Exploring the Neuroinflammatory Pathway in Epilepsy and Cognitive Impairment: Role of HMGB1 and Translational Challenges.

Neuroinflammation has emerged as a shared molecular mechanism in epilepsy and cognitive impairment, offering new insights into the complex interplay between immune responses and brain function. Evidence reveals involvement of High mobility group box 1 (HMGB1) in blood-brain barrier disruption and correlations with epilepsy severity and drug resistance. While anti-inflammatory treatments show promise, translating these discoveries faces challenges in elucidating mechanisms and developing reliable biomarkers. However, strategically targeting neuroinflammation and HMGB1-mediated inflammation holds therapeutic potential. This review synthesises knowledge on HMGB1 and related biomarkers in epilepsy and cognitive impairment to shape future research and treatments targeting these intricate inflammatory processes.

Incidence and predictors of posttraumatic epilepsy and cognitive impairment in patients with traumatic brain injury: A retrospective cohort study in Malaysia.

OBJECTIVE: Posttraumatic epilepsy (PTE) significantly impacts morbidity and mortality, yet local PTE data remain scarce. In addition, there is a lack of evidence on cognitive comorbidity in individuals with PTE in the literature. We sought to identify potential PTE predictors and evaluate cognitive comorbidity in patients with PTE. METHODS: A 2-year retrospective cohort study was employed, in which adults with a history of admission for traumatic brain injury (TBI) in 2019 and 2020 were contacted. Three hundred one individuals agreed to participate, with a median follow-up time of 30.75 months. The development of epilepsy was ascertained using a validated tool and confirmed by our neurologists during visits. Clinical psychologists assessed the patients' cognitive performance. RESULTS: The 2-year cumulative incidence of PTE was 9.3% (95% confidence interval [CI] 5.9-12.7). The significant predictors of PTE were identified as a previous history of brain injury [hazard ratio [HR] 4.025, p = .021], and intraparenchymal hemorrhage (HR: 2.291, p = .036), after adjusting for other confounders. TBI patients with PTE performed significantly worse on the total ACE-III cognitive test (73.5 vs 87.0, p = .018), CTMT (27.5 vs 33.0, p = .044), and PSI (74.0 vs 86.0, p = .006) than TBI patients without PTE. A significantly higher percentage of individuals in the PTE group had cognitive impairment, compared to the non-PTE group based on ACE-III (53.6% vs 46.4%, p = .001) and PSI (70% vs 31.7%, p = .005) scores at 2 years post-TBI follow-up. SIGNIFICANCE: This study emphasizes the link between TBI and PTE and the chance of developing cognitive impairment in the future. Clinicians can target interventions to prevent PTE by identifying specific predictors, which helps them make care decisions and develop therapies to improve patients' quality of life.

Feasibility of cardiac-based seizure detection and prediction: A systematic review of non-invasive wearable sensor-based studies.

A reliable seizure detection or prediction device can potentially reduce the morbidity and mortality associated with epileptic seizures. Previous findings indicating alterations in cardiac activity during seizures suggest the usefulness of cardiac parameters for seizure detection or prediction. This study aims to examine available studies on seizure detection and prediction based on cardiac parameters using non-invasive wearable devices. The Embase, PubMed, and Scopus databases were used to systematically search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Human studies that evaluated seizure detection or prediction based on cardiac parameters collected using wearable devices were included. The QUADAS-2 tool and proposed standards for validation for seizure detection devices were used for quality assessment. Twenty-four articles were identified and included in the analysis. Twenty studies evaluated seizure detection algorithms, and four studies focused on seizure prediction. Most studies used either a wrist-worn or chest-worn device for data acquisition. Among the seizure detection studies, cardiac parameters utilized for the algorithms mainly included heart rate (HR) (n = 11) or a combination of HR and heart rate variability (HRV) (n = 6). HR-based seizure detection studies collectively reported a sensitivity range of 56%-100% and a false alarm rate (FAR) of 0.02-8/h, with most studies performing retrospective validation of the algorithms. Three of the seizure prediction studies retrospectively validated multimodal algorithms, combining cardiac features with other physiological signals. Only one study prospectively validated their seizure prediction algorithm using HRV extracted from ECG data collected from a custom wearable device. These studies have demonstrated the feasibility of using cardiac parameters for seizure detection and prediction with wearable devices, with varying algorithmic performance. Many studies are in the proof-of-principle stage, and evidence for real-time detection or prediction is currently limited. Future studies should prioritize further refinement of the algorithm performance with prospective validation using large-scale longitudinal data. PLAIN LANGUAGE SUMMARY: This systematic review highlights the potential use of wearable devices, like wristbands, for detecting and predicting seizures via the measurement of heart activity. By reviewing 24 articles, it was found that most studies focused on using heart rate and changes in heart rate for seizure detection. There was a lack of studies looking at seizure prediction. The results were promising but most studies were not conducted in real-time. Therefore, more real-time studies are needed to verify the usage of heart activity-related wearable devices to detect seizures and even predict them, which will be beneficial to people with epilepsy.

An Interplay Between Post-Traumatic Epilepsy and Associated Cognitive Decline: A Systematic Review.

Background: Post-traumatic epilepsy (PTE) is a devastating neurological outcome of traumatic brain injury (TBI), which may negatively impact the quality of life of patients with TBI, and may impose a huge socioeconomic burden. This burden may be due to long-term functional outcomes associated with PTE, particularly cognitive dysfunction. To date, the relationship between TBI and PTE remains unclear, with little known about how the effect of their link on cognitive function as well. Objective: Thus, this systematic review aimed at elucidating the relationship between PTE and cognitive impairment in adults after TBI based on available clinical studies, in hopes to aid in the development of therapeutic strategies for PTE. Methods: A systematic literature search was performed using 6 databases; MEDLINE, Embase, CINAHL, Psych INFO, Web of Science, and Cochrane to retrieve relevant clinical studies investigating the link between PTE and cognition in the context of TBI. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of relevant studies. Results: A total of six eligible studies were included for critical appraisal in this review after performing the inclusion and exclusion criteria, which involved 1,100 individuals, from 1996 to 2021. The selected studies were derived from the civilian and military population, with a follow-up period that ranged from 6 months to 35 years. The average quality of the involved studies was moderate (6.6, SD = 1.89). Five out of six studies found poorer cognitive performance in people with PTE, compared with those without PTE. Although the association between PTE and cognitive impairment was insignificant after controlling for specific covariates, there was a statistical trend toward significance. Conclusion: This systematic review suggests that there may be a possible link between PTE and cognitive decline in TBI patients, with the latter being reported to occur up to 35 years post injury. Variations in sample sizes, follow-up periods, and neuropsychological assessment tools may be the limitations affecting the interpretation and significance of this relationship. Therefore, future studies with standard cognitive assessment tools may be warranted to solidify the link between TBI-PTE-cognitive dysfunction, prior to the development of therapeutic strategies.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020221702, prospero identifier: CRD42020221702.

Antibiotic and shared decision-making preferences among adolescents in Malaysia.

BACKGROUND: The purpose of this study was to establish baseline information on the current level of knowledge about, attitude toward, and experience with antibiotic usage, and preferences for shared decision making among adolescents in Malaysia. METHODS: A cross-sectional survey, involving 1,105 respondents who were aged between 13 and 17 years and who lived in Malaysia, was conducted using a validated questionnaire. The survey assessed knowledge, attitude, and experience with regard to antibiotic usage, and adolescents' preferences for the style of shared decision-making process. RESULTS: The majority (n=786 [71.13%]) of the respondents had a low level of knowledge, 296 (26.79%) had a moderate level of knowledge, and 23 (2.08%) had a high level of knowledge. Further, they demonstrated a slightly negative attitude mean score of 3.30±0.05 (range: 0-8 points) but a positive experience mean score of 2.90±0.029 (range: 0-4 points). There was a positive correlation between knowledge and attitude scores, with a higher knowledge level associated with a more positive attitude toward antibiotic usage (r=0.257, P<0.001). Higher knowledge scores were associated with a more negative experience with antibiotic usage (r=-0.83, P=0.006). When assessing preference in shared decision making, more adolescents preferred an active role (n=408 [37%]) compared with collaborative (n=360 [32.6%]) or passive (n=337 [30.5%]) (P=0.028) roles. CONCLUSION: Current health care settings should involve adolescents in the decision-making process. Education packages can be introduced to improve adolescents' knowledge of and practice of taking antibiotics, as well as to encourage their participation in decision making, in an attempt to reduce misuse of antibiotics.