{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:20:57Z","timestamp":1780327257411,"version":"3.54.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008358","name":"Hersenstichting","doi-asserted-by":"publisher","award":["2012(1)-91"],"award-info":[{"award-number":["2012(1)-91"]}],"id":[{"id":"10.13039\/501100008358","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Essential tremor is among the commonly observed movement disorders in clinical practice, however the exact pathophysiological mechanisms underlying tremor are unknown. It has been suggested that Purkinje cell alterations play a causal factor in tremorgenesis. Altered levels of inhibitory (GABA) and excitatory (glutamate+glutamine, Glx) neurotransmitters could be markers for Purkinje cell alterations. We hypothesize that GABA and Glx levels in the dentate nuclei could be differentially altered in patients responsive to either anticonvulsants or \u03b2-adrenergic blockers.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> In this explorative study in patients with essential tremor, we measured gamma-aminobutyric acid (GABA) and glutamate+glutamine (Glx) levels in the dentate nucleus region using <jats:sup>1<\/jats:sup>H-magnetic resonance spectroscopy (MRS) in seven patients using propranolol, five patients using anticonvulsants, and eight healthy controls.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> There were no group differences with respect to GABA+\/Cr, Glx\/Cr, NAA\/Cr, and GABA+\/Glx ratios. There was no correlation with tremor severity.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Our results are in line with previously published studies; however, additional studies on a larger number of patients are warranted to confirm these findings. Furthermore medication-subgroups did not exhibit differences with respect to GABA+\/Cr, Glx\/Cr, NAA\/Cr, and GABA+\/Glx ratios. A recent study, of similar size, found an inverse association between tremor severity and the GABA+\/Glx ratio in the cerebellum of essential tremor patients. We were unable to replicate these findings. The field of tremor research is plagued by heterogeneous results, and we would caution against drawing firm conclusions based on pilot studies.<\/jats:p>","DOI":"10.3389\/fneur.2021.664735","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T05:04:42Z","timestamp":1620277482000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["GABA, Glutamate, and NAA Levels in the Deep Cerebellar Nuclei of Essential Tremor Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Arthur W. G.","family":"Buijink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Prent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas A.","family":"Puts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk","family":"Schrantee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter V.","family":"Potters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Fleur","family":"van Rootselaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s12311-015-0692-6","article-title":"Linking essential tremor to the cerebellum: neuropathological evidence","volume":"15","author":"Louis","year":"2016","journal-title":"Cerebellum."},{"key":"B2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1093\/brain\/awr301","article-title":"Defective dentate nucleus GABA receptors in essential tremor","volume":"135","author":"Paris-Robidas","year":"2011","journal-title":"Brain."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1212\/01.WNL.0000065885.15875.0D","article-title":"Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy","volume":"60","author":"Pagan","year":"2003","journal-title":"Neurology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0304-3940(02)00966-7","article-title":"Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study","volume":"333","author":"Louis","year":"2002","journal-title":"Neurosci Lett."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40673-020-00116-y","article-title":"A pilot study of essential tremor: cerebellar GABA+\/Glx ratio is correlated with tremor severity","volume":"7","author":"Tapper","year":"2020","journal-title":"Cereb Ataxias."},{"key":"B6","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s12311-017-0891-4","article-title":"In vivo dentate nucleus gamma-aminobutyric acid concentration in essential tremor vs. controls","volume":"17","author":"Louis","year":"2018","journal-title":"Cerebellum."},{"key":"B7","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1002\/mds.27700","article-title":"MDS evidence-based review of treatments for essential tremor","volume":"34","author":"Ferreira","year":"2019","journal-title":"Mov Disord."},{"key":"B8","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/S1474-4422(10)70322-7","article-title":"Treatment of patients with essential tremor","volume":"10","author":"Deuschl","year":"2011","journal-title":"Lancet Neurol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1136\/jnnp.49.1.64","article-title":"A comparison of primidone, propranolol, and placebo in essential tremor, using quantitative analysis","volume":"49","author":"Gorman","year":"1986","journal-title":"J Neurol Neurosurg Psychiatry."},{"key":"B10","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.parkreldis.2016.10.002","article-title":"Knowledge gaps and research recommendations for essential tremor","volume":"33","author":"Hopfner","year":"2016","journal-title":"Parkinsonism Relat Disord."},{"key":"B11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/mds.27121","article-title":"Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society","volume":"33","author":"Bhatia","year":"2018","journal-title":"Mov Disord."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1002\/mds.25162","article-title":"Reliability of a new scale for essential tremor","volume":"27","author":"Elble","year":"2012","journal-title":"Mov Disord."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1002\/jmri.24478","article-title":"Gannet: a batch-processing tool for the quantitative analysis of gamma-aminobutyric acid-edited MR spectroscopy spectra","volume":"40","author":"Edden","year":"2014","journal-title":"J Magn Reson Imaging."},{"key":"B15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1097\/WNF.0000000000000127","article-title":"Effect of primidone on dentate nucleus \u03b3-aminobutyric acid concentration in patients with essential tremor","volume":"39","author":"Louis","year":"2016","journal-title":"Clin Neuropharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11064-013-1199-5","article-title":"A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra","volume":"39","author":"Rae","year":"2014","journal-title":"Neurochem Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nrn3475","article-title":"Power failure: why small sample size undermines the reliability of neuroscience","volume":"14","author":"Button","year":"2013","journal-title":"Nat Rev Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3652","DOI":"10.1002\/hbm.24201","article-title":"Age-related differences in GABA levels are driven by bulk tissue changes","volume":"39","author":"Maes","year":"2018","journal-title":"Hum Brain Mapp."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.664735\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T05:04:45Z","timestamp":1620277485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.664735\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,6]]},"references-count":18,"alternative-id":["10.3389\/fneur.2021.664735"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.664735","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,6]]},"article-number":"664735"}}