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Epilepsia Mar 2024KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a...
OBJECTIVE
KCTD7-related progressive myoclonic epilepsy (PME) is a rare autosomal-recessive disorder. This study aimed to describe the clinical details and genetic variants in a large international cohort.
METHODS
Families with molecularly confirmed diagnoses of KCTD7-related PME were identified through international collaboration. Furthermore, a systematic review was done to identify previously reported cases. Salient demographic, epilepsy, treatment, genetic testing, electroencephalographic (EEG), and imaging-related variables were collected and summarized.
RESULTS
Forty-two patients (36 families) were included. The median age at first seizure was 14 months (interquartile range = 11.75-22.5). Myoclonic seizures were frequently the first seizure type noted (n = 18, 43.9%). EEG and brain magnetic resonance imaging findings were variable. Many patients exhibited delayed development with subsequent progressive regression (n = 16, 38.1%). Twenty-one cases with genetic testing available (55%) had previously reported variants in KCTD7, and 17 cases (45%) had novel variants in KCTD7 gene. Six patients died in the cohort (age range = 1.5-21 years). The systematic review identified 23 eligible studies and further identified 59 previously reported cases of KCTD7-related disorders from the literature. The phenotype for the majority of the reported cases was consistent with a PME (n = 52, 88%). Other reported phenotypes in the literature included opsoclonus myoclonus ataxia syndrome (n = 2), myoclonus dystonia (n = 2), and neuronal ceroid lipofuscinosis (n = 3). Eight published cases died over time (14%, age range = 3-18 years).
SIGNIFICANCE
This study cohort and systematic review consolidated the phenotypic spectrum and natural history of KCTD7-related disorders. Early onset drug-resistant epilepsy, relentless neuroregression, and severe neurological sequalae were common. Better understanding of the natural history may help future clinical trials.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Young Adult; Electroencephalography; Epilepsies, Myoclonic; Myoclonic Epilepsies, Progressive; Potassium Channels; Seizures; Unverricht-Lundborg Syndrome
PubMed: 38231304
DOI: 10.1111/epi.17880 -
Epilepsy & Behavior : E&B Sep 2023Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence and predictive risk factors for drug-resistant IGE.
METHODS
We systematically searched three databases (PubMed, Embase, and Cochrane Library) in November 2022 and included 12 eligible studies which reported long-term outcomes (mean = 14.05) after antiseizure medications (ASMs) from 2001 to 2020. We defined drug resistance as the persistence of any seizure despite ASMs treatment (whether as monotherapies or in combination) given the criteria of drug resistance varied in original studies. A random-effects model was used to evaluate the prevalence of refractory IGE. Studies reporting potential poor prognostic factors were included for subsequent subgroup meta-analysis.
RESULTS
The pooled prevalence of drug resistance in IGE cohorts was 27% (95% CI: 0.19-0.36). Subgroup analysis of the risk factors revealed that the psychiatric comorbidities (odds ratio (OR): 4.87, 95% confidence interval (CI): 2.97-7.98), combined three seizure types (absences, myoclonic jerks, and generalized tonic-clonic seizures) (OR: 5.37, 95% CI: 3.16-9.13), the presence of absence seizure (OR: 4.38, 95% CI: 2.64-7.28), generalized polyspike trains (GPT) (OR: 4.83, 95% CI: 2.42-9.64), sex/catamenial epilepsy (OR: 3.25, 95% CI: 1.97-5.37), and status epilepticus (OR: 5.94, 95% CI: 2.23-15.85) increased the risk of poor prognosis. Other factors, including age onset, family history, and side effects of ASMs, were insignificantly associated with a higher incidence of refractory IGE.
CONCLUSION
Drug resistance is a severe complication of IGE. Further standardized research about clinical and electroencephalography factors is warranted.
Topics: Humans; Anticonvulsants; Prevalence; Epilepsy, Generalized; Seizures; Drug Resistant Epilepsy; Risk Factors; Immunoglobulin E
PubMed: 37523796
DOI: 10.1016/j.yebeh.2023.109364 -
Seizure Jun 2024Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and... (Review)
Review
Sleep disturbances significantly impact the lives of individuals with Juvenile Myoclonic Epilepsy (JME). This study aimed to investigate sleep studies, disturbances, and the impact of anti-seizure drugs on sleep in JME patients. Relevant studies were retrieved from the National Library of Medicine (Pubmed) database and the Cochrane Library utilizing the search terms "Juvenile Myoclonic Epilepsy" and "sleep". A total of 160 papers' review, data extraction, and resolution of discrepancies were performed independently by two reviewers according to the PRISMA protocol and were registered in PROSPERO (CRD42023472439). A systematic review of 31 studies was conducted, encompassing various methodologies, including sleep questionnaires (Pittsburgh Sleep Quality Index (n = 13), Epworth Sleepiness Scale (n = 10)), polysomnography (n = 8), EEG (n = 9), actigraphy (n = 1), and transcranial magnetic stimulation (n = 1). Most studies were hospital-based (n = 31), cross-sectional (n = 11), and prospective (n = 25). Patients with JME exhibit a higher prevalence of sleep disturbances, worse quality of sleep (n = 4), daytime sleepiness (n = 2), sleep efficiency (n = 7), and increased sleep latency (n = 1) compared to controls. These disruptions are characterized by increased wakefulness (n = 3), frequent arousals (n = 3), decreased REM sleep (n = 2), and conflicting NREM sleep findings (n = 3). Additional sleep-related issues observed in JME patients include insomnia (n = 1) and increased prevalence of parasomnias such as nightmares and sleep talking. Periodic limb movement and obstructive sleep apnea are similar or less frequent (3/28). REM behavioral disorders and sleepwalking were not seen. Valproate showed conflicting effects on sleep (n = 7), while levetiracetam did not impact sleep (n = 1). These findings underlined the need for more sufficient evidence of sleep studies in JME. Future research should prioritize understanding the nature of sleep in JME and its impact on management.
PubMed: 38908143
DOI: 10.1016/j.seizure.2024.05.014 -
Seizure Mar 2021Juvenile myoclonic epilepsy (JME), like other forms of idiopathic generalized epilepsy, shows a marked female predominance. However, few studies have specifically... (Review)
Review
PURPOSE
Juvenile myoclonic epilepsy (JME), like other forms of idiopathic generalized epilepsy, shows a marked female predominance. However, few studies have specifically addressed the role of sex in its long-term prognosis. We performed a systematic review of the literature relevant to JME prognosis, focusing on sex-based differences in prognostic factors and outcome.
METHODS
A comprehensive literature search of the PubMed and Scopus databases was performed, considering all articles up to April 2020 in which long-term prognosis in JME had been explored and sex differences in outcome or prognostic factors were specified.
RESULTS
We included 25 articles published between 1984 and 2020. Sex differences in epilepsy outcome were explored by 21 of the 25 studies, but only three reported different outcomes in male vs female patients. All three found female sex to be associated with a later response to antiseizure medications, worse seizure control, and a higher risk of relapse in their entire study samples, which included JME patients. Eight studies found sex-based differences in possible predictors of long-term outcome: prolonged epileptiform EEG runs and the presence of eye closure sensitivity, both more frequent in women, were factors possibly linked to a poorer prognosis, as were praxis induction and generalized EEG asymmetric changes, which instead were more common in men. Valproate use, more frequent in men, was associated with a better outcome.
CONCLUSION
Most studies do not highlight sex differences in JME prognosis. However, some sex specificities do emerge, especially with regard to particular reflex traits and EEG abnormalities. Finally, sex may condition therapeutic choices, and thus have a possible impact on long-term outcome.
Topics: Electroencephalography; Female; Humans; Male; Myoclonic Epilepsy, Juvenile; Prognosis; Seizures; Sex Characteristics
PubMed: 33524768
DOI: 10.1016/j.seizure.2021.01.005 -
EClinicalMedicine Nov 2022A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication...
Individualised prediction of drug resistance and seizure recurrence after medication withdrawal in people with juvenile myoclonic epilepsy: A systematic review and individual participant data meta-analysis.
BACKGROUND
A third of people with juvenile myoclonic epilepsy (JME) are drug-resistant. Three-quarters have a seizure relapse when attempting to withdraw anti-seizure medication (ASM) after achieving seizure-freedom. It is currently impossible to predict who is likely to become drug-resistant and safely withdraw treatment. We aimed to identify predictors of drug resistance and seizure recurrence to allow for individualised prediction of treatment outcomes in people with JME.
METHODS
We performed an individual participant data (IPD) meta-analysis based on a systematic search in EMBASE and PubMed - last updated on March 11, 2021 - including prospective and retrospective observational studies reporting on treatment outcomes of people diagnosed with JME and available seizure outcome data after a minimum one-year follow-up. We invited authors to share standardised IPD to identify predictors of drug resistance using multivariable logistic regression. We excluded pseudo-resistant individuals. A subset who attempted to withdraw ASM was included in a multivariable proportional hazards analysis on seizure recurrence after ASM withdrawal. The study was registered at the Open Science Framework (OSF; https://osf.io/b9zjc/).
FINDINGS
Our search yielded 1641 articles; 53 were eligible, of which the authors of 24 studies agreed to collaborate by sharing IPD. Using data from 2518 people with JME, we found nine independent predictors of drug resistance: three seizure types, psychiatric comorbidities, catamenial epilepsy, epileptiform focality, ethnicity, history of CAE, family history of epilepsy, status epilepticus, and febrile seizures. Internal-external cross-validation of our multivariable model showed an area under the receiver operating characteristic curve of 0·70 (95%CI 0·68-0·72). Recurrence of seizures after ASM withdrawal (n = 368) was predicted by an earlier age at the start of withdrawal, shorter seizure-free interval and more currently used ASMs, resulting in an average internal-external cross-validation concordance-statistic of 0·70 (95%CI 0·68-0·73).
INTERPRETATION
We were able to predict and validate clinically relevant personalised treatment outcomes for people with JME. Individualised predictions are accessible as nomograms and web-based tools.
FUNDING
MING fonds.
PubMed: 36467455
DOI: 10.1016/j.eclinm.2022.101732 -
Seizure Apr 2021Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on... (Review)
Review
Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on January 18, 2021, examining the number of clinical DS studies. We show that there are 208 studies on children exclusively, 28 studies on adults exclusively, and 116 studies involving adults and children combined. This 7:1 ratio of children to adult studies exclusively shows the dearth of research that addresses long-term natural history of DS into adulthood. Through this systematic review, we examine the most up-to-date information in DS adults as it pertains to seizures, electroencephalogram, imaging, treatment, motor abnormalities, cognitive and social behavior outcomes, cardiac abnormalities, sleep disturbances, diagnosis in adults, and mortality. Overall, the frequency of seizures increases in the first decade of life and then myoclonic, atypical absences and focal seizures with impaired awareness tend to decrease in frequency or even disappear in adulthood. Adults tend to have a notable reduction in status epilepticus, especially after 30 years of age. Parkinsonian features were seen in patients as young as 19 years old and are more severe in older patients, suggesting a progression of the parkinsonian symptoms. In adulthood, patients continue to present with behavior problems, associated with a lower health-related quality of life. The leading reported cause of death in DS adults is Sudden Unexpected Death in Epilepsy (SUDEP). Further studies in older adults are needed to understand the long-term outcomes of patients with DS.
Topics: Adult; Epilepsies, Myoclonic; Humans; Infant; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Quality of Life; Spasms, Infantile; Young Adult
PubMed: 33677403
DOI: 10.1016/j.seizure.2021.02.025 -
Epilepsy & Behavior : E&B Aug 2023Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Reading-induced seizures are presumed to be rare phenomena attributed to an epilepsy syndrome not clearly belonging to either focal or generalized epilepsies. The aim of the article was to summarize knowledge and recent developments in the field of reading-induced seizures by reviewing all cases for which data were reported within the last three decades.
METHODS
A scoping systematic review of demographic, clinical, electroencephalography (EEG) and imaging data of cases with reading-induced seizures reported in PubMed and Web of Science between 1991-01-01 and 2022-08-21 and a meta-analysis of the findings.
RESULTS
The review included 101 case reports of epilepsy with reading-induced seizures (EwRIS) from 42 articles. The phenomenon was more prevalent among males (67, 66.3% vs. 34, 33.7%) with an average age of onset of 18.3 ± 7.9 years. When reported, 30.8% of patients had a family history of epilepsy. Orofacial reflex myocloni (ORM) were the most frequent manifestation (68, 67.3% cases), other presentations, mostly in addition to ORM, included visual, sensory or cognitive symptoms, non-orofacial myoclonic seizures, and absence seizures. Within the sample, 75 (74.3%) patients were identified as having primary reading epilepsy (PRE), 13 (12.9%) idiopathic generalised epilepsy (IGE) and 13 (12.9%) focal epilepsies. Advanced EEG and functional imaging data suggest that the basic mechanism of reading-induced seizures is probably similar despite different symptoms and consists of upregulation of the complex cerebral subsystem involved in reading. Ictogenesis and resulting symptomatology may then depend on predominant sensory or proprioceptive stimuli during reading.
CONCLUSION
In most cases, reading-induced seizures were confirmed to belong to a particular epilepsy syndrome of PRE. However, there were substantial subgroups with IGE and focal epilepsies. Most likely, reading-induced seizures occur as an abnormal response to extero- or proprioceptive input into an upregulated cortical network subserving reading. Most recent researchers consider EwRIS a system epilepsy.
Topics: Adolescent; Adult; Child; Humans; Male; Young Adult; Electroencephalography; Epilepsies, Partial; Epilepsy, Absence; Epilepsy, Generalized; Epilepsy, Reflex; Immunoglobulin E; Myoclonus; Seizures
PubMed: 37437391
DOI: 10.1016/j.yebeh.2023.109346 -
Scientific Reports Dec 2021Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and... (Meta-Analysis)
Meta-Analysis
Despite the increased use of medical cannabinoids, the efficacy and safety of the treatment among children remain uncertain. The objective was to study the efficacy and safety of medical cannabinoids in children. The search included studies through 11-May-2020. Selection criteria included studies evaluating efficacy and safety outcomes of medical cannabinoids (tetrahydrocannabinol, cannabidiol and other cannabis derivatives) versus control in children, independently assessed by two reviewers. Eight studies were included, all of which are randomized controlled trials. Cannabidiol is associated with 50% reduction in seizures rate (Relative Risk (RR) = 1.69, 95% CI [1.20-2.36]) and caregiver global impression of change (Median Estimated difference = (- 1), 95%CI [- 1.39-(- 0.60)]) in Dravet syndrome, compared to placebo. While cannabidiol was associated with a reduction in reported seizure events (RR = 0.59, 95% CI [0.36-0.97]), no association was found in products contained also tetrahydrocannabinol (RR = 1.35, 95% CI [0.46-4.03]). Higher dose of cannabidiol was associated with decreased appetite (RR = 2.40, 95% CI [1.39-4.15]). A qualitative assessment suggests that medical cannabinoids might be associated with adverse mental events. In conclusion, cannabidiol is associated with clinical improvement in Dravet syndrome. However, cannabidiol is also associated with decreased appetite. Adverse mental events were reported as well, however, more research should be performed to assess well this outcome.
Topics: Animals; Cannabinoids; Child; Epilepsies, Myoclonic; Humans; Medical Marijuana
PubMed: 34873203
DOI: 10.1038/s41598-021-02770-6 -
Epileptic Disorders : International... Aug 2022Epileptic myoclonus or myoclonic seizures can occur in idiopathic generalized epilepsy (IGE) and progressive myoclonus epilepsy (PME). However, symptomatic myoclonus... (Review)
Review
Epileptic myoclonus or myoclonic seizures can occur in idiopathic generalized epilepsy (IGE) and progressive myoclonus epilepsy (PME). However, symptomatic myoclonus which is stimulus-sensitive and provoked by movement is typically seen in PME and Lance-Adams syndrome. Symptomatic myoclonus is not always associated with epileptiform discharges on the electroencephalogram. Therapeutic interventions such as anti-seizure medications (ASMs), the ketogenic diet and vagus nerve stimulation are not always effective. There is emerging evidence that perampanel (PER), an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, may be effective for the treatment of myoclonic seizures and symptomatic myoclonus. We performed a systematic review of the literature to assess the efficacy of PER as treatment for myoclonic seizures and symptomatic myoclonus. Twenty-seven studies with a total sample size of 260 patients were included. The efficacy of PER was analysed separately for myoclonic seizures and symptomatic myoclonus. In the group with myoclonic seizures, 50% responder, 75% responder and seizure freedom rates were reported as 74.3% (101/ 136), 60.3% (82/136) and 57.4% (78/136), respectively, with a follow-up duration of 6-12 months. However, in one post-hoc analysis of data from patients with IGE, the efficacy of PER as treatment for myoclonic seizures during the double-blind phase showed no significant difference compared to placebo. The efficacy of PER for symptomatic myoclonus was reported in a total of 119 patients. Four studies (n=88 patients) reported the efficacy of PER as a decrease in myoclonus score/scale. In the remaining 31 patients, symptomatic myoclonus resolved in three patients, decreased in 21 patients and seven patients showed no improvement. We also analysed the number of patients who were already on levetiracetam (LEV) or valproic acid (VPA) at the time of PER initiation; these data were available for 153 patients. Of these, 56.8% were on LEV and 75.1% were on VPA when PER was initiated. This systematic review suggests that PER maybe effective as treatment for drug-resistant myoclonic seizures and symptomatic myoclonus. It may also be effective in patients who have already failed to respond to LEV and VPA. These findings are preliminary yet encouraging. This study has several limitations, particularly given the scarcity of high-quality randomized controlled trials and marked heterogeneity regarding the type and results of the studies. Hence, the findings of this review should be viewed with considerable reservation.
Topics: Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Immunoglobulin E; Levetiracetam; Myoclonic Epilepsies, Progressive; Myoclonus; Nitriles; Pyridones; Randomized Controlled Trials as Topic; Seizures; Treatment Outcome; Valproic Acid
PubMed: 35770766
DOI: 10.1684/epd.2022.1439 -
Epilepsy & Behavior : E&B Mar 2024This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the efficacy and safety of six new antiseizure medications (ASMs) for adjunctive treatment in adult patients with focal epilepsy and adolescents with Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS), or tuberous sclerosis complex (TSC).
METHODS
A comprehensive literature search was performed using PubMed, Medline, Embase, and Cochrane library databases from inception to October 13, 2023. We included published studies for a systematic review and a network meta-analysis (NMA). The efficacy and safety were reported in terms of a 50% response rate and dropout rate along with serious adverse events (SAEs). The outcomes were ranked with the surface under the cumulative ranking curve (SUCRA).
RESULTS
Twenty eligible trials with 5516 patients and 21 interventions, including placebo, contributed to the analysis. Included ASMs were brivaracetam (BRV), cenobamate (CBM), cannabidiol (CBD), fenfluramine (FFM), everolimus (ELM), and soticlestat (SLT). The six new ASMs were compared in four different epilepsy subtypes. In focal epilepsy treatment, BRV seemed to be safe [vs placebo, risk ratio (RR) = 0.69, 95 % confidence interval (CI): 0.25-1.91] and effective (vs placebo, RR = 2.18, 95 % CI: 1.25-3.81). In treating focal epilepsy, CBM 300 mg was more effective at a 50 % response rate (SUCRA 91.8 %) compared with BRV and CBD. However, with the increase in dosage, more SAEs (SUCRA 85.6 %) appeared compared with other ASMs. CBD had good efficacy on LGS (SUCRA 88.4) and DS (SUCRA 66.2), but the effect on adult focal epilepsy was not better than that of placebo [vs placebo, RR = 0.83 (0.36-1.93)]. The NMA indicated that the likelihood of the most appropriate intervention (SUCRA 91.2 %) with minimum side effects(SUCRA 12.5 %)for the DS was FFM. Compared with CBD, high exposure to ELM demonstrated a more effective treatment of TSC (SUCRA 89.7 %). More high-quality SLT studies are needed to further evaluate the efficacy and safety. The comparison-adjusted funnel plots of annualized relapse rate and side effects in the included studies revealed no significant funnel plot asymmetry.
CONCLUSIONS
This NMA indicated that the most effective treatment strategy for focal epilepsy, DS, Lennox-Gastaut syndrome, and TSC, respectively, included CBM 300 mg, FFM, CBD, and ELM. However, the aforementioned findings need further confirmation.
Topics: Adult; Adolescent; Humans; Lennox Gastaut Syndrome; Network Meta-Analysis; Cannabidiol; Epilepsy; Epilepsies, Myoclonic; Epilepsies, Partial; Everolimus; Anticonvulsants; Carbamates; Chlorophenols; Tetrazoles
PubMed: 38277848
DOI: 10.1016/j.yebeh.2024.109653