GABA
            <sub>A</sub>
            receptor autoimmunity after alemtuzumab treatment for multiple sclerosis

Maniscalco, Giorgia Teresa; Mariotto, Sara; Höftberger, Romana; Capra, Ruggero; Servillo, Giovanna; Manzo, Valentino; Napolitano, Massimo; Candelaresi, Paolo; Gerevini, Simonetta; Ferrari, Sérgio; Bozzetti, Silvia; Spatola, Marianna; Florio, Ciro

doi:10.1212/wnl.0000000000010310

Cited by 11 publications

(11 citation statements)

References 7 publications

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“…4. Neurological autoimmunity has been reported in posttransplant patients and patients treated with alemtuzumab (156,157). In both cases, imbalance between B-and Tcell reconstitution after aggressive immunosuppression may rarely result in autoimmunity, including MOGAD (156).…”

Section: Special Settings Potentially At Higher Risk Of Neurological ...mentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

et al. 2022

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Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is the most recently defined inflammatory demyelinating disease of the central nervous system (CNS). Over the last decade, several studies have helped delineate the characteristic clinical-MRI phenotypes of the disease, allowing distinction from aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD) and multiple sclerosis (MS). The clinical manifestations of MOGAD are heterogeneous, ranging from isolated optic neuritis or myelitis to multifocal CNS demyelination often in the form of acute disseminated encephalomyelitis (ADEM), or cortical encephalitis. A relapsing course is observed in approximately 50% of patients. Characteristic MRI features have been described that increase the diagnostic suspicion (e.g., perineural optic nerve enhancement, spinal cord H-sign, T2-lesion resolution over time) and help discriminate from MS and AQP4+NMOSD, despite some overlap. The detection of MOG-IgG in the serum (and sometimes CSF) confirms the diagnosis in patients with compatible clinical-MRI phenotypes, but false positive results are occasionally encountered, especially with indiscriminate testing of large unselected populations. The type of cell-based assay used to evaluate for MOG-IgG (fixed vs. live) and antibody end-titer (low vs. high) can influence the likelihood of MOGAD diagnosis. International consensus diagnostic criteria for MOGAD are currently being compiled and will assist in clinical diagnosis and be useful for enrolment in clinical trials. Although randomized controlled trials are lacking, MOGAD acute attacks appear to be very responsive to high dose steroids and plasma exchange may be considered in refractory cases. Attack-prevention treatments also lack class-I data and empiric maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the presenting attack. A variety of empiric steroid-sparing immunosuppressants can be considered and may be efficacious based on retrospective or prospective observational studies but prospective randomized placebo-controlled trials are needed to better guide treatment. In summary, this article will review our rapidly evolving understanding of MOGAD diagnosis and management.

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Section: Special Settings Potentially At Higher Risk Of Neurological ...mentioning

confidence: 99%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

et al. 2022

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“…Cases of neurological autoimmunity including antibodyassociated encephalitis has been reported in multiple sclerosis patients treated with the CD52 (e.g., alemtuzumab) or CD25 (e.g., daclizumab) protein inhibitors (127)(128)(129).…”

Section: Other Immune-active Agentsmentioning

confidence: 99%

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Sechi

Flanagan

2021

Front. Neurol.

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Antibody-mediated disorders of the central nervous system (CNS) are increasingly recognized as neurologic disorders that can be severe and even life-threatening but with the potential for reversibility with appropriate treatment. The expanding spectrum of newly identified autoantibodies targeting glial or neuronal (neural) antigens and associated clinical syndromes (ranging from autoimmune encephalitis to CNS demyelination) has increased diagnostic precision, and allowed critical reinterpretation of non-specific neurological syndromes historically associated with systemic disorders (e.g., Hashimoto encephalopathy). The intracellular vs. cell-surface or synaptic location of the different neural autoantibody targets often helps to predict the clinical characteristics, potential cancer association, and treatment response of the associated syndromes. In particular, autoantibodies targeting intracellular antigens (traditionally termed onconeural autoantibodies) are often associated with cancers, rarely respond well to immunosuppression and have a poor outcome, although exceptions exist. Detection of neural autoantibodies with accurate laboratory assays in patients with compatible clinical-MRI phenotypes allows a definite diagnosis of antibody-mediated CNS disorders, with important therapeutic and prognostic implications. Antibody-mediated CNS disorders are rare, and reliable autoantibody identification is highly dependent on the technique used for detection and pre-test probability. As a consequence, indiscriminate neural autoantibody testing among patients with more common neurologic disorders (e.g., epilepsy, dementia) will necessarily increase the risk of false positivity, so that recognition of high-risk clinical-MRI phenotypes is crucial. A number of emerging clinical settings have recently been recognized to favor development of CNS autoimmunity. These include antibody-mediated CNS disorders following herpes simplex virus encephalitis or occurring in a post-transplant setting, and neurological autoimmunity triggered by TNFα inhibitors or immune checkpoint inhibitors for cancer treatment. Awareness of the range of clinical and radiological manifestations associated with different neural autoantibodies, and the specific settings where autoimmune CNS disorders may occur is crucial to allow rapid diagnosis and early initiation of treatment.

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“…The lack of both radiologic and clinical signs of active disease ruled out a diagnosis of psychosis secondary to multiple sclerosis. Treatment history was also considered, as treatment with monoclonal antibodies has been described as a possible cause of encephalitis [ 16 ]. Our patient, however, had not been receiving such treatment.…”

Section: Discussionmentioning

confidence: 99%

Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

et al. 2021

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Background Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ. Case presentation A 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve. Conclusions There is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.

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GABA _A receptor autoimmunity after alemtuzumab treatment for multiple sclerosis

Cited by 11 publications

References 7 publications

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

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GABA A receptor autoimmunity after alemtuzumab treatment for multiple sclerosis

Cited by 11 publications

References 7 publications

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD): A Review of Clinical and MRI Features, Diagnosis, and Management

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

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GABA _A receptor autoimmunity after alemtuzumab treatment for multiple sclerosis