-
Frontiers in Neural Circuits 2022Under physiological conditions, neuronal network synchronization leads to different oscillatory EEG patterns that are associated with specific behavioral and cognitive...
Under physiological conditions, neuronal network synchronization leads to different oscillatory EEG patterns that are associated with specific behavioral and cognitive functions. Excessive synchronization can, however, lead to focal or generalized epileptiform activities. It is indeed well established that in both epileptic patients and animal models, focal epileptiform EEG patterns are characterized by interictal and ictal (seizure) discharges. Over the last three decades, employing and recording techniques, several experimental studies have firmly identified a paradoxical role of GABA signaling in generating interictal discharges, and in initiating-and perhaps sustaining-focal seizures. Here, we will review these experiments and we will extend our appraisal to evidence suggesting that GABA signaling may also contribute to epileptogenesis, i.e., the development of plastic changes in brain excitability that leads to the chronic epileptic condition. Overall, we anticipate that this information should provide the rationale for developing new specific pharmacological treatments for patients presenting with focal epileptic disorders such as mesial temporal lobe epilepsy (MTLE).
Topics: Animals; Epilepsy, Temporal Lobe; Epilepsies, Partial; Seizures; Epilepsy; gamma-Aminobutyric Acid; Electroencephalography
PubMed: 36275847
DOI: 10.3389/fncir.2022.984802 -
The Cochrane Database of Systematic... May 2018This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane review last published in 2015 (Issue 10). For nearly 30% of people with epilepsy, seizures are not controlled by current treatments. Stiripentol is a new antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 for the treatment of Dravet syndrome as an adjunctive therapy with valproate and clobazam, with promising effects.
OBJECTIVES
To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with focal refractory epilepsy who are taking AEDs.
SEARCH METHODS
For the latest update, we searched the following databases on 21 August 2017: Cochrane Epilepsy Specialized Register, CENTRAL , MEDLINE, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). We contacted Biocodex (the manufacturer of stiripentol) and epilepsy experts to identify published, unpublished and ongoing trials.
SELECTION CRITERIA
Randomised, controlled, add-on trials of stiripentol in people with focal refractory epilepsy.
DATA COLLECTION AND ANALYSIS
Review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life.
MAIN RESULTS
On the basis of our selection criteria, we included no new studies in the present review. Only one study was included from the earlier review (32 children with focal epilepsy). This study adopted a 'responder enriched' design and found no clear evidence of a reduction in seizure frequency (≥ 50% seizure reduction) (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82, low-quality evidence) nor evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43, low-quality evidence) when add-on stiripentol was compared with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47, low-quality evidence). When specific adverse events were considered, confidence intervals were very wide and showed the possibility of substantial increases and small reductions in risks of neurological (RR 2.65, 95% CI 0.88 to 8.01, low-quality evidence) or gastrointestinal adverse effects (RR 11.56, 95% CI 0.71 to 189.36, low-quality evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47, low-quality evidence), which was high in both groups (35.0% in add-on placebo and 53.3% in stiripentol group, low-quality evidence). The external validity of this study was limited because only responders to stiripentol (i.e. patients experiencing a ≥ 50% decrease in seizure frequency compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole seemed to occur significantly more often with add-on stiripentol than with add-on placebo.
AUTHORS' CONCLUSIONS
Since the last version of this review was published, we have found no new studies. Hence, we have made no changes to the conclusions of this update as presented in the initial review. We can draw no conclusions to support the use of stiripentol as add-on treatment for focal refractory epilepsy. Additional large, randomised, well-conducted trials are needed.
Topics: Anticonvulsants; Child; Dioxolanes; Drug Therapy, Combination; Epilepsies, Partial; Humans; Randomized Controlled Trials as Topic; Seizures
PubMed: 29747241
DOI: 10.1002/14651858.CD009887.pub4 -
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 -
Vaccine Nov 2022Previous studies found conflicting results about the effect of rotavirus (RV) vaccination on seizure hospitalizations in children younger than 5 years old. (Review)
Review
BACKGROUND
Previous studies found conflicting results about the effect of rotavirus (RV) vaccination on seizure hospitalizations in children younger than 5 years old.
OBJECTIVES
To evaluate the evidence of the impact of RV vaccination on the prevention of seizure hospitalizations in children.
METHODS
A systematic review was conducted in the electronic database MEDLINE of all observational studies in children younger than 5 years old published since 2006. Two reviewers performed title/abstract, full-text review, and data extraction.
RESULTS
Thirteen studies met eligibility criteria. Nine studies reported a significant reduction in seizure hospitalizations upon RV vaccine introduction, three studies reported an absence of significant impact, and one study reported a significant rise in seizure hospitalization after the introduction of RV vaccines.
LIMITATIONS
The great variability between study designs, case definitions and potential biases prevent quantifying the impact of RV vaccination against seizure hospitalizations.
CONCLUSIONS
RV vaccination might prevent seizure hospitalizations in children; however, robust, and well-designed studies are needed to better determine the strength of this association.
Topics: Child; Humans; Infant; Child, Preschool; Rotavirus Infections; Rotavirus; Rotavirus Vaccines; Hospitalization; Vaccination; Seizures
PubMed: 36280558
DOI: 10.1016/j.vaccine.2022.09.096 -
British Journal of Pharmacology Oct 2020Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ... (Review)
Review
Embase and PubMed were systematically searched for articles addressing the neuroprotective properties of phytocannabinoids, apart from cannabidiol and Δ -tetrahydrocannabinol, including Δ -tetrahydrocannabinolic acid, Δ -tetrahydrocannabivarin, cannabidiolic acid, cannabidivarin, cannabichromene, cannabichromenic acid, cannabichromevarin, cannabigerol, cannabigerolic acid, cannabigerivarin, cannabigerovarinic acid, cannabichromevarinic acid, cannabidivarinic acid, and cannabinol. Out of 2,341 studies, 31 articles met inclusion criteria. Cannabigerol (range 5 to 20 mg·kg ) and cannabidivarin (range 0.2 to 400 mg·kg ) displayed efficacy in models of Huntington's disease and epilepsy. Cannabichromene (10-75 mg·kg ), Δ -tetrahydrocannabinolic acid (20 mg·kg ), and tetrahydrocannabivarin (range 0.025-2.5 mg·kg ) showed promise in models of seizure and hypomobility, Huntington's and Parkinson's disease. Limited mechanistic data showed cannabigerol, its derivatives VCE.003 and VCE.003.2, and Δ -tetrahydrocannabinolic acid mediated some of their effects through PPAR-γ, but no other receptors were probed. Further studies with these phytocannabinoids, and their combinations, are warranted across a range of neurodegenerative disorders.
Topics: Cannabidiol; Dronabinol; Humans; Huntington Disease; Seizures
PubMed: 32608035
DOI: 10.1111/bph.15185 -
Seizure May 2023To perform a systematic review and meta-analysis to identify whether tuberectomy and tuberectomy plus are associated with different postoperative seizure outcomes in... (Meta-Analysis)
Meta-Analysis Review
Influence of resective extent of epileptogenic tuber on seizure outcome in patients with tuberous sclerosis complex-related epilepsy: A systematic review and meta-analysis.
OBJECTIVE
To perform a systematic review and meta-analysis to identify whether tuberectomy and tuberectomy plus are associated with different postoperative seizure outcomes in patients with tuberous sclerosis complex (TSC) -related epilepsy.
METHODS
Electronic databases (PubMed, Embase, Cochrane, Proquest, Web of Science, Scopus, Biosis Previews) were searched without date restriction. Retrospective cohort studies of participants with TSC-associated epilepsy undergoing resective surgery that reported demographics, presurgical evaluation, extent of resection and postoperative seizure outcomes were included. Title, abstract and the full text were checked independently and in duplicate by two reviewers. Disagreements were resolved through discussion. One author extracted data which was verified by a second author using identified common standard in advance, including using a risk of bias tool we agreed on to evaluate study quality.
RESULTS
Five studies, with a total of 327 participants, were included. One hundred and sixty patients received tuberectomy, and 93 of them (58.1%) achieved postoperative seizure freedom, while the other 167 patients underwent tuberectomy plus, and 128 of them (76.6%) achieved seizure freedom after adequate follow-ups (RR=0.72, 95% CI [0.60, 0.87], P<0.05). Subgroup analysis found that 40 of 63 (63.5%) patients after tuberectomy and 66 of 78 (84.6%) patients after tuberectomy plus of a single tuber achieved seizure freedom (RR = 0.71, 95% CI [0.56,0.91], P<0.05). In the multituber subrgroup, 16 of 42 (38.1%) and 21 of 31 (67.7%) patients achieved seizure freedom, after tuberectomy and tuberectomy plus, respectively (RR = 0.57, 95% CI [0.32,1.03], P = 0.06).
CONCLUSIONS
Tuberectomy plus is a more effective treatment than tuberectomy for patients with TSC-related intractable epilepsy.
Topics: Humans; Retrospective Studies; Tuberous Sclerosis; Electroencephalography; Seizures; Epilepsy; Treatment Outcome
PubMed: 37116294
DOI: 10.1016/j.seizure.2023.04.002 -
The Cochrane Database of Systematic... Oct 2017Febrile seizures can be classified as simple or complex. Complex febrile seizures are associated with fever that lasts longer than 15 minutes, occur more than once... (Review)
Review
BACKGROUND
Febrile seizures can be classified as simple or complex. Complex febrile seizures are associated with fever that lasts longer than 15 minutes, occur more than once within 24 hours, and are confined to one side of the child's body. It is common in some countries for doctors to recommend an electroencephalograph (EEG) for children with complex febrile seizures. A limited evidence base is available to support the use of EEG and its timing after complex febrile seizures among children.
OBJECTIVES
To assess the use of EEG and its timing after complex febrile seizures in children younger than five years of age.
SEARCH METHODS
For the latest update of this review, we searched the Cochrane Epilepsy Group Specialized Register (23 January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 23 January 2017), MEDLINE (Ovid, 23 January 2017), and ClinicalTrials.gov (23 January 2017). We applied no language restrictions.
SELECTION CRITERIA
All randomised controlled trials (RCTs) that examined the utility of an EEG and its timing after complex febrile seizures in children.
DATA COLLECTION AND ANALYSIS
The review authors selected and retrieved the articles and independently assessed which articles should be included. Any disagreements were resolved by discussion and by consultation with the Cochrane Epilepsy Group. We applied standard methodological procedures expected by Cochrane.
MAIN RESULTS
Of 41 potentially eligible studies, no RCTs met the inclusion criteria.
AUTHORS' CONCLUSIONS
We found no RCTs as evidence to support or refute the use of EEG and its timing after complex febrile seizures among children. An RCT can be planned in such a way that participants are randomly assigned to the EEG group and to the non-EEG group with sufficient sample size. Since the last version of this review, we have found no new studies.
Topics: Child, Preschool; Electroencephalography; Humans; Seizures, Febrile; Time Factors
PubMed: 28986982
DOI: 10.1002/14651858.CD009196.pub4 -
Seizure Sep 2015To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to... (Review)
Review
PURPOSE
To evaluate the efficacy of surgery with neuronavigation compared to conventional neurosurgical treatment of epilepsy in terms of safety and seizure outcomes and to assess the quality of the evidence base of neuronavigation in this clinical context.
METHOD
Systematic review using the electronic databases of Cochrane, CRD, PubMed, Embase, SciELO and LILACS in Portuguese, English and Spanish. The [MeSH] terms included "epilepsy" and "neuronavigation".
ELIGIBILITY CRITERIA
Studies assessing surgery with neuronavigation for the surgical treatment of epilepsy or brain injuries associated with epileptic seizures.
RESULTS
We identified 28 original articles. All articles yielded scientific evidence of low quality. Outcome data presented in the articles identified was heterogeneous and did not amount to compelling evidence that epilepsy surgery with neuronavigation produces higher rates of seizure control, a reduced need for reoperations, or lower rates of complications or postoperative neurological deficits.
CONCLUSION
We were unable to find any publications providing convincing evidence that neuronavigation improves outcomes of epilepsy surgery. Whilst this does not mean that neuronavigation cannot improve neurosurgical outcomes in this clinical setting, well-designed research studies evaluating the role of neuronavigation are urgently needed.
Topics: Controlled Clinical Trials as Topic; Epilepsy; Humans; Neuronavigation; Review Literature as Topic; Seizures
PubMed: 26362385
DOI: 10.1016/j.seizure.2015.07.010 -
Neurosurgery Sep 2016Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve... (Review)
Review
BACKGROUND
Neuromodulation-based treatments have become increasingly important in epilepsy treatment. Most patients with epilepsy treated with neuromodulation do not achieve complete seizure freedom, and, therefore, previous studies of vagus nerve stimulation (VNS) therapy have focused instead on reduction of seizure frequency as a measure of treatment response.
OBJECTIVE
To elucidate rates and predictors of seizure freedom with VNS.
METHODS
We examined 5554 patients from the VNS therapy Patient Outcome Registry, and also performed a systematic review of the literature including 2869 patients across 78 studies.
RESULTS
Registry data revealed a progressive increase over time in seizure freedom after VNS therapy. Overall, 49% of patients responded to VNS therapy 0 to 4 months after implantation (≥50% reduction seizure frequency), with 5.1% of patients becoming seizure-free, while 63% of patients were responders at 24 to 48 months, with 8.2% achieving seizure freedom. On multivariate analysis, seizure freedom was predicted by age of epilepsy onset >12 years (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.38-2.58), and predominantly generalized seizure type (OR, 1.36; 95% CI, 1.01-1.82), while overall response to VNS was predicted by nonlesional epilepsy (OR, 1.38; 95% CI, 1.06-1.81). Systematic literature review results were consistent with the registry analysis: At 0 to 4 months, 40.0% of patients had responded to VNS, with 2.6% becoming seizure-free, while at last follow-up, 60.1% of individuals were responders, with 8.0% achieving seizure freedom.
CONCLUSION
Response and seizure freedom rates increase over time with VNS therapy, although complete seizure freedom is achieved in a small percentage of patients.
ABBREVIATIONS
AED, antiepileptic drugVNS, vagus nerve stimulation.
Topics: Adolescent; Adult; Drug Resistant Epilepsy; Female; Humans; Male; Middle Aged; Registries; Retrospective Studies; Seizures; Treatment Outcome; Vagus Nerve Stimulation; Young Adult
PubMed: 26645965
DOI: 10.1227/NEU.0000000000001165 -
Pediatric Neurology Jun 2024Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and... (Review)
Review
BACKGROUND
Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS.
METHODS
This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations.
RESULTS
Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications.
CONCLUSIONS
Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.
Topics: Humans; Seizures, Febrile; Practice Guidelines as Topic; Infant
PubMed: 38653182
DOI: 10.1016/j.pediatrneurol.2024.03.024