Caudate volumes in childhood predict symtom severity in adults with Tourette syndrome

Yale University, New Haven, Connecticut, United States
Neurology (Impact Factor: 8.29). 11/2005; 65(8):1253-8. DOI: 10.1212/01.wnl.0000180957.98702.69
Source: PubMed


Most children with Tourette syndrome (TS) experience a marked decline in the severity of tic symptoms during adolescence. Currently no clinical measures can predict whose tic symptoms will persist into adulthood. Previous cross-sectional imaging studies have identified reduced caudate nucleus volumes in subjects with TS.
To evaluate whether caudate nucleus volumes in childhood can predict the severity of tic or obsessive-compulsive symptoms at follow-up in early adulthood.
In a prospective longitudinal study, clinical status and basal ganglia volumes of 43 children with TS were measured on high-resolution magnetic resonance images before age 14 years. Follow-up clinical assessments were conducted after age 16 years, an average of 7.5 years later. Linear regression and Tobit regression analyses were used to assess the association of basal ganglia volumes measured in childhood with the severity of tic and obsessive-compulsive disorder (OCD) symptoms at the time of childhood MRI and at follow-up in early adulthood.
Volumes of the caudate nucleus correlated significantly and inversely with the severity of tic and OCD symptoms in early adulthood. Caudate volumes did not correlate with the severity of symptoms at the time of the MRI scan.
Caudate volumes in children with Tourette syndrome predict the severity of tic and obsessive-compulsive symptoms in early adulthood. This study provides compelling evidence that morphologic disturbances of the caudate nucleus within cortico-striatal-thalamo-cortical circuits are central to the persistence of both tics and obsessive-compulsive symptoms into adulthood.

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    • "It is of note that the exact etiology of GTS remains unknown. Volumetric MRI in GTS provided evidence for correlations between tic severities and volume of specific structures [e.g., caudate, see Ref. (47)] and also for abnormal gray matter volumes in prefrontal cortex in children and adults [see Ref. (48, 49), and for review see Ref. (50, 51)]. Functional neuroimaging techniques, such as single-photon emission computed tomography (SPECT), PET, and fMRI have provided some evidence for the underlying pathological mechanisms in GTS that enabled new hypotheses on its pathophysiology to be formulated (50, 51). "
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    ABSTRACT: Primary Dystonia (pD) is a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Gilles de la Tourette Syndrome (GTS) is a childhood-onset neuropsychiatric developmental disorder characterised by motor and phonic tics, which could progress to behavioural changes. GTS and obsessive-compulsive disorders (OCD) are often seen in comorbidity, also suggesting a possible overlap in the pathophysiological bases of these two conditions. PET techniques are of considerable value in detecting functional and molecular abnormalities in vivo, according to the adopted radioligands. For example, PET is the unique technique that allows in vivo investigation of neurotransmitter systems, providing evidence of changes in GTS or pD. For example, presynaptic and postsynaptic dopaminergic studies with PET have shown alterations compatible with dysfunction or loss of D2-bearing neurons, increased synaptic dopamine levels, or both. Measures of cerebral glucose metabolism with 18F-fluorodeoxyglucose (18F-FDG PET) are very sensitive in showing brain functional alterations as well. 18F-FDG PET data have shown metabolic changes within the cortico-striato-pallido-thalamo-cortical and cerebello-thalamo-cortical networks, revealing possible involvement of brain circuits not limited to basal ganglia in pD and GTS. The aim of this work is to overview PET consistent neuroimaging literature on pD and GTS that has provided functional and molecular knowledge of the underlying neural dysfunction. Furthermore we suggest potential applications of these techniques in monitoring treatments.
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    • "Tics may result from defective striatal inhibition of undesired motor patterns via loss of inhibition of motor cortical neurons (Mink, 2001; Wang et al., 2011). Decreased volume of the caudate nucleus, cortical thinning of primary sensory and motor cortices, and age-related slowing of fronto-striatal and fronto-parietal pathway maturation support the network scale of TS pathophysiology (Bloch et al., 2005; Worbe et al., 2012a). Nuclear imaging studies showed that these network abnormalities are associated with an increased dopaminergic tone, as well as abnormal GABAergic and other monoaminergic (noradrenaline, histamine , serotonine) transmission within striatal, thalamic, insular and cerebellar regions (Buse et al., 2013). "
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    ABSTRACT: Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses.
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    • " continue to have difficulty, and who belongs in the transient tic category would be most helpful to families and clinicians. Similarly, being able to understand who will experience a relief of tic burden with age, and who will continue to experience lifelong difficulties with TS would be of enormous importance to our understanding of the disorder. Bloch et al. (2005) provide one illustration of how a longitudinal study design may go a long way towards understanding and predicting TS burden by tracking how child anatomical measurements correlate to TS symptoms in those same participants in adulthood. CBIT is a clearly effective, but sorely underutilized (due to the dearth of clinicians with the exper"
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