Abstract
Overview: Autoimmune encephalitis (AE) comprises a heterogeneous group of immune-mediated, non-infectious inflammatory disorders affecting the brain parenchyma, meninges, and/or spinal cord (Dalmau J, N Engl J Med, 2018). Recent epidemiological studies suggest that the prevalence of AE is comparable to that of infectious encephalitis, approximately 13.7 per 100,000 population (Dubey D, Ann Neurol, 2018). Autoantibodies generated in response to underlying tumors, post-viral immune activation, or, more commonly, unknown triggers (with several genetic associations identified) initiate antibody- or cell-mediated immune responses that result in neuronal injury through multiple pathogenic mechanisms (Dalmau J, N Engl J Med, 2018). Clinical manifestations: A detailed medical history and neurological examination remain the cornerstone of diagnosis, while ancillary investigations provide supportive evidence. Autoimmune encephalitis typically presents with an acute or subacute onset (<3 months), although chronic progression may occur in selected subtypes (Graus F, Lancet, 2016). Approximately 60% of patients experience a prodromal phase characterized by low-grade fever, fatigue, and headache (Dalmau J, N Engl J Med, 2018). Central nervous system involvement is frequently diffuse or multifocal and may be accompanied by meningeal, spinal cord, and/or peripheral nervous system manifestations. Clinical presentations are highly heterogeneous, encompassing cognitive impairment, psychiatric symptoms, sleep disorders, movement disorders, seizures or epilepsy, and other neurological deficits. The disease course is usually monophasic, with relapse occurring infrequently, typically in patients receiving inadequate immunotherapy or after premature treatment discontinuation. Progressive deterioration is more common in paraneoplastic autoimmune encephalitis (Abboud, Neuroimmunology and Neuroinflammation, 2018). Diagnostic investigations: Brain magnetic resonance imaging (MRI) may demonstrate inflammatory or demyelinating lesions involving the gray matter and/or white matter, often with multifocal distribution, and is valuable for excluding alternative diagnoses such as Creutzfeldt–Jakob disease (CJD), brain tumors, and acute ischemic stroke (Heine J, Neuroscience, 2015). Cancer screening is recommended in all patients because paraneoplastic and non-paraneoplastic AE share similar clinical manifestations (Escudero D, Eur J Neurol, 2011). Imaging modalities should be selected according to the suspected primary tumor and may include ultrasonography, computed tomography (CT), or MRI. In patients with persistent clinical suspicion despite negative tumor screening, repeat evaluation after six months or whole-body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may be considered because of its higher sensitivity for occult malignancy detection (Titulaer MJ, Eur J Neurol, 2011). Electroencephalography (EEG) is useful for excluding non-convulsive status epilepticus, monitoring treatment response in patients with seizures, and identifying multifocal cerebral dysfunction when MRI findings are normal (Steriade C, Seizure, 2018). Cerebrospinal fluid (CSF) analysis commonly demonstrates inflammatory changes, including elevated protein concentration, pleocytosis (20–200 cells/mm³), and positive oligoclonal bands, while also facilitating exclusion of infectious etiologies such as bacterial, viral, and fungal infections. Testing for neuronal autoantibodies in both CSF and serum is recommended because the diagnostic sensitivity varies among different antibodies. Additional blood investigations are also required to exclude alternative diagnoses (Abboud, Neuroimmunology and Neuroinflammation, 2018). Treatment: Current therapeutic strategies are primarily based on expert consensus and include immunotherapy, surgical removal of underlying tumors when indicated, and supportive management of complications such as severe autonomic dysfunction, status epilepticus, and infections (Dalmau J, N Engl J Med, 2018). Acute immunotherapy should be initiated promptly in patients with a high clinical suspicion after excluding infectious encephalitis, primary central nervous system lymphoma, and neurosarcoidosis. First-line treatment may consist of high-dose corticosteroids, plasma exchange, or intravenous immunoglobulin (IVIg), administered either as monotherapy, sequentially, or in combination. Patients who fail to respond within 2–4 weeks should receive second-line immunotherapy, with rituximab generally preferred over cyclophosphamide. Maintenance or bridging therapy may subsequently include oral prednisolone, monthly IVIg, or intermittent intravenous methylprednisolone (Abboud, Neuroimmunology and Neuroinflammation, 2018).
