N-Methyl-D-Aspartate(NMDA) Receptor and Voltage-Gated Potassium Channel (VGKC) Antibody-Associated Encephalitides Presenting as First Episode Acute Psychosis

Tang, Charmaine; Tan, Kevin; Lim, Geraldine S.; Tan, Louis C.S.; Tay, Kay Yaw; Kandiah, Nagaendran; Abdin, Edimansyah; Verma, Swapna

doi:10.3389/fpsyt.2019.00913

Cited by 9 publications

(11 citation statements)

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“…83% of these patients recovered following immunotherapy or tumor removal, as had been diagnosed in 43% (Kayser et al 2013 ). Schizophreniform psychosis is a frequent phenomenon and has been supported by a recent study of a 60-patient cohort of patients suffering first-episode psychosis and additional neurological features such as seizures or autonomic symptoms [27% of these patients had been diagnosed with NMDAR encephalitis] (Tang et al 2019 ). The complex psychiatric presentation of NMDAR encephalitis was enriched in subsequent years to incorporate bipolar mood dysfunction and mania (Choe et al 2013 ; Fousse et al 2013 ), anxiety (Maat et al 2013 ) and behavioral abnormalities including agitation (Maat et al 2013 ).…”

Section: Resultsmentioning

confidence: 95%

Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge

Hansen

Timäus

2020

J Neural Transm

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Our review aims to delineate the psychiatric spectrum of autoantibody-associated autoimmune encephalitis over time through its discoveries of antibodies. We searched in PubMed for appropriate articles depicting the first appearance and spectrum of psychiatric symptomatology in autoantibody-positive encephalitis for this narrative review. Memory impairment was first associated with autoantibodies against intracellular antigens such as anti-HuD antibodies in 1993. 8 years later, autoantibodies against cell membrane surface antigens such as voltage-gated potassium channels were described in conjunction with memory dysfunction. The spectrum of psychiatric syndromes was amplified between 1990 and 2020 to include disorientation, behavior, cognitive dysfunction, obsessive compulsive behavior and suicidality in encephalitis patients occurring together mainly with antibodies against surface antigens, less so against intracellular antigens. In general, we found no specific psychiatric symptoms underlying specific autoantibody-associated encephalitis. As fundamental data on this issue have not been systemically assessed to date, we cannot know whether our specific findings would remain from systematic studies, i.e., on the association between cerebrospinal fluid N-methyl-D-aspartate receptor antibodies in catatonia. The psychiatric symptomatology overlaps between psychiatric domains and occurs frequently in antibody-positive encephalitis. No specific psychiatric symptoms imply an underlying, specifically autoantibody-associated encephalitis. The psychiatric phenotypology associated with antibody-positive encephalitis has evolved tremendously recently, and this new evidence reveals its relevance for future diagnostic and treatment aspects of autoimmune encephalitis patients.

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Section: Resultsmentioning

confidence: 95%

Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge

Hansen

Timäus

2020

J Neural Transm

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“…Type 3: Autoimmune antibodies to Glutamate receptor NMDA type, subunit NR2, called NMDA-NR2 antibodies (9,10,14,31,76,(89)(90)(91)(92)(93)(150)(151)(152)(153)(154)(155)(156)(157)(158)(159)(160)(161)(162)(163)(164)(165); Type 4: Autoimmune antibodies to GABA receptors, called GABA-R antibodies (57, 58, 60-62, 64-67, 169-170, 33, 43); Type 5: Autoimmune antibodies to Glutamic-aciddecarboxylase (GAD)65, called GAD-65 antibodies (13, 18, 26, 27, 29, 35, 36, 39, 44-46, 64, 66, 76, 166, 168); Type 6: Autoimmune antibodies to Voltage-gated potassium channels (VGKC), usually called VGKC antibodies (18,26,27,29,30,34,35,36,39,41,42,56); Type 7: Autoimmune antibodies to Leucine-rich gliomainactivated 1 (LGI1), called LGI1 antibodies (18,34,35,38,39,42,…”

Section: Cell Junction Secreted Synapsementioning

confidence: 99%

“…Type 6 : Autoimmune antibodies to Voltage-gated potassium channels (VGKC), usually called VGKC antibodies ( 18 , 26 , 27 , 29 , 30 , 34 , 35 , 36 , 39 , 41 , 42 , 56 );…”

Section: Twelve Types Of Autoimmune Antibodies Have Been Detected So Far In the Serum And/or Csf Of Subpopulations Of Epilepsy Patients Amentioning

confidence: 99%

“…Among epilepsy patients, those with certain types of autoimmune antibodies have been shown to have more neurobehavioral and cognitive comorbidities ( 15 , 35 , 39 , 45 , 50 , 53 , 56 , 63 , 90 , 91 , 92 , 93 , 150 , 151 ). This was revealed in regard to patients with any of three types of glutamate receptor antibodies: AMPA-GluR3 B peptide antibodies ( 15 ), NMDA-NR1 antibodies ( 35 , 50 , 53 , 56 , 63 , 88 ), or NMDA-NR2 antibodies ( 89 , 90 , 91 , 92 , 93 , 150 , 151 ), and for antibodies directed against TPO, GAD-65, VGKC and/or LGI1 ( 39 , 45 ).…”

Section: Specific Autoimmune Antibodies Correlate With Cognitive Behavioral and Psychiatric Impairments In Epilepsy Patients Glutamate Rementioning

confidence: 99%

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Autoimmune Epilepsy - Novel Multidisciplinary Analysis, Discoveries and Insights

Levite

Goldberg

2022

Front. Immunol.

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Epilepsy affects ~50 million people. In ~30% of patients the etiology is unknown, and ~30% are unresponsive to anti-epileptic drugs. Intractable epilepsy often leads to multiple seizures daily or weekly, lasting for years, and accompanied by cognitive, behavioral, and psychiatric problems. This multidisciplinary scientific (not clinical) ‘Perspective’ article discusses Autoimmune Epilepsy from immunological, neurological and basic-science angles. The article includes summaries and novel discoveries, ideas, insights and recommendations. We summarize the characteristic features of the respective antigens, and the pathological activity in vitro and in animal models of autoimmune antibodies to: Glutamate/AMPA-GluR3, Glutamate/NMDA-NR1, Glutamate/NMDA-NR2, GAD-65, GABA-R, GLY-R, VGKC, LGI1, CASPR2, and β2 GP1, found in subpopulations of epilepsy patients. Glutamate receptor antibodies: AMPA-GluR3B peptide antibodies, seem so far as the most exclusive and pathogenic autoimmune antibodies in Autoimmune Epilepsy. They kill neural cells by three mechanisms: excitotoxicity, Reactive-Oxygen-Species, and complement-fixation, and induce and/or facilitate brain damage, seizures, and behavioral impairments. In this article we raise and discuss many more topics and new insights related to Autoimmune Epilepsy. 1. Few autoimmune antibodies tilt the balance between excitatory Glutamate and inhibitory GABA, thereby promoting neuropathology and epilepsy; 2. Many autoantigens are synaptic, and have extracellular domains. These features increase the likelihood of autoimmunity against them, and the ease with which autoimmune antibodies can reach and harm these self-proteins. 3. Several autoantigens have ‘frenetic character’- undergoing dynamic changes that can increase their antigenicity; 4. The mRNAs of the autoantigens are widely expressed in multiple organs outside the brain. If translated by default to proteins, broad spectrum detrimental autoimmunity is expected; 5. The autoimmunity can precede seizures, cause them, and be detrimental whether primary or epiphenomenon; 6. Some autoimmune antibodies induce, and associate with, cognitive, behavioral and psychiatric impairments; 7. There are evidences for epitope spreading in Autoimmune Epilepsy; 8. T cells have different ‘faces’ in the brain, and in Autoimmune Epilepsy: Normal T cells are needed for the healthy brain. Normal T cells are damaged by autoimmune antibodies to Glutamate/AMPA GluR3, which they express, and maybe by additional autoantibodies to: Dopamine-R, GABA-R, Ach-R, Serotonin-R, and Adrenergic-R, present in various neurological diseases (summarized herein), since T cells express all these Neurotransmitter receptors. However, autoimmune and/or cytotoxic T cells damage the brain; 9. The HLA molecules are important for normal brain function. The HLA haplotype can confer susceptibility or protection from Autoimmune Epilepsy; 10. There are several therapeutic strategies for Autoimmune Epilepsy.

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“…Autoimmune encephalitis was formerly thought to be uncommon, but doctors are discovering more instances as their ability to detect it improves. According to a 2018 study, there are 13.7 incidences per 100,000 persons [5].…”

Section: Introductionmentioning

confidence: 99%

A Case Report on Schizophrenia with Autoimmune Encephalitis

Meshram

Wavare

Uke

et al. 2021

JPRI

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Schizophrenia is a severe mental illness with a high death rate and significant societal implications. Curative treatments are not available due to a lack of understanding of its etiopathogenesis. The mild encephalitis hypothesis of schizophrenia, established primarily by Karl Bechter and Norbert Müller, is one of the new research hypotheses. According to this theory, a significant subset of schizophrenia patients suffers from a mild but persistent form of encephalitis caused by a variety of etiology ranging from viral infections to traumas to autoimmune illnesses. This inflammatory method is believed to occur in the start or during the course of the disease. The authors present case of a 65-year-old female got admitted in female psychiatric ward AVBR Hospital Sawangi Meghe, Wardha Maharashtra with chief complaint of forgetfulness, interest in environment decline, unable to communicate, poor performance at work, muttering to self, sleep disturbance, seeing people which are not seen other, fearfulness. all necessary investigation done, in mental status examination founded impairment in memory, disorientation cognitive function impairment, RBC count 3.82, WBC count 5300, Hb% 12, calcium 8.1, urea 26, creatinine 0.6, sodium 142, potassium 4.0. Alkaline phosphate 89. HIV, HBSAG non-reactive, A large number of white blood cells in the CSF An MRI that reveals evidence of brain inflammation. There was a slight increase in antinuclear antibody (1: 40 titer). Blood and CSF were positive for oligoclonal bands. The patient was received symptomatic treatment antianxiety, antipsychotic drug alleviates hallucinations and delusion. Disturbances of consciousness and orientation, catatonia, speech dysfunction, focal neurological signs, epileptic seizures/EEG abnormalities or autonomic dysfunction are warning signs in psychiatric patients which should always induce cerebrospinal fluid analysis with determination of antineuronal autoantibodies. Currently established immunotherapy strategies are summarised, taking into account international expert advice. Guided by clinical warning signs, our qualitative review enables rapid and reliable diagnosis of definite autoimmune encephalitis. This is of high relevance for the affected individuals, since early and sufficiently intense immunotherapy often leads to a good prognosis despite severe illness.

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N-Methyl-D-Aspartate(NMDA) Receptor and Voltage-Gated Potassium Channel (VGKC) Antibody-Associated Encephalitides Presenting as First Episode Acute Psychosis

Cited by 9 publications

References 31 publications

Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge

Autoimmune encephalitis with psychiatric features in adults: historical evolution and prospective challenge

Autoimmune Epilepsy - Novel Multidisciplinary Analysis, Discoveries and Insights

A Case Report on Schizophrenia with Autoimmune Encephalitis

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