From the Research
Autoimmune encephalopathy associated with glutamic acid decarboxylase (GAD) antibodies typically follows a subacute to chronic course, developing over weeks to months rather than hours to days. The condition often presents with progressive neurological symptoms including cognitive impairment, seizures, memory problems, and psychiatric manifestations. First-line treatment involves immunotherapy with intravenous methylprednisolone (1000 mg daily for 3-5 days) followed by oral prednisone (starting at 1 mg/kg/day with gradual taper over months) as shown in a case report where a patient was treated with high-dose methylprednisolone and returned to baseline mental status 1. If response is inadequate, intravenous immunoglobulin (IVIG) at 2 g/kg divided over 2-5 days may be added. For refractory cases, rituximab (375 mg/m² weekly for 4 weeks or 1000 mg given twice, two weeks apart) or cyclophosphamide may be necessary. Treatment response varies significantly between patients, with some showing rapid improvement within weeks while others require months of therapy or develop a chronic course requiring maintenance immunosuppression. Early treatment initiation is associated with better outcomes, as prolonged immune activation can lead to irreversible neuronal damage, and the clinical characteristics of GAD 65-associated autoimmune encephalitis include chronic epilepsy, cerebellar ataxia, stiff-person syndrome, and limbic encephalitis, often combined with thyroid autoimmune diseases, type 1 diabetes, and thymoma 2. Regular monitoring of neurological function and antibody titers helps guide treatment duration, which typically continues for at least 6-12 months with careful tapering to prevent relapse. Some studies suggest that GAD autoimmunity might primarily be cell-mediated, and diagnosis relies on the detection of high titers of GAD Ab in serum and/or in the detection of GAD Ab in the cerebrospinal fluid 3. Key points to consider in the management of autoimmune encephalopathy associated with GAD antibodies include:
- Early recognition and diagnosis
- Prompt initiation of immunotherapy
- Monitoring of treatment response and adjustment of therapy as needed
- Regular follow-up to prevent relapse and manage chronic symptoms. The most recent and highest quality study on this topic is from 2021, which highlights the importance of considering a diagnosis of autoimmune encephalitis for patients with rapidly deteriorating mental status and the potential success of treatment with high-dose glucocorticoids 1.