The risk and causes of death in childhoodonset epilepsy: A 4-study collaboration

Rationale: Young people with epilepsy experience high death rates compared to the general population. Understanding the magnitude of risk and the causes of death (CoD) is essential for counseling and for potential prevention. Methods: We combined the mortality experiences of four cohort studies of newly diagnosed childhood epilepsy (onset 1m-16 or 17y). Deaths were ascertained by parent and physician report, review of national death indices and health records, and a surveillance system in place at one site. Death certificates, hospital records, and autopsy reports were obtained when available. CoD was categorized as SUDEP (Nasheff, 2012), other seizure-related, other natural, nonnatural, and unknown. Epilepsy was designated as complicated (neuro-deficit, intellectual impairment, brain lesion) or uncomplicated (normal exam and intellect, no identified underlying cause). Results: 2260 subjects were followed for 30,427 person-years (PY) for an average of 13.5 years (range 9.8 to 16.4y across studies). 79 deaths occurred; mean age at onset = 3.9y (range: 1m - 15.7y), age at death= 11y (range: 2m-30y). 42 (53%) were male; 71 (80%) had complicated epilepsy, and 60 (76%) had substantial cognitive impairment. Drug resistance was noted in 47 (59%), convulsions in 52 (66%), status epilepticus in 37 (47%), and 61 (77%) had seizures in the prior year. The crude death rate (CDR) was 260/100,000PY (95% CI=202, 317). The CDR for complicated epilepsy was 851 (653, 1049) and for uncomplicated epilepsy, 36 (95% CI=11, 61) per 100,000PY. Most deaths were due to natural causes and unrelated to seizures (N=58) with respiratory CoDs being the most common (N=43). These included 36 pneumonia (5 primary infectious, 19 aspiration, 12 unspecified), 5 respiratory insufficiency-NOS, and 2 other. Other natural CoDs were sepsis (N=3), shunt failure (N=3), and unspecified secondary to neurometabolic disease (N=3). 50/52 of these patients had moderate to severe cognitive impairment. Two children died of strokes occurring after the onset of seizures, and four died of medical conditions unrelated to their epilepsy (e.g. cancer). SUDEP accounted for 10 deaths (6 definite, 2 probable, 2 possible). Two of these deaths occurred in people with uncomplicated epilepsy. The CDR for SUDEP was 32.9 (CI=12.5, 53.2) overall and 9 (CI=0, 21.6) for uncomplicated and 95.1 (CI=29.5, 162.4) for complicated epilepsy. The remaining CoDs were other seizure-related (N=3), non-natural (2 suicide, 1 homicide, 2 accidental), and unknown (N=3). In all, 13 (16%) of deaths were seizure-related (including SUDEP). Conclusions: Deaths in young people with epilepsy are largely due to infections and complications of severe neurologic impairment. While seizure-related deaths account fo

The risk and causes of death in childhoodonset epilepsy: A 4-study collaboration

Rationale: Young people with epilepsy experience high death rates compared to the general population. Understanding the magnitude of risk and the causes of death (CoD) is essential for counseling and for potential prevention. Methods: We combined the mortality experiences of four cohort studies of newly diagnosed childhood epilepsy (onset 1m-16 or 17y). Deaths were ascertained by parent and physician report, review of national death indices and health records, and a surveillance system in place at one site. Death certificates, hospital records, and autopsy reports were obtained when available. CoD was categorized as SUDEP (Nasheff, 2012), other seizure-related, other natural, nonnatural, and unknown. Epilepsy was designated as complicated (neuro-deficit, intellectual impairment, brain lesion) or uncomplicated (normal exam and intellect, no identified underlying cause). Results: 2260 subjects were followed for 30,427 person-years (PY) for an average of 13.5 years (range 9.8 to 16.4y across studies). 79 deaths occurred; mean age at onset = 3.9y (range: 1m - 15.7y), age at death= 11y (range: 2m-30y). 42 (53%) were male; 71 (80%) had complicated epilepsy, and 60 (76%) had substantial cognitive impairment. Drug resistance was noted in 47 (59%), convulsions in 52 (66%), status epilepticus in 37 (47%), and 61 (77%) had seizures in the prior year. The crude death rate (CDR) was 260/100,000PY (95% CI=202, 317). The CDR for complicated epilepsy was 851 (653, 1049) and for uncomplicated epilepsy, 36 (95% CI=11, 61) per 100,000PY. Most deaths were due to natural causes and unrelated to seizures (N=58) with respiratory CoDs being the most common (N=43). These included 36 pneumonia (5 primary infectious, 19 aspiration, 12 unspecified), 5 respiratory insufficiency-NOS, and 2 other. Other natural CoDs were sepsis (N=3), shunt failure (N=3), and unspecified secondary to neurometabolic disease (N=3). 50/52 of these patients had moderate to severe cognitive impairment. Two children died of strokes occurring after the onset of seizures, and four died of medical conditions unrelated to their epilepsy (e.g. cancer). SUDEP accounted for 10 deaths (6 definite, 2 probable, 2 possible). Two of these deaths occurred in people with uncomplicated epilepsy. The CDR for SUDEP was 32.9 (CI=12.5, 53.2) overall and 9 (CI=0, 21.6) for uncomplicated and 95.1 (CI=29.5, 162.4) for complicated epilepsy. The remaining CoDs were other seizure-related (N=3), non-natural (2 suicide, 1 homicide, 2 accidental), and unknown (N=3). In all, 13 (16%) of deaths were seizure-related (including SUDEP). Conclusions: Deaths in young people with epilepsy are largely due to infections and complications of severe neurologic impairment. While seizure-related deaths account fo

Safety and efficacy of responsive neurostimulation in the pediatric population: Evidence from institutional review and patient-level meta-analysis

Background: Responsive neurostimulation (RNS) is a novel technology for drug-resistant epilepsy rising from bilateral hemispheres or eloquent cortex. Although recently approved for adults, its safety and efficacy for pediatric patients is under investigation. Methods: A comprehensive literature search (Pubmed/Medline, Scopus, Cochrane) was conducted for studies on RNS for pediatric epilepsy (<18 y/o) and supplemented by our institutional series (4 cases). Reduction in seizure frequency at last follow-up compared to preoperative baseline comprised the primary endpoint. Results: A total of 8 studies (49 patients) were analyzed. Median age at implant was 15 years (interquartile range [IQR] 12–17) and 63% were males. A lesional MRI was noted in 64% (14/22). Prior invasive EEG recording was performed in the majority of patients (90%) and the most common modality was stereoelectroencephalography (57%). The most common implant location (total of 94 RNS leads) was the frontal lobe (27%), followed by mesial temporal structures (23%) and thalamus (17%). At a median follow-up of 22 months, median seizure frequency reduction was 75% (IQR: 50–88%) and 80% were responders (>50% seizure reduction). Responses ranged from 50% for temporal lobe epilepsy to 81–93% for frontal, parietal, and multilobar epilepsy. Four infections were observed (8%) and there were no hematomas or postoperative neurological deficits. Conclusion: Current evidence, albeit limited by potential publication bias, supports the promising safety and efficacy profile of RNS for medically refractory pediatric epilepsy. Randomized controlled trial data are needed to further establish the role of this intervention in preoperative discussions with patients and their families. © 2022 Elsevier Inc