Use Of Antiseizure Medications Research Articles

Influence of Different Antiseizure Medications on Vascular Risk Factors in Children with Epilepsy.

Many studies have proposed that plasma homocysteine levels are increased as a side effect with the prolonged use of antiseizure medications. This is associated with an increase in carotid intima media thickness; hence, it increases the threat of atherosclerosis at a young age. We aimed to assess serum levels of homocysteine in epileptic children on long-standing antiseizure medications and its association with increased occurrence of cardiovascular disease. The study included 60 epileptic children aged between 2 and 15 years old who visited our pediatric neurology outpatient clinic and 25 apparently healthy children served as a control group. All included children were subjected to careful history taking, clinical examination, anthropometric measures, laboratory investigations including serum homocysteine levels and lipid profile, along with radiological assessment involving carotid intima media thickness and carotid stiffness. Results demonstrated a significant increase in the serum levels of homocysteine, carotid intima media thickness, and carotid stiffness in children on monotherapy of old generation antiseizure medications and polytherapy than that in children on monotherapy of new generation antiseizure medications and control children. Epileptic children on old generation and polytherapy antiseizure medications have an increased risk for cardiovascular diseases and need follow up for early intervention when needed.

Differences between men and women in response to antiseizure medication use and the likelihood of developing treatment resistant epilepsy.

The prevalence of epilepsy is slightly higher in women than in men and sensitivity to seizure stimuli differs between sexes. Some evidence suggests sex differences in response to antiseizure medications exist mainly due to inconsistent pharmacokinetic differences; however, there is a lack of real-world evidence examining differences in response to antiseizure medications between men and women. This was a retrospective population-based cohort study in five large US healthcare databases. The population included adult patients with epilepsy, newly exposed to levetiracetam, and naive to antiseizure medication. The first exposure to levetiracetam was the index date. The requirement that all patients received the same medication was done to avoid potential confounding due to differences in index treatment. The outcome was the development of treatment resistant epilepsy (TRE), defined as having at least three distinct antiseizure medications in 1 year. The proportion of patients who developed TRE within 1 year following the index date was calculated. To compare the risk of developing TRE between sexes, relative risks (RR) and 95% confidence intervals (CI) were calculated, and estimates were pooled using meta-analytic techniques stratified by gender and age. A total of 147 334 subjects were included in the databases, 50.8% were women, and 4.27% developed TRE. The comorbid profile differed greatly between men and women; however, the types of epilepsy syndromes observed during baseline were similar between the two groups. Across all databases, women were more likely to develop TRE than men (pooled RR 1.27, 95% CI 1.17-1.38). Results remained similar when stratified by age. This study assessed sex differences in response to antiseizure medications using the development of TRE as a proxy for effectiveness. Women newly exposed to levetiracetam were 27% more likely to develop TRE than men, independent of age.

Treatment gaps in epilepsy.

Over 50 million people around the world have epilepsy, and yet, epilepsy recognition and access to care are ongoing issues. Nearly 80% of people with epilepsy live in low-and middle-income countries and face the greatest barriers to quality care. However, there are substantial disparities in care within different communities in high-income countries as well. Across the world, under-recognition of seizures continues to be an issue, leading to diagnostic and treatment delays. This stems from issues surrounding stigma, public education, basic access to care, as well as healthcare worker education. In different regions, people may face language barriers, economic barriers, and technological barriers to timely diagnosis and treatment. Even once diagnosed, people with epilepsy often face gaps in optimal seizure control with the use of antiseizure medications. Additionally, nearly one-third of people with epilepsy may be candidates for epilepsy surgery, and many either do not have access to surgical centers or are not referred for surgical evaluation. Even those who do often experience delays in care. The purpose of this review is to highlight barriers to care for people with epilepsy, including issues surrounding seizure recognition, diagnosis of epilepsy, and the initiation and optimization of treatment.

Seizures and EEG characteristics in a cohort of pediatric patients with dystroglycanopathies

PurposeTo delineate the seizure type, phenotype and V-EEG patterns of dystroglycanopathy (DGP) and correlate them with the neuroradiological and genetic results. MethodsPatients with seizures were screened from our dystroglycanopathy database from January 2010 to March 2021. Detailed clinical information, including seizure type, brain magnetic resonance imaging (MRI), EEG and genetic analysis, was collected. ResultsThirteen patients (15.1%, 13/86) had seizures. Most patients had a severe phenotype. The mean age at first seizure onset was 2 years and 8 months. The most common seizure type was generalized tonic-clonic seizure (GTCS), with 92.3% (12/13) induced by fever. Three patients were diagnosed with epilepsy. Most patients did not take any medicine. A few patients had irregular use of antiseizure medications (ASMs). Of the 13 patients, seven patients were diagnosed with MEB, four patients with POMGNT1 mutations, two with ISPD mutations, and one with POMT1 mutation. Three patients were diagnosed with FCMD with FKTN mutations. Two patients were diagnosed with CMD-MR, one patient with ISPD mutation, and one with POMT1 mutation. One patient was diagnosed with LGMD with FKRP mutation. Nine patients underwent EEG examination, and eight patients had abnormal EEG results, including abnormal background activities in three patients, abnormal background activities combined with paroxysmal discharges in three patients, pure paroxysmal discharges in one patient and positive phase sharp waves in the occipital region in one patient. For radiology, brain MRI was available for 12 patients. The brain MRI of nine patients showed type II lissencephaly. Two patients showed cerebellar hypoplasia and brainstem hypoplasia. One patient had a normal brain MRI result. Patients with type II lissencephaly usually had abnormal background activities and paroxysmal discharges. ConclusionThe seizure phenotype of dystroglycanopathy (DGP) is characterized by GTCS, which was the most common seizure type, while focal seizures and epileptic spasms could also occur in DGP patients. Most seizures were induced by fever. Seizures were relatively more frequent in severe phenotypes of DGP, such as FCMD and MEB. Abnormal background activities were the most common EEG patterns, which were closely related to type II lissencephaly.

A multicentre observational study of the use of antiseizure medication in patients with aneurysmal subarachnoid haemorrhage in the PROMOTE-SAH study

Our objective was to describe antiseizure medication (ASM) prescription patterns, and associations between ASM use and death and disability outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) admitted to ICU. This was a multi-centre prospective observational study. The study took place in eleven ICUs across Australia and New Zealand. Data was collected from 1 April 2017 to 1 October 2018. Three hundred and fifty-seven adult patients with aSAH were enrolled. The primary outcome was to describe patterns of ASM prescription. The secondary outcome of interest was death or disability (modified Rankin Scale (mRS) score ≥ 4) at six months, and its association with ASM therapy, and relevant clinical subgroups. Forty percent of patients received an ASM and the most commonly used agent was levetiracetam. The median length of ASM administration was eight days (IQR 4.5–12.5). A number of patients with prehospital seizures did not receive ASM therapy (14/55, 2725%). There was a tendency towards ASM prescription with both higher radiological and clinical grade aSAH. There was no significant association between death or disability at six month (mRS ≥ 4) and ASM vs No ASM prescription. Testing for an interaction effect between ASM administration and WFNS grade suggested inferior outcomes with ASM use in lower aSAH grades (p = 0.04). In conclusion, the prescription of ASM for aSAH in Australia is variable across and within sites, with the majority of patients not receiving ASM chemoprophylaxis. We demonstrated no significant association between death or disability at six months and the use of ASM. There may be an association with poorer outcomes in patients with lower grade aSAH. This finding requires further exploration.

Estimate of Patients With Missed Seizures Because of Delay in Conventional EEG.

There is frequent delay between ordering and placement of conventional EEG. Here we estimate how many patients had seizures during this delay. Two hundred fifty consecutive adult patients who underwent conventional EEG monitoring at the University of Wisconsin Hospital were retrospectively chart reviewed for demographics, time of EEG order, clinical and other EEG-related information. Patients were stratified by use of anti-seizure medications before EEG and into low-risk, medium-risk, and high-risk groups based on 2HELPS2B score (0, 1, or >1). Monte Carlo simulations (500 trials) were performed to estimate seizures during delay. The median delay from EEG order to performing EEG was 2.00 hours (range of 0.5-8.00 hours) in the total cohort. For EEGs ordered after-hours, it was 2.00 hours (range 0.5-8.00 hours), and during business hours, it was 2.00 hours (range 0.5-6.00 hours). The place of EEG, intensive care unit, emergency department, and general floor, did not show significant difference (P = 0.84). Anti-seizure medication did not affect time to first seizure in the low-risk (P = 0.37), medium-risk (P = 0.44), or high-risk (P = 0.12) groups. The estimated % of patients who had a seizure in the delay period for low-risk group (2HELPS2B = 0) was 0.8%, for the medium-risk group (2HELPS2B = 1) was 10.3%, and for the high-risk group (2HELPS2B > 1) was 17.6%, and overall risk was 7.2%. The University of Wisconsin Hospital with 24-hour in-house EEG technologists has a median delay of 2 hours from order to start of EEG, shorter than published reports from other centers. Nonetheless, seizures were likely missed in about 7.2% of patients.

Seizure medication and planned pregnancy: balancing the risks and outcomes

ABSTRACT Introduction The therapeutic management of women with epilepsy (WWE) of childbearing age can be complicated by the need to balance maternal/fetal risks related to seizure occurrence during gestation with the potential teratogenic risks related to the use of anti-seizure medications (ASMs). Areas covered The authors review clinical evidence on seizure-related and ASM-related risks during pregnancy. Current regulatory indications are discussed, evaluating their impact on clinical practice, and ethical implications of pharmacological decisions are debated. Expert opinion If properly informed about the maternal/fetal risks carried by different pharmacological choices, WWE can become the final decision makers regarding their care in every phase of their life. Over the coming years, analysis of aggregated pregnancy registry data on the structural impact, on the fetus, of low doses of valproate and of newer ASMs, together with analysis of the main population study data on functional (cognitive and behavioral) outcomes, could lead to huge advances, making choosing an ASM a less complex process for the clinician and a less painful decision for the woman. Future objectives should include identification of the potential role of the pharmacogenomic profile of WWE in determining the risk of fetal malformations.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Associations between cognition and employment outcomes after epilepsy surgery

ObjectivesPrevious studies have shown that younger age, higher education, and seizure freedom after epilepsy surgery are associated with employment. However, very few studies have investigated associations with cognition and employment status in epilepsy surgery patients. MethodsThis retrospective study consists of 46 adult patients, who underwent resective epilepsy surgery in the Helsinki University Hospital between 2010 and 2018 and who had been assessed by a neuropsychologist prior to surgery and 6 months after surgery using a systematic test battery. In addition to neuropsychological evaluation, neurologists assessed the patients prior to surgery and followed up the patients up to 24 months after the surgery and evaluated work status of the patients. Logistic regression models were used to assess the effects of cognition on changes in employment status, while controlling for age and education. ResultsOut of the 46 patients 38 (82.6%) were seizure free and 7 (15.2%) had their seizures reduced 2 years postsurgically. From prior to surgery to 2 years postsurgery, use of antiseizure medication was reduced in most of the patients, mean reduction of the dosage being 26.9%. Employment status improved in 10 (21.7%) patients, remained unchanged in 27 (58.7%) and worsened in 3 (6.5%). An additional 6 patients were already not working prior to surgery. Subsequent analyses are based on the subsample of 37 patients whose employment status improved or remained unchanged. Mistakes in executive function tasks (p = 0.048) and working memory performance (p = 0.020) differentiated between the group whose employment status remained similar and those who were able to improve their employment status. Epilepsy surgery outcome or changes in antiseizure medication (ASM) use were not associated with changes in employment status. ConclusionsIn the subsample of 37 patients, errors in executive function tasks and poorer working memory differentiated patients whose employment status did not change from those patients who could improve their employment status. Problems in executive function and working memory tasks might hinder performance in a complex work environment. When assessing the risks and opportunities in returning to work after surgery, difficulties in working memory and executive function performance should be taken into consideration as they may predispose the patient to challenges at work.

Trends of Utilization of Antiseizure Medications Among Pregnant Women in Manitoba, Canada: A 20-Year Population-Based Study.

Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women. Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada. Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis. Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 (p < 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 (p < 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%). Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy.

Mechanisms Involved in Epileptogenesis in Alzheimer's Disease and Their Therapeutic Implications.

Epilepsy and Alzheimer’s disease (AD) incidence increases with age. There are reciprocal relationships between epilepsy and AD. Epilepsy is a risk factor for AD and, in turn, AD is an independent risk factor for developing epilepsy in old age, and abnormal AD biomarkers in PET and/or CSF are frequently found in late-onset epilepsies of unknown etiology. Accordingly, epilepsy and AD share pathophysiological processes, including neuronal hyperexcitability and an early excitatory–inhibitory dysregulation, leading to dysfunction in the inhibitory GABAergic and excitatory glutamatergic systems. Moreover, both β-amyloid and tau protein aggregates, the anatomopathological hallmarks of AD, have proepileptic effects. Finally, these aggregates have been found in the resection material of refractory temporal lobe epilepsies, suggesting that epilepsy leads to amyloid and tau aggregates. Some epileptic syndromes, such as medial temporal lobe epilepsy, share structural and functional neuroimaging findings with AD, leading to overlapping symptomatology, such as episodic memory deficits and toxic synergistic effects. In this respect, the existence of epileptiform activity and electroclinical seizures in AD appears to accelerate the progression of cognitive decline, and the presence of cognitive decline is much more prevalent in epileptic patients than in elderly patients without epilepsy. Notwithstanding their clinical significance, the diagnosis of clinical seizures in AD is a challenge. Most are focal and manifest with an altered level of consciousness without motor symptoms, and are often interpreted as cognitive fluctuations. Finally, despite the frequent association of epilepsy and AD dementia, there is a lack of clinical trials to guide the use of antiseizure medications (ASMs). There is also a potential role for ASMs to be used as disease-modifying drugs in AD.

A pharmacovigilance study on antiepileptic medications in a paediatric hospital in Italy

ObjectiveThe standard treatment for epilepsy is based on the appropriate use of antiseizure medications (ASMs) to prevent the recurrence of seizures. For the newer ASMs, however, little information on their...

Approach to the Medical Treatment of Epilepsy.

This article discusses the use of antiseizure medications in the treatment of focal and generalized epilepsies using an evidence-based approach. In recent years, several new antiseizure medications with differing mechanisms of action have been introduced in clinical practice, and their efficacy and safety has been evaluated in randomized controlled clinical trials. Currently, all antiseizure medications can prevent seizure occurrence, but they have no proven disease-modifying or antiepileptogenic effects in humans. The choice of therapy should integrate the best available evidence of efficacy, tolerability, and effectiveness derived from clinical trials with other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences. After the failure of a first antiseizure medication, inadequate evidence is available to inform policy. An alternative monotherapy (especially if the failure is because of adverse effects) or a dual therapy (especially if failure is because of inadequate seizure control) can be used. Currently, several antiseizure medications are available for the treatment of focal or generalized epilepsies. They differ in mechanisms of action, frequency of administration, and pharmacologic properties, with a consequent risk of pharmacokinetic interactions. Major unmet needs remain in epilepsy treatment. A substantial proportion of patients with epilepsy continue to experience seizures despite two or more antiseizure medications, with a negative impact on quality of life. Therefore, more antiseizure medications that could provide higher seizure control with good tolerability and that could positively affect the underlying disease are needed.

Women’s Issues in Epilepsy

Issues pertaining to women with epilepsy have advanced with a better understanding of multidirectional influences among hormones, seizures, and antiseizure medications, as well as pregnancy-related concerns around fertility, seizure destabilization, and antiseizure medication-associated teratogenicity. This article highlights important developments in this field and reviews best practices in the management of women with epilepsy. Important external hormonal influences may impact women with epilepsy particularly in the context of gender-affirming medications, hormonal replacement therapy, and fertility therapies. Fertility for women with epilepsy is influenced by multiple variables; however, in the absence of preexisting fertility issues, epilepsy per se is not associated with significantly impaired fertility. Once women with epilepsy are pregnant, the majority have a stable course. Antiseizure medication use in pregnancy is associated with major congenital malformations 2 to 5 times that of the general population and is highest with high-dose (≥1500 mg or greater total daily) valproate. Carefully considered changes in drug choice and dose may mitigate these risks. Therapeutic drug monitoring plays an important role in pregnancy care, and under expert supervision, women with epilepsy in pregnancy have similar seizure risks as women with epilepsy who are not pregnant. As women with epilepsy age, bone health and menopause may further be impacted by seizures and antiseizure medications. The care of women with epilepsy is a multifaceted discipline that recognizes the life-long impact of sex and gender influences on epilepsy care.

Maternal Epilepsy and Long-term Offspring Mortality: A Nationwide Cohort Study.

ObjectiveWe examined how maternal epilepsy and use of antiseizure medications in pregnancy was associated with offspring mortality.MethodsThis population‐based cohort study included all live‐ and stillborn singletons in Denmark between 1981 and 2016. We used nation‐wide registers to retrieve information on pregnancy characteristics, epilepsy diagnoses, use of antiseizure medications, and mortality. Adjusted mortality rate ratios (MRR) were estimated using log‐linear Poisson regression.ResultsThe cohort consisted of 1,862,474 children. In total, 12,026 live‐born children died during follow‐up, of whom 170 (1.4%) were offspring of mothers with epilepsy. Overall mortality was increased in offspring of mothers with epilepsy compared to offspring of mothers without epilepsy (MRR = 1.46, 95% CI: 1.23–1.71), driven by an excess mortality only in the first year of life. Mortality was increased for natural deaths (MRR = 1.50, 95% CI: 1.25–1.78) but not from unnatural deaths (MRR = 1.38, 95% CI: 0.84–2.14), and only in offspring of women with epilepsy who used antiseizure medications during pregnancy (MRR = 1.51, 95% CI: 1.00–2.17), but not in offspring of women with epilepsy who did not use antiseizure medications while pregnant (MRR = 0.97, 95% CI: 0.69–1.31). When analyses were restricted to children born from 2000 and onwards, the excess mortality that was observed in the first year of life among children of mothers with epilepsy, was no longer evident.InterpretationDuring the 1981 to 1999 epoch, offspring of women with epilepsy were at increased risk of dying in the first year of life. However, this risk did not extend to children born after 2000. Future retrospective studies of the effects of maternal epilepsy on the health of the offspring should take this difference into account. ANN NEUROL 2022;91:455–465

Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience.

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were “irritability” for both groups and “aggression” for patients with other focal epilepsies.

Auditory phoneme discrimination, articulation, and language disorders in patients with genetic epilepsy with febrile seizures plus: A case-control study

IntroductionGenetic epilepsy with febrile seizures plus (GEFS+) is an epilepsy syndrome with clinical heterogeneity that was first described in 1997. Central auditory processing (CAP) is defined as the neurophysiological process in decoding sound waves from the outer ear to the auditory cortex. The present study aimed to analyze CAP and phonological disorders in preschool-age children with GEFS+. Material and MethodThis is a prospective case-control study. Twenty-seven patients diagnosed with GEFS+ aged between 4 years and 6 years and 6 months and 31 healthy controls in the same age range were included in the study. Phonological sensitivity test (SAT) and auditory discrimination test (İAT) were applied to both groups, and the results of both groups were statistically compared. ResultsThe SAT and İAT raw and Z scores of the subjects in the study group were found to be significantly higher than those of the control group (p = 0.001; p < 0.01). Electroencephalography (EEG) status of the patients or the duration of antiseizure medication use did not have a statistically significant effect on the outcome. ConclusionPatients with GEFS+ have a significantly high impairment in both articulation and auditory discrimination of phonemes compared with the healthy population. Early diagnosis and early treatment of this condition can prevent potential literacy problems and the development of dyslexia in the future.

Antiseizure medication use and medical resource utilization after resective epilepsy surgery in children in the United States: A contemporary nationwide cross-sectional cohort analysis.

Antiseizure drug (ASD) therapy can significantly impact quality of life for pediatric patients whose epilepsy remains refractory to medications and who experience neuropsychological side effects manifested by impaired cognitive and social development. Contemporary patterns of ASD reduction after pediatric epilepsy surgery across practice settings in the United States are sparsely reported outside of small series. We assessed timing and durability of ASD reduction after pediatric epilepsy surgery and associated effects on health care utilization. We performed a retrospective analysis of 376 pediatric patients who underwent resective epilepsy surgery between 2007 and 2016 in the United States using the Truven MarketScan database. Filled ASD prescriptions during the pre- and postoperative periods were compared. Univariate and multivariate analyses identified factors associated with achieving a stable discontinuation of or reduction in number of ASDs. Health care utilization and costs were systematically compared. One hundred seventy-one patients (45.5%) achieved a >90-day ASD-free period after surgery, and 84 (22.3%) additional patients achieved a stable reduction in number of ASDs. Achieving ASD freedom was more common in patients undergoing total hemispherectomy (n=21, p=.002), and less common in patients with tuberous sclerosis (p=.003). A higher number of preoperative ASDs was associated with a greater likelihood of achieving ASD reduction postoperatively (hazard ratio [HR]: 1.85, 95% confidence interval [CI]: 1.50-2.28), but was not associated with a significant difference in the likelihood of achieving ASD freedom (0.83, 95% CI: 0.49-1.39). Achieving an ASD-free period was associated with fewer hospital readmissions within the first year after surgery. Patterns of ASD use and discontinuation after pediatric epilepsy surgery provide an unbiased surgical outcome endpoint extractable from administrative databases, where changes in seizure frequency are not captured. This quantitative measure can augment traditional surgical outcome scales, incorporating a significant clinical parameter associated with improved quality of life.

Treating Rhythmic and Periodic EEG Patterns in Comatose Survivors of Cardiac Arrest

BackgroundWhether the treatment of rhythmic and periodic electroencephalographic (EEG) patterns in comatose survivors of cardiac arrest improves outcomes is uncertain.MethodsWe conducted an open-label trial of suppressing rhythmic and periodic EEG patterns detected on continuous EEG monitoring in comatose survivors of cardiac arrest. Patients were randomly assigned in a 1:1 ratio to a stepwise strategy of antiseizure medications to suppress this activity for at least 48 consecutive hours plus standard care (antiseizure-treatment group) or to standard care alone (control group); standard care included targeted temperature management in both groups. The primary outcome was neurologic outcome according to the score on the Cerebral Performance Category (CPC) scale at 3 months, dichotomized as a good outcome (CPC score indicating no, mild, or moderate disability) or a poor outcome (CPC score indicating severe disability, coma, or death). Secondary outcomes were mortality, length of stay in the intensive care unit (ICU), and duration of mechanical ventilation.ResultsWe enrolled 172 patients, with 88 assigned to the antiseizure-treatment group and 84 to the control group. Rhythmic or periodic EEG activity was detected a median of 35 hours after cardiac arrest; 98 of 157 patients (62%) with available data had myoclonus. Complete suppression of rhythmic and periodic EEG activity for 48 consecutive hours occurred in 49 of 88 patients (56%) in the antiseizure-treatment group and in 2 of 83 patients (2%) in the control group. At 3 months, 79 of 88 patients (90%) in the antiseizure-treatment group and 77 of 84 patients (92%) in the control group had a poor outcome (difference, 2 percentage points; 95% confidence interval, −7 to 11; P=0.68). Mortality at 3 months was 80% in the antiseizure-treatment group and 82% in the control group. The mean length of stay in the ICU and mean duration of mechanical ventilation were slightly longer in the antiseizure-treatment group than in the control group.ConclusionsIn comatose survivors of cardiac arrest, the incidence of a poor neurologic outcome at 3 months did not differ significantly between a strategy of suppressing rhythmic and periodic EEG activity with the use of antiseizure medication for at least 48 hours plus standard care and standard care alone. (Funded by the Dutch Epilepsy Foundation; TELSTAR ClinicalTrials.gov number, NCT02056236.)

Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury

Early posttraumatic seizures (EPS) that may occur following a traumatic brain injury (TBI) are associated with poorer outcomes and development of posttraumatic epilepsy (PTE). To evaluate risk factors for EPS, associated morbidity and mortality, and contribution to PTE. Data were collected from an Australian registry-based cohort study of adults (age ≥18 years) with moderate to severe TBI from January 2005 to December 2019, with 2-year follow-up. The statewide trauma registry, conducted on an opt-out basis in Victoria (population 6.5 million), had 15 152 patients with moderate to severe TBI identified via Abbreviated Injury Scale (AIS) head severity score, with an opt-out rate less than 0.5% (opt-out n = 136). EPS were identified via International Statistical Classification of Diseases, Tenth Revision, Australian Modification (ICD-10-AM) codes recorded after the acute admission. Outcome measures also included in-hospital metrics, 2-year outcomes including PTE, and post-discharge mortality. Adaptive least absolute shrinkage and selection operator (LASSO) regression was used to build a prediction model for risk factors of EPS. Among the 15 152 participants (10 457 [69%] male; median [IQR] age, 60 [35-79] y), 416 (2.7%) were identified with EPS, including 27 (0.2%) with status epilepticus. Significant risk factors on multivariable analysis for developing EPS were younger age, higher Charlson Comorbidity Index, TBI sustained from a low fall, subdural hemorrhage, subarachnoid hemorrhage, higher Injury Severity Score, and greater head injury severity, measured using the AIS and Glasgow Coma Score. After adjustment for confounders, EPS were associated with increased ICU admission and ICU length of stay, ventilation and duration, hospital length of stay, and discharge to inpatient rehabilitation rather than home, but not in-hospital mortality. Outcomes in TBI admission survivors at 24 months, including mortality (relative risk [RR] = 2.14; 95% CI, 1.32-3.46; P = .002), development of PTE (RR = 2.91; 95% CI, 2.22-3.81; P < .001), and use of antiseizure medications (RR = 2.44; 95% CI, 1.98-3.02; P < .001), were poorer for cases with EPS after adjustment for confounders. The prediction model for EPS had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.66-0.79), sensitivity of 66%, and specificity of 73% in the validation set. We identified important risk factors for EPS following moderate to severe TBI. Early posttraumatic seizures were associated with longer ICU and hospital admissions, ICU ventilation, and poorer 24-month outcomes including mortality and development of PTE.