A Case Report on Schizophrenia with Autoimmune Encephalitis

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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Autoimmune encephalitis with psychosis: Warning signs, step-by-step diagnostics and treatment

The World Journal of Biological Psychiatry ◽

10.1080/15622975.2018.1555376 ◽

2019 ◽

Vol 21 (4) ◽

pp. 241-254 ◽

Cited By ~ 11

Author(s):

Johann Steiner ◽

Harald Prüss ◽

Stephan Köhler ◽

Thomas Frodl ◽

Alkomiet Hasan ◽

...

Keyword(s):

Autoimmune Encephalitis ◽

Warning Signs

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Autoimmune Encephalitis and Autism Spectrum Disorder

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.775017 ◽

2021 ◽

Vol 12 ◽

Author(s):

Paul Whiteley ◽

Ben Marlow ◽

Ritika R. Kapoor ◽

Natasa Blagojevic-Stokic ◽

Regina Sala

Keyword(s):

Autism Spectrum Disorder ◽

Autoimmune Encephalitis ◽

Preliminary Evidence ◽

Autism Spectrum ◽

Elevated Risk ◽

Spectrum Disorder ◽

Brain Inflammation ◽

Brain Cells ◽

Herpes Encephalitis ◽

Autoimmune Psychosis

The concept of “acquired autism” refers to the hypothesis that amongst the massive heterogeneity that encompasses autism spectrum disorder (ASD) there may be several phenotypes that are neither syndromic nor innate. Strong and consistent evidence has linked exposure to various pharmacological and infective agents with an elevated risk of a diagnosis of ASD including maternal valproate use, rubella and herpes encephalitis. Autoimmune encephalitis (AE) describes a group of conditions characterised by the body's immune system mounting an attack on healthy brain cells causing brain inflammation. The resultant cognitive, psychiatric and neurological symptoms that follow AE have also included ASD or autism-like traits and states. We review the current literature on AE and ASD. Drawing also on associated literature on autoimmune psychosis (AP) and preliminary evidence of a psychosis-linked subtype of ASD, we conclude that AE may either act as a potentially causative agent for ASD, and/or produce symptoms that could easily be mistaken for or misdiagnosed as autism. Further studies are required to discern the connection between AE and autism. Where autism is accompanied by regression and atypical onset patterns, it may be prudent to investigate whether a differential diagnosis of AE would be more appropriate.

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NMDA-receptor antibodies alter cortical microcircuit dynamics

10.1101/160309 ◽

2017 ◽

Author(s):

RE Rosch ◽

S Wright ◽

G Cooray ◽

M Papadopoulou ◽

S Goyal ◽

...

Keyword(s):

Nmda Receptor ◽

Mouse Model ◽

Spectral Composition ◽

Field Potential ◽

Autoimmune Encephalitis ◽

Neuronal Population ◽

Diverse Range ◽

Excitatory Neurotransmitter ◽

Eeg Abnormalities ◽

Receptor Antibodies

AbstractNMDA-receptor antibodies (NMDAR-Ab) cause an autoimmune encephalitis with a diverse range of electroencephalographic (EEG) abnormalities. NMDAR-Ab are believed to disrupt receptor function, but how blocking this excitatory neurotransmitter can lead to paroxysmal EEG abnormalities – or even seizures – is poorly understood. Here, we show that NMDAR-Ab change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity, and predispose to paroxysmal EEG abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in paediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab- related changes render microcircuitry critically susceptible to overt EEG paroxysms, when these key parameters are changed. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.

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Brain 18F-FDG PET for the diagnosis of autoimmune encephalitis: a systematic review and a meta-analysis

10.21203/rs.3.rs-243472/v1 ◽

2021 ◽

Author(s):

Manon Bordonne ◽

Mohammad.B Chawki ◽

Matthieu Doyen ◽

Aurelie Kas ◽

Eric Guedj ◽

...

Keyword(s):

Fdg Pet ◽

Search Strategy ◽

Meta Analysis ◽

Autoimmune Encephalitis ◽

Brain Inflammation ◽

Detection Sensitivity ◽

Metabolic Imaging ◽

Search Terms ◽

Original Case ◽

Pet Scans

Abstract Objective: To consolidate current understanding of detection sensitivity of brain 18F-FDG PET scans in the diagnosis of autoimmune encephalitis and to define specific metabolic imaging patterns for the most frequently occurring autoantibodies. Methods: A systematic and exhaustive search of data available in the literature was performed by querying the PubMed/MEDLINE and Cochrane databases for the search terms: "FDG PET" and “"encephalitis" or "brain inflammation"”. Studies had to satisfy the following criteria: i. include at least one patient suspected or diagnosed with autoimmune encephalitis according to the current recommendations, ii. be an original case-report iii. specifically present 18F-FDG PET and/or morphologic imaging findings. The diagnostic 18F-FDG PET detection sensitivity in autoimmune encephalitis was determined for all cases reported in the literature and a meta-analysis, according to the PRISMA method, was performed on a subset of these, which included PET scans for at least 10 patients, and whose quality was assessed with the QUADAS-2 tool.Results: The search strategy identified 1113 articles. The detection sensitivity of 18F-FDG PET was 90%, based on 176 publications and 720 patients and 80% [75%-84%] by meta-analysis based on 21 publications and 444 patients. We also report specific brain 18F-FDG PET imaging patterns for the main encephalitis autoantibody subtypes.Conclusion and Relevance: Brain 18F-FDG PET has a high detection sensitivity and should be included in future diagnostic autoimmune encephalitis recommendations. Specific metabolic 18F-FDG PET patterns corresponding to the main autoimmune encephalitis autoantibody subtypes further enhance the value of this diagnostic.

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Autoimmune encephalitis: clinical spectrum and management

Practical Neurology ◽

10.1136/practneurol-2020-002567 ◽

2021 ◽

pp. practneurol-2020-002567

Author(s):

Christopher E Uy ◽

Sophie Binks ◽

Sarosh R Irani

Keyword(s):

Patient Outcomes ◽

Neuronal Cell ◽

Autoimmune Encephalitis ◽

Surface Antigens ◽

Brain Inflammation ◽

Clinical Experiences ◽

Cell Surface Antigens ◽

Neuropsychiatric Diseases ◽

The Central Nervous System ◽

Improve Patient

Autoimmune encephalitis defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. It comprises a heterogeneous group of disorders that are at least as common as infectious causes of encephalitis. The rapid and ongoing expansion of this field has been driven by the identification of several pathogenic autoantibodies that cause polysymptomatic neurological and neuropsychiatric diseases. These conditions often show highly distinctive cognitive, seizure and movement disorder phenotypes, making them clinically recognisable. Their early identification and treatment improve patient outcomes, and may aid rapid diagnosis of an underlying associated tumour. Here we summarise the well-known autoantibody-mediated encephalitis syndromes with neuronal cell-surface antigens. We focus on practical aspects of their diagnosis and treatment, offer our clinical experiences of managing such cases and highlight more basic neuroimmunological advances that will inform their future diagnosis and treatments.

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Longitudinal CSF Findings in Autoimmune Encephalitis—A Monocentric Cohort Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.646940 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tobias Zrzavy ◽

Romana Höftberger ◽

Isabella Wimmer ◽

Thomas Berger ◽

Paulus Rommer ◽

...

Keyword(s):

Cohort Study ◽

Autoimmune Encephalitis ◽

Oligoclonal Bands ◽

Differential Diagnostics ◽

Diagnostic Challenge ◽

Protein Levels ◽

Cell Counts ◽

Normal Ranges ◽

Number Of Patients ◽

Csf Findings

Autoimmune encephalitis (AIE) poses a diagnostic challenge due to its heterogeneous clinical presentation, which overlaps with various neurological and psychiatric diseases. During the diagnostic work-up, cerebrospinal fluid (CSF) is routinely obtained, allowing for differential diagnostics as well as for the determination of antibody subclasses and specificities. In this monocentric cohort study, we describe initial and serial CSF findings of 33 patients diagnosed with antibody-associated AIE (LGI1 (n=8), NMDA (n=7), CASPR2 (n=3), IgLON5 (n=3), AMPAR (n=1), GAD65/67 (n=4), Yo (n=3), Ma-1/2 (n=2), CV2 (n=2)). Routine CSF parameters of 12.1% of AIE patients were in normal ranges, while 60.6% showed elevated protein levels and 45.4% had intrathecal oligoclonal bands (OCBs). Repeated CSF analyses showed a trend towards normalization of initial pathological CSF findings, while relapses were more likely to be associated with increased cell counts and total protein levels. OCB status conversion in anti-NMDARE patients coincided with clinical improvement. In summary, we show that in routine CSF analysis at diagnosis, a considerable number of patients with AIE did not exhibit alteration in the CSF and therefore, diagnosis may be delayed if antibody testing is not performed. Moreover, OCB status in anti-NMDAR AIE patients could represent a potential prognostic biomarker, however further studies are necessary to validate these exploratory findings.

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Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat

Frontiers in Neurology ◽

10.3389/fneur.2021.633999 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marie Süße ◽

Maria Zank ◽

Viola von Podewils ◽

Felix von Podewils

Keyword(s):

Late Onset ◽

Neuropsychological Testing ◽

Autoimmune Encephalitis ◽

Epileptic Seizures ◽

Oligoclonal Bands ◽

Seizure Outcome ◽

Csf Analysis ◽

Cerebral Mri ◽

The University ◽

Work Up

Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE).Methods: This is a single-institution prospective cohort study (2012–2019) conducted at the Epilepsy Center at the University of Greifswald, Germany. A total of 225 patients aged ≥50 years with epileptic seizures were enrolled and underwent an MRI/CT scan, profiling of neural antibodies (AB) in serum and cerebrospinal fluid (CSF), and neuropsychological testing. On the basis of their work-up, patients were categorized into the following three cohorts: definite, suspected, or no AE. Patients with definite and suspected AE were subsequently treated with immunosuppressive therapy (IT) and/or anti-seizure drug (ASD) therapy and were followed up (FU) regarding clinical and seizure outcome.Results: Of the 225 patients, 17 (8%) fulfilled the criteria for definite or suspected AE according to their AB profile and MRI results. Compared with patients with no evidence of AE, those with AE were younger (p = 0.028), had mesial temporal neuropsychological deficits (p = 0.001), frequently had an active or known malignancy (p = 0.006) and/or a pleocytosis (p = 0.0002), and/or had oligoclonal bands in CSF (p = 0.001). All patients with follow-up became seizure-free with at least one ASD. The Modified Rankin scale (mRS) at hospital admission was low for patients with AE (71% with mRS ≤2) and further decreased to 60% with mRS ≤2 at last FU.Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. AB testing in CSF and sera, cerebral MRI, CSF analysis, and neuropsychological testing for mesial temporal deficits should be part of the diagnostic protocol for AE following late-onset seizures.

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Rapidly Progressive Memory Loss, Mood Change, Mutism, and Abnormal Movements

10.1093/med/9780197583425.003.0025 ◽

2021 ◽

pp. 83-85

Author(s):

Shailee S. Shah ◽

Marie F. Grill

Keyword(s):

Cerebrospinal Fluid ◽

Short Term Memory ◽

White Blood Cells ◽

Memory Loss ◽

Autoimmune Encephalitis ◽

Complete Recovery ◽

Aspartate Receptor ◽

Normal Glucose ◽

Disorganized Speech ◽

Patient’S History

A 24-year-old woman sought care for 2 weeks of disorientation and short-term memory difficulties, as well as diffuse tremor of all extremities. She returned with further decline in memory and new severe headaches. She had intermittent agitation and emotional outbursts of crying or laughing, insomnia, spells consisting of disorganized speech and episodes of intermittent right gaze deviation with facial twitching and lip smacking. She was nearly mute. Her appetite had decreased and she had not had a bowel movement in several days. She was noted to have significant tachycardia and was intermittently febrile. Within several days she became unresponsive to all external stimuli, with nonpurposeful eye movements and frequent dyskinesias observed, and ultimately required ventilator support. Testing of the cerebrospinal fluid showed 236 white blood cells/µL, mildly increased protein concentration of 50 mg/dL, and normal glucose values. Electroencephalography initially demonstrated generalized slowing and generalized periodic epileptiform discharges and was also notable for an extreme delta brush pattern. Bilateral ovarian masses were identified on pelvic ultrasonography, and subsequent computed tomography of the abdomen and pelvis showed bilateral teratomas. An autoimmune encephalitis autoantibody panel was positive for antibodies targeting the N-methyl-d-aspartate receptor in the serum and cerebrospinal fluid, by both cell-based and immunofluorescence assays. The patient was diagnosed with anti- N-methyl-d-aspartate receptor encephalitis. The patient initially received intravenous methylprednisolone, followed by intravenous immunoglobulin. Benzodiazepines and propranolol were used to manage agitation and dysautonomia. Antiepileptic drugs were initiated for seizures. She required mechanical ventilation and parenteral nutrition given her persistent profound encephalopathic state. She underwent left ovarian cystectomy and right salpingo-oophorectomy. This patient’s history highlights the progressive clinical features characteristic of anti- N-methyl-d-aspartate receptor encephalitis and the long but often complete or near-complete recovery.

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CSF Findings in Acute NMDAR and LGI1 Antibody–Associated Autoimmune Encephalitis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000001086 ◽

2021 ◽

Vol 8 (6) ◽

pp. e1086

Author(s):

Marc Dürr ◽

Gunnar Nissen ◽

Kurt-Wolfram Sühs ◽

Philipp Schwenkenbecher ◽

Christian Geis ◽

...

Keyword(s):

Disease Duration ◽

Autoimmune Encephalitis ◽

Oligoclonal Bands ◽

Barrier Dysfunction ◽

Acute Therapy ◽

Cross Sectional ◽

Mrz Reaction ◽

Depth Analysis ◽

Z Scores ◽

Csf Findings

Background and ObjectivesCSF in antibody-defined autoimmune encephalitis (AE) subtypes shows subtype-dependent degrees of inflammation ranging from rare and often mild to frequent and often robust. AEs with NMDA receptor antibodies (NMDAR-E) and leucine-rich glioma-inactivated protein 1 antibodies (LGI1-E) represent opposite ends of this spectrum: NMDAR-E with typically frequent/robust and LGI1-E with rare/mild CSF inflammation. For a more in-depth analysis, we characterized CSF findings in acute, therapy-naive NMDAR-E and LGI1-E in a multicentric, retrospective, cross-sectional setting.MethodsEighty-two patients with NMDAR-E and 36 patients with LGI1-E from the GErman NEtwork for Research of AuToimmune Encephalitis (GENERATE) with lumbar puncture within 90 days of onset and before immunotherapy were included. CSF parameters comprised leukocytes, oligoclonal bands (OCBs), and CSF/serum ratios for albumin, immunoglobulin G (IgG), A (IgA), and M (IgM), the latter 3 converted to Z scores according to Reiber formulas. The MRZ reaction was tested in 14 patients with NMDAR-E and 6 patients with LGI1-E, respectively.ResultsCSF was abnormal in 94% of NMDAR-E but only in 36% of LGI1-E patients. Robust quantitative intrathecal immunoglobulin synthesis (IIS, IgG > IgM >> IgA) was characteristic for NMDAR-E, but absent in LGI-E. In NMDAR-E, CSF leukocytes were higher when IIS was present or more pronounced. In addition, in NMDAR-E, CSF leukocytes were lower and IIS occurred less often and if so to a lesser degree at older age. Patients with NMDAR-E with severe functional impairment more often had positive OCBs. In CSF obtained later than 3 weeks of onset, leukocytes were lower. In parallel, the correlation of leukocytes with IIS disappeared as IIS was partially independent of disease duration. The MRZ reaction was positive in 5 (36%) patients with NMDAR-E. All these associations were completely absent in LGI1-E. Here, younger patients showed more blood-CSF barrier dysfunction. In LGI1-E, but not in NMDAR-E, the blood-CSF barrier was more dysfunctional when CSF leukocytes were higher.DiscussionNMDAR-E and LGI-E differ in their typical extent of CSF inflammation. In addition, the patterns formed by the different inflammatory CSF parameters and their relationship with disease severity, age, and disease duration are subtype-characteristic. Moreover, signs for multiple sclerosis-like chronic inflammation are present in a subgroup of patients with NMDAR-E. These CSF patterns might be markers for the different immunopathogeneses of LGI1-E and NMDAR-E.

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Targeting MOG to skin macrophages prevents EAE in macaques through TGFβ-induced peripheral tolerance

10.1101/571828 ◽

2019 ◽

Author(s):

Claire-Maëlle Fovet ◽

Lev Stimmer ◽

Vanessa Contreras ◽

Philippe Horellou ◽

Audrey Hubert ◽

...

Keyword(s):

Recombinant Antibody ◽

Specific Antigen ◽

Autoimmune Encephalitis ◽

Lymphocyte Activation ◽

Peripheral Tolerance ◽

Brain Inflammation ◽

Macaque Model ◽

Vaccination Scheme ◽

Intradermal Administration ◽

Antigen Presenting

AbstractTo study the effect of vaccination on tolerization to the myelin antigen MOG we used a macaque model of experimental autoimmune encephalitis (EAE) in which immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) elicits brain inflammation and demyelination mediated by MOG-specific autoreactive CD4+ T lymphocytes and anti-MOG IgG. For antigen targeting to tolerizing antigen presenting cells, we used a recombinant antibody directed to the Dendritic Cells (DC)-Asialoglycoprotein receptor (DC-ASGPR). The intradermal administration of an anti-DC-ASGPR-MOG fusion protein, but not a control anti-DC-ASGPR-PSA (prostate specific antigen) protein, protected monkeys committed to develop EAE. Although effective treatment did not modify anti-MOG IgG production, it prevented the CD4+ T lymphocyte activation and pro-inflammatory cytokine production. Moreover, animals treated with anti-DC-ASGPR-MOG experienced a rise of MOG-specific CD4+CD25+FOXP3+CD39+ regulatory T cells as well as a TGFβ1, TGFβ2 and IL-8 upsurge after rhMOG re-immunization. Our results indicate that the pathogenicity of autoantibodies directed to MOG is mitigated in the presence of MOG-specific regulatory lymphocytes. This vaccination scheme appears suitable to treat relapsing autoimmune diseases with identified autoantigens such as that harboring anti-MOG or anti-AQP4 autoantibodies.

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