Tammy Hedderly

European clinical guidelines for Tourette Syndrome and other tic disorders. Part I: assessment

A working group of the European Society for the Study of Tourette Syndrome (ESSTS) has developed the first European assessment guidelines of Tourette Syndrome (TS). The available literature including national guidelines was thoroughly screened and extensively discussed in the expert group of ESSTS members. Detailed clinical assessment guidelines of tic disorders and their comorbidities in both children and adults are presented. Screening methods that might be helpful and necessary for specialists’ differential diagnosis process are suggested in order to further analyse cognitive abilities, emotional functions and motor skills. Besides clinical interviews and physical examination, additional specific tools (questionnaires, checklists and neuropsychological tests) are recommended.

SGCE mutations cause psychiatric disorders: clinical and genetic characterization

Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P < 0.001) in mutation positive cases, compulsivity being the predominant feature (P < 0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.

Diagnostic delays in paediatric stroke

Background Stroke is a major cause of mortality in children. Conditions that mimic stroke also cause severe morbidity and require prompt diagnosis and treatment. We have investigated the time to diagnosis in a cohort of children with stroke. Methods A population-based cohort of children with stroke was prospectively identified in the south of England. Case notes, electronic hospital admission databases and radiology records were reviewed. Timing of symptom onset, presentation to hospital, first neuroimaging, first diagnostic neuroimaging and presenting clinical features were recorded. Results Ninety-six children with an arterial ischaemic stroke (AIS) and 43 with a haemorrhagic stroke (HS) were identified. The median time from symptom onset to diagnostic neuroimaging was 24.3 h in AIS and 2.9 h in HS. The initial imaging modality was CT in 68% of cases of AIS. CT was diagnostic of AIS in 66% of cases. MRI was diagnostic in 100%. If initial neuroimaging was non-diagnostic in AIS, then median time to diagnosis was 44 h. CT was diagnostic in 95% of HS cases. Presentation outside normal working hours resulted in delayed neuroimaging in AIS (13 vs 3 h, p=0.032). Diffuse neurological signs or a Glasgow Coma Scale <9 resulted in more expeditious neuroimaging in both HS and AIS. Conclusions The diagnosis of AIS in children is delayed at every stage of the pathway but most profoundly when the first neuroimaging is CT scanning, which is non-diagnostic. MRI should be the initial imaging modality of choice in any suspected case of childhood AIS.

Benign hereditary chorea related to NKX2.1: expansion of the genotypic and phenotypic spectrum

Benign hereditary chorea is a dominantly inherited, childhood‐onset hyperkinetic movement disorder characterized by non‐progressive chorea and variable degrees of thyroid and respiratory involvement. Loss‐of‐function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.

Outcome and recurrence one year after paediatric arterial ischaemic stroke in a population-based cohort

Arterial ischemic stroke (AIS) is an important cause of acquired brain injury in children. Few prospective population‐based studies of childhood AIS have been completed. We aimed to investigate the outcome of childhood AIS 12 months after the event in a population‐based cohort.

Perceptions of treatment for tics among young people with Tourette syndrome and their parents: a mixed methods study

BackgroundTourette syndrome (TS) among young people is associated with psychosocial difficulties and parents play an important role in the management of the condition. Clinical guidelines have been developed for the treatment of TS and tics, but little is known about how young people and their parents perceive their treatment options or their desired outcomes of treatment. The aim of this study is to explore perceptions of treatments for tics among young people with TS and their parents.MethodsIn-depth interviews with 42 young people with TS and a mixed-methods, online survey of 295 parents of young people with TS. Participant recruitment was conducted through Tourettes Action (TA): a non-profit UK organisation for the support of people with TS. Interview transcripts were analysed using thematic analysis and responses to survey open-ended questions were analysed using content analysis. Triangulation of qualitative and quantitative data from the parents’ survey and qualitative data from the interviews with young people was used to increase the validity and depth of the findings.ResultsA strong theme was the perception that health professionals have limited knowledge of TS and its treatment. Medication was a common treatment for tics and both young people and parents described benefits of medication. However, adverse effects were frequently described and these were a common reason for stopping medication among young people. Aripiprazole was viewed most positively. Access to behavioural interventions for tics was limited and 76% of parents wanted this treatment to be available for their child. Some young people had reservations about the effectiveness or practicality of behavioural interventions. Reduction and abolition of tics were desired outcomes of treatment, but both parents and young people also identified the importance of increasing control over tics and reducing anxiety-related symptoms. For young people, managing the urge to tic was an important outcome of treatment.ConclusionsThe results suggest a need for more training in the identification and management of TS and wider availability of behavioural treatments. Clinical trials could explore the effectiveness of Aripiprazole used in combination with psycho-educational interventions to reduce anxiety and promote a sense of control.

Refractoriness to pharmacological treatment for tics: A multicentre European audit

Recently, a consensus definition of treatment responsiveness for obsessive-compulsive disorder has been reached through Delphi survey methodology, showing great potential for practical application in clinical care [1]. A standardized definition of refractoriness to pharmacological treatment of tics in TD (chronic tic disorders including Tourette Syndrome) would aid decisions on drug switch, psychological treatment or access to invasive treatments like functional surgery [2,3]. We conducted a European audit survey in order to: i) explore the main features that would define refractoriness of tics to pharmacological treatment, and ii) assess how consistently these features are taken into account in routine clinical practice. Itemsdefining treatment refractoriness in TDwas discussedwithin a panel of seven expert clinicians (panel clinicians) across different European countries. All panel members were invited to rate each item according to whether the domain measured was ‘essential’ or not for the definition of refractoriness. Only those items for which a unanimous judgement of ‘essential’was reachedwere then considered for the audit survey. This procedure yielded the following list of ‘essential’ items: duration of treatment (weeks); dichotomous judgement of improvement of tic severity (improved/not improved); documented change of the Yale Global Tic Severity Scale (YGTSS) 0–50 severity score; reason for themaximum dose reached; number of single doses missed on average over a 10-day period. A clinical questionnaire (Appendix file) was used to collect information related to the selected items from other seven European expert clinicians (survey clinicians). The questionnaire was completed by survey clinicians related to outpatients with a diagnosis of TD (according to DSM\\V) who had been previously judged by the clinician as refractory to an anti-tic monotherapy. A judgement of refractoriness implied that the clinician had already decided either to discontinue that particular anti-tic monotherapy, or to change the regime by adding on another treatment. With respect to the main reason for the refractoriness judgement, refractoriness was categorised either as due to lack of efficacy at the highest tolerated dose or as due to lack of tolerability at initial or effective dosage. This studywas selectively based on the clinical information carried out as part of the routine clinical care of the patients. Sixty-eight TD patients (56male, median age: 14 years; range 8–44) were enrolled consecutively across 7 European tertiary centres for TD; at each participating centre, all patients were identified by the same clinician throughout a period of 18 months. The median age at tic onset

Novel Psychological Formulation and Treatment of "Tic Attacks" in Tourette Syndrome.

One important, but underreported, phenomenon in Tourette syndrome (TS) is the occurrence of “tic attacks.” These episodes have been described at conferences as sudden bouts of tics and/or functional tic-like movements, lasting from 15 min to several hours. They have also been described by patients in online TS communities. To date, there are no reports of tic attacks in the literature. The aim of this article is to stimulate discussion and inform clinical practices by describing the clinical presentation of 12 children (mean age 11 years and 3 months; SD = 2 years and 4 months) with TS and tic attacks, with a detailed case report for one case (13-year-old male). These children commonly present acutely to casualty departments and undergo unnecessary medical investigations. Interestingly, all children reported comorbid anxiety, with worries about the tics themselves and an increased internal focus of attention on tics once the attacks had started. In keeping with other children, the index case reported a strong internal focus of attention, with a relationship between physiological sensations/tic urges, worries about having tic attacks, and behavioral responses (e.g., body scanning, situational avoidance, and other responses). In our experience, the attacks reduce with psychological therapy, for example, the index case attended 13 sessions of therapy that included metacognitive and attention training techniques, as well as cognitive–behavioral strategies. Following treatment, an improvement was seen across a range of measures assessing tics, mood, anxiety, and quality of life. Thus, psychological techniques used to treat anxiety disorders are effective at supporting a reduction in tic attacks through modifying attention, worry processes, and negative beliefs. It is hypothesized that an attentional style of threat monitoring, difficulties tolerating internal sensory urges, cognitive misattributions, and maladaptive coping strategies contribute to the onset and maintenance of tic attacks. These cases provide support for the view that tic attacks are triggered and maintained by psychological factors, thereby challenging the view that tic attacks merely reflect extended bouts of tics. As such, we propose that the movements seen in tic attacks may resemble a combination of tics and functional neurological movements, with tic attacks reflecting episodes of panic and anxiety for individuals with TS.

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent–child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case–control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive–compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Childhood motor stereotypies: questions of definition and management

When considering therapeutic management of motor stereotypies, there are some important concepts worthy of debate: ‘Why treat stereotypies at all? Are they benign? Will they not just go away? Should they be ignored?’ But such approaches may not always offer the needed support to the families. Motor stereotypies are common childhood onset movements. They are developmental movements that need a definitive description and name in their own right. Their phenomenology is intriguing, and terminology or definitions have been subject to recent debate. Aetiologies are likely to be multiple and complex. Despite the frequency of their occurence, there are diagnostic difficulties, confusion around comorbidities, and management uncertainty. Children are often incorrectly labelled with autism spectrum disorder on the basis of the motor phenotype alone. Social communication difficulties can be primary or secondary, while stereotypies can occur in otherwise typically developing children. Specht et al. considered autism spectrum disorder to be exclusionary criteria in their cohort. There are increasing referrals from well-informed families (often self-diagnosing) using online resources (for example, the excellent John Hopkins website: www.hopkinsmedicine.org). The families report distress over impairments in quality of life and the movements can appear to dominate everything else. Parents also report concerns that their child may be perceived as ‘odd’ – understandable when certain stereotypies are observed. Sometimes these movements are misdiagnosed as epilepsy. We have seen several children referred for electroencephalography and magnetic resonance imaging, and some even prescribed anticonvulsants. It is also surprisingly common to see children with complex motor stereotypies informed that the condition could be Tourette syndrome. Management advice given for stereotypies can be very different to that for tics. For example, ‘ignoring’ the motor aspects or ‘practicing non-suggesting’ can help tics subside as they are highly suggestible. Ignoring a gratifying motor stereotypy however, is very likely to have the opposite effect and result in escalation of movements. When interviewed alone, children often talk of intense enjoyment and preference of the motor activity to almost anything else. The motor phenomenon may also be associated with exciting or intense imagery or thoughts. So back to the debate about suggesting therapy. Who are we undertaking this for? Are we treating a socially constructed disorder? Such questions need careful philosophical exploration with children and their parents. We offer management when the movements are intrusive or impairing, i.e. when children report being unable to engage in tasks or to pay attention. Although initially hesitant to stop stereotypies, on doing so children can express relief, reporting a sense of freedom from the compulsion to perform them. Abilities to consciously control or suppress the movements emerge with time. It is intuitive that the necessary motor inhibitory networks develop at different rates. Attempting to suppress movements at a younger age can be frustrating and unsuccessful. In the study from Specht et al. behavioural therapy was offered to participants aged 7 to 17 years. The authors used a parent-delivered DVD programme to help children learn to suppress intrusive stereotypies. This is a novel, practical, and potentially time-efficient method. Their approach included awareness training and direct discussions. I would be interested in more personal feedback from the children about the most useful elements of this programme. These methods may be just as effective as more labourintensive cognitive behavioural strategies. We look forward to further exploration of Specht et al.’s proposals, whilst being mindful about which aspects of this package are most helpful. Simple psychoeducation coupled with reward strategies may be all that is required. If movements subside, will all be well? Research must not stop here. The association with inattentiveness and anxiety is a concern. There is frequently a family history of obsessive-compulsive traits or anxiety disorders. Sometimes these traits can be identified in the children as the movements subside. These important associations are seen in other situations, for example tics with obsessive-compulsive disorder in the Tourette spectrum (a term I prefer to syndrome). What happens to children with motor stereotypies in adulthood? Are there opportunities for preventative work to avoid future mental health difficulties? Finally, can the verbal and cognitively-able children provide further insight into the minds of the non-verbal children with severe autism spectrum disorder? Longitudinal studies are necessary and we look forward to future collaborations and ongoing important publications in this field.