Clinical and demographic factors, MOG-IgG titer, and follow-up time (median, 472.5 days for MMF+, 261.0 days for MMF-) were comparable between the groups. Relapse rates were 7.4% (4/54) in the MMF+ group and 44.0% (11/25) in the MMF- group. Of all potential confounders, only the use of MMF was associated with reduced risk of relapse. The HR for relapse among patients in the MMF+ group was 0.14 (95% CI, 0.05-0.45) and was 0.08 (95% CI, 0.02-0.28) in a model adjusted for age, sex, disease course, and MOG-IgG titer. MMF therapy also remained associated with a reduced relapse risk in sensitivity analyses. Only one patient (1.9%) discontinued MMF therapy because of adverse effect. CONCLUSIONS: These findings provide a clinical evidence that MMF immunosuppression therapy may prevent relapse in patients with MOGAD. CLASSIFICATION OF EVIDENCE: This study provides class IV evidence that for patients with MOGAD, MMF reduces relapse risk.


Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Immunologic Factors/pharmacology , Mycophenolic Acid/pharmacology , Myelin-Oligodendrocyte Glycoprotein/immunology , Outcome Assessment, Health Care , Adolescent , Adult , Child , Drug Therapy, Combination , Female , Follow-Up Studies , Glucocorticoids/pharmacology , Humans , Immunoglobulin G , Immunologic Factors/administration & dosage , Immunologic Factors/adverse effects , Male , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/adverse effects , Proportional Hazards Models , Prospective Studies , Recurrence , Secondary Prevention , Young Adult
11.
Mult Scler Relat Disord ; 41: 102019, 2020 Jun.
Article En | MEDLINE | ID: mdl-32151983

Few cases of late onset neutropenia after RITUXIMAB treatment (LONART) have been reported in patients with neuroinflammatory disorders. We conducted a retrospective analysis of patients treated with RITUXIMAB for neuromyelitis optica spectrum disorders (NMOSD), MOG-antibody-associated disease (MOGAD) and multiple sclerosis (MS) at the Toulouse University Hospital from November 2007 to October 2019. Ten patients with LONART were identified in a total of 385 patients: 4/25 were MOGAD patients, 2/20 were NMOSD patients and only 4/340 were MS patients (p < 0,05). Six required intravenous antibiotics whereas four were asymptomatic. Eight patients received new infusions of RITUXIMAB after resolution of their neutropenia. Neutropenia recurred in one patient.


Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Immunologic Factors/adverse effects , Neutropenia/chemically induced , Rituximab/adverse effects , Adult , Female , Humans , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunology , Myelin-Oligodendrocyte Glycoprotein/immunology , Neuromyelitis Optica/drug therapy , Neuromyelitis Optica/immunology
12.
Dev Med Child Neurol ; 62(3): 390-395, 2020 03.
Article En | MEDLINE | ID: mdl-31468511

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed.


Anti-Inflammatory Agents/therapeutic use , Demyelinating Autoimmune Diseases, CNS/drug therapy , Inflammation/drug therapy , Myelin-Oligodendrocyte Glycoprotein/immunology , Rituximab/therapeutic use , Adolescent , Autoantibodies/blood , Child , Demyelinating Autoimmune Diseases, CNS/blood , Demyelinating Autoimmune Diseases, CNS/immunology , Female , Humans , Inflammation/blood , Inflammation/immunology , Male , Treatment Outcome
14.
Mult Scler Relat Disord ; 29: 108-110, 2019 Apr.
Article En | MEDLINE | ID: mdl-30708307

There are no specific radiologic features in MOG-Ab (autoantibodies directed against myelin oligodendrocyte glycoprotein)-associated diseases. We present two MOG-Ab-positive patients with symmetrical lesions in the bilateral cingulate cortex of the frontal and parietal lobes. Those lesions showed hyperperfusion in acute phase and hypoperfusion in chronic phase on brain SPECT. In both patients, steroid therapy was effective in acute phase and for prevention of recurrence. High signal in the bilateral cingulate cortex on MR T2-weighted and FLAIR images might to be one of the unique findings considered MOG-Ab associated diseases.


Autoantibodies/immunology , Demyelinating Autoimmune Diseases, CNS/pathology , Gyrus Cinguli/pathology , Myelin-Oligodendrocyte Glycoprotein/immunology , Steroids/pharmacology , Acute Disease , Adult , Chronic Disease , Demyelinating Autoimmune Diseases, CNS/diagnostic imaging , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Female , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Secondary Prevention , Tomography, Emission-Computed, Single-Photon
15.
Mult Scler Relat Disord ; 27: 312-314, 2019 Jan.
Article En | MEDLINE | ID: mdl-30469022

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-related spectrum disorders (MOG-SD) are a heterogeneous group of inflammatory demyelinating diseases of the central nervous system, usually responsive to conventional immunosuppressive therapies. However, knowledge about treatment of non-responder patients is scarce. METHODS: We report on a 20-year-old MOG-SD patient who experienced clinical deterioration despite rituximab-induced B-cell depletion. RESULTS: Rescue therapy with tocilizumab (TCZ) prevented further relapses, with reduction of spinal-cord load on MRI, and a remarkable reduction of disability at the two-year follow-up. CONCLUSION: Our observations suggest that TCZ could induce clinico-radiologic improvements, which make it as an option for the treatment of MOG-SD.


Antibodies, Monoclonal, Humanized/therapeutic use , Demyelinating Autoimmune Diseases, CNS/drug therapy , Immunologic Factors/therapeutic use , Myelin-Oligodendrocyte Glycoprotein/immunology , Demyelinating Autoimmune Diseases, CNS/complications , Demyelinating Autoimmune Diseases, CNS/diagnostic imaging , Demyelinating Autoimmune Diseases, CNS/pathology , Humans , Male , Optic Neuritis/complications , Rituximab/therapeutic use , Spinal Cord/diagnostic imaging , Spinal Cord/drug effects , Treatment Outcome , Young Adult
16.
Mult Scler Relat Disord ; 26: 201-203, 2018 Nov.
Article En | MEDLINE | ID: mdl-30268041

BACKGROUND: Voltage gated calcium channels (VGCC) are well-known targets for antibody-associated disease. Of the 5 VGCC subtypes, the most well-known is the P/Q subtype associated with Lambert-Eaton Myasthenic Syndrome (LEMS). However, this case focuses on the much less understood N-type calcium channel antibody. The objective of this case is to review the literature regarding the clinical significance of the N-type calcium channel antibody and its relationship to MS. METHODS: A 37-year old male presented with vertigo, paranoia, and tremor and had MRI changes suggestive of demyelinating disease. Evaluation revealed positive N-type calcium channel antibodies. Steroids dramatically improved symptoms and normalized antibodies. Years later recurrent symptoms were again associated with elevated antibodies. RESULTS AND CONCLUSION: This patient likely has autoimmune encephalitis associated with elevated N-type calcium channel antibodies. This case highlights the clinical significance of N-type calcium channel antibodies and the importance of correctly diagnosing patients with antibody mediated disease that may very well mimic more common neurologic diseases such as multiple sclerosis (MS).


Autoantibodies/immunology , Calcium Channels, N-Type/immunology , Demyelinating Autoimmune Diseases, CNS/diagnosis , Encephalitis/diagnosis , Multiple Sclerosis/diagnosis , Adult , Demyelinating Autoimmune Diseases, CNS/drug therapy , Encephalitis/drug therapy , Humans , Magnetic Resonance Imaging , Male , Steroids/pharmacology
17.
Clin Neurophysiol ; 129(10): 2162-2169, 2018 10.
Article En | MEDLINE | ID: mdl-30144659

OBJECTIVE: To improve understanding of disease pathophysiology in anti-myelin-associated glycoprotein (anti-MAG) neuropathy to guide further treatment approaches. METHODS: Anti-MAG neuropathy patients underwent clinical assessments, nerve conduction and excitability studies, and ultrasound assessment. RESULTS: Patients demonstrated a distinctive axonal excitability profile characterised by a reduction in superexcitability [MAG: -14.2 ±â€¯1.6% vs healthy controls (HC): -21.8 ±â€¯1.2%; p < 0.01] without alterations in most other excitability parameters. Mathematical modelling of nerve excitability recordings suggested that changes in axonal function could be explained by a 72.5% increase in juxtaparanodal fast potassium channel activation and an accompanying hyperpolarization of resting membrane potential (by 0.3 mV) resulting in a 94.2% reduction in discrepancy between anti-MAG data and the healthy control model. Superexcitability changes correlated strongly with clinical and neurophysiological parameters. Furthermore, structural assessments demonstrated a proximal pattern of nerve enlargement (C6 nerve root cross-sectional area: 15.9 ±â€¯8.1 mm2 vs HC: 9.1 ±â€¯2.3 mm2; p < 0.05). CONCLUSIONS: The imaging and neurophysiological results support the pathogenicity of anti-MAG IgM. Widening between adjacent loops of paranodal myelin due to antibodies would expand the pathway from the node to the juxtaparanode, increasing activation of juxtaparanodal fast potassium channels, thereby impairing saltatory conduction. SIGNIFICANCE: Potassium channel blockers may prove beneficial in restoring conduction closer to its normal state and improving nerve function in anti-MAG neuropathy.


Demyelinating Autoimmune Diseases, CNS/metabolism , Models, Neurological , Myelin-Associated Glycoprotein/immunology , Polyneuropathies/metabolism , Potassium Channels/metabolism , Action Potentials , Aged , Aged, 80 and over , Axons/physiology , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/physiopathology , Female , Humans , Immunoglobulin M/immunology , Male , Middle Aged , Polyneuropathies/drug therapy , Polyneuropathies/immunology , Polyneuropathies/physiopathology , Potassium Channel Blockers/therapeutic use , Spinal Nerve Roots/metabolism , Spinal Nerve Roots/physiopathology
18.
Nat Rev Neurol ; 14(7): 433-445, 2018 07.
Article En | MEDLINE | ID: mdl-29925924

Immune-mediated disorders of the CNS in children are a complex group of demyelinating, inflammatory, parainfectious and postinfectious disorders with heterogeneous pathobiological mechanisms and clinical manifestations, often associated with fundamental derangement in immune regulation. In this Review, we aim to provide an update on our knowledge of neuroimmune disorders and highlight areas of research that are priorities for improving clinical management. We outline the clinical features of neuroimmune disorders, the current approaches to their treatment and new approaches in development. We then consider the pathological features, including biomarkers, pathological mechanisms and genetics, and discuss the value of immune assays in clinical investigation and basic research. On the basis of current knowledge and techniques, we propose four research priorities: rigorous and consistent collection of core clinical data, cooperative investigation of treatments, development of biological assays and genetic studies. These priorities should help us to achieve the shared goal of precision medicine for neuroimmune disorders. However, multicentre research and the creation of clinical consortia for these rare disorders will be necessary, and we hope that this Review serves as a call to action that is timely given current exciting advances in neuroimmune therapeutics.


Biomarkers , Central Nervous System Diseases/diagnosis , Demyelinating Autoimmune Diseases, CNS/diagnosis , Encephalitis/diagnosis , Immune System Diseases/diagnosis , Neuroimmunomodulation , Adolescent , Animals , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/immunology , Central Nervous System Diseases/metabolism , Child , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Demyelinating Autoimmune Diseases, CNS/metabolism , Encephalitis/drug therapy , Encephalitis/immunology , Encephalitis/metabolism , Humans , Immune System Diseases/drug therapy , Immune System Diseases/immunology , Immune System Diseases/metabolism
19.
Mult Scler Relat Disord ; 18: 90-92, 2017 Nov.
Article En | MEDLINE | ID: mdl-29141829

We report the case of a patient who initially presented with fever, headache and seizure. MRI revealed a fluid attenuation inversion recovery (FLAIR) high-intensity lesion involving the right temporal, parietal and occipital cortex. Afterwards, the patient developed three recurrent episodes, manifested as brainstem encephalitis, optic neuritis and ADEM-like illness successively, indicating demyelination. Both of his serum anti-MOG and CSF anti-NMDAR antibodies were proved positive by transfected cell based assays. We consider our case to have cortical encephalitis due to certain autoimmune mechanism initially, and then developed MOG-antibody mediated recurrent demyelination in the following episodes.


Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnosis , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , Demyelinating Autoimmune Diseases, CNS/diagnosis , Myelin-Oligodendrocyte Glycoprotein/immunology , Receptors, N-Methyl-D-Aspartate/immunology , Adult , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/drug therapy , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/immunology , Biomarkers/blood , Biomarkers/cerebrospinal fluid , Brain/diagnostic imaging , Demyelinating Autoimmune Diseases, CNS/diagnostic imaging , Demyelinating Autoimmune Diseases, CNS/drug therapy , Demyelinating Autoimmune Diseases, CNS/immunology , Diagnosis, Differential , Disease Progression , Humans , Male
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