Clinical Determinants of Longitudinal Disability in LGI-1-IgG Autoimmune Encephalitis

Abstract

Background and objectives: Longitudinal outcome studies in leucine-rich glioma inactivated-1 (LGI-1) immunoglobulin G (IgG) autoimmune encephalitis (AE) are needed to inform clinical management and prognostication. This study aims to evaluate longitudinal predictors of disability and disease severity in LGI-1-IgG AE.

Methods: This retrospective observational study of patients with LGI-1-IgG AE was conducted between 2013-2022. Disability and disease severity were defined by scores on the modified Rankin Scale (mRS) and the clinical assessment scale in AE (CASE), respectively. Demographic variables, clinical/paraclinical data, brain MRI, and Montreal Cognitive Assessment (MOCA) scores were examined as predictors of mRS and CASE scores in logistic and linear regression models, respectively.

Results: Thirty patients (60% male, median age = 68.5; interquartile range (IQR) = 63.0-75.0) were included, with a median follow-up time of 19.1 months (IQR = 5.3-47.1) The majority developed seizures (29, [97%]) and/or cognitive impairment (30, [100%]) and received acute (27, [90%]) and maintenance (23 [77%]) immunotherapy. The median initial MOCA was 23/30 (IQR = 21.0-25.0). Baseline mRS (median = 2.0, IQR = 2.0-3.0) and CASE (mean = 4.3, SD = 3.7) correlated with one another (r = 0.58, p < 0.001) and with initial MOCA score (mRS r = -0.60, p = 0.012; CASE r = -0.56, p = 0.021) After 12 months from symptom onset, mRS (OR = 0.88, [95% CI = 0.82-0.94], p < 0.001) and CASE (β = -0.03, [SE = 0.01], p < 0.001) improved significantly. Lower initial MOCA score (OR = 0.68, 95% CI = 0.47-0.98, p = 0.041) and temporal lobe(s) T2 hyperintensity (OR = 16.50, 95% CI = 2.29-119.16, p = 0.006) were associated with higher mRS longitudinally. At last follow-up, most patients had persistent memory dysfunction (25, [83%]) while few had ongoing seizure activity (3, [10%]).

Discussion: Overall, there was a high degree of correlation between mRS and CASE scores in patients with LGI-1-IgG AE, with both scores improving significantly after 12 months. Memory dysfunction and psychiatric disturbance were the most prevalent longitudinal symptoms. Cognitive impairment and temporal lobe T2 hyperintensity at baseline were both associated with greater disability at long-term follow-up, underscoring these as important determinants of disability outcomes in LGI-1-IgG AE.