Premature mortality risk in individuals with convulsive epilepsy: Results from a longitudinal, prospective, population-based study.

OBJECTIVE: To assess premature mortality and identify associated risk factors among individuals with convulsive epilepsy in resource-poor settings using a longitudinal, prospective, population-based approach. METHOD: The study recruited people with convulsive epilepsy who underwent assessment and management of epilepsy at primary healthcare centers in rural Northwest China, including newly diagnosed individuals and previously identified prevalent cases. All participants were confirmed to have epilepsy by neurologists according to strict criteria and were followed up monthly by primary care physicians. Demographic data and cause of death (COD) were obtained from death certificates or verbal autopsies conducted by neurologists, following the International Classification of Diseases, 10th Edition. The standardized mortality ratio (SMR) and proportionate mortality ratio (PMR) for each cause of death were estimated using the Cause-Of-Death Surveillance Dataset of China (2020). Survival analysis was used to identify risk factors associated with all-cause mortality and death directly due to epilepsy. RESULTS: During 5.9 years of follow-up with 40,947 person-years, there were 781 (11.2%) deaths among 6967 participants. The risk of premature death in people with convulsive epilepsy was 2.7-fold higher than that in the general population. Young participants had a significantly higher risk (standardized mortality ratio 26.5-52.5) of premature death. The proportionate mortality ratio was higher for cerebrovascular disease (15%), sudden unexpected death in epilepsy (SUDEP) (13.4%), cardiovascular disease (11.7%), status epilepsy (SE) (11.3%), and epilepsy-related accidents (14.0%) than other premature mortality cause of deaths. Additionally, the highest standardized proportional mortality ratio (SPMR) was observed from drowning in all cause of death (10.4, 95% confidence interval [CI]: 7.6-13.8), followed by burning (9.0, 95% CI: 3.7-18.9). Factors that increased the risk of all-cause mortality included male sex, late age of onset, short disease duration, high body mass index, monotherapy, and the frequency of generalized tonic-clonic seizures (GTCS). High frequency of generalized tonic-clonic seizures (> 3 attacks in the last year) was an independent risk factor for premature death directly due to epilepsy (including sudden unexpected death in epilepsy, status epilepsy, and epilepsy-related accidents), while early age of onset (≤ 14 years) and long duration of epilepsy (> 20 years) were independent risk factors for sudden unexpected death in epilepsy. In addition, short duration of epilepsy (≤ 20 years) was an independent risk factor for status epilepsy. CONCLUSIONS: This study demonstrated that individuals with poorly controlled seizures are more likely to experience premature death, with most deaths being epilepsy-related and preventable. These findings underline the importance of effective seizure treatment and the potential impact on reducing premature mortality among people with convulsive epilepsy.

Derivation and validation of a new prediction model for sudden unexpected death in epilepsy based on a longitudinal prospective population-based cohort.

OBJECTIVE: We conducted a population-based, prospective cohort study with a large sample size in Ningxia Province of the Northwest, a rural area in China, by developing a model to specifically assess risk factors of sudden unexpected death in epilepsy (SUDEP) in people with convulsive epilepsy by clinical variables. METHODS: Participants with convulsive epilepsy were recruited from January 1, 2008, to April 28, 2022, in rural Northwest China. They received regular assessments and management of epilepsy at the primary healthcare level and were followed up monthly. Information on the cause of death and relevant clinical details was obtained from death certificates or neurologist-conducted verbal autopsies. Survival analysis was employed to identify potential risk factors associated with SUDEP. RESULTS: Five variables were independently associated with SUDEP: generalized tonic-clonic seizures (GTCS) with ≥1 attack during the preceding month, GTCS with >3 attacks during the preceding year, body mass index (BMI) ≥24, age of onset ≤14 years, and duration >20 years. The area under receiver operator characteristic (ROC) curve (AUC) value (95% CI) of the model was 0.789 (0.735-0.843) in the derivation dataset and 0.830 (0.758-0.902) in the validation dataset. There was agreement between the observed and predicted probabilities of SUDEP. CONCLUSIONS: This study establishes that high GTCS frequency, early age of onset, long duration of epilepsy, and being overweight are associated with an increased risk of SUDEP in individuals with convulsive epilepsy. The study also developed and validated a personalized prediction model to accurately assess the risk of SUDEP.

Recurrent epileptic seizures following cardiac catheterization with iodixanol: a case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications. CASE PRESENTATION: Here, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient's EEG was normal. No antiepileptic drugs were administered throughout this process. CONCLUSIONS: CIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.

PI3K/Akt/uncoupling protein 2 signaling pathway may be involved in cell senescence and apoptosis induced by angiotensin II in human vascular endothelial cells.

Oxidative DNA damage contributes to replicative senescence. We explored the mechanism by which angiotensin II (Ang II) induces senescence in human vascular endothelial cells (HUVECs). Following weeklong incubation with Ang II, cell senescence, apoptosis, reactive oxygen species (ROS) content and mitochondrial membrane potential (MMP) were measured by ß-galactosidase, annexin V/propidium iodide, DCFH-DA and rhodamine 123 staining, respectively. The protein levels of telomerase reverse transcriptase (TERT), UCP2, Akt, phosphor (p)-Akt, c-myc, and p53 were assessed by immunoblot. LY294002 was applied to inhibit PI3K/Akt signaling. Ang II induced HUVEC senescence and apoptosis, and increased ROS content and depolarization of MMP in a dose-dependent manner. Ang II further elevated protein levels of TERT from 0.006 ± 0.041 at baseline, to 0.480 ± 00.031 in the presence of 10 µM Ang II, UCP2 from 0.297 ± 0.051 to 2.512 ± 0.024, p-Akt from 0.012 ± 0.024 to 0.874 ± 0.015, c-myc from 0.521 ± 0.015 to 1.064 ± 0.025, and p53 from 0.035 ± 0.047 to 1.195 ± 0.029 (all P < 0.01, vs. baseline). LY294002 pre-treatment significantly alleviated Ang II-induced HUVEC senescence, and partly reversed the elevation of TERT, UCP2, p-Akt, c-myc and p53 protein levels. PI3K/Akt/UCP2 signaling may be involved in cell senescence and apoptosis induced by Ang II in HUVECs.