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Epileptic Disorders : International... Apr 2018Idiopathic (genetic) generalized epilepsies (IGEs) are age-related epileptic syndromes with typical age onset in childhood or adolescence. We report a patient with de... (Review)
Review
Idiopathic (genetic) generalized epilepsies (IGEs) are age-related epileptic syndromes with typical age onset in childhood or adolescence. We report a patient with de novo late-onset absence status epilepticus (ASE) occurring at the age of 64 years, with clinical and EEG features suggestive of late-onset IGE. We also discuss the relationship between de novo late-onset ASE and late-onset IGE, and provide a comprehensive and critical review of the available literature on late-onset (i.e. onset ≥60 years) IGE. MEDLINE (1966-2016 [23 April]) was systematically searched in order to identify reports of patients with late-onset IGE. Grey literature was also comprehensively searched. We identified nine patients with electroclinical features suggestive of late-onset IGE. Median age at seizure onset was 71 years (range: 60-80), with a female prevalence (67%). A family history of epilepsy was reported in 67% of cases. All patients had generalized tonic-clonic seizures, and 44% also had myoclonic seizures. Treatment and outcome were reported for six patients; all of whom reached seizure freedom under monotherapy with valproic acid (83%) or lamotrigine (17%) (range of follow-up: 3 to 24 months). Late-onset IGE are entities with unknown prevalence and incidence, and should be differentiated on the basis of late-onset reactivation of previous IGE. Late-onset IGEs are probably unrecognized or misdiagnosed, based on a common misconception that all elderly individuals with first-ever seizures have focal symptomatic epilepsy. Late-onset IGE should be actively investigated by accurate history taking aimed at identifying seizures, which may have been unnoticed, and familial antecedents of epilepsy. In elderly patients presenting with de novo late-onset ASE, a diagnosis of late-onset IGE should be considered in the differential diagnosis, particularly in atypical cases (e.g. absence of triggering factors, coexistence of generalized tonic-clonic or myoclonic seizures, and interictal generalized epileptiform discharges).
Topics: Aged; Aged, 80 and over; Brain; Diagnosis, Differential; Electroencephalography; Epilepsy, Generalized; Female; Humans; Middle Aged; Status Epilepticus
PubMed: 29620008
DOI: 10.1684/epd.2018.0961 -
Tremor and Other Hyperkinetic Movements... 2018Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical... (Review)
Review
BACKGROUND
Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.
METHODS
We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.
RESULTS
Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.
DISCUSSION
Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.
Topics: Epilepsies, Myoclonic; Humans; Phenotype
PubMed: 29416935
DOI: 10.7916/D85155WJ -
Seizure Oct 2017Determine the impact of anti-epileptic drugs (AED) for drug resistant patients with idiopathic generalised epilepsy. (Meta-Analysis)
Meta-Analysis
PURPOSE
Determine the impact of anti-epileptic drugs (AED) for drug resistant patients with idiopathic generalised epilepsy.
METHODS
A systematic search of Medline, Cumulative Index to Nursing an Allied Health Literature (CINAHL), Cochrane Epilepsy Group Central Specialised Register, Cochrane Central Register of controlled Trials (CENTRAL), Embase and Lenus was performed. Nine randomised controlled trials were included. All trials compared antiepileptic drugs to placebo. Outcome measures assessed were 50% or greater reduction in seizure, seizure freedom and adverse events.
RESULTS
Seven trials report a 50% or greater reduction in seizure frequency. This was statistically significant (p=<0.00001) with a narrow confidence interval implying that the overall this meta-analysis has reasonable power to detect an effect. It demonstrated a significant statistical difference of seizure freedom occurring in the drug treatment group compared to placebo. Adverse events were identified with each drug and are reported. There were however methodological issues with the trials included. Quality appraisal was undertaken using the risk of bias assessment from Rev Man 5.3 tool for all randomised controlled trials retrieved.
CONCLUSION
This systematic review demonstrated efficacy of adjunctive anti-epileptic drugs with regard to 50% reduction and seizure freedom. Adverse events are identified in all of the studies in the drug treatment groups but are consistent with previous studies of these drugs. Additional adequately powered studies with long term follow up needs to be conducted to unequivocally establish the long term efficacy and tolerability of anti-epileptic drug's for patients with drug resistant idiopathic generalised epilepsy.
Topics: Anticonvulsants; Epilepsy, Generalized; Humans
PubMed: 28863398
DOI: 10.1016/j.seizure.2017.08.007 -
PloS One 2017Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we... (Review)
Review
BACKGROUND
Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating findings and provide an updated perspective of these studies.
METHODOLOGY
A systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.
RESULTS
Fifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.
CONCLUSIONS
Thus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.
PROSPERO REGISTRATION NUMBER
CRD42016036063.
Topics: Connexins; Databases, Factual; Genetic Association Studies; Humans; Myoclonic Epilepsy, Juvenile; Polymorphism, Single Nucleotide; Protein Serine-Threonine Kinases; Receptors, Metabotropic Glutamate; Transcription Factors; Gap Junction delta-2 Protein
PubMed: 28636645
DOI: 10.1371/journal.pone.0179629 -
The Cochrane Database of Systematic... May 2017This is an updated version of the original Cochrane review published in 2015, Issue 10.Severe myoclonic epilepsy in infants (SMEI), also known as Dravet syndrome, is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in 2015, Issue 10.Severe myoclonic epilepsy in infants (SMEI), also known as Dravet syndrome, is a rare, refractory form of epilepsy, for which stiripentol (STP) has been recently licensed as add-on therapy.
OBJECTIVES
To evaluate the efficacy and tolerability of STP and other antiepileptic drug treatments (including ketogenic diet) for patients with SMEI.
SEARCH METHODS
For the latest update we searched the Cochrane Epilepsy Group Specialized Register (20 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 20 December 2016), MEDLINE (Ovid, 1946 to 20 December 2016) and ClinicalTrials.gov (20 December 2016). Previously we searched the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP, but this was not usable at the time of this update. We also searched the bibliographies of identified studies for additional references. We handsearched selected journals and conference proceedings and imposed no language restrictions.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-randomised controlled trials; double- or single-blinded or unblinded trials; and parallel-group studies. Administration of at least one antiepileptic drug therapy given singly (monotherapy) or in combination (add-on therapy) compared with add-on placebo or no add-on treatment.
DATA COLLECTION AND ANALYSIS
Review authors independently selected trials for inclusion according to predefined criteria, extracted relevant data and evaluated the methodological quality of trials. We assessed the following outcomes: 50% or greater seizure reduction, seizure freedom, adverse effects, proportion of dropouts and quality of life. We assessed outcomes by using a Mantel-Haenszel meta-analysis to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs).
MAIN RESULTS
Since the last version of this review no new studies have been found. Specifically, we found no RCTs assessing drugs other than STP. The review includes two RCTs evaluating use of STP (total of 64 children). Both studies were generally at unclear risk of bias. A significantly higher proportion of participants had 50% or greater reduction in seizure frequency in the STP group compared with the placebo group (22/33 versus 2/31; RR 10.40, 95% CI 2.64 to 40.87). A significantly higher proportion of participants achieved seizure freedom in the STP group compared with the placebo group (12/33 versus 1/31; RR 7.93, 95% CI 1.52 to 41.21). Investigators found no significant differences in proportions of dropouts from the STP group compared with the placebo group (2/33 versus 8/31; RR 0.24, 95% CI 0.06 to 1.03). Only one study explicitly reported the occurrence of side effects, noting that higher proportions of participants in the STP group experienced side effects than in the placebo group (100% versus 25%; RR 3.73, 95% CI 1.81 to 7.67). We rated the quality of the evidence as low to moderate according to GRADE criteria, as most information is from studies judged to be at an unclear risk of bias.
AUTHORS' CONCLUSIONS
Data derived from two small RCTs indicate that STP is significantly better than placebo with regards to 50% or greater reduction in seizure frequency and seizure freedom. Adverse effects occurred more frequently with STP. Additional adequately powered studies with long-term follow-up should be conducted to unequivocally establish the long-term efficacy and tolerability of STP in the treatment of patients with SMEI.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Dioxolanes; Epilepsies, Myoclonic; Female; Humans; Male; Patient Dropouts; Randomized Controlled Trials as Topic; Seizures
PubMed: 28521067
DOI: 10.1002/14651858.CD010483.pub4 -
The Cochrane Database of Systematic... Apr 2017Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME. This is an updated version of the original Cochrane Review published in Issue 12, 2015.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate monotherapy in the treatment of JME.
SEARCH METHODS
For the latest update, on 21 February 2017 we searched Cochrane Epilepsy's Specialized Register, CENTRAL, MEDLINE, and ClinicalTrials.gov. We also searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted study authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
MAIN RESULTS
We included three studies with 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low.
AUTHORS' CONCLUSIONS
Since the last version of this review we found no new studies. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Treatment Outcome; Valproic Acid; Young Adult
PubMed: 28434203
DOI: 10.1002/14651858.CD010008.pub3 -
PloS One 2017We aimed to identify the consistent regions of gray matter volume (GMV) abnormalities in idiopathic generalized epilepsy (IGE), and to study the difference of GMV... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to identify the consistent regions of gray matter volume (GMV) abnormalities in idiopathic generalized epilepsy (IGE), and to study the difference of GMV abnormalities among IGE subsyndromes by applying activation likelihood estimation (ALE) meta-analysis.
METHODS
A systematic review of VBM studies on GMV of patients with absence epilepsy (AE), juvenile myoclonic epilepsy (JME), IGE and controls indexed in PubMed and ScienceDirect from January 1999 to June 2016 was conducted. A total of 12 IGE studies, including 7 JME and 3 AE studies, were selected. Meta-analysis was performed on these studies by using the pooled and within-subtypes analysis (www.brainmap.org). Based on the above results, between-subtypes contrast analysis was carried out to detect the abnormal GMV regions common in and unique to each subtype as well.
RESULTS
IGE demonstrated significant GMV increase in right ventral lateral nucleus (VL) and right medial frontal gyrus, and significant GMV decrease in bilateral pulvinar. For JME, significant GMV increase was seen in right medial frontal gyrus, right anterior cingulate cortex (ACC), while significant GMV decrease was found in right pulvinar. In AE, the most significant GMV increase was found in right VL, and slight GMV reduction was seen in right medial dorsal nucleus, right subcallosal gyrus, left caudate and left precuneus. No overlapped and unique regions with significant GMV abnormalities were found between JME and AE.
SIGNIFICANCE
This meta-analysis demonstrated that thalamo-frontal network was a structure with significant GMV abnormality in IGE, and the IGE subsyndromes showed different GMV abnormal regions. These observations may provide instructions on the clinical diagnosis of IGE.
Topics: Epilepsy, Generalized; Female; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Organ Size
PubMed: 28060866
DOI: 10.1371/journal.pone.0169076 -
Neuropsychology Review Dec 2016Psychiatric disorders and associated poor psychosocial outcomes are recognised to be a common sequelae of epilepsy. The extent to which this is true of genetic... (Review)
Review
Psychiatric disorders and associated poor psychosocial outcomes are recognised to be a common sequelae of epilepsy. The extent to which this is true of genetic generalised epilepsies (GGE), particularly syndromes other than juvenile myoclonic epilepsy (JME) is unclear. This systematic review synthesises findings regarding psychiatric and associated comorbidities in adults and children with GGE. Systematic review yielded 34 peer-reviewed studies of psychiatric and psychosocial outcomes in adults and children with GGE. Clinically significant psychiatric comorbidity was reported in over half of all children and up to a third of all adults with GGE. There was no evidence to support the presence of personality traits specific to JME or other syndromes; rather rates mirrored community samples. A small number of studies report poor psychosocial outcomes in GGE, however the interpretation of these findings is limited by paucity of healthy comparison groups. Some evidence suggests that anti-epileptic drug polytherapy in children and seizure burden at all ages may constitute risk factors for psychopathology. Findings highlight the importance of early screening so as not to overlook early or developing symptoms of psychopathology.
Topics: Anticonvulsants; Comorbidity; Epilepsy, Generalized; Humans; Mental Disorders
PubMed: 27726043
DOI: 10.1007/s11065-016-9333-1 -
Epilepsy Research Mar 2016We sought to systematically review and perform a meta-analysis of the magnetic resonance spectroscopy (MRS) findings regarding juvenile myoclonic epilepsy (JME). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We sought to systematically review and perform a meta-analysis of the magnetic resonance spectroscopy (MRS) findings regarding juvenile myoclonic epilepsy (JME).
METHODS
We searched for studies in the PubMed, Web of Science, and Embase electronic databases. Two authors collected articles and extracted data independently. A meta-analysis was performed for diverse metabolites in different brain areas. The mean difference (MD) and 95% confidence interval (CI) were used to compare continuous variables.
RESULTS
A decreased NAA/Cr was observed in the motor cortex (MD=0.14, 95%CI=0.09 to 0.20), and the NAA was reduced in the thalamus (MD=0.74, 95%CI=0.37 to 1.10) and the frontal lobe (MD=0.87, 95%CI=0.45 to 1.28); the GLX/Cr was increased in the insula (MD=-0.10, 95%CI=-0.14 to -0.06) and the striatum (MD=-0.11, 95%CI=-0.17 to -0.05).
CONCLUSIONS
JME may be a multi-regional, thalamo-frontal network epilepsy rather than an idiopathic generalized epilepsy syndrome.
Topics: Humans; Myoclonic Epilepsy, Juvenile; Proton Magnetic Resonance Spectroscopy
PubMed: 26871960
DOI: 10.1016/j.eplepsyres.2016.01.004 -
The Cochrane Database of Systematic... Dec 2015Topiramate is a newer broad-spectrum of antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Topiramate is a newer broad-spectrum of antiepileptic drug (AED). Some studies have shown the benefits of topiramate monotherapy in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate monotherapy in people with JME.
OBJECTIVES
To determine the efficacy and tolerability of topiramate monotherapy in the treatment of JME.
SEARCH METHODS
We searched the Cochrane Epilepsy Group Specialized Register (2 November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies CRSO, 2 November 2015), MEDLINE (Ovid, 2 November 2015), EMBASE (1 July 2015) and ClinicalTrials.gov (2 November 2015). In an effort to identify further published, unpublished and ongoing trials, we searched ongoing trials registers, reference lists and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate monotherapy versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders or experiencing adverse events (AEs).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality. We performed no meta-analyses due to the limited available data.
MAIN RESULTS
We included three studies with 83 participants. For the efficacy, a greater proportion of participants in the topiramate group had a 50% or more reduction in primarily generalized tonic-clonic seizures (PGTCS) compared with participants in the placebo group. There were no significant differences between topiramate versus valproate in participants responding with a 50% or more reduction in myoclonic seizures or in PGTCS or seizure-free. Concerning tolerability, we ranked AEDs associated with topiramate as moderate-to-severe, while we ranked 59% of AEDs linked to valproate as severe complaints. Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. We judged the quality of the evidence from the studies to be very low.
AUTHORS' CONCLUSIONS
This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but there were no more benefits of efficacy in topiramate compared with valproate. In the future, well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Adolescent; Anticonvulsants; Child; Fructose; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Treatment Outcome; Valproic Acid; Young Adult
PubMed: 26695884
DOI: 10.1002/14651858.CD010008.pub2