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Journal of Neuroimaging : Official... May 2022Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous... (Review)
Review
BACKGROUND AND PURPOSE
Angiocentric gliomas (AGs) are epileptogenic low-grade gliomas in young patients. We aimed to investigate the MRI findings of AGs and systematically review previous publications and three new cases.
METHODS
We searched PubMed, Elsevier's abstract and citation database, and Embase databases and included 50 patients with pathologically proven AGs with analyzable preoperative MRI including 3 patients from our institution and 47 patients from 38 publications (median age, 13 years [range, 2-83 years]; 35 men). Two board-certified radiologists reviewed all images. The relationships between seizure/epilepsy history and MRI findings were statistically analyzed. Moreover, clinical and imaging differences were evaluated between supratentorial and brainstem AGs.
RESULTS
Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain parenchymal atrophy were observed in 23 out of 50 (46.0%), 10 out of 50 (20.0%), and 14 out of 50 (28.0%) patients, respectively. Intratumoral T1-weighted high-intensity areas were observed significantly more frequently in patients with stalk-like signs (positive, 9/10 vs. negative, 14/40, p = .0031) and regional atrophy (13/14 vs. 10/36, p = .0001). There were significant relationships between the length of seizure/epilepsy history and presence of intratumoral T1-weighted high-intensity area (median 3 years vs. 0.5 years, p = .0021), stalk-like sign (13.5 vs. 1 year, p < .0001), and regional atrophy (14 vs. 0.5 years, p < .0001). Patients with brainstem AGs (n = 7) did not have a seizure/epilepsy history and were significantly younger than those with supratentorial AGs (median, 5 vs. 13 years, p < .0001, respectively).
CONCLUSIONS
Intratumoral T1-weighted high-intensity areas, stalk-like signs, and regional brain atrophy were frequent imaging features in AG. We also found that affected age was different between supratentorial and brainstem AGs.
Topics: Adolescent; Atrophy; Brain Neoplasms; Female; Glioma; Humans; Magnetic Resonance Imaging; Male; Neuroimaging; Seizures
PubMed: 35201652
DOI: 10.1111/jon.12983 -
PharmacoEconomics Jan 2023Fenfluramine, tradename Fintepla, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as... (Meta-Analysis)
Meta-Analysis Review
Fenfluramine, tradename Fintepla, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company's estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and 'real world evidence' from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥ 50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG's preferences (but were accepted by the appraisal committee). The company's revised and final incremental cost effectiveness ratio (ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service (NHS).
Topics: Child; Humans; Adolescent; Cannabidiol; Bayes Theorem; Prospective Studies; Quality of Life; Retrospective Studies; State Medicine; Epilepsies, Myoclonic; Cost-Benefit Analysis; Technology Assessment, Biomedical; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 36301414
DOI: 10.1007/s40273-022-01209-8 -
Neurology Jun 2024Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Tailoring epilepsy surgery using intraoperative electrocorticography (ioECoG) has been debated, and modest number of epilepsy surgery centers apply this diagnostic method. We assessed the current evidence to use ioECoG-tailored epilepsy surgery for improving postsurgical outcome.
METHODS
PubMed and Embase were searched for original studies reporting on ≥10 cases who underwent ioECoG-tailored surgery for epilepsy, with a follow-up of at least 6 months. We used a random-effects model to calculate the overall rate of patients achieving favorable seizure outcome (FSO), defined as Engel class I, ILAE class 1, or seizure-free status. Meta-regression was used to investigate potential sources of heterogeneity. We calculated the odds ratio (OR) for estimating variables on FSO:ioECoG vs non-ioECoG-tailored surgery (if included studies contained patients with non-ioECoG-tailored surgery), ioECoG-tailored epilepsy surgery in children vs adults, temporal (TL) vs extratemporal lobe (eTL), MRI-positive vs MRI-negative, and complete vs incomplete resection of tissue that generated interictal epileptiform discharges (IEDs). A Bayesian network meta-analysis was conducted for underlying pathologies. We assessed the evidence certainty using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).
RESULTS
Eighty-three studies (82 observational studies, 1 trial) comprising 3,631 patients with ioECoG-tailored surgery were included. The overall pooled rate of patients who attained FSO after ioECoG-tailored surgery was 74% (95% CI 71-77) with significant heterogeneity, which was predominantly attributed to pathologies and seizure outcome classifications. Twenty-two studies contained non-ioECoG-tailored surgeries. IoECoG-tailored surgeries reached a higher rate of FSO than non-ioECoG-tailored surgeries (OR 2.10 [95% CI 1.37-3.24]; < 0.01; very low certainty). Complete resection of tissue that displayed IEDs in ioECoG predicted FSO better compared with incomplete resection (OR 3.04 [1.76-5.25]; < 0.01; low certainty). We found insignificant difference in FSO after ioECoG-tailored surgery in children vs adults, TL vs eTL, or MRI-positive vs MRI-negative. The network meta-analysis showed that the odds of FSO was lower for malformations of cortical development than for tumors (OR 0.47 95% credible interval 0.25-0.87).
DISCUSSION
Although limited by low-quality evidence, our meta-analysis shows a relatively good surgical outcome (74% FSO) after epilepsy surgery with ioECoG, especially in tumors, with better outcome for ioECoG-tailored surgeries in studies describing both and better outcome after complete removal of IED areas.
Topics: Humans; Electrocorticography; Epilepsy; Intraoperative Neurophysiological Monitoring; Seizures; Treatment Outcome; Neurosurgical Procedures
PubMed: 38768406
DOI: 10.1212/WNL.0000000000209430 -
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 -
Heliyon Feb 2023Status epilepticus (SE) is a common neurological emergency that is defined as a prolonged seizure or a series of seizures which often leads to irreversible damage.... (Review)
Review
OBJECTIVE
Status epilepticus (SE) is a common neurological emergency that is defined as a prolonged seizure or a series of seizures which often leads to irreversible damage. Levetiracetam (LEV) and valproate (VPA) are second-line anti-seizure drugs that are frequently used in patients with established SE (ESE). This meta-analysis compared the efficacy and safety of LEV and VPA for the treatment of ESE.
METHOD
MEDLINE, EMBASE, Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched by two authors, which identified six randomized controlled trials (RCTs) that compared LEV and VPA for ESE.
RESULTS
The six RCTs included 1213 patients (LEV group, n = 593; VPA group, n = 620). Integrated patient data information display LEV was not superior to VPA in terms of clinical seizure termination (63.55% vs. 64.08%, respectively; relative risk [RR] = 1.03, 95% confidence interval [CI] = 0.94-1.11, p = 0.55), with no significant differences between LEV and VPA in terms of good functional outcome at discharge (Glasgow Outcome Scale [GOS] = 4 or 5), intensive care unit (ICU) admission, adverse events, and mortality. There was no statistically significant difference between the two drugs in different age groups. Previous multicenter studies have demonstrated that VPA was slightly more effective than LEV, whereas single-center studies showed the opposite results. In addition, LEV and VPA had similar rates of clinical seizure termination, ICU admission, and adverse events between the age subgroups (ages <18 and >18 years).
CONCLUSIONS
Levetiracetam (LEV) was not superior to valproate (VPA) in terms of efficacy or safety outcomes. In addition, children (<18 years) and adults (>18 years) might have similar responses to LEV and VPA. Additional RCTs are required to verify our results.
PubMed: 36816301
DOI: 10.1016/j.heliyon.2023.e13380 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923 -
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 -
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 Mar 2022The Laser interstitial thermal therapy (LITT) technique has been used recently for corpus callosotomy in patients with epilepsy, especially atonic seizures (drop...
PURPOSE
The Laser interstitial thermal therapy (LITT) technique has been used recently for corpus callosotomy in patients with epilepsy, especially atonic seizures (drop attacks) and Lennox-Gastaut Syndrome (LGS). However, there is little data on safety and outcomes. Therefore, the authors systematically studied and conducted a pooled analysis with special focus on feasibility, outcomes and complications.
METHODS
A systematic review was performed in accordance with the PRISMA guidelines. A total of 10 retrospective studies were identified, comprising 58 cases of MRI-guided LITT treatment.
RESULTS
MRI-guided LITT was successfully performed in 57 cases while one case was aborted due to hemorrhage. The average duration of clinical follow-up following LITT callosotomy was 20 months. In the 57 LITT callosotomies, complete seizure freedom and excellent seizure control (Engel I and II) were achieved in 21.1% and 49.1% of patients, respectively. For atonic seizures, the rate of complete freedom and excellent control was 52.5% and 72.5%, respectively. The median length of stay at hospital was 2 days. No death was encountered. Common complications included: fiber-related hemorrhage (8.6%), inaccurate placement (6.9%) followed with transient hemiparesis/hemineglect and supplementary motor area (SMA) syndrome 5.2% each. The rate of disconnection syndrome was 3.4%.
CONCLUSION
MRI-guided LITT for corpus callosotomy is feasible and safe, with low complication rates, short hospitalization and has comparable rates of seizure control to that of classic surgical callosotomy. The majority of patients with atonic seizures achieve complete seizure freedom and excellent control (Engel I and II). The risk for developing disconnection syndrome is low.
Topics: Corpus Callosum; Humans; Laser Therapy; Lennox Gastaut Syndrome; Retrospective Studies; Treatment Outcome
PubMed: 35245877
DOI: 10.1016/j.seizure.2022.02.002