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Autoimmune Encephalitis Criteria in Clinical Practice

In that algorithmic assessment, to meet at least possible AE criteria, patients require subacute onset (rapid progression of less than 3 months) of working memory deficits (short-term memory loss), altered mental status (altered level of consciousness, lethargy, or personality change) or psychiatric symptoms with at least 1 of new focal CNS findings, new-onset seizures, CSF pleocytosis, and supportive MRI. These tests are complemented by AE-specific IgG antibody testing, CSF IgG index and oligoclonal bands, EEG, and brain biopsy to further refine diagnostic certainty. Specificity is assured by the requirement for reasonable exclusion of other diagnoses and differing levels of diagnostic certainty (possible, probable, and definite). Discerning the characteristics and relative frequencies in the clinical practice of different AE disorder subcategories (possible, probable, definite, and seropositive or seronegative) and related encephalopathies not meeting at least possible AE criteria (e.g., those with primarily seizure disorders without encephalopathy, brainstem disorders without altered awareness, and atypical presentations) would be informative for clinical treatment decisions, epidemiologic studies, and clinical trial design.

In this study, we applied the AE guidelines to 538 adult patients diagnosed with diverse autoimmune encephalopathies within our practice (Autoimmune Neurology Clinic, Mayo Clinic, Rochester, MN). The scope of this assessment did not include pure ataxias, stiff-person syndrome, or other pure movement disorders.

Autoimmune encephalitis: recent clinical and biological advances

This is an update to the 2015 review.

This paper reviews the most common types of AE in detail, treatments, outcomes and new advances, and monitoring the disease. 

The field of autoimmune encephalitis has witnessed a number of advances in our understanding of the underlying biology and the correlation of this with more refined clinical observations. Our hope is that by the time of our next review, the use of early, targeted immunotherapies is commonplace in these conditions and has had an appreciable impact on the long-term outcomes of patients. To integrate the emerging biological insights with our progress around patient-relevant outcomes and the limitations of currently available therapies, the field now needs to embrace experimental medicine approaches. Some classical clinical trials are underway but may be hampered by difficulty recruiting immunotherapy-naïve patients. Nevertheless, a large pipeline of exciting new treatments will likely enter clinical trials in the near future. If incorporated with further dissection of the underlying biology, these trials are likely to provide a foundation for patient treatments over the next decade.

Autoimmune Encephalitis Misdiagnosis in Adults

CONCLUSIONS AND RELEVANCE When evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis
leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

Antibody Therapies in Autoimmune Encephalitis

Conclusion and Future Directions

Antibodies targeting the CD20 epitope on the surface of B cells are the cornerstone of second-line treatment in AE, originally combined with cyclophosphamide. They have a favorable side effect profile compared to second-line treatments with a different mode of action. Moreover, rituximab has shown to be effective in anti-NMDAR encephalitis as well as in many other AE cases when first-line therapies fail. However, anti-CD20 mAb do not deplete long-lived plasma cells which might underlie treatment-refractory cases and the occurrence of (early) relapses. Therefore, there is an emerging repertoire of mAb that aim to directly (inebulizumab, daratumumab) or indirectly (tocilizumab, sartralizumab) target long-lasting plasmablasts or plasma cells with or without additional B cell depletion. Alternatively, the plasma cell products (i.e. pathogenic antibodies) can be removed with mAb targeting the FcRn (efgartigimod, rozanolixizumab). mAbs that disrupt the complement cascade (eculizumab) are also explored but have fewer biological underpinnings. Future trials are needed to understand whether these third-line treatments are effective, when they need to be initiated and whether they have an acceptable safety profile in combination with previous rituximab administration.

Autoantibody Encephalitis: Presentation, Diagnosis, and Management

Autoantibody encephalitis involves distinct clinical syndromes that can be recognized in many cases. In other patients, cancer screening and rational antibody testing can lead to a precise diagnosis. Our knowledge about the optimal treatments is still hampered by the lack of randomized treatment trials, but new information from retrospective studies has provided important new information on treatment of anti-LGI1 and anti-NMDAR syndromes. In selecting treatments it is important to understand the underlying disease mechanisms and the evidence supporting treatment. There will almost certainly be additional autoantibody syndromes discovered in the coming year. Each disease teaches us about the neuroscience of the target antigens. It is not reasonable to expect a general neurologist to memorize the associations of each new antibody. Rather, the goal should be to read and review the cancer associations and treatment guidance for a specific antibody when encountering a case.

Seronegative Autoimmune Encephalitis: A Challenge for the Neurologist

The Antibody Prevalence in epilepsy and encephalopathy score [APE2] is an invaluable bedside clinical scoring system to estimate the probability of an autoimmune etiology in antibody negative patients.

An APE score of 4 or more indicates the necessity for antibody testing. The Response to immunotherapy in epilepsy and encephalopathy score [RITE2] score was derived from the analysis of retrospective studies to identify patients of autoimmune etiology who respond to immunotherapy (Table 1B). A score less than 7 is associated with refractoriness to immunotherapy. The combined use of both these scales enables clinicians to apply an efficient evidence-based approach for the diagnosis of autoimmune neurological diseases that require further evaluation and treatment.

Young children and the elderly are the vulnerable members of our society who are susceptible to antibody mediated illnesses and the neurocognitive outcome depends on the speed of instituting immunotherapy and disease modifying agents. These clinical rating scales are of immense importance to improve functional outcome and to achieve complete remission in patients affected with autoimmune neurological diseases.

Long-term cognitive outcome in anti-NMDA receptor encephalitis

In conclusion, this study presents comprehensive longitudinal data for the cognitive outcome in NMDAR encephalitis. All patients had cognitive deficits about 2 years after disease onset, mainly affecting memory and executive function. After 4 years, moderate or severe cognitive deficits persisted in 2/3 of patients despite good functional neurological outcome, indicating that cognitive function is an important outcome measure in addition to the functional neurological scales. Impaired cognitive outcome was predicted by delayed treatment and higher disease severity. However, continued improvement of cognitive function was observed for several years after disease onset in some patients.

Our results demonstrate that cognitive deficits are frequent and severe longterm sequelae following NMDAR encephalitis. These deficits show a slow and incomplete recovery and persist beyond recovery of other neuropsychiatric symptoms of the disease. Consequently, our findings call for rapid diagnosis and treatment at disease onset as well as for continued and customized cognitive rehabilitation to
improve the longterm outcome.


Comprehensive article on Autoimmune Encephalitis. The first to be published in Finnish. We hope this leads to increased awareness, accurate diagnosis and treatment for patients in Finland. Advocacy for this article was done by long time IAES Member who established the non-profit

Suomen Ultraharvinaiset

Antibody-mediated autoimmune encephalitis: A practical approach


  • AE is an umbrella term for a group of inflammatory central nervous system disorders associated with neuronal autoantibodies or other biomarkers of central nervous system autoimmunity.

  • Common clinical presentations include progressive neurocognitive symptoms with concomitant movement disorders, seizures, and autonomic dysfunction that worsens over weeks to months.

  • Objective clinical findings are needed to make the diagnosis of AE, including changes on magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis.

  • Paper contains a detailed section on differential diagnosis we highly recommend

Autoimmune Encephalitis–Related Seizures and Epilepsy: Diagnostic and Therapeutic Approaches

The identification of neural autoantibodies in patients with new-onset seizures of unknown etiology has led to the concept of acute symptomatic seizures secondary to autoimmune encephalitis (ASSAE) and autoimmune-associated epilepsy (AAE). In these patients, antiseizure medication (ASM)-resistant seizures occur as an early and prominent feature. When combined with other symptoms suggestive of immune-mediated seizures, urgent consultation with neurology is recommended. Early treatment with immunotherapy can drastically alter the course of the disease. First-line immunotherapies include intravenous steroids, intravenous immunoglobulin, and PLEX. In the case of insufficient response, cyclophosphamide and rituximab can be considered appropriate second-line treatments. Treatment also includes adjunct ASM therapy and non-CNS tumor resection (if paraneoplastic etiology is suspected) when found on screening.

As we continue to advance our knowledge in AAE and ASSAE, we need to clarify its definition and diagnostic criteria and promote recognition of relevant symptoms (detailed in Table 2) that would lead to early neurology referral and timely diagnosis. The recently developed APE2 and ACES scores have helped build a foundation for diagnosing ASSAE and AAE; however, there remains much ambiguity.

Supplemental video is included at the end of the paper. Downloadable .mp4

Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Detailed Review of the Different Psychiatric Presentations and Red Flags to Look for in Suspected Cases

This review aimed to discuss the different ways anti-NMDAR encephalitis could present and manifest on the psychological, mainly, and the neurological spectrum of signs and symptoms. The signs and symptoms expressed by anti-NMDAR encephalitis patients can be categorized into psychosis (represented by delusions and hallucinations), catatonia, seizures, speech and movement abnormalities, and autonomic instability, in addition to cognitive dysfunction.

The temporal association between those signs and symptoms varied among cases; first presentations tend to overlap with psychiatric diagnoses, especially on the schizophrenic spectrum. Catatonia is one of the disease hallmarks as well. Movement disorders are commonly seen among the anti-NMDAR encephalitis pediatric population. The autoimmune link between anti-NMDAR encephalitis and schizophrenia has been described before; antibody-positive patients go on to develop neurological manifestations later on. Anti-NMDAR encephalitis can also present with affective manifestations. Narcolepsy and hypersomnia as manifestations of anti-NMDAR encephalitis have been described, as well as the association between alcohol or drug abuse and NMDAR encephalitis. There are some clinical red flags that could be of use to make the diagnosis.

Hence, for physicians trying to familiarize themselves with this diagnosis, this is a good place to start. The review included a general scheme that covers almost all aspects of the psychiatric presentation, similarities, and differences in contrast to other differential diagnoses, in addition to clinical pearls that aid diagnosis. However, this paper did not discuss the different ways this disorder presents in pediatrics; hence, this remains an area future reviews might be more inclusive of.

GAD antibody-spectrum disorders: progress in clinical phenotypes, immunopathogenesis and therapeutic interventions

Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “GAD antibody-spectrum disorders” (GAD-SD). This review highlights that high-titer anti-GAD antibodies are associated with an array of distinct neurological syndromes including SPS, cerebellar ataxia, epilepsy, limbic encephalitis, abnormal eye movements. Although high anti-GAD antibodies in serum or their presence in CSF are important for diagnosis, the titers do not correlate with disease severity and do not generally predict response to immunotherapy. Despite considerable efforts, using both in vitro and in vivo preparations, the pathophysiological role of anti-GAD antibodies has not yet been clarified, suggesting that other autoantibodies affecting inhibitory neurotransmission might be of importance, because autoimmunity targeting inhibitory synaptic antigens point to a unifying theme of hyperexcitability as the underlying pathomechanism.

Collectively, the practicing neurologists need to be aware that anti-GAD antibody titers do matter: if high (>10,000 IU/mL), they are diagnostic for a true GAD-SD, necessitating immunotherapy; lower (<10,000 IU/mL) titers are associated with atypical or non-specific neurological disorders requiring further investigation, whereas very low titers (<2000 IU) are typically seen in DM-1 or are of unclear significance.74 Importantly, GAD-Abs can also be detected within the various IVIg preparations and anti-GAD antibodies can be detected in patients receiving IVIg.84 Most importantly, there is no association between GAD-Ab titer and disease severity or response to therapy without significant titer reduction after immunotherapies with either IVIg or rituximab based on two controlled studies we have performed.

Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

Objective The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS.

Results The panel proposed to substitute “classical syndromes” with the term “high-risk phenotypes” for cancer and introduce the concept of “intermediate-risk phenotypes.” The term “onconeural antibody” was replaced by “high risk” (>70% associated with cancer) and “intermediate risk” (30%–70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided.

Conclusions The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.

Autoimmune encephalitis: proposed recommendations for symptomatic and long-term management Part 1

This is part 1 of a two-part paper

In this first part of the best practice recommendations, we covered the clinical presentation, diagnostic workup and acute management of AE.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. 

Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management part 2

This is part 2 of a two-part paper

In this second part, we will cover symptomatic, bridging, and maintenance immunotherapy of AE.

The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. 

The autoantibody-mediated encephalitides: from clinical observations to molecular pathogenesis

Probably the best summary of how autoimmunity gets initiated is in this great review from Oxford Autoimmune Neurology Group,  which is generally a fantastic and up-to-date all-round primer for many of the clinical and mechanistic issues.

Outlines molecular observations with translational value. We focus on contemporary methodologies of autoantibody detection, the evolution and distinctive nature of the clinical phenotypes, generalisable therapeutic paradigms, and finally discuss the likely mechanisms of autoimmunity in these patients which may inform future precision therapies.

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.

See Correction to Figure 1

Diagnosing autoimmune encephalitis in a real‑world single‑centre setting

A syndrome-based diagnostic approach was published by Graus et al. (Lancet Neurol 15:391-404, 2016), but very little is known in the literature about its application in clinical practice.

AIM: Our aims are to test the feasibility of such approach in a real-world single-centre setting and to analyse the most relevant factors in criteria fulfilment.

Conclusion: Larger studies on prospective cohorts may be more helpful to explore possible important issues.

The autoantibody-mediated encephalitides: from clinical observations to molecular pathogenesis

Many of the early clinical observations in AE have been further refined to permit the accurate recognition of distinctive clinical phenotypes.
AE is now identifed as an important and previously underrecognised cause of CNS infammation—it is highly treatable, and early diagnosis and initiation of immunotherapy are paramount to optimise outcomes.

Innate Immunity in the Central Nervous System: A Missing Piece of the Autoimmune Encephalitis Puzzle?

The psychopathology of NMDAR-antibody encephalitis in adults

Decreased occipital lobe metabolism by FDG-PET/CT

Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis

Neuroimmune disorders of the central nervous system in children in the molecular era

Autoimmune Encephalitis With Multiple Autoantibodies: A Diagnostic and Therapeutic Challenge

Antibody tests Available at Mayo Clinic for AE spinal fluid

Physicians Guide to diagnosing Paraneoplastic Neurological Syndromes (AE) and Associated Disorders - PNS

Treatment strategies for autoimmune encephalitis

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis

Diagnostic Value of 18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis

Autoimmune encephalitis in psychiatric institutions: current perspectives

Role of FDG-PET imaging in the diagnosis of autoimmune encephalitis

Anti-LGI1-associated cognitive impairment: long-term outcome 35% fully recover

Antibody Mediated Psychosis

Will You Be Able to Help Your College-Age Child in a Medical Emergency? HIPAA Privacy can get in your way

Dr. Lancaster Could Your Loved One Have Autoimmune Encephalitis?

AE Masquerading as Psychiatric Disorders

Autoimmune encephalitis: paving the way for early diagnosis

A clinical approach to diagnosis of autoimmune encephalitis

Dr. Josef Dalmau's Blood and CSF test for NMDA: Test results for CSF is 100% but Blood 87.5-94.7%.

Autoimmune Encephalitis in Children

Autoimmune Encephalitis By: Frank Leypoldt

Dangers of taking probiotics when you are immuno suppressed

Mimics of Autoimmune Encephalitis Validation of the 2016 Clinical Autoimmune Encephalitis Criteria

239 patients were included In this retrospective cohort study. Researchers describe common AE mimics and validate the 2016 AE criteria using real-world data. In addition, we propose criteria for probable anti-LGI1 encephalitis. We demonstrate that the specificity for probable AE (NMDAR, SN-AE, and LGI1) and definite autoimmune LE criteria is reassuringly high (>95%). Furthermore, we show that AE mimics occur frequently and are diverse. The most common diagnostic categories are primary psychiatric disorders, CNS inflammatory disorders, epilepsy with a noninflammatory cause, CNS infections, neurodegenerative diseases, and primary CNS neoplasms. The sensitivity of the criteria for possible AE was relatively high (83%), which was comparable with previous studies.

Autoimmune encephalitis during pregnancy: a diagnostic and therapeutic challenge - A systematic review with individual patients’ analysis and clinical recommendations

The diagnosis and treatment of AE during pregnancy are challenging. Caution should be paid to the potential teratogenic effects of several medical and instrumental interventions. The maternal and fetal clinical outcomes are most of the time favorable. Nevertheless, the rate of miscarriage seems to be higher in women with AE. In addition, mothers may show long-term neurological deficits.

Encephalitis: diagnosis, management and recent advances in the field of encephalitides

By focusing on findings presented at the Encephalitis Society’s conference in December 2021, this article will review the causes, clinical manifestations and management of encephalitis and integrate recent advances and challenges of research into encephalitis.

A Sharp Rise in Autoimmune Encephalitis in the COVID-19 Era: A Case Series

Aims: To report an alarming increase in autoimmune encephalitis with mostly positive glutamic acid decarboxylase (GAD) and/or voltage-gated potassium channel (VGKC) antibodies over six months during 2022 in Downtown Los Angeles.

Results: Of the 29 patients tested, 12 reports came back positive. Ten had positive GAD and/or VGKC antibodies, one had a positive myelin oligodendrocyte glycoprotein antibody, and one had a positive leucine-rich glioma-inactivated 1 protein antibody; a 41% positive rate.

Conclusions: This observation has important implications: (1) We may be entering an era of heightened autoimmune encephalitis. (2) These occurrences may be post-infectious in nature at this point of the pandemic. (3) Mostly GAD and VGKC antibodies have been identified (10 of them), which may point toward a new direction of research from a molecular mimicry standpoint. (4) To benefit patients, clinicians need to be aware of such disease manifestations and increase testing; resources must be increased to improve test availability and shorten turnaround time; and treatment, which is expansive, must be made widely available for these potentially reversible diseases.

Autoimmune Encephalitis: A Physician’s Guide to the Clinical Spectrum Diagnosis and Management

This review aimed to provide primary care physicians and hospitalists who, together with psychiatrists, are often the first port of call for individuals presenting with new-onset neuropsychiatric symptoms, with an up-to-date data and evidence-based approach for the diagnosis and management of individuals with neuropsychiatric disorders of suspected autoimmune etiologies.

Life after autoantibody-mediated encephalitis: optimizing follow-up and management in recovering patients

Recent findings 

Cognitive impairment, fatigue, and sleep disturbances affect most recovering AME patients. This realization highlights the need for outcome measures that encompass more than motor function. Standardized questionnaires, surveys, and clinical assessment tools may be adapted to support comprehensive and reproducible clinical assessments and to identify patients who may benefit from additional therapies.


Good outcomes continue to be reported in recovering patients, emphasizing the high potential for recovery following AME. However, cognitive, behavioral, and physical sequelae may limit the potential for great outcomes following AME. Multidisciplinary follow-up is needed to recognize and treat sequelae that compromise long-term recovery and limit quality of life in recovering patients.

Risk Prediction Models for Early ICU Admission in Patients With Autoimmune Encephalitis: Integrating Scale-Based Assessments of the Disease Severity

Of 234 patients enrolled, forty developed critical illness and were early admitted to the ICU (within 14 days of hospitalization). Four prediction models were generated; the models were named CASE, CASE-plus (CASE + prodromal symptoms + elevated fasting blood glucose + elevated cerebrospinal fluid (CSF) white blood cell (WBC) count), mRS and mRS-plus (mRS + prodromal symptoms + abnormal EEG results + elevated fasting blood glucose + elevated CSF WBC count) and had areas under the ROC curve of 0.850, 0.897, 0.695 and 0.833, respectively. All four models had good calibrations. In general, the models containing “CASE” performed better than those including “mRS”, and the CASE-plus model demonstrated the best performance.

Paraneoplastic Neuropathies: What's New Since the 2004 Recommended Diagnostic Criteria

In summary, since the 2004 classification, several peripheral manifestations have been described, mainly with new antibodies, in patients affected by cancer. Whereas novel intracellular antibodies need more robust evidence to become relevant in clinical practice, the true novelty has been the discovery of NSAbs in diseases with prominent, or coexisting, peripheral involvement, which can be paraneoplastic.

Circulating autoantibodies are commonly considered a valuable tool for cancer diagnosis and are frequently requested in clinical practice for patients with unclear neurological peripheral symptoms. However, proper adherence to the use of biomarkers is critical in translating recommendations into clinical practice. At present, circulating classical onconeural antibodies and only a few NSAbs are considered a valuable tool for cancer diagnosis for patients with paraneoplastic neuropathy.

Finally, new cancer therapies seem to evoke immune-mediated neurological syndromes, which may mimic PN, but appear at different times during treatment. 

Autoimmune Encephalitis Resembling Dementia Syndromes

Objective As autoimmune encephalitis (AIE) can resemble neurodegenerative dementia syndromes, and patients do not always present as encephalitis, this study evaluates how frequently AIE mimics dementia and provides red flags for AIE in middle-aged and older patients.

Conclusions Red flags for AIE in patients with suspected dementia are: (1) rapidly progressive cognitive decline, (2) subtle seizures, and (3) abnormalities in ancillary testing atypical for neurodegeneration. Physicians should be aware that inflammatory changes are not always present in AIE, and that biomarkers often requested when dementia was suspected (including 14-3-3) can show abnormal results. Diagnosis is essential as most patients profit from immunotherapy.

Autoimmune encephalitis: clinical spectrum and management

This paper summarizes the well-known autoantibody-mediated encephalitis syndromes with neuronal cell-surface antigens. It focuses 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. Includes ‘seronegative’ cases, where there is a clinical suspicion of an autoantibody but no identified defined autoantigenic target.

The recognition of neuronal surface autoantibodies as a cause of encephalitis has had far-reaching implications. It has helped to define a group of immunotherapy responsive disorders, describe their pathogenesis, and develop therapies informed by these pathogenic mechanisms. Further, the scope of autoantibody-mediated diseases has expanded beyond the initial limbic encephalitis picture to include other polysymptomatic immunotherapy-responsive syndromes. Clinical suspicion of these disorders remains the cornerstone to their detection and there are now many clinically recognizable syndromes described. Interpretation of autoantibody results should similarly be in the context of this clinical picture. Earlier recognition, treatment and escalation of immunotherapy in many of these syndromes can lead to improved outcomes and reduced disability.

Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis

We aimed to retrospectively review 144 cases referred with suspected Hashimoto encephalopathy over a 13-year period, and to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients.

In total, 73% of the patients referred with suspected Hashimoto encephalopathy had an alternative non-immune-mediated diagnosis, and more than half had no evidence of a primary neurological disorder. Thyroid antibody prevalence is high in the general population, and does not support a diagnosis of autoimmune encephalopathy in the absence of objective neurological and CNS-specific immunological abnormalities. Thyroid antibody testing is of little value in the contemporary evaluation and diagnosis of autoimmune encephalopathies.

In our experience within our specialty referral practice, the diagnosis of HE/SREAT is assigned to a variety of patients with elevated thyroid antibody values and diverse neuropsychiatric symptomatic presentations, generally without objective demonstration of encephalopathy, CNS inflammation or objective steroid response.


We conclude that thyroid antibodies have served their time as diagnostic biomarkers in autoimmune encephalopathy well, but their role in the evaluation of autoimmune encephalopathy is likely redundant at this point, and certainly less specific than a clinical history of autoimmune disease and neural-specific antibodies. Our experience indicates that a diagnosis of HE/SREAT is often given to patients presenting with cognitive symptoms and a variety of neurological and non-neurological complaints, in the setting of elevated thyroid antibodies in serum without objective cognitive abnormalities. The utility of testing for thyroid antibodies seems questionable in the modern era which has brought availability of validated clinical criteria and advanced neuroimmunologic diagnostics. Over diagnosis of autoimmune encephalopathy brings undesired consequences such as iatrogenic harm, cost of unnecessary immunosuppressive therapies and delayed diagnosis of the correct neurological disorder. As always, test results need to be interpreted in the context of detailed clinical history and examination.

Hashimoto Encephalopathy in the 21st century

This important paper highlights the difficulties in using TPO antibodies as a marker of CNS autoimmunity, particularly as the antibodies do not bind to neuronal tissue. It also highlights that current criteria do not differentiate steroid responders from non-responders. It also leaves several questions: what are the mechanisms behind HE? What markers will help us identify the 30% of patients that need treatment, and spare the others the risks of high dose steroids? Listen to the corresponding podcast with Drs. Dalmau and Graus in our podcast section.

Understanding auto-immune encephalitis in the ICU

The outcome of AE is generally good, even after several weeks in ICU, stressing the continued need for aggressive supportive care. Recent studies point to a strong impact of autonomic dysfunction and systemic complications on outcome. In anti-NMDAR encephalitis, central hypoventilation, movement disorder, abnormal MRI, CSF inflammation, delayed immunotherapy and lack of early improvement are associated with poorer functional status, whereas the impact of seizures/status epilepticus deserves further investigation. Research priorities in the field of AE include creation of clinical consortia for collection of core data, investigation of treatments, development of biological assays, biobanking for genetic studies, and characterization of long-term outcomes.

A transdiagnostic pattern of psychiatric symptoms in autoimmune encephalitis

In a large series of data extracted from 464 individual reports from patients with definite NMDAR-antibody encephalitis and characteristic demographics, the psychopathology was found to be polymorphic and not to respect traditional psychiatric classifications. Rather, it encompassed catatonia, mood, behaviour, and psychosis domains, and was closely represented by a cluster of seven features which crossed the higher-level categorisations: agitation, aggression, hallucinations, delusions, mutism, irritability or mood instability, and depressed mood. This complex transdiagnostic psychopathology was remarkably consistent between patients and stable across diverse subgroups. Overall, the inference of a polymorphic psychopathology that is complex within individuals but fairly consistently reproduced between patients was particularly marked when data were extracted from reports sorted for proxy markers of psychiatric involvement in mental state description, strongly advocating for involvement of psychiatrists in the earliest assessment of patients with NMDAR-antibody encephalitis.

 Our findings should encourage reports to move away from crude, yet frequently reported features such as psychosis and behavioural disturbance. Indeed, patients who are phenotyped with rudimentary features might be more likely to erroneously receive potentially toxic immunotherapies. By contrast, a more nuanced, multifaceted architecture of NMDAR-antibody encephalitis psychopathology could enable psychiatrists to develop a clinical index of suspicion for patients with possible or probable NMDAR-antibody encephalitis, whose care will benefit from CSF analysis, with the aim of expediting diagnosis and thereby enabling earlier immunotherapy administration and improved clinical outcomes.

Autoimmune Epilepsy

Autoimmune neurology is a fascinating and evolving field, and this article serves as a guide to the evaluation and treatment of this challenging disease. The clinical presentation may be complex and testing may need to be repeated when findings are initially negative or if specific antibodies are not found. The diagnosis is not based on a single result but the comprehensive clinical picture. Each antibody has its unique clinical findings, cancer association, and response to treatment. Early diagnosis and treatment can drastically alter the course of the disease. Advances in the detection and identification of causative antibodies and other biomarkers will aid in diagnosis and prompt treatment of these patients in the future.

LIMR scientists create new diagnostic test for autoimmune encephalitis, isolate auto-antibodies for the disorder

Researchers at the Lankenau Institute for Medical Research (LIMR) have created a simple diagnostic test for an autoimmune disorder that can lead to serious psychiatric symptoms. As part of their work, they isolated and cloned auto-antibodies that may help elucidate the underlying cellular mechanisms of the disease, which is a kind of brain inflammation depicted in the 2016 docudrama “Brain on Fire.”

An Overview of Autoimmune and Paraneoplastic Encephalitides

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis

Evaluation and Management of Autoimmune Encephalitis: A Clinical Overview for the Practicing Child Psychiatrist

Anti-N-Methyl-D-aspartate Receptor Encephalitis: A Severe, Potentially Reversible Autoimmune Encephalitis

Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis

Explains the difference between T cell AE ( intracellular antigens) and B Cell (antibody mediated)

IgLON5 antibody new type of Autoimmune Encephalitis

Neuroleptic intolerance in patients with anti-NMDAR encephalitis

Game over-Voltage gated potassium channel antibodies must test positive for LGI1 or Casper2 for AE dx

Antibody-Mediated Autoimmune Encephalitis in Childhood

GAD-Anti-glutamic acid decarboxylase antibody positive neurological syndromes

Is it Psychiatric? Or is it an Autoimmune Encephalits? Antibodies to the CNS

A clinical approach to diagnosis of AE includes Dalmau podcast

Speech Disorder Called Apraxia can Progress to Neurodegenerative Disease includes videos

Antibody-Mediated Autoimmune Encephalopathies and Immunotherapies

What do doctors look for in blood test to diagnose AE?

What do doctors look for in Spinal Fluid to give diagnosis of AE

Dx value of CSF findings in antibody-associated limbic and anti-NMDAR-encephalitis

Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis

Autoimmune responses are directed against self antigens

Dr. Irani explains:Why some patients can stop immunotherapy without relapse and some can not.

High TPO is a marker in AE, it does not play an active role

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