title: Pathological ponto-cerebello-thalamo-cortical activations in primary orthostatic tremor during lying and stance.
abstract: Primary orthostatic tremor is a rare neurological disease characterized mainly by a high frequency tremor of the legs while standing. The aim of this study was to identify the common core structures of the oscillatory circuit in orthostatic tremor and how it is modulated by changes of body position. Ten patients with orthostatic tremor and 10 healthy age-matched control subjects underwent a standardized neurological and neuro-ophthalmological examination including electromyographic and posturographic recordings. Task-dependent changes of cerebral glucose metabolism during lying and standing were measured in all subjects by sequential18F-fluorodeoxyglucose-positron emission tomography on separate days. Results were compared between groups and conditions. All the orthostatic tremor patients, but no control subject, showed the characteristic 13-18 Hz tremor in coherent muscles during standing, which ceased in the supine position. While lying, patients had a significantly increased regional cerebral glucose metabolism in the pontine tegmentum, the posterior cerebellum (including the dentate nuclei), the ventral intermediate and ventral posterolateral nucleus of the thalamus, and the primary motor cortex bilaterally compared to controls. Similar glucose metabolism changes occurred with clinical manifestation of the tremor during standing. The glucose metabolism was relatively decreased in mesiofrontal cortical areas (i.e. the medial prefrontal cortex, supplementary motor area and anterior cingulate cortex) and the bilateral anterior insula in orthostatic tremor patients while lying and standing. The mesiofrontal hypometabolism correlated with increased body sway in posturography. This study confirms and further elucidates ponto-cerebello-thalamo-primary motor cortical activations underlying primary orthostatic tremor, which presented consistently in a group of patients. Compared to other tremor disorders one characteristic feature in orthostatic tremor seems to be the involvement of the pontine tegmentum in the pathophysiology of tremor generation. High frequency oscillatory properties of pontine tegmental neurons have been reported in pathological oscillatory eye movements. It is remarkable that the characteristic activation and deactivation pattern in orthostatic tremor is already present in the supine position without tremor presentation. Multilevel changes of neuronal excitability during upright stance may trigger activation of the orthostatic tremor network. Based on the functional imaging data described in this study, it is hypothesized that a mesiofrontal deactivation is another characteristic feature of orthostatic tremor and plays a pivotal role in development of postural unsteadiness during prolonged standing.
authors.affiliation: 1 Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schöberl
authors.affiliation: 1 Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Feil
authors.affiliation: 2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Guoming
authors.initials: G
authors.lastname: Xiong
authors.affiliation: 2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|3 Department of Nuclear Medicine, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|4 Munich Cluster of Systems Neurology, SyNergy, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: 2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|5 Department of Nuclear Medicine, Eberhard Karls University, Röntgenweg 11, 72076 Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: la Fougére
authors.affiliation: 2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|6 Neurology, Schön Klinik Bad Aibling, Kolbermoorer Str. 72, 83043 Bad Aibling, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jahn
authors.affiliation: 2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|7 Clinical Neurosciences, Ludwig-Maximilians-Unversity, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brandt
authors.affiliation: 1 Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Strupp
authors.affiliation: 1 Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.|4 Munich Cluster of Systems Neurology, SyNergy, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Dieterich
authors.affiliation: 1 Department of Neurology, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany andreas.zwergal@med.uni-muenchen.de.|2 German Center for Vertigo and Balance Disorders, DSGZ, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zwergal
mesh_terms: D000368:Aged; D002531:Cerebellum / Q000000981:diagnostic imaging*; D004244:Dizziness / Q000000981:diagnostic imaging* / Q000503:physiopathology; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging*; D065821:Pontine Tegmentum / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D004856:Postural Balance; D011187:Posture / Q000502:physiology*; D013787:Thalamic Nuclei / Q000000981:diagnostic imaging*; D014202:Tremor / Q000000981:diagnostic imaging* / Q000503:physiopathology
keywords: PET; cerebellum; imaging; orthostatic tremor; pons