Pathophysiologie des Gilles-de-la-Tourette-Syndroms

ZUSAMMENFASSUNG

Beim Gilles-de-la-Tourette-Syndrom (GTS) handelt es sich um eine häufige facettenreiche, typischerweise im Kindes- oder Jugendalter beginnende neuropsychiatrische Erkrankung. Die Pathophysiologie ist nicht sicher geklärt. Eine wichtige Rolle scheinen die Basalganglien und kortiko-striato-thalamo-kortikale Regelkreise einzunehmen. Eine der konstantesten Veränderungen stellt eine diskrete Volumenreduktion des Striatums bei Kindern dar. Auch konnten Veränderungen im Bereich der weißen Substanz innerhalb dieses Regelkreises nachgewiesen werden. Auf kortikaler Ebene wurden Veränderungen im Bereich des sensomotorischen und präfrontalen Kortex, der supplementär motorischen Region und des inferioren parietalen Kortex (BA 40) beschrieben. Auf biochemischer Ebene zeigt sich vor allem eine erhöhte dopaminerge Transmission. Auch Serotonin scheint durch den Wegfall Dopamin hemmender Effekte eine Rolle zu spielen. Kognitionspsychologische bzw. wahrnehmungspsychologische Ansätze gingen zunächst von einer gestörten inhibitorischen Kontrolle aus.

Aufgrund uneinheitlicher Ergebnisse wird eher eine Interferenz mit Kompensationsmechanismen zur Tic-Kontrolle vermutet. Auch zeigen sich Veränderungen der interozeptiven Wahrnehmung. Allerdings ist unsicher, ob diese ursächlich sind oder eine sekundäre Veränderung des GTS darstellen. Einer der aktuellsten Ansätze stützt sich auf die „Theory of Event Coding“, welche besagt, dass sowohl Wahrnehmungen als auch Handlungen gemeinsam in „event files“ gespeichert werden und in enger Verbindung stehen. Es gibt erste experimentelle Hinweise, dass bei Patienten mit einem GTS die Kopplung zwischen Wahrnehmung und Handlung besonders stark ausgeprägt ist und Tics aufgrund dieser starken Bindung durch verschiedene Stimuli ausgelöst werden könnten.

ABSTRACT

Gilles de la Tourette syndrome is a common multifaceted neuropsychiatric disorder typically commencing in childhood or adolescence. Its pathophysiology is still unclear. The basal ganglia and cortico-striato-thalamo-cortical circuits seem to play an important role. One of the most consistent alterations in children is a volume reduction of the striatum. Additionally, changes have been documented within the white matter of cortico-striato-thalamo-cortical circuit. On a cortical level, alterations have been shown in different regions including the sensorimotor and prefrontal cortex, the supplementary motor area and the inferior parietal cortex (BA 40). Biochemically, an increase in dopamine activity seems to be crucial. Also, serotonin, particularly its dopamine-inhibiting effect is considered to be important.

Cognitive-psychological and perceptual-psychological approaches initially focused on an impairment of inhibitory control in Tourette patients. However, different studies yielded inconsistent results. Currently, altered cognitive control in Tourette syndrome is viewed in the context of interference with compensatory mechanisms for tic control. Additionally, alterations of interoceptive awareness have been shown. However, it remains unclear whether they are causative or represent secondary compensatory mechanisms. One of the most recent approaches is based on the „Theory of Event Coding“ based on the concept that both perception and action are stored together in so called „event files“. Thus, perception and action are tightly connected, which is thought to be even stronger in Gilles de la Tourette Syndromes patients compared to healthy controls resulting in tics being triggered by various stimuli being linked to them.

Schlüsselwörter

Tourette-Syndrom - Pathophysiologie - Tic-Kontrolle

Key words

Tourette syndrome - pathophysiology - tic control

• Literatur

• 1 Association AP. Diagnostic and Statistical Manual of Mental Disorders. Washington: American Psychiatric Publishing; 2014
• 2 Leckman JF. Tourette’s syndrome. Lancet 2002; 360 9345 1577-86
• 3 Leckman JF, Walker DE, Cohen DJ. Premonitory urges in Tourette’s syndrome. Am J Psychiatry 1993; 150 (01) 98-102
• 4 Misirlisoy E, Brandt V, Ganos C. et al The relation between attention and tic generation in Tourette syndrome. Neuropsychology 2015; 29 (04) 658-65
• 5 Brandt VC, Beck C, Sajin V. et al Temporal relationship between premonitory urges and tics in Gilles de la Tourette syndrome. Cortex 2016; 77: 24-37
• 6 Freeman RD, Fast DK, Burd L. et al An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol 2000; 42 (07) 436-47
• 7 Bloch MH, Peterson BS, Scahill L. et al Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med 2006; 160 (01) 65-9
• 8 Pappert EJ, Goetz CG, Louis ED. et al Objective assessments of longitudinal outcome in Gilles de la Tourette’s syndrome. Neurology 2003; 61 (07) 936-40
• 9 Groth C. Tourette syndrome in a longitudinal perspective. Clinical course of tics and comorbidities, coexisting psychopathologies, phenotypes and predictors. Dan Med J 2018; 65: 4
• 10 Lowe TL, Capriotti MR, McBurnett K. Long-Term Follow-up of Patients with Tourette’s Syndrome. Mov Disord Clin Pract 2019; 6 (01) 40-5
• 11 Muller-Vahl K, Dodel I, Muller N. et al Health-related quality of life in patients with Gilles de la Tourette’s syndrome. Mov Disord 2010; 25 (03) 309-14
• 12 Piacentini J, Woods DW, Scahill L. et al Behavior therapy for children with Tourette disorder: a randomized controlled trial. JAMA 2010; 303 (19) 1929-37
• 13 Sallee F, Kohegyi E, Zhao J. et al Randomized, Double-Blind, Placebo-Controlled Trial Demonstrates the Efficacy and Safety of Oral Aripiprazole for the Treatment of Tourette’s Disorder in Children and Adolescents. J Child Adolesc Psychopharmacol 2017; 27 (09) 771-81
• 14 Pringsheim T, Holler-Managan Y, Okun MS. et al Comprehensive systematic review summary: Treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology 2019; 92 (19) 907-15
• 15 Marras C, Andrews D, Sime E. et al Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial. Neurology 2001; 56 (05) 605-10
• 16 Jankovic J. Botulinum toxin in the treatment of dystonic tics. Mov Disord 1994; 9 (03) 347-9
• 17 Johnson KA, Fletcher PT, Servello D. et al Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study. J Neurol Neurosurg Psychiatry 2019; 90 (10) 1078-1090
• 18 Meige H, Feindl E. Les tics et leur traitement: Masson et cie. 1902
• 19 Ganos C, Roessner V, Munchau A. The functional anatomy of Gilles de la Tourette syndrome. Neurosci Biobehav Rev 2013; 37 (06) 1050-62
• 20 DeLong MR. Activity of basal ganglia neurons during movement. Brain Res 1972; 40 (01) 127-35
• 21 Lanciego JL, Luquin N, Obeso JA. Functional neuroanatomy of the basal ganglia. Cold Spring Harb Perspect Med 2012; 2 (12) a009621
• 22 Alexander GE, DeLong MR. Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties. J Neurophysiol 1985; 53 (06) 1417-30
• 23 Singer HS, Reiss AL, Brown JE. et al Volumetric MRI changes in basal ganglia of children with Tourette’s syndrome. Neurology 1993; 43 (05) 950-6
• 24 Peterson BS, Thomas P, Kane MJ. et al Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry 2003; 60 (04) 415-24
• 25 Muller-Vahl KR, Kaufmann J, Grosskreutz J. et al Prefrontal and anterior cingulate cortex abnormalities in Tourette Syndrome: evidence from voxel-based morphometry and magnetization transfer imaging. BMC Neurosci 2009; 10: 47
• 26 Kalanithi PS, Zheng W, Kataoka Y. et al Altered parvalbumin-positive neuron distribution in basal ganglia of individuals with Tourette syndrome. Proc Natl Acad Sci U S A 2005; 102 (37) 13307-12
• 27 Kataoka Y, Kalanithi PS, Grantz H. et al Decreased number of parvalbumin and cholinergic interneurons in the striatum of individuals with Tourette syndrome. J Comp Neurol 2010; 518 (03) 277-91
• 28 Bronfeld M, Belelovsky K, Bar-Gad I. Spatial and temporal properties of tic-related neuronal activity in the cortico-basal ganglia loop. J Neurosci 2011; 31 (24) 8713-21
• 29 Zhuang P, Hallett M, Zhang X. et al Neuronal activity in the globus pallidus internus in patients with tics. J Neurol Neurosurg Psychiatry 2009; 80 (10) 1075-81
• 30 Israelashvili M, Smeets A, Bronfeld M. et al Tonic and phasic changes in anteromedial globus pallidus activity in Tourette syndrome. Mov Disord 2017; 32 (07) 1091-6
• 31 Fredericksen KA, Cutting LE, Kates WR. et al Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. Neurology 2002; 58 (01) 85-9
• 32 Makki MI, Govindan RM, Wilson BJ. et al Altered fronto-striato-thalamic connectivity in children with Tourette syndrome assessed with diffusion tensor MRI and probabilistic fiber tracking. J Child Neurol 2009; 24 (06) 669-78
• 33 Worbe Y, Marrakchi-Kacem L, Lecomte S. et al Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome. Brain 2015; 138 Pt 2 472-82
• 34 Church JA, Fair DA, Dosenbach NU. et al Control networks in paediatric Tourette syndrome show immature and anomalous patterns of functional connectivity. Brain 2009; 132 Pt 1 225-38
• 35 Beste C, Tubing J, Seeliger H. et al Altered perceptual binding in Gilles de la Tourette syndrome. Cortex 2016; 83: 160-6
• 36 Wittfoth M, Bornmann S, Peschel T. et al Lateral frontal cortex volume reduction in Tourette syndrome revealed by VBM. BMC Neurosci 2012; 13: 17
• 37 Draganski B, Martino D, Cavanna AE. et al Multispectral brain morphometry in Tourette syndrome persisting into adulthood. Brain 2010; 133 Pt 12 3661-75
• 38 Eidelberg D, Moeller JR, Antonini A. et al The metabolic anatomy of Tourette’s syndrome. Neurology 1997; 48 (04) 927-34
• 39 Bohlhalter S, Goldfine A, Matteson S. et al Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study. Brain 2006; 129 Pt 8 2029-37
• 40 Hampson M, Tokoglu F, King RA. et al Brain areas coactivating with motor cortex during chronic motor tics and intentional movements. Biol Psychiatry 2009; 65 (07) 594-9
• 41 Kwon HJ, Lim WS, Lim MH. et al 1-Hz low frequency repetitive transcranial magnetic stimulation in children with Tourette’s syndrome. Neurosci Lett 2011; 492 (01) 1-4
• 42 Finis J, Enticott PG, Pollok B. et al Repetitive transcranial magnetic stimulation of the supplementary motor area induces echophenomena. Cortex 2013; 49 (07) 1978-82
• 43 Petruo V, Bodmer B, Brandt VC. et al Altered perception-action binding modulates inhibitory control in Gilles de la Tourette syndrome. J Child Psychol Psychiatry 2018 ePub
• 44 Beste C, Munchau A. Tics and Tourette syndrome – surplus of actions rather than disorder?. Mov Disord 2018; 33 (02) 238-42
• 45 Costa RM. Plastic corticostriatal circuits for action learning: what’s dopamine got to do with it?. Ann N Y Acad Sci 2007; 1104: 172-91
• 46 Samanin R, Garattini S. The serotonergic system in the brain and its possible functional connections with other aminergic systems. Life Sci 1975; 17 (08) 1201-9
• 47 Seignot JN. The case of Gilles de la Tourette syndrome: a condition of nervous tics cured by R.1625. Annales médico-psychologiques 1961; 119 (01) 578-9
• 48 Roessner V, Plessen KJ, Rothenberger A. et al European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry 2011; 20 (04) 173-96
• 49 Cohen DJ, Shaywitz BA, Caparulo B. et al Chronic, multiple tics of Gilles de la Tourette’s disease. CSF acid monoamine metabolites after probenecid administration. Arch Gen Psychiatry 1978; 35 (02) 245-50
• 50 Singer HS, Hahn IH, Moran TH. Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette’s syndrome. Ann Neurol 1991; 30 (04) 558-62
• 51 Minzer K, Lee O, Hong JJ. et al Increased prefrontal D2 protein in Tourette syndrome: a postmortem analysis of frontal cortex and striatum. J Neurol Sci 2004; 219 1–2 55-61
• 52 Muller-Vahl KR, Berding G, Brucke T. et al Dopamine transporter binding in Gilles de la Tourette syndrome. J Neurol 2000; 247 (07) 514-20
• 53 Liu H, Dong F, Meng Z. et al Evaluation of Tourette’s syndrome by (99 m)Tc-TRODAT-1 SPECT/CT imaging. Ann Nucl Med 2010; 24 (07) 515-21
• 54 Malison RT, McDougle CJ, van Dyck CH. et al [123I]beta-CIT SPECT imaging of striatal dopamine transporter binding in Tourette’s disorder. Am J Psychiatry 1995; 152 (09) 1359-61
• 55 Palminteri S, Lebreton M, Worbe Y. et al Dopamine-dependent reinforcement of motor skill learning: evidence from Gilles de la Tourette syndrome. Brain 2011; 134 Pt 8 2287-301
• 56 van Campen AD, Kunert R, van den Wildenberg WPM. et al Repetitive transcranial magnetic stimulation over inferior frontal cortex impairs the suppression (but not expression) of action impulses during action conflict. Psychophysiology 2018; 55: 3
• 57 Georgiou N, Bradshaw JL, Phillips JG. et al The Simon effect and attention deficits in Gilles de la Tourette’s syndrome and Huntington’s disease. Brain 1995; 118 Pt 5 1305-18
• 58 Wylie SA, Claassen DO, Kanoff KE. et al Impaired inhibition of prepotent motor actions in patients with Tourette syndrome. J Psychiatry Neurosci 2013; 38 (05) 349-56
• 59 Channon S, Drury H, Martinos M. et al Tourette’s syndrome (TS): inhibitory performance in adults with uncomplicated TS. Neuropsychology 2009; 23 (03) 359-66
• 60 Ganos C, Kuhn S, Kahl U. et al Action inhibition in Tourette syndrome. Mov Disord 2014; 29 (12) 1532-8
• 61 Serrien DJ, Orth M, Evans AH. et al Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence. Brain 2005; 128 Pt 1 116-25
• 62 Stenner MP, Baumgaertel C, Heinze HJ. et al Intact automatic motor inhibition in patients with tourette syndrome. Mov Disord 2018; 33 (11) 1800-4
• 63 Mueller SC, Jackson GM, Dhalla R. et al Enhanced cognitive control in young people with Tourette’s syndrome. Curr Biol 2006; 16 (06) 570-3
• 64 Jackson GM, Mueller SC, Hambleton K. et al Enhanced cognitive control in Tourette Syndrome during task uncertainty. Exp Brain Res 2007; 182 (03) 357-64
• 65 Ganos C, Kahl U, Schunke O. et al Are premonitory urges a prerequisite of tic inhibition in Gilles de la Tourette syndrome?. J Neurol Neurosurg Psychiatry 2012; 83 (10) 975-8
• 66 Banaschewski T, Woerner W, Rothenberger A. Premonitory sensory phenomena and suppressibility of tics in Tourette syndrome: developmental aspects in children and adolescents. Dev Med Child Neurol 2003; 45 (10) 700-3
• 67 van der Salm SMA, van der Meer JN, Cath DC. et al Distinctive tics suppression network in Gilles de la Tourette syndrome distinguished from suppression of natural urges using multimodal imaging. Neuroimage Clin 2018; 20: 783-92
• 68 Ganos C, Bongert J, Asmuss L. et al The somatotopy of tic inhibition: Where and how much?. Mov Disord 2015; 30 (09) 1184-9
• 69 Ganos C, Kahl U, Brandt V. et al The neural correlates of tic inhibition in Gilles de la Tourette syndrome. Neuropsychologia 2014; 65: 297-301
• 70 Peterson BS, Skudlarski P, Anderson AW. et al A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry 1998; 55 (04) 326-33
• 71 Kawohl W, Bruhl A, Krowatschek G. et al Functional magnetic resonance imaging of tics and tic suppression in Gilles de la Tourette syndrome. World J Biol Psychiatry 2009; 10 4 Pt 2 567-70
• 72 Craig AD. How do you feel -now? The anterior insula and human awareness. Nat Rev Neurosci 2009; 10 (01) 59-70
• 73 Critchley HD, Wiens S, Rotshtein P. et al Neural systems supporting interoceptive awareness. Nat Neurosci 2004; 7 (02) 189-95
• 74 Dunn BD, Stefanovitch I, Evans D. et al Can you feel the beat? Interoceptive awareness is an interactive function of anxiety- and depression-specific symptom dimensions. Behav Res Ther 2010; 48 (11) 1133-8
• 75 Ganos C, Garrido A, Navalpotro-Gomez I. et al Premonitory urge to tic in Tourette’s is associated with interoceptive awareness. Mov Disord 2015; 30 (09) 1198-202
• 76 Schandry R. Heart beat perception and emotional experience. Psychophysiology 1981; 18 (04) 483-8
• 77 Pile V, Lau JYF, Topor M. et al Interoceptive Accuracy in Youth with Tic Disorders: Exploring Links with Premonitory Urge, Anxiety and Quality of Life. J Autism Dev Disord 2018; 48 (10) 3474-82
• 78 Graybiel AM. Habits, rituals, and the evaluative brain. Annu Rev Neurosci 2008; 31: 359-87
• 79 Delorme C, Salvador A, Valabregue R. et al Enhanced habit formation in Gilles de la Tourette syndrome. Brain 2016; 139 Pt 2 605-15
• 80 Nelson A, Killcross S. Amphetamine exposure enhances habit formation. J Neurosci 2006; 26 (14) 3805-12
• 81 Nelson AJ, Killcross S. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists. Front Neurosci 2013; 7: 76
• 82 Rueda-Orozco PE, Robbe D. The striatum multiplexes contextual and kinematic information to constrain motor habits execution. Nat Neurosci 2015; 18 (03) 453-60
• 83 Brandt VC, Patalay P, Baumer T. et al Tics as a model of over-learned behavior-imitation and inhibition of facial tics. Mov Disord 2016; 31 (08) 1155-62
• 84 Hommel B, Musseler J, Aschersleben G. et al The Theory of Event Coding (TEC): a framework for perception and action planning. Behav Brain Sci 2001; 24 (05) 849-78
• 85 Hommel B. Event files: feature binding in and across perception and action. Trends Cogn Sci 2004; 8 (11) 494-500
• 86 Stein BE, Stanford TR. Multisensory integration: current issues from the perspective of the single neuron. Nat Rev Neurosci 2008; 9 (04) 255-66
• 87 Hommel B. Action control according to TEC (theory of event coding). Psychol Res 2009; 73 (04) 512-26
• 88 Colzato LS, Warrens MJ, Hommel B. Priming and binding in and across perception and action: a correlational analysis of the internal structure of event files. Q J Exp Psychol (Hove) 2006; 59 (10) 1785-804
• 89 Hydock C, Patai EZ, Sohn MH. Distinct response components indicate that binding is the primary cause of response repetition effects. J Exp Psychol Hum Percept Perform 2013; 39 (06) 1598-611
• 90 Hommel B, Colzato L. Visual attention and the temporal dynamics of feature integration. Vis Cogn 2004; 11 (04) 483-521