Objective:

To describe the clinical course, diagnostic findings, and therapeutic challenges in a patient with KLHL11 antibody-associated autoimmune encephalitis complicated by refractory focal epilepsy and focal status epilepticus. 

Background:

KLHL11 antibody-associated encephalitis is a rare paraneoplastic syndrome, typically linked to germ cell tumors, often presenting with brainstem or limbic encephalitis, cognitive decline, and seizures. Management is challenging, especially in cases with persistent seizure activity despite immunotherapy and anti-seizure polytherapy. This report highlights a diagnostically and therapeutically complex case with recurrent encephalitis and drug-resistant seizures.

Design/Methods:

A retrospective case review of a 47-year-old male with KLHL11 antibody-positive autoimmune encephalitis, previously treated with IVIG, who presented with focal neurological deficits and language impairment. Clinical findings, imaging, EEG, laboratory evaluations, and treatment course were reviewed. Immunologic and oncologic evaluations were also undertaken to exclude recurrent malignancy or systemic inflammation. 

Results:

The patient was found to have electroclinical seizures with focal status epilepticus despite extensive anti-seizure medication (ASM) therapy, including brivaracetam, lacosamide, valproic acid, phenobarbital, cenobamate, perampanel, and clobazam. Imaging showed new right temporal lobe and insular T2/FLAIR hyperintensities, raising concern for recurrent autoimmune encephalitis. EEG revealed frequent right posterior quadrant focal seizures. Rituximab was initiated due to recurrence of symptoms and failure of prior IVIG therapy. Clinical improvement was initially observed, but the patient experienced subsequent neurological deterioration with focal status epilepticus requiring ICU care and further optimization of immunotherapy and ASM regimen.

Conclusions:

This case illustrates the recurrent and refractory nature of KLHL11 antibody-associated autoimmune encephalitis, particularly when complicated by drug-resistant epilepsy. Early recognition of recurrence and escalation of immunotherapy, including rituximab, may be necessary in managing such cases. Comprehensive neurologic, immunologic, and oncologic evaluations are essential to guide ongoing therapy and improve clinical outcomes.