Encephalitis lethargica: clinical features and aetiology.

Area of Science:

• Neuroscience
• Neurology
• Epidemiology

Background:

• Encephalitis lethargica (EL) is a rare neurological disorder characterized by sleep disturbances and parkinsonism.
• Understanding of EL relies on historical accounts and limited case studies, with proposed causes including infection, toxins, and autoimmune processes.
• Diagnostic and etiological theories for EL require further investigation.

Purpose of the Study:

• To describe the clinical presentation of Encephalitis lethargica.
• To evaluate proposed diagnostic and etiological theories for EL, including infectious, environmental, and autoimmune links.

Main Methods:

• Retrospective case series analysis of 614 Encephalitis lethargica cases from 1918-1946 at a UK hospital.
• Examination of case notes for clinical features, temporality, and cerebrospinal fluid results.
• Comparison of clinical presentations with modern criteria for EL, catatonia, and autoimmune encephalitis; case-control analysis for febrile illness and environmental exposures.

Main Results:

• Cases presented with a median age of 29, featuring prominent motor (97.6%), cranial nerve (91.0%), and ophthalmological (77.4%) symptoms.
• A history of febrile illness was more common in EL cases (31.8%) than controls (OR 2.70, P=0.05), but with reporting bias.
• No association found with solvent/heavy metal exposure; 45.0% of cases met possible autoimmune encephalitis criteria, but only 0.5% met probable NMDA receptor encephalitis criteria.

Conclusions:

• Encephalitis lethargica is a distinct neuropsychiatric condition with a broad clinical spectrum.
• Evidence for infectious or occupational etiology is weak.
• While autoimmune encephalitis is a potential explanation, typical EL cases do not align with NMDA receptor encephalitis.