From the Guidelines
GAD positive encephalopathy should be treated with aggressive immunotherapy, starting with high-dose corticosteroids and intravenous immunoglobulin (IVIG), to prevent permanent neuronal damage and improve outcomes. GAD positive encephalopathy is an autoimmune neurological condition where antibodies target glutamic acid decarboxylase (GAD), an enzyme involved in producing the inhibitory neurotransmitter GABA. Treatment typically involves immunotherapy, starting with high-dose corticosteroids such as methylprednisolone 1000mg IV daily for 3-5 days, followed by oral prednisone taper over several weeks, as suggested by studies on neuronal surface antibody associated syndromes 1. Intravenous immunoglobulin (IVIG) at 2g/kg divided over 2-5 days is often added as first-line therapy. For refractory cases, plasma exchange (5-7 exchanges over 10-14 days) or rituximab (375mg/m² weekly for 4 weeks) may be necessary. Long-term immunosuppression with mycophenolate mofetil (starting at 500mg twice daily, increasing to 1000-1500mg twice daily) or azathioprine (1-3mg/kg/day) is typically required for maintenance therapy. It's worth noting that the pathogenic role of GAD antibodies is not entirely clear, as they are directed against an intracellular antigen, and T cell cytotoxicity may also contribute to the neuronal cell loss 1. Symptomatic treatment with antiseizure medications like levetiracetam or lamotrigine may be needed for seizures, and benzodiazepines for anxiety or muscle spasms. Early aggressive treatment improves outcomes as GAD antibodies can cause permanent neuronal damage if left untreated. Regular monitoring of neurological symptoms, antibody titers, and medication side effects is essential, with treatment adjustments based on clinical response.
Some key points to consider in the treatment of GAD positive encephalopathy include:
- The importance of early aggressive treatment to prevent permanent neuronal damage
- The use of high-dose corticosteroids and IVIG as first-line therapy
- The potential need for plasma exchange or rituximab in refractory cases
- The importance of long-term immunosuppression for maintenance therapy
- The need for regular monitoring of neurological symptoms, antibody titers, and medication side effects.
From the Research
GAD Positive Encephalopathy
- GAD positive encephalopathy is a condition associated with antibodies against glutamic acid decarboxylase (GAD) 2, 3, 4, 5.
- The condition can present with a range of neurological symptoms, including seizures, encephalopathy, and cerebellar ataxia 2, 3, 4, 5.
- Diagnosis can be challenging, and the condition may be mistaken for other encephalopathies, such as herpes encephalitis or Hashimoto's encephalitis 3.
- Treatment with immunotherapy, including intravenous immunoglobulin (IVIG), high-dose corticosteroids, and plasmapheresis, can be effective in reducing symptoms and improving outcomes 2, 4, 5.
- In some cases, treatment with tocilizumab may be necessary to achieve significant clinical improvement 2.
Clinical Features
- Seizures are a common presenting feature of GAD positive encephalopathy, and can be refractory to treatment with conventional antiseizure medication 2, 3, 4, 5.
- Encephalopathy, characterized by altered mental status and cognitive impairment, is also a common feature of the condition 2, 3, 5.
- Cerebellar ataxia, characterized by gait disturbance, dysmetria, and nystagmus, can also occur in patients with GAD positive encephalopathy 4.
Treatment Outcomes
- Treatment with immunotherapy can lead to significant improvement in symptoms, including reduction in seizure frequency and improvement in cognitive function 2, 4, 5.
- Long-term follow-up has shown that patients with GAD positive encephalopathy can experience sustained improvement in symptoms and quality of life with ongoing immunosuppressive treatment 5.
- However, some patients may experience a decline in efficacy of treatment over time, highlighting the need for ongoing monitoring and adjustment of treatment as needed 4.