Angela Vincent

Imperial College Healthcare NHS Trust, Londinium, England, United Kingdom

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Publications (536)

  • Sarosh R. Irani · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Voltage-gated potassium channel (VGKC)–complex antibodies are defined by the radioimmunoprecipitation of Kv1 potassium channel subunits from brain tissue extracts and were initially discovered in patients with peripheral nerve hyperexcitability (PNH). Subsequently, they were found in patients with PNH plus psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) with prominent amnesia and frequent seizures. Most recently, they have been described in patients with pure epilepsies, especially in patients with the novel and distinctive semiology termed faciobrachial dystonic seizures (FBDS). In each of these conditions, there is a close correlation between clinical measures and antibody levels.
    Chapter · Dec 2016
  • Ester Coutinho · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: The immune system's role in the pathophysiology of several neuropsychiatric disorders has been the subject of research for many decades. Despite suggestive evidence from genetic, epidemiologic, and immunologic studies, those findings did not translate into clinical practice. Recent recognition of antibody-mediated central nervous system (CNS) disorders has fueled the search for a subgroup of patients with an antibody-mediated psychiatric illness. This chapter focuses on the current understanding of autoimmune CNS disorders and how they may be relevant to psychiatric disorders, particularly schizophrenia and autism. We review the results provided by antibody screening in psychiatric patient groups and discuss future directions to establish whether those findings will be meaningful in clinical practice.
    Chapter · Dec 2016
  • Sean J. Pittock · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Considering the diversity and numbers of targets expressed on the estimated 500 billion glia and slightly less numerous but more diverse neurons, if any channel, receptor or protein on such a cell can be the target of the immune system, we need only imagine the possibilities. As those before us looked to the heavens and ultimately walked on the moon, we need to recognize the potential implications of autoimmune neurology – a new subspecialty in neurology that has truly launched! Its importance cannot be overstated as many of the disorders now recognized as autoimmune are treatable and reversible, representing a shift from the traditional view held by many in the lay and medical community that neurologists diagnose but don’t treat! In this introductory chapter we provide a brief over-view of how the field developed, tabulate the authors and contents of the individual topics covered in each chapter, and describe some of the on-going challenges of the field.
    Chapter · Dec 2016
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    Thashi Chang · Bethan Lang · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Background Stiff person syndrome is a highly disabling, progressive autoimmune disorder of the central nervous system characterized by muscle rigidity and spasms. Stiff person syndrome is rare, but is believed to be under diagnosed with only 14 cases been reported among a 1.7 billion population in South Asia. We report the first authenticated case from Sri Lanka. Case presentationA 55-year-old Sri Lankan female presented with difficulty in walking and recurrent falls due to progressive muscular rigidity in her lower limbs and trunk with superimposed muscle spasms that occurred in response to unexpected noise, startle or emotional upset. She had anxiety and specific phobias to open spaces, walking unaided and being among crowds of people. She had insulin-dependent diabetes mellitus and was on thyroxine replacement. On examination, she had hyperlordosis combined with board-like rigidity of her anterior abdomen and rigidity of her lower limbs bilaterally. Upper limbs were normal. Magnetic resonance imaging of her neuraxis was normal. Electromyography showed continuous motor unit activity at rest. Glutamic acid decarboxylase antibodies were detected in her serum at a titre of 15,500 IU/ml (normal <5). She showed a remarkable and sustained improvement to treatment with intravenous immunoglobulins, immunosuppressive and muscle relaxant medications, regaining independent ambulation. Conclusions Diagnosis of stiff person syndrome remains clinical, supported by electromyography and serology for glutamic acid decarboxylase antibodies, facilitated by a high index of clinical suspicion. An autoimmune basis lends stiff person syndrome amenable to treatment highlighting the importance of diagnosis. This case adds to map the worldwide distribution of stiff person syndrome.
    Full-text available · Article · Dec 2016 · BMC Research Notes
  • [Show abstract] [Hide abstract] ABSTRACT: Importance Chronic, intractable neuropathic pain is a common and debilitating consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no satisfactory treatment; few studies have yet to explore its aetiology. Objective To establish if myelitis-associated chronic pain in NMOSD is related to the craniocaudal location of spinal cord lesions. Method (1) Retrospective cohort of 76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpool's national NMOSD clinics, assessing current pain and craniocaudal location of cord lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab-positive Oxford patients, a subset of the retrospective cohort, assessing current craniocaudal lesion location and current pain. Results Patients with isolated thoracic cord myelitis at the time of pain onset were significantly more disabled and suffered more pain. Cervical and thoracic lesions that persisted from pain onset to ‘out of relapse’ follow-up (current MRI) had highly significant (p<0.01) opposing effects on pain scores (std. β=−0.46 and 0.48, respectively). Lesion length, total lesion burden and number of transverse myelitis relapses did not correlate with pain. Conclusions Persistent, caudally located (ie, thoracic) cord lesions in AQP4-Ab-positive patients associate with high postmyelitis chronic pain scores, irrespective of number of myelitis relapses, lesion length and lesion burden. Although disability correlated with pain in isolation, it became an insignificant predictor of pain when analysed alongside craniocaudal location of lesions.
    Article · Nov 2016 · Journal of Neurology Neurosurgery & Psychiatry
  • Maria Pia Giannoccaro · Patrick Waters · Fabio Pizza · [...] · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Study objectives: Recently, antibodies to the hypocretin receptor 2 (HCRTR2-Abs) were reported in a high proportion of narcolepsy patients who developed the disease following Pandemrix® vaccination. We tested a group of narcolepsy patients for the HCRTR2-Abs using a newly established cell-based assay. Methods: Sera from 50 narcolepsy type 1 (NT1) and 11 with type 2 (NT2), 22 patients with other sleep disorders, 15 healthy controls and 93 disease controls were studied. CSFs from 3 narcoleptic patients were also subsequently included. Human embryonic kidney cells were transiently transfected with human HCRTR2, incubated with patients' sera for 1 hour at 1:20 dilution and then fixed. Binding of antibodies was detected by fluorescently-labelled secondary antibodies to human IgG and the different IgG subclasses. A non-linear visual scoring system was used from 0 to 4; samples scoring ≥ 1 were considered positive. Results: Only 3/61 patients (5%) showed a score ≥ 1, one with IgG1- and two with IgG3-antibodies, but titers were low (1:40 - 1:100). CSFs from these patients were negative. The three positive patients included one NT1 case with associated psychotic features, one NT2 patient and a NT1 patient with normal hypocretin CSF levels. Conclusions: Low levels of IgG1 or IgG3 antibodies against HCRTR2 were found in 3/61 patients with narcolepsy, although only one presented with full-blown NT1. HCRTR2-Abs are not common in narcolepsy unrelated to vaccination.
    Article · Nov 2016 · Sleep
  • [Show abstract] [Hide abstract] ABSTRACT: Importance Neuromyelitis optica spectrum disorders (NMOSD) can present with very similar clinical features to multiple sclerosis (MS), but the international diagnostic imaging criteria for MS are not necessarily helpful in distinguishing these two diseases. Objective This multicentre study tested previously reported criteria of ‘(1) at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or (2) the presence of a subcortical U-fibre lesion or (3) a Dawson's finger-type lesion’ in an independent cohort of relapsing-remitting multiple sclerosis (RRMS) and AQP4-ab NMOSD patients and also assessed their value in myelin oligodendrocyte glycoprotein (MOG)-ab positive and ab-negative NMOSD. Design Brain MRI scans were anonymised and scored on the criteria by 2 of 3 independent raters. In case of disagreement, the final opinion was made by the third rater. Participants 112 patients with NMOSD (31 AQP4-ab-positive, 21 MOG-ab-positive, 16 ab-negative) or MS (44) were selected from 3 centres (Oxford, Strasbourg and Liverpool) for the presence of brain lesions. Results MRI brain lesion distribution criteria were able to distinguish RRMS with a sensitivity of 90.9% and with a specificity of 87.1% against AQP4-ab NMOSD, 95.2% against MOG-ab NMOSD and 87.5% in the heterogenous ab-negative NMOSD cohort. Over the whole NMOSD group, the specificity was 89.7%. Conclusions This study suggests that the brain MRI criteria for differentiating RRMS from NMOSD are sensitive and specific for all phenotypes.
    Article · Oct 2016 · Journal of Neurology Neurosurgery & Psychiatry
  • Massimiliano Godani · Marco Zoccarato · Alessandro Beronio · [...] · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Background: The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. Objective: The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). Methods: We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. Results: The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Conclusion: Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression.
    Article · Oct 2016 · Neurodegenerative Diseases
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    [Show abstract] [Hide abstract] ABSTRACT: Background Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. Methods We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. Results A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). Conclusions Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX number, NCT00294658 .).
    Full-text available · Article · Aug 2016 · New England Journal of Medicine
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    William D. Phillips · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.
    Full-text available · Article · Jun 2016 · F1000 Research
  • [Show abstract] [Hide abstract] ABSTRACT: Expressive dysphasia and mutism are common clinical features in children and adults with N-methyl-d-aspartate receptor antibodies (NMDAR-Ab) encephalitis, and are likely to result from NMDAR hypofunction. A prodromal loss of social and communication skills can typify that of an autistic regression, particularly when presenting under the age of 3 years. Here we describe two toddlers who presented with developmental regression, particularly of their social communication skills, mimicking an autistic regression, who were found to have NMDAR-Ab in the serum and cerebrospinal fluid. Although both patients had some other neurological features, they were subtle, which resulted in delayed diagnosis of NMDAR-Ab encephalitis. Importantly, immunotherapy was beneficial in both patients, with significant improvement of their language skills and behaviour.
    Article · Jun 2016 · Developmental Medicine & Child Neurology
  • Sarosh R. Irani · Thomas D. Miller · Angela Vincent
    Chapter · Jun 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Table S1. Clinical features of latent antibody‐positive epilepsy patients.
    File available · Data · May 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Figure S1. The fidelity of the central tolerance checkpoint is compromised in patients with MG: Central tolerance checkpoint polyreactivity ELISAs. The BCR from single new emigrant/transitional B cells (CD19 + CD21loCD10 + IgMhiCD27–) derived from three AChR MG patients (MGAChR‐1, MG‐AChR‐2, MG‐AChR‐3) and two MuSK MG patients (MG‐MuSK‐1, MG‐MuSK‐2) were cloned, expressed as recombinant antibodies and then tested for reactivity against dsDNA, insulin and LPS by ELISA. Dotted lines show the positive control, a monoclonal antibody (ED38) cloned from a VpreB+L+ peripheral B cell that is highly poly‐ and self‐reactive. Solid lines show the binding curve of each cloned recombinant antibody. Horizontal lines at 0.5 OD405 nm marks the cut‐off for positive reactivity. Negative control group includes antibodies from two healthy individuals (HD‐1, HD‐2). For each individual subject the proportion of polyreactive and non‐polyreactive new emigrant B cells is summarized in the pie charts with the total number of tested clones in the center. Black shading indicates the frequency (%) of polyreactive antibodies and white shading indicates the frequency (%) of non‐polyreactive antibodies. Figure S2. The fidelity of the peripheral tolerance checkpoint is compromised in patients with MG: Peripheral tolerance checkpoint polyreactivity ELISAs. The BCR from single mature naive B cells (CD19 + CD21 + CD10–IgM+CD27–) derived from three AChR MG patients (MG‐AChR‐1, MGAChR‐ 2, MG‐AChR‐3) and MuSK MG patients (MG‐MuSK‐1, MG‐MuSK‐2) were cloned, expressed as recombinant antibodies and then tested for reactivity against dsDNA, insulin and LPS by ELISA. Dotted lines show the positive control, a monoclonal antibody (ED38) cloned from a VpreB+L+ peripheral B cell that is highly poly‐ and self‐reactive. Solid lines show the binding curve of each cloned recombinant antibody. Horizontal lines at 0.5 marks the cut off OD405 nm for positive reactivity. The control group includes antibodies from two healthy individuals (HD‐1, HD‐2). For each individual subject the frequency (%) of polyreactive and non‐polyreactive mature naive B cells is summarized in the pie charts with the total number of tested clones in the center. Black shading indicates the frequency (%) of polyreactive antibodies and white shading indicates the frequency (%) of non‐polyreactive antibodies. Figure S3. Mature naive B cell‐derived BCRs reactivity toward AChR and MuSK. The BCR from single mature naive B cells (CD19 + CD21 + CD10–IgM+CD27–) derived from three AChR MG patients (MG‐AChR‐1, MG‐AChR‐2, MG‐AChR‐3), two MuSK MG patients (MGMuSK‐1, MG‐MuSK‐2) and two healthy individuals (HD‐1, HD‐2) were cloned, expressed as recombinant antibodies (rIgG) and then tested for reactivity against AChR or MuSK. A radioimmunoassay (RIA) was first used to evaluate the specificity of the rIgG to AChR (A) or MuSK (B). Recombinant antibody (2.5 μg) was diluted to 50 μL in Hartmann's solution and mixed with 1 μL normal human serum and 50 μl of radioactive antigen (either AChR or MuSK from RSR Ltd). These mixtures were incubated overnight at 4°C. Polyreactive goat anti‐human Ig (25 μL) was incubated with the mix for 1 h to allow precipitation. The pellet was centrifuged and washed twice and counted on an automatic gamma counter. Cell‐based assays (CBA) were used further evaluate the same recombinant antibodies using transfected human embryonic kidney (HEK) 293T
    File available · Data · Apr 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Table S1. Single cell PCR efficiency. Table S2. Sequence and reactivity tables for the MG and HD study subjects.
    File available · Data · Apr 2016
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    [Show abstract] [Hide abstract] ABSTRACT: Objective: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). Methods: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). Results: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. Conclusions: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.
    Full-text available · Article · Apr 2016 · Journal of Neurology Neurosurgery & Psychiatry
  • [Show abstract] [Hide abstract] ABSTRACT: Introduction: We determined the frequencies of antibodies (Abs) directed against muscle specific kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4) in the sera of a South African cohort of acetylcholine receptor (AChR) antibody-negative generalized MG and determined outcomes to therapies. Methods: Sera negative by commercial AChR radioimmunoassay (RIA) were tested by MuSK RIA (n=30; 2006-2012) and AChR, MuSK, and LRP4 RIA ± cell-based assays (CBA) (n=53; 2012-2015). Results: AChR-Abs were detected in 4 of 53 and MuSK-Abs in 20 of 83 (24%). Thirty-six of 53 (68%) negative for MuSK, AChR, and LRP4-Abs were triple-seronegative (triple-SNMG). Individuals with MuSK-MG compared to triple-SNMG had younger onset (P=0.008), more likely African genetic ancestry (P=0.008), 4 times higher odds of reaching MGFA grade IVB/V (P=0.018), but also 9 times more likely to reach at least minimal manifestations status after ≥12 months on therapy (P=0.003). Conclusions: Individuals with African genetic ancestry and severe bulbar/respiratory AChR antibody-negative MG are likely to have MuSK-MG, but most respond favorably to maintenance immunotherapies. This article is protected by copyright. All rights reserved.
    Article · Apr 2016 · Muscle & Nerve
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    Jae-Yun Lee · Panos Stathopoulos · Sasha Gupta · [...] · Kevin C. O'Connor
    [Show abstract] [Hide abstract] ABSTRACT: Objective: Myasthenia gravis (MG) is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (AChR) or, in a minority of patients, to muscle specific kinase (MuSK). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two MG subtypes (AChR or MuSK). The antibodies are thought to be T-cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of MG. Methods: An established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors (BCR) in naive populations was applied to specimens collected from patients with either AChR or MuSK MG and healthy controls. Radioimmuno- and cell-based assays were used to measure BCR binding to AChR and MuSK. Results: The frequency of polyreactive and autoreactive BCRs (n = 262) was higher in both AChR and MuSK MG patients than in healthy controls. None of the MG-derived BCRs bound AChR or MuSK. Interpretation: The results indicate that both these MG subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in MG and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells.
    Full-text available · Article · Apr 2016
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: In autoimmune encephalitis the etiologic role of neuronal cell-surface antibodies is clear; patients diagnosed and treated early have better outcomes. Neuronal antibodies have also been described in patients with pediatric epilepsy without encephalitis. The aim was to assess whether antibody presence had any effect on long-term outcomes in these patients. Methods: Patients (n = 178) were recruited between 1988 and 1992 as part of the prospective Dutch Study of Epilepsy in Childhood; none received immunotherapy. Healthy age-matched bone-marrow donors served as controls (n = 112). All sera were tested for serum N-methyl-d-aspartate receptor (NMDAR), alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor, leucine rich glioma inactivated 1, contactin associated protein like 2 (CASPR2), contactin-2, glutamic acid decarboxylase, and voltage gated potassium channel (VGKC)-complex antibodies by standard techniques. No cerebrospinal fluid (CSF) samples were available. Results were correlated with clinical data collected over 15 years. Results: Seventeen patients (9.5%) were positive for VGKC complex (n = 3), NMDAR (n = 7), CASPR2 (n = 4), and contactin-2 (n = 3), compared to three (3/112; 2.6%) healthy controls (VGKC complex [n = 1], NMDAR [n = 2]; p = 0.03; Fisher's exact test). Titers were relatively low (≤1:100 for cell-surface antibodies), but 8 (47%) of the 17 positive samples bound to the surface of live hippocampal neurons consistent with a potential pathogenic antibody. Preexisting cognitive impairment was more frequent in antibody-positive patients (9/17 vs. 33/161; p = 0.01). Fourteen antibody-positive patients were treated with standard antiepileptic drugs (AEDs); three (17%) became intractable but this was not different from the 16 (10%) of 161 antibody-negative patients. In 96 patients with available follow-up samples at 6 and/or 12 months, 6 of 7 positive antibodies had disappeared and, conversely, antibodies had appeared for the first time in a further 7 patients. Significance: Neuronal antibodies were found at low levels in 9.5% of patients with new-onset pediatric epilepsy but did not necessarily persist over time, and the development of antibodies de novo in later samples suggests they could be due to a secondary response to neuronal damage or inflammation. Moreover, as the response to standard AEDs and the long-term outcome did not differ from those of antibody-negative pediatric patients, these findings suggest that routine neuronal antibody testing is unlikely to be helpful in pediatric epilepsy. However, the higher incidence of preexisting cognitive problems in the antibody-positive group, the CASPR2 and contactin-2 antibodies in 7 of 17 patients, and the binding of 8 of 17 of serum samples to live hippocampal neurons suggest that neuronal antibodies, even if secondary, could contribute to the comorbidities of pediatric epilepsy.
    Article · Mar 2016 · Epilepsia
  • Yael Hacohen · Yukihiro Nishimoto · Yuki Fukami · [...] · Angela Vincent
    [Show abstract] [Hide abstract] ABSTRACT: Aim: Central nervous system (CNS) autoantibodies have been reported in a range of neuroimmune diseases, but there has not been a systematic evaluation of autoantibodies in paediatric patients with brainstem encephalitis. Method: Serum samples from 57 children (40 male, 17 female, median age 12y, range 0.6-18y) with a diagnosis of brainstem encephalitis were tested retrospectively for antibodies to GQ1b, aquaporin-4 (AQP4), myelin oligodendrocyte glycoprotein (MOG), N-methyl-D-aspartate receptor, LGI1, CASPR2, glycine receptor (GlyR), DPPX, and the voltage gated potassium channel (VGKC)-complex. Results: Disease localized to the brainstem was seen in 19 patients: Bickerstaff's brainstem encephalitis (n=14) and clinically isolated syndrome (n=5). Polyfocal presentation was seen in 38 children, with predominantly white matter disease in 18 patients and grey matter in 20 patients. CNS surface antibodies were found in 22/57 patients (two patients with double positivity): GQIb (n=6), NMDAR (n=7), GlyR (n=5), MOG (n=5), and one AQP4. Three patients were positive for VGKC-complex antibodies. All patients were negative for antibodies to DPPX and the VGKC-complex antigens LGI1, CASPR2, and contactin-2. Although there were some partial differences in the presentations, the clinical features and outcomes did not relate clearly to the presence or absence of specific antibodies. Interpretation: As determined retrospectively, 39% of patients had cell surface antibodies. The results did not suggest any relationship with treatment or outcomes obtained but it is possible that specific antibody detection could be a helpful guide to more intensive immunotherapies in some cases.
    Article · Feb 2016 · Developmental Medicine & Child Neurology

Publication Stats

19k Citations


  • 2013
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2007
    • Khon Kaen University
      • Department of Medicine
      Khon Kaen, Changwat Khon Kaen, Thailand
  • 1996-2003
    • Oxford University Hospitals NHS Trust
      • Department of Clinical Neurology
      Oxford, England, United Kingdom
  • 2001
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom