LGI1 and CASPR2 antibodies target parts of voltage-gated potassium channel (VGKC) complexes. They can produce autoimmune encephalitis presenting as seizures, cognitive decline, and memory impairment. Both these most commonly affect older males. Pediatric cases remain rare, and dual positivity at any age is extremely rare. In approximately half of the confirmed LGI1 cases MRI findings are normal, posing a diagnostic challenge.

A 15-year-old female who was previously healthy was admitted with subacute onset of profound anterograde and retrograde amnesia, disorientation to time and place, dizziness, headache and drowsiness. Despite significant memory impairment, verbal communication was preserved. An electroclinical seizure was detected on EEG, with altered consciousness, leftward eye deviation, and perioral automatism lasting one minute. Rhythmic 6-8 Hz left frontotemporal activity was recorded that evolved to 2-4 Hz complexes spread across the right-side region. Two additional subclinical seizures of temporal onset were recorded as well. No features of autonomic dysfunction or peripheral nerve excitability were found.

A comprehensive autoimmune encephalitis panel was conducted, with LGI1 antibodies at 1:80 and CASPR2 at 1:640 in serum. CSF values were 1:1 for both. All other antibodies were negative. Infectious workup was unremarkable and empirical acyclovir was discontinued. IV Methylprednisolone pulse therapy and levetiracetam were initiated. EEG normalized prior to discharge, while significant memory deficits persisted. Patient was discharged in a stabilized condition on oral prednisolone taper and levetiracetam with follow-up neuroimaging and prolonged EEG monitoring scheduled.

This case illustrates that dual LGI1/CASPR2 autoimmune encephalitis can present with pure limbic encephalitis and predominant amnesia in a pediatric patient. This phenotype is unreported in published literature. Normal MRI did not exclude active limbic disease with electroclinically confirmed seizures. Comprehensive autoimmune testing, including testing for dual VGKC antibodies, should be considered for pediatric cases with subacute amnesia and new-onset seizures regardless of neuroimaging findings.