Long-term cognitive and neuropsychiatric outcomes of anti-GABA_BR encephalitis patients: A prospective study

Highlights

• Most patients with anti-GABA_BR encephalitis had residual cognitive deficits and NPSes.

• Cognitive deficits occurred in memory, executive function and nonverbal reasoning.

• Age of disease onset ≥45 years was a risk factor for long-term cognitive deficits.

Abstract

Long-term cognitive and neuropsychiatric outcomes of anti-gamma-aminobutyric-acid B receptor (anti-GABA_BR) encephalitis are unclear. In this prospective study, 31 patients with anti-GABA_BR encephalitis were underwent cognitive and neuropsychiatric evaluations every 6 months. At 24 months' follow-up, cognitive impairments were observed in 80% of patients that mainly included deficits in memory, executive functions and nonverbal reasoning; and neuropsychiatric symptoms were observed in 50% of patients that mainly included depressive symptoms and irritation. The risk factors associated with cognitive deficits was age > 45 years. This study demonstrated that most patients with anti-GABA_BR encephalitis had persistent cognitive deficits and neuropsychiatric symptoms.

Introduction

Anti-gamma-aminobutyric-acid B receptor (anti-GABA_BR) encephalitis, which was first described by Lancaster et al. in 2010, is a rare type of autoimmune encephalitis (AE) (Lancaster et al., 2010). Different types of AE have different clinical characteristics and prognoses (Yao et al., 2019). Compared to other types of AE, patients with anti-GABA_BR encephalitis have a poorer long-term functional prognosis (Yao et al., 2019). Previous studies showed that the fatality rate of anti-GABA_BR encephalitis (22–45%) (van Coevorden-Hameete et al., 2019; Guan et al., 2015; Hoftberger et al., 2013; Lancaster et al., 2010; Lin et al., 2019; Maureille et al., 2019; Onugoren et al., 2015) was significantly higher than that of anti-leucine-rich glioma-inactivated protein-1 (anti-LGI1) encephalitis (6–19%) (Arino et al., 2016; Lai et al., 2010; van Sonderen et al., 2016) and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis (2–11%) (Chi et al., 2017; Titulaer et al., 2013a; Titulaer et al., 2013b; Xu et al., 2020). Several studies reported prolonged cognitive impairments and neuropsychiatric problems in patients with anti-NMDAR encephalitis anti-LGI1 encephalitis (Arino et al., 2016; de Bruijn et al., 2018; Finke et al., 2012; van Sonderen et al., 2016). However, it is unclear whether anti-GABA_BR encephalitis shares these features.

GABA_B receptors are G-protein-coupled receptors that are composed of GABA_B1 and GABA_B2 subunits (Enna and Bowery, n.d.). GABA_B receptors are mainly distributed in the hippocampus, frontal cortex, thalamus and cerebellum. It has been reported that GABA_BR dysfunction is associated with spontaneous seizures, memory impairment, executive dysfunction, learning impairments, depression and anxiety (Gassmann et al., 2004; Kitamura et al., 2009; Sibbe and Kulik, 2017; Wang et al., 2013). Although several reports suggest that cognitive impairments (67%–100% of patients previously reported) and psychiatric behavior changes (61%–100% of patients previously reported) almost always occur at disease onset, long-term cognitive and neuropsychiatric recovery are poorly understood (Guan et al., 2015; Lancaster et al., 2010; Maureille et al., 2019). Furthermore, prospective studies on long-term cognitive and neuropsychiatric outcomes are still lacking. Here, for the first time, we performed a prospective follow-up study to evaluate the long-term cognitive and neuropsychiatric outcomes in a series of Chinese patients with anti-GABA_BR encephalitis and to identify the potential factors affecting cognitive and neuropsychiatric outcomes.