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Epilepsy & Behavior : E&B Oct 2021In selected children with drug-resistant epilepsy (DRE), epilepsy surgery is the most effective treatment option, but unfortunately remains highly underutilized. One of... (Review)
Review
OBJECTIVE
In selected children with drug-resistant epilepsy (DRE), epilepsy surgery is the most effective treatment option, but unfortunately remains highly underutilized. One of the critical obstacles to pursuing surgical therapy is parents/caregivers' decision against surgery or to delay the surgery until no other treatment option exists. Understanding caregiver decision-making around epilepsy surgery can improve patient/caregiver experience and satisfaction while facilitating appropriate decision-making that optimizes clinical outcomes. The current review systematically explores the existing evidence on caregiver experience and the decision-making process toward epilepsy surgery.
METHODS
The study was conducted as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic literature review. Databases (PubMed Ovid, PubMed Medline, Web of Science, CINHAL, PsycInfo) were systematically searched in February 2021 using a defined search strategy and inclusion/exclusion criteria. Total 1304 articles were screened for titles and abstracts, and 54 full-text articles were retrieved for further assessment. We included 14 articles with critical quality assessment using two different tools for qualitative and questionnaire-based studies. A qualitative content analysis was performed to characterize caregiver experience, perception, and decision-making toward favorable or unfavorable opinions of epilepsy surgery.
RESULTS
Four concepts generated from the analysis may act as enablers or barriers to decision-making around epilepsy surgery: 1. Access to knowledge and information, 2. Communication and coordination issues, 3. Caregiver's emotional state, and 4. Socioeconomic effects. Subsequently, we provided a narrative synthesis of practice recommendations and a conceptual framework to adopt multi-pronged interventions to overcome identified diverse barriers to effective caregiver decision-making.
CONCLUSION
Multiple influences impact how caregivers decide about epilepsy surgery for their children, with no single factor identified as the primary driver for or against surgery. However, limited research has explored these influences. Future studies should focus on quantitatively examining factors to identify significant variables most likely to influence caregiver decision-making, ultimately overcoming barriers that limit utilization of epilepsy surgery as a treatment tool.
Topics: Caregivers; Child; Communication; Epilepsy; Humans; Parents; Personal Satisfaction
PubMed: 34428615
DOI: 10.1016/j.yebeh.2021.108263 -
Seizure Feb 2017To estimate the frequency and strength of fatigue in epilepsy patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To estimate the frequency and strength of fatigue in epilepsy patients.
METHODS
The MEDLINE, EMBASE, COCHRANE, Web of Science, and SCOPUS databases were searched, and hand-searched data were added. For inclusion, the studies had to be original research articles that included fatigue data from adult epilepsy patients. The strength was estimated using studies reporting fatigue scores of standardized inventories for the patients and healthy controls. The fatigue frequency was estimated based on studies reporting the number of fatigue events in patients. We also investigated risk factors for fatigue and the correlation of depression with fatigue in epilepsy patients.
RESULTS
Of 25,613 abstracts screened, we included 12 articles or proceedings with distinctive data. The Fatigue Severity Scale (FSS) was the most commonly used inventory for fatigue in epilepsy patients. Four studies compared FSS scores between 499 epilepsy patients and 295 healthy controls. The overall mean difference in the FSS scores was significant. Seven of the 12 studies reported the frequency of fatigue determined by the FSS for 700 epilepsy patients. As stated by the studies, the overall frequency of fatigue was 47.1%. The risk factors for fatigue in epilepsy patients were depression, sleep-related impairment, and sleep quality. Of the 12 studies, 7 revealed a significant correlation between depression and fatigue.
CONCLUSIONS
Fatigue is common in epilepsy patients and is closely correlated with depression. The identification and management of fatigue and its risk factors, especially depression, is mandatory for the management of epilepsy.
Topics: Epilepsy; Fatigue; Humans
PubMed: 28063374
DOI: 10.1016/j.seizure.2016.11.006 -
BMC Veterinary Research May 2016The safety profile of anti-epileptic drugs (AEDs) is an important consideration for the regulatory bodies, owners and prescribing clinicians. Information on their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The safety profile of anti-epileptic drugs (AEDs) is an important consideration for the regulatory bodies, owners and prescribing clinicians. Information on their adverse effects still remains limited. A systematic review including a meta-analytic approach was designed to evaluate existing evidence for the safety profile of AEDs in canine patients. Electronic searches of PubMed, CAB Direct and Google scholar were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies reporting adverse effects of AEDs in epileptic and healthy non-epileptic dogs were included. Studies were allocated to three groups based on their design. Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (proportion of specific adverse effects for each AED, prevalence and 95% confidence interval of the affected population in each study and comparative odds ratio of adverse effects for AEDs).
RESULTS
Ninety studies, including six conference proceedings, reporting clinical outcomes of AEDs' adverse effects were identified. Few studies were designed as blinded randomised controlled clinical trials. Many studies included low canine populations with unclear criteria of subject enrolment and short treatment periods. Direct comparisons suggested that imepitoin and levetiracetam might have a better safety profile than phenobarbital, whilst the latter might have a better safety profile than potassium bromide. However, none of these comparisons showed a statistically significant difference. Comparisons between other AEDs were not possible as a considerable amount of studies lacked power calculations or adequate data to allow further statistical analysis. Individual AED assessments indicated that levetiracetam might be one of the safest AEDs, followed by imepitoin and then phenobarbital and potassium bromide; these findings were all supported by a strong level of evidence. The safety profile in other AEDs was variable, but weak evidence was found to permit firm conclusions or to compare their safety to other AEDs.
CONCLUSIONS
This systematic review provides objective evaluation of the most commonly used AEDs' adverse effects. Adverse effects usually appeared mild in all AEDs and subsided once doses and/or serum levels were monitored or after the AED was withdrawn. Although phenobarbital might be less safe than imepitoin and levetiracetam, there was insufficient evidence to classify it as an AED with a high risk of major adverse effects. It is important for clinicians to evaluate both AEDs' effectiveness and safety on an individual basis before the selection of the appropriate monotherapy or adjunctive AED therapy.
Topics: Animals; Anticonvulsants; Dogs; Epilepsy; Outcome and Process Assessment, Health Care
PubMed: 27206489
DOI: 10.1186/s12917-016-0703-y -
The Cochrane Database of Systematic... Jan 2022The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs... (Review)
Review
BACKGROUND
The ideal objective of treating a person with epilepsy is to induce remission (free of seizures for some time) using antiepileptic drugs (AEDs) and withdraw the AEDs without causing seizure recurrence. Prolonged usage of AEDs may have long-term adverse effects. Hence, when a person with epilepsy is in remission, it is logical to attempt to discontinue the medication. The timing of withdrawal and the mode of withdrawal arise while contemplating withdrawal of AEDs. This review examines the evidence for the rate of withdrawal of AEDs (whether rapid or slow tapering) and its effect on seizure recurrence. This is an updated version of the Cochrane Review previously published in 2020.
OBJECTIVES
To quantify risk of seizure recurrence after rapid (tapering period of three months or less) or slow (tapering period of more than three months) discontinuation of antiepileptic drugs in adults and children with epilepsy who are in remission, and to assess which variables modify the risk of seizure recurrence.
SEARCH METHODS
For the latest update, on 8 November 2021, we searched: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid), and SCOPUS. There were no language restrictions. CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), CENTRAL, and the Specialized Registers of Cochrane Review Groups including Epilepsy.
SELECTION CRITERIA
Randomized controlled trials that evaluated withdrawal of AEDs in a rapid or slow tapering after varying periods of seizure control in people with epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the trials for inclusion and extracted the data. The outcomes assessed included seizure freedom after one, two, or five years of AED withdrawal; time to recurrence of seizure following withdrawal; occurrence of status epilepticus; mortality; morbidity due to seizure, such as injuries, fractures, and aspiration pneumonia; and quality of life (assessed by validated scale).
MAIN RESULTS
There are two included studies in this review. One study randomized 57 children with epilepsy with seizure freedom for at least two years to taper down the AED over one or six months. The study was not blinded and there were no details of randomization. Over the period of 54 months of follow-up, 20/30 participants in the one-month group remained seizure-free compared to 15/27 participants in the six-month group (no evidence of a difference). There was no information on time of seizure recurrence for each group to allow a comparison. The other study involved 149 children. There was a non-significant trend towards a lower risk of seizure recurrence after one year of AED withdrawal in participants allocated to slow tapering (risk ratio (RR) 0.76, 95% confidence interval (CI) 0.58 to 1.01; P = 0.06; very low-certainty evidence). At the end of two years, 30 participants were seizure free in the rapid-tapering group and 29 participants in the slow-tapering group (RR 0.87, 95% CI 0.58 to 1.29; P = 0.48; very low-certainty evidence). At the end of five years, 10 participants were seizure free in the rapid-tapering group and six participants in the slow-tapering group (RR 1.40, 95% CI 0.54 to 3.65; P = 0.49; very low-certainty evidence). There were no data for the other outcomes. Due to the methodological heterogeneity and the difference in the duration of tapering, we did not perform a quantitative synthesis of these studies. Currently, one Italian trial is ongoing that is investigating if a slow or a rapid withdrawal schedule of AEDs influences return of seizures (relapse) in adults with focal or generalized epilepsy who have been seizure free for at least two years (no preliminary results available).
AUTHORS' CONCLUSIONS
In view of methodological deficiencies, and small sample size of the two included studies, we cannot draw any reliable conclusions regarding the optimal rate of tapering of AEDs. Using GRADE, we assessed the certainty of the evidence as very low for outcomes for which data were available. We judged both studies to be at an overall high risk of bias. Further studies are needed in adults and children to investigate the optimal rate of withdrawal of AEDs and to study the effects of variables such as seizure types, aetiology, intellectual disability, electroencephalography abnormalities, presence of neurological deficits, and other comorbidities on the rate of tapering.
Topics: Adult; Anticonvulsants; Child; Epilepsy; Epilepsy, Generalized; Humans; Quality of Life; Seizures
PubMed: 35005782
DOI: 10.1002/14651858.CD005003.pub4 -
Epilepsia Jul 2014Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery.... (Review)
Review
Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery. Despite recent advances in the cellular and molecular biology of these conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The purpose if this work is to review the molecular underpinnings of FCDs and to highlight potential therapeutic targets. A systematic review of the literature regarding the histologic, molecular, and electrophysiologic aspects of FCDs was conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling comprises a common pathway underlying the structural and electrical disturbances of some FCDs. Other mechanisms such as viral infections, prematurity, head trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have shown positive results on seizure management in animal models and in a small cohort of patients with FCD. Encouraging progress has been achieved on the molecular and electrophysiologic basis of constitutive cells in the dysplastic tissue. Despite the promising results of mTOR inhibitors, large-scale randomized trials are in need to evaluate their efficacy and side effects, along with additional mechanistic studies for the development of novel, molecular-based diagnostic and therapeutic approaches.
Topics: Animals; Anticonvulsants; Drug Delivery Systems; Epilepsy; Gene Targeting; Humans; Malformations of Cortical Development; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 24861491
DOI: 10.1111/epi.12650 -
The Cochrane Database of Systematic... Jul 2018This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the treatment of new focal or generalized seizures. A Cochrane systematic review for clobazam monotherapy is expected to define its place in the treatment of new-onset or untreated seizures and highlight gaps in evidence.
OBJECTIVES
To evaluate the efficacy, effectiveness, tolerability and safety of clobazam as monotherapy in people with new-onset focal or generalized seizures.
SEARCH METHODS
For the latest update we searched the following databases on 19 March 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946- ), BIOSIS Previews (1969- ), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). There were no language restrictions.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials comparing clobazam monotherapy versus placebo or other anti-seizure medication in people with two or more unprovoked seizures or single acute symptomatic seizure requiring short-term continuous anti-seizure medication, were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Primary outcome measure was time on allocated treatment (retention time), reflecting both efficacy and tolerability. Secondary outcomes included short- and long-term effectiveness measures, tolerability, quality of life, and tolerance measures. Two authors independently extracted the data.
MAIN RESULTS
We identified three trials fulfilling the review criteria, which included 206 participants. None of the identified studies reported the preselected primary outcome measure. A meta-analysis was not possible. Lack of detail regarding allocation concealment and a high risk of performance and detection bias in two studies prompted us to downgrade the quality of evidence (by using the GRADE approach) for some of our results due to risk of bias.Regarding retention at 12 months, we detected no evidence of a statistically significant difference between clobazam and carbamazepine (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.61 to 1.12; low-quality evidence). There was low-quality evidence that clobazam led to better retention compared with phenytoin (RR 1.43, 95% CI 1.08 to 1.90). We could not determine whether participants receiving clobazam were found to be less likely to discontinue it due to adverse effects as compared to phenytoin (RR 0.10, 95% CI 0.01 to 1.65, low-quality evidence).
AUTHORS' CONCLUSIONS
We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naive children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each. At present, the available evidence is insufficient to inform clinical practice.
Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Carbamazepine; Child; Clobazam; Epilepsies, Partial; Epilepsy, Generalized; Humans; Phenytoin; Randomized Controlled Trials as Topic; Seizures
PubMed: 29995989
DOI: 10.1002/14651858.CD009258.pub3 -
International Journal of Molecular... Mar 2018Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic... (Review)
Review
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.
Topics: Anticonvulsants; Brain Diseases, Metabolic; Diet Therapy; Epilepsy; Humans
PubMed: 29543761
DOI: 10.3390/ijms19030871 -
PLoS Neglected Tropical Diseases 2013The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors, including the distribution of infectious diseases with neurologic sequels. To define the burden of epilepsy in Latin American Countries (LAC) and to investigate the strength of association with neurocysticercosis (NCC), considered one of the leading causes of epilepsy, we performed a systematic review and meta-analysis of the literature.
METHODOLOGY
Studies published until 2012 were selected applying predefined inclusion criteria. Lifetime epilepsy (LTE) prevalence, active epilepsy (AE) prevalence, incidence, mortality, treatment gap (TG) and NCC proportion among people with epilepsy (PWE) were extracted. Median values were obtained for each estimate using random effects meta-analysis. The impact of NCC prevalence on epilepsy estimates was determined using meta-regression models. To assess the association between NCC and epilepsy, a further meta-analysis was performed on case-control studies.
PRINCIPAL FINDINGS
The median LTE prevalence was 15.8/1,000 (95% CI 13.5-18.3), the median AE prevalence was 10.7/1,000 (95% CI 8.4-13.2), the median incidence was 138.2/100,000 (95% CI 83.6-206.4), the overall standardized mortality ratio was 1.4 (95% CI 0.01-6.1) and the overall estimated TG was 60.6% (95% CI 45.3-74.9). The median NCC proportion among PWE was 32.3% (95% CI 26.0-39.0). Higher TG and NCC estimates were associated with higher epilepsy prevalence. The association between NCC and epilepsy was significant (p<0.001) with a common odds ratio of 2.8 (95% CI 1.9-4.0).
SIGNIFICANCE
A high burden of epilepsy and of NCC in LAC and a consistent association between these two diseases were pointed out. Furthermore, NCC prevalence and TG were identified as important factors influencing epilepsy prevalence to be considered in prevention and intervention strategies.
Topics: Epilepsy; Humans; Incidence; Latin America; Neurocysticercosis; Prevalence
PubMed: 24205415
DOI: 10.1371/journal.pntd.0002480 -
Dialogues in Clinical Neuroscience 2021Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better... (Review)
Review
Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.
Topics: Brain; Brain Mapping; Child; Cognition; Electroencephalography; Epilepsy; Humans; Magnetic Resonance Imaging; Nerve Net; Neurodevelopmental Disorders
PubMed: 35860177
DOI: 10.1080/19585969.2022.2043128 -
Epilepsy & Behavior : E&B May 2022Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has... (Review)
Review
Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has changed considerably, and a comprehensive systematic review of the contemporary literature is lacking. Here we synthesized published evidence on the occurrence of clinical impacts by age, the economic and humanistic (health-related quality-of-life [HRQoL]) burden, and health state utility. We provide an evidence-based, contemporary visualization of the clinical manifestations, highlighting that DS is not limited to seizures; non-seizure manifestations appear early in life and increase over time, contributing significantly to the economic and humanistic burden of disease. The primary drivers of HRQoL in DS include seizure severity, cognition, and motor and behavioral problems; in turn, these directly affect caregivers through the extent of assistance required and consequent impact on activities of daily living. Unsurprisingly, costs are driven by seizure-related events, hospitalizations, and in-home medical care visits. This systematic review highlights a paucity of longitudinal data; most studies meeting inclusion criteria were cross-sectional or had short follow-up. Nonetheless, available data illustrate the substantial impact on individuals, their families, and healthcare systems and establish the need for novel therapies to address the complex spectrum of DS manifestations.
Topics: Activities of Daily Living; Epilepsies, Myoclonic; Epileptic Syndromes; Humans; Seizures; Spasms, Infantile
PubMed: 35334258
DOI: 10.1016/j.yebeh.2022.108661