Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis

Tüzün, Erdem; Erdağ, Ece; Durmuş, Hacer; Brenner, Tanja; Türkoğlu, Recai; Kürtüncü, Murat; Lang, Bethan; Akman‐Demir, Gülşen; Eraksoy, Mefküre; Vincent, Angela

doi:10.4103/0028-3886.76857

Cited by 49 publications

(25 citation statements)

References 8 publications

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“…On the other hand, with evolving case studies of anti-NMDAR encephalitis, more and more authors regard HE as an important differential diagnosis [16-20]. Recently, Tüzün and colleagues compared serum autoantibodies to neuronal surface antigens in serum thyroid antibody-positive and -negative limbic encephalitis, suggesting patients with anti-thyroid antibodies are inclined to develop anti-neuronal immune responses and autoimmune encephalitis such as anti-NMDAR encephalitis, which supported the notion that neuronal and thyroid autoimmunities might represent a pathogenic spectrum [21]. Interestingly, although prednisone is known to reduce thyroid antibodies titers, several courses of immunotherapy had no effect on sera anti-TPO antibodies reduction in current case.…”

Section: Discussionmentioning

confidence: 99%

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

Liu

Zhao

et al. 2011

BMC Neurol

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BackgroundAnti-N-methyl-D-aspartate receptor encephalitis is an increasingly common autoimmune disorder mediated by antibodies to certain subunit of the N-methyl-D-aspartate receptor. Recent literatures have described anti-thyroid and infectious serology in this encephalitis but without follow-up.Case presentationA 17-year-old Chinese female patient presented with psychiatric symptoms, memory deficits, behavioral problems and seizures. She then progressed through unresponsiveness, dyskinesias, autonomic instability and central hypoventilation during treatment. Her conventional blood work on admission showed high titers of IgG antibodies to thyroglobulin, thyroid peroxidase and IgM antibodies to Epstein-Barr virus viral capsid antigen. An immature ovarian teratoma was found and removal of the tumor resulted in a full recovery. The final diagnosis of anti-N-methyl-D-aspartate receptor encephalitis was made by the identification of anti-N-methyl-D-aspartate receptor antibodies in her cerebral spinal fluid. Pathology studies of the teratoma revealed N-methyl-D-aspartate receptor subunit 1 positive ectopic immature nervous tissue and Epstein-Barr virus latent infection. She was discharged with symptoms free, but titers of anti-thyroid peroxidase and anti-thyroglobulin antibodies remained elevated. One year after discharge, her serum remained positive for anti-thyroid peroxidase and anti-N-methyl-D-aspartate receptor antibodies, but negative for anti-thyroglobulin antibodies and IgM against Epstein-Barr virus viral capsid antigen.ConclusionsPersistent high titers of anti-thyroid peroxidase antibodies from admission to discharge and until one year later in this patient may suggest a propensity to autoimmunity in anti- N-methyl-D-aspartate receptor encephalitis and support the idea that neuronal and thyroid autoimmunities represent a pathogenic spectrum. Enduring anti-N-methyl-D-aspartate receptor antibodies from admission to one year follow-up but seroreversion of Epstein-Barr virus viral capsid antigen IgM may raise the important issue of elucidating the triggers and boosters of anti- N-methyl-D-aspartate receptor encephalitis.

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Section: Discussionmentioning

confidence: 99%

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

Liu

Zhao

et al. 2011

BMC Neurol

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“…6,33–35 Additionally, the increasing recognition of autoimmune encephalitis with neuronal cell-surface antibodies and concurrent thyroid peroxidase antibodies (as in four of 18 patients in this study) suggests that Hashimoto’s encephalitis should be a diagnosis of exclusion—that is, the detection of thyroid peroxidase antibodies and symptom response to steroids are not sufficient criteria to establish the diagnosis of Hashimoto’s encephalitis. 9,35,36 …”

Section: Discussionmentioning

confidence: 99%

Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies

Petit‐Pedrol

Armangué

Peng

et al. 2014

The Lancet Neurology

556

539

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Summary Background Increasing evidence suggests that seizures and status epilepticus can be immune-mediated. We aimed to describe the clinical features of a new epileptic disorder, and to establish the target antigen and the effects of patients’ antibodies on neuronal cultures. Methods In this observational study, we selected serum and CSF samples for antigen characterisation from 140 patients with encephalitis, seizures or status epilepticus, and antibodies to unknown neuropil antigens. The samples were obtained from worldwide referrals of patients with disorders suspected to be autoimmune between April 28, 2006, and April 25, 2013. We used samples from 75 healthy individuals and 416 patients with a range of neurological diseases as controls. We assessed the samples using immunoprecipitation, mass spectrometry, cell-based assay, and analysis of antibody effects in cultured rat hippocampal neurons with confocal microscopy. Findings Neuronal cell-membrane immunoprecipitation with serum of two index patients revealed GABAA receptor sequences. Cell-based assay with HEK293 expressing α1/β3 subunits of the GABAA receptor showed high titre serum antibodies (>1:160) and CSF antibodies in six patients. All six patients (age 3–63 years, median 22 years; five male patients) developed refractory status epilepticus or epilepsia partialis continua along with extensive cortical-subcortical MRI abnormalities; four patients needed pharmacologically induced coma. 12 of 416 control patients with other diseases, but none of the healthy controls, had low-titre GABAA receptor antibodies detectable in only serum samples, five of them also had GAD-65 antibodies. These 12 patients (age 2–74 years, median 26·5 years; seven male patients) developed a broader spectrum of symptoms probably indicative of coexisting autoimmune disorders: six had encephalitis with seizures (one with status epilepticus needing pharmacologically induced coma; one with epilepsia partialis continua), four had stiff-person syndrome (one with seizures and limbic involvement), and two had opsoclonus-myoclonus. Overall, 12 of 15 patients for whom treatment and outcome were assessable had full (three patients) or partial (nine patients) response to immunotherapy or symptomatic treatment, and three died. Patients’ antibodies caused a selective reduction of GABAA receptor clusters at synapses, but not along dendrites, without altering NMDA receptors and gephyrin (a protein that anchors the GABAA receptor). Interpretation High titres of serum and CSF GABAA receptor antibodies are associated with a severe form of encephalitis with seizures, refractory status epilepticus, or both. The antibodies cause a selective reduction of synaptic GABAA receptors. The disorder often occurs with GABAergic and other coexisting autoimmune disorders and is potentially treatable. Funding The National Institutes of Health, the McKnight Neuroscience of Brain Disorders, the Fondo de Investigaciones Sanitarias, Fundació la Marató de TV3, the Netherlands Organisation for Scientific Rese...

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“…84 Given the high frequency of thyroid antibodies in the normal population, it is likely that in some cases they are incidental and that NSAbs are the real pathogenic agent; indeed, thyroid antibodies were found coexisting with NMDAR or VGKC-complex-Abs in a recent study of LE. 85 Finally, there are many forms of childhood encephalitis and epilepsy which are often treated with steroids but are not yet recognised as antibody mediated, although cases with VGKC complex, GAD or NMDAR-Abs are beginning to be reported. 86 87 Below we consider how one might go about recognising these conditions and defining NSAS for future diagnosis and management.…”

Section: Other Possible Nsasmentioning

confidence: 99%

Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition

Zuliani

Graus

Giometto

et al. 2012

J Neurol Neurosurg Psychiatry

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275

258

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The concept of antibody mediated CNS disorders is relatively recent. The classical CNS paraneoplastic neurological syndromes are thought to be T cell mediated, and the onconeural antibodies merely biomarkers for the presence of the tumour. Thus it was thought that antibodies rarely, if ever, cause CNS disease. Over the past 10 years, identification of autoimmune forms of encephalitis with antibodies against neuronal surface antigens, particularly the voltage gated potassium channel complex proteins or the glutamate N-methyl-D-aspartate receptor, have shown that CNS disorders, often without associated tumours, can be antibody mediated and benefit from immunomodulatory therapies. The clinical spectrum of these diseases is not yet fully explored, there may be others yet to be discovered and some types of more common disorders (eg, epilepsy or psychosis) may prove to have an autoimmune basis. Here, the known conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of further disorders are suggested.

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Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis

Cited by 49 publications

References 8 publications

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

Anti-N-methyl-D-aspartate receptor encephalitis with serum anti-thyroid antibodies and IgM antibodies against Epstein-Barr virus viral capsid antigen: a case report and one year follow-up

Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies

Central nervous system neuronal surface antibody associated syndromes: review and guidelines for recognition

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