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Neuroethics 2018Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory...
INTRODUCTION
Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory patients, Deep Brain Stimulation (DBS) may be considered.
METHODS AND RESULTS
We discuss ethical problems encountered in two adolescent TS patients treated with DBS and systematically review the literature on the topic. Following surgery one patient experienced side effects without sufficient therapeutic effects and the stimulator was turned off. After a second series of behavioural treatment, he experienced a tic reduction of more than 50%. The second patient went through a period of behavioural disturbances that interfered with optimal programming, but eventually experienced a 70% tic reduction. Sixteen DBS surgeries in adolescent TS patients have been reported, none of which pays attention to ethical aspects.
DISCUSSION
Specific ethical issues arise in adolescent TS patients undergoing DBS relating both to clinical practice as well as to research. Attention should be paid to selecting patients fairly, thorough examination and weighing of risks and benefits, protecting the health of children and adolescents receiving DBS, special issues concerning patient's autonomy, and the normative impact of quality of life. In research, registration of all TS cases in a central database covering a range of standardized information will facilitate further development of DBS for this indication.
CONCLUSION
Clinical practice should be accompanied by ongoing ethical reflection, preferably covering not only theoretical thought but providing also insights in the views and perspectives of those concerned, that is patients, family members and professionals.
PubMed: 29937946
DOI: 10.1007/s12152-018-9359-6 -
The Cochrane Database of Systematic... Jan 2018Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before... (Review)
Review
BACKGROUND
Gilles de la Tourette syndrome, or Tourette's syndrome, is defined as the presence of both motor and vocal (phonic) tics for more than 12 months, that manifest before the age of 18 years, in the absence of secondary causes. Treatment of motor and phonic tics is difficult and challenging.
OBJECTIVES
To determine the safety and effectiveness of botulinum toxin in treating motor and phonic tics in people with Tourette's syndrome, and to analyse the effect of botulinum toxin on premonitory urge and sensory tics.
SEARCH METHODS
We searched the Cochrane Movement Disorders Group Trials Register, CENTRAL, MEDLINE, and two trials registers to 25 October 2017. We reviewed reference lists of relevant articles for additional trials.
SELECTION CRITERIA
We considered all randomised, controlled, double-blind studies comparing botulinum toxin to placebo or other medications for the treatment of motor and phonic tics in Tourette's syndrome for this review. We sought both parallel group and cross-over studies of children or adults, at any dose, and for any duration.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods to select studies, assess risk of bias, extract and analyse data. All authors independently abstracted data onto standardized forms; disagreements were resolved by mutual discussion.
MAIN RESULTS
Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette's syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum.
AUTHORS' CONCLUSIONS
We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette's syndrome.
Topics: Botulinum Toxins, Type A; Humans; Neuromuscular Agents; Tics; Time Factors; Tourette Syndrome
PubMed: 29304272
DOI: 10.1002/14651858.CD012285.pub2 -
Journal of Research in Pharmacy Practice 2017The aim of this study was to review empirical studies examining associations between candidate genes and adverse events (AEs) from methylphenidate (MPH) use in children... (Review)
Review
The aim of this study was to review empirical studies examining associations between candidate genes and adverse events (AEs) from methylphenidate (MPH) use in children and adolescents. The PubMed, EMBASE, CINAHL, and Web of Science databases were searched from their inception until March 2017. We included empirically based articles on pharmacogenetic studies in 0-17-year-old patients that investigated associations between specific candidate genes, their polymorphisms, and reported AEs. We extracted information about study design, setting, type of AE reporter, studied genes and their polymorphisms, age and gender, administered doses, method of genotyping, outcome measures, and main findings. A total of nine articles reporting information about four double-blind, placebo-controlled, cross-over studies and five open-label cohort studies were eligible for inclusion. Studies were published from 2006 onward and included a total of 998 patients (3-17-year-olds) diagnosed with attention-deficit hyperactivity disorder (ADHD). Studies predominantly involved males and lasted from 1 to 12 weeks. Studies used polymerase chain reaction and single nucleotide polymorphism genotyping methodology. Reported AEs were significantly associated with the following genes: appetite reduction (CES1*G); buccal-lingual movements (T1065G); diastolic blood pressure (ADRA2A Mspl C/C-GC); emotionality (DAT1*9/9); irritability (SNAP25 T1065G); picking (DRD4*7/DRD4*4); social withdrawal (DRD4*7/DRD4*4); somatic complaints (DAT1*10/10); tics (5-HTTLRP*S/L*L/L; SNAP25 T1065G); sadness (CES1*rsl12443580); and vegetative symptoms (5-HTTLPR). In conclusion, only few MPH pediatric pharmacogenetic studies were located, and large between-study heterogeneity was found. Studies were of naturalistic design and of short duration. They included small patient samples, poorly standardized treatment regimens, and limited outcome assessments. In the future, more pharmacogenomic studies in ADHD are needed, preferably using randomized, controlled study designs and of longer duration (more than 6 months).
PubMed: 28616427
DOI: 10.4103/jrpp.JRPP_16_161 -
Movement Disorders : Official Journal... Mar 2017Several clinician, informant, and self-report instruments for tics and associated phenomena have been developed that differ in construct, comprehensiveness, and ease of... (Review)
Review
BACKGROUND
Several clinician, informant, and self-report instruments for tics and associated phenomena have been developed that differ in construct, comprehensiveness, and ease of administration.
OBJECTIVE
A Movement Disorders Society subcommittee aimed to rate psychometric quality of severity and screening instruments for tics and related sensory phenomena.
METHODS
Following the methodology adopted by previous Movement Disorders Society subcommittee papers, a review of severity and screening instruments for tics was completed, applying a classification as "recommended," "suggested," or "listed" to each instrument.
RESULTS
A total of 5 severity scales (Yale Global Tic Severity Scale, Tourette Syndrome Clinical Global Impression, Tourette's Disorder Scale, Shapiro Tourette syndrome Severity Scale, Premonitory Urges for Tics Scale) were "recommended," and 6 (Rush Video-Based Tic Rating Scale, Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey, Tourette Syndrome Global Scale, Global Tic Rating Scale, Parent Tic Questionnaire, Tourette Syndrome Symptom List) were "suggested." A total of 2 screening instruments (Motor tic, Obsession and compulsions, Vocal tic Evaluation Survey and Autism-Tics, Attention Deficit/Hyperactivity Disorder and Other Comorbidities Inventory) were "recommended," whereas 2 others (Apter 4-questions screening and Proxy Report Questionnaire for Parents and Teachers) were "suggested."
CONCLUSIONS
Our review does not support the need for developing new tic severity or screening instruments. Potential objectives of future research include developing a rating instrument targeting the full spectrum of tic-related abnormal behaviors, assessing/screening malignant forms of tic disorders, and developing patient-reported outcome measures. © 2017 International Parkinson and Movement Disorder Society.
Topics: Humans; Severity of Illness Index; Tic Disorders
PubMed: 28071825
DOI: 10.1002/mds.26891 -
Systematic review of immunoglobulin use in paediatric neurological and neurodevelopmental disorders.Developmental Medicine and Child... Feb 2017A systematic literature review of intravenous immunoglobulin (IVIG) treatment of paediatric neurological conditions was performed to summarize the evidence, provide... (Review)
Review
AIM
A systematic literature review of intravenous immunoglobulin (IVIG) treatment of paediatric neurological conditions was performed to summarize the evidence, provide recommendations, and suggest future research.
METHOD
A MEDLINE search for articles reporting on IVIG treatment of paediatric neuroinflammatory, neurodevelopmental, and neurodegenerative conditions published before September 2015, excluding single case reports and those not in English. Owing to heterogeneous outcome measures, meta-analysis was not possible. Findings were combined and evidence graded.
RESULTS
Sixty-five studies were analysed. IVIG reduces recovery time in Guillain-Barré syndrome (grade B). IVIG is as effective as corticosteroids in chronic inflammatory demyelinating polyradiculoneuropathy (grade C), and as effective as tacrolimus in Rasmussen syndrome (grade C). IVIG improves recovery in acute disseminated encephalomyelitis (grade C), reduces mortality in acute encephalitis syndrome with myocarditis (grade C), and improves function and stabilizes disease in myasthenia gravis (grade C). IVIG improves outcome in N-methyl-d-aspartate receptor encephalitis (grade C) and opsoclonus-myoclonus syndrome (grade C), reduces cataplexy symptoms in narcolepsy (grade C), speeds recovery in Sydenham chorea (grade C), reduces tics in selected cases of Tourette syndrome (grade D), and improves symptoms in paediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (grade B).
INTERPRETATION
IVIG is a useful therapy in selected neurological conditions. Well-designed, prospective, multi-centre studies with standardized outcome measures are required to compare treatments.
Topics: Humans; Immunoglobulins; Immunologic Factors; MEDLINE; Nervous System Diseases; Neurodevelopmental Disorders; Pediatrics
PubMed: 27900773
DOI: 10.1111/dmcn.13349 -
The Cochrane Database of Systematic... Nov 2016Clinical trials and observational data have variously shown a protective, harmful or neutral effect of antihypertensives on cognitive function. In theory, withdrawal of... (Review)
Review
BACKGROUND
Clinical trials and observational data have variously shown a protective, harmful or neutral effect of antihypertensives on cognitive function. In theory, withdrawal of antihypertensives could improve cerebral perfusion and reduce or delay cognitive decline. However, it is also plausible that withdrawal of antihypertensives may have a detrimental effect on cognition through increased incidence of stroke or other vascular events.
OBJECTIVES
To assess the effects of complete withdrawal of at least one antihypertensive medication on incidence of dementia, cognitive function, blood pressure and other safety outcomes in cognitively intact and cognitive impaired adults.
SEARCH METHODS
We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP on 12 December 2015. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) provided they compared withdrawal of antihypertensive medications with continuation of the medications and included an outcome measure assessing cognitive function or a clinical diagnosis of dementia. We included studies with healthy participants, but we also included studies with participants with all grades of severity of existing dementia or cognitive impairment.
DATA COLLECTION AND ANALYSIS
Two review authors examined titles and abstracts of citations identified by the search for eligibility, retrieving full texts where needed to identify studies for inclusion, with any disagreement resolved by involvement of a third author. Data were extracted independently on primary and secondary outcomes. We used standard methodological procedures expected by Cochrane.The primary outcome measures of interest were changes in global and specific cognitive function and incidence of dementia; secondary outcomes included change in systolic and diastolic blood pressure, mortality, adverse events (including cardiovascular events, hospitalisation and falls) and adherence to withdrawal. The quality of the evidence was evaluated using the GRADE approach.
MAIN RESULTS
We included two RCTs investigating withdrawal of antihypertensives in 2490 participants. There was substantial clinical heterogeneity between the included studies, therefore we did not combine data for our primary outcome. Overall, the quality of included studies was high and the risk of bias was low. Neither study investigated incident dementia.One study assessed withholding previously prescribed antihypertensive drugs for seven days following acute stroke. Cognition was assessed using telephone Mini-Mental State Examination (t-MMSE) and Telephone Interview for Cognitive Status (TICS-M) at 90 days as a secondary outcome. The t-MMSE score was a mean of 1.0 point higher in participants who withdrew antihypertensive medications compared to participants who continued them (95% confidence interval (CI) 0.35 to 1.65; 1784 participants) and the TICS-M was a mean of 2.10 points higher (95% CI 0.69 to 3.51; 1784 participants). However, in both cases the evidence was of very low quality downgraded due to risk of bias, indirectness and evidence from a single study. The other study was community based and included participants with mild cognitive impairment. Drug withdrawal was for 16 weeks. Cognitive performance was assessed using a composite of at least five out of six cognitive tests. There was no evidence of a difference comparing participants who withdrew antihypertensive medications and participants who continued (mean difference 0.02 points, 95% CI -0.19 to 0.21; 351 participants). This evidence was of low quality and was downgraded due to risk of bias and evidence from single study.In one study, the systolic blood pressure after seven days of withdrawal was 9.5 mmHg higher in the intervention compared to the control group (95% CI 7.43 to 11.57; 2095 participants) and diastolic blood pressure was 5.1 mmHg higher (95% CI 3.86 to 6.34; 2095 participants). This evidence was low quality, downgraded due to indirectness, because the data must be interpreted in the context of the wider study looking at glyceryl trinitrate administration or not, and evidence from a single study. In the other study, systolic blood pressure increased by 7.4 mmHg in the withdrawal group compared to the control group (95% CI 7.08 to 7.72; 356 participants) and diastolic blood pressure increased by 2.6 mmHg (95% CI 2.42 to 2.78; 356 participants). This was moderate quality evidence, downgraded as evidence was from a single study. We combined data for mortality and cardiovascular events. There was no clear evidence that antihypertensive medication withdrawal affected adverse events, although there was a possible trend to increased cardiovascular events in the large post-stroke study (pooled mortality risk ratio 0.88, 95% CI 0.72 to 1.08; 2485 participants; and cardiovascular events risk ratio 1.29, 95% CI 0.96 to 1.72). Certain prespecified outcomes of interest (falls, hospitalisation) were not reported.
AUTHORS' CONCLUSIONS
The effects of withdrawing antihypertensive medications on cognition or prevention of dementia are uncertain. There was a signal of a positive effect in one study looking at withdrawal after acute stroke but these results are unlikely to be generalisable to non-stroke settings and were not a primary outcome of the study. Withdrawing antihypertensive drugs was associated with increased blood pressure. It is unlikely to increase mortality at three to four months' follow-up, although there was a signal from one large study looking at withdrawal after stroke that withdrawal was associated an increase in cardiovascular events.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Cognition; Cognitive Dysfunction; Dementia; Humans; Randomized Controlled Trials as Topic; Stroke; Time Factors; Withholding Treatment
PubMed: 27802359
DOI: 10.1002/14651858.CD011971.pub2 -
European Child & Adolescent Psychiatry Sep 2016Gilles de la Tourette syndrome (GTS) and other chronic tic disorders are neurodevelopmental conditions characterized by the presence of tics and associated behavioral... (Review)
Review
Gilles de la Tourette syndrome (GTS) and other chronic tic disorders are neurodevelopmental conditions characterized by the presence of tics and associated behavioral problems. Whilst converging evidence indicates that these conditions can affect patients' quality of life (QoL), the extent of this impairment across the lifespan is not well understood. We conducted a systematic literature review of published QoL studies in GTS and other chronic tic disorders to comprehensively assess the effects of these conditions on QoL in different age groups. We found that QoL can be perceived differently by child and adult patients, especially with regard to the reciprocal contributions of tics and behavioral problems to the different domains of QoL. Specifically, QoL profiles in children often reflect the impact of co-morbid attention-deficit and hyperactivity symptoms, which tend to improve with age, whereas adults' perception of QoL seems to be more strongly affected by the presence of depression and anxiety. Management strategies should take into account differences in age-related QoL needs between children and adults with GTS or other chronic tic disorders.
Topics: Adolescent; Adult; Anxiety; Child; Depression; Female; Humans; Hyperkinesis; Male; Quality of Life; Tic Disorders; Tics; Tourette Syndrome
PubMed: 26880181
DOI: 10.1007/s00787-016-0823-8 -
Health Technology Assessment... Jan 2016Tourette 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... (Review)
Review
Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis.
BACKGROUND
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.
OBJECTIVE
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).
DATA SOURCES
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.
REVIEW/RESEARCH METHODS
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.
RESULTS
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.
LIMITATIONS
The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions.
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.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42012002059.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adolescent; Antipsychotic Agents; Behavior Therapy; Child; Complementary Therapies; Cost-Benefit Analysis; Humans; Parents; Tics; Tourette Syndrome
PubMed: 26786936
DOI: 10.3310/hta20040 -
Neurotherapeutics : the Journal of the... Oct 2015Cannabis has been used for many medicinal purposes, including management of spasms, dystonia, and dyskinesias, with variable success. Its use for tetanus was described... (Review)
Review
Cannabis has been used for many medicinal purposes, including management of spasms, dystonia, and dyskinesias, with variable success. Its use for tetanus was described in the second century BCE, but the literature continues to include more case reports and surveys of its beneficial effects in managing symptoms of hyperkinetic movement disorders than randomized controlled trials, making evidence-based recommendations difficult. This paper reviews clinical research using various formulations of cannabis (botanical products, oral preparations containing ∆(9)-tetrahydrocannabinol and/or cannabidiol) and currently available preparations in the USA (nabilone and dronabinol). This has been expanded from a recent systematic review of cannabis use in several neurologic conditions to include case reports and case series and results of anonymous surveys of patients using cannabis outside of medical settings, with the original evidence classifications marked for those papers that followed research protocols. Despite overlap in some patients, dyskinesias will be treated separately from dystonia and chorea; benefit was not established beyond individual patients for these conditions. Tics, usually due to Tourettes, did respond to cannabis preparations. Side effects reported in the trials will be reviewed but those due to recreational use, including the dystonia that can be secondary to synthetic marijuana preparations, are outside the scope of this paper.
Topics: Animals; Cannabinoids; Cannabis; Dyskinesias; Dystonia; Humans; Tics
PubMed: 26271953
DOI: 10.1007/s13311-015-0376-4 -
Chest Jul 2015We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline... (Review)
Review
Somatic Cough Syndrome (Previously Referred to as Psychogenic Cough) and Tic Cough (Previously Referred to as Habit Cough) in Adults and Children: CHEST Guideline and Expert Panel Report.
BACKGROUND
We conducted a systematic review on the management of psychogenic cough, habit cough, and tic cough to update the recommendations and suggestions of the 2006 guideline on this topic.
METHODS
We followed the American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework. The Expert Cough Panel based their recommendations on data from the systematic review, patients' values and preferences, and the clinical context. Final grading was reached by consensus according to Delphi methodology.
RESULTS
The results of the systematic review revealed only low-quality evidence to support how to define or diagnose psychogenic or habit cough with no validated diagnostic criteria. With respect to treatment, low-quality evidence allowed the committee to only suggest therapy for children believed to have psychogenic cough. Such therapy might consist of nonpharmacologic trials of hypnosis or suggestion therapy, or combinations of reassurance, counseling, and referral to a psychologist, psychotherapy, and appropriate psychotropic medications. Based on multiple resources and contemporary psychologic, psychiatric, and neurologic criteria (Diagnostic and Statistical Manual of Mental Disorders, 5th edition and tic disorder guidelines), the committee suggests that the terms psychogenic and habit cough are out of date and inaccurate.
CONCLUSIONS
Compared with the 2006 CHEST Cough Guidelines, the major change in suggestions is that the terms psychogenic and habit cough be abandoned in favor of somatic cough syndrome and tic cough, respectively, even though the evidence to do so at this time is of low quality.
Topics: Adult; Child; Cough; Habits; Humans; Practice Guidelines as Topic; Somatoform Disorders; Syndrome; Tics
PubMed: 25856777
DOI: 10.1378/chest.15-0423