Teacher Knowledge of Tourette Syndrome and Associated Factors.

BACKGROUND: Tourette syndrome (TS) is associated with learning disabilities and educational impairment. Teacher knowledge about TS may have a positive impact on students with TS, but factors associated with teacher knowledge of TS are not known. METHODS: In this cross-sectional study, teachers of youth with TS and of a community control group completed a Teacher Understanding of Tourette Syndrome Survey (TUTS), a pilot questionnaire enquiring about self-perceived understanding, teacher knowledge, and sources of information. We compared TUTS scores between TS and control groups and between those who did and did not use specific sources of information about TS using Wilcoxon rank-sum tests. Bivariate correlation analyses were used to evaluate associations between teacher knowledge and potential contributing factors. RESULTS: Data from 114 teachers of children with TS and 78 teachers of control subjects were included. Teachers of youth with TS had significantly more knowledge, had higher self-perceived understanding, and used more sources of information than teachers of the control group. Teachers who knew of the Tourette Association of America and who gathered information themselves had higher knowledge about TS than those who did not. CONCLUSION: Teachers of children with TS know more about TS and use more sources to learn about TS than teachers of children without TS.

Neuropathology and morphometry of dentate nucleus neurons in DYT1 brains: Cerebellar abnormalities in isolated dystonia.

Brain lesions exclusive to dystonia, or specific forms of it, such as isolated dystonia, have been rarely described. While the identification of distinctive intra- or extraneuronal abnormalities in childhood-onset generalized dystonia (DYT1) brains remains lacking, recent stereology-based findings demonstrated hypertrophy of neurons in the substantia nigra (SN) of DYT1-carriers manifesting dystonia (DYT1-manif) versus DYT1-carriers nonmanifesting dystonia (DYT1-nonmanif), and age-matched control subjects (C). Because other brain regions including the cerebellum (CRB) have been implicated in the pathomechanisms of dystonia, we investigated neurons of the dentate nucleus (DN), the "door-out" nucleus of the CRB. We performed systematic neuropathologic assessments and stereology-based measurements of 7 DN from DYT1-carriers (DYT1-DN; 4 DYT1-manif and 3 DYT1-nonmanif), and 5 age-matched control (C-DN) subjects. Data demonstrated larger cell body (+14.1%), nuclear (+10.6%), and nucleolar (+48.3%) volumes of DYT1-DN versus C-DN neurons. No differences in intra- and extracellular pathological indicators (ß-amyloid, pTau, α-synuclein, Torsin1A, Negri, Bunina, Hirano, Marinesco, Nissl bodies, Buscaino bodies, granulovacuolar degeneration, or cerebrovascular lesions) were detected in DYT1-DN versus C-DN. Astroglial reactivity (GFAP) and microglial activation (IBA1) were observed in some DYT1-DNs. These novel findings confirm involvement of the DN and CRB in the pathogenesis of DYT1 and perhaps of other forms of isolated dystonia.

Risk Behaviors in Youth With and Without Tourette Syndrome.

BACKGROUND: Specific health-risk behaviors are present in older adolescents and young adults wtih Tourette syndrome (TS), but little is known about health-risk behaviors in youth with TS. METHODS: We compared responses on the Youth Risk Behavior Surveillance System (YRBS) in youth with TS with those in a concurrent community control group. The YRBS evaluates risk behaviors most closely associated with morbidity and mortality in young people. Tic severity, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), measures of ADHD symptom severity, and whether or not the individual had been bullied in school were also compared between the groups. RESULTS: Data from 52 youth with TS and 48 control youth were included. We did not detect any differences between control youth and youth with TS in the reporting of risky behaviors. Tic severity was not significantly associated with high-risk behavior. However, ADHD was significantly more common in youth with TS (P < 0.0002), and youth with TS who identified themselves as victims of bullying had significantly higher ADHD symptom severity scores (P = 0.04) compared with those who were not bullied. CONCLUSIONS: Risk behaviors are not reliably or clinically different in youth with TS compared with control youth. ADHD severity, but not tic severity, was associated with being bullied in youth with TS.

Anxiety Symptoms Differ in Youth With and Without Tic Disorders.

We compared anxiety symptoms in youth with and without tic disorders by comparing scores on the Multidimensional Anxiety Scale for Children (MASC) in youth with tic disorders to those in a concurrent community control group and in a group of treatment-seeking anxious youth from the Child/Adolescent Anxiety Multimodal Study (CAMS). Data from 176 youth with tic disorders, 93 control subjects, and 488 CAMS participants were included. Compared to youth with tic disorders, controls had lower total MASC scores (p < 0.0001) and CAMS participants had similar total MASC scores (p = 0.13). Separation Anxiety (p = 0.0003) and Physical Symptom (p < 0.0001) subscale scores were higher in youth with tic disorders than in CAMS participants. We conclude that the anxiety symptom profile differs in youth with and without tic disorders, which may have important implications for targeting treatment of anxiety in youth with tic disorders.

Tic Disorders are Associated With Lower Child and Parent Quality of Life and Worse Family Functioning.

OBJECTIVE: Chronic tic disorders occur in approximately 3% of children. Neuropsychiatric symptoms of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and depression are common. We evaluated the impact of tic disorders and comorbid symptoms on individual and parent quality of life and family functioning. METHOD: In two cross-sectional studies children with tic disorders were enrolled at the University of Rochester or the University of South Florida; data were pooled for analyses. Control subjects were enrolled at the University of Rochester. We compared quality of life and function in youth and families with and without tic disorders. We evaluated the associations between comorbid symptoms and individual quality of life and family impact in youth with tic disorders using multiple regression analyses. RESULTS: We enrolled 205 youths with tic disorders and 100 control subjects. Psychosocial (P < 0.0001) and physical (P < 0.0001) quality of life were lower in individuals with tic disorders compared with controls. Severity of attention-deficit/hyperactivity disorder (P < 0.0001) and depression (P = 0.046) symptoms were associated with lower psychosocial quality of life in youth with tic disorders. Families of youths with tic disorders had worse parent quality of life (P < 0.001) and family functioning (P < 0.001) than control families. Severity of attention-deficit/hyperactivity disorder (P < 0.0001), obsessive-compulsive disorder (P = 0.0004), and depression (P = 0.01) symptoms were associated with predicted worse family impact. CONCLUSION: Youths with tic disorders had lower individual and parent quality of life and worse family functioning than controls. The impact of tic disorders on the family may have significant implications for approaches to providing comprehensive care to these families.

Hypertrophy of nigral neurons in Torsin1A deletion (DYT1) carriers manifesting dystonia.

OBJECTIVE: To individuate morphometric changes and prevalent types of intraneuronal inclusions in nigral neurons of DYT1 dystonia autopsy-brains. METHODS: Using precise methods of quantification, such as unbiased stereology, we measured cellular and subcellular volumes of neuromelanin-containing (pigmented) neurons in the substantia nigra (SN) of DYT1 carriers with and without manifestation of generalized dystonia (manif-DYT1 and non-manif-DYT1, respectively), non-DYT1 carriers manifesting generalized dystonia (manif-non-DYT1) patients, and age-matched control subjects (controls). A total of four DYT1 carriers (two manif-DYT1 and two non-manif-DYT1), six manif-non-DYT1 carriers, and six controls autopsy-brains were available for these neuropathological-morphometric analyses. The search of brain lesions was performed for: tau neurofibrillary tangles and neurites, extracellular ß-amyloid deposits, Lewy bodies and neurites, TorsinA, Laminin A + C, Ubiquitin, p62, pTDP43 intraneuronal inclusions; and Negri, Bunina, Hirano, Marinesco, Nissl, and Buscaino bodies. RESULTS: An increased mean cell body, nuclear, and nucleolar volume of nigral neurons in manif-DYT1 vs. non-manif-DYT1 (p < 0.0001), manif-non-DYT1 (p < 0.0001), and controls (p < 0.00001) was found. Increased nuclear and nucleolar volumes in manif-non-DYT1 vs. controls were also found. None of the considered possible intraneuronal lesions were more frequent or prevalent in nigral neurons of manif-DYT1 vs. all the other groups. CONCLUSIONS: Unbiased stereology-based measurements of nigral neurons enlargement in manif-DYT1 in the absence of intraneuronal inclusions or neurodegenerative processes, is novel. These findings suggest distinct pathogenetic mechanisms between manif-DYT1 vs. non-manif-DYT1 and manif-non-DYT1 dystonia, especially in terms of possible nigral dopaminergic abnormalities. These data could open new pathophysiologic views on specific dopamino-associated pathomechanisms related to the clinical manifestation of generalized dystonia.

Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study.

BACKGROUND: Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. METHODS: Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. RESULTS: Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). CONCLUSIONS: Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society.

Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette's Disorder in Children and Adolescents.

OBJECTIVES: Aripiprazole modulates dopaminergic and serotonergic pathways that may play a role in the pathogenesis of Tourette's disorder (TD). This trial evaluated the efficacy and safety of oral aripiprazole in the suppression of tics in children and adolescents with TD. METHODS: This phase 3, randomized, double-blind, placebo-controlled trial ( ClinicalTrials.gov , NCT01727700) recruited patients who were 7-17 years old with a diagnosis of TD from hospitals, private practices, and research clinics at 76 sites in the United States, Canada, Hungary, and Italy. Patients were randomized in a 1:1:1 ratio by using an interactive voice/web-response system to low-dose aripiprazole (5 mg/day if <50 kg; 10 mg/day if ≥50 kg), high-dose aripiprazole (10 mg/day if <50 kg; 20 mg/day if ≥50 kg), or placebo for 8 weeks. Randomization was stratified by region (North America or Europe) and baseline body weight (<50 kg vs. ≥50 kg). The primary efficacy endpoint was mean change from baseline to week 8 in the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) for the intent-to-treat population. RESULTS: Between November 2012 and May 2013, 133 patients were recruited and randomized to low-dose aripiprazole (n = 44), high-dose aripiprazole (n = 45), or placebo (n = 44). Least-squares mean treatment differences versus placebo in change from baseline to week 8 in the YGTSS-TTS were statistically significant (high dose, -9.9 [95% confidence interval, CI, -13.8 to -5.9], low dose, -6.3 [95% CI, -10.2 to -2.3]). At week 8, 69% (29/42) of patients in the low-dose and 74% (26/35) of patients in the high-dose aripiprazole groups demonstrated a Clinical Global Impression-Tourette's Syndrome improvement score of 1 (very much improved) or 2 (much improved) compared with 38% (16/42) in the placebo group. The most common adverse events (AEs) were sedation (low dose, 8/44 [18.2%], high dose, 4/45 [8.9%], placebo, 1/44 [2.3%]), somnolence (low dose, 5/44 [11.4%], high dose, 7/45 [15.6%], placebo, 1/44 [2.3%]), and fatigue (low dose, 3/44 [6.8%], high dose, 7/45 [15.6%], placebo, 0). No serious AEs or deaths occurred. CONCLUSIONS: This study indicates that oral aripiprazole is a safe and effective treatment for tics in children and adolescents with TD.

Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease.

BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.

Early Clinical Predictors of Treatment-Resistant and Functional Outcomes in Parkinson's Disease.

BACKGROUND: The aim of this work was to identify early clinical predictors of important outcomes in Parkinson's disease (PD). In PD, treatment-resistant (e.g., dementia, falling) and other important functional outcomes (e.g., declines in quality of life [QOL] and activities of daily living [ADL]) emerge and become increasingly disabling. METHODS: We analyzed longitudinal data from 491 early, untreated PD subjects who enrolled in the PreCEPT trial, had baseline SPECT dopamine transporter deficit, and have continued in the PostCEPT observational cohort. After PreCEPT, antiparkinsonian medications were added if needed. Baseline clinical precursors were examined as potential predictors of selected outcomes. Separate and multivariate logistic regressions, adjusted for certain baseline factors, were performed for dichotomized outcomes evaluated at the last PostCEPT visit. RESULTS: On enrollment, subjects had average disease duration of 0.8 years and were followed for an average of 5.5 years. Some baseline precursors were found to be predictive: disease stage, cognitive, and ADL scores for dementia; disease stage, ADL, and motor and freezing scores for hallucinations; disease stage, depression, ADL, and freezing and walking scores for falling; and ADL, depression, and motor and walking scores and disease stage for QOL decline. No baseline clinical feature predicted decline in ADL. Being on levodopa was not a significant predictor of any outcome, but subjects on a dopamine agonist were significantly less impaired with respect to falling, abnormal Mini-Mental State Examination, and QOL. CONCLUSIONS: Although there are limitations, results support the value of longitudinal follow-up of clinical trial populations to identify early clinical precursors of important outcomes and thereby identify high-risk patients early on.

Postural, Bone, and Joint Disorders in Parkinson's Disease.

BACKGROUND: Stooped posture was mentioned in the original description of the characteristic features of Parkinson's disease (PD). Since then, a variety of postural, bone, and joint problems have become recognized as common aspects of the illness and deserve attention. METHODS: A Medline literature search for the period from 1970 to 2016 was performed to identify articles relevant to this topic. Keywords for the search included posture, spine, bone disorders, fractures, joint disorders, kyphosis, scoliosis, stooping, camptocormia, Pisa syndrome, frozen shoulder, anterocollis, dropped head syndrome, and pain in combination with PD. The articles were then reviewed to summarize clinical features, frequency, impact, pathophysiology, and treatment options for these conditions. RESULTS: Postural disorders (kyphoscoliosis, camptocormia, Pisa syndrome, dropped head syndrome), bone mineralization disorders (osteoporosis, bone fractures), and joint disorders (frozen shoulder, dystonia involving joints, joint pain) are often seen in association with PD. Treatment options for these conditions are varied and may include medications, physical therapy, or surgical interventions. CONCLUSIONS: Posture, bone, and joint disorders are common in patients with PD; they often produce added disability, and they may be treatable.

Practice guideline: Idiopathic normal pressure hydrocephalus: Response to shunting and predictors of response: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: We evaluated evidence for utility of shunting in idiopathic normal pressure hydrocephalus (iNPH) and for predictors of shunting effectiveness. METHODS: We identified and classified relevant published studies according to 2004 and 2011 American Academy of Neurology methodology. RESULTS: Of 21 articles, we identified 3 Class I articles. CONCLUSIONS: Shunting is possibly effective in iNPH (96% chance subjective improvement, 83% chance improvement on timed walk test at 6 months) (3 Class III). Serious adverse event risk was 11% (1 Class III). Predictors of success included elevated Ro (1 Class I, multiple Class II), impaired cerebral blood flow reactivity to acetazolamide (by SPECT) (1 Class I), and positive response to either external lumbar drainage (1 Class III) or repeated lumbar punctures. Age may not be a prognostic factor (1 Class II). Data are insufficient to judge efficacy of radionuclide cisternography or aqueductal flow measurement by MRI. RECOMMENDATIONS: Clinicians may choose to offer shunting for subjective iNPH symptoms and gait (Level C). Because of significant adverse event risk, risks and benefits should be carefully weighed (Level B). Clinicians should inform patients with iNPH with elevated Ro and their families that they have an increased chance of responding to shunting compared with those without such elevation (Level B). Clinicians may counsel patients with iNPH and their families that (1) positive response to external lumbar drainage or to repeated lumbar punctures increases the chance of response to shunting, and (2) increasing age does not decrease the chance of shunting being successful (both Level C).

Parkinson disease and incidental Lewy body disease: Just a question of time?

OBJECTIVE: To quantify the loss of pigmented neurons in the substantia nigra (SN) of autopsy-confirmed Parkinson disease (PD) and incidental Lewy body disease (ILBD) vs age-matched controls (C). METHODS: Unbiased stereology methods were used to rigorously count number and measure volumes of nigral pigmented neurons in PD, ILBD, and C brains. The obtained stereologic results were correlated with Lewy body (LB), amyloid plaque (AP), neurofibrillary tangle (NFT), and vascular pathology loads assessed in nigral and extranigral regions of each PD, ILBD, and C brain. The stereologic measurements were also correlated to predeath motor and cognitive scores as available for each participant. RESULTS: A marked nigral neuronal loss (NNL) in PD (-82%) and ILBD (-40%) compared to C (p < 0.0001) was found. While there was significant correlation between NNL and LB in some cortical areas of PD (i.e., olfactory bulb), there were no correlations between NNL and LB, AP, or NFT loads or cerebral infarct volumes in any other examined regions for PD and ILBD brains. CONCLUSIONS: Using unbiased stereology methods, we show that there is a significant loss and absence of hypertrophic changes in nigral pigmented neurons of ILBD in comparison to C brains. Intriguingly, no significant correlations were found between NNL and LB loads in the SN of both PD and ILBD brains. These autopsy-verified stereologically based findings are novel and support ILBD as a pathologic condition. These results suggest possible new and alternative pathophysiologic hypotheses on the actual relationship between NNL and LB pathology.

Augmentation in Restless Legs Syndrome: Treatment with Gradual Medication Modification.

Dopaminergic drugs can cause augmentation during the treatment of restless legs syndrome (RLS). We previously reported that sudden withdrawal of dopaminergic treatment was poorly tolerated. We now report our experience with gradual withdrawal of the dopaminergic drug during the drug substitution process using a retrospective chart review with comparison to previous data. Seven patients with RLS and dopaminergic drug-induced augmentation were treated with a gradual withdrawal of the offending drug and replacement with an alternative medication. Compared to sudden withdrawal, measured outcomes were similar but gradual tapering was better tolerated. We conclude that for augmentation in RLS, gradual tapering of the augmentation-inducing dopaminergic drug is better tolerated than sudden withdrawal. The optimal approach to treating augmentation has not been established and may differ between patients. Further study with direct comparison of strategies and a larger patient population is needed to confirm our preliminary observations.

Withdrawal-Emergent Dyskinesias following Varenicline Therapy.

Varenicline (Chantix[R]) is a nicotinic acetylcholine receptor partial agonist used to aid smoking cessation. Adverse psychiatric and behavioral effects of the drug are recognized and national drug monitoring has included reports of tardive dyskinesia, but no cases have been described in the literature. We now report the first two cases of varenicline-related withdrawal emergent dyskinesias.

Reduced Number of Pigmented Neurons in the Substantia Nigra of Dystonia Patients? Findings from Extensive Neuropathologic, Immunohistochemistry, and Quantitative Analyses.

BACKGROUND: Dystonias (Dys) represent the third most common movement disorder after essential tremor (ET) and Parkinson's disease (PD). While some pathogenetic mechanisms and genetic causes of Dys have been identified, little is known about their neuropathologic features. Previous neuropathologic studies have reported generically defined neuronal loss in various cerebral regions of Dys brains, mostly in the basal ganglia (BG), and specifically in the substantia nigra (SN). Enlarged pigmented neurons in the SN of Dys patients with and without specific genetic mutations (e.g., GAG deletions in DYT1 dystonia) have also been described. Whether or not Dys brains are associated with decreased numbers or other morphometric changes of specific neuronal types is unknown and has never been addressed with quantitative methodologies. METHODS: Quantitative immunohistochemistry protocols were used to estimate neuronal counts and volumes of nigral pigmented neurons in 13 SN of Dys patients and 13 SN of age-matched control subjects (C). RESULTS: We observed a significant reduction (∼20%) of pigmented neurons in the SN of Dys compared to C (p<0.01). Neither significant volumetric changes nor evident neurodegenerative signs were observed in the remaining pool of nigral pigmented neurons in Dys brains. These novel quantitative findings were confirmed after exclusion of possible co-occurring SN pathologies including Lewy pathology, tau-neurofibrillary tangles, ß-amyloid deposits, ubiquitin (ubiq), and phosphorylated-TAR DNA-binding protein 43 (pTDP43)-positive inclusions. DISCUSSION: A reduced number of nigral pigmented neurons in the absence of evident neurodegenerative signs in Dys brains could indicate previously unconsidered pathogenetic mechanisms of Dys such as neurodevelopmental defects in the SN.

Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

IMPORTANCE: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS. OBJECTIVE: To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142). MAIN OUTCOMES AND MEASURES: Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history. RESULTS: The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD. CONCLUSIONS AND RELEVANCE: This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS.

Complementary Therapies for Parkinson's Disease: What's Promoted, Rationale, Potential Risks and Benefits.

BACKGROUND: Nearly half of all patients with Parkinson's disease (PD) utilize some form of complementary therapy often identified on the Internet and frequently not reported to their physicians. Treating physicians are sometimes unaware of such treatments, including their rationale, mechanisms, potential efficacy, and potential adverse effects. METHODS: Methods for this study included systematic Internet search of products recommended for PD, medical literature review to determine scientific rationale, any evidence of efficacy, and potential risks. RESULTS: A large number of complementary therapies are recommended for patients with PD, generally falling into the following categories: dietary and nutritional; chelation; and physical. Most have reasonable justifications based on mechanism of action and current theories on causes of neurodegeneration in PD, but few have documented evidence of benefit. Fortunately, most have few risks and side effects, although some are very expensive. The protein redistribution diet has substantial evidence of symptomatic benefit. Some antioxidative or -inflammatory supplements, aerobic exercise, Tai chi, and dance and music therapy have preliminary evidence of symptomatic benefit or potential neuroprotective effects, but more research is needed to establish efficacy. CONCLUSIONS: Patients with PD are faced with many recommendations for complementary therapies. Physicians should know about these in order to have informed discussions with their patients. Some deserve further study.

Tics and shorter stature: should we be looking for an association?

BACKGROUND: Tic disorders have commonly occurring and well recognized comorbidities including obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). Shorter stature is not generally appreciated as an associated feature. METHODS: Case reports and a literature review. RESULTS: We describe four recently encountered patients with tics and shorter stature. The literature suggests that in addition to OCD and ADHD, shorter stature may also commonly accompany tic disorders. A variety of neuroendocrine mechanisms have been proposed. DISCUSSION: The potential associations between shorter stature and tic disorders and the common comorbidities OCD and ADHD deserve more attention. More research is needed to establish the strength of these associations and the underlying neurobiological mechanisms.

Temporal course of the tourette syndrome clinical triad.

BACKGROUND: Tourette syndrome (TS) is a disorder characterized by childhood onset of motor and phonic tics, often with improvement of tic symptoms by young adult years. The temporal course of tics and commonly comorbid behavioral symptoms is still not well characterized. METHODS: In order to clarify the time course of tics and comorbid attention deficit hyperactivity disorder (ADHD) or obsessive compulsive disorder (OCD) in TS, we administered a brief survey regarding the course of symptoms at a single point in time to 53 TS patients aged 13-31 years. RESULTS: Mean age (±SD) at symptom onset was 7.9 (±3.6) years for tics, 7.9 (±3.5) for ADHD, and 9.2 (±5.0) for OCD. Age at peak symptom severity was 12.3 (±4.6) years for tics, 10.8 (±3.8) for ADHD, and 12.6 (±5.5) for OCD. Tics, ADHD, and OCD were reported to be no longer present in 32.0%, 22.8%, and 21.0% of subjects, respectively. Decline in symptom severity began at age 14.7 (±3.7) years for tics, 13.9 (±2.9) for ADHD, and 15.1 (±5.0) for OCD. Remission of symptoms occurred at age 17.4 (±3.8) years for tics, 17.4 (±1.3) for ADHD, and 15.6 (±2.3) for OCD. DISCUSSION: Our data confirm and expand previously reported TS spectrum symptom milestones and may guide design of future research aimed at improving the course of TS.