EEG Contribution to the Diagnosis of Antibody-Negative Autoimmune Encephalitis: A Case Report

Autoimmune encephalitis (AE) is a group of inflammatory brain diseases that are characterized by prominent neuropsychiatric symptoms. Early therapeutic intervention is important for AE. Therefore, without waiting for autoantibody test results, clinicians must consider the possibility of AE based solely on clinical symptoms and conventional test results. The case described herein is of antibody-negative encephalitis with abnormalities shown only by EEG, which contributed to the diagnosis and treatment. The patient, a 20-year-old woman, showed autonomic seizures in addition to movement disorders, psychiatric symptoms, and cognitive dysfunction, which worsened subacutely. Her seizures and movement disorders were not responsive to antiepileptic medications. Results obtained from MRI and cerebrospinal fluid (CSF) were normal; EEG findings showed repeated spikes in the right temporal area, with changes over time. Based on the clinical course and EEG, along with administered immunotherapy, which resolved seizures, movement disorders, and psychiatric symptoms, we suspected AE. For diagnosis of AE and for evaluating treatment responsiveness, EEG was useful. Results indicate that EEG can assist clinicians even with AE cases for which MRI and CSF findings are normal.

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Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

Frontiers in Neurology ◽

10.3389/fneur.2021.611597 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zsófia Hayden ◽

Beáta Bóné ◽

Gergely Orsi ◽

Monika Szots ◽

Ferenc Nagy ◽

...

Keyword(s):

Clinical Characteristics ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Brain Mri ◽

Disease Onset ◽

Neuronal Cell ◽

Autoimmune Encephalitis ◽

Ovarian Teratoma ◽

Test Results ◽

Nmdar Encephalitis

Background: In our previous single-center study of autoimmune encephalitis (AE) related autoantibody test results we found positivity in 60 patients out of 1,034 with suspected AE from 2012 through 2018 as part of a Hungarian nationwide program. In our current multicenter retrospective study, we analyzed the clinical characteristics and outcome of AE patients with positive neuronal cell surface autoantibody test results.Methods: A standard online questionnaire was used to collect demographic and clinical characteristics, laboratory and imaging data, therapy and prognosis of 30 definitive AE patients in four major clinical centers of the region.Results: In our study, 19 patients were positive for anti-NMDAR (63%), 6 patients (20%) for anti-LGI1, 3 patients for anti-GABABR (10%) and 3 patients for anti-Caspr2 (10%) autoantibodies. Most common prodromal symptoms were fever or flu-like symptoms (10/30, 33%). Main clinical features included psychiatric symptoms (83%), epileptic seizures (73%) and memory loss (50%). 19 patients (63%) presented with signs of central nervous system (CNS) inflammation, which occurred more frequently in elder individuals (p = 0.024), although no significant differences were observed in sex, tumor association, time to diagnosis, prognosis and immunotherapy compared to AE patients without CNS inflammatory markers. Anti-NMDAR encephalitis patients were in more severe condition at the disease onset (p = 0.028), although no significant correlation between mRS score, age, sex and immunotherapy was found. 27% of patients (n = 8) with associated tumors had worse outcome (p = 0.045) than patients without tumor. In most cases, immunotherapy led to clinical improvement of AE patients (80%) who achieved a good outcome (mRS ≤ 2; median follow-up 33 months).Conclusion: Our study confirms previous publications describing characteristics of AE patients, however, differences were observed in anti-NMDAR encephalitis that showed no association with ovarian teratoma and occurred more frequently among young males. One-third of AE patients lacked signs of inflammation in both CSF and brain MRI, which emphasizes the importance of clinical symptoms and autoantibody testing in diagnostic workflow for early introduction of immunotherapy, which can lead to favorable outcome in AE patients.

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Th17 lymphocytes drive vascular and neuronal deficits in a mouse model of postinfectious autoimmune encephalitis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1911097117 ◽

2020 ◽

Vol 117 (12) ◽

pp. 6708-6716 ◽

Cited By ~ 6

Author(s):

Maryann P. Platt ◽

Kevin A. Bolding ◽

Charlotte R. Wayne ◽

Sarah Chaudhry ◽

Tyler Cutforth ◽

...

Keyword(s):

Microglial Activation ◽

Neural Circuit ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Abrupt Onset ◽

Synaptic Proteins ◽

Excitatory Synapses ◽

Odor Processing ◽

Th17 Lymphocytes

Antibodies against neuronal receptors and synaptic proteins are associated with a group of ill-defined central nervous system (CNS) autoimmune diseases termed autoimmune encephalitides (AE), which are characterized by abrupt onset of seizures and/or movement and psychiatric symptoms. Basal ganglia encephalitis (BGE), representing a subset of AE syndromes, is triggered in children by repeated group AStreptococcus(GAS) infections that lead to neuropsychiatric symptoms. We have previously shown that multiple GAS infections of mice induce migration of Th17 lymphocytes from the nose into the brain, causing blood–brain barrier (BBB) breakdown, extravasation of autoantibodies into the CNS, and loss of excitatory synapses within the olfactory bulb (OB). Whether these pathologies induce functional olfactory deficits, and the mechanistic role of Th17 lymphocytes, is unknown. Here, we demonstrate that, whereas loss of excitatory synapses in the OB is transient after multiple GAS infections, functional deficits in odor processing persist. Moreover, mice lacking Th17 lymphocytes have reduced BBB leakage, microglial activation, and antibody infiltration into the CNS, and have their olfactory function partially restored. Th17 lymphocytes are therefore critical for selective CNS entry of autoantibodies, microglial activation, and neural circuit impairment during postinfectious BGE.

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Autoimmune encephalitis: a review of diagnosis and treatment

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20170176 ◽

2018 ◽

Vol 76 (1) ◽

pp. 41-49 ◽

Cited By ~ 14

Author(s):

Lívia Almeida Dutra ◽

Fabiano Abrantes ◽

Fabio Fieni Toso ◽

José Luiz Pedroso ◽

Orlando Graziani Povoas Barsottini ◽

...

Keyword(s):

Movement Disorders ◽

Psychiatric Symptoms ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Diagnosis And Treatment ◽

Diagnostic Approach ◽

Neurological Manifestations ◽

Common Causes ◽

Autonomic Disturbances

ABSTRACT Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. It can be triggered by tumors, infections, or it may be cryptogenic. The neurological manifestations can be either acute or subacute and usually develop within six weeks. There are a variety of clinical manifestations including behavioral and psychiatric symptoms, autonomic disturbances, movement disorders, and seizures. We reviewed common forms of AIE and discuss their diagnostic approach and treatment.

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Apheresis in Autoimmune Encephalitis and Autoimmune Dementia

Journal of Clinical Medicine ◽

10.3390/jcm9092683 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2683 ◽

Cited By ~ 1

Author(s):

Rosa Rössling ◽

Harald Prüss

Keyword(s):

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Synaptic Proteins ◽

First Line ◽

First Line Therapy ◽

Neuronal Autoantibodies ◽

Neurodegenerative Dementia ◽

Pathogenic Antibodies ◽

Clinical Conditions

Autoimmune encephalitis (AE) is a rapidly progressive inflammatory neurological disease. Underlying autoantibodies can bind to neuronal surfaces and synaptic proteins resulting in psychiatric symptoms, focal neurological signs, autonomic dysfunction and cognitive decline. Early and effective treatment is mandatory to reduce clinical symptoms and to achieve remission. Therapeutic apheresis, involving both plasma exchange (PE) and immunoadsorption (IA), can rapidly remove pathogenic antibodies from the circulation, thus representing an important first-line treatment in AE patients. We here review the most relevant studies regarding therapeutic apheresis in AE, summarizing the outcome for patients and the expanding clinical spectrum of treatment-responsive clinical conditions. For example, patients with slowly progressing cognitive impairment suggesting a neurodegenerative dementia can have underlying autoantibodies and improve with therapeutic apheresis. Findings are encouraging and have led to the first ongoing clinical studies assessing the therapeutic effect of IA in patients with anti-neuronal autoantibodies and the clinical presentation of dementia. Therapeutic apheresis is an established and well tolerated option for first-line therapy in AE and, potentially, other antibody-mediated central nervous system diseases.

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Acute Psychosis as Major Clinical Presentation of Legionnaires’ Disease

Case Reports in Psychiatry ◽

10.1155/2016/3519396 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Ricardo Coentre ◽

Amílcar Silva-dos-Santos ◽

Miguel Cotrim Talina

Keyword(s):

Legionella Pneumophila ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Lower Lobe ◽

Epidemiological Data ◽

Clinical History ◽

Psychotic Symptoms ◽

Acute Psychosis ◽

Legionnaires Disease ◽

The Right

We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires’ disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggestedLegionella pneumophilaas possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms.

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Characterizing the features and course of psychiatric symptoms in children and adolescents with autoimmune encephalitis

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-021-01293-5 ◽

2021 ◽

Author(s):

R Rosello ◽

B Girela-Serrano ◽

S Gómez ◽

B Baig ◽

M Lim ◽

...

Keyword(s):

Side Effects ◽

Psychiatric Disorder ◽

Children And Adolescents ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Emotional Lability ◽

Liaison Psychiatry ◽

Paediatric Cohort ◽

Psychiatric Manifestations

AbstractAutoimmune encephalitis (AE) can present like a psychiatric disorder. We aimed to illustrate the psychiatric manifestations, course and management of AE in a paediatric cohort. Neuropsychiatric symptoms, investigations and treatment were retrospectively retrieved in 16 patients (mean age 11.31, SD 2.98) with an AE diagnosis at the liaison psychiatry services in two UK tertiary paediatric centres. Psychiatric presentation was characterised by an acute polysymptomatic (predominantly agitation, anger outbursts/aggressiveness, hallucinations, and emotional lability) onset. Antipsychotics produced side effects and significant worsening of symptoms in four cases, and benzodiazepines were commonly used. This psychiatric phenotype should make clinicians suspect the diagnosis of AE and carefully consider use of treatments.

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Paraneoplastic Cerebellar Degeneration Secondary to BRAF Mutant Melanoma Metastasis from an Occult Primary Cancer

Case Reports in Oncology ◽

10.1159/000507729 ◽

2020 ◽

Vol 13 (2) ◽

pp. 633-642

Author(s):

Omar Jiménez-Zarazúa ◽

Lourdes Noemí Vélez-Ramírez ◽

María Alcocer-León ◽

Diego Armando Hernández-Domínguez ◽

Juana Elizabeth Tadeo-González ◽

...

Keyword(s):

Malignant Melanoma ◽

Movement Disorders ◽

Mapk Pathway ◽

Neuropsychiatric Symptoms ◽

Cerebellar Degeneration ◽

Paraneoplastic Cerebellar Degeneration ◽

Unknown Primary ◽

Melanoma Metastasis ◽

Primary Cancer ◽

The Right

Melanoma metastasis from an unknown primary cancer has an incidence of 3.2% among melanoma patients. Furthermore, paraneoplastic neurological syndromes (PNS) are rare, occurring in 1–3% of patients with malignancies. Paraneoplastic cerebellar degeneration (PCD) is one of the classic PNS and is characterized by acute or subacute onset of ataxia and/or presence of onconeural antibodies. A 61-year-old male with ataxia, vertigo, and headache later developed dysarthria, multidirectional nystagmus, hyperactive delirium, auditory hallucinations, psychomotor agitation, and myoclonus. Toxicological, metabolic, infectious, and autoimmune etiologies were assessed and reported negative. An osteolytic lesion was observed in the right iliac crest via computed tomography (CT). A positron emission tomography-CT reported increased fluorodeoxyglucose uptake of a right iliac and right inguinal ganglion. After biopsy of the right inguinal ganglion, a BRAF mutation-positive melanoma metastasis from an occult primary cancer was diagnosed. Dermatologic, ophthalmologic, and endoscopic gastrointestinal assessment did not reveal a primary malignant melanoma. The patient’s movement disorders and neuropsychiatric symptoms improved with quetiapine, prednisone, azathioprine, and cyclophosphamide. Oncological management was conducted with MAPK pathway inhibitors (i.e., dabrafenib and trametinib). Movement disorders associated with neuropsychiatric symptoms are complex to diagnose. PNS are rare and often associated with antibodies against neural antigens expressed by the tumor. The case presented above describes a patient with a BRAF-positive malignant melanoma metastasis from an occult primary associated with PCD – to the best of our knowledge, the first reported in the literature.

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Autoimmune Movement Disorders: A Video-Based Case Series of 11 Patients

European Neurology ◽

10.1159/000514106 ◽

2021 ◽

pp. 1-5

Author(s):

Anjali Chouksey ◽

Sanjay Pandey

Keyword(s):

Movement Disorder ◽

Movement Disorders ◽

Clinical Symptoms ◽

Tertiary Care ◽

Case Series ◽

Autoimmune Encephalitis ◽

Intravenous Immunoglobulins ◽

Thyroid Peroxidase ◽

Tertiary Care Centre ◽

Abnormal Movements

Autoimmune encephalitis (AIE) constitutes an important treatable cause of movement disorders. We aimed to highlight the spectrum of movement disorder and other salient features of AIE patients diagnosed at our tertiary care centre and describe their clinical symptoms, diagnostic approach, treatment, and outcome. We evaluated 11 patients who presented with movement disorder in association with AIE at our centre. Various abnormal movements observed were tremor, dyskinesias, stereotypy, dystonia, ataxia, asterixis, myoclonus, and parkinsonism. Antibodies were detected against NMDAR (n = 3), LGI-1 (n = 2), GAD-65 (n = 1), CASPR-2 (n = 1), Sox-1 (n = 1), Yo (n = 1), and thyroid peroxidase (n = 1). One patient was diagnosed with opsoclonus myoclonus syndrome associated with the suspected neuroblastic tumour. Six patients responded well to first-line immunotherapy (intravenous immunoglobulins or steroid or both). Three patients with anti-NMDAR antibodies received second-line therapy consisting of rituximab. Movement disorder is one of the most consistent features of AIE. Understanding of the ever-expanding spectrum of antibodies associated with movement disorders helps in the early diagnosis and better management of patients of autoimmune movement disorder.

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Anti-N-methyl-D-aspartate receptor encephalitis presenting as atypical psychosis in multiple sclerosis: a case report

BMC Psychiatry ◽

10.1186/s12888-021-03351-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Khushminder Chahal ◽

Tara Endeman ◽

Sarah Scapinello ◽

Michal Sapieha

Keyword(s):

Multiple Sclerosis ◽

Psychiatric Symptoms ◽

Neuropsychiatric Symptoms ◽

Psychiatric Inpatient ◽

Treatment Protocol ◽

Autoimmune Encephalitis ◽

Ovarian Teratoma ◽

Atypical Symptoms ◽

Aspartate Receptor ◽

Nmdar Encephalitis

Abstract Background Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder which often presents with neuropsychiatric symptoms. A large proportion of cases are associated with an identifiable tumor, most commonly ovarian teratoma. However, recent literature has also described an overlap of anti-NMDAR encephalitis and demyelinating syndromes. Cases have been reported of anti-NMDAR encephalitis in patients with ADEM, optic neuritis, myelitis and multiple sclerosis. This link is considered rare, however has important clinical implications as treatments and prognosis may differ. Case presentation A 33-year-old female with a history of multiple sclerosis presented with new-onset neuropsychiatric symptoms. After substance-induced psychosis was ruled out, she was admitted to the medical ward for work up of psychosis secondary to multiple sclerosis. However, the consultation-liaison psychiatry service noted atypical symptoms which were concerning for autoimmune encephalitis. Admission to a psychiatric inpatient ward was deferred. Anti-NMDAR encephalitis was diagnosed with CSF analysis demonstrating lymphocytic pleocytosis and anti-NMDAR antibodies. In addition to first-line treatment of encephalitis with steroids, second-line immunotherapies were also implemented given the patient’s underlining demyelinating syndrome. The patient’s neurologic and psychiatric symptoms began to improve. Conclusions There is literature to demonstrate a possible connection between anti-NMDAR encephalitis and demyelinating syndromes. As such, autoimmune encephalitis should be considered in patients with multiple sclerosis presenting with atypical symptoms. Determining the correct diagnosis is crucial to inform the appropriate treatment protocol, and to improve prognosis.

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Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases

Journal of Neuroinflammation ◽

10.1186/s12974-021-02293-x ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Veronika Vasilevska ◽

Paul C. Guest ◽

Hans-Gert Bernstein ◽

Matthias L. Schroeter ◽

Christian Geis ◽

...

Keyword(s):

Nmda Receptor ◽

Molecular Mimicry ◽

Psychiatric Symptoms ◽

Auditory Hallucination ◽

Neuropsychiatric Symptoms ◽

Autoimmune Encephalitis ◽

Altered Mental Status ◽

Warning Signs ◽

High Dose ◽

Nmda Receptor Encephalitis

AbstractApproximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.

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