Materiały źródłowe

• #1 The Laboratory Diagnosis of Autoimmune Encephalitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5206099/

  Autoimmune encephalitis is a group of encephalitis syndromes that cause altered mentality, memory decline, or seizures in association with the presence of serum and cerebrospinal fluid (CSF) autoantibodies (auto-Abs). An early diagnosis enables early treatments. The detection of auto-Abs is a confirmatory diagnosis. […] The laboratory diagnosis of autoimmune encephalitis consists in the detection of auto-Abs, EEG, MRI, functional neuroimaging, and work-up for systemic tumors. […] Although detection of auto-Abs is the best diagnostic method for autoimmune encephalitis, there are many Ab-negative probable autoimmune encephalitis cases. […] The Ab tests using both CSF and serum are necessary and CSF sometimes reflects disease activity. […] The detection of auto-Abs is a confirmatory diagnostic test.

• #1 Autoimmune Encephalitis | Choose the Right Test

  https://arupconsult.com/content/autoimmune-encephalitis

  Autoimmune encephalitis is an autoimmune neurologic disease that affects the central nervous system, resulting in subacute onset of memory problems, mental status changes, and psychiatric symptoms. […] The prompt and accurate diagnosis of autoimmune encephalitis is important because early and appropriate treatment is associated with improved outcomes, whereas misdiagnosis may result in adverse events. […] Making a presumptive diagnosis of autoimmune encephalitis allows for the early administration of immunotherapy before the identification of specific antineural autoantibodies, which is important because it may take many days to receive antibody testing results. […] Antineural antibody testing should be performed to confirm the diagnosis, but immunotherapy should not be withheld pending test results.

• #1 The Diagnosis and Treatment of Autoimmune Encephalitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4712273/

  Autoimmune encephalitis is a difficult clinical diagnosis due to the similarities in the clinical, imaging and laboratory findings of many forms of autoimmune and infectious encephalitis. […] A broad approach to testing for infectious diseases and various neuronal autoantibodies can lead to the correct diagnosis. […] Autoantibody testing is extremely important for the proper diagnosis of autoimmune encephalitis. […] Commercial tests for autoantibodies to NMDAR, LGI1, Caspr2, AMPAR (GluR1, GluR2 subunits), and GABA-B-R are widely available. […] The availability of titers for NMDAR antibodies has led some practitioners to attempt to use these titers to guide treatment. […] Brain MRI in patients with NMDAR, AMPAR, LGI1, Caspr2, and GABA-B antibodies may be normal or show increased T2 signal, especially in the medial temporal lobes. […] EEG is useful in patients with autoimmune or infectious encephalitis for excluding subclinical seizures, for prognosis, and sometimes for suggesting particular diagnoses. […] The proper diagnosis and management of autoimmune encephalitis requires an organized approach.

• #1 Autoimmune encephalitis // Middlesex Health

  https://middlesexhealth.org/6D451120-E1D2-9288-17CEEAF7E672AFCA

  Autoimmune encephalitis diagnosis involves a review of your symptoms, a physical exam and several tests. It’s important to get an accurate diagnosis because autoimmune encephalitis, also known as AE, can be mistaken for other diseases. […] Experts have created autoimmune encephalitis criteria to help healthcare professionals diagnose people with AE. Healthcare professionals look for patterns of symptoms that signal AE. They also test for signs that antibodies are attacking receptors in the brain to cause AE. […] Tests also help rule out other possible causes of your symptoms, such as infections or other autoimmune conditions. […] Sometimes people are incorrectly diagnosed with autoimmune encephalitis. It’s important for healthcare professionals to consider all potential conditions when making a diagnosis.

• #1 Diagnosis and Management of Autoimmune Encephalitis | Cleveland Clinic

  https://my.clevelandclinic.org/departments/neurological/depts/multiple-sclerosis/ms-approaches/diagnosis-and-management-of-autoimmune-encephalitis

  Autoimmune encephalitis (AE) is a heterogeneous group of non-infectious, immune-mediated inflammatory disorders that primarily affect the brain but can also have multifocal involvement of the spinal cord, peripheral nervous system and/or systemic manifestations. AE is a common cause of encephalitis that can present in all age groups with several studies showing it to be as common as infectious etiologies. A diagnosis of AE should be considered in patients presenting with progressive neurocognitive symptoms evolving over the course of weeks to months. Typical features include cognitive dysfunction (poor short-term memory, attention deficits), and seizures which are often refractory to antiseizure medication. […] The most recent diagnostic criteria (published in 2016) reflect the consensus opinion of international experts to expedite the diagnosis and facilitate early treatment. These criteria focus on serological, cerebrospinal fluid (CSF), electroencephalogram (EEG), and radiographic evidence to support the diagnosis. In all patients with suspected AE, serum and CSF studies should be performed to rule out metabolic, infectious, and nutritional causes of encephalopathy while testing both samples for NAA.

• #1 A clinical approach to diagnosis of autoimmune encephalitis. – ean.org

  https://www.ean.org/research/resources/neurology-updates/detail/a-clinical-approach-to-diagnosis-of-autoimmune-encephalitis

  The progress made over the past 15 years in the field of autoimmune encephalitis has transformed the diagnostic approach to these disorders and led to the identification of new syndromes and biomarkers. […] This paper focuses on how to establish a prompt diagnosis of autoimmune encephalitis when the patient is presenting with subacute onset of memory deficits or altered mental status. […] The diagnosis of autoimmune encephalitis is made when all three of the following criteria have been met: 1 Subacute onset (rapid progression of less than 3 months) of working memory deficits, altered mental status or psychiatric symptoms. 2 At least one of the following: new focal CNS deficits; seizures not explained by a previously known seizure disorder; CSF pleocytosis; MRI features suggestive of encephalitis. 3. Reasonable exclusion of alternative causes.

• #1 SciELO Brazil – Autoimmune encephalitis: a review of diagnosis and treatment Autoimmune encephalitis: a review of diagnosis and treatment

  https://www.scielo.br/j/anp/a/mqLMtVDZLLF566CwstHwyhy/

  Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious encephalitis. […] We reviewed common forms of AIE and discuss their diagnostic approach and treatment. […] Autoimmune encephalitis is typically an acute or subacute onset and that may become chronic later. […] We reviewed common causes of AIE and discuss their pathophysiology, diagnostic approach and management. […] For improving the recognition of immune-mediated cases, diagnostic criteria for suspected AIE were recently established including criteria for seronegative AIE. […] Definite soropositive AIE requires typical clinical picture and positive anti-neuronal antibodies. […] Table 3 summarizes the diagnostic criteria for anti-NMDAR encephalitis. […] Diagnosis can be made when all four of the following criteria have been met: 1 Subacute onset (rapid progression of less than three months) of working memory deficits, seizures, or psychiatric symptoms suggesting involvement of the limbic system 2 Bilateral brain abnormalities on MRI T2-weighted FLAIR sequence restricted to the medial temporal lobes 3 At least one of the following: EEG with epileptic or slow-wave activity involving the temporal lobes CSF pleocytosis 4 Reasonable exclusion of alternative causes.

• #1 Autoimmune Encephalitis Testing Recommendations

  https://testguide.labmed.uw.edu/guideline/autoimmune_encephalitis

  Acute and subacute encephalitis are a debilitating group of inflammatory disorders of the brain with a complex differential diagnosis. […] Within the autoimmune encephalitis category, certain subcategories have been associated with specific antibodies, although identification of the specific antibody is not a requirement for diagnosis. […] Conventional neurological evaluation and standard diagnostic tests (MRI, CSF, EEG studies) prevail in the initial assessment of autoimmune encephalitis. The presence of CSF pleocytosis (5 cells per mm3) can also lend support to the diagnosis. […] The preliminary diagnosis and decision for initiating treatment of autoimmune encephalitis cases are often not dependent on antibody status. The detection of specific autoantibodies aids in the establishment of a definitive diagnosis of autoimmune encephalitis (versus possible or probable categories).

• #1 Autoimmune Encephalitis – The Ectopic Brain

  https://ectopicbrain.bwh.harvard.edu/index.php?title=Autoimmune_Encephalitis

  Absence of well characterized autoantibodies in serum and CSF, and at least 2 of the following criteria: MRI abnormalities suggestive of autoimmune encephalitis […] CSF pleocytosis, CSF-specific oligoclonal bands or elevated CSF IgG index, or both […] Brain biopsy showing inflammatory infiltrates and excluding other disorders (e.g., tumor) […] Reasonable exclusion of alternative causes […] Antibodies in the diagnosis of autoimmune encephalitis (Graus et al, 2016) […] Antibodies against intracellular antigens […] Antibodies against synaptic receptors […] Antibodies against ion channels and other cell-surface proteins.

• #1 Diagnosis and Management of Autoimmune Encephalitis | Cleveland Clinic

  https://my.clevelandclinic.org/departments/neurological/depts/multiple-sclerosis/ms-approaches/diagnosis-and-management-of-autoimmune-encephalitis

  To optimize the sensitivity and specificity of NAA testing, both serum and CSF samples need to be analyzed in patients with suspected AE. […] When deciding upon who should be screened for malignancy there are several factors to consider: age, smoking history, personal or family history of cancer, specific NAA and its known association with cancer. […] There are no validated biological markers or clinical measures to assess treatment response or clinical disease activity in AE. Disease monitoring is therefore primarily based on the clinical history and examination in combination with objective measures such as validated bedside cognitive tests should be performed regularly. […] Broadly speaking, AE associated with intracellular antigens portends a poor outcome and are less responsive to immune therapies. Conversely, patients with NAA targeting cell surface or synaptic antigens have a better response to immune therapy and if treated in a timely fashion show good long-term functional outcomes.

• #1 Antibody-mediated autoimmune encephalitis: A practical approach | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/88/8/459

  Antibody-mediated autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders. The diagnosis should be based on objective neurologic dysfunction in combination with auto antibody testing. Objective clinical findings are needed to make the diagnosis of AE, including changes on magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis. AE may be considered in patients presenting with subacute onset (over 1 to 3 months) of cognitive or memory deficits, alterations in consciousness, seizures, movement disorders, or other neuropsychiatric symptoms. It is also important to recognize that AE can be antibody-negative. Antibody-negative AE may occur due to limitations of currently available testing, especially as novel autoantibodies are being discovered. Despite the challenges, the diagnosis of AE should be driven by the patients clinical presentation and diagnostic evaluation. A comprehensive evaluation for suspected AE includes a range of laboratory studies and imaging. When AE is highly suspected, initial testing should include an antibody panel. Both serum and CSF should be tested for antibodies since CSF is more sensitive and specific for certain antibodies such as NMDA receptor IgG, GAD65 IgG, and GFAP IgG, whereas serum is more sensitive for other antibodies such as LGI1 IgG and Caspr2 IgG.

• #1 Autoimmune Encephalitis Testing Recommendations

  https://testguide.labmed.uw.edu/guideline/autoimmune_encephalitis

  NMDA Receptor IgG Antibody with Reflex, CSF (Sendout) [RCNMDA] is the preferred first-line test for autoimmune encephalitis. […] Confirmatory testing for other autoimmune encephalitis syndromes can be conducted by ordering the Autoimmune Encephalitis Panel, CSF (Sendout) [RCAENP] and/or the Autoimmune Encephalitis Panel, Serum (Sendout) [RSAENP]. […] There is little evidence to support monitoring titers of these antibodies over time. Antibody titers do not necessarily normalize with response to therapy.

• #1 Diagnosis – International Autoimmune Encephalitis Society

  https://autoimmune-encephalitis.org/diagnosis/

  Through evaluations and testing, the clinician will eliminate the possibilities of what disease process is occurring with the patient. Many diseases of the central nervous system present similarly to Autoimmune Encephalitis. As a complete diagnostic work-up is done, possibilities of the cause are ruled out. Diagnosis is confirmed through lab testing for antibodies known to cause these disorders; it is recommended that blood (serum) be tested at the same time as the spinal fluid is tested. However, some of these tests have been found to be less reliable than CSF testing. Cerebral spinal fluid (CSF) is 100% sensitive and 100% accurate when testing for NMDA. For example, where blood or serum testing can give a false reading as the sensitivity of finding Anti-NDMA antibodies in serum is only ~75% with a 97%+ specificity. This means you may miss about 25% of cases. So, if there is a high index of suspicion, even if the serum test is negative, a CSF sample should be acquired and evaluated. Negative results in antibody testing does NOT rule out a diagnosis of autoimmune encephalitis. This is because not all antibodies in autoimmune encephalitis have been discovered yet. If the antibody test comes back negative and the patient has all the other findings confirming AE, the patient is considered to have seronegative AE aka antibody-negative AE.

• #1 Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/7/757

  In addition to ruling out alternative diagnoses, standard Brain MRI with contrast can show changes consistent with one or more of the AE anatomical syndromes. […] The immune reaction in AE is usually diffuse, resulting in multifocal brain inflammation and occasionally additional involvement of the meninges, spinal cord and/or the peripheral nervous system. […] This is the most important test in AE evaluation and is usually the second step in the workup after brain MRI. […] In many patients, testing NAAs in both CSF and serum is needed because CSF detection is more sensitive for some antibodies while serum is more sensitive for other antibodies. […] Most AE cases with normal brain MRI or typical MRI patterns do not require a brain biopsy. […] It is nearly impossible to predict whether AE is paraneoplastic or non-paraneoplastic based on symptoms as both AE subtypes present similarly.

• #1 Autoimmune Encephalitis | Encephalitis International

  https://www.encephalitis.info/types-of-encephalitis/autoimmune-encephalitis/

  Diagnosing autoimmune encephalitis can be challenging, as the symptoms can be non-specific and may resemble those of other conditions, such as infectious encephalitis or psychiatric disorders. […] A definitive diagnosis typically requires a combination of clinical evaluation, imaging studies, and laboratory tests, including: […] Cerebrospinal fluid (CSF) analysis: This test helps detect the presence of autoantibodies, which are crucial for diagnosing autoimmune encephalitis. […] Magnetic resonance imaging (MRI) or computed tomography (CT) scans: These imaging studies are used to rule out other causes of brain inflammation and to identify characteristic changes associated with autoimmune encephalitis. […] Electroencephalogram (EEG): This test evaluates for seizures or abnormal brain activity, which are common in autoimmune encephalitis. […] Blood tests: These tests help evaluate for underlying infections or autoimmune disorders that could be contributing to the condition.

• #1 Autoimmune Encephalitis – EMCrit Project

  https://emcrit.org/ibcc/ae/

  Describing a single set of diagnostic criteria for autoimmune encephalitis is largely impossible, since these disorders are so heterogeneous. Nonetheless, the criteria below may be useful to highlight some core aspects of these disorders. […] CSF abnormalities seem to be relatively uniform across different types of autoimmune encephalitis. […] Normal CSF studies don’t exclude autoimmune encephalitis. Thus, a CSF autoimmune encephalitis panel may be considered even if the routine CSF tests are normal. […] MRI can reveal T2/FLAIR hyperintensities or abnormal contrast enhancement in specific regions that may point towards a specific syndrome. […] EEG may show focal or multifocal abnormalities when MRI is negative. Abnormal EEG findings may support a diagnosis of encephalitis (rather than metabolic encephalopathy or schizophrenia), for example: Focal slowing or seizures, especially when localized to the temporal lobes.

• #1 Autoimmune Encephalitis – EMCrit Project

  https://emcrit.org/ibcc/ae/

  In patients where an autoimmune encephalitis is known or highly suspected, it may be reasonable to evaluate for an underlying malignancy. […] Autoimmune encephalitides can be subclassified into groups based on which neuroanatomic structures are involved. […] Autoimmune limbic encephalitis is generally symmetric, whereas viral (e.g. HSV encephalitis) tends to be asymmetric. […] EEG may show bilateral temporal slowing or epileptiform discharges. […] MRI may show T2 or FLAIR hyperintensity in the medial temporal lobes. […] The key test is CSF evaluation for IgG against the GluN1 subunit of the NMDA receptor, which is highly sensitive and specific. However, serum testing for antibodies has a lower performance. […] Serum testing for antibodies has lower sensitivity (85%), so CSF must be sent.

• #1 The Laboratory Diagnosis of Autoimmune Encephalitis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5206099/

  The tissue-based assay is a screening method. […] In the diagnosis of specific autoimmune encephalitis, the cell-based immunoassay is used for the detection of cell-surface or synaptic Abs, and immunoblotting is used for the detection of intra-cellular paraneoplastic Abs. […] The diagnostic steps used in our hospital are summarized in Fig. 4. The screening test is performed using the tissue-based assay in all patients with suspected autoimmune encephalitis. […] The Ab test can be negative even in the presence of autoimmune encephalitis. […] EEG was abnormal in 90% of cases of anti-NMDAR encephalitis. […] Unilateral or bilateral medial temporal T2 high signals with an extrahippocampal cortical or subcortical lesion are common findings in onconeuronal autoimmune encephalitis. […] FDG-PET scan is useful in the detection of abnormalities, even in patients with a normal MRI. […] Autoimmune encephalitis is a group of epilepsy and encephalitis syndromes that are associated with serum and CSF auto-Abs. The detection of auto-Abs is a confirmatory diagnosis.

• #1 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2016.12.1.1

  Autoantibody testing is extremely important for the proper diagnosis of autoimmune encephalitis. However, the tests have complexities that require consideration, and taking certain test results as conclusive evidence of autoimmune encephalitis can be a mistake. […] Brain MRI in patients with NMDAR, AMPAR, LGI1, Caspr2, and GABA-B antibodies may be normal or show increased T2 signal, especially in the medial temporal lobes. This pattern is similar to the findings seen in HSV encephalitis, where 95% of patients have abnormalities on MRI, or other viral causes of encephalitis. […] EEG is useful in patients with autoimmune or infectious encephalitis for excluding subclinical seizures, for prognosis, and sometimes for suggesting particular diagnoses. In patients with HSV encephalitis, EEG may predict prognosis in addition to helping exclude non-convulsive seizures; normal EEG correlates with good outcomes independent of other prognostic factors.

• #1 Autoimmune encephalitis: Is FDG PET the key to diagnosis? | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/63/supplement_2/2940

  Autoimmune encephalitis (AE) is a relatively rare neurological disorder, which develops as a rapidly progressive encephalopathy caused by brain inflammation that, when it is diagnosed lately its prognosis is poor reaching up to 7-12% of deaths. […] For patients with AE treatment should be implemented quickly to avoid irreversible sequelae and death, for this reason is important to find an early biomarker for no delaying therapy. […] 18F-FDG-PET has been recognized as a potentially useful biomarker in the initial evaluation and subsequent monitoring of patients with suspected autoimmune encephalitis. […] In our study, 100% patients had abnormal FDG PET, while only 3 had abnormal MRI, suggesting the limited sensitivity of MRI in AE. […] We describe the main findings corresponding to AE, these metabolic patterns can add value to the diagnostic evaluation of AE. […] It is necessary more prospective studies to demonstrate the specificity and accuracy of FDG PET so that this study can be included in the future diagnostic recommendations for AE.

• #1 The Laboratory Diagnosis of Autoimmune Encephalitis

  https://www.j-epilepsy.org/journal/view.php?viewtype=pubreader&number=113

  EEG was abnormal in 90% of cases of anti-NMDAR encephalitis. However, these findings were nonspecific. […] Unilateral or bilateral medial temporal T2 high signals with an extrahippocampal cortical or subcortical lesion are common findings in onconeuronal autoimmune encephalitis. […] FDG-PET scan is useful in the detection of abnormalities, even in patients with a normal MRI. It usually shows medial temporal hypo- or hypermetabolic changes in limbic encephalitis. […] Autoimmune encephalitis is a group of epilepsy and encephalitis syndromes that are associated with serum and CSF auto-Abs. The detection of auto-Abs is a confirmatory diagnosis. A tissue-based assay is used as a screening method, and a cell-based immunoassay is applied for the detection of synaptic Abs, whereas immunoblotting is used for the detection of intracellular paraneoplastic Abs.

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

  https://www.mdpi.com/2076-3425/12/9/1130

  The diagnosis of autoimmune encephalitis can be challenging due to the wide spectrum of clinical presentations, prevalence of psychiatric features that mimic primary psychiatric illnesses, frequent absence of diagnostic abnormalities on conventional brain MR-imaging, non-specific findings on EEG testing, and the lack of identified IgG class neuronal autoantibodies in blood or CSF in a subgroup of patients. […] Thus, the diagnosis requires a high index of clinical suspicion after reasonable exclusion of alternative causes and a lower threshold to test paired CSF/serum for confirmation of the presence of neuronal autoantibodies, particularly in those with red flags suggestive of underlying autoimmunity. […] The challenge of establishing a diagnosis is greatest in those cases where neuronal autoantibodies are not identified in the CSF, despite a very high index of clinical suspicion and a reasonable exclusion of alternative etiologies including infectious etiologies, rheumatologic causes, toxic-metabolic disturbances, vascular disorders, neoplastic diseases, rapidly progressive neurodegenerative diseases, primary psychiatric illnesses, mitochondrial disorders, metabolic diseases, and medication-related syndromes.

• #1 Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/7/757

  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 aim of this paper is to emphasise the practical acute and long-term management of AE as a broad category rather than focusing on individual antibody syndromes. […] A detailed history and examination is the first and most important step in AE diagnosis. […] After AE is suspected clinically, a detailed workup is needed to confirm the diagnosis and exclude competing possibilities like infective encephalitis or systemic/metabolic causes. […] The diagnostic algorithm follows the structure summarised in figure 2 and detailed below:

• #1 Autoimmune encephalitis | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/autoimmune-encephalitis?lang=us

  Autoimmune encephalitis can be divided according to the presence or absence of an underlying tumor, or on the type of antibody responsible. […] In patients with underlying malignancy, treatment of this underlying malignancy is important. Otherwise, management is predominantly with immunosuppression, with options including high-dose glucocorticoids, intravenous immunoglobulin, plasmapheresis, cyclophosphamide, and rituximab.

• #1 :: JCN :: Journal of Clinical Neurology

  https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2016.12.1.1

  The proper diagnosis and management of autoimmune encephalitis requires an organized approach. Evaluation should begin with a detailed history and physical examination to detect clues to specific causes. A diverse range of infections should be considered, and appropriate testing should be done to exclude relevant pathogens. Ancillary testing with MRI, EEG, and lumbar puncture may further support a diagnosis of encephalitis and potentially suggest particular causes. A broad group of autoantibody tests may be used to diagnose or exclude particular autoimmune causes, but these tests are complex and not every positive result is definite evidence of an autoimmune disorder. The risk of neoplasm should always be considered during initial treatment and follow-up visits, both in terms of diagnosing serious cancers and because specific tumors may suggest particular autoimmune causes. Treatment should depend on the pathophysiology of the disorder (e.g., T-cell-mediated or antibody mediated) and the clinical situation of the patient. Patients may relapse and should receive appropriate follow-up care from a physician familiar with the diseases.

• #1 Seronegative Autoimmune Encephalitis – Autoimmune Encephalitis Alliance

  https://aealliance.org/ae-types/seronegative-autoimmune-encephalitis/

  Seronegative AE means AE without any identifiable pathogenic antibody. […] When physicians say the patient has seronegative AE, it means that the doctors excluded other etiologies as much as they can, and their reasoning based on the clinical presentation, MRI, CSF analysis, and other autoimmune biomarkers lead the conclusion that the patient can be diagnosed as AE even though a pathogenic antibody has not been detected. […] Because the diagnosis of AE is made after exclusion of other etiologies, such as infectious, tumor, vascular, degenerative, metabolic, and congenital causes, the diagnosis of seronegative AE always remains uncertain, while autoantibody can be the diagnostic hallmark of seropositive AE. […] However, the real-world diagnosis of seronegative AE largely depends on the individual patient data and the experience of the physician.

• #1 Autoimmune Encephalitis – The Ectopic Brain

  https://ectopicbrain.bwh.harvard.edu/index.php?title=Autoimmune_Encephalitis

  At least one of the following: New focal CNS findings […] Seizures not explained by a previously known seizure disorder […] CSF pleocytosis (white blood cell count of more than 5 cells / mm) […] MRI features suggestive of encephalitis (hyperintense signal on FLAIR highly restricted to one or both medial temporal lobes (limbic encephalitis), or in multifocal areas involving grey matter, white matter, or both compatible with demyelination or inflammation) […] Reasonable exclusion of alternative causes […] Diagnostic criteria for autoantibody-negative but probable autoimmune encephalitis (all 4 criteria must be met) […] Rapid progression (less than 3 months) of working memory deficits (short-term memory loss), altered mental status, or psychiatric symptoms […] Exclusion of well-defined syndromes of autoimmune encephalitis (e.g., typical limbic encephalitis, Bickerstaffs brainstem encephalitis, acute disseminated encephalomyelitis)

• #1 Autoimmune Encephalitis | Choose the Right Test

  https://arupconsult.com/content/autoimmune-encephalitis

  Autoimmune encephalitis is rare, and misdiagnosing an individual with autoimmune encephalitis can have serious adverse consequences, including inappropriate immunotherapy or the failure to address a treatable cause of encephalitis. […] A careful laboratory workup should be performed to exclude these conditions and avoid missing the diagnosis of a condition that may be treated differently. […] Laboratory testing for autoimmune encephalitis should be performed in the context of a robust clinical history, thorough neurologic exam, and imaging. […] Detection of a particular antibody in the appropriate clinical context confirms the diagnosis of autoimmune encephalitis. However, failure to detect an antibody does not exclude autoimmune encephalitis. […] Empiric acute immunotherapy should not be withheld while waiting for the results of antibody testing.

• #1 Autoimmune Encephalitis Misdiagnosis   – Insights

  https://news.mayocliniclabs.com/2023/02/20/autoimmune-encephalitis-misdiagnosis/

  Autoimmune encephalitis is a rare condition, and it’s important to remember that many of the mimics are much more common. […] There’s been many studies on patients in whom the initial diagnosis of autoimmune encephalitis was overlooked, and they eventually had a true diagnosis of autoimmune encephalitis. […] Overall, we found that autoimmune encephalitis misdiagnosis occurred in just over a quarter of the referrals, and the median age was 48 years, and a slight majority were female. […] To meet autoimmune encephalitis diagnostic criteria, you have to fulfill what we term here, the possible autoimmune encephalitis diagnostic criteria, and then there’s an algorithm where you may fit into other categories. […] In our study, just 28% fulfilled these diagnostic criteria. […] We looked at the most common reasons for misdiagnosis, and the major one was overinterpretation of a nonspecific serum antibody.

• #1 Autoimmune Encephalitis Misdiagnosis   – Insights

  https://news.mayocliniclabs.com/2023/02/20/autoimmune-encephalitis-misdiagnosis/

  Some of the problematic antibodies that we found in our study were thyroid peroxidase antibodies, so, TPO antibodies are not a good marker of autoimmune encephalitis and often contributed to misdiagnosis. […] The median delay to the actual diagnosis was 16 months. […] If there’s no evidence of inflammation, a normal white blood cell count and no oligoclonal bands in the CSF, or if the MRI is normal or shows no inflammation, that might be a red flag. […] Remember to use the diagnostic criteria for autoimmune encephalitis, and if patients don’t fulfill that, consider that to be a red flag. […] Misdiagnosis of autoimmune encephalitis is not trivial because the treatments that we use like immunotherapies can have harm, and 20% in our study had adverse effects of treatment.

• #1 Emerging Challenges in the Diagnosis and Treatment of Autoimmune Encephalitis | Frontiers Research Topic

  https://www.frontiersin.org/research-topics/6767/emerging-challenges-in-the-diagnosis-and-treatment-of-autoimmune-encephalitis/magazine

  Early suspicion and diagnosis of autoimmune etiologies are of particular importance due to the need for early institution of immunosuppressive therapies to improve outcome. […] However, limited knowledge about and the wide spectrum of clinical presentation as well as similarities of the clinical, imaging and laboratory findings in infectious encephalitis, different forms of encephalopathies and acute psychiatric disorders hinder clinical suspicion and steps towards mandatory investigations. […] This Research Topic aims to improve the understanding of clinical presentation and course of autoimmune encephalitis. […] Moreover, we want to provide insights to basic and ancillary investigations and emerging treatment options in autoimmune encephalitis.

• #1 Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management | Journal of Neurology, Neurosurgery & Psychiatry

  https://jnnp.bmj.com/content/92/7/757

  The main indications for intensive care unit (ICU) admission in AE include refractory status epilepticus, severe dysautonomia and respiratory compromise. […] Several retrospective studies have shown that early and aggressive immunotherapy is associated with better outcomes in AE patients. […] The 2016 AE clinical criteria emphasise the importance of starting immunotherapy once AE is highly suspected and infectious etiologies are excluded based on CSF results. […] If there is no meaningful clinical or radiological response to optimised first-line therapy after 24 weeks, the addition of a second-line agent with both rapid and sustained immunosuppressive effects can improve the outcome. […] In this first part of the best practice recommendations, we covered the clinical presentation, diagnostic workup and acute management of AE guided by published studies and the results of the AEACN survey providing updated recommendations for management of patients with suspected AE.

• #1 Autoimmune encephalitis: clinical spectrum and management | Practical Neurology

  https://pn.bmj.com/content/21/5/412

  In NMDAR-antibody encephalitis, early treatment independently predicted good outcome (modified Rankin score 2) whereas delays in immunotherapy of 4 weeks were associated with poor functional outcomes at 1 year. […] Whenever possible, paired cerebrospinal fluid and serum should be tested, and clinicians should emphasise the clinical hypothesis when interpreting the results.

• #1 Autoimmune encephalitis: clinical spectrum and management | Practical Neurology

  https://pn.bmj.com/content/21/5/412

  In this pragmatic review, which reflects our experience of managing 200 cases with surface-directed autoantibodies, we highlight key clinical features to help identify these patients, outline immunological findings that inform laboratory testing and describe the clinically relevant disease biology of relevance to treatment decisions. […] The importance of early recognition and diagnosis in autoimmune encephalitis is paramount to the ultimate goal of optimal immunotherapy. […] In LGI1-antibody encephalitis, ~80% of patients noticed that faciobrachial dystonic seizures typically precede onset of marked cognitive impairment. […] Given that immunotherapy is more effective than antiseizure medications in treating LGI1-antibody-associated seizures, early treatment with immunotherapy has shown great promise for preventing otherwise incipient cognitive impairment and functional disability.

• #1 Autoimmune Encephalitis: A Practical Guide to Diagnosis and Management | Cleveland Clinic

  https://my.clevelandclinic.org/podcasts/neuro-pathways/autoimmune-encephalitis-a-practical-guide-to-diagnosis-and-management

  Not certain we have any specific data on that question, but generally, it’s much more easier to give patients intravenous steroids, to give the equivalent dose. […] I think in the United States, most of the laboratories offer panel testing as opposed to individual antibody testing. […] So we use our clinical assessment to judge clinical response, and this is because we don’t have all that great tests that we can use to longitudinally follow patients. […] Often, the titer doesn’t necessarily correlate with the clinical activity. […] I think if a patient has a clinical relapse, it probably is useful to repeat a spinal fluid and look for evidence of inflammation. […] The very early testing for VGKC did identify that some patients do have limbic encephalitis and that’s why it became a biomarker.

• #1 Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management S | IJGM

  https://www.dovepress.com/anti-nmda-receptor-autoimmune-encephalitis-diagnosis-and-management-st-peer-reviewed-fulltext-article-IJGM

  It is important to note there are no known serological biomarkers to date that help in clinical decision making during the course of the disease. The presence of NMDA antibody is critical to confirming the diagnosis, but there is limited clinical utility in following antibody titers during the disease. […] After recovery, most patients still have antibodies in serum and CSF. […] When assessing relapse, CSF titers may be more useful than serum titers and only when compared to earlier samples. […] There is consensus that corticosteroids should be the first agent used in anti-NMDAR encephalitis, often in conjunction with IVIG and/or PLEX. […] The majority of patients respond to first-line immunotherapy. In those who fail to improve within two weeks of initiation of two or more first-line therapies, second-line treatment is recommended over continuing or repeating first-line therapies, with rituximab preferred over cyclophosphamide. […] In patients with inadequate response to second-line therapies and exhibit persistent neurological issues, it is important to note that anti-NMDAR encephalitis symptoms may take weeks or months to improve.

• #1 Seronegative Autoimmune Encephalitis – Autoimmune Encephalitis Alliance

  https://aealliance.org/ae-types/seronegative-autoimmune-encephalitis/

  If the physicians find more evidence for the diagnosis of seronegative AE, such as partial response to initial empirical immunotherapy, more exclusion of other etiologies, and clues of autoimmunity other than antibody, then they can try advanced immunotherapeutic agents using rituximab, cyclophosphamide, tocilizumab, anakinra, bortezomib, in cases with remaining neurological deficits. […] The outcome of seronegative AE is poorer than that of seropositive AE. […] More than half of the seronegative AE patients are improved by immunotherapy, and become able to look after their own affairs without assistance. […] Factors associated with good outcomes include younger age, milder baseline neurologic deficits, and early initiation of immunotherapy. […] More researchers are focusing on the seronegative AE to find out hidden antibodies, pathogenesis, and definite diagnostic markers, and more effective treatments. […] Upcoming studies in years should significantly improve the diagnosis, treatment and prognosis for the many patients and families suffering from the disease.

• #2 Autoimmune encephalitis: clinical spectrum and management | Practical Neurology

  https://pn.bmj.com/content/21/5/412

  In this pragmatic review, which reflects our experience of managing 200 cases with surface-directed autoantibodies, we highlight key clinical features to help identify these patients, outline immunological findings that inform laboratory testing and describe the clinically relevant disease biology of relevance to treatment decisions. […] The importance of early recognition and diagnosis in autoimmune encephalitis is paramount to the ultimate goal of optimal immunotherapy. […] In LGI1-antibody encephalitis, ~80% of patients noticed that faciobrachial dystonic seizures typically precede onset of marked cognitive impairment. […] Given that immunotherapy is more effective than antiseizure medications in treating LGI1-antibody-associated seizures, early treatment with immunotherapy has shown great promise for preventing otherwise incipient cognitive impairment and functional disability.

• #2 A clinical approach to diagnosis of autoimmune encephalitis. – ean.org

  https://www.ean.org/research/resources/neurology-updates/detail/a-clinical-approach-to-diagnosis-of-autoimmune-encephalitis

  The progress made over the past 15 years in the field of autoimmune encephalitis has transformed the diagnostic approach to these disorders and led to the identification of new syndromes and biomarkers. […] This paper focuses on how to establish a prompt diagnosis of autoimmune encephalitis when the patient is presenting with subacute onset of memory deficits or altered mental status. […] The diagnosis of autoimmune encephalitis is made when all three of the following criteria have been met: 1 Subacute onset (rapid progression of less than 3 months) of working memory deficits, altered mental status or psychiatric symptoms. 2 At least one of the following: new focal CNS deficits; seizures not explained by a previously known seizure disorder; CSF pleocytosis; MRI features suggestive of encephalitis. 3. Reasonable exclusion of alternative causes.

• #2 SciELO Brazil – Autoimmune encephalitis: a review of diagnosis and treatment Autoimmune encephalitis: a review of diagnosis and treatment

  https://www.scielo.br/j/anp/a/mqLMtVDZLLF566CwstHwyhy/

  Diagnostic criteria for possible autoimmune encephalitis (all three of the following criteria met): 1 Subacute onset (rapid progression of less than three months) of working memory deficits (short-term memory loss), altered mental status (decreased level of consciousness, lethargy or personality changes), or psychiatric symptoms 2 At least one of the following: New focal CNS findings Seizures not explained by previously-known seizure disorder CSF pleocytosis MRI suggestive of encephalitis 3 Reasonable exclusion of alternative causes. […] Probable anti-NMDA receptor encephalitis Diagnosis require all three of the following criteria 1 Less than three months of at least four of the six following major group of symptoms: Abnormal (psychiatric) behavior or cognitive dysfunction Speech dysfunction (pressured speech, verbal reduction, mutism) Seizures Movement disorder, dyskinesias, or rigidity/abnormal postures Decreased level of consciousness Autonomic dysfunction or central hypoventilation 2 At least one of the following laboratory study results: Abnormal EEG (focal or diffuse slow or disorganized activity, epileptic activity, or extreme delta brush) CSF with pleocytosis or oligoclonal bands 3 Reasonable exclusion of other disorders.

• #2 Antibody-mediated autoimmune encephalitis: A practical approach | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/88/8/459

  Antibody-mediated autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders. The diagnosis should be based on objective neurologic dysfunction in combination with auto antibody testing. Objective clinical findings are needed to make the diagnosis of AE, including changes on magnetic resonance imaging, electroencephalography, and cerebrospinal fluid analysis. AE may be considered in patients presenting with subacute onset (over 1 to 3 months) of cognitive or memory deficits, alterations in consciousness, seizures, movement disorders, or other neuropsychiatric symptoms. It is also important to recognize that AE can be antibody-negative. Antibody-negative AE may occur due to limitations of currently available testing, especially as novel autoantibodies are being discovered. Despite the challenges, the diagnosis of AE should be driven by the patients clinical presentation and diagnostic evaluation. A comprehensive evaluation for suspected AE includes a range of laboratory studies and imaging. When AE is highly suspected, initial testing should include an antibody panel. Both serum and CSF should be tested for antibodies since CSF is more sensitive and specific for certain antibodies such as NMDA receptor IgG, GAD65 IgG, and GFAP IgG, whereas serum is more sensitive for other antibodies such as LGI1 IgG and Caspr2 IgG.

• #2 Seronegative Autoimmune Encephalitis – Autoimmune Encephalitis Alliance

  https://aealliance.org/ae-types/seronegative-autoimmune-encephalitis/

  Seronegative AE means AE without any identifiable pathogenic antibody. […] When physicians say the patient has seronegative AE, it means that the doctors excluded other etiologies as much as they can, and their reasoning based on the clinical presentation, MRI, CSF analysis, and other autoimmune biomarkers lead the conclusion that the patient can be diagnosed as AE even though a pathogenic antibody has not been detected. […] Because the diagnosis of AE is made after exclusion of other etiologies, such as infectious, tumor, vascular, degenerative, metabolic, and congenital causes, the diagnosis of seronegative AE always remains uncertain, while autoantibody can be the diagnostic hallmark of seropositive AE. […] However, the real-world diagnosis of seronegative AE largely depends on the individual patient data and the experience of the physician.

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