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

ObjectiveAutoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.MethodsA subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.ResultsExisting 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.ConclusionsDiagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.

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Autoimmune encephalitis in a South Asian population

BMC Neurology ◽

10.1186/s12883-021-02232-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Nilanka Wickramasinghe ◽

Dhanushka Dasanayake ◽

Neelika Malavige ◽

Rajiva de Silva ◽

Thashi Chang

Keyword(s):

Sri Lanka ◽

Psychiatric Symptoms ◽

South Asians ◽

Laboratory Data ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Asian Population ◽

South Asian Population ◽

Clinical Presentations

Abstract Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

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The Laboratory Diagnosis of HIV Infections

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2005/515063 ◽

2005 ◽

Vol 16 (1) ◽

pp. 26-30 ◽

Cited By ~ 18

Author(s):

Margaret Fearon

Keyword(s):

Point Of Care ◽

Diagnostic Testing ◽

Clinical Information ◽

Hiv Infections ◽

Laboratory Diagnosis ◽

The United States ◽

Specific Information ◽

Antibody Testing ◽

Diagnostic Laboratory ◽

Laboratory Results

HIV diagnostic testing has come a long way since its inception in the early 1980s. Current enzyme immunoassays are sensitive enough to detect antibody as early as one to two weeks after infection. A variety of other assays are essential to confirm positive antibody screens (Western blot, polymerase chain reaction [PCR]), provide an adjunct to antibody testing (p24 antigen, PCR), or provide additional information for the clinician treating HIV-positive patients (qualitative and quantitative PCR, and genotyping). Most diagnostic laboratories have complex testing algorithms to ensure accuracy of results and optimal use of laboratory resources. The choice of assays is guided by the initial screening results and the clinical information provided by the physician; both are integral to the laboratory's ability to provide an accurate laboratory diagnosis. Laboratories should also provide specific information on specimen collection, storage and transport so that specimen integrity is not compromised, thereby preserving the accuracy of laboratory results. Point of Care tests have become increasingly popular in the United States and some places in Canada over the past several years. These tests provide rapid, on-site HIV results in a format that is relatively easy for clinic staff to perform. However, the performance of these tests requires adherence to good laboratory quality control practices, as well as the backup of a licensed diagnostic laboratory to provide confirmation and resolution of positive or indeterminate results. Laboratory quality assurance programs and the participation in HIV proficiency testing programs are essential to ensure that diagnostic laboratories provide accurate, timely and clinically relevant laboratory results.

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Laboratory Diagnosis of Porphyria

Diagnostics ◽

10.3390/diagnostics11081343 ◽

2021 ◽

Vol 11 (8) ◽

pp. 1343

Author(s):

Elena Di Pierro ◽

Michele De Canio ◽

Rosa Mercadante ◽

Maria Savino ◽

Francesca Granata ◽

...

Keyword(s):

Molecular Analysis ◽

Diagnostic Testing ◽

Laboratory Diagnosis ◽

Clinical Suspicion ◽

Enzymatic Activities ◽

Heme Biosynthesis ◽

Present Review ◽

Biosynthesis Pathway ◽

Clinical Presentations

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

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Prenatal Screening and Diagnosis

10.2310/tywc.19170 ◽

2018 ◽

Author(s):

Barbara O’Brien ◽

Emily Willner

Keyword(s):

Diagnostic Testing ◽

Chorionic Villus ◽

Clinical History ◽

Maternal Serum ◽

Specific Gene ◽

Chorionic Villus Sampling ◽

Genetic Syndromes ◽

Cell Free Dna ◽

Free Dna ◽

Ultrasound Evaluation

Prenatal genetic testing offers patients and providers the opportunity to screen for aneuploidy, genetic syndromes, and congenital malformations during pregnancy. Screening options include taking a clinical history, evaluation of maternal serum markers or noninvasive cell-free DNA, and ultrasound evaluation during the first and second trimesters. Invasive diagnostic testing such as amniocentesis or chorionic villus sampling allows for further investigation of positive screening results and a directed test to identify aneuploidy as well as specific gene mutations and gain, loss, or rearrangement of genetic information. Laboratory methods for testing fetal samples differ by types of genetic abnormalities that can be detected and turnaround time for results; these methods include karyotype, fluorescence in situ hybridization, and microarray. This review contains 5 figures, 5 tables and 43 references Key words: amniocentesis, aneuploidy, cell-free DNA, chorionic villus sampling, karyotype, microarray, prenatal genetic screening, ultrasonography

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Diagnostic Reasoning in the Pain-Focused Encounter

Pain Care Essentials ◽

10.1093/med/9780199768912.003.0008 ◽

2019 ◽

pp. 103-116

Author(s):

Beth B. Hogans

Keyword(s):

Differential Diagnosis ◽

Negative Impact ◽

Diagnostic Testing ◽

Clinical History ◽

Diagnostic Reasoning ◽

Problem List ◽

Patient Centered ◽

Clinical Model ◽

Error Disclosure ◽

The Impact

Chapter 7 addresses the processes and pitfalls of evaluating, reasoning about, and attending to the needs of patients with pain. This chapter builds on Chapter 6, which addressed clinical assessment, explaining in detail the process of extracting and abstracting information from the pain narrative (clinical history or interview) to lay the foundation for a problem list and differential diagnosis. The problem list and differential diagnosis are described and contrasted so that clinicians will be comfortable with both. A clinical model explains the need for patient-centered approaches to be omnipresent but balanced with an appropriate disease-centered knowledge base that is likewise informed by understanding the patient’s healthcare-related values and motivations. A balanced approach is emphasized. The process of planning for diagnostic testing, including imaging, laboratory testing, provocative maneuvers, and targeted referrals, is described. The last section of the chapter addresses the impact and nature of cognitive and affective biases that can mitigate the effectiveness of diagnostic reasoning. A coordinated strategy to limit the negative impact of diagnostic reasoning biases is presented in a memorable way. Finally, the ethics of errors and error disclosure are discussed as well as the process of error disclosure.

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Fulminant thymomatous AMPAR-antibody limbic encephalitis with hypertonic coma, bruxism, an isoelectric electroencephalogram and temporal cortical atrophy, with recovery

BMJ Case Reports ◽

10.1136/bcr-2018-227893 ◽

2019 ◽

Vol 12 (2) ◽

pp. e227893

Author(s):

Nicolás Urriola ◽

Kavie Soosapilla ◽

James Drummond ◽

Mark Thieben

Keyword(s):

Botulinum Toxin ◽

Glutamate Receptor ◽

Limbic Encephalitis ◽

Botulinum Toxin Injection ◽

Autoimmune Encephalitis ◽

Cortical Atrophy ◽

Impaired Consciousness ◽

Clinical Recovery ◽

Clinical Presentations ◽

Electroencephalogram Eeg

Autoimmune encephalitides are a potentially devastating group of treatable disorders with a wide variety of clinical presentations. The most studied autoimmune encephalitis is caused by antibodies to the N-methyl-D-aspartate glutamate receptor. A rarer cause is due to antibodies against the evolutionarily related α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). The full assortment of electroencephalogram (EEG) and clinical descriptions of the latter are yet to be fully described. A 44-year-old woman with impaired consciousness and subsequent coma characterised by an isoelectric EEG was diagnosed with AMPAR-antibody limbic encephalitis. MRI revealed temporal T2 hyperintensities that improved with immunosuppression, although leaving marked cortical atrophy. Gradual clinical improvement saw the development of aggressive bruxism requiring botulinum toxin injection with eventual meaningful clinical recovery. This case expands the clinical spectrum of AMPAR limbic encephalitis to include aggressive bruxism, and highlights that despite poor clinical and EEG findings at the outset, recovery is still possible.

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Clinical approach to obscure GI bleeding - Diagnostic testing and management

Journal of Digestive Endoscopy ◽

10.4103/0976-5042.129966 ◽

2013 ◽

Vol 04 (03) ◽

pp. 061-070 ◽

Cited By ~ 1

Author(s):

Prashanth Prabakaran ◽

Nalini Guda ◽

Jacob Thomas ◽

Charles Heise ◽

Deepak Gopal

Keyword(s):

Small Bowel ◽

Diagnostic Testing ◽

Radiographic Evaluation ◽

Clinical Approach ◽

Gi Bleeding ◽

Diagnostic Dilemma ◽

Double Balloon Enteroscopy ◽

Balloon Enteroscopy ◽

Entire Small Bowel ◽

Single Balloon

AbstractObscure gastrointestinal bleeding (OGIB) can present as a diagnostic dilemma and management can be challenging. The search for causes of OGIB is usually centered on visualizing the small bowel, and in the past decade, the technology to visualize the entire small bowel has significantly advanced. Moreover, small bowel endoscopic imaging has replaced, in many instances, prior radiographic evaluation for obscure GI bleeding. These new modalities, such as small bowel capsule endoscopy (CE), balloon-assisted deep enteroscopy [double balloon enteroscopy (DBE) and single balloon enteroscopy (SBE)], and overtube-assisted deep enteroscopy (spiral enteroscopy), are paving the way toward more accurately identifying and treating patients with OGIB. We will review the diagnostic modalities available in evaluating a patient with OGIB and also propose the management based on clinical and endoscopic findings.

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Practice Current: When do you suspect autoimmune encephalitis and what is the role of antibody testing?

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000423 ◽

2018 ◽

Vol 8 (1) ◽

pp. 67-73 ◽

Cited By ~ 10

Author(s):

Aravind Ganesh ◽

Sarah F. Wesley

Keyword(s):

Lumbar Puncture ◽

Sensitivity And Specificity ◽

Clinical Characteristics ◽

Online Survey ◽

Clinical Presentation ◽

Autoimmune Encephalitis ◽

Differential Diagnoses ◽

Antibody Testing ◽

Case Based

Diagnosing autoimmune encephalitis (AE) is complicated by several factors, including issues with availability, sensitivity, and specificity of antibody testing, particularly with variability in assay techniques and new antibodies being rapidly identified; nonspecific findings on MRI, EEG, and lumbar puncture; and competing differential diagnoses. Through case-based discussions with 3 experts from 3 continents, this article discusses the challenges of AE diagnosis, important clinical characteristics of AE, preferences for methods of autoantibody testing and interpretation, and treatment-related questions. In particular, we explore the following question: If a patient's clinical presentation seems consistent with AE but antibody testing is negative, can one still diagnose the patient with AE? Furthermore, what factors does one consider when making this determination, and should treatment proceed independent of antibody testing in suspected cases? The same case-based questions were posed to the rest of our readership in an online survey, the results of which are also presented.

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Neuronal antibody prevalence in children with seizures under 3 years

Neurology ◽

10.1212/wnl.0000000000010318 ◽

2020 ◽

Vol 95 (11) ◽

pp. e1590-e1598

Author(s):

Joseph D. Symonds ◽

Teresa C. Moloney ◽

Bethan Lang ◽

Ailsa McLellan ◽

Mary E. O'Regan ◽

...

Keyword(s):

Early Childhood ◽

Gaba Receptor ◽

Glycine Receptor ◽

Autoimmune Encephalitis ◽

Febrile Seizures ◽

Population Based ◽

Clinical Test ◽

Antibody Testing ◽

Serum Samples ◽

Antibody Positivity

ObjectiveTo report the prevalence of anti-neuronal antibodies in a prospective whole-nation cohort of children presenting with seizures before their third birthday.MethodsThis was a prospective population-based national cohort study involving all children presenting with new-onset epilepsy or complex febrile seizures before their third birthday over a 3-year period. Patients with previously identified structural, metabolic, or infectious cause for seizures were excluded. Serum samples were obtained at first presentation and tested for 7 neuronal antibodies using live cell-based assays. Clinical data were collected with structured proformas at recruitment and 24 months after presentation. In addition, patients with seizures and clinically suspected autoimmune encephalitis were independently identified by a review of the case records of all children <3 years of age in Scotland who had undergone EEG.ResultsTwo hundred ninety-eight patients were identified and recruited and underwent autoantibody testing. Antibody positivity was identified in 18 of 298 (6.0%). The antibodies identified were GABA receptor B (n = 8, 2.7%), contactin-associated protein 2 (n = 4, 1.3%), glycine receptor (n = 3, 1.0%), leucine-rich glioma inactivated 1 (n = 2, 0.7%), NMDA receptor (n = 1, 0.3%), and GABA receptor A (n = 1, 0.3%). None of these patients had a clinical picture of autoimmune encephalitis. Seizure classification and clinical phenotype did not correlate with antibody positivity.ConclusionsAutoimmune encephalitis is very rare in early childhood. However serum neuronal antibodies are identified in 6.4% of children presenting with seizures at <3 years of age. Antibody testing should not be a routine clinical test in early childhood-onset epilepsy because, in the absence of other features of autoimmune encephalitis, antibody positivity is of doubtful clinical significance. Antibody testing should be reserved for patients with additional features of encephalitis.

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