Anti-GABA_B receptor encephalitis

Anti-GABA_B (gamma aminobutyric acid-B) receptor encephalitis is an autoimmune disease mediated by GABA_B -related antibodies and often involves the limbic system. GABA is the major inhibitory neurotransmitter in the CNS. It is widely distributed in the brain and plays a principal role in reducing neuronal excitability throughout the CNS. There is evidence that disruption of the GABA_B-R structure and function can cause spontaneous seizures. In vitro studies have found that antibodies in the CSF of patients with anti- GABA_B receptor encephalitis can prevent the activation of the GABA_B receptor and block its function. The disease is linked to lung cancer, which requires long-term follow-up observation.

Anti-GABA_BR encephalitis affects mostly men, but it is seen in women also.

The onset of Anti-GABA_BR encephalitis is relatively sudden. Before disease onset, some patients might experience fever and non-specific respiratory symptoms. This type of AE presents with epilepsy, cognitive dysfunction, and mental behavioral abnormalities, and epilepsy is often the first symptom.

In a recent study (Zhu et al) it was found that 100% of the patients had epilepsy, with frequent attacks occurring up to four to five times/day. A majority of patients had mental behavioral abnormalities and character alterations. Mental behavioral abnormalities manifested as non-sensical and forced behaviors. Personality changes manifested as a loss of interest in things, a worsened temper, increased aggressive behaviors such as beating and scolding people, high emotional instability, and an increased tendency to become sad.

Antibodies (mainly IgG1) against GABA_B receptor are found in serum or CSF. In the majority of patients oligoclonal bands are found in the CSF and 24h IgG levels are increased in 92% of patients. EEG results often indicated slow waves, sharp waves, or spike waves in temporal areas. Brain MRI showed abnormalities in the medial temporal lobe, hippocampus, and amygdala.

Approximately 50% of patients are diagnosed with small cell lung cancer, and in rare cases, thymoma, malignant melanoma, breast carcinoma, and others have also been found.

Treatment consists of first-line immunotherapy (IVIG and corticosteroids) and treatment specific to the tumor, if present (chemotherapy and radiation therapy). Antiepileptic medicines are often part of a treatment plan.

The limited number of patients reported in literature have indicated that patients with anti-GABA_BR encephalitis can do well with immunotherapy, especially when no tumor is present or the tumor is treatable.

• Lancaster et al., Antibodies to the GABA(B) receptor in limbic encephalitis with seizures: case series and characterisation of the antigen, Lancet Neurology, 2010
• Zhu et al., Clinical Characteristics of Anti-GABA-B Receptor Encephalitis, Front Neurol. 2020
• Lin et al., Encephalitis With Antibodies Against the GABA_B Receptor: High Mortality and Risk Factors, Front Neurol. 2019
• McKay et al., A systematic review of Gamma-aminobutyric Acid Receptor Type B autoimmunity, Neurol Neurochir Pol, 2019
• Coevoorden-Hameete et al., The expanded clinical spectrum of anti-GABA_BR encephalitis and added value of KCTD16 autoantibodies, Brain 2019