Psychometric deficits in autoimmune encephalitis: A retrospective study from the Australian Autoimmune Encephalitis Consortium.

BACKGROUND AND PURPOSE: Despite the rapid increase in research examining outcomes in autoimmune encephalitis (AE) patients, there are few cohort studies examining cognitive outcomes in this population. The current study aimed to characterise psychometric outcomes in this population, and explore variables that may predict psychometric outcomes. METHODS: This retrospective observational study collected psychometric data from 59 patients across six secondary and tertiary referral centres in metropolitan hospitals in Victoria, Australia between January 2008 and July 2019. Frequency and pattern analysis were employed to define and characterize psychometric outcomes. Univariable logistic regression was performed to examine predictors of intact and pathological psychometric outcomes. RESULTS: Deficits in psychometric markers of executive dysfunction were the most common finding in this cohort, followed by deficits on tasks sensitive to memory. A total of 54.2% of patients were classified as having psychometric impairments across at least two cognitive domains. Twenty-nine patterns were observed, suggesting outcomes in AE are complex. None of the demographic data, clinical features or auxiliary examination variables were predictors of psychometric outcome. CONCLUSIONS: Cognitive outcomes in AE are complex. Further detailed and standardized cognitive testing, in combination with magnetic resonance imaging volumetrics and serum/cerebrospinal fluid biomarkers, is required to provide rigorous assessments of disease outcomes.

Exploring the Semantic Structure of WMS-IV Verbal Paired Associates using the Hub-and-Spoke Model.

OBJECTIVES: This study aimed to identify a well-fitting and theoretically justified item-level latent factor structure for the Wechsler Memory Scales (WMS)-IV verbal paired associates (VerbalPA) subtest to facilitate the ease and accuracy of score interpretations for patients with lateralized temporal lobe epilepsy (TLE). METHODS: Archival data were used from 250 heterogeneous neurosciences patients who were administered the WMS-IV as part of a standard neuropsychological assessment. Three theoretically motivated models for the latent structure of VerbalPA were tested using confirmatory factor analysis. The first model, based on cognitive principles of semantic processing from hub-and-spoke theory, tested whether performance is related to specific semantic features of target words. The second, motivated by the Cattell-Horn-Carroll (CHC) model of cognitive abilities, investigated whether the associative properties of items influence performance. A third, Hybrid model tested whether performance is related to both semantic and associative properties of items. The best-fitting model was tested for diagnostic group effects contrasting the heterogeneous neuroscience patients with subsets of left and right TLE (n = 51, n = 26, respectively) patients. RESULTS: The Hybrid model was found to have the best fit. Patients with left TLE scored significantly less well than the heterogeneous neurosciences sample on selected semantic factor scores, although the effect size was small. CONCLUSIONS: Future editions of the WMS may consider implementing a semantic scoring structure for the VerbalPA to facilitate test score interpretation. Additionally, these results suggest that principles of hub-and-spoke theory may be integrated into CHC cognitive ability taxonomy.

Latent Semantic Structure of the WMS-III Verbal Paired-Associates.

OBJECTIVE: To investigate the factor structure of the verbal paired-associates (VPA) subtest in the WMS-III using a theoretically driven model of semantic processing previously found to be well-fitting for the WMS-IV version of the test. METHOD: Archival data were used from 267 heterogeneous neurosciences patients and 223 seizure disorder patients who completed the WMS-III as part of a standard neuropsychological evaluation. Confirmatory factor analysis was used to test theoretically driven models for VPA based on principles of semantic processing. Four nested models of different complexities were examined and compared for goodness-of-fit using chi-squared difference testing. Measurement invariance testing was conducted across heterogeneous neuroscience and seizure disorder samples to test generality of the factor model. RESULTS: After removing items with limited variability (very easy or very hard; 12 of 40 items), a four-factor model was found to be best-fitting in the present patient samples. The four factors were "recreational", "functional", "material", and "symbolic", each representing semantic knowledge associated with the function of the target word referent. This model subsequently met the criteria for the strict measurement invariance, showing good overall fit when factor loadings, thresholds, and residuals were held to equality across samples. CONCLUSIONS: The results of this study provide further evidence that "arbitrary" associations between word pairs in VPA items have an underlying semantic structure, challenging the idea that unrelated hard-pairs are semantic-free. These results suggest that a semantic-structure model may be implemented as an alternative scoring in future editions of the WMS to facilitate interpretation.

Comparative Utility of Manual versus Automated Segmentation of Hippocampus and Entorhinal Cortex Volumes in a Memory Clinic Sample.

Structural neuroimaging is a useful non-invasive biomarker commonly employed to evaluate the integrity of mesial temporal lobe structures that are typically compromised in Alzheimer's disease. Advances in quantitative neuroimaging have permitted the development of automated segmentation protocols (e.g., FreeSurfer) with significantly increased efficiency compared to earlier manual techniques. While these protocols have been found to be suitable for large-scale, multi-site research studies, we were interested in assessing the practical utility and reliability of automated FreeSurfer protocols compared to manual volumetry on routinely acquired clinical scans. Independent validation studies with newer automated segmentation protocols are scarce. Two FreeSurfer protocols for each of two regions of interest-the hippocampus and entorhinal cortex-were compared against manual volumetry. High reliability and agreement was found between FreeSurfer and manual hippocampal protocols, however, there was lower reliability and agreement between FreeSurfer and manual entorhinal protocols. Although based on a the relatively small sample of subjects drawn from a memory clinic (n = 27), our study findings suggest further refinements to improve measurement error and most accurately depict true regional brain volumes using automated segmentation protocols are required, especially for non-hippocampal mesial temporal structures, to achieve maximal utility for routine clinical evaluations.

Specificity of psychopathology in temporal lobe epilepsy.

An investigation into the specificity of psychopathology in temporal lobe epilepsy was conducted using the Minnesota Multiphase Personality Inventory second edition (MMPI-2) profiles. Consecutive series of patients with left temporal lobe epilepsy (n = 49) and those with right temporal lobe epilepsy (n = 45) were compared with patients with other forms of epilepsy (n = 46) and other heterogeneous neurological conditions (n = 69). The investigation focused on the Clinical, Content, and Subscales scales that resembled descriptions of the Interictal Dysphoric Disorder symptoms and Temporal Lobe Epilepsy Personality Traits. Patients with right temporal lobe epilepsy and those with left temporal lobe epilepsy did not have different patterns of scale elevation, nor did they have clinical elevations compared with patients with other types of epilepsy or neurological controls. The MMPI-2 scales that resemble descriptions of the Interictal Dysphoric Disorder or Temporal Lobe Epilepsy Personality Syndrome were not elevated in either group of patients with temporal lobe epilepsy compared with the group of patients with non-temporal lobe epilepsy or heterogeneous neurological controls. This study adds to the mounting body of empirical research that has used standardized measures and matched groups, but failed to detect a special affinity between psychopathology and temporal lobe epilepsy.

Exploring the dimensionality of digit span.

The Digit Span subtest from the Wechsler Scales is used to measure Freedom from Distractibility or Working Memory. Some published research suggests that Digit Span forward should be interpreted differently from Digit Span backward. The present study explored the dimensionality of the Wechsler Memory Scale-III Digit Span (forward and backward) items in a sample of heterogeneous neuroscience patients (n = 267) using confirmatory factor analysis (CFA) for dichotomous items. Results suggested that four correlated factors underlie Digit Span, reflecting easy and hard items in both forward and backward presentation orders. The model for Digit Span was then cross-validated in a seizure disorders sample (n = 223) by replication of the CFA and by examination of measurement invariance. Measurement invariance tests of the precise numerical generalization of trait estimation across groups. Results supported measurement invariance and it was concluded that forward and backward digit span scores should be interpreted as measures of the same cognitive ability.

Rhinal cortex asymmetries in patients with mesial temporal sclerosis.

PURPOSE: The rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices, is one component of the limbic system that may be affected in patients with epilepsy and other temporal lobe pathologies. This study extended quantitative examination of the limbic system through development and validation of volumetric protocols to measure the ErC and PrC. METHODS: Volumes were calculated from MRI studies using ANALYZE 7.5 and based on detailed anatomical definitions developed for the study. Subjects were 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS: 33 left, 28 right) and 20 neurologically normal controls. Inter-rater reliabilities for the ErC and PrC volume protocols were found to be high (range 0.86-0.92). RESULTS: Ipsilateral hippocampal volume was reduced in patients with MTS, while contralateral volume did not differ significantly from controls. In the patients, rhinal cortex volumes were reduced as a function of laterality of disease. The pattern of correlations between ErC and PrC differed between disease groups. Hippocampal and rhinal cortex volumes were not significantly correlated. A significant four-way interaction was found between side of MTS, hemisphere, structure and handedness. CONCLUSIONS: This quantitative study demonstrates reliable in vivo evidence of morphometric changes in ErC and PrC in a substantial number of patients with unilateral MTS. The relationship observed between handedness, structure and disease status may suggest a role for cerebral dominance in modulating the expression of MTS.