[Letter to the editor] Sustained effects of a neural-based intervention in a refractory case of Tourette syndrome

There are only a few treatments available for Tourette syndrome (TS). These treatments frequently do notwork in patients with moderate to severe TS [1]. Neuroimaging studies show a correlation between tics severity and increased activation over motor pathways, along with reduced activation over the control areas of the cortico-striato-thalamo-cortical circuits [2]. Moreover, the temporal pattern of tic generation suggests that cortical activation especially in the SMA precedes subcortical activation [3]. Following this assumption, here we explored the brain effects of 10-daily sessions of cathodal transcranial Direct Current Stimulation (tDCS) delivered over the pre-SMA in a patient with refractory and severe TS and also assessed whether those changes were long lasting (up to 6 months).

Multispectral brain morphometry in Tourette syndrome persisting into adulthood.

Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

Factum pour dame Jeanne de Roffignac, veuve de... Mre Jean-Louis de Vassal de la Tourette... de Montviel... et Mre Louis de Roffignac de Sardiny... intimez... contre damoiselle Marguerite Ruin, femme de Charles Guyot, se disant aux droicts de Louis du Ponseau et Marie de Vernaison, qui se disoit seule... héritière de deffunte damoiselle Luce de Vernaison, légataire de deffunt Mre Paul de Sardiny, appellante d'une sentence rendue... le 12 janvier 1685... et contre les abbesse, prieure et convent de l'abbaye de Moncé, aussi appellantes...

[Factum. Sardiny, Paul de. 1685?]

Grey-matter abnormalities in boys with Tourette syndrome: magnetic resonance imaging study using optimised voxel-based morphometry

The genesis of Tourette syndrome is still unknown, but a core role for the pathways of cortico-striatal-thalamic-cortical circuitry (CSTC) is supposed. Volume-rendering magnetic resonance imaging data-sets were analysed in 14 boys with Tourette syndrome and 15 age-matched controls using optimised voxel-based morphometry. Locally increased grey-matter volumes (corrected P < 0.001) were found bilaterally in the ventral putamen. Regional decreases in grey matter were observed in the left hippocampal gyrus. This unbiased analysis confirmed an association between striatal abnormalities and Tourette syndrome, and the hippocampal volume alterations indicate an involvement of temporolimbic pathways of the CSTC in the syndrome.

Eye Movement Measures of Cognitive Control in Children with Tourette Syndrome

Tourette Syndrome begins in childhood and is characterized by uncontrollable repetitive actions like neck craning or hopping and noises such as sniffing or chirping. Worst in early adolescence, these tics wax and wane in severity and occur in bouts unpredictably, often drawing unwanted attention from bystanders. Making matters worse, over half of children with Tourette Syndrome also suffer from comorbid, or concurrent, disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). These disorders introduce anxious thoughts, impulsivity, inattention, and mood variability that further disrupt children with Tourette Syndrome from focusing and performing well at school and home. Thus, deficits in the cognitive control functions of response inhibition, response generation, and working memory have long been ascribed to Tourette Syndrome. Yet, without considering the effect of medication, age, and comorbidity, this is a premature attribution. This study used an infrared eye tracking camera and various computer tasks requiring eye movement responses to evaluate response inhibition, response generation, and working memory in Tourette Syndrome. This study, the first to control for medication, age, and comorbidity, enrolled 39 unmedicated children with Tourette Syndrome and 29 typically developing peers aged 10-16 years who completed reflexive and voluntary eye movement tasks and diagnostic rating scales to assess symptom severities of Tourette Syndrome, ADHD, and OCD. Children with Tourette Syndrome and comorbid ADHD and/or OCD, but not children with Tourette Syndrome only, took longer to respond and made more errors and distracted eye movements compared to typically-developing children, displaying cognitive control deficits. However, increasing symptom severities of Tourette Syndrome, ADHD, and OCD correlated with one another. Thus, cognitive control deficits were not specific to Tourette Syndrome patients with comorbid conditions, but rather increase with increasing tic severity, suggesting that a majority of Tourette Syndrome patients, regardless of a clinical diagnosis of ADHD and/or OCD, have symptoms of cognitive control deficits at some level. Therefore, clinicians should evaluate and counsel all families of children with Tourette Syndrome, with or without currently diagnosed ADHD and/or OCD, about the functional ramifications of comorbid symptoms and that they may wax and wane with tic severity.

Le Corbusier y el proyecto para Saint Marie de la Tourette: De la celda al espacio inefable

El convento de la Tourette se concibe en un marco temporal concreto. Sin embargo sería erróneo limitarse a él a la hora de intentar desentrañar las claves del proyecto y llegar a un entendimiento completo del mismo. Es necesario analizarlo atendiendo al conjunto global de la producción del arquitecto, la cual ha ido forjando una forma propia de hacer que condicionará en gran medida las decisiones tomadas en cada momento. Esta tesis realiza una investigación de doble sentido (recogida en los dos volúmenes que la componen). Por un lado analiza el proceso evolutivo en el que se enhebra la obra intentando desentrañar la influencia de aquel en ésta, pero por otro, invirtiendo el sentido, también desvela ciertas claves de la arquitectura de Le Corbusier a través del preciso análisis de proyecto de la Tourette. Pero aún más, la pertenencia del convento de la Tourette al “tipo monacal” introduce la presencia de un tiempo histórico “ab origine, in hillo tempore” del que la investigación se hace eco. Un tiempo al que Le Corbusier siempre volverá la mirada, y que en este caso se encuentra muy presente, determinando el devenir del proyecto de una forma particular y definitiva. Por tanto este trabajo pretende convocar los dos tiempos que conviven en el proyecto del convento de la Tourette, el corto, concreto y cerrado de su génesis y desarrollo, que se circunscribe al periodo de proyecto comprendido entre los años 1953 y 1956, y el más dilatado, abstracto y abierto, que enlaza el proyecto con la producción de Le Corbusier, y aún más atrás, con el tiempo histórico. En la primera parte del trabajo (A. “PROYECTO”) se realiza un análisis cronológico de la documentación gráfica ‐incluyendo su re‐dibujo‐ y escrita del proyecto, desde los croquis que el arquitecto esboza en su primera visita al valle del Turdine hasta el documento final del project d’exécution, a partir del cual se materializará la obra. El objetivo de la investigación no es describir la realidad construida, sino participar del secreto de su génesis analizando y intentando comprender los dibujos o el pensamiento de sus creadores. Frente a la multitud de escritos sobre la obra del convento de la Tourette el foco de atención de la tesis se centra en el proyecto. Es en esta fase de elaboración y desarrollo de las ideas, previa a la acción de construir, donde pensamos que La deriva de la propia actividad del arquitecto avala esta decisión. A lo largo de su carrera Le Corbusier va reduciendo progresivamente su presencia en la obra centrándose cada vez más en las fases de la concepción y proyecto arquitectónico. Considera que en ellas se produce lo “esencial” mientras que deja las decisiones de obra en manos de sus colaboradores y de los diversos “operadores”, participando tan solo en el visto bueno final de las mismas (esta posición contrasta con la entrega de los constructores para quienes el arquitecto encarna la innovación tecnológica). En la Tourette realiza exclusivamente tres visitas de obra en las que actúa como un mero escenógrafo, ajustando aquí y allá pequeñas decisiones de la construcción. Esta distancia refuerza su posición en el proceso y subraya su búsqueda de un ideal teórico desarrollado sobre todo en la fase de proyecto frente a lo subsidiario de la realidad práctica. En la segunda parte de la tesis, denominada “RE‐VISIONES”, se abre el campo de acción a otras facetas de la ingente actividad de Le Corbusier como la pintura, la escritura o incluso la escultura; una nueva MIRADA bajo el prisma de una serie de conceptos‐llave recurrentes en su Petit vocabulaire (l’homme, la céllule, la bôite, l’organisme). Se amplía, por tanto, el marco temporal, repasando de modo genérico y transversal la evolución de los mismos en la trayectoria del arquitecto, comprobándose como el convento de la Tourette es un eslabón característico y clave en todos ellos. ABSTRACT The Convent of La Tourette is conceived in a specific time frame. However, it would be erroneous to limit oneself simply to this when trying to unravel the keys to the project and to fully understand it. It is necessary to analyse the project attending to the entire production of the architect, who progressively shaped his own way of doing things which would condition to a large extent the decisions taken at each point in time. This thesis carries out its research in a dual sense (brought together in both its volumes). On the one hand, it analyses the development process threading the work attempting to fathom the influence of the former on the latter but, on the other hand, inverting the sense which also reveals certain keys to the architecture of Le Corbusier by means of a detailed analysis of the project for La Tourette. Even more so, the Convent of La Tourette belonging to the “monastic type” introduces the presence of a historical period “ab origine, in hillo tempore" reflected in the research. A period to which Le Corbusier would always look back on and which is extremely present in this case, determining the evolution of the project in a particular and definitive manner. Therefore, this piece of work attempts to bring together both time periods co‐existing in the project for the Convent of La Tourette, the short, specific and closed one regarding its genesis development, encompassing the project period going from 1953 to 1956, and the broader, more abstract and open one linking the project with the production by Le Corbusier, and even further back, with the historical period. The first part of this work (A. “PROJECT") performs a chronological analysis of the graphic – including its re‐drawing –and written documentation of the project, from the outlines the architect sketched in his first visit to the Turdine valley up to the final document of the project d’exécution from which the works would materialise. The main object of the investigation is not intend to describe the reality constructed, but to participate in the secret of its genesis, analysing and trying to understand the drawings or the thoughts of its creators. As opposed to the many writings on the work of the Convent of La Tourette, the attention of this thesis focusses on the project. It is in this preparation and development stage, previous to the construction action, where it is believed the real keys to understand and explain it lie. The enormous work collecting, ordering and analysing the abundant graphic and written information reveals “a multidirectional process, full of regrets and securities, errors and certainties, leaps backwards and tremendous foresight in the process” directed not only by the conditions of the assignment, but also by the way of doing things of Le Corbusier and his collaborator I. Xenakis. A web of hidden relationships is weaved in this open space of the process, often distant in time, allowing us to draw a new route, not only towards the constructed works of the Convent of La Tourette, but towards understanding his entire production. It is in the creation of this new path of knowledge, and not only in its conclusion, where the “thesis” acquires its true meaning. In second place, the drift in the actual activity of the architect backs this decision. Throughout his career, Le Corbusier progressively reduced his presence on site, focussing more and more on the conception and architectural project stages. He considered that which was “essential” took place in these, while leaving the on‐site decisions to his collaborators and the different “operators”, only participating in their final approval (this position is in contrast with the delivery by the constructors for whom the architect embodies the technological innovation). In La Tourette he exclusively made three on‐site visits, in which acted as a pure stage designer, adjusting small construction decisions here and there. This distance reinforces his position in the process and underlines his search for a theoretical ideal developed primarily in the project stage as opposed to that which is secondary of the practical reality. The second part of the thesis, called “RE‐VISIONS”, widens the scope of action to other aspects of the huge activity by Le Corbusier, encompassing painting, writing or even sculpture; a new VIEW under the prism of a series of recurrent key concepts in his Petit vocabulaire (l’homme, la céllule, la bôite, l’organisme). The time frame is therefore extended, revising in a generic and transversal manner the development of these concepts throughout the career of Le Corbusier, confirming how the Convent of La Tourette is a characteristic and key link to each of them.

L'hypnotisme et les et́ats analogues au point de vue med́ico-leǵal, les et́ats hypnotiques et les et́ats analogues les suggestions criminelles cabinets de somnambules et societ́eś de magnet́isme et de spiritisme l'hypnotisme devant la loi /

Mode of access: Internet.

Histaminergic modulation in Tourette syndrome

Introduction: Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor tics and at least one vocal/phonic tic. Clinical phenotypes show a wide variability, often incorporating behavioral symptoms. The exact pathophysiology of Tourette syndrome is unknown, however genetic vulnerability and alterations in dopaminergic neurotransmission have consistently been reported. Other biochemical pathways, including histaminergic neurotransmission, are likely to be involved but have received relatively little attention until recently. Areas covered: We conducted a systematic literature review focusing on the role of histaminergic neurotransmission and its pharmacological modulation in Tourette syndrome. We identified a number of relevant original studies published over the last five years, mainly focusing on genetic aspects. Expert opinion: There is converging evidence from recent studies supporting the hypothesis that histaminergic neurotransmission may play a role in the pathophysiology of Tourette syndrome. Most studies focused on the role of the histidine decarboxylase gene and the potential usefulness of histidine decarboxylase knockout mice as an experimental model for studying neurochemical function in Tourette syndrome. There have been no large scale studies assessing the use of histaminergic medications in the management of Tourette syndrome. This would be an important area for future research, with direct implications for the clinical management of selected phenotypes.

Investigation into the biochemical changes in Tourette Syndrome with a potential for pharmacological manipulation

Kynurenine (KYN) is the first stable metabolite of the kynurenine pathway, which accounts for over 95% of tryptophan metabolism. Two previous studies by this research group reported elevated plasma KYN in Tourette syndrome (TS) patients when compared with age and sex matched controls and another study showed that KYN potentiated 5-HT2A-mediated head-shakes (HS) in rodents. These movements have been suggested to model tics in TS. This raised the questions how KYN acts in eliciting this response and whether it is an action of its own or of a further metabolite along the kynurenine pathway. In the liver, where most of the kynurenine pathway metabolism takes place under physiological conditions, the first and the rate limiting enzyme is tryptophan-dioxygenase (TDO) which can be induced by cortisol. In extrahepatic tissues the same step of the pathway is catalyzed by indoleamine-dioxygenase (IDO), which is induced by cytokines, predominantly interferon-y (INF-y). Plasma neopterin, which shows parallel increase with KYN following immune stimulation, was also found elevated in one of these studies positively correlating with KYN. In the present work animal studies suggested that KYN potentiates and quinolinic acid (QUINA) dose dependently inhibits the 5-HT2A-mediated HS response in mice. The potentiating effect seen with KYN was suggested to be an effect of KYN itself. Radioligand binding and phosphoinositide (PI) hydrolysis studies were done to explore the mechanisms by which kynurenine pathway metabolites could alter a 5-HT2A-receptor mediated response. None of the kynurenine pathway metabolites tested showed direct binding to 5-HT2A-receptors. PI hydrolysis studies with KYN and QUINA showed that KYN did not have any effect while QUINA inhibited 5-HT2A-mediated PI hydrolysis. Plasma cortisol determination in TS patients with elevated plasma KYN did not show elevated plasma cortisol levels, suggesting that the increase of plasma KYN in these TS patients is unlikely to be due to an increased TDO activity induced by increased cortisol. Attention deficit hyperactivity disorder (ADHD) is commonly associated with TS. Salivary cortisol detected in a group of children primarily affected with ADHD showed significantly lower salivary cortisol levels when compared with age and sex matched controls. Plasma tryptophan, KYN, neopterin, INF-y and KYN/tryptophan ratio and night-time urinary 6-sulphatoxymelatonin (aMT6s) excretion measured in a group of TS patients did not show any difference in their levels when compared with age and sex matched controls, but TS patients failed to show the expected positive correlation seen between plasma INF-y, neopterin and KYN and the negative correlation seen between plasma KYN and night-time urinary aMT6s excretion seen in healthy controls. The relevance of the kynurenine pathway, melatonin secretion and cortisol to Tourette Syndrome and associated conditions and the mechanism by which KYN and QUINA alter the 5-HT2A-receptor mediated HS response are discussed.

Premonitory urges for tics in adult patients with Tourette syndrome

Objective: Patients with Tourette syndrome (TS) often report characteristic sensory experiences, also called premonitory urges (PUs), which precede tic expression and have high diagnostic relevance. This study investigated the usefulness of a scale developed and validated in children and adolescents-the Premonitory Urge for Tics Scale (PUTS, Woods et al., 2005 [13])-for the assessment of PUs in adult patients with TS. Method: Standard statistical methods were applied to test the psychometric properties of the PUTS in 102 adult TS outpatients recruited from two specialist clinics in the United Kingdom. Results: The PUTS showed good acceptability and endorsement rates, with evenly distributed scores and low floor and ceiling effects. Item-total correlations were moderate to strong; PUTS total scores were significantly correlated with quantitative measures of TS severity. The PUTS showed excellent internal consistency reliability (Cronbach's alpha=0.85) and Spearman's correlations demonstrated satisfactory convergent and discriminant validity. Conclusions: Although originally devised to assess urges to tic in young patients with TS, the PUTS demonstrated good psychometric properties in a large sample of adults recruited at specialist TS clinics. This instrument is therefore recommended for use across the life span as a valid and reliable self-report measure of sensory experiences accompanying tic expression. © 2013 The Japanese Society of Child Neurology.

Personality profile of male adolescents with Tourette syndrome:a controlled study

Tourette syndrome is a neurodevelopmental disorder characterized by multiple tics and commonly associated with behavioral problems, especially obsessive-compulsive disorder and attention-deficit hyperactivity disorder (ADHD). The presence of specific personality traits has been documented in adult clinical populations with Tourette syndrome but has been underresearched in younger patients. We assessed the personality profiles of 17 male adolescents with Tourette syndrome and 51 age- and gender-matched healthy controls using the Minnesota Multiphasic Personality Inventory-Adolescent version, along with a standardized psychometric battery. All participants scored within the normal range across all Minnesota Multiphasic Personality Inventory-Adolescent version scales. Patients with Tourette syndrome scored significantly higher than healthy controls on the Obsessiveness Content Scale only (P = .046). Our findings indicate that younger male patients with Tourette syndrome do not report abnormal personality traits and have similar personality profiles to healthy peers, with the exception of obsessionality traits, which are likely to be related to the presence of comorbid obsessive compulsive symptoms rather than tics.

Premonitory urges and sensorimotor processing in Tourette syndrome

Most patients with Tourette syndrome report characteristic sensory experiences (premonitory urges) associated with the expression of tic symptoms. Despite the central role of these experiences to the clinical phenomenology of Tourette syndrome, little is known about their underlying brain processes. In the present article we present the results of a systematic literature review of the published studies addressing the pathophysiological mechanisms of premonitory urges. We identified some preliminary evidence for specific alterations in sensorimotor processing at both cortical and subcortical levels. A better insight into the brain correlates of premonitory urges could lead to the identification of new targets to treat the sensory initiators of tics in patients with Tourette syndrome. © 2013 - IOS Press and the authors. All rights reserved.

DBS in Dystonia and Other Hyperkinetic Movement Disorders.

OPINION STATEMENT: The diagnosis and appropriate treatment of hyperkinetic movement disorders require a work up of potentially reversible metabolic, infectious and structural disorders as well as side effects of current medication. In pharmacoresistant movement disorders with a disabling impact on quality of life, deep brain stimulation (DBS) should be considered. At different targets, DBS has become an established therapy for Parkinson's disease (GPi-STN), tremor (VIM) and primary dystonia (GPi) with reasonable perioperative risks and side effects, established guidelines and some clinical and radiological predictive factors. In contrast, for other hyperkinetic movement disorders, including secondary dystonia, Gilles de la Tourette, chorea and ballism, only few data are available. Definite targets are not well defined, and reported results are of less magnitude than those of the recognized indications. In this expanding therapeutical field without worked out recommendations, an individual approach is needed with DBS indication assessment only after rigorous multidisciplinary scrutiny, restricted to expert centres.

Validation of the University of Sao Paolo Sensory Phenomena Scale: Initial Psychometric Properties

Introduction: Although obsessions and compulsions comprise the main features of obsessive-compulsive disorder (OCD), many patients report that their compulsions are preceded by a sense of ""incompleteness"" or other unpleasant feelings such as premonitory urges or a need perform action`s until feeling ""just right."" These manifestations have been characterized as Sensory Phenomena (SP). The current study presents initial psychometric data for a new scale designed to measure SP. Methods: Seventy-six adult OCD subjects were probed twice. Patients were assessed with an open clinical interview (considered as the ""gold standard"") and with the following standardized instruments: Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders, Yale-Brown Obsessive-Compulsive Scale, Dimensional Yale-Brown Obsessive-Compulsive Scale, Yale Global Tic Severity Scale, Beck Anxiety Inventory, and Beck Depression Inventory. Results: SP were present in 51 OCD patients (67.1%). Tics were present in 16 (21.1%) of the overall sample. The presence of SP was significantly higher in early-onset OCD patients. There were no significant differences in the presence of SP according to comorbidity with tics or gender. The comparison between the results from the open clinical interviews and the University of Sao Paulo Sensory Phenomena Scale (USP-SPS) showed an excellent concordance between them, with no significant differences between interviewers. The inter-rater reliability between the expert raters for the USP-SPS was high, with K=.92. The Pearson correlation coefficient between the SP severity scores given by the two raters was .89. Conclusion: Preliminary results suggest that the USP-SPS is a valid and reliable instrument for assessing the presence and severity of SP in OCD subjects. CNS Spectr. 2009;14(6):315-323