RESUMEN

INTRODUCTION: Nonadherence to antiseizure medications (ASMs) is associated with increased mortality, morbidity, health care utilization, and costs. AREAS COVERED: This article reviewed 18 randomized controlled trials published between Jan 2010 and Feb 2024 on Medication Adherence Enhancing Intervention (MAEI) for people with epilepsy. The adequacy of reporting intervention development process was assessed using the GUIDance for the rEporting of intervention Development (GUIDED). The adequacy of the intervention description was assessed using the Template for Intervention Description and Replication (TIDieR) checklist. The interventions were categorized as educational (n = 7), behavioral (n = 5), or mixed (n = 6). The impact of MAEIs on adherence is mixed with majority of studies either reporting no difference between intervention and control groups (n = 6) or improvement in the intervention group (n = 7). The shortcomings in the reporting of MAEIs development, MAEIs description, and MAEIs impact measurement were discussed. EXPERT OPINION: Future research needs to accomplish the following tasks: 1) develop and test valid epilepsy-specific self-report measures for assessing adherence; 2) optimize intervention design; and 3) increase transparency in reporting all stages of research.

Asunto(s)

Anticonvulsivantes , Epilepsia , Cumplimiento de la Medicación , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Proyectos de Investigación , Autoinforme , Aceptación de la Atención de Salud , Educación del Paciente como Asunto

RESUMEN

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Asunto(s)

Anticonvulsivantes , Lesiones Traumáticas del Encéfalo , Cuidados Críticos , Levetiracetam , Convulsiones , Humanos , Lesiones Traumáticas del Encéfalo/complicaciones , Anticonvulsivantes/uso terapéutico , Convulsiones/etiología , Convulsiones/prevención & control , Convulsiones/tratamiento farmacológico , Levetiracetam/uso terapéutico , Cuidados Críticos/normas , Adulto , Fenitoína/uso terapéutico , Fenitoína/análogos & derivados , Hospitalización , Guías de Práctica Clínica como Asunto

RESUMEN

There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate­severe traumatic brain injury (TBI). We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate­severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate­severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate­severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Asunto(s)

Humanos , Adulto , Convulsiones/prevención & control , Lesiones Traumáticas del Encéfalo/complicaciones , Anticonvulsivantes/uso terapéutico

RESUMEN

OBJECTIVE: To investigate the relationships between stress, anxiety, and depression and medication adherence behavior in patients with epilepsy (PEW). METHODS: A cross-sectional study design was conducted on 235 PEW in the Qazvin's Boo Ali Sian Hospital. Data collection tools included socio demographic and clinical data form, morisky medication adherence scale (MMAS-8), depression anxiety stress scales -21(DASS-21). We used adjusted multivariate logistic regression model for statistical analysis. RESULTS: A considerable proportion of patients reported mild, moderate, severe and extremely severe symptoms of depression (177 [75/3%]), anxiety (169 [71.9 %]), and stress (158 [67.2 %]). However, 61/8% of the participant had proper medication adherence and 38/3% had poor medication adherence. The results of adjusted multivariate logistic regression showed that in patients who had severe and extremely severe depression and anxiety, the probability of poor medication adherence was higher (P < 0.05). The levels of stress were not significant predictors for medication adherence behavior (P > 0.05). CONCLUSION: According to this study, severe and extremely severe depression and anxiety can be considered as an important predicting factor in the lack of adherence to antiepileptic medication. PRACTICE IMPLICATIONS: Healthcare professionals can improve care of patients with PEW by considering patients' mental and psychological health problems in educational, counseling and supportive programs.

Asunto(s)

Depresión , Epilepsia , Humanos , Estudios Transversales , Depresión/psicología , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Epilepsia/psicología , Cumplimiento de la Medicación/psicología

RESUMEN

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

RESUMEN

OBJECTIVE: There are no clinical guidelines dedicated to the treatment of epilepsy in older adults. We investigated physician opinion and practice regarding the treatment of people with epilepsy aged 65 years or older. We also sought to study how our opinion and practice varied between geriatricians, general neurologists, and epilepsy neurologists (i.e., epileptologists). METHODS: We initially piloted our survey to measure test-retest reliability. Once finalized, we disseminated the survey via two rounds of facsimiles, and then conventional mail, to eligible individuals listed in a national directory of Canadian physicians. We used descriptive statistics such as stacked bar charts and tables to illustrate our findings. RESULTS: One hundred forty-four physicians (104 general neurologists, 25 geriatricians, and 15 epileptologists) answered our survey in its entirety (overall response rate of 13.2%). Levetiracetam and lamotrigine were the preferred antiseizure medications (ASMs) to treat older adults with epilepsy. Two thirds of epileptologists and almost half of general neurologists would consider prescribing lacosamide in >50% of people aged >65 years; only one geriatrician was of the same opinion. More than 40% of general neurologists and geriatricians erroneously believed that none of the ASMs mentioned in our survey was previously studied in randomized controlled trials specific to the treatment of epilepsy in older adults. Epileptologists were more likely as compared to general neurologists and geriatricians to recommend epilepsy surgery (e.g., 66.6% vs. 22.9%-37.5% among older adults). SIGNIFICANCE: Therapeutic decisions for older adults with epilepsy are heterogeneous between physician groups and sometimes misalign with available clinical evidence. Our surveyed physicians differed in their approach to ASM choice as well as perception of surgery in older adults with epilepsy. These findings likely reflect the lack of clinical guidelines dedicated to this population and the deficient implementation of best practices.

Asunto(s)

Epilepsia , Humanos , Anciano , Reproducibilidad de los Resultados , Canadá , Epilepsia/tratamiento farmacológico , Epilepsia/cirugía , Epilepsia/epidemiología , Anticonvulsivantes/uso terapéutico , Levetiracetam/uso terapéutico

RESUMEN

Up to 10% of people living to 80 years of age have one or more seizures; and many will not require anti-seizure medication (ASMs). In 85% of patients, the diagnosis comes from the history of the index event. One-third of patients with an apparent "first seizure" have previous events, changing their diagnosis to epilepsy. Targeted investigations are important for classification and risk prediction. Patients with a low risk of seizure recurrence are not usually offered ASM treatment. High-risk patients have multiple seizures, neurological deficits, intellectual disability and/or relevant abnormal investigations; and are offered ASMs. Individual factors modulate this decision-making. Future integrated technologies offer the game-changing potential for seizure monitoring and prediction, but are not yet robust, convenient or affordable. Therapeutic drug monitoring in patients taking ASMs may confirm ASM toxicity, or when non-adherence, malabsorption, or rapid metabolism are suspected causes of breakthrough seizures. They are less useful when these factors are intermittent or irregular. Current evidence does not favour routine monitoring of serum levels, as it neither reliably predicts control, relapse, or adverse effects. The decision to discontinue ASM should follow a full discussion with the patient of risks and benefits. Along with population risk factors for seizure recurrence, the patient's lifestyle and preferences must be considered. ASM are usually discontinued in a slow step-wise fashion, one at a time, after at least two years of remission. Seizure recurrence risk plateaus only after 2 years following ASM discontinuation, and patients need access to specialist follow-up over that period.

Asunto(s)

Anticonvulsivantes , Epilepsia , Humanos , Adulto , Anticonvulsivantes/efectos adversos , Epilepsia/tratamiento farmacológico , Factores de Riesgo , Inducción de Remisión , Factores de Tiempo

RESUMEN

Background: Medication adherence is a fundamental determinant of effective treatment. However, people with epilepsy have poor compliance with their treatment because of the chronic nature of the disease. Limited studies have been conducted to address antiepileptic medication adherence in Africa, including Ethiopia. Thus, the aim of this study was to assess antiepileptic drug adherence and its asociated factors among patients with epilepsy attending outpatient department of Amanuel Mental Specialized Hospital. Methods: A cross-sectional study design was conducted on 439 patients with epilepsy in Amanuel Mental Specialized Hospital. Medication adherence reporting scale-5 (MARS-5) was used to assess adherence to antiepileptic drugs. The Oslo social support, Jacob perceived stigma scale, and hospital anxiety and depression scale (HADS) were the instruments used to assess associated factors. Simple and multiple linear regression analysis models were fitted. Then, the adjusted unstandardized beta (ß) coefficient at a 95% confidence level was used. Results: The mean(SD) score of antiepileptic medication adherence was 16.38(±3.76) with 95%CI:(16.03, 16.72). Depressive symptoms (ß= -1.35, 95% CI: (-2.04, -0.65)), anxiety symptoms (ß=-1.12,95%CI:(-1,79,-0.44), perceived stigma (ß= -1.64, 95% CI:-2.16,-1.12), being single (ß=-0.67, 95%CI:-1.20,-0.14), presence of seizure per month(ß=-2.11,95% CI: (-2.81,-1.41) and antiepileptic drug adverse effect(ß=-0.07,95%CI:-0.11,-0.03) were factors associated with anti-epileptic medication adherence. Conclusions: The results suggest that the mean score of adherence to antiepileptic drugs was poor as compared to other settings. Antiepileptic medication adherence screening tool should be included in the patient's treatment protocol.

Asunto(s)

Anticonvulsivantes , Epilepsia , Humanos , Anticonvulsivantes/uso terapéutico , Estudios Transversales , Etiopía , Estudios de Seguimiento , Epilepsia/tratamiento farmacológico , Cumplimiento de la Medicación , Hospitales Psiquiátricos

RESUMEN

Palliative care patients experience seizures in different stages of their disease and may not tolerate oral medications toward the end of life. Subcutaneous infusions of levetiracetam and sodium valproate are increasingly used off-label. This retrospective analysis (conducted from January 2019 to July 2020 in Australia) reports the effectiveness and adverse effects of levetiracetam and sodium valproate delivered via subcutaneous infusion. The doses ranged from 500 to 3000 mg/d of levetiracetam and 500 to 2500 mg/d of sodium valproate. The concentrations ranged from 20 to 83 mg/mL of levetiracetam and 20 to 50 mg/mL of sodium valproate. Subcutaneous levetiracetam was given for a median duration of 6.5 days, with no seizure recurrences in 75% of patients and no reported adverse effects in any patients. Subcutaneous sodium valproate was given for a median duration of 3.5 days, with no reported seizure recurrences in 83% of patients and one report of a localized skin reaction. This analysis suggests that subcutaneous levetiracetam and sodium valproate can effectively control seizures in palliative care populations, with minimal localized reactions.

Asunto(s)

Piracetam , Ácido Valproico , Humanos , Levetiracetam/uso terapéutico , Ácido Valproico/efectos adversos , Anticonvulsivantes/efectos adversos , Cuidados Paliativos , Estudios Retrospectivos , Piracetam/efectos adversos , Resultado del Tratamiento , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico

RESUMEN

BACKGROUND: Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear. METHODS: A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged < 18 years), preclinical, reviews, case reports, and articles that included patients with a preexisting seizure condition or epilepsy were excluded. The coprimary meta-analyses examined first seizure events in (1) levetiracetam versus no antiseizure medication and (2) levetiracetam versus other antiseizure medications in all ICH, TBI, SAH, and supratentorial neurosurgery populations. Secondary meta-analyses evaluated the same comparator groups in individual disease populations. Risk of bias in non-randomised studies - of interventions (ROBINS-I) and risk-of-bias tool for randomized trials (RoB-2) tools were used to assess risk of bias. RESULTS: A total of 30 studies (n = 6 randomized trials, n = 9 prospective studies, and n = 15 retrospective studies), including 7609 patients (n = 4737 with TBI, n = 701 with SAH, n = 261 with ICH, and n = 1910 with neurosurgical diseases) were included in analyses. Twenty-seven of 30 (90%) studies demonstrated moderate to severe risk of bias, and 11 of 30 (37%) studies used low-dosage levetiracetam (250-500 mg twice daily). In the primary meta-analyses, there were no differences in seizure events for levetiracetam prophylaxis (n = 906) versus no antiseizure medication (n = 2728; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.53-1.16, P = 0.23, fixed-effect, I2 = 26%, P = 0.23 for heterogeneity) or levetiracetam (n = 1950) versus other antiseizure prophylaxis (n = 2289; OR 0.84, 95% CI 0.55-1.28, P = 0.41, random-effects, I2 = 49%, P = 0.005 for heterogeneity). Only patients with supratentorial neurosurgical diseases benefited from levetiracetam compared with other antiseizure medications (median 0.70 seizure events per-patient-year with levetiracetam versus 2.20 seizure events per-patient-year for other antiseizure medications, OR 0.34, 95% CI 0.20-0.58, P < 0.001, fixed-effects, I2 = 39%, P = 0.13 for heterogeneity). There were no significant differences in meta-analyses of patients with ICH, SAH, or TBI. Adverse events of any severity were reported in a median of 8% of patients given levetiracetam compared with 21% of patients in comparator groups. CONCLUSIONS: Based on the current moderately to seriously biased heterogeneous data, which frequently used low and possibly subtherapeutic doses of levetiracetam, our meta-analyses did not demonstrate significant reductions in seizure incidence and neither supports nor refutes the use of levetiracetam prophylaxis in TBI, SAH, or ICH. Levetiracetam may be preferred post supratentorial neurosurgery. More high-quality randomized trials of prophylactic levetiracetam are warranted.

Asunto(s)

Anticonvulsivantes , Convulsiones , Adolescente , Anticonvulsivantes/uso terapéutico , Niño , Humanos , Levetiracetam/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Convulsiones/prevención & control

RESUMEN

Medication adherence is a fundamental determinant of effective treatment. However, people with epilepsy have poor compliance with their treatment because of the chronic nature of the disease. Limited studies have been conducted to address antiepileptic medication adherence in Africa, including Ethiopia. Thus, the aim of this study was to assess antiepileptic drug adherence and its asociated factors among patients with epilepsy attending outpatient department of Amanuel Mental Specialized Hospital. METHODS: A cross-sectional study design was conducted on 439 patients with epilepsy in Amanuel Mental Specialized Hospital. Medication adherence reporting scale-5 (MARS-5) was used to assess adherence to antiepileptic drugs. The Oslo social support, Jacob perceived stigma scale, and hospital anxiety and depression scale (HADS) were the instruments used to assess associated factors. Simple and multiple linear regression analysis models were fitted. Then, the adjusted unstandardized beta (ß) coefficient at a 95% confidence level was used. RESULTS: The mean (SD) score of antiepileptic medication adherence was 16.38(±3.76) with 95%CI:(16.03, 16.72). Depressive symptoms (ß= -1.35, 95% CI: (-2.04, -0.65)), anxiety symptoms (ß=-1.12,95%CI:(-1,79, -0.44), perceived stigma (ß= -1.64, 95% CI: -2.16, -1.12), being single (ß=-0.67, 95%CI: -1.20, -0.14), presence of seizure per month (ß=-2.11,95% CI: (-2.81, -1.41) and antiepileptic drug adverse effect (ß=-0.07,95%CI: -0.11, -0.03) were factors associated with anti-epileptic medication adherence. CONCLUSION: The results suggest that the mean score of adherences to antiepileptic drugs was poor as compared to other settings. Antiepileptic medication adherence screening tool should be included in the patient's treatment protocol

Asunto(s)

Epilepsia , Cumplimiento de la Medicación , Accesibilidad a los Servicios de Salud , Anticonvulsivantes

RESUMEN

BACKGROUND: Epilepsy is the most common chronic neurological disease in dogs that adversely affects the quality of life (QoL) of affected dogs and their owners. Research on epilepsy in dogs is expanding internationally, but where best to focus limited research time, funds, and expertise to achieve better outcomes for affected dogs and their owners has not been studied. OBJECTIVE: To explore idiopathic epilepsy (IE) research priorities of owners of dogs with IE, general practice veterinarians, and veterinary neurologists. METHODS: An international online survey was conducted in 2016 and repeated in 2020. Participants rated the absolute importance and relative rank of 18 areas of IE research, which were compared between groups and time points. RESULTS: Valid responses were received from 414 respondents in 2016 and 414 respondents in 2020. The development of new anti-seizure drugs (ASD) and improving the existing ASD management were considered the most important research priorities. Areas of research with increasing priority between 2016 and 2020 included non-ASD management, with the greatest potential seen in behavioral and dietary-based interventions. Disagreements in priorities were identified between groups; owners prioritized issues that impacted their and their dog's QoL, for example, adverse effects and comorbidities, whereas general practitioner vets and neurologists prioritized clinical issues and longer-term strategies to manage or prevent IE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Ensuring that voices of owners are heard in the planning of future research should be a broader goal of veterinary medicine, to target research efforts toward areas most likely to improve the QoL of the dog-owner dyad.

Asunto(s)

Enfermedades de los Perros , Epilepsia , Medicina General , Neurología , Veterinarios , Animales , Enfermedades de los Perros/tratamiento farmacológico , Perros , Epilepsia/tratamiento farmacológico , Epilepsia/veterinaria , Humanos , Calidad de Vida , Investigación , Especialización , Encuestas y Cuestionarios

RESUMEN

OBJECTIVE: We report data from the Raoul Wallenberg Australian Register of Antiepileptic Drugs in Pregnancy (APR) to see if there are significant differences in relation to the courses and outcomes of the twin pregnancies contained in the register, as compared with the singleton ones. METHODS: The APR has been under the oversight of Melbourne institutional Human Ethics Research Committees; all women enrolled in the APR have provided written informed consent. Data from the APR were transferred to a spreadsheet and then analyzed using simple statistical techniques including logistic regression. RESULTS: The population studied comprised 44 twin and 2261 singleton pregnancies; thus, twin pregnancies accounted for 1.91% of all pregnancies studied. The women carrying twins tended to be older than the women with singleton pregnancies to a statistically significant extent, their pregnancies more often originated from assisted fertilization techniques, and their babies were more often delivered by cesarean section. There were no statistically significant differences in relation to antiepileptic drug (AED) therapy. Individual twins had statistically significantly lower mean birthweights than singleton babies and they were statistically significantly more often involved structurally malformed foetuses. In the first year of life, the twin pregnancies statistically significantly more often produced offspring that were affected by seizures in infancy. SIGNIFICANCE: The data suggest that there may be an increased hazard of fetal malformation in the offspring of twin pregnancy in women with epilepsy, but that with contemporary standards of management of epilepsy and pregnancy, there is unlikely to be an increased hazard of seizure-affected pregnancy.

Asunto(s)

Epilepsia/complicaciones , Complicaciones del Embarazo/patología , Embarazo Gemelar , Australia/epidemiología , Estudios de Casos y Controles , Cesárea/estadística & datos numéricos , Anomalías Congénitas/epidemiología , Femenino , Humanos , Embarazo , Resultado del Embarazo , Embarazo Gemelar/estadística & datos numéricos , Sistema de Registros

RESUMEN

Epilepsy affects approximately 1% of the population. First-line treatment for epilepsy is the administration of anti-seizure medication, also referred to as antiepileptic drugs (AEDs), although this nomenclature is erroneous as these medications typically do not impact underlying epileptogenic processes; the goal of these medications is to control symptoms. Over 30% of patients are classified as having "medically refractory" epilepsy, i.e., lack of adequate seizure control despite trials of two or three AEDs (Kwan and Brodie, N Engl J Med 342:314-9, 2000). Epilepsy is associated with worse quality of life in children, adolescents, and their families (Cianchetti et al., Seizure 24:93-101, 2015). Patients with epilepsy have a two to three times greater risk of death than the general population, by various causes including sudden unexplained death in epilepsy patients (SUDEP) (Abdel-Mannan et al., Epilepsy Behav 90:99-106, 2019). It is these factors, among others, that have motivated the continued development of AEDs. This chapter will review the history and evolution of AED development, features of specific AEDs with a focus on the newest generation, and examples of AEDs in development.

Asunto(s)

Anticonvulsivantes/farmacología , Epilepsia , Pediatría , Adolescente , Niño , Humanos , Calidad de Vida

RESUMEN

BACKGROUND: Current international guidelines for traumatic brain injury (TBI) recommend the use of phenytoin for the prevention of early post traumatic seizures (PTS) when the benefits are thought to outweigh the risks. In practice however, alternative antiepileptic drugs (AEDs) such as levetiracetam and valproate are being used as they are believed to have a more favourable risk profile. This is despite there being insufficient evidence to support their efficacy. The purpose of this study was to identify which AED was prescribed to patients presenting with a TBI at a single institution, and to determine the rate of early PTSs. METHODS: This was a retrospective case-note review study done at the Flinders Medical Centre including patients admitted from May 2013 to June 2017. All patients with traumatic intracranial haematomas were included. Patients were excluded if they had seizures prior to presentation to hospital or died within 24 h of injury. The primary outcomes were rate of early PTSs and the type of prophylactic AED prescribed. RESULTS: During this study period, 610 patients presented with a mild, moderate or severe traumatic brain injury. Overall, 16% of patients were prescribed an AED, with more than 90% of these patients being prescribed levetiracetam. Overall, the rate of early PTSs for patients prescribed AEDs was 2.9% compared with 3.5% for patients not prescribed AEDs (OR 0.83 CI 0.24-2.85 p = 1). CONCLUSIONS: This study showed that levetiracetam was the most commonly prescribed AED. It also demonstrated no statistically significant difference in the rate of early PTSs in patients with TBI, with or without prophylactic AEDs. This is in keeping with other contemporary studies, and therefore the routine administration of prophylactic AEDs may need to be re-examined.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Lesiones Traumáticas del Encéfalo/complicaciones , Epilepsia Postraumática/etiología , Epilepsia Postraumática/prevención & control , Pautas de la Práctica en Medicina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Neuronal ceroid lipofuscinoses type 2 disease (CLN2) is a very rare, autosomal recessive neurodegerative disease caused by deficient activity of the enzyme tripeptidyl peptidase 1 (TPP1). The seizures in CLN2 are polymorphic and resistant to antiepileptic drugs. In particular, myoclonus (epileptic and non-epileptic) predominant as the disease progresses. Herein, we present a child of CLN2 disease, who had near-continuous myoclonus, and was subsequently attenuated by administration of Perampanel. This girl had initially presented with language delay and generalized tonic clonic seizure at 3 years of age. The diagnosis of CLN2 was made via genetic study, which showed compound heterozygous mutation on TPP1 gene (c.622 C > T and partial gene deletion including at least exons 1-3). Currently, at the age of 8 years, there was near-continuous myoclonus (epileptic and non-epileptic), which worsen during acute illness. Eventually, she was given Perampanel with starting dose of 1 mg/day and slowly titrated upto 6 mg/day in 4 weeks. There was significant attenuation of myoclonus (>50% seizure reduction). To our knowledge, this is the first case in the literature describing the efficacy of perampanel in treating myoclonus in CLN2 disease.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Mioclonía/tratamiento farmacológico , Lipofuscinosis Ceroideas Neuronales/tratamiento farmacológico , Piridonas/uso terapéutico , Aminopeptidasas/genética , Niño , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Femenino , Humanos , Mutación , Mioclonía/diagnóstico por imagen , Mioclonía/genética , Mioclonía/fisiopatología , Lipofuscinosis Ceroideas Neuronales/diagnóstico por imagen , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/fisiopatología , Nitrilos , Serina Proteasas/genética , Tripeptidil Peptidasa 1

RESUMEN

High-dose busulfan (BU) followed by high-dose cyclophosphamide (CY) before allogeneic hematopoietic cell transplantation (HCT) has long been used as treatment for hematologic malignancies. Administration of phenytoin or newer alternative antiepileptic medications (AEMs) prevents seizures caused by BU. Phenytoin induces enzymes that increase exposure to active CY metabolites in vivo, whereas alternative AEMs do not have this effect. Lower exposure to active CY metabolites with the use of alternative AEMs could decrease the risk of toxicity but might increase the risk of recurrent malignancy after HCT. Previous studies have not determined whether outcomes with alternative AEMs differ from those with phenytoin in patients treated with BU/CY before allogeneic HCT. We studied a cohort of 2155 patients, including 1460 treated with phenytoin and 695 treated with alternative AEMs, who received BU/CY before allogeneic HCT between 2004 and 2014. We found no differences suggesting decreased overall survival or relapse-free survival or increased risks of relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or regimen-related toxicity associated with the use of alternative AEMs compared with phenytoin. The risk of dialysis was lower in the alternative AEM group than in the phenytoin group. Alternative AEMs are safe for prevention of seizures after BU administration and can avoid the undesirable toxicities and drug interactions caused by phenytoin.

Asunto(s)

Anticonvulsivantes/administración & dosificación , Busulfano/administración & dosificación , Ciclofosfamida/administración & dosificación , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Fenitoína/administración & dosificación , Convulsiones , Acondicionamiento Pretrasplante , Adolescente , Adulto , Anciano , Aloinjertos , Anticonvulsivantes/efectos adversos , Busulfano/efectos adversos , Niño , Preescolar , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Femenino , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Persona de Mediana Edad , Fenitoína/efectos adversos , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Convulsiones/mortalidad , Tasa de Supervivencia

RESUMEN

INTRODUCTION: Counseling for women with epilepsy of childbearing potential surrounding pregnancy issues is of the utmost importance and should be done when antiepileptic medications are prescribed and reviewed regularly at clinic visits. Physicians must be familiar with risks associated with antiepileptic medication, and endeavor to minimize risks to a fetus while selecting best medications for epilepsy type. AREAS COVERED: The authors discuss the role of folic acid, updated evidence relating to the occurrence of major congenital malformations and neurocognitive risks associated with antiepileptic medication. They also examine the rationale for monitoring drug levels, optimum delivery strategies, and evidence for the safety of breastfeeding while taking antiepileptic medication. EXPERT OPINION: Valproate carries the highest known teratogenic risk in pregnancy and should only be prescribed to women of child-bearing potential in a specialist setting. There is a need for the ongoing register collection of risks associated with newer AEDs which lack substantial (major) data. Choosing these newer medications can create a dilemma for physicians, particularly when seizures are not well controlled or where treatment options are limited. The authors advocate a multidisciplinary team approach to managing women with epilepsy so that pregnancies in such women can be well managed in an optimum and individualized fashion.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Animales , Anticonvulsivantes/efectos adversos , Epilepsia/complicaciones , Femenino , Humanos , Embarazo , Complicaciones del Embarazo/fisiopatología

RESUMEN

Drug eruptions represent a wide spectrum of cutaneous reactions to various pharmaceutical agents. Given their complexity and varied patterns of presentation, these phenomena are the subject of study of many fields of medicine. Gabapentin is a widely prescribed medication, with numerous drug reactions previously reported. We present a unique case of a gabapentin-induced drug eruption primarily affecting the feet.

Asunto(s)

Analgésicos/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Dermatosis del Pie/inducido químicamente , Dermatosis del Pie/patología , Gabapentina/efectos adversos , Adulto , Femenino , Humanos

RESUMEN

Neonatal seizures are treated with phenobarbital and prolonged treatment does not prevent postneonatal epilepsy. The authors documented factors influencing phenobarbital use and determined whether published data changed practice. A total of 83 neonates with symptomatic seizures, clinical or electrographic, were evaluated for treatment, incidence of postneonatal epilepsy, and associated factors. Median phenobarbital treatment was 81 days. Nineteen children (23%) developed postneonatal epilepsy. Longer duration of seizures and an infectious etiology were associated with postneonatal epilepsy suggesting no impact on duration of phenobarbital treatment. Treatment duration was associated with duration of seizures and use of a second antiseizure medication. This study supports early discontinuation of phenobarbital and suggests providers utilize factors such as use of a second antiseizure medication and time to seizure control to determine phenobarbital duration, despite prior studies suggesting no impact of treatment length.

Asunto(s)

Anticonvulsivantes/administración & dosificación , Fenobarbital/administración & dosificación , Pautas de la Práctica en Medicina , Convulsiones/tratamiento farmacológico , Epilepsia/prevención & control , Femenino , Estudios de Seguimiento , Humanos , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Tiempo