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Neurology Jan 2017To review population-based studies of the prevalence and incidence of epilepsy worldwide and use meta-analytic techniques to explore factors that may explain... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review population-based studies of the prevalence and incidence of epilepsy worldwide and use meta-analytic techniques to explore factors that may explain heterogeneity between estimates.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed. We searched MEDLINE and EMBASE for articles published on the prevalence or incidence of epilepsy since 1985. Abstract, full-text review, and data abstraction were conducted in duplicate. Meta-analyses and meta-regressions were used to explore the association between prevalence or incidence, age group, sex, country level income, and study quality.
RESULTS
A total of 222 studies were included (197 on prevalence, 48 on incidence). The point prevalence of active epilepsy was 6.38 per 1,000 persons (95% confidence interval [95% CI] 5.57-7.30), while the lifetime prevalence was 7.60 per 1,000 persons (95% CI 6.17-9.38). The annual cumulative incidence of epilepsy was 67.77 per 100,000 persons (95% CI 56.69-81.03) while the incidence rate was 61.44 per 100,000 person-years (95% CI 50.75-74.38). The prevalence of epilepsy did not differ by age group, sex, or study quality. The active annual period prevalence, lifetime prevalence, and incidence rate of epilepsy were higher in low to middle income countries. Epilepsies of unknown etiology and those with generalized seizures had the highest prevalence.
CONCLUSIONS
This study provides a comprehensive synthesis of the prevalence and incidence of epilepsy from published international studies and offers insight into factors that contribute to heterogeneity between estimates. Significant gaps (e.g., lack of incidence studies, stratification by age groups) were identified. Standardized reporting of future epidemiologic studies of epilepsy is needed.
Topics: Databases, Bibliographic; Epilepsy; Female; Humans; Incidence; International Cooperation; Male; Prevalence
PubMed: 27986877
DOI: 10.1212/WNL.0000000000003509 -
BMC Veterinary Research Oct 2014Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic... (Review)
Review
BACKGROUND
Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic review was designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine IE. Electronic searches of PubMed and CAB Direct were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies describing objectively the efficacy of AEDs in dogs with IE were included. Studies were allocated in two groups, i.e. blinded randomized clinical trials (bRCTs), non-blinded randomized clinical trials (nbRCTs) and non-randomized clinical trials (NRCTs) (group A) and uncontrolled clinical trials (UCTs) and case series (group B). 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 (in particular the proportion of dogs with ≥ 50% reduction in seizure frequency).
RESULTS
Twenty-six studies, including two conference proceedings, reporting clinical outcomes of AEDs used for management of IE were identified. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. Only four bRCTs were identified in group A and were considered to offer higher quality of evidence among the studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam. For the remaining AEDs, favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use due to lack of bRCTs.
CONCLUSIONS
Oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of IE. However, variations in baseline characteristics of the dogs involved, significant differences between study designs and several potential sources of bias preclude definitive recommendations. There is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE.
Topics: Animals; Anticonvulsants; Dog Diseases; Dogs; Epilepsy
PubMed: 25338624
DOI: 10.1186/s12917-014-0257-9 -
The Cochrane Database of Systematic... Jun 2020Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018.
OBJECTIVES
To assess the effects of ketogenic diets for people with drug-resistant epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies.
SELECTION CRITERIA
RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction. Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate. Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported.
AUTHORS' CONCLUSIONS
The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty. More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.
Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Diet, Carbohydrate-Restricted; Diet, High-Protein Low-Carbohydrate; Diet, Ketogenic; Dietary Carbohydrates; Dietary Fats; Drug Resistant Epilepsy; Humans; Infant; Intention to Treat Analysis; Middle Aged; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Sample Size; Young Adult
PubMed: 32588435
DOI: 10.1002/14651858.CD001903.pub5 -
Seizure May 2019To summarize definitions, prevalence, risk factors, consequences, and acute management of seizure clusters using rescue medications.
PURPOSE
To summarize definitions, prevalence, risk factors, consequences, and acute management of seizure clusters using rescue medications.
METHODS
We searched MEDLINE for studies that assessed definitions, clinical characteristics, outcomes, and use of rescue medication for aborting seizure clusters.
RESULTS
Different clinical and statistical definitions for seizure clusters have been proposed, including: ≥3 seizures in 24 h, ≥2 seizures in 24 h, and ≥2 seizures in 6 h. Most studies of seizure clusters have been conducted in tertiary epilepsy centers, with refractory epilepsy patients. Patients with severe and poorly controlled epilepsy are more likely to experience seizure clusters. Seizure clusters can result in increased health care utilization and have negative impact on the quality of life of patients and caregivers. Use of benzodiazepine rescue medications in acute management of seizure clusters can help avoid progression to status epilepticus and reduce emergency room visits. Rescue medications are underutilized in seizure clusters. Currently, rectal diazepam gel is the only FDA approved rescue medication for seizure clusters. In addition, buccal midazolam is approved in European countries for treatment of prolonged seizures. However, various non-rectal non-IV benzodiazepines are safe and effective in treating acute seizures and clusters. Most patients and caregivers preferred non-rectal routes.
CONCLUSION
Identifying patients that are at high risk for seizure clusters, providing them with formal action plans and educating them about use of rescue medication for seizure clusters can help ameliorate the outcomes in this group of epilepsy patients.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Epilepsy; Humans; Infant; Middle Aged; Seizures; Young Adult
PubMed: 29871784
DOI: 10.1016/j.seizure.2018.05.013 -
Sleep Medicine Reviews Oct 2022Idiopathic generalized epilepsies are a group of sleep related epilepsy syndromes with sleep deprivation as a strong trigger for seizures and increased spike-wave... (Meta-Analysis)
Meta-Analysis Review
Idiopathic generalized epilepsies are a group of sleep related epilepsy syndromes with sleep deprivation as a strong trigger for seizures and increased spike-wave activity during sleep and transition to sleep. Neuropsychological deficits are common in Idiopathic generalized epilepsy patients. Learning and memory processes are closely linked to sleep. Therefore, this systematic review and meta-analysis investigates the evidence of sleep disturbances in Idiopathic generalized epilepsy patients. A search of the databases EMBASE, Medline and Scopus identified 22 studies comparing polysomnographic parameters and scores of sleep questionnaires between Idiopathic generalized epilepsy patients and healthy controls. Random effect univariate meta-analyses revealed reduced sleep efficiency, total sleep time, proportion of N2 stage and prolonged REM onset latency in Idiopathic generalized epilepsy patients. Self-assessed sleep quality of patients measured by the Pittsburgh sleep quality index was lower in two thirds of reporting studies. Considering the influence on behavioral issues, cognitive performance and quality of life, the revealed alteration in sleep architecture and lower subjective sleep quality emphasizes the importance of screening for sleep disturbances in the medical care of patients with Idiopathic generalized epilepsy.
Topics: Epilepsy, Generalized; Humans; Polysomnography; Quality of Life; Sleep; Sleep Quality; Sleep Wake Disorders
PubMed: 36037570
DOI: 10.1016/j.smrv.2022.101689 -
The Journal of Headache and Pain May 2019Migraine aura (MA) is a common and disabling neurological condition, characterized by transient visual, and less frequently sensory and dysphasic aura disturbances. MA...
BACKGROUND
Migraine aura (MA) is a common and disabling neurological condition, characterized by transient visual, and less frequently sensory and dysphasic aura disturbances. MA is associated with an increased risk of cardiovascular disorders and is often clinically difficult to distinguish from other serious neurological disorders such as transient ischemic attacks and epilepsy. Optimal clinical classification of MA symptoms is important for more accurate diagnosis and improved understanding of the pathophysiology of MA through clinical studies.
MAIN BODY
A systematic review of previous prospective and retrospective systematic recordings of visual aura symptoms (VASs) was performed to provide an overview of the different types of visual phenomena occurring during MA and their respective frequencies in patients. We found 11 retrospective studies and three prospective studies systematically describing VASs. The number of different types of VASs reported by patients in the studies ranged from two to 23. The most common were flashes of bright light, "foggy" vision, zigzag lines, scotoma, small bright dots and 'like looking through heat waves or water'.
CONCLUSIONS
We created a comprehensive list of VAS types reported by migraine patients based on all currently available data from clinical studies, which can be used for testing and validation in future studies. We propose that, based on this work, an official list of VAS types should be developed, preferably within the context of the International Classification of Headache Disorders of the International Headache Society.
Topics: Adult; Epilepsy; Female; Hallucinations; Humans; Ischemic Attack, Transient; Male; Migraine with Aura; Prospective Studies; Retrospective Studies; Vision, Ocular
PubMed: 31146673
DOI: 10.1186/s10194-019-1008-x -
Orphanet Journal of Rare Diseases Jul 2021No curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative... (Review)
Review
BACKGROUND
No curative therapy for mitochondrial disease (MD) exists, prioritizing supportive treatment for symptom relief. In animal and cell models ketones decrease oxidative stress, increase antioxidants and scavenge free radicals, putting ketogenic diets (KDs) on the list of management options for MD. Furthermore, KDs are well-known, safe and effective treatments for epilepsy, a frequent symptom of MD. This systematic review evaluates efficacy and safety of KD for MD.
METHODS
We searched Pubmed, Cochrane, Embase and Cinahl (November 2020) with search terms linked to MD and KD. From the identified records, we excluded studies on Pyruvate Dehydrogenase Complex deficiency. From these eligible reports, cases without a genetically confirmed diagnosis and cases without sufficient data on KD and clinical course were excluded. The remaining studies were included in the qualitative analysis.
RESULTS
Only 20 cases (14 pediatric) from the 694 papers identified met the inclusion criteria (one controlled trial (n = 5), 15 case reports). KD led to seizure control in 7 out of 8 cases and improved muscular symptoms in 3 of 10 individuals. In 4 of 20 cases KD reversed the clinical phenotype (e.g. cardiomyopathy, movement disorder). In 5 adults with mitochondrial DNA deletion(s) related myopathy rhabdomyolysis led to cessation of KD. Three individuals with POLG mutations died while being on KD, however, their survival was not different compared to individuals with POLG mutations without KD.
CONCLUSION
Data on efficacy and safety of KD for MD is too scarce for general recommendations. KD should be considered in individuals with MD and therapy refractory epilepsy, while KD is contraindicated in mitochondrial DNA deletion(s) related myopathy. When considering KD for MD the high rate of adverse effects should be taken into account, but also spectacular improvements in individual cases. KD is a highly individual management option in this fragile patient group and requires an experienced team. To increase knowledge on this-individually-promising management option more (prospective) studies using adequate outcome measures are crucial.
Topics: Adult; Animals; Child; Diet, Ketogenic; Drug Resistant Epilepsy; Epilepsy; Humans; Mitochondrial Diseases; Prospective Studies
PubMed: 34217336
DOI: 10.1186/s13023-021-01927-w -
Orphanet Journal of Rare Diseases Mar 2023Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with multiple seizure types starting in... (Review)
Review
BACKGROUND
Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with multiple seizure types starting in childhood, a typical slow spike-wave pattern on electroencephalogram, and cognitive dysfunction.
METHODS
We performed a systematic literature review according to the PRISMA guidelines to identify, synthesize and appraise the burden of illness in LGS (including "probable" LGS). Studies were identified by searching MEDLINE, Embase and APA PsychInfo, Cochrane's database of systematic reviews, and Epistemonikos. The outcomes were epidemiology (incidence, prevalence or mortality), direct and indirect costs, healthcare resource utilization, and patient and caregiver health-related quality of life (HRQoL).
RESULTS
The search identified 22 publications evaluating the epidemiology (n = 10), direct costs and resource (n = 10) and/or HRQoL (n = 5). No studies reporting on indirect costs were identified. With no specific ICD code for LGS in many regions, several studies had to rely upon indirect methods to identify their patient populations (e.g., algorithms to search insurance claims databases to identify "probable" LGS). There was heterogeneity between studies in how LGS was defined, the size of the populations, ages of the patients and length of the follow-up period. The prevalence varied from 4.2 to 60.8 per 100,000 people across studies for probable LGS and 2.9-28 per 100,000 for a confirmed/narrow definition of LGS. LGS was associated with high mortality rates compared to the general population and epilepsy population. Healthcare resource utilization and direct costs were substantial across all studies. Mean annual direct costs per person varied from $24,048 to $80,545 across studies, and home-based care and inpatient care were significant cost drivers. Studies showed that the HRQoL of patients and caregivers was adversely affected, although only a few studies were identified. In addition, studies suggested that seizure events were associated with higher costs and worse HRQoL. The risk of bias was low or moderate in most studies.
CONCLUSIONS
LGS is associated with a significant burden of illness featuring resistant seizures associated with higher costs and worse HRQoL. More research is needed, especially in evaluating indirect costs and caregiver burden, where there is a notable lack of studies.
Topics: Humans; Lennox Gastaut Syndrome; Quality of Life; Seizures; Algorithms; Cost of Illness
PubMed: 36859290
DOI: 10.1186/s13023-023-02626-4 -
BMJ Open Jul 2017Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. (Meta-Analysis)
Meta-Analysis Review
Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.
OBJECTIVES
Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.
DESIGN AND SETTING
Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.
PARTICIPANTS
29 cohort studies including 5100 infants/children.
INTERVENTIONS
Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.
PRIMARY AND SECONDARY OUTCOME MEASURES
Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.
RESULTS
The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.
CONCLUSIONS
Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.
TRIAL REGISTRATION NUMBER
PROSPERO database (CRD42014008925).
Topics: Anticonvulsants; Autistic Disorder; Bayes Theorem; Breast Feeding; Carbamazepine; Child; Epilepsy; Female; Humans; Lamotrigine; Observational Studies as Topic; Oxcarbazepine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Triazines; Valproic Acid
PubMed: 28729328
DOI: 10.1136/bmjopen-2017-017248 -
The Cochrane Database of Systematic... Jun 2019This is an updated version of the original Cochrane review, published in 2015.Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the original Cochrane review, published in 2015.Focal epilepsies are caused by a malfunction of nerve cells localised in one part of one cerebral hemisphere. In studies, estimates of the number of individuals with focal epilepsy who do not become seizure-free despite optimal drug therapy vary between at least 20% and up to 70%. If the epileptogenic zone can be located, surgical resection offers the chance of a cure with a corresponding increase in quality of life.
OBJECTIVES
The primary objective is to assess the overall outcome of epilepsy surgery according to evidence from randomised controlled trials.Secondary objectives are to assess the overall outcome of epilepsy surgery according to non-randomised evidence, and to identify the factors that correlate with remission of seizures postoperatively.
SEARCH METHODS
For the latest update, we searched the following databases on 11 March 2019: 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 to March 08, 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).
SELECTION CRITERIA
Eligible studies were randomised controlled trials (RCTs) that included at least 30 participants in a well-defined population (age, sex, seizure type/frequency, duration of epilepsy, aetiology, magnetic resonance imaging (MRI) diagnosis, surgical findings), with an MRI performed in at least 90% of cases and an expected duration of follow-up of at least one year, and reporting an outcome related to postoperative seizure control. Cohort studies or case series were included in the previous version of this review.
DATA COLLECTION AND ANALYSIS
Three groups of two review authors independently screened all references for eligibility, assessed study quality and risk of bias, and extracted data. Outcomes were proportions of participants achieving a good outcome according to the presence or absence of each prognostic factor of interest. We intended to combine data with risk ratios (RRs) and 95% confidence intervals (95% CIs).
MAIN RESULTS
We identified 182 studies with a total of 16,855 included participants investigating outcomes of surgery for epilepsy. Nine studies were RCTs (including two that randomised participants to surgery or medical treatment (99 participants included in the two trials received medical treatment)). Risk of bias in these RCTs was unclear or high. Most of the remaining 173 non-randomised studies followed a retrospective design. We assessed study quality using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses, we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across domains.In terms of freedom from seizures, two RCTs found surgery (n = 97) to be superior to medical treatment (n = 99); four found no statistically significant differences between anterior temporal lobectomy (ATL) with or without corpus callosotomy (n = 60), between subtemporal or transsylvian approach to selective amygdalohippocampectomy (SAH) (n = 47); between ATL, SAH and parahippocampectomy (n = 43) or between 2.5 cm and 3.5 cm ATL resection (n = 207). One RCT found total hippocampectomy to be superior to partial hippocampectomy (n = 70) and one found ATL to be superior to stereotactic radiosurgery (n = 58); and another provided data to show that for Lennox-Gastaut syndrome, no significant differences in seizure outcomes were evident between those treated with resection of the epileptogenic zone and those treated with resection of the epileptogenic zone plus corpus callosotomy (n = 43). We judged evidence from the nine RCTs to be of moderate to very low quality due to lack of information reported about the randomised trial design and the restricted study populations.Of the 16,756 participants included in this review who underwent a surgical procedure, 10,696 (64%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to recording of adverse events to be very poor.In total, 120 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography, history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection, and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation, and presence of postoperative discharges were prognostic factors of outcome.Twenty-nine studies reported multi-variable models of prognostic factors, and showed that the direction of association of factors with outcomes was generally the same as that found in univariate analyses.We observed variability in many of our analyses, likely due to small study sizes with unbalanced group sizes and variation in the definition of seizure outcome, the definition of prognostic factors, and the influence of the site of surgery AUTHORS' CONCLUSIONS: Study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcomes. Future research should be of high quality, follow a prospective design, be appropriately powered, and focus on specific issues related to diagnostic tools, the site-specific surgical approach, and other issues such as extent of resection. Researchers should investigate prognostic factors related to the outcome of surgery via multi-variable statistical regression modelling, where variables are selected for modelling according to clinical relevance, and all numerical results of the prognostic models are fully reported. Journal editors should not accept papers for which study authors did not record adverse events from a medical intervention. Researchers have achieved improvements in cancer care over the past three to four decades by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.
Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Child; Epilepsies, Partial; Female; Hippocampus; Humans; Male; Prognosis; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 31237346
DOI: 10.1002/14651858.CD010541.pub3