Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome (original) (raw)
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European Journal of Neurology, 2017
Background and purpose: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltagegated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. Methods: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. Results: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barr e syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. Conclusions: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
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.
Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation
Annals of Indian Academy of Neurology, 2015
cases include the N-methyl D-aspartate receptor (NMDAR); [4] the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR); the γ-aminobutyric acid receptor-B (GABA B receptor); and proteins that associate with voltage-gated potassium channel (VGKCs)-leucine-rich glioma-inactivated protein 1(LGI1) and contactin-associated protein-like 2 (Caspr2). [5,6] It is often difficult to distinguish these from mimics like obscure central nervous system (CNS) infections, mitochondrial encephalopathy, and occult focal cortical dysplasia by clinical features alone. Failure to identify the etiology as autoimmune may deprive the patient of treatment for a potentially curable entity. Our objective was to screen a large number of patients admitted to neurology intensive care service with fulminant seizures that eluded specific diagnosis in order to identify and characterize those with autoimmune encephalitis.
Journal of the neurological sciences, 2018
To address practical issues in measuring autoantibodies to neuronal cell-surface antigens (NSAs) in various autoimmune neurological disorders (ANDs). We retrospectively reviewed the clinical information of 221 patients with clinically suspected ANDs who underwent antibody testing for NSAs between January 2007 and September 2017. 31 were excluded. In 190 patients, antibody-detection rate (ADR) and antibody-phenotype association were assessed. Fifty-four patients had NSA-antibodies: NMDA receptor (NMDAR) (n = 39), AMPA receptor (n = 3), leucine-rich glioma inactivated 1 (LGI1) (n = 3), glycine receptor (GlyR) (n = 3), GABA(A) receptor (n = 2), GABA(B) receptor (n = 1), metabotrophic glutamate receptor 5 (n = 1), or unknown (n = 6); 3 had multiple NSA-antibodies. ADR in patients with diagnostic criteria for "possible autoimmune encephalitis (AE)", "probable anti-NMDAR encephalitis", "definite autoimmune limbic encephalitis (ALE)", and "stiff-person sp...
Defining and treating leucine-rich glioma inactivated 1 antibody associated autoimmunity
Brain, 2013
The identification of subtypes of autoimmune encephalitis, associated with autoantibodies to cell surface components of CNS ion channels and related proteins, has had great impact on the practice of clinical neurology in the last decade. The new classifications based on mechanism-related autoantibodies herald a new era which bridges neurology, psychiatry, immunology and synaptic biology. Leucine-rich glioma-inactivated (LGI) proteins 1-4 have roles in synaptic transmission and myelination (Kegel et al., 2013), and LGI1 is one of the novel autoantigens in autoimmune encephalitis. The LGI1 gene on chromosome 10 was identified in high grade gliomas in 1998 and found to be mutated in autosomal dominant partial epilepsy with auditory features (ADPEAF) in 2002. LGI1 protein is notable for being secreted, and contains a leucine-rich (LRR) domain and an epilepsy-associated or epitempin (EPTP) domain. LGI1 may regulate synaptic strength at excitatory synapses through interaction with postsynaptic ADAM22, PSD95 and presynaptic ADAM23; and LGI +/À and LGI À/À mice are proving to be useful animal models of focal epilepsy (Chabrol et al., 2010). One type of autoimmune encephalitis, notable for variable combinations of seizures, amnesia, psychosis, hyponatraemia, low prevalence of remote tumour and high response rate to immunotherapy was identified in 2001 by Angela Vincent and colleagues. The cases had serum autoantibodies directed to voltage gated potassium channel complexes (VGKC) measured by radioimmunoprecipitation assay of whole rabbit-brain homogenates using 125 I-labelled dendrotoxin (Vincent et al., 2004). These are the
Anti-CNS antibodies in neurological and psychiatric disorders
Journal of Neurology, Neurosurgery & Psychiatry, 1988
TO investigate the possibility that anti-CNS antibodies may play a pathogenic role in a number of neurological and psychiatric disorders, a population study was undertaken. Serum Samples were obtained from a total of 257 adults and were screened against sodium dodecyl sulphate polyacrylamide gel electrophoretic blots of various normal, necropsy-derived adult human brain regions. The incidence of IgG immunoreactive banding in the total sample was 30%. Within the diagnostic groups the incidence of banding was: controls 32%, schizophrenia 28%, mental retardation 279'6, cerebellar ataxia 33%, Parkinson's disease 22%, myasthenia gravis 45% and epilepsy 3 1 %. The differences are not statistically significant. There was no significant difference in the numbers and locations of bands between the various diagnostic groups and the controls. The overall incidence of immunoreactivity corresponding to the high molecular weight subunit of neurofilaments was only 6%, thus not confirming a previously reported incidence of 95%. The similarity between the diagnostic and the control sera suggests that caution should be exerted in interpreting the pathogenic significance of anti-CNS immunoreactive banding on Western blots.
Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed...