Memory function in autoimmune encephalitis: a cross-sectional prospective study utilising multiple memory paradigms.

BACKGROUND AND OBJECTIVE: Autoimmune encephalitis (AE) is often associated with clinically significant memory impairment. This study aimed to evaluate memory in a cross-sectional prospective AE cohort using multiple memory paradigms. METHODS: 52 patients (50% seropositive) meeting Graus criteria for possible AE were prospectively recruited between October 2019 and August 202. A comprehensive examination of memory was performed, including tests of supraspan verbal memory (list learning), logicosemantic memory (story learning), figural memory (learning of geometric designs), and verbal associative learning (verbal paired associates). Memory scores were compared to demographically adjusted normative data. Pattern analysis was conducted to assist in the identification of patterns in memory performances. RESULTS: Mean memory scores were not significantly below the normative mean. At an individual patient level, over 20% of the cohort exhibited impaired delayed figural memory, supraspan verbal memory learning and recall. Observed performances were significantly below expected performance for story learning (p = 0.017) and recall (p = 0.003), figural recall (p < 0.0001), initial acquisition (p < 0.001) and final acquisition of a list (p < 0.001) and all delayed recall measures of the list (p < 0.00001). 54.76% of patients exhibited intact psychometrics, and 16 distinct patterns of impairment emerged, indicating variability in memory outcomes. DISCUSSION: While statistical evidence for memory impairment did not emerge at an aggregate level, a proportion of patients present with evidence of abnormal memory performance on psychometrics. Variability in impaired memory measures argues for an individualised patient-focused approach to clinical assessment in AE. Future research should validate these findings with a larger sample size and explore the relationships between memory profiles and other cognitive functions.

Does Hyperventilation Increase the Diagnostic Yield of the Routine Electroencephalogram: A Retrospective Analysis of Adult and Pediatric Cohorts.

PURPOSE: While hyperventilation (HV) increases the diagnostic yield of EEG in children, there is conflicting evidence to support its application in adults. For the first time in history, a large cohort of patients has undergone EEGs without HV during the COVID-19 pandemic. Utilizing this opportunity, we sought to investigate whether HV increases the diagnostic yield of EEG in children compared with adults. METHODS: Patients aged six years and above who had routine EEGs at Monash Health between January 2019 and December 2020 were studied. The cohort was divided into two, pediatric (younger than 18 years) and adult (18 years or older). Epileptiform abnormalities (ictal and interictal) were the outcomes investigated. The effect of HV was examined with logistic regression to determine odds ratios with 95% confidence intervals. RESULTS: In total, we studied 3,273 patients (pediatric = 830, adult = 2,443). In the pediatric cohort, HV significantly increased the diagnostic yield of absence seizures (p = 0.01, odds ratios 2.44, 95% confidence intervals 1.21-4.93). In adults, HV did not increase the yield of absence seizures (p = 0.34, odds ratios 0.36, 95% confidence intervals 0.05-2.88). Interictal epileptiform discharges during HV were significantly more frequent in children compared with adults (p < 0.001, odds ratios 3.81, 95% confidence intervals 2.51-5.77). CONCLUSIONS: Hyperventilation is useful to increase the yield of interictal epileptiform discharges and absence seizures in pediatric patients but not in adults. Hence, routine EEG may be recorded in adults without HV when it is unsafe to perform.

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.

Diagnostic utility of prolonged ambulatory video-electroencephalography monitoring.

OBJECTIVES: Ambulatory video-electroencephalography (video-EEG) represents a low-cost, convenient and accessible alternative to inpatient video-EEG monitoring, however few studies have examined their diagnostic yield. In this large-scale retrospective study conducted in Australia, we evaluated the efficacy of prolonged ambulatory video-EEG recordings in capturing diagnostic events and resolving the referring question. METHODS: Sequential adult and paediatric ambulatory video-EEG reports from April 2020 to June 2021 were reviewed retrospectively. Data collection included patient demographics, clinical information, and details of events and EEG abnormalities. Clinical utility was assessed by examining i) time to first diagnostic event, and ii) ability to resolve the referring questions - seizure localisation, quantification, classification, and differentiation (differentiating seizures from non-epileptic events). RESULTS: Of the 600 reports analysed, 49 % captured at least one event, and 45 % captured interictal abnormalities (epileptiform or non-epileptiform). Seizures, probable psychogenic events (mostly non-convulsive), and other non-epileptic events occurred in 13 %, 23 % and 21 % of recordings respectively, with overlap. Unreported events were captured in 53 (9 %) recordings, and unreported seizures represented more than half of all seizures captured (51 %, 392/773). Nine percent of events were missing clinical, video or electrographic data. A diagnostic event occurred in 244 (41 %) recordings, of which 14 % were captured between the fifth and eighth day of recording. Reported event frequency ≥ 1/week was the only significant predictor of diagnostic event capture. In recordings with both seizures and psychogenic events, unrecognized seizures were frequent, and seizures may be missed if recording is terminated early. The referring question was resolved in 85 % of reports with at least one event, and 53 % of all reports. Specifically, this represented 46 % of reports (235/512) for differentiation of events, and 75 % of reports (27/36) for classification of seizures. CONCLUSION: Ambulatory video-EEG recordings are of high diagnostic value in capturing clinically relevant events and resolving the referring clinical questions.

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.

Circadian distribution of epileptiform discharges in epilepsy: Candidate mechanisms of variability.

Epilepsy is a serious neurological disorder characterised by a tendency to have recurrent, spontaneous, seizures. Classically, seizures are assumed to occur at random. However, recent research has uncovered underlying rhythms both in seizures and in key signatures of epilepsy-so-called interictal epileptiform activity-with timescales that vary from hours and days through to months. Understanding the physiological mechanisms that determine these rhythmic patterns of epileptiform discharges remains an open question. Many people with epilepsy identify precipitants of their seizures, the most common of which include stress, sleep deprivation and fatigue. To quantify the impact of these physiological factors, we analysed 24-hour EEG recordings from a cohort of 107 people with idiopathic generalized epilepsy. We found two subgroups with distinct distributions of epileptiform discharges: one with highest incidence during sleep and the other during day-time. We interrogated these data using a mathematical model that describes the transitions between background and epileptiform activity in large-scale brain networks. This model was extended to include a time-dependent forcing term, where the excitability of nodes within the network could be modulated by other factors. We calibrated this forcing term using independently-collected human cortisol (the primary stress-responsive hormone characterised by circadian and ultradian patterns of secretion) data and sleep-staged EEG from healthy human participants. We found that either the dynamics of cortisol or sleep stage transition, or a combination of both, could explain most of the observed distributions of epileptiform discharges. Our findings provide conceptual evidence for the existence of underlying physiological drivers of rhythms of epileptiform discharges. These findings should motivate future research to explore these mechanisms in carefully designed experiments using animal models or people with epilepsy.

Seizure-induced reversible magnetic resonance imaging abnormalities: A retrospective cohort study.

PURPOSE: Seizure-induced reversible magnetic resonance imaging (MRI) abnormalities (SRMA) present challenges in seizure management. We sought to investigate the frequency, risk factors, evolution and prognostic value of SRMA. METHODS: A retrospective observational cohort study of consecutive seizure patients investigated with an MRI of the brain was conducted. Clinical and MRI data were reviewed to determine the clinical characteristics and imaging findings of SRMA. Outcomes (seizure freedom versus uncontrolled seizures and deaths) were assessed upon the last clinic follow-up. Mann-Whitney U test and chi-square test for independence with Bonferroni correction were used to explore the statistical significance of predictive factors. RESULTS: The study included 483 consecutive seizure patients with 7.6% developing SRMA. Patients with SRMA were older (median age 57 years, interquartile range-IQR 52-66, p < 0.001) and experienced longer seizures (median 5 minutes, IQR 2-15, p = 0.002) compared with seizure patients with normal MRI. Seizure type (provoked versus unprovoked), recurrence (first versus recurrent) and epileptiform EEG changes did not demonstrate a significant association. Diffusion restriction and ADC reduction observed in SRMA resolved earlier, while T2, FLAIR hyperintensities and temporal lobes changes persisted longer on follow-up scans. The median time interval from seizure to complete resolution of SRMA was 87 days (IQR 45-225). No statistical difference in outcomes was seen between patients with SRMA and normal MRIs (p = 0.19). CONCLUSIONS: SRMA is an uncommon finding following seizures. It is not associated with poor seizure control or mortality. Risk factors associated with SRMA include older age and longer seizure duration including status epilepticus.

The efficacy and tolerability of adjunctive brivaracetam for the treatment of adult epilepsy: An Australian multi-center retrospective real-world observational cohort study.

OBJECTIVE: Assess the efficacy and tolerability of add-on therapy brivaracetam (BRV) in adult patients with epilepsy in a real-world setting. METHODS: This multi-center retrospective observational cohort study examined all adult patients who commenced on BRV at 11 Australian epilepsy centers between 2017 and 2020. Primary outcomes were seizure response (≥50% reduction in frequency) and seizure freedom 12 months post BRV commencement, and tolerability. We report three approaches to missing data (complete case analysis, CCA; last observation carried forward, LOCF; and intention to treat, ITT). Secondary outcomes included the durability of early BRV response and continuous seizure freedom from BRV initiation. Subgroup analysis examined patients with focal and generalized epilepsy and patients with refractory (≥4 prior ASMs) and highly refractory (≥7 prior ASMs) epilepsy. Outcomes were also assessed at 'personalized' seizure outcome time points based on baseline seizure frequency. RESULTS: Baseline and follow-up data were available for 228 patients. The mean age was 41.5 years (IQR 30, 50). Most had focal epilepsy (188/228, 82.5%). Median number of previous ASMs was 4 (2, 7), and concomitant ASMs 2 (2, 3). Twelve-month responder rate was: 46.3% using CCA (95% CI 34.0, 58.9); 39.5% using LOCF (33.1, 46.1); and 15.4% using ITT (10.9, 20.7). Twelve-month seizure freedom was: 23.9% using CCA (14.3, 35.9); 24.6% using LOCF (19.1, 30.7); and 7.9% using ITT (4.7, 12.1). The most frequent adverse effects were sedation or cognitive slowing (33/228, 14.5%), irritability or aggression (16/228, 7.0%), and low mood (14/228, 6.1%). Outcomes were similar using continuous outcome definitions and 'personalized' outcome assessment time points. Early responses were highly durable, with 3-month response maintained at all subsequent time points at 83%, and seizure freedom maintained at 85%. Outcomes were similar in focal (n = 187) and generalizsed (n = 25) subgroups. Outcomes were similar in refractory patients (n = 129), but lower in the highly refractory group (n = 62), however improvement with BRV was still observed with 12-month seizure freedom of 8.3% using CCA (1.0, 27), 6.5% using LOCF (1.8, 15.7); and 3.2% using ITT (0.4, 11.2). CONCLUSIONS: Meaningful real-world responder and seizure freedom rates can be still observed in a refractory epilepsy population. Brivaracetam response can occur early and appears to be maintained with minimal later relapse. The results should be interpreted with caution given the retrospective nature of the study and the quantities of missing data at later time points.

Mapping topography and network of brain injury in patients with disorders of consciousness.

Background: There is a growing interest in the topography of brain regions associated with disorders of consciousness. This has caused increased research output, yielding many publications investigating the topic with varying methodologies. The objective of this study was to ascertain the topographical regions of the brain most frequently associated with disorders of consciousness. Methods: We performed a cross-sectional text-mining analysis of disorders of consciousness studies. A text mining algorithm built in the Python programming language searched documents for anatomical brain terminology. We reviewed primary PubMed studies between January 1st 2000 to 8th February 2023 for the search query "Disorders of Consciousness." The frequency of brain regions mentioned in these articles was recorded, ranked, then built into a graphical network. Subgroup analysis was performed by evaluating the impact on our results if analyses were based on abstracts, full-texts, or topic-modeled groups (non-negative matrix factorization was used to create subgroups of each collection based on their key topics). Brain terms were ranked by their frequency and concordance was measured between subgroups. Graphical analysis was performed to explore relationships between the anatomical regions mentioned. The PageRank algorithm (used by Google to list search results in order of relevance) was used to determine global importance of the regions. Results: The PubMed search yielded 24,944 abstracts and 3,780 full texts. The topic-modeled subgroups contained 2015 abstracts and 283 full texts. Text Mining across all document groups concordantly ranked the thalamus the highest (Savage score = 11.716), followed by the precuneus (Savage score = 4.983), hippocampus (Savage score = 4.483). Graphical analysis had 5 clusters with the thalamus once again having the highest PageRank score (PageRank = 0.0344). Conclusion: The thalamus, precuneus and cingulate cortex are strongly associated with disorders of consciousness, likely due to the roles they play in maintaining awareness and involvement in the default mode network, respectively. The findings also suggest that other areas of the brain like the cerebellum, cuneus, amygdala and hippocampus also share connections to consciousness should be further investigated.

Peripheral monocytes and soluble biomarkers in autoimmune encephalitis.

BACKGROUND AND OBJECTIVES: Autoimmune encephalitis (AE) is an inflammatory disease of the central nervous system which can result in long-term seizures and cognitive dysfunction despite treatment with immunotherapy. The role of the innate immune system in AE is not well established. To investigate the contribution of innate immunity to AE and its long-term outcomes we evaluated peripheral monocytes and serum cytokines in the periphery of patients with AE. METHODS AND RESULTS: We recruited 40 patients with previously diagnosed AE and 28 healthy volunteers to our cross-sectional observation study and evaluated their peripheral blood monocytes via flow cytometry and serum cytokines (CCL-2, CCL-17, G-CSF, GM-CSF, IFNγ, IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, TNFα) via ELISA.Compared with controls the AE cohort had expansion of the 'pro-inflammatory' CD14+CD16+ monocyte sub-population (7.13% vs 5.46%, p < 0.01) with higher levels of serum IL-6 (2.34 pg/mL vs 0.54 pg/mL, p < 0.001). These changes were most significant in anti-LGI-1 antibody mediated AE, an AE subtype with poor long-term cognitive outcomes. CONCLUSION: Expansion of the peripheral CD14+CD16+ monocyte population and increased serum IL-6 in AE is reflective of changes seen in other systemic inflammatory and neurodegenerative conditions. These changes may indicate a persistent pro-inflammatory state in AE and may contribute to poor long-term outcomes.

A cross-sectional investigation of cognition and epileptiform discharges in juvenile absence epilepsy.

OBJECTIVES: Despite the prevalence of cognitive symptoms in the idiopathic generalized epilepsies (IGEs), cognitive dysfunction in juvenile absence epilepsy (JAE), a common yet understudied IGE subtype, remains poorly understood. This descriptive study provides a novel, comprehensive characterization of cognitive functioning in a JAE sample and examines the relationship between cognition and 24-h epileptiform discharge load. METHOD: Forty-four individuals diagnosed with JAE underwent cognitive assessment using Woodcock Johnson III Test of Cognitive Abilities with concurrent 24-h ambulatory EEG monitoring. Generalized epileptiform discharges of any length, and prolonged generalized discharges ≥3 s were quantified across wakefulness and sleep. The relationship between standardized cognitive scores and epileptiform discharges was assessed through regression models. RESULTS: Cognitive performances in overall intellectual ability, acquired comprehension-knowledge, processing speed, long-term memory storage and retrieval, and executive processes were 0.63-1.07 standard deviation (SD) units lower in the JAE group compared to the population reference mean, adjusted for educational attainment. Prolonged discharges (≥3 s) were recorded in 20 patients (47.6%) from 42 available electroencephalography (EEG) studies and were largely unreported. Duration and number of prolonged discharges were associated with reduced processing speed and long-term memory storage and retrieval. SIGNIFICANCE: Cognitive dysfunction is seen in patients with JAE across various cognitive abilities, including those representing more stable processes like general intellect. During 24-h EEG, prolonged epileptiform discharges are common yet underreported in JAE despite treatment, and they show moderate effects on cognitive abilities. If epileptiform burden is a modifiable predictor of cognitive dysfunction, therapeutic interventions should consider quantitative 24-h EEG with routine neuropsychological screening. The growing recognition of the spectrum of neuropsychological comorbidities of IGE highlights the value of multidisciplinary approaches to explore the causes and consequences of cognitive deficits in epilepsy.

Neuroimaging characteristics may aid in diagnosis, subtyping, and prognosis in autoimmune encephalitis.

OBJECTIVE: To examine the utility of neuroimaging characteristics as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). METHODS: In this multi-center study, we retrospectively analyzed 66 cases of seropositive AE. The MRI and PET imaging was assessed by independent visual inspection. Whole brain and regional volumes were imputed by IcoMetrix, an automated volumetric assessment package. The modified Rankin Scale (mRS) was utilized to assess the patients' follow-up disability. Other outcomes were mortality, first line treatment failure, medial temporal lobe (MTL) atrophy, and clinical relapse. Univariate and multivariable regression analysis was performed. RESULTS: Abnormalities on MRI were detected in 35.1% of patients, while PET was abnormal in 46.4%. Initial median whole brain and hippocampal volumes were below the 5th and 20th percentile respectively compared to an age-matched healthy database. After a median follow-up of 715 days, 85.2% had good functional outcome (mRS ≤ 2). Nine patients developed MTL atrophy during follow-up. On multivariable analysis, inflammatory MTL changes were associated with development of MTL atrophy (HR 19.6, p = 0.007) and initial hippocampal volume had an inverse relationship with mortality (HR 0.04, p = 0.011). Patients who developed MTL atrophy had a reduced chance of good final mRS (HR 0.16, p = 0.015). CONCLUSIONS: Neuroimaging on initial hospital admission may be provide important diagnostic and prognostic information. This study demonstrates that structural and inflammatory changes of the MTL may have importance in clinical and radiological prognosis in seropositive AE.

Response to photic stimulation as a measure of cortical excitability in epilepsy patients.

Studying states and state transitions in the brain is challenging due to nonlinear, complex dynamics. In this research, we analyze the brain's response to non-invasive perturbations. Perturbation techniques offer a powerful method for studying complex dynamics, though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition. Therefore, biomarkers of the brain's perturbation response or "cortical excitability" could be used to indicate seizure transitions. However, perturbing the brain often involves invasive intracranial surgeries or expensive equipment such as transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups, or animal model studies. Photic stimulation is a widely used diagnostic technique in epilepsy that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalized epilepsy (GGE), with (n = 10) and without (n = 10) PPR, and patients with psychogenic non-epileptic seizures (PNES; n = 10), compared to resting controls (n = 10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiologic mechanisms. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics.

Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.

Background: A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME. Methods: We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/). Findings: Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73). Interpretation: We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools. Funding: MING fonds.

Semiologic differences between bilateral tonic-clonic seizures of focal onset and generalized onset.

BACKGROUND: Focal semiologies have been described in idiopathic generalized epilepsies (IGE) and generalized-onset bilateral tonic-clonic seizures (GBTCS). These focal signs may lead to wrong diagnosis and inappropriate choice of antiseizure medications. We sought to investigate the differences in focal semiologic features between GBTCS and focal-onset bilateral tonic-clonic seizures (FBTCS). METHODS: We retrospectively reviewed video-EEG data of captured GBTCS and FBTCS over a period of five years. The presence or absence of 12 focal signs as well seizure duration and time to head version was tabulated for each seizure. We used the chi-square test for independence and Fisher's exact test to investigate the occurrence of each focal sign in FBTCS compared with GBTCS. Additionally, we used receiver operating characteristic (ROC) curves to explore if the seizure duration and time to head version from the ictal onset can reliably differentiate between FBTCS and GBTCS. Finally, we employed hierarchical cluster analysis to visualize how these focal signs appear in combination. RESULTS: Head version (p <.001), preceding automatisms (p <.001), eye version (p <.001), unilateral facial clonic activity (p <.001), and mouth deviation (p =.004) were found to be significantly more frequent in FBTCS. Longer seizures were highly in favor of FBTCS whereas shorter time to head version from the ictal onset indicated GBTCS in the ROC curve analysis. CONCLUSIONS: Though focal signs occur in GBTCS, careful evaluation of semiology can help the clinician distinguish FBTCS from GBTCS.

Using Semiology to Classify Epileptic Seizures vs Psychogenic Nonepileptic Seizures: A Meta-analysis.

Background and Objectives: A misdiagnosis of psychogenic nonepileptic seizures (PNES) and epileptic seizures (ES) is common. In the absence of the diagnostic gold standard (video EEG), clinicians rely on semiology and clinical assessment. However, questions regarding the diagnostic accuracy of different signs remain. This meta-analysis aimed to evaluate the diagnostic accuracy of semiology in PNES and ES. Methods: We systematically searched PubMed, PsycInfo, and Medline for original research publications published before 8 February 2021 with no restriction on search dates to identify studies that compared semiology in ES and PNES in epilepsy monitoring units. Non-English publications, review articles, studies reporting on only PNES or ES, and studies limited to patients with developmental delay were excluded. Study characteristics and proportions of event groups and patient groups demonstrating signs were extracted from each article. A bivariate analysis was conducted, and data were pooled in a random effects model for meta-analysis. The I 2 statistic was calculated to assess statistical heterogeneity. The revised Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the risk of bias in included studies. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were calculated. A PLR >10 or an NLR <0.1 largely affected the posttest probability of a diagnosis (ES or PNES), whereas a PLR between 5 and 10 or an NLR between 0.1 and 0.2 moderately affected the posttest probability of a diagnosis (ES or PNES). Results: The meta-analysis included 14 studies comprising 800 patients with ES and 452 patients with PNES. For PNES, ictal eye closure (PLR 40.5 95% confidence interval [CI] 16.2-101.3; I 2 = 0, from 3 studies) and asynchronous limb movements (PLR 10.2; 95% CI 2.8-37.7; I 2 = 0, from 3 studies) reached a PLR threshold >5. No single sign reached a PLR threshold >5 for ES. Discussion: While all signs require an interpretation in the overall clinical context, the presence of ictal eye closure and asynchronous limb movements are reliable discriminative signs for PNES.

Prevalence, risk factors, and prognosis of drug-resistant epilepsy in autoimmune encephalitis.

OBJECTIVE: To evaluate the prevalence and biomarkers of drug-resistant epilepsy (DRE) in patients with autoimmune encephalitis (AIE). METHODS: Sixty-nine patients with AIE were recruited retrospectively and electroencephalographies (EEGs) were reviewed using a standard reporting proforma. Associations between EEG biomarkers and DRE development at 12 months were examined using logistic regression modeling and were utilized to create a DRE risk score. RESULTS: Sixteen percent of patients with AIE developed DRE at 12-month follow-up. The presence of status epilepticus (SE) (OR 11.50, 95% CI [2.81, 51.86], p-value <0.001), temporal lobe focality (OR 9.90, 95% CI [2.60, 50.71], p-value 0.001) and periodic discharges (OR 19.12, 95% CI [3.79, 191.10], p-value 0.001) on the admission EEG were associated with the development of DRE at 12 months. These variables were utilized to create a clinically applicable risk score for the prediction of DRE development. CONCLUSIONS: Drug-resistant epilepsy is an infrequent complication of AIE. Electroencephalography changes during the acute illness can predict the risk of DRE at 12 months post-acute AIE. SIGNIFICANCE: The identified EEG biomarkers provide the basis to generate a clinically applicable prediction tool which could be used to inform treatment, prognosis, and select patients for acute treatment trials.

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.

Serious Cardiac Arrhythmias Detected by Subcutaneous Long-term Cardiac Monitors in Patients With Drug-Resistant Epilepsy.

BACKGROUND AND OBJECTIVES: Epilepsy is associated with an increased risk of cardiovascular disease and premature mortality, including sudden unexpected death in epilepsy (SUDEP). Serious cardiac arrythmias might go undetected in routine epilepsy and cardiac investigations. METHODS: This prospective cohort study aimed to detect cardiac arrhythmias in patients with chronic drug-resistant epilepsy (≥5 years duration) using subcutaneous cardiac monitors for a minimum follow-up duration of 12 months. Participants with known cardiovascular disease or those with abnormal 12-lead ECGs were excluded. The device was programmed to automatically record episodes of tachycardia ≥140 beats per minute (bpm), bradycardia ≤40 bpm for ≥3 seconds, or asystole ≥3 seconds. FINDINGS: Thirty-one patients underwent subcutaneous cardiac monitoring for a median recording duration of 2.2 years (range 0.5-4.2). During this time, 28 patients (90.3%) had episodes of sustained (≥30 seconds) sinus tachycardia, 8/31 (25.8%) had sinus bradycardia, and 3 (9.7%) had asystole. Three patients (9.7%) had serious cardiac arrhythmias requiring additional cardiac interventions. Among them, 2 patients had prolonged sinus arrest and ventricular asystole (>6 seconds), leading to pacemaker insertion in one, and another patient with epileptic encephalopathy had multiple episodes of recurrent nonsustained polymorphic ventricular tachycardia and bundle branch conduction abnormalities. The time to first detection of a clinically significant cardiac arrhythmia ranged between 1.2 and 26.9 months following cardiac monitor insertion. DISCUSSION: Implantable cardiac monitors detected a high incidence of clinically significant cardiac arrhythmias in patients with chronic drug-resistant epilepsy, which may contribute to the incidence of premature mortality, including SUDEP.