Background
Ketogenic diets (KDs), being high in fat and low in carbohydrates, have been suggested to reduce seizure frequency in people with epilepsy. At present, such diets are mainly recommended ...for children who continue to have seizures despite treatment with antiepileptic drugs (AEDs) (drug‐resistant epilepsy). Recently, there has been interest in less restrictive KDs, including the modified Atkins diet (MAD), and the use of these diets has extended into adult practice. This is an update of a review first published in 2003 and last updated in 2016.
Objectives
To assess the effects of KDs for drug‐resistant epilepsy by reviewing the evidence from randomised controlled trials.
Search methods
For the latest update we searched the Cochrane Epilepsy Group's Specialized Register (11 April 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 11 April 2017), MEDLINE (Ovid, 11 April 2017), ClinicalTrials.gov (11 April 2017) and the WHO International Clinical Trials Registry Platform (ICTRP, 11 April 2017). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
Selection criteria
Randomised controlled trials or quasi‐randomised controlled trials of ketogenic diets for people with drug‐resistant epilepsy.
Data collection and analysis
Two review authors independently applied predefined criteria to extract data and assessed study quality.
Main results
We identified 11 randomised controlled trials (RCTs) that generated 15 publications.
All trials applied an intention‐to‐treat analysis with varied randomisation methods. The 11 studies recruited 778 patients; 712 children and adolescents and 66 adults. We assessed all 11 studies to be at low to unclear risk of bias for the following domains: random sequence generation, allocation concealment and selective reporting. For the other domains (blinding, incomplete outcome data, other bias) assessments were varied (low, unclear and high risk of bias). We could not conduct a meta‐analysis due to the heterogeneity of the studies and the quality of the evidence was low to very low (GRADE ratings).
Reported rates of seizure freedom reached as high as 55% in a classical 4:1 KD group after three months and reported rates of seizure reduction reached as high as 85% in a classical 4:1 KD group after three months (GRADE rating low).
One trial found no significant difference between the fasting‐onset and gradual‐onset KD for rates of seizure freedom, and reported a greater rate of seizure reduction in the gradual‐onset KD group.
Studies assessing the efficacy of the MAD reported seizure freedom rates of up to 25% and seizure reduction rates of up to 60% in children. One study used a simplified MAD (sMAD) and reported seizure freedom rates of 15% and seizure reduction rates of 56% in children. One study utilised a MAD in adults and reported seizure reduction rates of 35%, but no patients became seizure free (GRADE rating low).
Adverse effects of the dietary interventions were experienced in all studies. The most commonly reported adverse effects were gastrointestinal syndromes. It was common that adverse effects were the reason for participants dropping out of trials (GRADE rating low). Other reasons for dropout included lack of efficacy and non‐acceptance of the diet (GRADE rating low).
Although there was some evidence for greater antiepileptic efficacy for a classical 4:1 KD over lower ratios, the classical 4:1 KD was consistently associated with more adverse effects.
One study assessed the effect of dietary interventions on quality of life, cognition and behavioural functioning, reporting participants in the KD group to be more active, more productive and less anxious after four months, compared to the control group. However, no significant difference was found in quality‐adjusted life years (QALYs) between the KD group and control group at four or 16 months (GRADE rating very low).
Authors' conclusions
The RCTs discussed in this review show promising results for the use of KDs in epilepsy. However, the limited number of studies, small sample sizes and the limited studies in adults, resulted in a low to very low overall quality of evidence.
There were adverse effects within all of the studies and for all KD variations, such as short‐term gastrointestinal‐related disturbances and increased cholesterol. However, study periods were short, therefore the long‐term risks associated with these adverse effects is unknown. Attrition rates remained a problem with all KDs and across all studies; reasons for this being lack of observed efficacy and dietary tolerance.
Only one study reported the use of KDs in adults with epilepsy; therefore further research would be of benefit.
Other more palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but this assumption requires more investigation. For people who have medically intractable epilepsy or people who are not suitable for surgical intervention, KDs remain a valid option; however, further research is required.
During development and metastasis, cells migrate large distances through complex environments. Migration is often guided by chemotaxis, but simple chemoattractant gradients between a source and sink ...cannot direct cells over such ranges. We describe how self-generated gradients, created by cells locally degrading attractant, allow single cells to navigate long, tortuous paths and make accurate choices between live channels and dead ends. This allows cells to solve complex mazes efficiently. Cells' accuracy at finding live channels was determined by attractant diffusivity, cell speed, and path complexity. Manipulating these parameters directed cells in mathematically predictable ways; specific combinations can even actively misdirect them. We propose that the length and complexity of many long-range migratory processes, including inflammation and germ cell migration, means that self-generated gradients are needed for successful navigation.
FRET biosensors have proven very useful tools for studying the activation of specific signalling pathways in living cells. Most biosensors designed to date have been predicated on fluorescent protein ...pairs that were identified by, and for use in, intensity based measurements, however fluorescence lifetime provides a more reliable measurement of FRET. Both the technology and fluorescent proteins available for FRET have moved on dramatically in the last decade. Lifetime imaging systems have become increasingly accessible and user-friendly, and there is an entire field of biology dedicated to refining and adapting different characteristics of existing and novel fluorescent proteins. This growing pool of fluorescent proteins includes the long-lifetime green and cyan fluorescent proteins Clover and mTurquoise2, the red variant mRuby2, and the dark acceptor sREACh. Here, we have tested these donors and acceptors in appropriate combinations against the standard or recommended norms (EGFP and mTFP as donors, mCherry and either Ypet or Venus as acceptors) to determine if they could provide more reliable, reproducible and quantifiable FLIM-FRET data to improve on the dynamic range compared to other donors and breadth of application of biosensor technologies. These tests were performed for comparison on both a wide-field, frequency domain system and a multiphoton, TCSPC time domain FLIM system. Clover proved to be an excellent donor with extended dynamic range in combination with mCherry on both platforms, while mRuby2 showed a high degree of variability and poor FRET efficiencies in all cases. mTFP-Venus was the most consistent cyan-yellow pair between the two FLIM methodologies, but mTurquoise2 has better dynamic range and transfers energy consistently over time to the dark acceptor sRCh. Combination of mTFP-sRCh with Clover-mCherry would allow the simultaneous use of two FLIM-FRET biosensors within one sample by eliminating the crosstalk between the yellow acceptor and green donor emissions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neurotrophins are growth factors that are important in neuronal development and survival as well as synapse formation and plasticity. Many of the effects of neurotrophins are mediated by changes in ...protein expression as a result of altered transcription or translation. To determine whether neurotrophins regulate the production of microRNAs (miRNAs), small RNA species that modulate protein translation or mRNA stability, we used deep sequencing to identify BDNF (brain-derived neurotrophic factor)-induced miRNAs in cultured primary cortical mouse neurons. This revealed that the miR-212/132 cluster contained the miRNAs most responsive to BDNF treatment. This cluster was found to produce four miRNAs: miR-132, miR-132*, miR-212 and miR-212*. Using specific inhibitors, mouse models and promoter analysis we have shown that the regulation of the transcription of the miR-212/132 miRNA cluster and the miRNAs derived from it are regulated by the ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, via both MSK (mitogen and stress-activated kinase)-dependent and -independent mechanisms.
Clobazam add‐on therapy for drug‐resistant epilepsy Bresnahan, Rebecca; Martin‐McGill, Kirsty J; Williamson, John ...
Cochrane database of systematic reviews,
10/2019, Letnik:
2019, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Background
Epilepsy affects approximately 1% of the population, with up to 30% of patients continuing to have seizures, despite antiepileptic drug treatment. Clobazam is a 1,5‐benzodiazepine and is ...commonly used as an add‐on treatment for drug‐resistant epilepsy. This review is an updated version of the original Cochrane Review, first published in 2008, and examines the most current literature regarding clobazam as an add‐on for drug‐resistant epilepsy.
Objectives
To assess the efficacy, effectiveness and tolerability of clobazam as an add‐on therapy for drug‐resistant generalised‐onset and focal‐onset seizures, with or without secondary generalisation, in adults and children.
Search methods
For the latest update, we searched the following databases on 9 October 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (Ovid) 1946 to 8 October, 2018, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP). For some previous updates we also searched SCOPUS, DARE, and BIOSIS Previews, but these are no longer needed. (SCOPUS was searched as a substitute for EMBASE, but randomised and quasi‐randomised controlled trials in EMBASE are now included in CENTRAL; DARE ceased operation at the end of March 2015; BIOSIS Previews yielded no relevant items that were not found in the other databases).
Selection criteria
Randomised trials of add‐on clobazam, with adequate methods of allocation concealment, recruiting patients with drug‐resistant focal or generalised‐onset seizures, with a minimum treatment period of eight weeks.
Data collection and analysis
Two review authors independently selected trials for inclusion and extracted relevant data. The following outcomes were assessed: 50% or greater reduction in seizures, seizure freedom, treatment withdrawal and adverse events.
Main results
Four double‐blind, placebo‐controlled, cross‐over studies, representing 197 participants, were included in the review. All four studies were assessed as having unclear risk of bias due to the unavailability of methodological details. The studies demonstrated significant methodological heterogeneity and differences in outcome measures were noted. Consequently, it was not possible to summarise the data in a meta‐analysis. Instead, findings were summarised in a narrative data synthesis, Only two of the studies reported 50% or greater seizure reduction. They respectively reported that 57.7% and 52.4% of participants receiving add‐on clobazam experienced a 50% or greater reduction in seizure frequency, although publication bias needs to be considered (2 RCTs, n = 47, very low‐quality evidence). Seizure freedom was reported by three of the included studies. Collectively, 27 out of 175 patients were seizure‐free during treatment with clobazam (3 RCTs, n = 175, very low‐quality evidence). Two studies specifically stated that seizure freedom was not observed in any of the participants receiving add‐on placebo. Treatment withdrawal was reported by all four studies. There was a slightly higher incidence of treatment withdrawal associated with receiving clobazam, although the overall incidence was still fairly low (4 RCTs, n = 197, very low‐quality evidence). Adverse events were only described in two of the studies, reportedly 36% and 85% of participants experienced one or more adverse events whilst receiving clobazam. The most commonly reported adverse event was drowsiness.
Authors' conclusions
Clobazam as an add‐on treatment may reduce seizure frequency and may be most effective in focal‐onset seizures. It is important to recognise that this finding has been derived from very low‐quality evidence and from studies judged to have an unclear risk of bias. It remains unclear which population demographic will best benefit from clobazam and over what time‐frame. A large‐scale, randomised controlled trial, conducted over a greater period of time, incorporating subgroups with differing seizure types, is required to effectively inform clinical practice.
Background
Epilepsy is a common neurological condition that affects up to 1% of the population. Nearly 30% of people with epilepsy are resistant to currently available antiepileptic drugs (AEDs) and ...require treatment with multiple antiepileptic drugs in combination. Tiagabine is one of the newer AEDs that can be used as an adjunct (add‐on) to standard AEDs.
Objectives
To evaluate the efficacy and tolerability of tiagabine when used as an add‐on treatment for people with drug‐resistant focal seizures.
Search methods
This is an updated Cochrane review, last published in 2014. For the latest update, we searched the following databases on 22 January 2019: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials, MEDLINE (Ovid, 1946 to January 21, 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. We imposed no language restrictions. We also contacted the manufacturers of tiagabine and experts in the field to identify any ongoing or unpublished studies.
Selection criteria
We included randomised placebo‐controlled add‐on trials conducted in people of any age with focal epilepsy. The studies could be double‐, single‐, or unblinded and of parallel or cross‐over design. They had to have a minimum treatment period of eight weeks. We also included trials using an active drug control group.
Data collection and analysis
Two review authors independently assessed trials for inclusion and extracted data according to the standard methodological procedures expected by the Cochrane Collaboration for this review update. We resolved disagreements by discussion. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, effects on cognition and quality of life. The primary analyses were performed by intention‐to‐treat. We calculated worst‐case and best‐case analyses for seizure outcomes. We evaluated dose response using regression models. Two review authors assessed risk of bias in each study using the Cochrane 'Risk of bias' tool.
Main results
No further studies were added since the previous update in 2014. The review included six trials (four parallel‐group and two cross‐over group trials) consisting of 948 participants. For the main comparison, tiagabine versus placebo, all participants were aged between 12 and 77 years and the study treatment periods ranged from 12 to 22 weeks. The overall risk ratio (RR) with 95% confidence intervals (CIs) for a 50% or greater reduction in seizure frequency (tiagabine versus placebo) was 3.16 (95% CI 1.97 to 5.07; 3 trials; 769 participants; high‐certainty evidence). Because of differences in response rates among trials, regression models were unable to provide reliable estimates of response to individual doses. The RR for treatment withdrawal (tiagabine versus placebo) was 1.81 (95% CI 1.25 to 2.62; 3 trials, 769 participants; moderate‐certainty evidence). Dizziness and tremor were significantly associated with tiagabine therapy. For cognitive and quality‐of‐life outcomes, the limited available data suggested no significant effects on cognition, mood, or adjustment. One trial comparing tiagabine with an active drug control group (tiagabine versus topiramate) found no significant differences between the two add‐on drugs for a 50% or greater reduction in seizure frequency (RR 0.54, 95% CI 0.19 to 1.58; 1 trial; 41 participants) or for treatment withdrawal (RR 1.43, 95% CI 0.74 to 2.74; one trial; 41 participants). We judged two of the six included studies to have low risk of bias, three studies to have an unclear risk of bias, and one study to have a high risk of bias. Methods for randomisation sequence generation were the least reported trial design factor and generated the most concerns regarding risk of bias. We rated the overall certainty of the evidence as largely moderate to high using the GRADE approach. We rated the evidence for two of the adverse effect outcomes, nausea and tremor, as low certainty.
Authors' conclusions
Tiagabine reduced seizure frequency but was associated with some adverse effects when used as an add‐on treatment in people with drug‐resistant focal epilepsy. The findings of the current review are mainly applicable to adults and adolescents, and may not necessarily be applicable to children as none of the trials included participants aged under 12 years. We found no significant differences between tiagabine and topiramate as add‐on drugs; however, evidence was provided by a single trial and was therefore limited.
Background
This is an updated version of the Cochrane Review previously published in 2017.
Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up ...to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second‐generation antiepileptic drug that can be used as add‐on therapy to standard antiepileptic drugs.
Objectives
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add‐on treatment for people with drug‐resistant focal‐onset epilepsy.
Search methods
For the latest update we searched the Cochrane Register of Studies (CRS Web), MEDLINE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), on 18 December 2018. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.
Selection criteria
We searched for randomised placebo‐controlled add‐on studies of people of any age with drug‐resistant focal seizures. The studies could be double‐blind, single‐blind or unblinded and could be of parallel‐group or cross‐over design.
Data collection and analysis
Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, the third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.
Main results
We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel‐group design, the third had a two‐period cross‐over design, and the fourth had a three‐period cross‐over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta‐analysis of the extracted data.
Only one study reported the outcome, 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add‐on felbamate while another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add‐on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add‐on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo‐randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate‐randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate‐randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were: headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate‐treated participants versus 3% to 15% of placebo‐treated participants.
We assessed the evidence for all outcomes using GRADE and found it as being very‐low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update.
Authors' conclusions
In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add‐on therapy in people with drug‐resistant focal‐onset epilepsy. A large‐scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.
Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both ...chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells. Pancreatic cancer cells break lysophosphatidic acid down as they respond to it, setting up a self-generated gradient driving tumor egress. N-WASP-depleted cells do not recognize lysophosphatidic acid gradients, leading to altered RhoA activation, decreased contractility and traction forces, and reduced metastasis. We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread.
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•N-WASP is a crucial mediator of pancreatic ductal adenocarcinoma metastasis•Pancreatic cancer cells respond to self-generated gradients of LPA, driving tumor egress•N-WASP controls trafficking of LPAR1 receptor toward recycling versus degradation•N-WASP and LPAR1 trafficking control contractility, matrix remodeling, and invasion
Pancreatic ductal adenocarcinoma is highly metastatic; recycling of the receptor LPAR1 drives metastasis in response to self-generated chemotactic gradients of LPA. Juin et al. show that the signaling adapter protein N-WASP coordinates recycling of LPAR1 back to the cell surface after internalization, driving efficient matrix remodeling, invasion, and tumor egress.
Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily ...conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion-retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. It thus behaves like a 'local inhibitor' as predicted in widely accepted mathematical models, but not previously identified in cells. CYRI therefore regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity and plasticity of protrusions.
Sulthiame add‐on therapy for epilepsy Bresnahan, Rebecca; Martin‐McGill, Kirsty J; Milburn‐McNulty, Philip ...
Cochrane database of systematic reviews,
08/2019, Letnik:
2019, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Background
This is an updated version of the Cochrane Review previously published in the Cochrane Database of Systematic Reviews 2015, Issue 10. Epilepsy is a common neurological condition, ...characterised by recurrent seizures. Most people respond to conventional antiepileptic drugs, however, around 30% will continue to experience seizures, despite treatment with multiple antiepileptic drugs. Sulthiame, also known as sultiame, is a widely used antiepileptic drug in Europe and Israel. We present a summary of the evidence for the use of sulthiame as add‐on therapy in epilepsy.
Objectives
To assess the efficacy and tolerability of sulthiame as add‐on therapy for people with epilepsy of any aetiology compared with placebo or another antiepileptic drug.
Search methods
For the latest update, we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group's Specialized Register and CENTRAL (17 January 2019), MEDLINE Ovid (1946 to January 16, 2019), ClinicalTrials.gov and the WHO ICTRP Search Portal (17 January 2019). We imposed no language restrictions. We contacted the manufacturers of sulthiame, and researchers in the field to seek any ongoing or unpublished studies.
Selection criteria
Randomised controlled trials of add‐on sulthiame, with any level of blinding (single, double or unblinded) in people of any age, with epilepsy of any aetiology.
Data collection and analysis
Two review authors independently selected trials for inclusion, and extracted relevant data. We assessed these outcomes: (1) 50% or greater reduction in seizure frequency between baseline and end of follow‐up; (2) complete cessation of seizures during follow‐up; (3) mean seizure frequency; (4) time‐to‐treatment withdrawal; (5) adverse effects; and (6) quality of life. We used intention‐to‐treat for primary analyses. We presented results as risk ratios (RR) with 95% confidence intervals (CIs). However, due to the paucity of trials, we mainly conducted a narrative analysis.
Main results
We included one placebo‐controlled trial that recruited 37 infants with newly diagnosed West syndrome. This trial was funded by DESITIN Pharma, Germany. During the study, sulthiame was given as an add‐on therapy to pyridoxine. No data were reported for the outcomes: 50% or greater reduction in seizure frequency between baseline and end of follow‐up; mean seizure frequency; or quality of life. For complete cessation of seizures during a nine‐day follow‐up period for add‐on sulthiame versus placebo, the RR was 11.14 (95% CI 0.67 to 184.47; very low‐certainty evidence), however, this difference was not shown to be statistically significant (P = 0.09). The number of infants experiencing one or more adverse events was not significantly different between the two treatment groups (RR 0.85, 95% CI 0.44 to 1.64; very low‐certainty evidence; P = 0.63). Somnolence was more prevalent amongst infants randomised to add‐on sulthiame compared to placebo, but again, the difference was not statistically significant (RR 3.40, 95% CI 0.42 to 27.59; very low‐certainty evidence; P = 0.25). We were unable to conduct meaningful analysis of time‐to‐treatment withdrawal and adverse effects due to incomplete data.
Authors' conclusions
Sulthiame may lead to a cessation of seizures when used as an add‐on therapy to pyridoxine in infants with West syndrome, however, we are very uncertain about the reliability of this finding. The included study was small and had a significant risk of bias, largely due to the lack of details regarding blinding and the incomplete reporting of outcomes. Both issues negatively impacted the certainty of the evidence. No conclusions can be drawn about the occurrence of adverse effects, change in quality of life, or mean reduction in seizure frequency. No evidence exists for the use of sulthiame as an add‐on therapy in people with epilepsy outside West syndrome.
Large, multi‐centre randomised controlled trials are needed to inform clinical practice, if sulthiame is to be used as an add‐on therapy for epilepsy.
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