Antiepileptic Drug Initiation Research Articles

Recent Hospitalization and Initiation of Antiepileptics Among Persons With Alzheimer's Disease.

Antiepileptic drugs (AEDs) are frequently prescribed for persons with Alzheimer's disease (AD), but little is known on factors associated with AED initiation in this population. We investigated whether recent hospitalization is associated with AED initiation in persons with AD. Nested case-control study in the nationwide register-based Medication use and Alzheimer's disease (MEDALZ) cohort. The MEDALZ cohort includes 70,718 persons diagnosed with AD during 2005-2011 in Finland. Altogether 6814 AED initiators and 6814 age-, sex-, and time since AD diagnosis-matched noninitiators were included in this study. Matching date was the date of AED initiation. AED purchases were identified from the Prescription Register and hospitalizations from the Care Register for Health Care. Recent hospitalization was defined as hospitalization ending within 2weeks before the matching date. Association between recent hospitalization and AED initiation was assessed with conditional logistic regression. The most frequently initiated AEDs were pregabalin (42.9%) and valproic acid (32.2%). A bigger proportion of AED initiators (36.9%) than noninitiators (5.3%) were recently hospitalized [odds ratio (OR) 10.5, 95% CI 9.22-11.9]. Dementia was the most frequent discharge diagnosis among AED initiators (29.1%) and noninitiators (27.9%). Among AED initiators, the next most frequent diagnosis was epilepsy (20.6%). Musculoskeletal diagnoses and use of analgesics including opioids was more common among gabapentinoid initiators compared with other AED initiators. Recent hospitalization was significantly related to AED initiation. Initiations of AED might have been related to common symptoms in persons with AD like neuropathic pain, epilepsy, and neuropsychiatric symptoms.

Cognitive profile, psychopathological symptoms, and quality of life in newly diagnosed pediatric epilepsy: A six-month, naturalistic follow-up study

Long-term studies indicated changes in aspects of cognition, psychopathology, and quality of life (QOL) in children and adolescents followed up after the diagnosis of epilepsy. However, evidence is limited regarding what happens during the first few months after epilepsy is diagnosed because at this phase is possible to adjust and/or change an AED regimen or add other treatment interventions, if needed. This is a naturalistic, six months follow-up study that evaluated changes in overall cognitive profiles, levels of psychopathological symptoms, and quality of life (QOL) in newly diagnosed, uncomplicated pediatric epilepsy. In total, 61 (35 [57.4%] males) children and adolescents aged 7–18 years were assessed at the time of diagnosis and the initiation of antiepileptic drug (AED) treatment and six months afterward. The Revised Wechsler Intelligence Scale for Children, the Revised Child Anxiety and Depression Scale (RCADS), Nisonger Child Behavior Rating Form for typically developing children and adolescents (NCBRF), KIDSCREEN-10 Quality of Life Measure, and Adverse Event Profile (AEP) were used. The RCADS and NCBRF scores significantly increased over time, while the KIDSCREEN-10 scores significantly decreased. The most significant increases were observed in scores measuring social phobia and depressive symptoms and inattentiveness. Verbal cognitive abilities and full-scale intelligence scores changed slightly, while more changes were found in aspects of non-verbal cognitive abilities. This study showed that six months after epilepsy diagnosis and AED initiation, there were marked increases in anxiety levels, depressive symptoms, and behavioral problems, with deteriorations in QOL, while cognitive changes were relatively minimal. Therefore, monitoring levels of psychopathological symptoms and QOL in newly diagnosed epilepsy is highly recommended.

P12.01 The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

Abstract BACKGROUND Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide. MATERIAL AND METHODS In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity. RESULTS We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI: 26–51%) versus 30% (95%CI: 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI: 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide. CONCLUSION Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

The effectiveness of antiepileptic drug treatment in glioma patients: lamotrigine versus lacosamide

PurposeOptimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide.MethodsIn this multicenter study we retrospectively analyzed data of patients with diffuse grade 2–4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity.ResultsWe included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26–51%) versus 30% (95%CI 20–41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46–1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide.ConclusionLamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy.

Editors' Note: Association of Guideline Publication and Delays to Treatment in Pediatric Status Epilepticus

In “Association of guideline publication and delays to treatment in pediatric status epilepticus,” Fernandez et al. reported that despite publication of evidence of delays in treatment of refractory status epilepticus (SE) in the Pediatric Status Epilepticus Research Group (pSERG) at the end of 2014, there was no difference in time to initiation of benzodiazepines, nonbenzodiazepine antiepileptic drugs (AEDs), and continuous infusions to patients with refractory SE in pSERG in the hospital between 2011–2014 and 2015–2019. The authors identified a number of proposed actions to overcome potential barriers to the timely initiation of AEDs. Albuja et al. commented that they improved the time to administration of second-line AEDs at their institution by creating a SE alert system to contact neurology, pharmacy, the rapid response team, and the bed manager simultaneously when an inpatient is suspected to be in SE. Amengual-Gual et al. applauded them for implementing this initiative. It is imperative to continue to identify quality improvement measures to identify SE and ensure that AEDs are given in a timely fashion to patients with SE because it becomes more resistant over time, which may lead to increased morbidity and mortality.[1][1],[2][2] In “Association of guideline publication and delays to treatment in pediatric status epilepticus,” Fernandez et al. reported that despite publication of evidence of delays in treatment of refractory status epilepticus (SE) in the Pediatric Status Epilepticus Research Group (pSERG) at the end of 2014, there was no difference in time to initiation of benzodiazepines, nonbenzodiazepine antiepileptic drugs (AEDs), and continuous infusions to patients with refractory SE in pSERG in the hospital between 2011–2014 and 2015–2019. The authors identified a number of proposed actions to overcome potential barriers to the timely initiation of AEDs. Albuja et al. commented that they improved the time to administration of second-line AEDs at their institution by creating a SE alert system to contact neurology, pharmacy, the rapid response team, and the bed manager simultaneously when an inpatient is suspected to be in SE. Amengual-Gual et al. applauded them for implementing this initiative. It is imperative to continue to identify quality improvement measures to identify SE and ensure that AEDs are given in a timely fashion to patients with SE because it becomes more resistant over time, which may lead to increased morbidity and mortality.1,2 [1]: #ref-1 [2]: #ref-2

Psychiatric Comorbidities in Pediatric Epilepsy.

Psychiatric comorbidities are close to 5-times higher in children and youth with epilepsy (CYE) compared to general population. With epilepsy being one of the most common neurological disorders in children, we provide a timely review of psychiatric issues in CYE. A meta-analysis found a pooled prevalence of anxiety in 18.9% and depression in 13.5% of CYE. Attention deficit hyperactivity disorder (ADHD) is 2.5 to 5.5 times higher in CYE compared to healthy counterparts. Recent evidence highlights that behavioral adverse effects may lead to discontinuation of anti-epileptic drugs (AEDs) in more than 10% of CYE. Up to 70% CYE shows elevation in baseline psychological symptoms after AED initiation. Identifying psychiatric symptoms can be easily accomplished by the routine use of psychiatric screening instruments in CYE clinics, which is associated with improved health-related quality of life (HRQOL). Psychoeducation is a key component for any visit with CYE. There is some evidence of the effectiveness of behavioral psychological interventions for CYE. There are no therapeutic trials of psychotropics in CYE, but treatment recommendations based on the experience in adults with epilepsy and general population are applicable. Early diagnosis and management of psychiatric comorbidities leads to improvement in HRQOL of CYE. This requires routine screening and a multidisciplinary teamwork.

Longitudinal changes in insulin resistance in children with epilepsy on ketogenic diet: Prevalence and risk factors

IntroductionThe aim of the study was to evaluate the incidence of insulin resistance (IR) and the associated risk factors in children with epilepsy on a ketogenic diet (KD). MethodsThis longitudinal cohort study analyzed data of children with epilepsy on KD. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR value, fasting serum insulin levels, fasting glucose (FG) levels, and lipid profiles were measured before the initiation of the KD and at 6- to 12-month intervals. ResultsA total of 28 children were enrolled. The median age at the initiation of KD was 2.7 ± 2.4 years, and the median follow-up duration was 2.1 ± 1.4 years. The median HOMA-IR (HOMA-IR-1) value before the initiation of KD was 1.2 ± 0.2, which significantly increased to 1.8 ± 0.3 at the last follow-up (HOMA-IR-2; ∆HOMA-IR = 0.6 ± 0.3, p < 0.001). The following factors were associated with patients with higher HOMA-IR-2 values (≥1.9): younger age at seizure onset (0.3 ± 0.2 years, p < 0.001), at the initiation of antiepileptic drugs (AEDs; 0.3 ± 0.3 years, p < 0.001), and at the initiation of KD (1.3 ± 0.5 years, p < 0.001) and higher serum alanine transaminase (ALT; 84.0 ± 17.8 U/L, p = 0.022), total cholesterol (TC; 245.0 ± 20.1 mg/dL, p = 0.001), low-density lipoprotein cholesterol (LDL-C, 103.0 ± 6.7 mg/dL, p = 0.003), and triglyceride (387.0 ± 28.8 mg/dL, p < 0.001) levels. Multivariate regression analysis revealed that the age at seizure onset (p = 0.002), at initiation of AEDs (p = 0.021), and at initiation of KD (p = 0.022) and serum levels of LDL-C (p = 0.012) and triglycerides (p = 0.026) were associated with a significantly high HOMA-IR-2 value. ConclusionClose monitoring of serum lipids levels, especially at younger age, may aid in detecting exacerbation of IR.

Antiepileptic drug use and mortality among community-dwelling persons with Alzheimer disease.

ObjectiveTo evaluate the risk of death in relation to incident antiepileptic drug (AED) use compared with nonuse in people with Alzheimer disease (AD) through the assessment in terms of duration of use, specific drugs, and main causes of death.MethodsThe MEDALZ (Medication Use and Alzheimer Disease) cohort study includes all Finnish persons who received a clinically verified AD diagnosis (n = 70,718) in 2005–2011. Incident AED users were identified with 1-year washout period. For each incident AED user (n = 5,638), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional regression models and inverse probability of treatment weighting (IPTW).ResultsNearly 50% discontinued AEDs within 6 months. Compared with nonusers, AED users had an increased relative risk of death (IPTW hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.12–1.36). This was mainly due to deaths from dementia (IPTW HR, 1.62; 95% CI, 1.42–1.86). There was no difference in cardiovascular and cerebrovascular deaths (IPTW HR, 0.98; 95% CI, 0.67–1.44). The overall mortality was highest during the first 90 days of AED use (IPTW HR, 2.40; 95% CI, 1.91–3.03). Among users of older AEDs, relative risk of death was greater compared to users of newer AEDs (IPTW HR, 1.79; 95% CI, 1.52–2.16).ConclusionIn older vulnerable patients with a cognitive disorder, careful consideration of AED initiation and close adverse events monitoring are needed.

Cognitive functioning in new-onset juvenile myoclonic epilepsy

PurposeJuvenile myoclonic epilepsy (JME) is a common genetic generalized epilepsy syndrome. Adult patients with JME have shown a neuropsychological profile suggestive of subtle frontal dysfunction, but studies of cognitive functioning in the early phases of JME are rare. We analyzed the cognitive performance data of 18 patients who had undergone a neuropsychological assessment either at the time of JME diagnosis and before the initiation of an antiepileptic drug (AED) treatment (11 patients) or during the first 6 years after JME diagnosis (seven patients). MethodsThe cognitive performance of the18 patients with JME (mean age: 18.1, range: 15–33 years) and 18 healthy controls (mean age: 18.7, range: 15–25 years) was compared in a retrospective study. The assessed cognitive domains were visuomotor speed, attention, executive function, and verbal memory. ResultsThe patients with JME and the healthy controls did not differ in any of the assessed cognitive domains. The clinical variables did not correlate to cognitive performance. Furthermore, cognitive performance did not differ between the patients evaluated at the time of diagnosis and before the initiation of AEDs and the patients evaluated during the first 6 years after diagnosis and with an AED treatment. ConclusionsThe cognitive performance of patients with new-onset JME was similar to healthy controls. We could not detect the frontal dysfunction that has been suggested to be associated with JME. Patients were in adolescence or early adulthood with a short duration of epilepsy, which may have contributed to the discovery of no cognitive impairments.

Vitamin D Status in Epileptic Children on Valproic Acid; a Case-Control Study.

Much attention has been paid to the association between valproic acid treatment and bone health. The objective of this study is to compare the serum vitamin D3 level in the epileptic children under valproic acid treatment with the healthy control group. A case-control study has been carried out to compare vitamin D3 levels in 50 epileptic children who were treated with valproic acid with 50 healthy children selected from children visiting the hospital for routine checkup as control group. 100 cases with the mean age of 7.57± 3.62 years (range: 2 - 15 years) were studied (44% boys). Among the 50 epileptic cases; 41 (82%) had generalized and 9 (18%) had partial seizure (56% well controlled and 44% poorly controlled). 15 (30%) of epileptic cases were using anti-epileptic drugs for 6-12 months, 36% for 12-24 months, and 34% for more than 24 months. The case and control groups were similar regarding gender (p =0.99), age (p = 0.24), and BMI (p = 0.64). 49 (49%) patients had some grade of vitamin D3 deficiency. There was a significant difference between case and control groups regarding vitamin D3 levels (p = 0.001). None of the controls had severe vitamin D3 deficiency, while 14% of cases did. 36 (72%) individuals in control group had sufficient or optimal vitamin D3 levels; while only 15 (30%) case patients had such levels. Generally, the control group had higher vitamin D3 levels in comparison to case group (p = 0.001). The study revealed that there was a higher prevalence of vitamin D3 insufficiency in epileptic children receiving valproate monotherapy compared with healthy children. Vitamin D3 supplementation should be given to all epileptic children even before initiation of anti-epileptic drugs.

Economic Value of Adjunctive Brivaracetam Treatment Strategy for Focal Onset Seizures in Finland.

IntroductionThere is an unmet need for well-tolerated antiepileptic drugs (AEDs) that effectively control focal onset seizures. This study aimed to evaluate the economic value of new AEDs in the treatment of focal onset seizure, with or without secondary generalization, in Finnish adults and adolescents with epilepsy, comparing brivaracetam with perampanel as adjunctive AEDs.MethodsEconomic value was assessed using cost-utility analysis. Periods of AED initiation, titration, response assessment (seizure freedom, ≥ 50% reduction, no response), switching in no response or treatment-emergent adverse events (TEAEs), and death were simulated using a discrete-event simulation model. Responses and switching were simulated based on a comprehensive Bayesian network meta-analysis. The primary modeled outcome was the 3%/year discounted incremental cost-effectiveness ratio (ICER). Discounted quality-adjusted life-years (QALYs), payer costs (year 2017 Euro) per patient, and net monetary benefit (NMB) were secondary outcomes. Probabilistic and comprehensive deterministic sensitivity analyses were conducted.ResultsBrivaracetam was more efficacious and had fewer TEAEs than perampanel and other AEDs. Modeled average 5-year QALYs and costs were 3.671 and €28,297 for brivaracetam and 3.611 and €27,979 for perampanel, respectively. The resulting ICER for brivaracetam versus perampanel was only €5345/QALY gained in a deterministic base case scenario. Brivaracetam had a positive NMB and high probability of cost-effectiveness of €1190 and 71% or €1944 and 80% with the assumed willingness to pay of €25,358 or €38,036/QALY gained, respectively. The primary result was robust, with a positive NMB persistent in all sensitivity analysis scenarios. When switching from brivaracetam to perampanel was excluded from the modeling or switching from perampanel to brivaracetam was included, brivaracetam was cost-saving and more effective than perampanel (dominant).ConclusionThese simulated comparisons demonstrated that brivaracetam was more effective and potentially also more affordable than perampanel. Thus, brivaracetam is likely a cost-effective and net beneficial alternative to perampanel for treatment of focal onset seizures.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01155-6) contains supplementary material, which is available to authorized users.

EVALUATION OF COGNITIVE FUNCTION AMONG NEWLY DIAGNOSED IDIOPATHIC EPILEPTIC PATIENTS

Background: Neuropsychological study of new-onset idiopathic epilepsy is considered an exciting opportunity to document cognitive effects of epilepsy before initiation of antiepileptic drugs. Recent studies revealed significant affection of executive functions in new onset seizure without medication. Aim of the Work: To evaluate cognitive functions including (IQ, visual memory and executive functions) in patients with idiopathic epilepsy at onset of disorder before drug treatment or within one week of treatment. Patients and Methods: An observational case -control study was conducted on 30 patients with new onset idiopathic epilepsy recruited from the outpatient clinic of the department of neurology (Ain ShamsUniversity) and 30 healthy cross matched control in the period from June 2016 to June 2018. Both patients and control were subjected to cognitive assessments (Wechsler IQ, Benton visual retention test and Wisconsin card sorting test).Results:In our study we found significant poor performance of patient group before treatment compared to control group in all domains of intellectual abilities measured by Wechsler IQ test (verbal IQ, performance IQ and total IQ), visual memory measured by Benton visual retention test (obtained correct score, expected error scores and difference between them, obtained error score and expected error score and difference between them) and executive functions measuredby Wisconsin card sorting test (conceptual level, category completed, perseverative errors and non-perseverative errors).Conclusion: cognitive functions impairment including (intellectual level, visual memory and executive functions) were found in patients with idiopathic epilepsy at onset of epilepsy and before treatment.

Antiepileptic Drug Treatment of Epilepsy in Children.

The treatment of epilepsy in children is highly individualized at each and every major step in the management. This review examines various factors that modify the treatment from the point of initiation of therapy to the decision to stop an antiepileptic drug (AED). AED therapy leads to seizure freedom in about 70% of all children with epilepsy. AED initiation could be delayed until a second seizure in most children and may be avoided altogether in many children with self-limited childhood focal epilepsies. Three key factors influence the choice of AED: seizure type(s), efficacy of the drug for the seizure type, and the side effect profile of the drug(s). For epileptic spasms, steroids and vigabatrin are the most effective treatment options. For absence seizures, ethosuximide and valproic acid are superior to lamotrigine. For focal seizures, many newer AEDs have favorable side effect profiles with efficacy comparable to older-generation drugs. For generalized epilepsies, valproic acid remains the most effective drug for a broad range of seizure types. Genetic and metabolic etiologies may guide unique treatment choices in some children. After 2 years or more of seizure freedom, if the recurrence risk after AED withdrawal is acceptable, slow weaning of AEDs should be done over the span of 6 weeks or longer. After discontinuation, about 70% of patients remain seizure free, and of those with recurrence, the majority achieve seizure control with restarting an AED. When treatment with two or more AEDs fails, other treatment opportunities for drug-resistant epilepsy, including epilepsy surgery, vagal nerve stimulation, and dietary therapies should be considered. Carefully selected medical therapy guided by seizure type and AED characteristics is effective in more than two-thirds of children with epilepsy.

Epilepsy and traditional healers in the Republic of Guinea: A mixed methods study

PurposeThe purpose of this study was to characterize the reasons, extent, and impact of traditional medicine use among people with epilepsy (PWE) in the Republic of Guinea. MethodsGuinea is a low-income country in sub-Saharan Africa (SSA) with limited healthcare resources. People with epilepsy and their caregivers were seen at a public referral hospital in Conakry, the capital city, where they completed semi-structured interviews with physicians regarding their beliefs about epilepsy, medical care, and engagement with traditional healers. ResultsOf 132 participants (49% children, 44% female, 55% with a university-educated head of household), 79% had seen a traditional healer, and 71% saw a traditional healer before seeing a medical provider for their epilepsy. Participants were treated by a traditional healer for a mean of 39 months before seeing a medical provider. By contrast, 58% of participants reported taking antiepileptic drugs (AEDs) regularly; 46% reported having undergone a head computed tomography (CT) scan; 58% reported having had an electroencephalogram, and 4% reported having had a brain magnetic resonance imaging (MRI) scan. ConclusionsTraditional healers in Guinea provide frontline care for PWE in Guinea with considerable delays in AED initiation, even among a cohort of PWE actively seeking medical care. Engaging with these healers is critical for both influencing community perceptions and appropriately managing epilepsy throughout the country.

Antiepileptic Drugs and Accumulation of Hospital Days Among Persons With Alzheimer's Disease

ObjectivesTo compare the accumulation of hospital days between initiators and noninitiators of antiepileptic drugs (AEDs) among persons with Alzheimer's disease (AD). DesignExposure-matched cohort study. Setting and participantsPersons newly diagnosed with AD in 2005-2011 (n = 70,718) and initiating AED use identified from Finnish health care registers. For each AED initiator, 1 noninitiator matched on age, sex, and time since AD diagnosis was selected. Persons with epilepsy were excluded from the study. MethodsAssociation between AED initiation or use of individual AEDs and accumulation of hospital days during a 2-year follow-up was assessed using negative binomial model. ResultsAED initiators (n = 4432) were hospitalized on average for 43.7 (SD: 88.3) days and matched noninitiators for 32.2 (SD: 71.3) days during the 2-year follow-up. Altogether, 27.3% of the AED initiators and 35.6% of the noninitiators had no hospital days during the study period. Number of accumulated hospital days during the follow-up was 31% higher [adjusted incidence rate ratio (aIRR): 1.31, 95% confidence interval (CI): 1.19-1.43] among AED initiators than the noninitiators. Hospital days due to diseases of the nervous system excluding dementia (aIRR: 2.72, 95% CI: 1.72-4.31), musculoskeletal system (aIRR: 2.49, 95% CI: 1.73-3.58), respiratory system (aIRR: 1.89, 95% CI: 1.47-2.43), and mental and behavioral disorders excluding dementia (aIRR: 1.96, 95% CI: 1.02-3.79) were more common among the AED initiators than noninitiators. Among pregabalin (aIRR: 0.65, 95% CI: 0.56-0.77), gabapentin (aIRR: 0.66, 95% CI: 0.49-0.88), and clonazepam (aIRR: 0.73, 95% CI: 0.55-0.96) initiators, the number of accumulated hospital days was 27% to 35% lower than the days accumulated among the initiators of valproic acid. Conclusions and implicationsAED initiators had more hospital days than noninitiators. Pregabalin and gabapentin were associated with a lower number of hospital days than valproic acid. Further research is needed on the reasons for these findings.

Mortality & recurrent seizure risk after new-onset seizure in HIV-positive Zambian adults

BackgroundRecurrent seizure risks in HIV-positive people with new-onset seizure are largely unknown, making it challenging to offer optimal recommendations regarding antiepileptic drug (AED) initiation. Existing outcomes data is limited, and risk factor identification requires a diagnostic assessment, which is often unavailable in regions heavily effected by HIV, like sub-Saharan Africa.MethodsHIV-positive Zambian adults with new-onset seizure were enrolled in a prospective cohort study to determine seizure recurrence and risk factors for recurrence. Seizure etiology was evaluated, and recurrent seizures and medication usage were assessed during clinic visits. Due to unexpectedly high mortality rates, predictors of death were evaluated using proportional hazards with Gray’s test to compare cumulative incidence functions for recurrent seizure across groups adjusting for the competing outcome of death.Results95 patients were enrolled (mean age 37 years, 43% female, 83% with Karnofsky > 50) and followed for a mean of 293 days (median 241 (IQR: 29–532)). At presentation, 50 (53%) were in status epilepticus. The majority (91, 85%) had advanced HIV disease and 65 (68%) were not on combined antiretroviral therapy (cART). After extensive workup, seizure etiology remained unknown in 16 (17%). Average time to cART initiation after enrollment was 61 days. During follow up, 37 (39%) died and 23 (24%) had recurrent seizure. Most deaths (25/37, 68%) occurred in the first 60 days post-index seizure. Individuals with advanced HIV were more likely to die (HR: 19.1 [95% CI: 1.1–333.4]) as were those whose seizure etiology remained unknown (HR: 2.2 [95% CI: 1.1–4.4]). Among participants that survived from enrolment to the end of data collection on 10 May 2013 (n = 58), 20 (34%) experienced recurrent seizures.ConclusionsNew-onset seizure among HIV-positive Zambian adults is associated with high mortality despite good functional status prior to presentation. Advanced HIV infection and failure to identify an underlying seizure etiology are associated with greater mortality. Recurrent seizures occur in over a third of survivors within only 2 years of follow-up. This provides evidence to support AED initiation after first seizure in HIV-positive individuals with advanced HIV disease at the time of presentation though the risks of AED-cART interactions remain a concern and warrant further study.

Lipid and thyroid hormone levels in children with epilepsy treated with levetiracetam or carbamazepine: A prospective observational study

Although previous studies have investigated the influence of antiepileptic drugs (AEDs) on lipid profiles and thyroid hormone levels, there is little evidence regarding the effects of levetiracetam (LEV). Therefore, we conducted a prospective longitudinal study to evaluate the effects of LEV and carbamazepine (CBZ) treatment on lipid profile and thyroid hormone levels in patients newly diagnosed with epilepsy. Inclusion criteria were as follows: (a) age between 4 and 15 years, (b) diagnosis of epilepsy with at least two focal seizures within a year, and (c) newly treated with LEV or CBZ monotherapy. Serum lipid profile and thyroid hormone levels were measured before and after 1 and 6 months of AED initiation. Among the 21 included patients (LEV: 13 patients, CBZ: 8 patients), all but one patient in the LEV group continued AED monotherapy during the study period. Although triglyceride (TG) levels tended to be increased in the CBZ group (baseline: 58.3 ± 22.0 mg/dl, 1 month: 63.8 ± 21.6 mg/dl, 6 months: 92.3 ± 63.6 mg/dl, p = 0.22, analyses of variance (ANOVA)), there were no significant changes in total cholesterol (TC), TG levels, high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) in either group. Serum free thyroxine (fT4) levels were significantly decreased in the CBZ group (baseline: 1.15 ± 0.06 ng/dl, 1 month: 1.00 ± 0.16 ng/dl, 6 months: 0.98 ± 0.14 ng/dl, p = 0.03, ANOVA). In contrast, there were no significant changes in fT4 or thyroid-stimulating hormone (TSH) levels in the LEV group. The results of the present study suggest that LEV monotherapy does not affect lipid profile or thyroid function while CBZ monotherapy may cause thyroid dysfunction.

Antiepileptic drugs and suicide-related behavior: Is it the drug or comorbidity?

We sought to compare trends of suicide-related behavior (SRB) before and after initiation of antiepileptic drug (AED) therapy among AED users (with and without epilepsy) to that of individuals without AED use controlling for sociodemographic characteristics and mental health comorbidity. We used national Veterans Health Administration (VHA) data for post-9/11 veterans who received VHA care (2013-2014) without prior AED use. We conducted generalized estimation equation (GEE) analyses, stratified by epilepsy status and type of AED received, to assess the trend of SRB prevalence the year prior to and after the index date (date of first AED prescription/date of first health care encounter for non-AED users) controlling for sociodemographic factors and mental health comorbidity. The GEE analysis showed significant curvilinear trends of SRB prevalence over the 24-month study period among the AED users, indicating that the probability of SRB diagnoses increased over time with a peak before the index month and decreased thereafter. Similar patterns were observed among non-AED users, but significantly lower odds for SRB. Among AED users, there were no significant differences by epilepsy status; however, higher SRB prevalence and differential SRB trajectory measures were observed among those who received AEDs with mood-stabilizing action. The peak of SRB prior to and rapid reduction in SRB after initiation of AED, and the finding that individuals eventually prescribed a mood-stabilizing AED (vs other AED or levetiracetam) had higher odds of SRB, suggests a strong possibility that the relationship of AED and SRB is one of residual confounding.

Epilepsy treatment patterns among patients with tuberous sclerosis complex

IntroductionTuberous sclerosis complex (TSC) is a rare congenital disorder often associated with epilepsy. However, real-world treatment patterns for epilepsy in patients with TSC are not yet well categorized. MethodsThis study included patients with TSC and epilepsy from fifteen clinics in the United States and one in Belgium who were enrolled in the TSC Natural History Database (2006–2014). Patient demographics and epilepsy treatment patterns, including the use of anti-epileptic drugs (AEDs), epilepsy surgeries, and dietary therapies were assessed. ResultsOf the 1328 patients with TSC in the database, 1110 (83.6%) were diagnosed with epilepsy. The median age of epilepsy diagnosis was 0.7 years. Of those who received treatment for epilepsy (92.3%), 99.5% were prescribed AEDs, 25.3% underwent surgery, 7.9% were prescribed special diets, and 1% were prescribed mammalian target of rapamycin (mTOR) inhibitors. Of the patients receiving AEDs, over half (64.5%) used ≥3 different AEDs, and 22.5% underwent surgical treatment following AED initiation. Of the patients who underwent surgery, 35.1% had subsequent surgery. ConclusionThe use of multiple AEDs and surgical interventions may indicate a need for new therapies to reduce the treatment burden among patients with TSC and epilepsy.

S82. Paroxysmal sympathetic hyperactivity evident as cyclical pattern on quantitative EEG analysis

Introduction Episodic fluctuations in sympathetic activity following traumatic brain injury (TBI) have been described for decades, with paroxysmal sympathetic hyperactivity (PSH) being the currently accepted term for this entity. While early reports postulated an epileptic mechanism, our understanding of the pathophysiology of PSH has evolved. Current hypotheses center around deregulation of central descending inhibitory inputs from the insula and cingulate cortex, resulting in increased sympathetic output from the hypothalamus, diencephalon and brainstem. We present a case of PSH with evidence of disrupted sympathetic arousal networks. Methods A 41-year-old woman suffered a TBI with multifocal supratentorial hemorrhages and intraparenchymal contusions. Eight days post-MVA she developed episodes of tachycardia, hypertension, diaphoresis, back-arching and extensor posturing of the upper extremities upon stimulus. These events were assumed to be epileptic and treated with lorazepam (up to 16 mg/24 h) and phenobarbital (up to 345 mg/24 h) to no avail. Episodes improved with dexmedetomidine and clonidine. Continuous video-EEG was ordered for event characterization. Results EEG background was characterized by reactive generalized theta activity without interictal discharges. Multiple stimulus-induced stereotypical events were captured on the first EEG, prior to initiation of anti-epileptic drugs and dexmedetomidine. These were time-locked with static generalized rhythmic delta activity, often sharply contoured (GRDA + S). Quantitative EEG cycled between GRDA+S and polymorphic theta; transitions were often associated with stimulation or arousal. Thus, the events were shown to be stimulus/arousal-induced PSH time-locked with GRDA+S. The second EEG on lorazepam (2 mg q6h) and dexmedetomidine (26 mcg/kg/h) demonstrated less GRDA and no PSH. The third EEG on phenobarbital (130 mg qhs) and less dexmedetomidine (1.5 mcg/kg/h) demonstrated polymorphic delta slowing during episodes of PSH. Therefore, PSH was seen prior to initiation of dexmedetomidine and while on a low dose, but not while on a higher dose. Phenobarbital did not improve PSH. Conclusion Episodes of PSH were non-epileptic and concordant with cyclical stimulus or arousal-induced GRDA. This pattern is thought to represent cortical-subcortical dysfunction rather than hyperexcitability, as shown in a recent retrospective analysis of critical care continuous EEG in which no association was found between GRDA and seizures. The cyclical pattern on scalp and quantitative EEG reflected increased generalized rhythmicity with arousal and episodes of PSH; akin to stimulus/arousal-induced rhythmic or periodic or ictal discharges (SIRPIDs) seen in critically ill patients. The pattern seen on the cEEG reflects network disruption during PSH rather than a hyperirritable cortex; we believe that treatment of PSH should target sympathetic arousal networks rather than cortical hyperexcitability.