Failure of alemtuzumab therapy to control MOG encephalomyelitis

Wildemann, Brigitte; Jarius, Sven; Schwarz, Alexander; Diem, Ricarda; Viehöver, Andrea; Hähnel, Stefan; Reindl, Markus; Korporal-Kuhnke, Mirjam

doi:10.1212/wnl.0000000000004087

Cited by 27 publications

(10 citation statements)

References 7 publications

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“…To the knowledge of the current authors, so far only one case has been published detailing treatment with alemtuzumab, a highly effective treatment in MS. Similar to reports of alemtuzumab use in AQP-4 antibody NMOSD ( 105 ), treatment failed and disease activity resumed ( 106 ). The failure of a treatment effective in MS is well-known in NMOSD, suggesting a distinct pathomechanism in antibody-associated disorders.…”

Section: Treatmentsupporting

confidence: 78%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Berger

2018

Front. Immunol.

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Inflammatory demyelinating CNS syndromes include, besides their most common entity multiple sclerosis (MS), several different diseases of either monophasic or recurrent character—including neuromyelitis optica spectrum disorders (NMOSDs) and acute disseminated encephalomyelitis (ADEM). Early diagnostic differentiation is crucial for devising individual treatment strategies. However, due to overlapping clinical and paraclinical features diagnosis at the first demyelinating event is not always possible. A multiplicity of potential biological markers that could discriminate the different diseases was studied. As the use of autoantibodies in patient management of other autoimmune diseases, is well-established and evidence for the critical involvement of B cells/antibodies in disease pathogenesis in inflammatory demyelinating CNS syndromes increases, antibodies seem to be valuable diagnostic tools. Since the detection of antibodies against aquaporin-4 (AQP-4), the understanding of immunopathogenesis and diagnostic management of NMOSDs has dramatically changed. However, for most inflammatory demyelinating CNS syndromes, a potential antigen target is still not known. A further extensively studied possible target structure is myelin oligodendrocyte glycoprotein (MOG), found at the outermost surface of myelin sheaths and oligodendrocyte membranes. With detection methods using cell-based assays with full-length, conformationally correct MOG, antibodies have been described in early studies with a subgroup of patients with ADEM. Recently, a humoral immune reaction against MOG has been found not only in monophasic diseases, but also in recurrent non-MS diseases, particularly in pediatric patients. This review presents the findings regarding MOG antibodies as potential biological markers in discriminating between these different demyelinating CNS diseases, and discusses recent developments, clinical implementations, and data on immunopathogenesis of MOG antibody-associated disorders.

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Section: Treatmentsupporting

confidence: 78%

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Berger

2018

Front. Immunol.

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“…None of the patients received alemtuzumab, which was reported to cause disease worsening in patients with NMOSD 27 and MOG-Ab-associated disease. 28 Interestingly, 6 of 7 patients (85.7%) who received rituximab alone continued to relapse despite B-cell depletion.…”

Section: Discussionmentioning

confidence: 97%

Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease

et al. 2018

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“…Given comparable EDSS scores, we consider the different levels of task difficulty between studies the most likely explanation. Obviously, the patients' higher level of exhaustion and depression – which are typical symptoms of MS [25] – did not interfere with the precision in target‐oriented movements. Moreover, targeting performance did not mirror the patients' moderate impairment in the NHPT, indicating that their neurofunctional status and VAT performance were independent.…”

Section: Discussionmentioning

confidence: 99%

Impaired consolidation of visuomotor adaptation in patients with multiple sclerosis

Nguemeni

Nakchbandi

Homola

et al. 2020

Euro J of Neurology

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Background Apart from inflammation and neurodegeneration, the individual clinical course of multiple sclerosis (MS) might be determined by differential adaptive capacities of the central nervous system. It has been postulated that the retention of adaptive training effects may be impaired in persons with MS (PwMS). Objective To investigate motor adaptation and consolidation capacities of people with MS in a visual motor adaptation task (VAT). Methods A total of 23 PwMS (Expanded Disability Status Scale (EDSS) score < 6) and 20 matched healthy controls were recruited. All participants completed three sessions of a VAT where a clockwise rotation angle of 30° was introduced as perturbation during the active learning part of the paradigm. The training session (T0) was repeated after 24 h (T1) and 72 h (T2). Directional errors and parameters of adaptation and retention were evaluated. Results PwMS showed similar adaptation and online learning abilities as controls. However, the retention ratio was significantly lower in patients compared to controls at T1 (p = 0.036) and T2 (p = 0.039). There was no significant correlation between the overall adaptation or retention ratio and the EDSS score, respectively. Conclusion Our findings indicate intact adaptation, but limited consolidation, in patients with mild‐to‐moderate MS. Future studies are needed to define the neurobiological substrates of this plasticity and the extent to which it can influence clinical outcomes.

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Failure of alemtuzumab therapy to control MOG encephalomyelitis

Cited by 27 publications

References 7 publications

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorders: Toward a New Spectrum of Inflammatory Demyelinating CNS Disorders?

Disease Course and Treatment Responses in Children With Relapsing Myelin Oligodendrocyte Glycoprotein Antibody–Associated Disease

Impaired consolidation of visuomotor adaptation in patients with multiple sclerosis

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