Roger D. Freeman

An international perspective on Tourette syndrome: selected findings from 3500 individuals in 22 countries

We have established a multisite, international database of 3500 individuals diagnosed with Tourette syndrome (TS). The male:female ratio is 4.3:1 for the total sample, with wide variation among sites; the male excess occurs at every site. Anger control problems, sleep difficulties, coprolalia, and self‐injurious behavior only reach impressive levels in individuals with comorbidity. Anger control problems are strongly correlated with comorbidity, regardless of site, region, or whether assessed by neurologists or psychiatrists. The mean age at onset of tics is 6.4 years. At all ages, about 12% of individuals with TS have no reported comorbidity. The most common reported comorbidity is attention‐deficit‐hyperactivity disorder. Males are more likely to have comorbid disorders than females. The earlier the age at onset, the greater the likelihood of a positive family history of tics. An understanding of the factors producing these and other variations might assist in better subtyping of TS. Because behavioral problems are associated with comorbidity, their presence should dictate a high index of suspicion of the latter, whose treatment may be at least as important as tic reduction. The established database can be used as the entry point for further research when large samples are studied and generalizability of results is important.

Tic disorders and ADHD: answers from a world-wide clinical dataset on Tourette syndrome.

BackgroundTourette syndrome (TS) is a neurodevelopmental disorder with frequent comorbidity with Attention- deficit-Hyperactivity disorder (ADHD). The impact of this association is still a matter of debate.MethodUsing the TIC database containing 6,805 cases, the clinical differences were ascertained between subjects with and without ADHD.ResultsThe reported prevalence of ADHD in TS was 55%, within the range of many other reports. If the proband was diagnosed with ADHD, a family history of ADHD was much more likely. ADHD was associated with earlier diagnosis of TS and a much higher rate of anger control problems, sleep problems, specific learning disability, OCD, Oppositional-defiant disorder, mood disorder, social skill deficits, sexually inappropriate behaviour, and self-injurious behaviour. Subjects with seizures and with Developmental Coordination Disorder also had high rates of ADHD. Anxiety disorder, however, was not more frequent. Preliminary data suggest that most behavioural difficulties in ADHD are associated with the Combined or Hyperactive-Impulsive Subtypes of ADHD. Every large site (>200 cases) had a significantly increased rate of anger control problems in cases with ADHD.ConclusionSubjects with TS have high rates of ADHD and complex associations with other disorders. Clinically the findings confirm other research indicating the importance of ADHD in understanding the behavioural problems often associated with the diagnosis of TS. Additional ADHD comorbidity should be taken into account in diagnosis, management, and training.Tourette syndrome (TS) is a neurodevelopmental disorder with frequent comorbidity with Attention- deficit-Hyperactivity disorder (ADHD). The impact of this association is still a matter of debate. Using the TIC database containing 6,805 cases, the clinical differences were ascertained between subjects with and without ADHD. The reported prevalence of ADHD in TS was 55%, within the range of many other reports. If the proband was diagnosed with ADHD, a family history of ADHD was much more likely. ADHD was associated with earlier diagnosis of TS and a much higher rate of anger control problems, sleep problems, specific learning disability, OCD, Oppositional-defiant disorder, mood disorder, social skill deficits, sexually inappropriate behaviour, and self-injurious behaviour. Subjects with seizures and with Developmental Coordination Disorder also had high rates of ADHD. Anxiety disorder, however, was not more frequent. Preliminary data suggest that most behavioural difficulties in ADHD are associated with the Combined or Hyperactive-Impulsive Subtypes of ADHD. Every large site (>200 cases) had a significantly increased rate of anger control problems in cases with ADHD. Subjects with TS have high rates of ADHD and complex associations with other disorders. Clinically the findings confirm other research indicating the importance of ADHD in understanding the behavioural problems often associated with the diagnosis of TS. Additional ADHD comorbidity should be taken into account in diagnosis, management, and training.

Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia.

Learning Objectives: After participating in this CME activity, the obstetrician/gynecologist should be better able to: 1. Accurately counsel patients on the risks and benefits of initiating hormone therapy (HT) for vasomotor symptoms (VMS). 2. Apply current evidence to select appropriate HT for treatment of VMS in uncomplicated postmenopausal women. 3. Compare the risks and benefits of HT for special subpopulations of menopausal patients, such as women with a history of breast cancer, BRCA mutation carriers, those with hypertension, women older than 65 years, and those at a high risk for or with a history of venous thromboembolism.

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities

Abstract:  The purpose of this study was to determine the efficacy of controlled‐release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double‐blind, placebo‐controlled crossover trial of CR melatonin (5 mg) followed by a 3‐month open‐label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty‐one children (age range 2–18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open‐label phase. Recordings of total night‐time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open‐label somnolog measures of sleep efficiency and the longest sleep episode in the open‐label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

Melatonin treatment of sleep–wake cycle disorders in children and adolescents

Lerner, a dermatologist who isolated melatonin (MLT) in 1959, was the first to report on its hypnotic properties, and was also the first to self-administer this hormone. Later, in 1971, Anton-Tay and coworkers injected MLT into volunteers who quickly fell asleep. In adults, MLT treatment appears to have beneficial effects in those who have sleep disorders due to delayed sleep onset, shift work, and jet lag. MLT can enhance adaptation to forced phase shift in simulated shift-work and jet-lag conditions. However, better controlled, long-term studies are still required. MLT may also benefit certain types of adult insomnia.

Sleep Hygiene for Children With Neurodevelopmental Disabilities

Sleep disturbances in children with neurodevelopmental disabilities are common and have a profound effect on the quality of life of the child, as well as the entire family. Although interventions for sleep problems in these children often involve a combination of behavioral and pharmacologic strategies, the first line of treatment is the promotion of improved sleep habits or “hygiene.” Despite the importance of sleep-hygiene principles, defined as basic optimal environmental, scheduling, sleep-practice, and physiologic sleep-promoting factors, clinicians often lack appropriate knowledge and skills to implement them. In addition, sleep-hygiene practices may need to be modified and adapted for this population of children and are often more challenging to implement compared with their healthy counterparts. This first comprehensive, multidisciplinary review of sleep hygiene for children with disabilities presents the rationale for incorporating these measures in their treatment, outlines both general and specific sleep-promotion practices, and discusses problem-solving strategies for implementing them in a variety of clinical practice settings.

Long-term sleep disturbances in children: A cause of neuronal loss

Short-term sleep loss is known to cause temporary difficulties in cognition, behaviour and health but the effects of persistent sleep deprivation on brain development have received little or no attention. Yet, severe sleep disorders that last for years are common in children especially when they have neurodevelopmental disabilities. There is increasing evidence that chronic sleep loss can lead to neuronal and cognitive loss in children although this is generally unrecognized by the medical profession and the public. Without the restorative functions of sleep due to total sleep deprivation, death is inevitable within a few weeks. Chronic sleep disturbances at any age deprive children of healthy environmental exposure which is a prerequisite for cognitive growth more so during critical developmental periods. Sleep loss adversely effects pineal melatonin production which causes disturbance of circadian physiology of cells, organs, neurochemicals, neuroprotective and other metabolic functions. Through various mechanisms sleep loss causes widespread deterioration of neuronal functions, memory and learning, gene expression, neurogenesis and numerous other changes which cause decline in cognition, behaviour and health. When these changes are long-standing, excessive cellular stress develops which may result in widespread neuronal loss. In this review, for the first time, recent research advances obtained from various fields of sleep medicine are integrated in order to show that untreated chronic sleep disorders may lead to impaired brain development, neuronal damage and permanent loss of developmental potentials. Further research is urgently needed because these findings have major implications for the treatment of sleep disorders.

Melatonin therapy for circadian rhythm sleep disorders in children with multiple disabilities: what have we learned in the last decade?

In this discussion, children are considered to have multiple disabilities and low functioning when they have a combination of severe neurodevelopmental disabilities, such as visual impairment, epilepsy, intellectual deficits, cerebral palsy, attention-deficit–hyperactivity disorder (ADHD), autism, eating difficulties, and other neuropsychiatric problems.

Coprophenomena in Tourette syndrome.

The aims of this descriptive study were to examine the prevalence and associations of coprophenomena (involuntary expression of socially unacceptable words or gestures) in individuals with Tourette syndrome. Participant data were obtained from the Tourette Syndrome International Database Consortium. A specialized data collection form was completed for each of a subset of 597 consecutive new patients with Tourette syndrome from 15 sites in seven countries. Coprolalia occurred at some point in the lifetime of 19.3% of males and 14.6% of females, and copropraxia in 5.9% of males and 4.9% of females. Coprolalia was three times as frequent as copropraxia, with a mean onset of each at about 11 years, 5 years after the onset of tics. In 11% of those with coprolalia and 12% of those with copropraxia these coprophenomena were one of the initial symptoms of Tourette syndrome. The onsets of tics, coprophenomena, smelling of non‐food objects, and spitting were strongly intercorrelated. Early onset of coprophenomena was not associated with its longer persistence. The most robust associations of coprophenomena were with the number of non‐tic repetitive behaviors, spitting, and inappropriate sexual behavior. Although coprophenomena are a frequently feared possibility in the course of Tourette syndrome, their emergence occurs in only about one in five referred patients. Because the course and actual impact of coprophenomena are variable, additional prospective research is needed to provide better counseling and prognostic information.

Tourette syndrome and learning disabilities

BackgroundTourette Syndrome (TS) is a neurodevelopmental disorder of childhood. Learning disabilities are frequently comorbid with TS. Using the largest sample of TS patients ever reported, we sought to identify differences between subjects with TS only and subjects with TS and a comorbid learning disability.MethodsWe used the Tourette Syndrome International Consortium database (TIC) to compare subjects with comorbid Tourette Syndrome and learning disabilities (TS + LD) to subjects who did not have a comorbid learning disability (TS - LD). The TIC database contained 5,500 subjects. We had usable data on 5,450 subjects.ResultsWe found 1,235 subjects with TS + LD. Significant differences between the TS + LD group and the TS - LD group were found for gender (.001), age onset (.030), age first seen (.001), age at diagnosis (.001), prenatal problems (.001), sibling or other family member with tics (.024), two or more affected family members (.009), and severe tics (.046). We used logistic modeling to identify the optimal prediction model of group membership. This resulted in a five variable model with the epidemiologic performance characteristics of accuracy 65.2% (model correctly classified 4,406 of 5,450 subjects), sensitivity 66.1%, and specificity 62.2%.ConclusionSubjects with TS have high prevalence rates of comorbid learning disabilities. We identified phenotype differences between the TS - LD group compared to TS + LD group. In the evaluation of subjects with TS, the presence of a learning disability should always be a consideration. ADHD may be an important comorbid condition in the diagnosis of LD or may also be a potential confounder. Further research on etiology, course and response to intervention for subjects with TS only and TS with learning disabilities is needed.