The contemporary spectrum of paediatric autoimmune encephalitis is reviewed, including anti-NMDAR encephalitis, MOG antibody-associated disease overlap syndromes, and seronegative AE phenotypes, with emphasis on early recognition, diagnostic algorithms, immunotherapy, and long-term outcomes.
Abstract
Autoimmune encephalitis (AE) is an increasingly recognised cause of subacute encephalopathy, behavioural change, seizures, and movement disorders in children. The recognition of antibody-mediated syndromes—principally anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis—has transformed the field, and refined diagnostic criteria now allow earlier treatment initiation. However, diagnostic delay remains common in paediatric practice and contributes to long-term neurocognitive morbidity. We review the contemporary spectrum of paediatric autoimmune encephalitis, including anti-NMDAR encephalitis, MOG antibody-associated disease overlap syndromes, and seronegative AE phenotypes, with emphasis on early recognition, diagnostic algorithms, immunotherapy, and long-term outcomes. Anti-NMDAR encephalitis is the most frequent paediatric AE worldwide, characterised by behavioural change, language regression, seizures, dyskinesias, and autonomic instability; ovarian teratoma is uncommon in prepubertal children. MOG antibody-associated disease can present with encephalopathy, particularly in younger children, often with concurrent demyelinating features. Seronegative AE poses particular diagnostic challenges. Across cohorts, diagnostic delay is associated with worse outcomes, more relapses, and persistent cognitive, behavioural, and academic difficulties. Earlier recognition through clinician education, paediatric-specific diagnostic algorithms, and rapid antibody testing pathways is essential. Long-term neurocognitive surveillance and individualised rehabilitation are critical, even in children with apparently good motor recovery. Research priorities include validation of paediatric-specific diagnostic criteria, biomarker-guided immunotherapy escalation, and population-based cohorts capturing developmental trajectories.
Abstract Autoimmune epilepsy, once regarded as a rare and poorly understood subset of seizure disorders, has now emerged as a clinically significant and potentially reversible cause of epilepsy. Advances in neuroimmunology have substantially broadened the spectrum of neural autoantibodies implicated in epileptogenesis—particularly those directed against neuronal cell surface and synaptic proteins, such as the N-methyl-D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Distinct autoantibody profiles are now recognized to correlate with characteristic clinical syndromes, facilitating earlier and more targeted diagnosis. For instance, faciobrachial dystonic seizures are highly suggestive of LGI1 antibody-mediated encephalitis, while neuropsychiatric manifestations and movement disorders are typical of NMDAR antibody encephalitis, and chronic temporal lobe epilepsy frequently accompanies GAD65 autoimmunity. Early identification of these immune-mediated forms is critical, as antibody-mediated epilepsies involving cell surface antigens often respond favorably to immunotherapy, leading to substantial recovery. In contrast, epilepsies associated with intracellular antigen targets or cytotoxic T-cell–driven mechanisms, such as Rasmussen encephalitis, typically show poor therapeutic response due to irreversible neuronal injury. Some autoimmune encephalitides also occur as paraneoplastic syndromes, underscoring the importance of comprehensive oncological evaluation in affected patients. Moreover, immune dysregulation has been implicated in catastrophic epileptic conditions such as new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome, further broadening the clinical spectrum of autoimmune-mediated seizures. Although seizures may arise from diverse etiologies, immune mechanisms have gained increasing recognition as an important and potentially modifiable contributor to epileptogenesis. This recognition has been formally endorsed by the International League Against Epilepsy, which classifies autoimmune epilepsy as a distinct diagnostic entity. Nevertheless, true autoimmune epilepsy, in which seizure susceptibility persists after resolution of encephalitic activity, remains relatively uncommon. In most cases, seizures associated with autoimmune encephalitis are acute and reversible with timely immunotherapy. Thus, precise terminology—differentiating acute symptomatic seizures from chronic autoimmune-associated epilepsy—is essential for appropriate management, prognostication, and research standardization.
Monika Singla, Abhishek Dixit, M. Mehndiratta· International Journal of Epi...· 0 citations
ABSTRACT
Autoimmune encephalitis (AE) is a heterogeneous group of immune-mediated disorders of the central nervous system characterized by neuropsychiatric symptoms, seizures, cognitive decline, and movement abnormalities. Timely recognition and initiation of immunotherapy are critical to improving outcomes. We report three cases of AE presenting with varied clinical phenotypes from the Neurology department of Madras Medical College. The first, a 44-year-old male, presented with altered sensorium, action tremor, and myokymia, and was diagnosed with LGI1 and CASPR2 antibody-positive AE. The second, a 16-year-old girl, presented with seizures, progressive cognitive decline, behavioral disturbance, and focal weakness, confirmed as anti-NMDAR encephalitis. The third, a 14-year-old boy, developed seizures and behavioral changes following herpes simplex encephalitis and was later confirmed to have anti-NMDAR antibody-positive AE with features of Kluver-Bucy syndrome. All patients received first-line immunotherapy (steroids, IVIg), with escalation to rituximab in resistant cases.
BACKGROUND
Autoimmune encephalitis (AE) is one of the treatable cause of pediatric encephalitis and is increasingly being recognised as area where timely detection and treatment can limit significant morbidity in such patients. However, data on its occurrence in Indian children remain limited.
OBJECTIVES
To determine the proportion of AE among acute encephalitic syndrome (AES) cases and characterise the clinical and antibody profile in children.
METHODS
This observational cross-sectional study was conducted from May 2023 to October 2024 in a tertiary care hospital in northern India. Children aged one month to12 years with AES were screened for AE using Graus criteria. Cerebrospinal fluid and/or serum antibodies against neuronal antigens (NMDAR, AMPAR1/2, CASPR2, LGI1, GABARB1/B2) were detected using indirect immunofluorescent assay with HEK-293 transfected cells. All children were classified into possible, definite antibody positive and probable antibody-negative paediatric AE as per established definitions.
RESULTS
Of 188 children with AES, 50 (26.5%) met criteria for possible AE. After excluding two Parvovirus B19-positive cases, 48 children (25.5%) underwent antibody testing. Four children (8.3% of possible AE; 2.1% of all AES) tested positive for anti-NMDAR antibodies. Additionally, four cases (8.3%) were identified as probable antibody-negative AE. Common presentations included seizures (70.8%), focal neurological deficits (31.2%), and altered mental status (29.2%). All laboratory-confirmed cases were anti-NMDAR positive.
CONCLUSION
All AE cases diagnosed in the study were anti-NMDAR (N-Methyl-D-aspartic acid receptor) positive encephalitis. A significant proportion of possible/probable AE cases remain non-reactive with the testing antibody panel suggesting undiscovered antigens. Routine antibody screening should be considered in all microbiologically negative AES cases.
Jai Bhagwan, Urvashi Suman, Vikas Manchanda et al.· Indian Journal of Medical Mi...· 0 citations
Comprehensive care extends beyond seizure management and includes addressing developmental, educational, and psychosocial needs, and a multidisciplinary, family-centred approach involving neurologists, dietitians, psychologists, and educators is essential.
Jayesh S. Patil, Hitendra S. Chaudhari, S. Pawar et al.· Research and reviews : a jou...· 0 citations
Current evidence regarding diagnosis, typical and atypical radiological findings, aetiologies, tertiary-care experiences, pathophysiological mechanisms, emerging genetic associations, and an algorithmic approach to management are summarized.
Rachna Sehgal, Archana Kashyap, Bhavna Anand et al.· International Journal of Con...· 0 citations
Autoimmune encephalitis (AE) is an immune‐mediated disorder that may present with prominent psychiatric symptoms, posing diagnostic challenges, particularly in seronegative cases. We report a 57‐year‐old male presenting with acute behavioral changes, psychosis, and cognitive impairment, initially managed in a psychiatric setting without clinical improvement. Subsequent evaluation revealed EEG abnormalities and elevated cerebrospinal fluid (CSF) protein, while autoimmune antibody panels were negative, leading to a diagnosis of seronegative probable AE. The patient showed marked clinical improvement following immunotherapy. This case highlights the importance of considering AE in patients with atypical psychiatric presentations, particularly when accompanied by cognitive decline or neurological findings. At the same time, careful clinical judgment is essential, as overdiagnosis and indiscriminate testing may lead to unnecessary interventions. Early recognition, guided by clinical red flags and supported by objective findings, remains critical for optimal outcomes.
Sercan Karabulut, Hüseyin Oğuz Uyaroğlu, Ebru Barçın· Case Reports in Psychiatry· 0 citations
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