Neuropsychological and psychiatric outcomes in encephalitis: A multi-centre case-control study

Abstract

Objectives: Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and encephalitis of unknown cause (Unknown).

Methods: Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments.

Results: Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved.

Conclusions: Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes.

Fig 1. Flowchart to outline the details of the recruitment process of patients with encephalitis into the short- and medium-term and long-term outcome cohorts, and of healthy controls.

Fig 2. Mean anterograde memory scores for each aetiological group (Doors & People test).

The error bars represent the standard deviation of the mean score within each group. (a) At the short-term assessment, a mean of 4 months post-discharge (in the short- and medium-term outcome cohort) and (b) at the long-term assessment, at least 1 year post-discharge (in the long-term outcome cohort). Notations: *p≤0.05, **p≤0.01; † Hochberg GT2/Games-Howell post hoc (parametric); ▪Bonferroni-corrected pairwise analysis (ANCOVA post hoc). ◊ Mann Whitney U post hoc (non-parametric).

Fig 3. Subjective cognitive complaints for each group (ABNAS subscale scores).

The error bars represent the standard deviation of the mean score within each group. (a) At the short-term assessment, a mean of 4 months post-discharge (in the short- and medium-term outcome cohort) and (b) at the long-term assessment, at least 1-year post-discharge (in the long-term outcome cohort). Notations: For main analyses of subscales (all Kruskal Wallis), significance is labelled adjacent to the subscale name along the x-axis, alpha p = 0.05, * p ≤ 0.05, ** p ≤ 0.01; For the breakdown of main analyses using Mann Whitney U post hoc, significance is labelled adjacent to data points within the figure, corrected alpha p = 0.02, * p ≤ 0.02, ** p ≤ 0.01, ^ trending significance (p = 0.03); Abbreviations: ABNAS (A-B Neuropsychological Assessment Schedule).