Language impairments in seropositive and seronegative autoimmune encephalitis.

BACKGROUND AND OBJECTIVE: Autoimmune encephalitis (AE) is a rare neuroinflammatory disease affecting the central nervous system. To examine language functions in patients with different subsets of AE consisting of seropositive and seronegative groups. METHODS: Fifty-two patients were recruited from neurology departments in Melbourne, Australia, who met clinical criteria for possible AE. Language tests include the Naming Test from the Sydney Language Battery (SydBat), the semantic fluency trial from the Controlled Oral Word Association Test (COWAT), and the Vocabulary and Similarities subtests of the Weschler Abbreviated Scale of Intelligence-Second Edition. The results were standardised with normative data. RESULTS: The mean age of our cohort was 52.5 years old, with the average time from hospital admission to recruitment being 38.41 months. At an aggregate level, none of the mean language test z-scores were below normative data. At the patient level, impairment rates were 18.37% for COWAT (animals), 28.57% for SydBat (naming), 4.65% for Similarities, and 4.55% for Vocabulary. Chi-squared goodness of fit tests indicated that observed performances were significantly below expected performances for the SydBat (naming) test (p < 0.0001) and COWAT (animals) (p = 0.004). DISCUSSION: While, on average, language functions were within normal limits in patients with AE, but a subgroup exhibited lower performance in semantic fluency and visual confrontation naming, with impairment rates below expected norms. To advance understanding of language in chronic AE patients, exploring the impact of seizure burden, antiseizure medication use, and the relationship of language functions with other cognitive functions is crucial.

Neuropsychological outcomes of patients with haematological malignancies undergoing chimeric antigen receptor T-cell therapy: protocol for a prospective study.

Introduction: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common side-effect of chimeric antigen receptor T-cell (CAR-T) therapy, with symptoms ranging from mild to occasionally life-threatening. The neurological, cognitive, psychiatric and psychosocial sequelae of ICANS are diverse and not well defined, posing a challenge for diagnosis and management. The recovery trajectory of the syndrome is uncertain. Patients are rarely examined in this population pretherapy, adding a layer of complexity to specifying symptoms pertinent solely to CAR-T treatment. We present a protocol of a prospective longitudinal research study of adult patients in a single Australian haematology service undergoing CAR-T therapy. The study will describe neurocognitive features specific to ICANS, characterise the underlying syndrome, capture recovery, identify predictors of differential postinfusion outcomes and determine a set of cognitive instruments necessary to monitor patients acutely. Methods and analysis: This is a prospective longitudinal study that comprises neuropsychological and neurological examinations occurring prior to CAR-T, during the acute post-treatment period, 28 days, 6 months and 12 months post infusion. Data will be sourced from objective psychometric measures, clinical examinations, self-report questionnaires of psychopathology and accounts of subjective cognitive complaint. Ethics and dissemination: This study aims to guide diagnosis, management and monitoring of neurocognitive features of CAR-T cell therapy. Results of this study will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences. All procedures involving human subjects/patients were approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (21/145).

Verbosity with retelling: Narrative discourse production in temporal lobe epilepsy.

To examine micro- and macrolinguistic underpinnings of circumstantiality in temporal lobe epilepsy (TLE), we examined the elicited narrative output of 15 individuals with TLE and 14 controls. To replicate and extend Field and colleagues' (2000) work, participants were asked to produce five immediately consecutive elicitations of an eight-frame cartoon "Cowboy Story" (Joanette et al., 1986). Following transcription and coding, detailed multi-level discourse analysis demonstrated a typical pattern of compression in controls. The narratives produced by individuals with TLE were less fluent, cohesive, and coherent across trials: producing fewer novel units and more repetitive and extraneous content. Significant group by trial interactions in sample length, spontaneous duration, and statements, were not explained by seizure burden, age, or lexical retrieval deficits. These findings suggest that they do not benefit from repeated engagement with a narrative in the same manner as controls. Disturbed social cognition and pragmatics in TLE might underpin communication inefficiencies.

Vague retellings of personal narratives in temporal lobe epilepsy.

PURPOSE: Aside from deficits identified in single-word level retrieval, individuals with temporal lobe epilepsy (TLE) exhibit clinical oddities, such as circumstantiality in their language production. Circumstantiality refers to the use of language which is pedantic, repetitive, and overly detailed. This becomes particularly evident when elicitation tasks impose minimal structure, or when impersonal narratives are retold over consecutive occasions. Personal reminiscence is highly specific and localised in time, placing unique demands on cognitive-linguistic systems. It is hypothesised that the nature of this elicitation paradigm will produce a unique psycholinguistic phenotype in those with TLE. Among controls there is a compression of output for impersonal narratives, meaning that they use fewer words over less time and are more fluent. The opposite effect is observed when personal narratives are retold. METHODS: To investigate the micro- and macrolinguistic processes underpinning personal discourse production in TLE, we examined the elicited language output of 15 surgically naïve individuals with TLE and 14 healthy controls. Participants were asked to recall and re-tell an autobiographical memory on four immediately consecutive occasions, representing an alternative unstructured elicitation. Following transcription and coding of output, a detailed multi-level discourse analysis of output volume, fluency, cohesion, and coherence was conducted. RESULTS: As anticipated, a distinctly different pattern emerged in TLE when compared with controls who did not compress their output volume across repetitions but instead produced greater novelty, and a more coherent and refined account over time. Individuals with TLE consistently told a less distinct story across repetitions, with disturbances in fluency, cohesion, and coherence. CONCLUSION: This reflects a reduced capacity to produce a coherent mental representation, in all likelihood related to the neurolinguistic demands of recalling and retelling specific personal events.

Modelling the Anatomical Distribution of Neurological Events in COVID-19 Patients: A Systematic Review.

BACKGROUND: Neuropathology caused by the coronavirus disease 2019 (COVID-19) has been reported across several studies. The characterisation of the spatial distribution of these pathology remains critical to assess long and short-term neurological sequelae of COVID-19. To this end, Mathematical models can be used to characterise the location and aetiologies underlying COVID-19-related neuropathology. METHOD: We performed a systematic review of the literature to quantify the locations of small neurological events identified with magnetic resonance imaging (MRI) among COVID-19 patients. Neurological events were localised into the Desikan-Killiany grey and white matter atlases. A mathematical network diffusion model was then used to test whether the spatial distribution of neurological events could be explained via a linear spread through the structural connectome of the brain. FINDINGS: We identified 35 articles consisting of 123 patients that assessed the spatial distribution of small neurological events among COVID-19 patients. Of these, 91 patients had grey matter changes, 95 patients had white matter changes and 72 patients had confirmed cerebral microbleeds. White matter events were observed within 14 of 42 white matter bundles from the IIT atlas. The highest proportions (26%) of events were observed within the bilateral corticospinal tracts. The splenium and middle of the corpus callosum were affected in 14% and 9% of the cases respectively. Grey matter events were spatially distributed in the 41 brain regions within the Desikan-Killiany atlas. The highest proportions (∼10%) of the events were observed in areas including the bilateral superior temporal, precentral, and lateral occipital cortices. Sub-cortical events were most frequently identified in the Pallidum. The application of a mathematical network diffusion model suggested that the spatial pattern of the small neurological events in COVID-19 can be modelled with a linear diffusion of spread from epicentres in the bilateral cerebellum and basal ganglia (Pearson's r =0.41, p <0.001, corrected). INTERPRETATION: To our knowledge, this is the first study to systematically characterise the spatial distribution of small neurological events in COVID-19 patients and test whether the spatial distribution of these events can be explained by a linear diffusion spread model. The location of neurological events is consistent with commonly identified neurological symptoms including alterations in conscious state among COVID-19 patients that require brain imaging. Given the prevalence and severity of these manifestations, clinicians should carefully monitor neurological symptoms within COVID-19 patients and their potential long-term sequelae .