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Purpose To assess disease-related patterns of in vivo pathology in 11 patients with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild cognitive impairment (MCI) patients due to Alzheimer’s disease. Methods We assessed tau aggregates with [18F]AV1451 PET, amyloid-β depositions with [18F]AV45 PET, and volumetric microstructural changes with MRI. We validated for [18F]AV1451 standardised uptake value ratio (SUVRs) against input functions from arterial metabolites and found that SUVRs and arterial-derived distribution volume ratio (DVRs) provide equally robust measures of [18F]AV1451 binding. Results CBS patients showed increases in [18F]AV1451 SUVRs in parietal (P

Background:Akathisia is a common and distressing neuropsychiatric syndrome associated with antipsychotic medication, characterised by subjective and objective psychomotor restlessness. The goal of this guideline is to provide clinicians with recommendations on the assessment and treatment of akathisia.Methods:We performed a systematic review of therapeutic studies assessing the treatment of antipsychotic-induced extrapyramidal symptoms. Forty studies on akathisia and 4 systematic reviews evaluating the adverse effects of antipsychotics were used in the formulation of recommendations. Studies were rated for methodological quality using the American Academy of Neurology Risk of Bias Classification system. The overall level of evidence classifications and grades of recommendation were made using the Scottish Intercollegiate Guidelines Network framework.Results:As a good practice point, clinicians should systematically assess akathisia with a validated scale before starting antipsychotics and during antipsychotic dosage titration. For the management of akathisia, there was adequate evidence to allow recommendations regarding antipsychotic dose reduction, antipsychotic polypharmacy, switching antipsychotic medication, and the use of adjuvant medications including beta-blockers, anticholinergics, 5HT2Aantagonists, benzodiazepines, and vitamin B6.Conclusion:The treatment of antipsychotic-induced akathisia should be personalised, with consideration of antipsychotic dose reduction, cessation of antipsychotic polypharmacy, and switching to an antipsychotic with a perceived lower liability for akathisia, before the use of adjuvant medications. The choice of adjuvant medications should favour the more established treatments, with careful consideration of contraindications and side effects. Limitations in the evidence should be acknowledged and prompt cautious prescribing, particularly with respect to the duration of use of adjuvant medications, is warranted.

Objective: To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson disease (PD) reported in the last 25 years by a systematic review and meta-analysis. Methods: We searched for articles published between 1988 and August 2014. Studies were included if reporting diagnostic parameters regarding clinical diagnosis of PD or crude data. The selected studies were subclassified based on different study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses of available data were performed. Results: We selected 20 studies, including 11 using pathologic examination as gold standard. Considering only these 11 studies, the pooled diagnostic accuracy was 80.6% (95% credible interval [CrI] 75.2%–85.3%). Accuracy was 73.8% (95% CrI 67.8%–79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of clinical diagnosis performed by movement disorders experts rose from 79.6% (95% CrI 46%–95.1%) of initial assessment to 83.9% (95% CrI 69.7%–92.6%) of refined diagnosis after follow-up. Using UK Parkinson9s Disease Society Brain Bank Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI 62.6%–93%). Conclusion: The overall validity of clinical diagnosis of PD is not satisfying. The accuracy did not significantly improve in the last 25 years, particularly in the early stages of disease, where response to dopaminergic treatment is less defined and hallmarks of alternative diagnoses such as atypical parkinsonism may not have emerged. Misclassification rate should be considered to calculate the sample size both in observational studies and randomized controlled trials. Imaging and biomarkers are urgently needed to improve the accuracy of clinical diagnosis in vivo.

Background and aims Impaired emotional facial expressiveness is an important feature in Parkinson's disease (PD). Although there is evidence of a possible relationship between reduced facial expressiveness and altered emotion recognition or imagery in PD, it is unknown whether other aspects of the emotional processing, such as subjective emotional experience (alexithymia), might influence hypomimia in this condition. In this study wee aimed to investigate possible relationship between reduced facial expressiveness and altered emotion processing (including facial recognition and alexithymia) in patients with PD. Methods Forty PD patients and seventeen healthy controls were evaluated. Facial expressiveness was rated on video recordings, according to the UPDRS-III item 19 and using an ad hoc scale assessing static and dynamic facial expression and posed emotions. Six blind raters evaluated the patients' videos. Emotion facial recognition was tested using the Ekman Test; alexithymia was assessed using Toronto Alexithymia Scale (TAS-20). Results PD patients had a significantly reduced static and dynamic facial expressiveness and a deficit in posing happiness and surprise. They performed significantly worse than healthy controls in recognizing surprise (p = 0.03). The Ekman total score positively correlated with the global expressiveness (R^2 = 0.39, p = 0.01) and with the expressiveness of disgust (R^2 = 0.32, p = 0.01). The occurrence of alexithymia was not different between PD patients and HC; however, a significant negative correlation between the expressiveness of disgust was found for a subscore of TAS (R^2 = − .447, p = 0.007). Conclusions Reduced facial expressiveness in PD may be in part related to difficulties with emotional recognition in a context of an unimpaired subjective emotional experience.

Pain is a key unmet need and a major aspect of non-motor symptoms of Parkinson's disease (PD). No specific validated scales exist to identify and grade the various types of pain in PD. We report an international, cross-sectional, open, multicenter, one-point-in-time evaluation with retest study of the first PD-specific pain scale, the King's PD Pain Scale. Its seven domains include 14 items, each item scored by severity (0-3) multiplied by frequency (0-4), resulting in a subscore of 0 to 12, with a total possible score range from 0 to 168. One hundred seventy-eight PD patients with otherwise unexplained pain (age [mean ± SD], 64.38 ± 11.38 y [range, 29-85]; 62.92% male; duration of disease, 5.40 ± 4.93 y) and 83 nonspousal non-PD controls, matched by age (64.25 ± 11.10 y) and sex (61.45% males) were studied. No missing data were noted, and floor effect was observed in all domains. The difference between mean and median King's PD Pain Scale total score was less than 10% of the maximum observed value. Skewness was marginally high (1.48 for patients). Factor analysis showed four factors in the King's PD Pain Scale, explaining 57% of the variance (Kaiser-Mayer-Olkin, 0.73; sphericity test). Cronbach's alpha was 0.78, item-total correlation mean value 0.40, and item homogeneity 0.22. Correlation coefficients of the King's PD Pain Scale domains and total score with other pain measures were high. Correlation with the Scale for Outcomes in PD-Motor, Non-Motor Symptoms Scale total score, and quality of life measures was high. The King's PD Pain Scale seems to be a reliable and valid scale for grade rating of various types of pain in PD. © 2015 International Parkinson and Movement Disorder Society. (Less)

Background A contribution of aberrant interoceptive awareness to the perception of premonitory urges in Gilles de la Tourette syndrome (GTS) has been hypothesized. Methods We assessed interoceptive awareness in 19 adults with GTS and 25 age-matched healthy controls using the heartbeat counting task. We also used multiple regression to explore whether the severity of premonitory urges was predicted by interoceptive awareness or severity of tics and obsessive-compulsive symptoms. Results We observed lower interoceptive awareness in GTS compared with controls. Interoceptive awareness was the strongest predictor of premonitory urges in GTS, with greater interoceptive awareness being associated with more urges. Greater tic severity was also associated with higher rates of premonitory urges. Conclusion The observed relationship between severity of premonitory urges and interoceptive awareness suggests that interoception might be involved in self-reported premonitory urges in GTS. High levels of interoceptive awareness might reflect a self-attentive capacity to perceive urges. © 2015 International Parkinson and Movement Disorder Society

Background and purpose: Pain is highly prevalent in Parkinson's disease (PD), impacting patients’ ability, mood and quality of life. Detecting the presence of pain in its multiple modalities is necessary for adequate personalized management of PD. A 14-item, PD-specific, patient-based questionnaire (the King's Parkinson's Disease Pain Questionnaire, KPPQ) was designed corresponding to the rater-based KPP Scale (KPPS). The present multicentre study was aimed at testing the validity of this screening tool. Methods: First, a comparison between the KPPQ scores of patients and matched controls was performed. Next, convergent validity, reproducibility (test–retest) and diagnostic performance of the questionnaire were analysed. Results: Data from 300 patients and 150 controls are reported. PD patients declared significantly more pain symptoms than controls (3.96 ± 2.56 vs. 2.17 ± 1.39; P < 0.0001). The KPPQ convergent validity was high with KPPS total score (rS = 0.80) but weak or moderate with other pain assessments. Test–retest reliability was satisfactory with kappa values ≥0.65 except for item 5, Dyskinetic pains (κ = 0.44), and the intraclass correlation coefficient (ICC) for the KPPQ total score was 0.98. After the scores of the KPPS were adapted for screening (0, no symptom; ≥1, symptom present), a good agreement was found between the KPPQ and the KPPS (ICC = 0.88). A strong correlation (rS = 0.80) between the two instruments was found. The diagnostic parameters of the KPPQ were very satisfactory as a whole, with a global accuracy of 78.3%–98.3%. Conclusions: These results suggest that the KPPQ is a useful, reliable and valid screening instrument for pain in PD to advance patient-related outcomes. (Less)

Tics are neurodevelopmental hyperkinetic symptoms typically associated with unpleasant sensory experiences called premonitory urges. Tourette syndrome (TS) is the primary chronic tic disorder for which medical surveillance is most frequently required, and is associated with a complex phenotypical spectrum encompassing different types of abnormal behaviors. Animal models of tics support their link to phasic activity changes throughout the sensorimotor loop of the cortico-basal ganglia-thalamo-cortical network. Event-related functional magnetic resonance imaging (fMRI) studies on patients with TS showed that the supplementary motor area relays preparatory signals related to tics to the primary motor area and other cortical regions relevant to action monitoring, following which cortico-basal ganglia-thalamo-cortical activation leads to the manifestation of tics. Despite their methodological heterogeneity, structural MRI studies highlighted the existence of anatomical markers of distinct sub-phenotypes of the TS spectrum. Initial evidence suggests that combining MRI structural methods and functional intrinsic connectivity assessed during resting state could even discriminate between TS patients and control groups. MR-spectroscopy and positron emission tomography studies suggest that TS may be related to a complex interplay between different neurotransmitters (particularly dopamine, GABA and glutamate), but discrepancy across studies prevents firm conclusions. Recent volumetric, cortical thickness and fMRI studies results showed an association between premonitory urges and somatosensory and insular cortical regions, involved in the processing of interoceptive and enteroceptive stimuli and motor output modulation. Finally, both structural and functional MRI studies have provided important support to the subtyping of the TS spectrum with respect to behavioral co-morbidities, in line with a "dimensional approach" to the classification of neuropsychiatric disorders, which is based on the identification of neurocognitive endophenotypes and of their anatomical substrate.

Background Tics are the hallmark feature of Tourette syndrome. The basic phenomenological and neurophysiological characteristics of tics have been widely investigated. Interestingly, the spatial distribution of tics across different body parts has received little attention. No previous study has investigated whether the capacity for voluntary tic inhibition also varies across body parts. Methods We analyzed video sequences of 26 adolescents with Tourette syndrome in a “tic freely” condition, and in a “voluntary tic inhibition” condition, to obtain absolute tic counts for different body parts. Two measures of the spatial distribution of tics were then analyzed. Linear regression analyses were employed to investigate the relation between the contribution of each body part to overall tic behavior and the ability to inhibit tics in that body part, averaged over our patient group. Results Tic distribution across patients showed a characteristic somatotopic pattern, with the face most strongly represented. A significant negative relation was found between the ability to inhibit tics and pooled tic frequency across body parts. The body parts that exhibited the fewest tics were the ones for which tic inhibition was most effective. Conclusions Our data are consistent with the idea that tic recruitment order reflects a “tic generator” spreading across a somatotopic map in the brain. Voluntary tic inhibition did not simply cause a proportional reduction of tics in each body part. Rather, the least affected body parts showed most effective voluntary tic inhibition. The results are discussed in terms of signal and noise within cortical-subcortical motor loops. © 2015 International Parkinson and Movement Disorder Society

The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation.

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care.

International audience; Youth with Tourette syndrome (TS) exhibit, compared to healthy, abnormal ability to lateral-ize digital sequential tasks. It is unknown whether this trait is related to inter-hemispheric connections, and whether it is preserved or lost in patients with TS persisting through adult life. We studied 13 adult TS patients and 15 age-matched healthy volunteers. All participants undertook: 1) a finger opposition task, performed with the right hand (RH) only or with both hands, using a sensor-engineered glove in synchrony with a metronome at 2 Hz; we calculated a lateralization index [(single RH–bimanual RH)/single RH X 100) for percentage of correct movements (%CORR); 2) MRI-based diffusion tensor imaging and probabilistic tractography of inter-hemispheric corpus callosum (CC) connections between supplementary motor areas (SMA) and primary motor cortices (M1). We confirmed a significant increase in the %CORR in RH in the bimanual vs. single task in TS patients (p

Highlights • Screening tests can diagnose PD-MCI but do not give detailed cognitive profiles. • Criteria based on a complete neuropsychological battery identify more PD patients with MCI. • The overall cognitive profile is similar in PD-MCI and MCI. • Neuropsychological batteries and definition of impairment cut-offs should be refined.

Introduction Evidence is emerging that nonmotor symptoms (NMS) such as neuropsychiatric, sensory and sleep disturbances play an important role in dystonia. Methods In this observation, 102 patients with cervical dystonia (CD) were included. We evaluated the complaints about NMS with an adapted NMS Questionnaire and motor severity measured with Unified Dystonia Rating Scale. Results 95% of CD patients experienced NMS with 36% presenting with at least seven NMS. Mean UDRS score was 5.09 points (standard deviation (SD) ± 2.64 points, range 0.5–14.0). 42% patients had additional head tremor. The total number of experienced NMS was not significantly correlated with the age of the patients and disease duration of dystonia. There was also no significant association between number of NMS and sex. The correlation between number of NMS and motor severity assessed with UDRS was weak ( r S = 0.23; p = 0.02). Conclusion The number of NMS as a whole has been shown to be a key determinant of health related quality of live in patients with Parkinson's disease and we would assume that can influence this construct in patients with dystonia, too. As 95% of our patients with focal CD present with NMS, especially loss of self-confidence, insomnia, fatigue and pain, higher awareness for NMS needs to be raised in the context of routine clinical consultations in patients with focal dystonia.

In movement disorders, emphasis on pure phenomenology to make diagnoses can lead to significant variability and diagnostic disagreement.1 2 This is illustrated by difficulty among experts in deciding whether possibly equivocal signs (‘soft’ signs) are present or absent. A tight pen grip, slightly asymmetric arm swing, or hyperextended fingers may be judged by some to be within the broad spectrum of normal. Others may consider such signs to be pathological. Hence, the relevance of such signs can be uncertain. Furthermore, we are often asked to judge on the presence and clinical relevance of soft signs in ‘neurologically healthy’ individuals and this can be challenging (eg, in clinical genetic studies). Although classification systems tend to include clinical signs to define boundaries of disease, the relevance of soft signs may be questionable if inter-rater reliability is variable. Initially introduced in the psychiatric literature,3 the term ‘soft signs’ has also recently been applied to movement disorders. In the recent Consensus Statement on the Classification of Tremor, the detection of soft signs has, for the first time, become an integral part of tremor classification.4 Because of the uncertainty surrounding the interpretation of soft signs, we asked movement disorders experts (MDE) and experts in fields other than movement disorders (non-MDE) to rate videos of patients and healthy control subjects to assess inter-rater reliability on the presence or absence of soft signs. We asked seven MDE (AJE, AEL, TL, DM, FM, NPQ, MV) and six non-MDE (listed in the Acknowledgements section) to rate 30 videos for the presence or absence of soft signs. Raters were advised that videos may feature control subjects or patients, but no other clinical information was provided. Twenty-five control subjects were recorded (9 …

Background Adult-onset primary dystonia is thought to be a purely motor disorder. Nevertheless, several studies provided evidence that sensory and psychiatric disturbances may contribute to the clinical spectrum of of dystonia, whereas evidence supporting cognitive impairment is still limited. Methods A set of neuropsychological tests was administered to non depressed, non demented patients with cranial-cervical dystonia and healthy control subjects. The test battery included n -Back Task, Wechsler Memory Scale, Trail Making Test version A and B, and Wisconsin Card Sorting Test. Results As compared with healthy control subjects of similar age, sex and socio-economic status, patients with cranial-cervical dystonia showed deficit on working memory functions revealed by n -Back task, impairment of mental control and visual reproduction subtests of Wechsler memory scale, deficit on information processing speed and set-shifting capacity revealed by Trail Making Test A and B. Conclusion Patients with cranial-cervical dystonia may have impairment in specific cognitive domains relative to working memory, processing speed, visual motor ability and short term memory. Probably, these deficits are not dependent on the clinical expression of dystonia but might rather reflect the cortical and subcortical changes highlighted by functional and VBM imaging studies in patients with different forms of dystonia.

Primary tic disorders are complex, multifactorial disorders in which tics are accompanied by other sensory features and an array of comorbid behavioral disorders. Secondary tics are proportionally much less frequent, but their etiology is diverse. This review aims to guide clinicians in the recognition of the phenomenology, pathophysiology, and treatment of these disorders.Advances include greater phenomenologic insights, particularly of nonmotor (sensory) features; increased knowledge of disease mechanisms, particularly coming from neuropsychological, functional imaging, pathologic, and animal model studies; growing evidence on the efficacy of alpha-2 agonists and the newer generation of dopamine-modulating agents; and recent strides in the evaluation of cognitive-behavioral therapy and deep brain stimulation surgery.The correct diagnostic approach to tic disorders requires accurate historical gathering, a thorough neurologic examination, and detailed definition of the patient's psychopathologic profile. Treatment should always begin with individualized psychoeducational strategies. Although pharmacologic treatments remain beneficial for most patients, cognitive-behavioral treatments have thus far shown promising efficacy. Deep brain stimulation surgery should still be limited to adult patients refractory to pharmacotherapy and cognitive-behavioral therapy.

Environmental exposures during the prenatal period, perinatal stages, and postnatal life may contribute to onset and course of Tourette syndrome (TS). Pregnancy-related noxious exposures may be more frequent in pregnancies of children who will develop TS, particularly maternal smoking and prenatal life stressors. Lower birth weight and use of forceps at delivery may be associated with tic severity in the offspring; moreover, low birth weight and maternal smoking during pregnancy may affect the risk of co-morbid attention-deficit/hyperactivity and obsessive-compulsive disorders. Group A streptococcal infections as risk-modifier for TS has not been convincingly demonstrated to date, although an interaction with stressors was suggested. The PANDAS hypothesis is currently undergoing a nosological revision. Only limited anecdotal evidence supports a link of TS to other pathogens. Nevertheless, the relationship between infections and TS may be complex. Recent data point to intrinsically altered immune regulation in TS, which might predispose to both infections and autoimmune mechanisms; however, evidence of cell-mediated and antibody-mediated autoimmunity in TS is still insufficient. Psychosocial stress remains the most important contextual factor influencing tic severity, as confirmed by prospective studies. This might in part be related to enhanced reactivity of the stress response in TS patients, the mechanisms of which need to be explored further. New studies on large prospective cohorts of patients of different age and the identification of reliable biomarkers or endophenotypes indicating early, prenatal exposure to environmental insults are needed. (C) 2012 Elsevier Ltd. All rights reserved.

The spectrum of “poststreptococcal” movement disorders and other behavioral abnormalities has expaanded and the array of neuropsychiatric features associated with rheumatic fever (RF) has been broadened. However, it is difficult to establish a causal link between Group A Streptococcus (GAS) and neuropsychiatric symptoms beyond RF, which has fuelled a long-lasting, and still unsolved, debate as to whether putative “poststreptococcal” disorders such as the PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection) phenotype are distinct entities or not. This chapter provides an up-to-date overview of the conditions that are well established (Sydenham’s chorea) or proposed (poststreptococcal tic and obsessive-compulsive disorders) as secondary to an immune response toward GAS.

Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions.

Gilles de la Tourette syndrome (GTS) and depression are both common disorders. It has been suggested that depression occurs in 13%-76% GTS patients. Despite this, there are few studies into the specific relationships and correlates between the two disorders. There is only some consensus as to the precise relationship between the two disorders.We undertook the study to investigate the relationship between depressive symptomatology and the core clinical features of GTS in a well-characterized clinical population of youth with this disorder. Our aim was to verify the association between depression and comorbid obsessive-compulsive disorder and explore further other potential associations highlighted in some, but not all, of the studies focused on this topic.Our results demonstrated that (1) the GTS patients were significantly older than the controls, (2) the GTS patients were significantly more depressed than controls, (3) depression was associated with tic severity, (4) the Diagnostic Confidence Index scores were higher in GTS patients without depression, (5) anxiety, attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and behavioral problems were significantly associated with depression, and (6) finally, patients with GTS and depression have a positive family history of depression. However, obsessionality (CY-BOCS) did not differentiate between depressed and not depressed GTS patients.Depression is common in patients with GTS and occurs significantly more in GTS than in controls. Depression is significantly associated with GTS factors such as tic severity, comorbidity with ADHD, and the presence of coexistent anxiety, CDs, and behavior problems. Depression is importantly significantly associated with a positive family history of depression. Intriguingly, depression in our sample was not related to obsessionality.

The clinical surveillance and active management of Tourette syndrome (TS) and other primary chronic tic disorders cannot be limited to tics, as these patients manifest a spectrum of sensory-, behavioral-, cognitive-, and sleep-related problems that have a major impact on their functioning and quality of life, influencing enormously clinical decision making on a routine basis. The sensory phenomena of primary tic disorders consist of premonitory urges and heightened sensitivity to external somatosensory and interoceptive stimuli. Recent evidence suggests that raised interoceptive awareness may be related to the classical premonitory urges associated with tics. The burden of behavioral comorbidities is very important in determining the degree of disability of patients with primary tic disorders. Only 10%-15% of these patients presents exclusively with a tic disorder. Obsessive-compulsive disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. "Tic-related OCD" represents a phenomenologically characteristic subtype of OCD, also associated with "just right" phenomena. Probably the presence of comorbid attention deficit/hyperactivity disorder is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Mood and anxiety disorders, impulse control disorders, rage attacks, "impulsive" tic-like behaviors (e.g., nonobscene socially inappropriate behaviors, and self-injurious behaviors), and autism spectrum disorders complete the wide psychopathological spectrum of primary chronic tic disorders. Moreover, specific sleep abnormalities have been reported in TS patients, although more research is needed on this specific clinical problem. As in other areas of clinical neuroscience, a comprehensive approach to both motor and nonmotor aspects of this group of disorders will help personalizing treatment interventions and, ultimately, improve quality of care.

Movement disorders comprise hyperkinetic involuntary movements (eg tremor, myoclonus, tics, dystonia and chorea) and hypokinetic (parkinsonism) disorders. Tics are cardinal features of primary tic disorders encompassing Tourette syndrome (TS), but are also found in some neurodegenerative conditions and may be induced by psychoactive substances. The first line treatment for tics is pharmacological (mainly dopamine receptor blockers or alpha-2 adrenergic agonists) and behavioural. Dystonia and chorea syndromes are considerably heterogeneous in aetiology, and age at onset, body distribution of the movement disorder, accompanying neurological motor and non-motor features, and systemic manifestations are all important to reach a correct aetiological diagnosis. While symptomatic pharmacological treatment remains the mainstay of treatment for choreas, deep brain stimulation surgery has a well-defined place in the management of medically refractory dystonia.

The objective of this study was to examine: (1) the prevalence of diagnosed Tourette syndrome in Canada by sex in youth (aged 12-17) and adults and (2) socioeconomic factors in this population.The majority of epidemiological studies of tics have focused on children and youth, with few studies describing the prevalence of tics in adult populations.Canadian data on Tourette syndrome prevalence were derived from the Canadian Community Health Survey 2010 and 2011 cycles, a Statistics Canada population-based cross-sectional survey that collects information related to health status. We determined the prevalence of diagnosed Tourette syndrome and examined sociodemographic factors, including age, sex, education, income, employment, and birthplace.Overall, 122,884 Canadians participated in the surveys, with 122 participants diagnosed with Tourette syndrome. The prevalence of Tourette syndrome was higher in males in youth: 6.03 per 1000 (95% confidence interval: 3.24-8.81) in males versus 0.48 per 1,000 (95% confidence interval: 0.05-0.91) in females, with a prevalence risk ratio of 5.31 (95% confidence interval: 2.38-11.81). In adults, the prevalence of Tourette syndrome was 0.89 per 1,000 (95% confidence interval: 0.48-1.29) in males versus 0.44 (95% confidence interval: 0.16.0-0.71) in females, with a prevalence risk ratio of 1.93 (95% confidence interval: 1.21-3.08). After adjusting for age and sex, adults with Tourette syndrome had lower odds of receiving postsecondary education or being employed and higher odds of having income lower than the median and receiving governmental support.Data on the prevalence of Tourette syndrome in adults are scarce because most studies focus on children. Our data demonstrate a decreasing prevalence risk ratio for sex in adults compared to children. A diagnosis of Tourette syndrome is associated with lower education, income, and employment in adulthood. © 2016 International Parkinson and Movement Disorder Society.

Factors modifying the clinical penetrance of DYT1 dystonia are incompletely defined. Particularly, the contribution of extragenetic factors has been subject to only limited investigation and remains largely unexplored. A possible effect of childhood infections has been proposed, and the effect of other factors, such as perinatal adversity and trauma, has not been systematically investigated. We performed an exploratory analysis of the exposure to perinatal adversity, childhood infections, general anaesthesia and trauma comparing 39 manifesting carriers of the ∆GAG mutation, 23 non-manifesting carriers and 48 non-carriers from a multi-centre European series of 28 families with DYT1 dystonia, by means of a self-completed questionnaire and clinical interview. Detailed information on perinatal adversities (pre-term birth, complications at natural delivery, urgent caesarean section), previous childhood infections, and prior general anaesthesia or physical trauma was recorded. A positive association between a history of complications of vaginal delivery and manifestation of dystonia was detected, which was not confounded by age, gender, or education level (odds ratio 8.47, 95 % confidence interval 1.45-49.4, p = 0.02). We could not observe any significant association between presence of dystonia and the other investigated variables. Comparing non-manifesting carriers to non-carriers, the presence of the ∆GAG mutation per se was not associated with any of the environmental exposures explored. Perinatal adversities might modulate the clinical penetrance of DYT1 dystonia; their interaction with known genetic factors modifying penetrance of this condition should be investigated in new, larger collaborative studies.

A growing number of progressive heredodegenerative conditions mimic the presentation of Huntington's disease (HD). Differentiating among these HD-like syndromes is necessary when a patient with a combination of movement disorders, cognitive decline, behavioural abnormalities and progressive disease course proves negative to the genetic testing for HD causative mutations, that is, IT15 gene trinucleotide-repeat expansion. The differential diagnosis of HD-like syndromes is complex and may lead to unnecessary and costly investigations. We propose here a guide to this differential diagnosis focusing on a limited number of clinical features (‘red flags’) that can be identified through accurate clinical examination, collection of historical data and a few routine ancillary investigations. These features include the ethnic background of the patient, the involvement of the facio-bucco-lingual and cervical district by the movement disorder, the co-occurrence of cerebellar features and seizures, the presence of peculiar gait patterns and eye movement abnormalities, and an atypical progression of illness. Additional help may derive from the cognitive–behavioural presentation of the patient, as well as by a restricted number of ancillary investigations, mainly MRI and routine blood tests. These red flags should be constantly updated as the phenotypic characterisation and identification of more reliable diagnostic markers for HD-like syndromes progress over the following years.

Background: The site of dystonia onset is known to affect the risk of spread in primary adult-onset focal dystonia, but other factors possibly influencing spread are unknown. This study explored the relationship between age and spread of dystonia in primary adult-onset focal dystonia. Methods: Two survival models analyzed spread of dystonia in a large cohort of patients with primary blepharospasm (BSP) and cervical dystonia. The first model was based on time interval between onset and spread of dystonia, and the second model was based on age at spread. Results: Patients presenting with BSP had a 2-fold higher rate of spread than those presenting with cervical dystonia, regardless of the survival model used. However, survival analysis, based on age at spread, showed that spread develops at a similar age period in both groups, with most spread events occurring after the age of 50. Conclusions: The convergent age of spread in BSP and cervical dystonia is a novel finding indicating age as a factor modulating spread of dystonia. These findings may assist in informing prognostication for patients with primary adult-onset focal dystonia. © 2012 Movement Disorder Society

Spatial attention is a key factor in the exploration and processing of the surrounding environment, and plays a role in linking magnitudes such as space, time, and numbers. The present work evaluates whether shifting the coordinates of spatial attention through rotational head movements may affect the ability to estimate the duration of different time intervals. A computer-based implicit timing task was employed, in which participants were asked to concentrate and report verbally on colour changes of sequential stimuli displayed on a computer screen; subsequently, they were required to reproduce the temporal duration (ranging between 5 and 80 sec.) of the perceived stimuli using the computer keyboard. There was statistically significant overestimation of the 80-sec. intervals exclusively on the rightward rotation head posture, whereas head posture did not affect timing performances on shorter intervals. These findings support the hypothesis that the coordinates of spatial attention influence the ability to process time, consistent with the existence of common cortical metrics of space and time in healthy humans.

Background: Gilles de la Tourette syndrome is a childhood-onset disorder characterized by persistent motor and vocal tics fluctuating in severity. Although structural changes observed in Gilles de la Tourette syndrome concern brain structures involved in voluntary motor control such as the basal ganglia, the frontoparietal cortex, and the corpus callosum, movement lateralization and bimanual coordination have been underinvestigated. Methods: Using a sensor-engineered glove, we analyzed the performance of repetitive externally paced single-hand and bimanual finger movements in 11 children with Gilles de la Tourette syndrome. Results: When requested to perform sequential single-hand finger movements, patients with Gilles de la Tourette syndrome showed longer touch duration, shorter movement time, and more errors than healthy subjects. When requested to execute the task bimanually, healthy subjects exhibited a slight loss in accuracy and an increase in touch duration compared with the single-hand task, whereas patients with Gilles de la Tourette syndrome did not. Further, healthy subjects presented great asymmetry in terms of movement accuracy between left and right hands during the bimanual task, whereas patients with Gilles de la Tourette syndrome did not. Conclusions: These findings suggest that patients with Gilles de la Tourette syndrome may present an abnormal process of sensorimotor integration, movement lateralization, and bimanual coordination during sequential finger movements. © 2011 Movement Disorder Society

Previous voxel-based morphometry studies of patients with primary blepharospasm documented gray matter volumetric differences of the striatum, cerebellum, thalamus, and parietal lobe areas. However, these results were inconsistent across studies, which recruited relatively small samples and did not always provide detailed clinical information on patients with blepharospasm. The objective of this study was to analyze whole-brain gray matter volume in a larger sample of patients with blepharospasm and to expand on previous works by evaluating whether clinical features of blepharospasm correlate to whole-brain gray matter changes. Voxel-based morphometry was performed on 25 patients with primary adult-onset blepharospasm and 24 healthy subjects (controls) matched for age, sex, and handedness. Clinical data were collected through a standardized interview. Severity of blepharospasm was measured using the Jankovic Rating Scale. Patients with blepharospasm had greater gray matter volume than controls in the right middle frontal gyrus, whereas patients with blepharospasm had smaller gray matter volume than controls in the left postcentral gyrus and left superior temporal gyrus. Spearman correlation analysis with Bonferroni correction failed to show significant correlations between gray matter volume and the explored clinical variables, comprising age at onset, disease duration, blepharospasm severity, presence of an effective geste antagoniste, and dose and duration of botulinum toxin treatment. Patients with blepharospasm exhibited gray matter volume differences exclusively in cortical regions highly relevant to sensory processing and cognitive modulation of motor behavior. Gray matter changes in the primary sensory cortex may represent a common trait of primary dystonias, including blepharospasm. © 2011 Movement Disorder Society

International audience; 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.

The geste antagoniste (GA), a relatively common feature of adult-onset primary dystonia, has been systematically evaluated only in cervical dystonia, but it is still unclear whether its frequency and phenomenology differ among the various forms of focal dystonia. We analysed the frequency, phenomenology, effectiveness, and relationship of the GA with demographic/clinical features of dystonia in a representative clinical series of patients with the two most common forms of adult-onset primary dystonia, blepharospasm (BSP) and cervical dystonia (CD). Clinical data were gathered using a standardized questionnaire, which showed substantial test-retest reliability (kappa = 0.79, P < 0.00001). The frequency of GA was similar among patients with BSP (42/59, 71.2%) and patients with CD (27/32, 84.4%), and in both groups GA showed similar effectiveness in reducing dystonia. The repertoire of GA was heterogenous in both BSP and CD patients, in whom seven BSP-related and five CD-related types of GA were recorded, and a "forcible" type of GA was present in 69% of BSP patients and in 48.1% of CD patients. In our whole patient population, age at dystonia onset was significantly lower among patients reporting a GA compared to those without GA (P = 0.01). GA features shared by BSP and CD predominate over differences, suggesting common mechanisms underlying this phenomenon in the two forms of primary adult-onset dystonia.

Post-streptococcal neuropsychiatric disorders encompass a broad spectrum of movement disorders, including tics, stereotypies, dystonia and tremor. We report the case of a 15-year-old boy who presented with a relapsing-remitting combination of psychogenic and organic movement disorders. Both relapses occurred after an episode of streptococcal pharyngitis and consisted in motor and phonic tics, an atypical gait disorder, and severe worsening of a pre-existing psychogenic tremor of the right hand. After each relapse, both psychogenic and 'organic' symptoms concomitantly remitted after the administration of an association of oral steroids and antibiotics. The peculiarity of this case consists in the coexistence of psychogenic and organic symptoms subsequent to streptococcal infection, and broadens the clinical spectrum of post-streptococcal neuropsychiatric disorders.

Background: Sleep disturbances are common in patients with movement disorders. Evaluating quality of sleep is of primary importance because of the effect that nocturnal and daytime sleep abnormalities exert on general health status. However, quality of sleep has never been addressed in detail in patients with dystonia. The aim of this case–control study was to analyse quality of sleep in patients with the two most common forms of primary focal dystonia, blepharospasm (BSP) and cervical dystonia (CD). Methods: We evaluated quality of sleep (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) in 98 patients with focal adult-onset dystonia (52 with BSP; 46 with CD) and in a group of 56 age-and gendermatched healthy subjects. The Beck Depression Inventory (BDI) was used for the evaluation of depressive symptomatology. Results: Quality of sleep was impaired (significantly higher PSQI scores) in both groups of patients. However, differences in PSQI scores between patients with CD and control subjects were partly confounded by BDI scores, whereas differences in PSQI scores between patients with BSP and control subjects were not influenced by BDI. Excessive daytime sleepiness was not significantly more frequent than in control subjects in either patients with BSP or patients with CD. Conclusions: This study suggests that the assessment and treatment of insomniarelated complaints should be considered in global management plans of patients with focal dystonia, particularly in those affected by BSP.

Tourette syndrome (TS) has a multifactorial etiology, in which genetic, environmental, immunological and hormonal factors interact to establish vulnerability. This review: (i) summarizes research exploring the exposure of TS patients to immune-activating environmental factors, and (ii) focuses on recent findings supporting a role of the innate and adaptive immune systems in the pathogenesis of TS and related disorders. A higher exposure prior to disease onset to group A beta-haemolytic streptococcal (GABHS) infections in children with tics and obsessive-compulsive (OC) symptoms has been documented, although their influence upon the course of disease remains uncertain. Increased activation of immune responses in TS is suggested by changes in gene expression profiles of peripheral immune cells, relative frequency of lymphocyte subpopulations, and synthesis of immune effector molecules. Increased activity of cell-mediated mechanisms is suggested by the increased expression of genes controlling natural killer and cytotoxic T cells, increased plasma levels of some pro-inflammatory cytokines which correlate with disease severity, and increased synthesis of antineuronal antibodies. Important methodological differences might account for some inconsistency among results of studies addressing autoantibodies in TS. Finally, a general predisposition to autoimmune responses in TS patients is indicated by the reduced frequency of regulatory T cells, which induce tolerance towards self-antigens. Although the pathogenic role of immune activation in TS has not been definitively proven, a pathophysiological model is proposed to explain the possible effect of immunity upon dopamine transmission regulation and the generation of tics.

Contains fulltext : 81193.pdf (Publisher’s version ) (Closed access) BACKGROUND: The syndrome of fixed dystonia includes both CRPS-dystonia and psychogenic dystonia. The underlying mechanisms are unclear, but a high prevalence of neuropsychiatric illness has previously been reported. METHODS: Clinical and neuropsychiatric follow-up study by telephone and self-administered instruments (HADS, SDQ-20, DES II, EQ-5D), on 41 patients with fixed dystonia after a mean of 7.6 (+/-3.6) years. RESULTS: We obtained information on clinical outcome in 35 (85.4%) patients and neuropsychiatric questionnaire data in 22 (53.7%). Eighty-three percent were women. Thirty-one percent had worsened, 46% were the same and 23% had improved, of whom 6% had major remissions. At follow-up, mean duration of illness was 11.8 (+/-4.9) years and mean age 43.2 (+/-14.8) years. Except for 1 patient who was re-diagnosed with corticobasal degeneration, the diagnosis remained unchanged in others. Forty-one percent had scores indicating anxiety and 18% indicating depression; 18% scored within the range of dissociative/somatoform disorders on DES II and 19% on SDQ-20. The mean EQ-5D index and VAS scores were 0.34 and 56.1%. Comparison between the 3 outcome groups revealed significant difference only in the EQ-5D (p=0.003). Only baseline CRPS predicted a worse outcome (chi(2)=0.006). CONCLUSIONS: Our findings revealed that the prognosis of this syndrome is poor, with improvement in less than 25% of patients, major remission in only 6% and continued worsening in a third. A high rate of neuropsychiatric findings was noted and new neuropsychiatric features had occurred in some. Average health status was poor. Of the baseline parameters, only CRPS predicted poorer outcome.

The present paper explores the possibility of applying to an aircraft a novel constrained control methodology known as the command governor to improve flight safety and comfort. The proposed strategy is based on predictive control ideas and consists of the separate design of two control actions: an inner primal linear controller that guarantees the tracking of the controlled variables in the absence of constraints and an outer nonlinear static device (the command governor) that is compelled to modify, whenever necessary, the reference signals supplied to the inner controller by taking into account the limitations imposed by the aerodynamics, structures, actuators, and onboard comfort requirements. The reference signal modification is accomplished through an online constrained optimization procedure, which embodies the future plant evolution computed along a finite virtual time horizon. Two numerical examples are developed on a high-performance military aircraft and a small commercial aircraft. Copyright © 2008 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

Background: Primary late-onset focal dystonias may spread over time to adjacent body regions, but differences in the risk of spread over time among the various focal forms and the influence of age at dystonia onset on the risk of spread are not well established. Methods: Patients presenting with primary late-onset focal blepharospasm (BSP, n = 124), cervical dystonia (CD, n = 73) and focal hand dystonia (FHD, n = 24) with 10 years or more of disease duration (mean ± SD, 15.3 (SD 4.9) years) were included in the study. The relationship between demographic/clinical variables and spread of dystonia was assessed by Kaplan–Meier survival curves and Cox proportional hazard regression models. Results: Patients starting with BSP, CD and FHD had similar age, sex and disease duration. Age at dystonia onset, age at initial spread and the risk of initial spread were significantly higher, whereas time elapsing from onset to initial spread was significantly lower in the BSP group than in those with onset in the neck or in the upper extremities. Conversely, these parameters were similar in the CD and FHD groups. The greater risk of spread in the BSP group was mainly evident in the first 5 years of history; thereafter, it declined and became similar to that of patients with CD/FHD. The difference in the risk of initial spread by site of onset was partly confounded by age at dystonia onset. Site of and age at dystonia onset, and age at first spread, were not significant predictors of the risk of a second spread. Conclusion: This study adds new insights into the phenomenon of spread of primary late-onset focal dystonia and provides the framework for future studies aimed at an indepth investigation of the mechanism(s) of spread.

Antineuronal antibodies (ANAs) have been implicated in the pathophysiology of postinfectious movement disorders, such as Sydenham's chorea. However, their relevance in other movement disorders--in the absence of infectious triggers--remains much disputed. We sought to assess the frequency of ANAs in idiopathic Parkinson's disease (IPD) and to explore whether a specific phenotype is associated with the presence of ANAs. For this purpose, we recruited 76 IPD patients, 9 patients with genetic parkinsonism, and 10 with one of the parkinson-plus syndromes. They were all subjected to a comprehensive clinical review. In addition, 50 patients with non-extrapyramidal neurological disease and 30 healthy blood donors served as control populations. Blood samples were tested for the presence of ANAs with Western blotting, using recombinant proteins of the three putative antigens (aldolase C, neuron-specific enolase, and pyruvate kinase M1). We found these antibodies in 11.8% of the 76 IPD patients, which differed significantly from healthy controls (0%, P = 0.043), but nonsignificantly from patients with genetic parkinsonism (11.1%), with a parkinson-plus syndrome (10%), or from neurological disease controls (4%). With respect to relevant disease characteristics, IPD patients with or without ANAs were indistinguishable, except for atypical disease features (mainly early falls or freezing and marked Pisa syndrome), which were more frequent in the ANA-positive IPD group. We conclude that ANAs do not play a role in the majority of patients with IPD, but might be relevant in the pathogenesis of IPD with atypical features.