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Background: This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy., Objectives: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy., Search Methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, 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 Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions., Selection Criteria: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin., Data Collection and Analysis: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models., Main Results: We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs., Authors' Conclusions: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Nausea and vomiting are experienced by most women during pregnancy. The onset is usually related to Last Menstrual Period (LMP) the date of which is often unreliable. This study describes the time to onset of nausea and vomiting symptoms from date of ovulation and compares this to date of last menstrual period METHODS: Prospective cohort of women seeking to become pregnant, recruited from 12 May 2014 to 25 November 2016, in the United Kingdom. Daily diaries of nausea and vomiting were kept by 256 women who were trying to conceive. The main outcome measure is the number of days from last menstrual period (LMP) or luteinising hormone surge until onset of nausea or vomiting., Results: Almost all women (88%) had Human Chorionic Gonadotrophin rise within 8 to 10 days of ovulation; the equivalent interval from LMP was 20 to 30 days. Many (67%) women experience symptoms within 11 to 20 days of ovulation., Conclusions: Onset of nausea and vomiting occurs earlier than previously reported and there is a narrow window for onset of symptoms. This indicates that its etiology is associated with a specific developmental stage at the foetal-maternal interface., Trial Registration: NCT01577147 . Date of registration 13 April 2012.

Background: Nausea and vomiting in pregnancy is usually called 'morning sickness'. This is felt by sufferers to trivialise the condition. Symptoms have been described as occurring both before and after noon, but daily symptom patterns have not been clearly described and statistically modelled to enable the term 'morning sickness' to be accurately analysed., Aim: To describe the daily variation in nausea and vomiting symptoms during early pregnancy in a group of sufferers., Design and Setting: A prospective cohort study of females recruited from 15 May 2014 to 17 February 2017 by Swiss Precision Diagnostics (SPD) Development Company Limited, which was researching hormone levels in early pregnancy and extended its study to include the description of pregnancy symptoms., Method: Daily symptom diaries of nausea and vomiting were kept by females who were trying to conceive. They also provided daily urine samples, which when analysed enabled the date of ovulation to be determined. Data from 256 females who conceived during the first month of the study are included in this article. Daily symptom patterns and changes in daily patterns by week of pregnancy were modelled. Functional data analysis was used to produce estimated symptom probability functions., Results: There was a peak probability of nausea in the morning, a lower but sustained probability of nausea throughout the day, and a slight peak in the evening. Vomiting had a defined peak incidence in the morning., Conclusion: Referring to nausea and vomiting in pregnancy as simply 'morning sickness' is inaccurate, simplistic, and therefore unhelpful., (© British Journal of General Practice 2020.)

Background: Drug resistance is common in focal epilepsy. In this update, we summarised the current evidence regarding add-on levetiracetam in treating drug-resistant focal epilepsy. The original review was published in 2001 and last updated in 2012., Objectives: To evaluate the effectiveness of levetiracetam when used as an add-on treatment for people with drug-resistant focal epilepsy., Search Methods: We searched the Cochrane Register of Studies (CRS Web, which includes the Cochrane Epilepsy Group Specialized Register and CENTRAL), MEDLINE Ovid, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to November 2018. We contacted the manufacturers of levetiracetam and researchers in the field to seek any ongoing or unpublished trials., Selection Criteria: Randomised, placebo-controlled trials of add-on levetiracetam treatment in people with drug-resistant focal epilepsy., Data Collection and Analysis: Two review authors independently selected trials for inclusion, assessed trials for bias, extracted data, and evaluated the overall certainty of the evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response), treatment withdrawal, adverse effects (including a specific analysis of changes in behaviour), cognitive effects, and quality of life (QoL). Primary analysis was intention-to-treat. We performed meta-analysis for all outcomes using a Mantel-Haenszel approach and calculated risk ratios (RR), with 95% confidence intervals (CI) for all estimates apart from adverse effects (99% CIs). We assessed heterogeneity using a Chi² test and the I² statistic., Main Results: This update included 14 trials (2455 participants), predominantly possessing low risks of bias. Participants were adults in 12 trials (2159 participants) and children in the remaining two (296 participants). The doses of levetiracetam tested were 500 mg/day to 4000 mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24 weeks. When individual doses were examined, levetiracetam at either 500 mg/day or 4000 mg/day did not perform better than placebo for the 50% or greater reduction in seizure frequency outcome (500 mg: RR 1.60, 95% CI 0.71 to 3.62; P = 0.26; 4000 mg: RR 1.64, 95% CI 0.59 to 4.57; P = 0.34). Levetiracetam was significantly better than placebo at all other individual doses (1000 mg to 3000 mg). RR was significantly in favour of levetiracetam compared to placebo when results were pooled across all doses (RR 2.37, 95% CI 2.02 to 2.78; 14 studies, 2455 participants; moderate-certainty evidence). Dose-response analysis demonstrated that the odds of achieving response (50% or greater reduction in seizure frequency) were increased by nearly 40% (odds ratio (OR) 1.39, 95% CI 1.23 to 1.58) for each 1000 mg increase in dose of levetiracetam. There were important levels of heterogeneity across multiple comparisons. Participants were not significantly more likely to experience treatment withdrawal with levetiracetam than with placebo (pooled RR 1.11, 95% CI 0.89 to 1.40; 13 studies, 2428 participants; high-certainty evidence). Somnolence was the most common adverse effect, affecting 13% of participants, and it was significantly associated with levetiracetam compared to placebo (pooled RR 1.62, 99% CI 1.19 to 2.20; 13 studies, 2423 participants; moderate-certainty evidence). Changes in behaviour were negligible in adults (1% affected; RR 1.79, 99% CI 0.59 to 5.41), but significant in children (23% affected; RR 1.90, 99% CI 1.16 to 3.11). Levetiracetam had a positive effect on some aspects of cognition and QoL in adults and worsened certain aspects of child behaviour., Authors' Conclusions: Overall, this review update finds that in both adults and children with drug-resistant focal epilepsy, levetiracetam added on to usual care is more effective than placebo at reducing seizure frequency, it is unlikely to be stopped by patients, and it has minimal adverse effects outside of potential worsening behaviour in children. These findings are unchanged from the previous review update in 2012. This review update contributes two key additional findings: 1. a 500 mg daily dose of levetiracetam is no more effective than placebo at reducing seizures; and 2. the odds of response (50% reduction in seizure frequency) are increased by nearly 40% for each 1000 mg increase in dose of levetiracetam. It seems reasonable to continue the use of levetiracetam in both adults and children with drug-resistant focal epilepsy., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Predictive models within epilepsy are frequently developed via Cox's proportional hazards models. These models estimate risk of a specified event such as 12-month remission. They are relatively simple to produce, have familiar output, and are useful to answer questions about short-term prognosis. However, the Cox model only considers time to first event rather than all seizures after starting treatment for example. This makes assessing change in seizure rates over time difficult. Variants to the Cox model exist enabling recurrent events to be modelled. One such variant is the Prentice, Williams and Peterson - Total Time (PWP-TT) model. An alternative is the negative binomial model for event counts. This study aims to demonstrate the differences between the three approaches, and to consider the benefits of the PWP-TT approach for assessing change in seizure rates over time., Methods: Time to 12-month remission and time to first seizure after randomisation were modelled using the Cox model. Risk of seizure recurrence was modelled using the PWP-TT model, including all seizures across the whole follow-up period. Seizure counts were modelled using negative binomial regression. Differences between the approaches were demonstrated using participants recruited to the UK-based multi-centre Standard versus New Antiepileptic Drug (SANAD) study., Results: Results from the PWP-TT model were similar to those from the conventional Cox and negative binomial models. In general, the direction of effect was consistent although the variables included in the models and the significance of the predictors varied. The confidence intervals obtained via the PWP-TT model tended to be narrower due to the increase in statistical power of the model., Conclusions: The Cox model is useful for determining the initial response to treatment and potentially informing when the next intervention may be required. The negative binomial model is useful for modelling event counts. The PWP-TT model extends the Cox model to all included events. This is useful in determining the longer-term effects of treatment policy. Such a model should be considered when designing future clinical trials in medical conditions typified by recurrent events to improve efficiency and statistical power as well as providing evidence regarding changes in event rates over time.

Background: The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies, and up to 30% from clinical series (not population-based), develop drug-resistant epilepsy, especially those with focal-onset seizures. In this review, we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add-on treatment for drug-resistant focal epilepsy.This is an update of a Cochrane Review first published in 1999, and last updated in 2014., Objectives: To evaluate the efficacy and tolerability of topiramate when used as an add-on treatment for people with drug-resistant focal epilepsy., Search Methods: For the latest update of this review we searched the following databases on 2 July 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- ); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies., Selection Criteria: Randomised, placebo-controlled add-on trials of topiramate, recruiting people with drug-resistant focal epilepsy., Data Collection and Analysis: Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal (any reason); (4) adverse effects. Primary analyses were intention-to-treat (ITT), and summary risk ratios (RRs) with 95% confidence intervals (95% CIs) are presented. We evaluated dose-response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach., Main Results: We included 12 trials, representing 1650 participants. Baseline phases ranged from four to 12 weeks and double-blind phases ranged from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency with add-on topiramate compared to placebo was 2.71 (95% CI 2.05 to 3.59; 12 studies; high-certainty evidence). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an odds ratio (OR) of 1.45 (95% CI 1.28 to 1.64; P < 0.001) per 200 mg/d increase in topiramate dosage. The proportion of participants achieving seizure freedom was also significantly increased with add-on topiramate compared to placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies; moderate-certainty evidence). Treatment withdrawal was significantly higher for add-on topiramate compared to placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies; high-certainty evidence). The RRs for the following adverse effects indicate that they are significantly more prevalent with topiramate, compared to placebo: ataxia 2.29 (99% CI 1.10 to 4.77; 4 studies); concentration difficulties 7.81 (99% CI 2.08 to 29.29; 6 studies; moderate-certainty evidence); dizziness 1.52 (99% CI 1.07 to 2.16; 8 studies); fatigue 2.08 (99% CI 1.37 to 3.15; 10 studies); paraesthesia 3.65 (99% CI 1.58 to 8.39; 7 studies; moderate-certainty evidence); somnolence 2.44 (99% CI 1.61 to 3.68; 9 studies); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 studies; high-certainty evidence); and weight loss 3.99 (99% CI 1.82 to 8.72; 9 studies; low-certainty evidence). Evidence of publication bias for the primary outcome was found (Egger test, P = 0.001). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate to high certainty due to the evidence of publication bias, statistical heterogeneity and imprecision, which was partially compensated for by large effect sizes., Authors' Conclusions: Topiramate has efficacy as an add-on treatment for drug-resistant focal epilepsy as it is almost three times more effective compared to a placebo in reducing seizures. The trials reviewed were of relatively short duration and provided no evidence for the long-term efficacy of topiramate. Short-term use of add-on topiramate was shown to be associated with several adverse events. The results of this review should only be applied to adult populations as only one study included children. Future research should consider further examining the effect of dose.

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 2013.Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy., Objectives: To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy., Search Methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web, 20 March 2018), which includes the Cochrane Epilepsy Group's Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 March 2018), ClinicalTrials.gov (20 March 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 20 March 2018). We imposed no language restrictions., Selection Criteria: Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin., Data Collection and Analysis: For this update, two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models., Main Results: We included 12 trials representing 2607 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall RR for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 trials, 1206 participants; moderate-quality evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-quality evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-quality evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-quality evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-quality evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-quality evidence). There were no significant differences for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-quality evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-quality evidence). Overall, the studies were rated at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall quality of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals., Authors' Conclusions: Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types.

Aim: Hyperkinetic movement disorders (HMDs) can be assessed using impairment-based scales or functional classifications. The Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFM-M) evaluates dystonia impairment, but may not reflect functional ability. The Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) are widely used in the literature on cerebral palsy to classify functional ability, but not in childhood movement disorders. We explore the concordance of these three functional scales in a large sample of paediatric HMDs and the impact of dystonia severity on these scales., Method: Children with HMDs (n=161; median age 10y 3mo, range 2y 6mo-21y) were assessed using the BFM-M, GMFCS, MACS, and CFCS from 2007 to 2013. This cross-sectional study contrasts the information provided by these scales., Results: All four scales were strongly associated (all Spearman's rank correlation coefficient rs >0.72, p<0.001), with worse dystonia severity implying worse function. Secondary dystonias had worse dystonia and less function than primary dystonias (p<0.001). A longer proportion of life lived with dystonia is associated with more severe dystonia (rs =0.42, p<0.001)., Interpretation: The BFM-M is strongly linked with the GMFCS, MACS, and CFCS, irrespective of aetiology. Each scale offers interrelated but complementary information and is applicable to all aetiologies. Movement disorders including cerebral palsy can be effectively evaluated using these scales., (© 2015 Mac Keith Press.)

DCs are potent APCs and key regulators of innate and adaptive immunity. After allo-SCT, their reconstitution in the peripheral blood (PB) to levels similar to those in healthy individuals tends to be slow. We investigate the age- and sex-dependant immune reconstitution of myeloid (mDC) and plasmacytoid DC (pDC) in the PB of 45 children with leukaemia or myelodysplastic syndrome (aged 1-17 years, median 10) after allo-SCT with regard to relapse, acute GVHD (aGVHD) and relapse-free survival. Low pDC/μL PB up to day 60 post SCT are associated with higher incidence of moderate or severe aGVHD (P=0.035), whereas high pDC/μL PB up to day 60 are associated with higher risk of relapse (P<0.001). The time-trend of DCs/μL PB for days 0-200 is a significant predictor of relapse-free survival for both mDCs (P<0.001) and pDCs (P=0.020). Jointly modelling DC reconstitution and complications improves on these simple criteria. Compared with BM, PBSC transplants tend to show slower mDC/pDC reconstitution (P=0.001, 0.031, respectively), but have no direct effect on relapse-free survival. These results suggest an important role for both mDCs and pDCs in the reconstituting immune system. The inclusion of mDCs and pDCs may improve existing models for complication prediction following allo-SCT.