Gilles de la Tourette Syndrome (GTS) is characterized by multiple motor and one or more vocal/phonic tics. Psychopathology and co-morbidity occur in approximately 80-90% of clinical cohorts. The most common psychopathologies are attention deficit hyperactivity disorder, obsessive-compulsive behaviours, obsessive-compulsive disorder, depression, anxiety and certain behavioural disorders. In severe GTS patients who are refractory to medication and other therapies, deep brain stimulation (DBS) is investigated. To date there have been some 50-55 patients who have received DBS in 19 centres worldwide. Nine different brain targets in the thalamus, the pallidum, and the ventral caudate and anterior internal capsule have been stimulated. This paper reviews critically and in detail all studies published to date. Only two studies on just a few patients fulfil some of the evidence-based criteria. DBS for GTS is therefore still highly experimental.
"). Third, these disorders share symptomatology, showing considerable overlap in the core and associated symptoms , that is, issues with attention, impulsivity, repetitive behaviors , impairments in socialization and communication, anxiety, sleep disturbance, obsessive compulsive behaviors, sensory processing abnormalities, depression, and ritualistic behaviors, such as counting, repeating, or ordering and arranging (see Table 1 for a comparison of the shared symptomatology) (Grzadzinski et al., 2011; Hariz and Robertson, 2010; Hattori et al., 2006; Taylor, 2009; Terband et al., 2014; Tourette Syndrome Fact Sheet, 2013). Fourth, these disorders share neuropathology. "
[Show abstract][Hide abstract] ABSTRACT: The prevalence of neurodevelopmental disorders, including autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), and Tourette syndrome (TS), has increased over the past two decades. Currently, about 1 in 6 children in the United States is diagnosed with a neurodevelopmental disorder. Evidence suggests that ASD, ADHD, and TS have similar neuropathology, which includes long-range under-connectivity and short-range over-connectivity. They also share similar symptomatology, with considerable overlap in their core and associated symptoms and a frequent overlap in their comorbid conditions. Consequently, it is apparent that ASD, ADHD, and TS diagnoses belong to a broader spectrum of neurodevelopmental illness. Biologically, long-range under-connectivity and short-range over-connectivity are plausibly related to neuronal insult (e.g., neurotoxicity, neuroinflammation, excitotoxicity, sustained microglial activation, proinflammatory cytokines, toxic exposure, oxidative stress, etc.). Therefore, these disorders may a share a similar etiology. The main purpose of this review is to critically examine the evidence that ASD, ADHD, and TS belong to a broader spectrum of neurodevelopmental illness, an abnormal connectivity spectrum disorder (ACSD), which results from neural long-range under-connectivity and short-range over-connectivity. The review also discusses the possible reasons for these neuropathological connectivity findings. In addition, this review examines the role and issue of axonal injury and regeneration in order to better understand the neuropathophysiological interplay between short- and long-range axons in connectivity issues.
"Significant symptomatic improvements of motor dysfunctions were reported in these studies, but the stimulation parameters were not communicated. Since then, impressive reductions in tic frequency and severity, perhaps with greater effectiveness against motor than vocal tics, have been reported, although the number of TS patients treated with CM/Pf DBS remains small (Visser-Vandewalle et al., 2003, 2004, 2006; Temel and Visser-Vandewalle, 2004; Houeto et al., 2005; Ackermans et al., 2006, 2008, 2010, 2011; Bajwa et al., 2007; Maciunas et al., 2007; Servello et al., 2008, 2010; Shields et al., 2008; Porta et al., 2009; Hariz and Robertson, 2010; Sassi et al., 2011; Maling et al., 2012; Savica et al., 2012; Visser-Vandewalle and Kuhn, 2013). The time course of tic improvement varies between individuals, ranging from immediate effects (Visser-Vandewalle et al., 2003; Maciunas et al., 2007) to a more protracted time course (Maciunas et al., 2007; Servello et al., 2008). "
[Show abstract][Hide abstract] ABSTRACT: Because of our limited knowledge of the functional role of the thalamostriatal system, this massive network is often ignored in models of the pathophysiology of brain disorders of basal ganglia origin, such as Parkinson's disease (PD). However, over the past decade, significant advances have led to a deeper understanding of the anatomical, electrophysiological, behavioral and pathological aspects of the thalamostriatal system. The cloning of the vesicular glutamate transporters 1 and 2 (vGluT1 and vGluT2) has provided powerful tools to differentiate thalamostriatal from corticostriatal glutamatergic terminals, allowing us to carry out comparative studies of the synaptology and plasticity of these two systems in normal and pathological conditions. Findings from these studies have led to the recognition of two thalamostriatal systems, based on their differential origin from the caudal intralaminar nuclear group, the center median/parafascicular (CM/Pf) complex, or other thalamic nuclei. The recent use of optogenetic methods supports this model of the organization of the thalamostriatal systems, showing differences in functionality and glutamate receptor localization at thalamostriatal synapses from Pf and other thalamic nuclei. At the functional level, evidence largely gathered from thalamic recordings in awake monkeys strongly suggests that the thalamostriatal system from the CM/Pf is involved in regulating alertness and switching behaviors. Importantly, there is evidence that the caudal intralaminar nuclei and their axonal projections to the striatum partly degenerate in PD and that CM/Pf deep brain stimulation (DBS) may be therapeutically useful in several movement disorders.
Frontiers in Systems Neuroscience 01/2014; 8:5. DOI:10.3389/fnsys.2014.00005
"This is supported by the observation that our two best responders to DBS similarly showed the largest response to short-term stimulation. A key factor to attaining therapeutic benefit from DBS is target selection, and optimal implantation locations in TS are still under debate , . In our subjects, we experienced a spectrum of clinical benefits that we believe is due in part to variation in final lead location. "
[Show abstract][Hide abstract] ABSTRACT: Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.
PLoS ONE 11/2012; 7(9):e44215. DOI:10.1371/journal.pone.0044215 · 3.23 Impact Factor
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