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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 -
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 -
Epilepsia May 2022In the last two decades new noninvasive mobile electroencephalography (EEG) solutions have been developed to overcome limitations of conventional clinical EEG and to... (Review)
Review
In the last two decades new noninvasive mobile electroencephalography (EEG) solutions have been developed to overcome limitations of conventional clinical EEG and to improve monitoring of patients with long-term conditions. Despite the availability of mobile innovations, their adoption is still very limited. The aim of this study is to review the current state-of-the-art and highlight the main advantages of adopting noninvasive mobile EEG solutions in clinical trials and research studies of people with epilepsy or suspected seizures. Device characteristics are described, and their evaluation is presented. Two authors independently performed a literature review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of different digital libraries was used (Embase, MEDLINE, Global Health, PsycINFO and https://clinicaltrials.gov/). Twenty-three full-text, six conference abstracts, and eight webpages were included, where a total of 14 noninvasive mobile solutions were identified. Published studies demonstrated at different levels how EEG recorded via mobile EEG can be used for visual detection of EEG abnormalities and for the application of automatic-detection algorithms with acceptable specificity and sensitivity. When the quality of the signal was compared with scalp EEG, many similarities were found in the background activities and power spectrum. Several studies indicated that the experience of patients and health care providers using mobile EEG was positive in different settings. Ongoing trials are focused mostly on improving seizure-detection accuracy and also on testing and assessing feasibility and acceptability of noninvasive devices in the hospital and at home. This review supports the potential clinical value of noninvasive mobile EEG systems and their advantages in terms of time, technical support, cost, usability, and reliability when applied to seizure detection and management. On the other hand, the limitations of the studies confirmed that future research is needed to provide more evidence regarding feasibility and acceptability in different settings, as well as the data quality and detection accuracy of new noninvasive mobile EEG solutions.
Topics: Electroencephalography; Epilepsy; Health Personnel; Humans; Reproducibility of Results; Seizures
PubMed: 35271736
DOI: 10.1111/epi.17220 -
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 -
Seizure Nov 2023To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness and side-effect profile of the modified Atkins diet (MAD) compared to the usual diet (UD) in reducing seizure frequency among patients with drug-resistant epilepsy (DRE).
METHODS
In February 2023, we conducted an extensive search in PubMed, EMBASE, and Cochrane databases to find randomized controlled trials (RCTs) comparing MAD to UD in patients with drug-resistant epilepsy (DRE) on standard anti-seizure medication (ASM). We used random-effects meta-analyses and the Risk of Bias 2 tool to evaluate treatment effects and assess the quality of the included RCTs, respectively.
RESULTS
Six studies were evaluated in the meta-analysis, including 575 patients, of whom 288 (50.1 %) were randomized to the MAD. Average follow-up period was 12 weeks. MAD plus standard drug therapy was associated with a higher rate of 50 % or greater reduction in seizure frequency compared to UD plus drug therapy (RR 6.28; 95 % CI 3.52-10.50; p<0.001), both in children (RR 6.28; 95 % CI 3.43-11.49; p<0.001) and adults with DRE (RR 6.14; 95 % CI 1.15-32.66; p = 0.033). MAD was also associated with a higher seizure freedom rate compared to UD (RR 5.94; 95 % CI 1.93-18.31; p = 0.002). Five studies reported adverse events with MAD; constipation was reported in 17 % of patients (95 % CI 5-44 %), lethargy in 11 % (95 % CI 4-25 %), and anorexia in 12 % (95 % CI 8-19 %). Due to limited information about the ASM regimens, we were unable to further analyze the interaction between MAD and ASM.
SIGNIFICANCE
This meta-analysis, comprising 575 patients from 6 RCTs, revealed that MAD led to higher rates of seizure freedom and underscored its role in seizure frequency reduction by 50 % or more in both adults and children, with no significant adverse events concerns.
Topics: Adult; Child; Humans; Diet, High-Protein Low-Carbohydrate; Randomized Controlled Trials as Topic; Drug Resistant Epilepsy; Diet, Ketogenic; Seizures; Anticonvulsants
PubMed: 37769548
DOI: 10.1016/j.seizure.2023.09.010 -
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 -
Journal of Neuro-oncology Sep 2023Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life.
METHODS
We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors.
RESULTS
We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors.
CONCLUSION
Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.
Topics: Child; Humans; Retrospective Studies; Prospective Studies; Quality of Life; Electroencephalography; Treatment Outcome; Seizures; Supratentorial Neoplasms; Brain Neoplasms
PubMed: 37707753
DOI: 10.1007/s11060-023-04446-9 -
Neurosurgical Review Apr 2022Seizures are common presenting symptoms of intracranial arteriovenous malformations (AVMs). This systematic review and meta-analysis aims to assess the current evidence... (Meta-Analysis)
Meta-Analysis Review
Seizures are common presenting symptoms of intracranial arteriovenous malformations (AVMs). This systematic review and meta-analysis aims to assess the current evidence regarding complete seizure freedom rates following surgical resection, stereotactic radiosurgery (SRS), and/or endovascular embolization of intracranial AVMs. A systematic review of PubMed, Ovid MEDLINE, and Ovid EMBASE was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included manuscripts were methodically scrutinized for quality, spontaneous AVM-associated or hemorrhage-associated seizures, complete seizure-free rates following each interventional treatment, follow-up duration; determination methods of seizure outcomes, and average time-to-onset of recurrent seizures after each treatment. Manuscripts that described patients with nondisabling seizures or reduced seizure frequency in their seizure-free calculations were excluded. Seizure freedom rates following surgical resection, SRS, and endovascular embolization were compared via random-effect analysis. Thirty-four studies with a total of 1765 intracranial AVM patients presenting with spontaneous AVM-associated seizures and 408 patients presenting with hemorrhage-associated seizures were qualitatively analyzed. For patients presenting with AVM-associated seizures, the complete seizure-free rates were 73.0% (321/440 patients; 95% CI 68.8-77.1%) following surgical resection, 60.5% (376/622 patients; 95% CI 56.6-64.3%) following SRS, and 44.6% (29/65 patients; 95% CI 32.5-56.7%) following endovascular embolization alone. For patients presenting with either AVM-associated or hemorrhage-associated seizures, the complete seizure-free rates were 73.0% (584/800 patients; 95% CI 69.9-76.1%) following surgical resection, 46.4% (572/1233 patients; 95% CI 43.6-49.2%) following SRS, and 44.6% (29/65 patients; 95% CI 32.5-56.7%) following embolization. For patients presenting with either AVM-associated or hemorrhage-associated seizures, the overall improvements in seizure outcomes regardless of complete seizure freedom were 82.6% (661/800 patients; 95% CI 80.0-85.3%), 70.6% (870/1233 patients; 95% CI 68.0-73.1%), and 70.8% (46/65 patients; 95% CI 59.7-81.1%) following surgical resection, SRS, and embolization, respectively. No study reported information about the time-to-onset for recurrent seizures in any patient following treatment, as seizure outcomes were only described at the last follow-up visit. The available data suggests that surgical resection results in the highest rate of complete seizure freedom. The rate of seizure improvement following surgery increased further to 82.3% when including patients who had improved seizure frequency without achieving true seizure freedom. Complete seizure-free rates following SRS or embolization were more ambiguous and lower when compared to surgical resection. There is a need for high quality studies evaluating AVM treatment modalities and clearly defined seizure outcomes, as the current literature consists mostly of heterogenous patient populations.
Topics: Embolization, Therapeutic; Follow-Up Studies; Humans; Intracranial Arteriovenous Malformations; Radiosurgery; Retrospective Studies; Seizures; Treatment Outcome
PubMed: 34988732
DOI: 10.1007/s10143-021-01724-w -
Epilepsia Feb 2024In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development.... (Meta-Analysis)
Meta-Analysis Review
In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development. Although the efficacy of surgical treatment for seizure control has been established, the long-term intellectual and developmental trajectories are yet to be delineated. We conducted a systematic review and meta-analysis of studies reporting pre- and postsurgical intelligence or developmental quotients (IQ/DQ) of children with focal lesional epilepsy aged ≤18 years at epilepsy surgery and assessed at >2 years after surgery. We determined the IQ/DQ change and conducted a random-effects meta-analysis and meta-regression to assess its determinants. We included 15 studies reporting on 341 patients. The weighted mean age at surgery was 7.1 years (range = .3-13.8). The weighted mean postsurgical follow-up duration was 5.6 years (range = 2.7-12.8). The overall estimate of the mean presurgical IQ/DQ was 60 (95% confidence interval [CI] = 47-73), the postsurgical IQ/DQ was 61 (95% CI = 48-73), and the change was +.94 IQ/DQ (95% CI = -1.70 to 3.58, p = .486). Children with presurgical IQ/DQ ≥ 70 showed a tendency for higher gains than those with presurgical IQ/DQ < 70 (p = .059). Higher gains were determined by cessation of antiseizure medication (ASM; p = .041), not just seizure freedom. Our findings indicate, on average, stabilization of intellectual and developmental functioning at long-term follow-up after epilepsy surgery. Once seizure freedom has been achieved, ASM cessation enables the optimization of intellectual and developmental trajectories in affected children.
Topics: Child; Humans; Child, Preschool; Adolescent; Epilepsy; Epilepsies, Partial; Intelligence; Intelligence Tests; Seizures; Treatment Outcome; Retrospective Studies
PubMed: 38031640
DOI: 10.1111/epi.17834 -
Journal of Clinical Neurophysiology :... Sep 2023In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic...
In this review, authors discuss epilepsy originating from posterior cingulate regions, a challenging entity to diagnose and most likely underrecognized. A systematic review of posterior middle and posterior cingulate epilepsy cases was conducted to present a summary of current knowledge about this localization-based type of epilepsy. The literature search identified 32 articles, for a total of 69 patients (34 with posterior middle cingulate epilepsy [pMCE] and 35 with posterior cingulate epilepsy [PCE]). Most patients were children and young adults with drug-resistant lesional epilepsy with high seizure burden. In both groups, most patients reported auras, mainly sensory, but various types were reported, including autonomic, behavioral, and cognitive manifestations. Most pMCE and PCE showed motor manifestations (mainly respectively asymmetric tonic posturing and automotor features). Impaired awareness during seizures was more frequently reported in PCE than in pMCE. As for ictal scalp EEG, epileptogenic abnormalities were poorly lateralized and did not localize the seizure onset zone. An ictal temporal involvement was only observed in PCE. Interictal EEG findings were nonspecific. As for other presurgical noninvasive investigations, data are limited, and no studies have adequately assessed their value. Partly explained by our inclusion criteria, most patients underwent a surgical procedure (either lesionectomy or resection of epileptogenic zone as defined by intracranial EEG study results), which overall yielded good outcomes.
Topics: Child; Young Adult; Humans; Epilepsy, Frontal Lobe; Gyrus Cinguli; Seizures; Electroencephalography; Electrocorticography; Drug Resistant Epilepsy
PubMed: 36930208
DOI: 10.1097/WNP.0000000000000975