Cognitive and psychopathological outcomes in acute disseminated encephalomyelitis.

Individuals with acute disseminated encephalomyelitis (ADEM) can experience persistent cognitive deficits and psychopathology, which significantly interferes with daily functioning and quality of life. Here, we review the current literature to characterise the cognitive and psychological sequelae, suggest avenues for further research and discuss the implications for clinical practice. Research on this topic is largely limited to the paediatric population with a few case studies in the adult population. The current evidence demonstrates persistent cognitive deficits in attention and information processing speed, as well as elevated symptoms of depression and anxiety. Results are mixed for executive functions and memory, while language and visuospatial functions are relatively undisturbed. There is emerging evidence to suggest that individuals-particularly children-with ADEM experience persistent cognitive deficits and suffer from elevated symptoms of depression and anxiety. Comprehensive neuropsychological assessments are recommended to guide intervention and monitor progress. Further research is required to clarify our understanding of the cognitive and psychological outcomes following ADEM and the factors that influence them.

Cognitive and psychopathological features of neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease: A narrative review.

Clinicians are becoming increasingly aware of the cognitive and psychopathological consequences of neurological diseases, which were once thought to manifest with motor and sensory impairments only. The cognitive profile of multiple sclerosis, in particular, is now well-characterised. Similar efforts are being made to better characterise the cognitive profile of other central nervous system inflammatory demyelinating autoimmune disorders. This review discusses the current understanding of the cognitive and psychological features of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Detailed analysis of the cognitive sequelae of the above conditions can not only assist with understanding disease pathogenesis but also can guide appropriate management of the symptoms and consequently, improve the quality of life and long-term outcomes for these patients. This narrative review will also identify research gaps and provide recommendations for future directions in the field.

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.

Characterizing cognitive function in patients with autoimmune encephalitis: an Australian prospective study.

OBJECTIVE: This study uses the Wechsler intelligence and memory scales to characterize the cognitive function of patients with autoimmune encephalitis (AE) in the chronic stage of the disease. AE is a group of neuroinflammatory disorders, and cognitive impairment is a significant source of chronic morbidity in these patients. METHODS: Fifty patients with an average disease duration of 3.2 years after diagnosis were prospectively recruited from four hospitals. They underwent a comprehensive cognitive examination using the Wechsler Abbreviated Scale of Intelligence (WASI-II), Wechsler Adult Intelligence Scale (WAIS-IV) and Wechsler Memory Scale (WMS-IV). Summary statistics were computed, and single-sample and independent-samples t tests were used to compare the cohort to normative data. RESULTS: The results revealed significantly reduced performances in perceptual reasoning, processing speed, and working memory among AE patients. Seropositive AE patients exhibited below-norm processing speed, while the seronegative group showed reduced working memory and processing speed. Delayed memory performance was significantly below expectations only in seronegative patients. Pattern analysis indicated that intact cognition was the most observed outcome after AE, but significant heterogeneity was observed among the impaired patients. CONCLUSIONS: The study identified deficits in perceptual reasoning, processing speed, and working memory among chronic AE patients. Pattern analysis highlighted positive long-term cognitive outcomes for many but varied outcomes for those with ongoing difficulties. Although severely cognitively impaired patients were not included, the findings apply to  AE cohorts who attend outpatient clinical neuropsychology consultations emphasizing the need for thorough cognitive assessment. The results suggest a need for further research targeting other cognitive domains, including executive functions.

Content or context? A study protocol for a three-arm parallel randomised controlled trial of Re-PROGRAM, a brief internet-based intervention for patients with functional seizures.

INTRODUCTION: Functional seizures (FS) mimic epilepsy but are not caused by epileptic electrical activity in the brain and are believed to have a psychological origin. There is a well-documented gap between the needs of patients with FS and available therapeutic resources. While there is potential for reducing seizure burden in patients via psychosocial intervention, there is no evidence-based care pathway or consistent availability of treatment and no effective pharmacological treatment. The objective of this study is to investigate the clinical efficacy and tolerability of a novel internet-based intervention in reducing seizure frequency. METHODS AND ANALYSIS: A 3-arm parallel randomised controlled trial will compare the efficacy of brief guided internet-based therapy to unguided internet-based therapy and to standard care. Approximately 100 participants with FS will be recruited, with diagnostic criteria based on gold standard video-electroencephalogram (v-EEG) monitoring; patients will be randomly assigned to one of the three study arms. The primary study outcome will be FS frequency at 6 weeks and at follow-up (6 and 12 months) compared with baseline. Seizure frequency will be modelled using Poisson regression. Secondary outcomes include psychosocial functioning, healthcare resource usage, anxiety, depression, somatisation and life impact. Between-group differences will be evaluated using analysis of variance. Analysis of covariance will estimate within-group changes on secondary outcomes. Cognitive and psychological factors will be used as predictors of seizure reduction in exploratory analyses. A qualitative survey using a semi-structured interview will use thematic analyses to explore participants' treatment experiences, their impressions of FS management and perceived mechanisms for change. ETHICS AND DISSEMINATION: The study was approved by the Human Research and Ethics Committee of the Alfred Hospital Human Research Ethics Committee as part of the Australian Multisite Ethics approval system. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000262707.

Cognition following chimeric antigen receptor T-cell therapy: A systematic review.

BACKGROUND: This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. METHODS: A systematic search of the literature was performed using PubMed, PsycINFO, SCOPUS, EMBASE, Medline, and CINAHL (February 2023). Risk of bias was assessed using the JBI Checklist for Case Reports and the Risk of Bias Assessment Tool for Non-randomised Studies. RESULTS: Twenty-two studies met inclusion criteria with a total of 1104 participants. There was considerable methodological heterogeneity with differing study designs (e.g., cohort studies, clinical trials, case studies, a qualitative interview, and a focus group), measures of cognition (e.g., self-report, neuropsychological measures, clinician assessed/neurological examinations), and longest follow-up time points (i.e., five days to five years). DISCUSSION: Results of the studies were heterogenous with studies demonstrating stable, improved, or reduced cognition across differing time points. Overall, cognitive symptoms are common particularly in the acute stage (<2 weeks) post-infusion. Most deficits that arise in the acute stage resolve within one to two weeks, however, there is a subset of patients who continue to experience and self-report persistent deficits in the subacute and chronic stages. Future studies are needed to comprehensively analyse cognition using a combination of self-report and psychometric measures following chimeric antigen receptor T-cell therapy in the acute, subacute, and chronic settings.

An international survey of SEEG cortical stimulation practices.

OBJECTIVE: Cortical stimulation is an important component of stereoelectroencephalography (SEEG). Despite this, there is currently no standardized approach and significant heterogeneity in the literature regarding cortical stimulation practices. Via an international survey of SEEG clinicians, we sought to examine the spectrum of cortical stimulation practices to reveal areas of consensus and variability. METHODS: A 68-item questionnaire was developed to understand cortical stimulation practices including neurostimulation parameters, interpretation of epileptogenicity, functional and cognitive assessment and subsequent surgical decisions. Multiple recruitment pathways were pursued, with the questionnaire distributed directly to 183 clinicians. RESULTS: Responses were received from 56 clinicians across 17 countries with experience ranging from 2 to 60 years (M = 10.73, SD = 9.44). Neurostimulation parameters varied considerably, with maximum current ranging from 3 to 10 mA (M = 5.33, SD = 2.29) for 1 Hz and from 2 to 15 mA (M = 6.54, SD = 3.68) for 50 Hz stimulation. Charge density ranged from 8 to 200 µC/cm2 , with up to 43% of responders utilizing charge densities higher than recommended upper safety limits, i.e. 55 µC/cm2 . North American responders reported statistically significant higher maximum current (P < 0.001) for 1 Hz stimulation and lower pulse width for 1 and 50 Hz stimulation (P = 0.008, P < 0.001, respectively) compared to European responders. All clinicians evaluated language, speech, and motor function during cortical stimulation; in contrast, 42% assessed visuospatial or visual function, 29% memory, and 13% executive function. Striking differences were reported in approaches to assessment, classification of positive sites, and surgical decisions guided by cortical stimulation. Patterns of consistency were observed for interpretation of the localizing capacity of stimulated electroclinical seizures and auras, with habitual electroclinical seizures induced by 1 Hz stimulation considered the most localizing. SIGNIFICANCE: SEEG cortical stimulation practices differed vastly across clinicians internationally, highlighting the need for consensus-based clinical guidelines. In particular, an internationally standardized approach to assessment, classification, and functional prognostication will provide a common clinical and research framework for optimizing outcomes for people with drug-resistant epilepsy.

Improving the treatment of functional seizures through a public specialist outpatient clinic.

OBJECTIVES: We performed an audit of the first 12 months of clinical operations to assess the feasibility of a newly established public outpatient clinic for the assessment and treatment of functional (psychogenic nonepileptic) seizures (FS). METHOD: Clinical notes for the first 12 months of the FSclinic weresystematicallyreviewed with data compiled onreferral pathways, clinic attendance, clinical features, treatments, and outcomes. RESULTS: Of eighty-two new FS patients referred to the clinic, over 90% attended. Patients were diagnosed with FS after comprehensive epileptological and neuropsychiatric review, mostly with typical seizure-like episodes captured during video-EEG monitoring, and most accepted the diagnosis. Most had FS at least weekly, with little sense of control and significant impairment. The majority of individuals had significant psychiatric and medical comorbidity. Predisposing, precipitating, and perpetuating factors were readily identified in >90% of cases. Of 52 patients with follow-up data within12 months, 88% were either stable or improved in terms of the control of their FS. CONCLUSION: The Alfred functional seizure clinic model, the first dedicated public outpatient clinic for FS in Australia, provides a feasible and potentially effective treatment pathway for this underserved and disabled patient group.

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.

The neuropsychological spectrum of anti-LGI1 antibody mediated autoimmune encephalitis.

Anti-Leucine Glioma Inactivated 1 (LGI-1) autoimmune encephalitis (AE) is a rare neuroinflammatory brain condition. Individuals afflicted with this condition can present with cognitive and psychological manifestations that can impact the individual's quality of life, day to day functioning, independence, return to work and interpersonal relationships. Our knowledge of the cognitive profiles and disease associated psychopathology is severely lacking. This review provides a comprehensive summary of the currently available literature, conceptualising our current understanding of the neuropsychological manifestations of anti LGI-1 AE and summarises methodological limitations of the current research to inform and improve future investigations. Key Terms: Autoimmune Diseases; Neuroimmunology; Autoimmune Encephalitis, Limbic Encephalitis; Anti-LGI1 Encephalitis, LGI1; Neuropsychology, Cognitive Assessment.

Surgery for pharmacoresistant epilepsy in the developing world: A pilot study.

Epilepsy prevalence in the developing world is many fold that found in developed countries. For individuals whose conditions failed to respond to pharmacotherapy, surgery is the only opportunity for cure. In Uganda, we developed a center for treatment of intractable temporal lobe epilepsy (iTLE) that functions within the technologic and expertise constraints of a severely low resource area. Our model relies on partnership with epilepsy professionals and training of local staff. Patients were prescreened at regional clinics for iTLE. Individuals meeting inclusion criteria were referred to the treating Ugandan hospital (CURE Children's' Hospital of Uganda, CCHU) for video-EEG (electroencephalography), computed tomography (CT) imaging, and neuropsychological evaluation. Data were transferred to epilepsy experts for analysis and treatment recommendations. Ten patients were diagnosed with iTLE and surgically treated at CCHU. Six (60%) were seizure free, and there was no neurologic morbidity or mortality. Our model for surgical treatment of pharmacoresistant TLE has functioned successfully in a true developing world low resource setting.