Diagnostic Delay and Early Clinical Clues in LGI1 Encephalitis: A Structured Review of Published Cases

Objective To characterize early clinical presentations of LGI1 encephalitis, identify common causes of diagnostic delay, and determine features that most often prompted eventual recognition. Background LGI1 encephalitis is a treatable autoimmune encephalitis in which delayed diagnosis may prolong seizures, cognitive decline, and psychiatric morbidity. Early symptoms are often nonspecific or mistaken for more common neurological or psychiatric disorders. Better recognition of early clinical patterns may support earlier testing and treatment. Design/Methods We performed a structured review of published case reports and case series identified using the search terms (“anti-LGI1 encephalitis” OR “LGI1 encephalitis”) AND (“case report” OR “case series”). Fifty records were screened. Thirty-four individual cases with extractable clinical presentation and diagnostic pathway data were included. Descriptive analysis was performed of presenting symptoms, early misdiagnoses, diagnostic delay, and clues leading to LGI1 antibody testing. Results Seizure-spectrum symptoms were the most common initial presentations (8/34), followed by cognitive symptoms (6/34), psychiatric symptoms (5/34), and seizure-like paroxysmal weakness or dystonic episodes (5/34). Diagnostic delay was reported in 23/34 cases, ranging from several days to 3 years. Common early misdiagnoses included epilepsy or seizure disorder, psychiatric illness, dementia/delirium, ischemic stroke, and neurodegenerative or movement disorders. Recognition of faciobrachial dystonic seizures was the most frequent trigger for reconsideration of the diagnosis. Other common prompts included mesial temporal, hippocampal, limbic, or basal ganglia MRI abnormalities; hyponatremia accompanying neuropsychiatric symptoms; and progressive cognitive decline inconsistent with the initial diagnosis. Several reports noted normal early MRI, EEG, or CSF studies despite later confirmed disease. Conclusions LGI1 encephalitis frequently presents with seizure, cognitive, or psychiatric symptoms and is commonly misdiagnosed before recognition. Diagnostic delay was frequent in this review. Faciobrachial dystonic seizures, unexplained hyponatremia, evolving limbic MRI abnormalities, and progressive mixed neuropsychiatric syndromes may represent practical red flags that support earlier LGI1 antibody testing and treatment.