Christopher L Groth1,2, Mark Brown3, Justin M Honce3, Erika Shelton2, Stefan H Sillau2, Brian D Berman2,3,4. 1. Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States. 2. Department of Neurology, University of Colorado Anschutz Medical, Aurora, CO, United States. 3. Department of Radiology, University of Colorado Anschutz Medical, Aurora, CO, United States. 4. Neurology Section, Denver VA Medical Center, Aurora, CO, United States.
Abstract
Objective: The objective of this study is to investigate whether alterations in the neurotransmission of gamma-aminobutyric acid (GABA) in the thalamus are present in patients with cervical dystonia compared to healthy controls. Methods: GABA magnetic resonance spectroscopy was used to investigate concentration levels of GABA in the thalamus of cervical dystonia patients (n = 17) compared to healthy controls (n = 18). Additionally, a focused post hoc analysis of thalamic GABAA receptor availability data in a similar cohort (n = 15 for both groups) using data from a previously collected 11C-flumazenil positron emission tomography study was performed. Group comparisons for all evaluations were performed using two-sided t-tests with adjustments for age and sex, and Bonferroni correction for multiple comparisons was applied. Spearman's coefficient was used to test correlations. Results: We found significantly reduced GABA+/Cre levels in the thalamus of cervical dystonia patients compared to controls, and these levels positively correlated with disease duration. Although mean thalamic GABAA receptor availability did not differ between patients and controls, GABAA availability negatively correlated with both disease duration and dystonia severity. Conclusions: These findings support that aberrant inhibitory signaling within the thalamus contributes to the pathophysiology of cervical dystonia. Additionally, these results suggest that an inadequate ability to compensate for the loss of GABA through upregulation of GABAA receptors may underlie more severe symptoms.
Objective: The objective of this study is to investigate whether alterations in the neurotransmission of gamma-aminobutyric acid (GABA) in the thalamus are present in patients with cervical dystonia compared to healthy controls. Methods:GABA magnetic resonance spectroscopy was used to investigate concentration levels of GABA in the thalamus of cervical dystoniapatients (n = 17) compared to healthy controls (n = 18). Additionally, a focused post hoc analysis of thalamic GABAA receptor availability data in a similar cohort (n = 15 for both groups) using data from a previously collected 11C-flumazenil positron emission tomography study was performed. Group comparisons for all evaluations were performed using two-sided t-tests with adjustments for age and sex, and Bonferroni correction for multiple comparisons was applied. Spearman's coefficient was used to test correlations. Results: We found significantly reduced GABA+/Cre levels in the thalamus of cervical dystoniapatients compared to controls, and these levels positively correlated with disease duration. Although mean thalamic GABAA receptor availability did not differ between patients and controls, GABAA availability negatively correlated with both disease duration and dystonia severity. Conclusions: These findings support that aberrant inhibitory signaling within the thalamus contributes to the pathophysiology of cervical dystonia. Additionally, these results suggest that an inadequate ability to compensate for the loss of GABA through upregulation of GABAA receptors may underlie more severe symptoms.
Authors: Joost Janssen; Yasser Alemán-Gómez; Santiago Reig; Hugo G Schnack; Mara Parellada; Montserrat Graell; Carmen Moreno; Dolores Moreno; J M Mateos-Pérez; J M Udias; Celso Arango; Manuel Desco Journal: Br J Psychiatry Date: 2011-11-24 Impact factor: 9.319
Authors: Priyantha Herath; Cecile Gallea; Jan Willem van der Veen; Silvina G Horovitz; Mark Hallett Journal: Mov Disord Date: 2010-12-15 Impact factor: 10.338
Authors: Ursula M H Klumpers; Dick J Veltman; Ronald Boellaard; Emile F Comans; Cassandra Zuketto; Maqsood Yaqub; Jurgen E M Mourik; Mark Lubberink; Witte J G Hoogendijk; Adriaan A Lammertsma Journal: J Cereb Blood Flow Metab Date: 2007-10-10 Impact factor: 6.200
Authors: Esther A Pelzer; Corina Melzer; Lars Timmermann; D Yves von Cramon; Marc Tittgemeyer Journal: Brain Struct Funct Date: 2016-04-18 Impact factor: 3.270
Authors: Brian D Berman; Rebecca Tran Pollard; Erika Shelton; Ramesh Karki; Peter M Smith-Jones; Yubin Miao Journal: Front Neurol Date: 2018-04-04 Impact factor: 4.003
Authors: Christopher L Groth; Arun Singh; Qiang Zhang; Brian D Berman; Nandakumar S Narayanan Journal: Tremor Other Hyperkinet Mov (N Y) Date: 2021-11-10