A Tale of Two Brothers: Familial Voltage-Gated Potassium Channel Autoimmune Encephalitis

This is the first reported case of familial voltage-gated potassium channel (VGKC) autoimmune encephalitis. The symptoms of autoimmune encephalitis can mimic infectious encephalitis with headache, fatigue, and neuropsychiatric symptoms. Autoimmunity is emerging as a distinct cause of encephalitis in the children. Prompt recognition, diagnosis, and treatment are important to prevent brain damage. Two brothers presented two years apart with different symptoms. The explanation for their distinct symptoms lies in the multifactorial development of autoimmunity. The presentation of autoimmune encephalitis can depend on the offending antibodies. The most common are antibodies against the N-methyl-D-aspartic acid (NMDA) receptor and the VGKC complex. Antibodies to the VGKC complex are divided into three different groups depending on their antigenic target: leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), or neither. Anti-VGKC antibodies in children are associated with neuroinflammation and encephalitis. Autoimmunity to LGI1 and CASPR2 antigens is associated with distinct human leukocyte antigen (HLA) alleles. Different HLA isotypes are involved in antigen processing and presentation and can lead to a genetic predisposition to autoimmunity. VGKC autoimmune encephalitis can present with memory changes, psychiatric symptoms, and motor abnormalities. Both brothers presented with these symptoms in their own unique way. Efficient diagnosis and immunosuppression helped improve their outcomes.

Keywords: autoimmune; autoimmune encephalitis; caspr2; channelopathies; encephalitis; lgi1; neuroimmunology; vgkc; vgkc encephalitis; voltage-gated potassium channel autoimmune encephalitis.