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  • Autoimmune epilepsies.

    24 October 2018

    PURPOSE OF REVIEW: To review the recent literature describing the detection and clinical importance of serum antibodies in patients with various epilepsies and other seizure-related disorders. RECENT FINDINGS: Auto-antibodies to the NMDA, GABAB and AMPA receptors and to LGI1, CASPR2 and Contactin-2, components of the voltage-gated potassium channel complex, have been detected in the serum of patients with seizures. These antigenic targets are ion channels, receptors and accessory proteins important in both cellular homeostasis and governing the electrical activity of the brain. Antibodies to glutamic acid decarboxylase (GAD) have been found in patients with temporal lobe epilepsy. Antibodies to LGI1 have been described in around 90% of patients with the newly described epileptic syndrome of faciobrachial dystonic seizures. SUMMARY: An increasing number of antibodies have been described in the epilepsies and other seizure-related disorders. Evidence of direct pathogenicity comes from the extracellular domain targeted by all of these antibodies (other than GAD) and the often dramatic clinical and serological response to immunotherapies, when antiepileptic drugs may be ineffective. Definitive proof as to the pathological relevance of these antibodies will be achieved in the generation of an animal model that demonstrates the clinical phenotype of these antibody-mediated disorders.

  • The growing recognition of immunotherapy-responsive seizure disorders with autoantibodies to specific neuronal proteins.

    24 October 2018

    PURPOSE OF REVIEW: The concept of epilepsy and seizure disorders caused by autoantibodies to specific neuronal membrane proteins has developed significantly during the past few years. RECENT FINDINGS: Antibodies to cell-surface membrane proteins such as voltage-gated potassium channels or N-methyl-D-aspartate receptors, or to glutamic acid decarboxylase, are found in patients with different forms of limbic encephalitis, and in a few patients with epilepsy as their main or only condition. Many of these patients do not show a good response to conventional antiepileptic drugs, but respond to immunotherapies. By contrast, studies of other antibodies in idiopathic forms of epilepsy, or epilepsy associated with systemic lupus erythematosus or coeliac disease, have not in general disclosed consistent, clinically helpful results. SUMMARY: There are a growing number of specific antibodies associated with new onset epilepsy. These patients are likely to have an immune-mediated disorder that may benefit from immunotherapies. In autoimmune diseases such as systemic lupus erythematosus or coeliac disease, antibodies to specific membrane targets may also prove to be important in the future.

  • Clinical and serological study of myasthenia gravis in HuBei Province, China.

    24 October 2018

    BACKGROUND: Ocular and childhood myasthenia gravis (MG) cases seem relatively more common in Oriental than in Caucasian populations, but there have been no comprehensive serological studies on patients from mainland China. METHODS: 391 unselected patients with MG attending Tongji Hospital in WuHan (the largest hospital in the province of HuBei, China) were studied during a 15-month period; most had already received treatment for their condition. RESULTS: The male to female ratio was 0.8. 50% of the patients were children (<15 years), and age at onset showed a single peak at between 5 and 10 years of age. 64% of the children and 66% of the adults were positive for acetylcholine receptor (AChR) antibodies but the antibody titres were lower than in similar Caucasian studies, although this was partly due to the high incidence of ocular MG. Of the 43 patients with generalised MG without AChR antibodies, only 1 had muscle-specific kinase antibodies (2.5%) and 2 had voltage-gated calcium channel antibodies indicating probable Lambert-Eaton myasthenic syndrome. 75% of the children, compared with only 28% of the adults, had ocular MG. Thymoma was evident by MRI in 1.5% of children and in 20% of adults. Despite most patients having received prednisone, very few had obtained full clinical remission. CONCLUSION: This study emphasises the frequency of early childhood onset with ocular symptoms and shows that many of these patients have AChR antibodies. By contrast, patients presenting in later age seem to be very uncommon in comparison with recent studies in Caucasian populations.

  • IgG subclass distribution of autoantibodies in pediatric opsoclonus-myoclonus syndrome.

    24 October 2018

    Opsoclonus-myoclonus syndrome (OMS) in children is a rare disorder including a severe eye movement disturbance, myoclonia, ataxia and often developmental retardation. Both OMS forms, idiopathic or neuroblastoma-associated (paraneoplastic), have been suspected to be autoimmune. Recently, autoantibodies have been found in OMS sera. We here show that autoantibodies in OMS, both intracellular and surface binding, belong mainly to the IgG3 subclass, although the total serum IgG3 level is normal. These results support the autoimmune hypothesis and point to a protein autoantigen as antigenic target.

  • IgG from "seronegative" myasthenia gravis patients binds to a muscle cell line, TE671, but not to human acetylcholine receptor.

    24 October 2018

    Antibodies to acetylcholine receptor (AChR) are found in 85% of patients with myasthenia gravis (seropositive MG [SPMG]) and are thought to be pathogenic; but in 15% of MG patients, the standard immunoprecipitation test for anti-AChR is negative (seronegative MG [SNMG]). Here, we used a novel approach, fluorescence-activated cell sorting analysis, to measure binding of SPMG and SNMG IgG antibodies to rhabdomyosarcoma cell lines that express human adult (TE671-epsilon) or fetal (TE671-gamma) AChR, and to human embryonic kidney (HEK) fibroblasts that express adult human AChR (HEK-AChR). We found that whereas most SPMG antibodies bind to all three cell lines, IgG from 8 of 15 SNMG sera/plasmas bind to the surface of both TE671 cell lines but not to HEK-AChR cells. These results indicate that SNMG antibodies bind to a muscle surface antigen that is not the AChR, which strongly supports previous studies that suggest that SNMG should be considered a distinct subtype of MG.

  • Sequential fluctuating paraneoplastic ocular flutter-opsoclonus-myoclonus syndrome and Lambert-Eaton myasthenic syndrome in small-cell lung cancer.

    24 October 2018

    Paraneoplastic cerebellar degeneration may occur in association with Lambert-Eaton myasthenic syndrome (LEMS), but to our knowledge, the co-occurrence of paraneoplastic opsoclonus-myoclonus syndrome and LEMS has not been previously reported. A 67-year-old woman presented with a complex partial seizure and evolving ocular flutter, opsoclonus, myoclonus and 'cerebellar' signs, all of which improved spontaneously within 6 weeks. Approximately 8 weeks after symptom onset, the patient became encephalopathic, she had a further complex partial seizure, and she became areflexic with potentiation of deep tendon reflexes. Radiological, bronchoscopic and histological investigations revealed small-cell lung cancer, and neurophysiological investigations confirmed a diagnosis of LEMS. High-titre anti-P/Q-type voltage-gated calcium-channel antibodies were identified in the serum, which increased as the signs of opsoclonus and myoclonus resolved. The encephalopathy and clinical features of LEMS responded dramatically to chemotherapy and radiotherapy. Spontaneous improvement of paraneoplastic opsoclonus-myoclonus syndrome may occur, and this syndrome may occur in association with LEMS. Antivoltage-gated calcium-channel antibodies are not implicated in the pathogenesis of paraneoplastic opsoclonus-myoclonus syndrome.