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.

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.

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.

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions.

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.

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.

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.

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.

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.

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

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. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2- 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 F-fluorodeoxyglucose (FDG) PET imaging.

Design of a Multisite Study Assessing the Impact of Tic Disorders on Individuals, Families, and Communities.

Background: Tic disorders, including Tourette syndrome, are complex, multisymptom diseases, yet the impact of these disorders on affected children, families, and communities is not well understood.

Methods: To improve the understanding of the impacts of Tourette syndrome, two research groups conducted independent cross-sectional studies using qualitative and quantitative measures. They focused on similar themes, but distinct scientific objectives, and the sites collaborated to align methods of independent research proposals with the aim of increasing the analyzable sample size.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.

Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls.