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NeuroImage. Clinical 2023Current evidences show an increased risk of white matter hyperintensities (WMHs) in migraineurs compared to age-matched controls. However, WMHs prevalence and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Current evidences show an increased risk of white matter hyperintensities (WMHs) in migraineurs compared to age-matched controls. However, WMHs prevalence and the associations between WMHs and clinical characteristics in migraineurs have not been systematically evaluated using a meta-analytical approach. This study explored the pooled prevalence of WMHs and the associations of WMHs with the clinical characteristics in patients with migraine.
METHODS
A systematic review and meta-analysis of observational studies reporting the occurrence and clinical characteristics of patients with WMHs attributed to migraine was performed. We searched the PubMed, Web of Science, and Embase databases. Random-effects models were used to calculate the pooled prevalence rate, odds ratio (OR), or mean difference (MD) with corresponding 95% confidence intervals (CIs).
RESULTS
Thirty eligible studies were identified including 3,502 migraineurs aged 37.2 (mean) years. The pooled WMHs prevalence was 44 %, 45 %, and 38 % in migraine, migraine with aura, and migraine without aura groups, respectively. In migraineurs with WMHs, the frontal lobe and subcortical white matter were the most susceptible area. Compared with non-migraine controls, patients with migraine had increased odds for WMHs (OR 4.32, 95 % CI = 2.56-7.28, I = 67 %). According to reported univariable results from included studies, pooled analysis showed that clinical characteristics including age, presence of aura, disease duration, hypertension, diabetes mellitus and right-to-left shunt were associated with the presence of WMHs. Migraine pain and aura characteristics were not related to WMHs.
CONCLUSIONS
These data suggest that WMHs are common in migraine, especially in those who are older or have aura, hypertension, diabetes mellitus, or right-to-left shunt. A better understanding of the WMHs attributed to migraine is needed in future studies.
Topics: Humans; White Matter; Prevalence; Magnetic Resonance Imaging; Migraine Disorders; Epilepsy; Hypertension; Leukoaraiosis
PubMed: 36610309
DOI: 10.1016/j.nicl.2023.103312 -
PLoS Neglected Tropical Diseases Feb 2015Toxoplasmosis is an important, widespread, parasitic infection caused by Toxoplasma gondii. The chronic infection in immunocompetent patients, usually considered as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Toxoplasmosis is an important, widespread, parasitic infection caused by Toxoplasma gondii. The chronic infection in immunocompetent patients, usually considered as asymptomatic, is now suspected to be a risk factor for various neurological disorders, including epilepsy. We aimed to conduct a systematic review and meta-analysis of the available literature to estimate the risk of epilepsy due to toxoplasmosis.
METHODS
A systematic literature search was conducted of several databases and journals to identify studies published in English or French, without date restriction, which looked at toxoplasmosis (as exposure) and epilepsy (as disease) and met certain other inclusion criteria. The search was based on keywords and suitable combinations in English and French. Fixed and random effects models were used to determine odds ratios, and statistical significance was set at 5.0%.
PRINCIPAL FINDINGS
Six studies were identified, with an estimated total of 2888 subjects, of whom 1280 had epilepsy (477 positive for toxoplasmosis) and 1608 did not (503 positive for toxoplasmosis). The common odds ratio (calculated) by random effects model was 2.25 (95% CI 1.27-3.9), p = 0.005.
CONCLUSIONS
Despite the limited number of studies, and a lack of high-quality data, toxoplasmosis should continue to be regarded as an epilepsy risk factor. More and better studies are needed to determine the real impact of this parasite on the occurrence of epilepsy.
Topics: Chronic Disease; Epilepsy; Humans; Middle Aged; Odds Ratio; Risk Factors; Toxoplasma; Toxoplasmosis
PubMed: 25695802
DOI: 10.1371/journal.pntd.0003525 -
European Review For Medical and... Jul 2023The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy.
MATERIALS AND METHODS
A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals.
RESULTS
A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain.
CONCLUSIONS
Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis.
Topics: Adult; Child; Adolescent; Humans; Anticonvulsants; Epilepsies, Partial; Retrospective Studies; Prospective Studies; Epilepsy; Nitriles; Treatment Outcome
PubMed: 37458642
DOI: 10.26355/eurrev_202307_32957 -
Indian Journal of Dermatology,...Epileptic seizures were noted as one of the most overlooked manifestations in syphilis; therefore a few clinicians are concerned about the relationship between epilepsy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epileptic seizures were noted as one of the most overlooked manifestations in syphilis; therefore a few clinicians are concerned about the relationship between epilepsy and syphilis. Our study sought to clarify the prevalence and clinical features of epileptic seizures in patients with syphilis.
METHODS
We retrieved relevant articles from different databases, using the keywords "syphilis and epilepsy" and then performed statistical analysis to characterize the relationship between these diseases.
RESULTS
Forty one articles were included in this study: eight described the prevalence of syphilis and epilepsy and the remaining 33 were case reports on syphilis with epileptic seizures. The meta-analysis included 1252 patients with syphilis. The pooled estimate of proportion of prevalence (95% confidence interval) was 0.1384 (0.0955-0.2005), and the proportion and heterogeneity showed different degrees of change among three subgroups. The systematic review included 46 cases of syphilis with epileptic seizures. Thirty two (80%) patients had motor seizures, among whom 20 (62.5%) had tonic-clonic seizures. In addition, 30 (75%) patients had impaired awareness and 18 (45%) had status seizures. Twenty five (62.5%) patients were 35-55 years of age, and 77.5% of the included patients were men. Thirty seven (97.4%) patients were seizure-free after anti-syphilis treatment.
LIMITATIONS
Research in this field has been conducted for a relatively short period and publication bias may exist. Furthermore, some patients with syphilis and epileptic seizures may not have received a clear diagnosis.
CONCLUSION
The proportion of prevalence was 0.1384. Most of the included patients were 35-55 years of age and had impaired awareness and motor seizures. Many patients with syphilis and epileptic seizure showed full recovery or the development of minor neurological sequelae, and nearly all patients were seizure-free after timely anti-syphilis treatment.
Topics: Epilepsy; Humans; Syphilis
PubMed: 34219436
DOI: 10.25259/IJDVL_681_19 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures.... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
SEARCH METHODS
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
MAIN RESULTS
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.
AUTHORS' CONCLUSIONS
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
Topics: Anticonvulsants; Epilepsy; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazines
PubMed: 34554571
DOI: 10.1002/14651858.CD010062.pub3 -
The Cochrane Database of Systematic... Jul 2022This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator.
OBJECTIVES
To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform.
SELECTION CRITERIA
We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood
MAIN RESULTS
We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes.
AUTHORS' CONCLUSIONS
VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.
Topics: Adult; Anticonvulsants; Child; Cough; Drug Resistant Epilepsy; Drug Therapy, Combination; Dyspnea; Hoarseness; Humans; Pain; Paresthesia; Seizures; Vagus Nerve Stimulation
PubMed: 35833911
DOI: 10.1002/14651858.CD002896.pub3 -
Developmental Medicine and Child... Nov 2022We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat... (Meta-Analysis)
Meta-Analysis Review
AIM
We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms.
METHOD
All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed.
RESULTS
Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO ) combination, low dose ACTH, and high dose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO combination, high dose ACTH (with/without vitamin B ), high dose prednisolone, and low dose ACTH were 'best'.
INTERPRETATION
Treatments including ACTH and high dose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms.
WHAT THIS PAPER ADDS
Adrenocorticotropic hormone and high dose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.
Topics: Adrenocorticotropic Hormone; Anticonvulsants; Child; Humans; Infant; Magnesium Sulfate; Methylprednisolone; Network Meta-Analysis; Spasms, Infantile; Treatment Outcome; Vitamins
PubMed: 35765990
DOI: 10.1111/dmcn.15330 -
The Cochrane Database of Systematic... Jul 2017Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological... (Review)
Review
BACKGROUND
Epilepsy is a common neurological condition, with an estimated incidence of 50 per 100,000 persons. People with epilepsy may present with various types of immunological abnormalities, such as low serum immunoglobulin A (IgA) levels, lack of the immunoglobulin G (IgG) subclass and identification of certain types of antibodies. Intravenous immunoglobulin (IVIg) treatment may represent a valuable approach and its efficacy has important implications for epilepsy management. This is an updated version of the original Cochrane review published in Issue 1, 2011.
OBJECTIVES
To examine the effects of IVIg on the frequency and duration of seizures, quality of life and adverse effects when used as monotherapy or as add-on treatment for people with epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Epilepsy Group Specialized Register (2 February 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (2 February 2017), MEDLINE (Ovid, 1946 to 2 February 2017), Web of Science (1898 to 2 February 2017), ISRCTN registry (2 February 2017), WHO International Clinical Trials Registry Platform (ICTRP, 2 February 2017), the US National Institutes of Health ClinicalTrials.gov (2 February 2017), and reference lists of articles.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials of IVIg as monotherapy or add-on treatment in people with epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the trials for inclusion and extracted data. We contacted study authors for additional information. Outcomes included percentage of people rendered seizure-free, 50% or greater reduction in seizure frequency, adverse effects, treatment withdrawal and quality of life.
MAIN RESULTS
We included one study (61 participants). The included study was a randomized, double-blind, placebo-controlled, multi-centre trial which compared the treatment efficacy of IVIg as an add-on with a placebo add-on in patients with refractory epilepsy. There was no significant difference between IVIg and placebo in 50% or greater reduction in seizure frequency. The study reported a statistically significant effect for global assessment in favour of IVIg. No adverse effects were demonstrated. We found no randomized controlled trials that investigated the effects of IVIg monotherapy for epilepsy. Overall, the included study was rated as low/unclear risk of bias. Using GRADE methodology, the quality of the evidence was rated as low.
AUTHORS' CONCLUSIONS
We cannot draw any reliable conclusions regarding the efficacy of IVIg as a treatment for epilepsy. Further randomized controlled trials are needed.
Topics: Epilepsy; Humans; Immunoglobulins, Intravenous; Randomized Controlled Trials as Topic
PubMed: 28675262
DOI: 10.1002/14651858.CD008557.pub3 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may... (Review)
Review
BACKGROUND
This is an updated version of a Cochrane Review previously published in 2019. Catamenial epilepsy describes worsening seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses. Catamenial epilepsy and seizure exacerbation is common in women with epilepsy. Women may not receive appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aims to address these issues to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised and quasi-randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases on 20 July 2021 for the latest update: Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to 19 July 2021). CRS Web includes randomised controlled trials (RCTs) or quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included RCTs and quasi-RCTs of blinded or open-label design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. We included the following types of interventions: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone, and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses. Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the two RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results for the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported a decrease in seizure frequency from baseline in the progesterone group that was significantly higher than the decrease in seizure frequency from baseline in the placebo group. The results of secondary efficacy outcomes showed no significant difference between groups in the pooled progesterone RCTs in terms of treatment withdrawal for any reason (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals were reported from the norethisterone RCTs. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life. We judged the evidence for outcomes related to the included progesterone RCTs to be of low to moderate certainty due to risk of bias, and for outcomes related to the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out. Our review highlights an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those women who do not have regular menses. Further clinical trials are needed in this area.
Topics: Adolescent; Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Menstruation; Middle Aged; Randomized Controlled Trials as Topic; Seizures; Young Adult
PubMed: 34528245
DOI: 10.1002/14651858.CD013225.pub3 -
The Cochrane Database of Systematic... Nov 2021Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME).... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate in the treatment of JME.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) on 26 August 2021, and MEDLINE (Ovid 1946 to 26 August 2021). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants 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 of the studies.
MAIN RESULTS
We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or greater reduction in primarily generalized tonic-clonic seizures (PGTCS), compared with participants in the placebo group (RR 4.00, 95% CI 1.08 to 14.75; 1 study, 22 participants; very low-certainty evidence). There were no significant differences between topiramate and valproate for participants responding with a 50% or greater reduction in myoclonic seizures (RR 0.88, 95% CI 0.67 to 1.15; one study, 23 participants; very-low certainty evidence) or in PGTCS (RR 1.22, 95% CI 0.68 to 2.21; one study, 16 participants, very-low certainty evidence), or participants becoming seizure-free (RR 1.13, 95% CI 0.61 to 2.11; one study, 27 participants; very-low certainty evidence). Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints (2 studies, 61 participants; very low-certainty evidence). Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged the studies to be at low to unclear risk of bias for the remaining domains (selection bias, performance bias, detection bias and other bias). We judged the overall certainty of the evidence for the outcomes as very low using the GRADE approach.
AUTHORS' CONCLUSIONS
We have found no new studies since the last version of this review was published in 2019. 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 has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Anticonvulsants; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Valproic Acid
PubMed: 34817852
DOI: 10.1002/14651858.CD010008.pub5