Angela Vincent

Oxford University Hospitals NHS Trust, Oxford, England, United Kingdom

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Publications (460)2817.97 Total impact

  • Sarah J. Crisp · Dimitri M. Kullmann · Angela Vincent

    No preview · Article · Jan 2016 · Nature reviews Neuroscience

  • No preview · Article · Jan 2016 · Neurology
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    ABSTRACT: Rasmussen's encephalitis is a rare progressive childhood disorder characterized by frequent severe seizures, hemiparesis, encephalitis and mental deterioration, and associated with severe unilateral neuroinflammation. Autoantibodies, particularly to the GluA3 subtype of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propinonic acid receptor (AMPAR) were reported in the 1990s but not always confirmed. To explore further, sera from 52 patients with Rasmussen’s encephalitis were tested by cell-based assays for antibodies to AMPAR GluA1/2/3, N-methyl-D-aspartate (NMDA NR1/2b), γ-aminobutyric acid type A and B (GABAAR α1/γ2/β2 and GABABR b1/b2) receptors, for potassium channel complex proteins, and for binding to live cortical and hippocampal neuronal cultures. Two patients’ sera (3.8%) bound to HEK cells co-transfected with the GluA2 and GluA3 subunits. One additional patient had a low level of VGKC-complex antibodies. These three, and seven additional, sera bound to hippocampal cultures. No other antibodies were detected. Thus, despite the rarity of GluA2/3 antibodies, 10 patients (19.2%) had evidence of antibodies to neuronal antigens. Whether these antibodies play a primary role in RE, or appear secondary to the neuro-inflammatory damage in this highly destructive disease, requires further study.
    Full-text · Article · Jan 2016 · European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society
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    ABSTRACT: Autonomic dysfunction has frequently been reported in autoimmune encephalitis associated with seizures and there is growing evidence that epilepsy patients may display neuronal autoantibodies (NAAb). The aim of this study was to investigate the frequency of NAAb in epilepsy patients with peri-ictal autonomic findings. Fifty-eight patients (37 women/21 men; average age of 34.2 ± 9.9 years and epilepsy duration of 19.1 ± 9.6 years) who had at least one video-EEG recorded focal or secondary generalized seizure with clear-cut documented peri-ictal autonomic findings, or consistently reported seizures with autonomic semiology, were included. NAAb were tested by RIA or cell based assays. NAAb were present in 17 of 58 (29.3 %) patients. Among seropositive patients, antibodies were directed against N-methyl-D-aspartate receptor (NMDAR) in 5 (29 %), contactin-associated protein-like 2 (CASPR2) in 5 (29 %), uncharacterized voltage gated potassium channel (VGKC)-complex antigens in 3 (18 %), glutamic acid decarboxylase (GAD) in 2 (12 %), glycine receptor (GLYR) in one (6 %) and type A gamma aminobutyric acid receptor (GABAAR) in one patient (6 %). Peri-ictal gastrointestinal manifestations, piloerection, ictal fever, urinary urge, and cough occurred more commonly in the seropositive group. The prevalences of psychotic attacks and status epilepticus were significantly increased in the seropositive group. Seropositivity prevalence in our patient group with peri-ictal autonomic findings is higher than other previously reported epilepsy cohorts. In our study, ictal fever-VGKC-complex antibody and pilomotor seizure-GABAAR antibody associations were documented for the first time. Chronic epilepsy patients with peri-ictal autonomic semiology, history of status epilepticus and psychotic disorder may benefit from autoantibody screening.
    Full-text · Article · Jan 2016 · Journal of Neurology
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    Sophie Binks · Angela Vincent · Jacqueline Palace
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    ABSTRACT: Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to acetylcholine receptors cause fatigable weakness of skeletal muscles. In the rest, a variable proportion possesses antibodies to muscle-specific tyrosine kinase while the remainder of seronegative MG is being explained through cell-based assays using a receptor-clustering technique and, to a lesser extent, proposed new antigenic targets. The incidence and prevalence of MG are increasing, particularly in the elderly. New treatments are being developed, and results from the randomised controlled trial of thymectomy in non-thymomatous MG, due for release in early 2016, will be of particular clinical value. To help navigate an evidence base of varying quality, practising clinicians may consult new MG guidelines in the fields of pregnancy, ocular and generalised MG (GMG). This review focuses on updates in epidemiology, immunology, therapeutic and clinical aspects of GMG in adults.
    Preview · Article · Dec 2015 · Journal of Neurology
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    ABSTRACT: We report a 3-year-old boy with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with a typical syndrome of movement disorder and encephalopathy and evidence of herpes simplex virus (HSV) type 1 infection on brain biopsy. HSV type 1 infection and anti-NMDAR encephalitis are temporally linked in some cases: this case suggests that prodromal HSV type-1 infection may be clinically subtle, and easily missed.
    No preview · Article · Dec 2015 · The Pediatric Infectious Disease Journal
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    Full-text · Dataset · Nov 2015
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    Full-text · Dataset · Nov 2015
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    ABSTRACT: Purpose: Favourable small cell lung carcinoma (SCLC) survival outcomes have been reported in patients with paraneoplastic neurological disorders (PNDs) associated with neuronal antibodies (Neur-Abs), but the presence of a PND might have expedited diagnosis. Our aim was to establish whether neuronal antibodies, independent of clinical neurological features, correlate with SCLC survival. Experimental design: 262 consecutive SCLC patients were examined: of these, 24 with neurological disease were excluded from this study. The remaining 238 were tested for a broad array of Neur-Abs at the time of cancer diagnosis; survival time was established from follow-up clinical data. Results: Median survival of the non-PND cohort (n = 238) was 9.5 months. 103 patients (43%) had one or more antigen-defined Neur-Abs. We found significantly longer median survival in 23 patients (10%) with HuD/anti-neuronal nuclear antibody type 1 (ANNA-1, 13.0 months P = 0.037), but not with any of the other antigen-defined antibodies, including the PND-related SOX2 (n = 56, 24%). An additional 28 patients (12%) had uncharacterised anti-neuronal nuclear antibodies (ANNA-U); their median survival time was longer still (15.0 months, P = 0.0048), contrasting with the survival time in patients with non-neuronal anti-nuclear antibodies (detected using HEp-2 cells, n = 23 (10%), 9.25 months). In multivariate analyses, both ANNA-1 and ANNA-U independently reduced the mortality hazard by a ratio of 0.532 (P = 0.01) and 0.430 (P<0.001) respectively. Conclusions: ANNAs, including the newly described ANNA-U, may be key components of the SCLC immunome and have a potential role in predicting SCLC survival; screening for them could add prognostic value that is similar in magnitude to that of limited staging at diagnosis.
    Preview · Article · Nov 2015 · PLoS ONE
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    ABSTRACT: Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome. Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and ≥1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was associated with an increased risk of miscarriage (cohort of 40 women) or preeclampsia (cohort of 57 women). Results: Miscarriage rate was higher in pregnancies after NMOSD onset (42.9% [95% confidence interval 17.7%-71.1%] vs 7.04% [2.33%-15.7%]). Pregnancies conceived after, or up to 3 years before, NMOSD onset had an increased odds ratio of miscarriage (7.28 [1.03-51.6] and 11.6 [1.05-128], respectively), independent of maternal age or history of miscarriage. Pregnancies after, or up to 1 year before, NMOSD onset ending in miscarriage were associated with increased disease activity from 9 months before conception to the end of pregnancy, compared to viable pregnancies (mean annualized relapse rate 0.707 vs 0.100). The preeclampsia rate (11.5% [6.27%-18.9%]) was significantly higher than reported in population studies. The odds of preeclampsia were greater in women with multiple other autoimmune disorders or miscarriage in the most recent previous pregnancy, but NMOSD onset was not a risk factor. Conclusions: Pregnancy after NMOSD onset is an independent risk factor for miscarriage, and pregnancies conceived at times of high disease activity may be at increased risk of miscarriage. Women who develop NMOSD and have multiple other autoimmune disorders have greater odds of preeclampsia, independent of NMOSD onset timing.
    Full-text · Article · Nov 2015 · Neurology
  • Michael S Zandi · Belinda R Lennox · Angela Vincent

    No preview · Article · Nov 2015
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    ABSTRACT: To define the risk factors for postencephalitic epilepsy (PE) and drug-resistant epilepsy (DRE) in childhood following infectious and autoimmune encephalitis, we included 147 acute encephalitis patients with a median follow-up of 7.3 years (range 2-15.8 years). PE was defined as the use of antiepileptic drugs (AEDs) for ≥24 months, and DRE was defined as the persistence of seizures despite ≥2 appropriate AEDs at final follow-up. PE and DRE were diagnosed in 31 (21%) and 15 (10%) of patients, respectively. The features during acute encephalitis predictive of DRE (presented as odds ratio [OR] with confidence intervals [CIs]) were status epilepticus (OR 10.8, CI 3.4-34.3), visual disturbance (6.4, 1.4-29.9), focal seizures (6.2, 1.9-20.6), magnetic resonance imaging (MRI) hippocampal/amygdala involvement (5.0, 1.7-15.4), intensive care admission (4.7, 1.4-15.4), use of >3 AEDs (4.5, 1.2-16.1), MRI gadolinium enhancement (4.1, 1.2-14.2), any seizure (3.9, 1.1-14.4), and electroencephalography (EEG) epileptiform discharges (3.9, 1.3-12.0). On multivariable regression analysis, only status epilepticus remained predictive of DRE in all models. DRE was common in herpes simplex virus (3/9, 33%) and unknown (8/40, 20%) encephalitis, but absent in acute disseminated encephalomyelitis (ADEM) (0/32, 0%), enterovirus (0/18), and anti-N-methyl-d-aspartate receptor-NMDAR encephalitis (0/9). We have identified risk factors for DRE and demonstrated "high-risk," and "low-risk" etiologies.
    Full-text · Article · Nov 2015 · Epilepsia
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    ABSTRACT: Background Antibodies against glycine receptors (GlyR Ab) have been strongly linked to progressive encephalomyelitis with rigidity and myoclonus (PERM). Their association with other neurological disorders is poorly understood. Methods We looked retrospectively at all patients who were tested for (GlyR Abs) in the Walton Centre between 2010–2014. Results 138 patients were tested. The pre-test diagnoses (n) were transverse myelitis (34), NMO (22, (7 AQP4 IgG+ve and 15 AQP4 IgG-ve), optic neuritis (17), MS (22), ADEM (4), other atypical demyelination (4), encephalitis (11), epilepsy (4), dementia (4), parkinsonism (3), functional disorders (3) and others (10). 53.6% (74) had a relapsing course 6/138 (4%) were positive for GlyR Ab. The diagnoses (n) were optic neuritis (2) one of which was AQP4 IgG+ve, NMO-AQP4-IgG negative (1), transverse myelitis (1), tumefactive demyelination (1) and undiagnosed spastic ataxic syndrome with normal imaging (1). 5/6 had a relapsing course and are on immunosuppressants. Conclusion Antibodies against GlyR are not common and seem to be associated with some non-PERM inflammatory CNS diseases, with a relapsing course. Larger studies are required to understand the clinical and prognostic significance of these early findings.
    No preview · Article · Nov 2015 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: There is an increasing incidence and prevalence of MG in older patients (>50 years) – defined as Late Onset Myasthenia Gravis (LOMG). This study aims to define the demographics, clinical features, response to treatment and immunological features which may distinguish LOMG from the early onset patients (who will also be recruited as controls). Who to refer? ▸ All patients should be over the age of 18 years, able to provide informed consent. ▸ The study aims to recruit patients who are willing to travel to one of the myasthenia clinics in Birmingham, Nottingham or Oxford ▸ All patients with a new diagnosis of MG (or diagnosed in the last 12 months) prior to immunosuppression. ▸ Diagnosis of MG based on typical clinical features and the presence of AChR or MuSK Abs, or evidence of neuromuscular transmission defect on single fibre EMG. What it involves for patients ▸ Management will be as per usual practice ▸ Annual serum samples at follow up with QoL and MG composite scores ▸ Follow up for 5 years (3 years by the clinical research fellow and 2 years optionally by the local participating neurologists).
    No preview · Article · Nov 2015 · Journal of Neurology Neurosurgery & Psychiatry
  • Angela Vincent

    No preview · Article · Nov 2015
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    ABSTRACT: Objective: To evaluate the clinical relevance of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in a cohort of adults with inflammatory demyelinating disease (IDD) of the CNS. Methods: Live cell-based assays for MOG-Ab (IgG1 subset) and antibody to aquaporin-4 (AQP4-Ab) were performed in a cohort of 270 adult patients with IDD and 72 controls. Patients were first grouped by positive antibody result as MOG-Ab or AQP4-Ab, and the remainder were grouped by published diagnostic criteria. Results: Seventeen patients with IDD (6.3%) had MOG-Abs and 49 patients (18.1%) had AQP4-Abs; none had both antibodies. The MOG-Ab patients predominantly manifested with isolated symptoms of optic neuritis (83%). One-third of these patients experienced relapses, which involved only the optic nerve, and all relapsed within 1 year of disease onset. At onset, MRI in the MOG-Ab group uniquely demonstrated perineural enhancement, extending to the soft tissues around the optic nerves (33%). Although about 30% of MOG-Ab patients had brain MRI lesions, they had fewer periventricular lesions than the 26 patients with relapsing-remitting multiple sclerosis (MS); none of these lesions were ovoid or perpendicular to the ventricle. Moreover, MOG-Ab patients did not meet the diagnostic criteria for definite neuromyelitis optica (NMO) and had less spinal cord involvement than the AQP4-Ab group. Four patients (23.5%) had poor visual outcomes (<0.2) or paraplegia. Conclusions: MOG-Abs may be a disease-specific biomarker in adult patients with IDD who have a disease distinct from NMO or MS. The radiologic as well as clinical manifestations of MOG-Ab patients can be useful in their differential diagnosis.
    Preview · Article · Oct 2015
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    ABSTRACT: Most patients with N-methyl D-aspartate-receptor antibody encephalitis develop seizures but the epileptogenicity of the antibodies has not been investigated in vivo. Wireless electroencephalogram transmitters were implanted into 23 C57BL/6 mice before left lateral ventricle injection of antibody-positive (test) or healthy (control) immunoglobulin G. Mice were challenged 48 h later with a subthreshold dose (40 mg/kg) of the chemo-convulsant pentylenetetrazol and events recorded over 1 h. Seizures were assessed by video observation of each animal and the electroencephalogram by an automated seizure detection programme. No spontaneous seizures were seen with the antibody injections. However, after the pro-convulsant, the test mice (n = 9) had increased numbers of observed convulsive seizures (P = 0.004), a higher total seizure score (P = 0.003), and a higher number of epileptic 'spike' events (P = 0.023) than the control mice (n = 6). At post-mortem, surprisingly, the total number of N-methyl D-aspartate receptors did not differ between test and control mice, but in test mice the levels of immunoglobulin G bound to the left hippocampus were higher (P < 0.0001) and the level of bound immunoglobulin G correlated with the seizure scores (R2 = 0.8, P = 0.04, n = 5). Our findings demonstrate the epileptogenicity of N-methyl D-aspartate receptor antibodies in vivo, and suggest that binding of immunoglobulin G either reduced synaptic localization of N-methyl D-aspartate receptors, or had a direct effect on receptor function, which could be responsible for seizure susceptibility in this acute short-term model. © 2015 The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: [email protected] /* */
    No preview · Article · Sep 2015 · Brain
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    ABSTRACT: To assess the clinical and immunologic findings in children with voltage-gated potassium channel (VGKC)-complex antibodies (Abs). Thirty-nine of 363 sera, referred from 2 pediatric centers from 2007 to 2013, had been reported positive (>100 pM) for VGKC-complex Abs. Medical records were reviewed retrospectively and the patients' condition was independently classified as inflammatory (n = 159) or noninflammatory (n = 204). Positive sera (>100 pM) were tested/retested for the VGKC-complex Ab-positive complex proteins LGI1 and CASPR2, screened for binding to live hippocampal neurons, and 12 high-titer sera (>400 pM) tested by radioimmunoassay for binding to VGKC Kv1 subunits with or without intracellular postsynaptic density proteins. VGKC-complex Abs were found in 39 children, including 20% of encephalopathies and 7.6% of other conditions (p = 0.001). Thirty children had inflammatory conditions and 9 had noninflammatory etiologies but titers >400 pM (n = 12) were found only in inflammatory diseases (p < 0.0001). Four sera, including from 2 children with coexisting NMDA receptor Abs and one with Guillain-Barré syndrome and Abs to both LGI1 and CASPR2, bound to hippocampal neurons. None of the sera bound detectably to VGKC Kv1 subunits on live HEK cells, but 4 of 12 >400 pM sera immunoprecipitated VGKC Kv1 subunits, with or without postsynaptic densities, extracted from transfected cells. Positive VGKC-complex Abs cannot be taken to indicate a specific clinical syndrome in children, but appear to be a nonspecific biomarker of inflammatory neurologic diseases, particularly of encephalopathy. Some of the Abs may bind to intracellular epitopes on the VGKC subunits, or to the intracellular interacting proteins, but in many the targets remain undefined. © 2015 American Academy of Neurology.
    No preview · Article · Aug 2015 · Neurology
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    ABSTRACT: To assess the clinical relevance of the differential binding of antibodies against the 2 main aquaporin-4 (AQP4) isoforms in neuromyelitis optica (NMO) patient sera using stably transfected human embryonic kidney cells. Flow cytometry of human embryonic kidney cells stably transfected with either M23 or M1 AQP4 was used to measure antibody endpoint titers in 52 remission samples and 26 relapse samples from 34 patients with clinically well-characterized AQP4 antibody-positive NMO/NMO spectrum disorder. The AQP4 M23 (40-61,440) and AQP4 M1 (<20-20,480) titers varied widely between patients, as did the M23:M1 antibody ratio (1-192). In 76 of 78 samples, binding to M23 was higher than binding to M1, including during relapses and remissions (p < 0.0001), and the M23:M1 ratio was relatively constant within an individual patient. Titers usually fell after immunosuppression, but the titers at which relapses occurred varied markedly; no threshold level for relapses could be identified, and relapses could occur without a rise in titers. Relapse severity did not correlate with M23 or M1 antibody titers, although there was a correlation between the earliest M23 titers and annualized relapse rates. The M23:M1 ratio and absolute M23 and M1 titers did not relate to age at disease onset, ethnicity, disease severity, phenotype, or relapses at different anatomical sites. Relative AQP4 antibody binding to M23 and M1 isoforms differs between patients but there is no consistent association between these differences and clinical characteristics of disease. Nevertheless, the M23 isoform provided a slightly more sensitive substrate for AQP4-antibody assays, particularly for follow-up studies.
    Full-text · Article · Aug 2015
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    Full-text · Article · Aug 2015

Publication Stats

17k Citations
2,817.97 Total Impact Points

Institutions

  • 1988-2016
    • Oxford University Hospitals NHS Trust
      • Department of Clinical Neurology
      Oxford, England, United Kingdom
    • Royal Free London NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2015
    • University of Nottingham
      Nottigham, England, United Kingdom
    • The Walton Centre NHS Foundation Trust
      Liverpool, England, United Kingdom
    • Seoul National University Bundang Hospital
      • Department of Neurology
      Sŏul, Seoul, South Korea
  • 1997-2015
    • University of Oxford
      • • Nuffield Department of Clinical Neurosciences
      • • Neurosciences Research Group
      • • Weatherall Institute of Molecular Medicine
      Oxford, England, United Kingdom
  • 2013
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1999-2012
    • Institute of Genetics and Molecular Medicine
      Edinburgh, Scotland, United Kingdom
  • 2010
    • University of Cambridge
      Cambridge, England, United Kingdom
  • 2007-2008
    • Cardiff University
      • Department of Medical Biochemistry and Immunology
      Cardiff, Wales, United Kingdom
    • Tongji Hospital
      Wu-han-shih, Hubei, China
    • Khon Kaen University
      • Department of Medicine
      Khon Kaen, Changwat Khon Kaen, Thailand
  • 2006
    • Institute of Molecular Medicine (India)
      New Dilli, NCT, India
  • 1994-2002
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2001
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1995
    • Maastricht University
      • MHeNS School for Mental Health and Neuroscience
      Maestricht, Limburg, Netherlands
  • 1987
    • Mayo Clinic - Rochester
      • Department of Neurology
      Рочестер, Minnesota, United States
    • The Royal Society of Medicine
      Londinium, England, United Kingdom