Progressive Encephalomyelitis, Rigidity, and Myoclonus: A Novel Glycine Receptor Antibody

Hutchinson, Michael; Waters, Patrick; McHugh, John; Gorman, Gráinne; O’Riordan, Stephen; Connolly, Seán; Hager, Henrik; Yu, P.; Becker, Cord‐Michael; Vincent, Angela

doi:10.1212/01.wnl.0000327606.50322.f0

Cited by 345 publications

(231 citation statements)

References 6 publications

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“…Glycine-receptor antibody disease, or 'stiff-person syndrome plus', is a lifethreatening disorder that involves progressive encephalomyelitis, rigidity, and myoclonus [70]. Immunotherapy is an effective treatment [71].…”

Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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Neuroinflammation is the response of the central nervous system (CNS) to disturbed homeostasis and typifies all neurological diseases. The main reactive components of the CNS include microglial cells and infiltrating myeloid cells, astrocytes, oligodendrocytes, and the blood-brain b a r r i e r , c y t o k i n e s , a n d c y t o k i n e s i g n a l i n g . Neuroinflammatory responses may be helpful or harmful, as mechanisms associated with neuroinflammation are involved in normal brain development, as well as in neuropathological processes. This review examines the roles of various cell types that contribute to the immune dysregulation associated with neuroinflammation. Microglia enter the CNS very early in embryonic development and, as such, play an essential role in both the healthy and diseased brain. B-cell diversity contributes to CNS disease through both antibody-dependent and antibody-independent mechanisms. The influences of these B-cell mechanisms on other cell types, including myeloid cells and T cells, are reviewed in relationship to antibody-mediated CNS disorders, paraneoplastic neurological diseases, and multiple sclerosis. New insights into neuroinflammation offer exciting opportunities to investigate potential therapeutic targets for debilitating CNS diseases.

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Section: Antibodies To Identified Cns Proteinsmentioning

confidence: 99%

Neuroinflammation: Ways in Which the Immune System Affects the Brain

et al. 2015

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“…Antibodies to NMDAR (n = 103), voltage-gated potassium channel complex (VGKC-complex) (n = 102), leucine-rich glioma-inactivated 1 (LGI1) (n = 99), contactin-associated protein-like 2 (CASPR2) (n = 99), glycine receptor (n = 102), and glutamic acid decarboxylase (n = 102) were tested as previously described. [11][12][13][14] Only 5 patients had combined testing of CSF and serum for autoantibodies (NMDAR only). VGKC-complex antibody positivity was based on titers .150 pM, as suggested in children.…”

Section: Immune-mediated/autoantibodyassociated Encephalitismentioning

confidence: 99%

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

et al. 2015

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BACKGROUND AND OBJECTIVES: Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immunemediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome.METHODS: By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis).RESULTS: An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. CONCLUSIONS:We have defined clinical and radiologic phenotypes of infectious and immunemediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/ autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. WHAT'S KNOWN ON THIS SUBJECT:Encephalitis is a serious and disabling condition. There are infectious and immune-mediated causes of encephalitis, but many cases remain undiagnosed. WHAT THIS STUDY ADDS:This large single-center study on childhood encephalitis provides insight into the relative frequency and clinicoradiologic phenotypes of infectious, autoantibody-associated, and unknown encephalitis. Risk factors for an abnormal outcome are also defined. 4 and a prospective study of adults (n = 134) and children (n = 69) with encephalitis found that infectious encephalitis and immunemediated forms were identified in 42% and 21% of the cohort, respectively. 5 However, most of the previous larger studies of encephalitis in children were undertaken before the advent of neuronal autoantibody testing. [6][7][8] We studied clinical and radiologic features, serum autoantibodies in acute archived samples, and longterm outcomes in a large ret...

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“…Progressive encephalomyelitis with rigidity and myoclonus (PERM) has long been associated with GAD-antibodies, however as GAD is an intracellular enzyme, these antibodies are unlikely to be causative. Therefore, it is more disease-relevant that PERM has recently been associated with antibodies that target the extracellular domain of the glycine receptor 29 . A few patients with LE, without VGKC-complex antibodies, may have antibodies directed against the glycine, GABA B or AMPA receptors.…”

Section: Other Antigen Targetsmentioning

confidence: 99%

The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

Irani

Vincent

2012

Arq. Neuro-Psiquiatr.

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The autoimmune encephalopathies are a group of conditions that are associated with autoantibodies against surface neuronal proteins, which are likely to mediate the disease. They are established as a frequent cause of encephalitis. Characteristic clinical features in individual patients often allow the specificity of the underlying antibody to be confidently predicted. Antibodies against the VGKC-complex, mainly LGI1(leucine-rich glioma-inactivated 1), CASPR2 (contactin-associated protein 2), and contactin-2, and NMDA (N-methyl, D-aspartate) -receptor are the most frequently established serological associations. In the minority of cases, an underlying tumour can be responsible. Early administration of immunotherapies, and tumour removal, where it is relevant, offer the greatest chance of improvement. Prolonged courses of immunotherapies may be required, and clinical improvements often correlate well with the antibody levels. In the present article, we have summarised recent developments in the clinical and laboratory findings within this rapidly expanding field.

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Progressive Encephalomyelitis, Rigidity, and Myoclonus: A Novel Glycine Receptor Antibody

Cited by 345 publications

References 6 publications

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Neuroinflammation: Ways in Which the Immune System Affects the Brain

Infectious and Autoantibody-Associated Encephalitis: Clinical Features and Long-term Outcome

The expanding spectrum of clinically-distinctive, immunotherapy-responsive autoimmune encephalopathies

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