Summary Background Arterial ischaemic stroke is an important cause of acquired brain injury in children. Few prospective population-based studies of childhood arterial ischaemic stroke have been ...undertaken. We aimed to investigate the epidemiology and clinical features of childhood arterial ischaemic stroke in a population-based cohort. Methods Children aged 29 days to less than 16 years with radiologically confirmed arterial ischaemic stroke occurring over a 1-year period (July 1, 2008, to June 30, 2009) residing in southern England (population denominator 5·99 million children) were eligible for inclusion. Cases were identified using several sources (paediatric neurologists and trainees, the British Paediatric Neurology Surveillance Unit, paediatricians, radiologists, physiotherapists, neurosurgeons, parents, and the Paediatric Intensive Care Audit Network). Cases were confirmed by personal examination of cases and case notes. Details of presenting features, risk factors, and investigations for risk factors were recorded by analysis of case notes. Capture–recapture analysis was used to estimate completeness of ascertainment. Findings We identified 96 cases of arterial ischaemic stroke. The crude incidence of childhood arterial ischaemic stroke was 1·60 per 100 000 per year (95% CI 1·30–1·96). Capture–recapture analysis suggested that case ascertainment was 89% (95% CI 77–97) complete. The incidence of arterial ischaemic stroke was highest in children aged under 1 year (4·14 per 100 000 per year, 95% CI 2·36–6·72). There was no difference in the risk of arterial ischaemic stroke between sexes (crude incidence 1·60 per 100 000 per year 95% CI 1·18–2·12 for boys and 1·61 per 100 000 per year 1·18–2·14 for girls). Asian (relative risk 2·14, 95% CI 1·11–3·85; p=0·017) and black (2·28, 1·00–4·60; p=0·034) children were at higher risk of arterial ischaemic stroke than were white children. 82 (85%) children had focal features (most commonly hemiparesis) at presentation. Seizures were more common in younger children (≤1 year) and headache was more common in older children (>5 years; p<0·0001). At least one risk factor for childhood arterial ischaemic stroke was identified in 80 (83%) cases. Interpretation Age and racial group, but not sex, affected the risk of arterial ischaemic stroke in children. Investigation of such differences might provide causative insights. Funding The Stroke Association, UK.
In 2011 a working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines for Tourette syndrome (TS). Now, we present an ...updated version 2.0 of these European clinical guidelines for Tourette syndrome and other tic disorders, part I: assessment. Therefore, the available literature has been thoroughly screened, supplemented with national guidelines across countries and discussions among ESSTS experts. Diagnostic changes between DSM-IV and DSM-5 classifications were taken into account and new information has been added regarding differential diagnoses, with an emphasis on functional movement disorders in both children and adults. Further, recommendations regarding rating scales to evaluate tics, comorbidities, and neuropsychological status are provided. Finally, results from a recently performed survey among ESSTS members on assessment in TS are described. We acknowledge that the Yale Global Tic Severity Scale (YGTSS) is still the gold standard for assessing tics. Recommendations are provided for scales for the assessment of tics and psychiatric comorbidities in patients with TS not only in routine clinical practice, but also in the context of clinical research. Furthermore, assessments supporting the differential diagnosis process are given as well as tests to analyse cognitive abilities, emotional functions and motor skills.
This is the first study to systematically explore the lived experiences of sudden and new onset of severe functional tics from the perspective of the mother's experiences and describes their attempts ...to access support services in the United Kingdom.
Twenty-One mothers of young people aged between 12 to 17 years with functional tic-like behaviour (FTLB) took part in semi-structured interviews. Thematic analysis of the transcribed interviews revealed gaps and inconsistencies within the process of gaining access to professional services and a lack of support for the management of tics and functional tic-like movements, in addition to highlighting the impact it had on daily family life.
The themes generated included the occurrence and development of tics, the severity and intensity of symptoms, the psychological impact on the family and the need to make recommendations for a clear care pathway. Managing the impact of the FTLB and co-occurring conditions such as suicidal ideation and self-harm, as well as the physical and emotional trauma, commonly contributed to feelings of isolation and helplessness, which impacted negatively on the family's ability to function and participate in society.
The findings emphasize the urgent need to create a clear management pathway for those experiencing FTLB, including the need for more professionals with relevant knowledge, to improve the dialogue with families during the referral process, whilst prioritising the treatment of anxiety and other identified mental health concerns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some ...patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins.
Background
Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1–2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we ...conducted a systematic review of interventions for children and young people.
Methods
Databases were searched from inception to 1 October 2014 for placebo‐controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach.
Results
Forty trials were included pharmacological (32), behavioural (5), physical (2), dietary (1). For tics/global score there was evidence favouring the intervention from four trials of α2‐adrenergic receptor agonists clonidine and guanfacine, standardised mean difference (SMD) = −0.71; 95% CI −1.03, −0.40; N = 164 and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD = −0.64; 95% CI −0.99, −0.29; N = 133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD = −0.54; 95% CI −0.92, −0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD = −0.74; 95% CI −1.08, −0.40; N = 76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit.
Conclusions
When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours α2‐adrenergic receptor agonists (clonidine and guanfacine) as first‐line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when α2‐adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments.
Tourette syndrome (TS) is a common neurodevelopmental condition affecting approximately 1% of children and young people (c. 70,000 people age 7–17 years in England) which if untreated has a major adverse impact on mental health, social functioning and quality of life. Despite the prevalence of TS in young people being greater than diabetes and epilepsy, it remains a frequently misunderstood condition and its seriousness at a population level is typically overlooked, as evidenced by the absence of evidence‐based clinical guidelines. TS is characterised by persistent and impairing motor and vocal tics which typically emerge in childhood, run a waxing and waning course and carry on into adult life in about 30% of young people. Tics can be highly stigmatising, especially for teenagers, and often lead to bullying, peer victimisation, social exclusion, depression and self‐harm. TS is associated and frequently coexists with other neurodevelopmental and mental health conditions including ADHD (60%), anxiety disorder (40%), OCD (30%) and ASD (20%) which add to the complexity of clinical management. Evidence from this major systematic review and meta‐analysis shows that clinically effective treatments for tics in children and young people exist and include medication (e.g. α2‐noradrenergic agonists and antipsychotics) and behavioural interventions, including exposure and response prevention, habit reversal training (HRT) and the comprehensive behavioural intervention for tics programme which combines psychoeducation with HRT. The results of this review suggest that both medication and behavioural interventions have similar efficacy (moderate effect size) in treating tics, with behavioural interventions having a more favourable adverse effect profile. When considering medication, the more favourable adverse effect profile of α2‐noradrenergic agonists suggests that these agents should be offered before antipsychotics. However, psychoeducation and behavioural interventions are generally the preferred treatment option, particularly as first‐line interventions, by young people and their parents. Despite demonstrated efficacy, access in most healthcare systems to evidence‐based behavioural interventions for tics is extremely poor. Therefore, given the healthcare challenge of delivering behavioural interventions at scale with existing numbers of therapists and the traditional model of face‐to‐face delivery there is a pressing need to develop and evaluate digitally delivered interventions for young people with tics using a stepped‐care model of therapist support.
Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant ...distress and psychosocial impairment.
To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2).
For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013.
For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10-17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK.
For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -1.08 to -0.41; n = 75 and noradrenergic agents clonidine (Dixarit(®), Boehringer Ingelheim) and guanfacine: SMD -0.72, 95% CI -1.03 to -0.40; n = 164 are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD -0.64, 95% CI -0.99 to -0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects.
The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions.
Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal(®), Janssen), clonidine and aripiprazole (Abilify(®), Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications ('apps') and video consultation.
This study is registered as PROSPERO CRD42012002059.
The National Institute for Health Research Health Technology Assessment programme.
Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism ...spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (
n
= 709, 23.3% females) recruited as part of the
European Multicenter Tics in Children Study
(EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.
Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and ...genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.
There has been an increase in the occurrence of sudden onset functional tic-like behaviours in adolescents during the COVID-19 pandemic, which has had a significant impact on the affected ...individual's ability to engage with education. The aim of this article is to generate discussion and inform practice within schools with regard to the management of functional tic-like behaviours. An advice sheet for schools has been produced based on clinical expertise and experience of consulting with schools around the management within education settings. Case examples are presented highlighting the importance and impact of these strategies. We also highlight the need for further evaluation of the effectiveness of the advice sheet in collaboration with schools and families.
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