Abstract
Essential tremor (ET) is the most common pathological tremor disorder in the world, and post-mortem evidence has shown that the cerebellum is the most consistent area of pathology in ET. In the last few years, advanced neuroimaging has tried to confirm this evidence. The aim of the present review is to discuss to what extent the evidence provided by this field of study may be generalised. We performed a systematic literature search combining the terms ET with the following keywords: MRI, VBM, MRS, DTI, fMRI, PET and SPECT. We summarised and discussed each study and placed the results in the context of existing knowledge regarding the cerebellar involvement in ET. A total of 51 neuroimaging studies met our search criteria, roughly divided into 19 structural and 32 functional studies. Despite clinical and methodological differences, both functional and structural imaging studies showed similar findings but without defining a clear topography of neurodegeneration. Indeed, the vast majority of studies found functional and structural abnormalities in several parts of the anterior and posterior cerebellar lobules, but it remains to be established to what degree these neural changes contribute to clinical symptoms of ET. Currently, advanced neuroimaging has confirmed the involvement of the cerebellum in pathophysiological processes of ET, although a high variability in results persists. For this reason, the translation of this knowledge into daily clinical practice is again partially limited, although new advanced multivariate neuroimaging approaches (machine-learning) are proving interesting changes of perspective.
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References
Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord. 2010;25:534–41.
Jain S, Se L, Louis ED. Common misdiagnosis of a common neurological disorder: how are we misdiagnosing essential tremor? Arch Neurol. 2006;63:1100–4.
Bermejo-Pareja F, Puertas-Martín V. Cognitive features of essential tremor: a review of the clinical aspects and possible mechanistic underpinnings. Tremor Other Hyperkinet Mov (NY) 2012;2. pii: 02-74-541-1.
Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol. 2010;9(6):613–22.
Deuschl G, Elble R. Essential tremor—neurodegenerative or nondegenerative disease towards a working definition of ET. Mov Disord. 2009;24(14):2033–41.
Quattrone A, Cerasa A, Messina D, Nicoletti G, Hagberg GE, Lemieux L, et al. Essential head tremor is associated with cerebellar vermis atrophy: a volumetric and voxel-based morphometry MR imaging study. AJNR Am J Neuroradiol. 2008;29(9):1692–7.
Cerasa A, Messina D, Nicoletti G, Novellino F, Lanza P, Condino F, et al. Cerebellar atrophy in essential tremor using an automated segmentation method. AJNR Am J Neuroradiol. 2009;30(6):1240–3.
Nicoletti G, Manners D, Novellino F, Condino F, Malucelli E, Barbiroli B, et al. Diffusion tensor MRI changes in cerebellar structures of patients with familial essential tremor. Neurology. 2010;74(12):988–94.
Shin DH, Han BS, Kim HS, Lee PH. Diffusion tensor imaging in patients with essential tremor. AJNR Am J Neuroradiol. 2008;29(1):151–3.
Benito-León J, Alvarez-Linera J, Hernández-Tamames JA, Alonso-Navarro H, Jiménez-Jiménez FJ, Louis ED. Brain structural changes in essential tremor: voxel-based morphometry at 3-Tesla. J Neurol Sci. 2009;287(1–2):138–42.
Bagepally BS, Bhatt MD, Chandran V, Saini J, Bharath RD, Vasudev M, et al. Decrease in cerebral and cerebellar gray matter in essential tremor: a voxel-based morphometric analysis under 3T MRI. J Neuroimaging. 2012;22(3):275–8.
Klein JC, Lorenz B, Kang JS, Baudrexel S, Seifried C, van de Loo S, et al. Diffusion tensor imaging of white matter involvement in essential tremor. Hum Brain Mapp. 2011;32(6):896–904.
Saini J, Bagepally BS, Bhatt MD, Chandran V, Bharath RD, Prasad C, et al. Diffusion tensor imaging: tract based spatial statistics study in essential tremor. Parkinsonism Relat Disord. 2012;18(5):477–82.
Buijink AW, Caan MW, Tijssen MA, Hoogduin JM, Maurits NM, van Rootselaar AF. Decreased cerebellar fiber density in cortical myoclonic tremor but not in essential tremor. Cerebellum. 2013;12(2):199–204.
Lin CH, Chen CM, Lu MK, Tsai CH, Chiou JC, Liao JR, et al. VBM reveals brain volume differences between Parkinson’s disease and essential tremor patients. Front Hum Neurosci. 2013;14:7–247.
Prodoehl J, Li H, Planetta PJ, Goetz CG, Shannon KM, Tangonan R, et al. Diffusion tensor imaging of Parkinson’s disease, atypical parkinsonism, and essential tremor. Mov Disord. 2013;28(13):1816–22.
Bhalsing KS, Upadhyay N, Kumar KJ, Saini J, Yadav R, Gupta AK, et al. Association between cortical volume loss and cognitive impairments in essential tremor. Eur J Neurol. 2014;21(6):874–83.
Jia L, Jia-Lin S, Qin D, Qing L, Yan Z. A diffusion tensor imaging study in essential tremor. J Neuroimaging. 2011;21(4):370–4.
Bhalsing KS, Kumar KJ, Saini J, Yadav R, Gupta AK, Pal PK. White matter correlates of cognitive impairment in essential tremor. AJNR Am J Neuroradiol. 2015;36(3):448–5.
Daniels C, Peller M, Wolff S, Alfke K, Witt K, Gaser C, et al. Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor. Neurology. 2006;67(8):1452–6.
Martinelli P, Rizzo G, Manners D, Tonon C, Pizza F, Testa C, et al. Diffusion-weighted imaging study of patients with essential tremor. Mov Disord. 2007;22(8):1182–5.
Manni E, Petrosini L. A century of cerebellar somatotopy: a debated representation. Nat Rev Neurosci. 2004;5:241–9.
Louis ED, Faust PL, Ma KJ, Yu M, Cortes E, Vonsattel JP. Torpedoes in the cerebellar vermis in essential tremor cases vs. controls. Cerebellum. 2011;10:812–9.
Nicoletti V, Cecchi P, Frosini D, Pesaresi I, Fabbri S, Diciotti S, et al. Morphometric and functional MRI changes in essential tremor with and without resting tremor. J Neurol. 2015;262(3):719–28.
Novellino F, Cherubini A, Chiriaco C, Morelli M, Salsone M, Arabia G, et al. Brain iron deposition in essential tremor: a quantitative 3-Tesla magnetic resonance imaging study. Mov Disord. 2013;28(2):196–200.
Louis ED, Shungu DC, Chan S, Mao X, Jurewicz EC, Watner D. Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study. Neurosci Lett. 2002;333(1):17–20.
Pagan FL, Butman JA, Dambrosia JM, Hallett M. Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy. Neurology. 2003;60(8):1344–7.
Kendi AT, Tan FU, Kendi M, Erdal HH, Tellioglu S. Magnetic resonance spectroscopy of the thalamus in essential tremor patients. J Neuroimaging. 2005;15(4):362–6.
Kaufman MJ, Madras BK. Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson’s diseased striatum. Synapse. 1991;9:43–9.
Booth TC, Nathan M, Waldman AD, Quigley AM, Schapira AH, Buscombe J. The role of functional dopamine-transporter SPECT imaging in parkinsonian syndromes, part 1. AJNR Am J Neuroradiol. 2015;36(2):229–35.
Hallett M. Tremor: pathophysiology. Parkinsonism Relat Disord. 2014;20 Suppl 1:S118–22.
Sharifi S, Nederveen AJ, Booij J, van Rootselaar AF. Neuroimaging essentials in essential tremor: a systematic review. Neuroimage Clin. 2014;5:217–31.
Klaming R, Annese J. Functional anatomy of essential tremor: lessons from neuroimaging. AJNR Am J Neuroradiol. 2014;35(8):1450–7.
Bhalsing KS, Saini J, Pal PK. Understanding the pathophysiology of essential tremor through advanced neuroimaging: a review. J Neurol Sci. 2013;335(1–2):9–13.
Breit S, Reimold M, Reischl G, Klockgether T, Wüllner U. [(11)C]d-threo-methylphenidate PET in patients with Parkinson’s disease and essential tremor. J Neural Transm. 2006;113(2):187–93.
Brooks DJ, Playford ED, Ibanez V, Sawle GV, Thompson PD, Findley LJ, et al. Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study. Neurology. 1992;42(8):1554–60.
Antonini A, Moresco RM, Gobbo C, De Notaris R, Panzacchi A, Barone P, et al. The status of dopamine nerve terminals in Parkinson’s disease and essential tremor: a PET study with the tracer [11-C]FE-CIT. Neurol Sci. 2001;22(1):47–8.
Doepp F, Plotkin M, Siegel L, Kivi A, Gruber D, Lobsien E, et al. Brain parenchyma sonography and 123I-FP-CIT SPECT in Parkinson’s disease and essential tremor. Mov Disord. 2008;23(3):405–10.
Wang J, Jiang YP, Liu XD, Chen ZP, Yang LQ, Liu CJ, et al. 99mTc-TRODAT-1 SPECT study in early Parkinson’s disease and essential tremor. Acta Neurol Scand. 2005;112(6):380–5.
Asenbaum S, Pirker W, Angelberger P, Bencsits G, Pruckmayer M, Brücke T. [123I]beta-CIT and SPECT in essential tremor and Parkinson’s disease. J Neural Transm. 1998;105(10–12):1213–28.
Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord. 2000;15(3):503–10.
Di Giuda D, Camardese G, Bentivoglio AR, Cocciolillo F, Guidubaldi A, Pucci L, et al. Dopaminergic dysfunction and psychiatric symptoms in movement disorders: a 123I-FP-CIT SPECT study. Eur J Nucl Med Mol Imaging. 2012;39(12):1937–48.
Isaias IU, Marotta G, Hirano S, Canesi M, Benti R, Righini A, et al. Imaging essential tremor. Mov Disord. 2010;25(6):679–86.
Roselli F, Pisciotta NM, Pennelli M, Aniello MS, Gigante A, De Caro MF, et al. Midbrain SERT in degenerative parkinsonisms: a 123I-FP-CIT SPECT study. Mov Disord. 2010;25(12):1853–9.
Gerasimou G, Costa DC, Papanastasiou E, Bostanjiopoulou S, Arnaoutoglou M, Moralidis E, et al. SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is there any correlation with Parkinson’s disease? Ann Nucl Med. 2012;26(4):337–44.
Isaias IU, Canesi M, Benti R, Gerundini P, Cilia R, Pezzoli G, et al. Striatal dopamine transporter abnormalities in patients with essential tremor. Nucl Med Commun. 2008;29(4):349–53.
Colebatch JG, Findley LJ, Frackowiak RS, Marsden CD, Brooks DJ. Preliminary report: activation of the cerebellum in essential tremor. Lancet. 1990;336(8722):1028–30.
Hallett M, Dubinsky RM. Glucose metabolism in the brain of patients with essential tremor. J Neurol Sci. 1993;114(1):45–8.
Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Ann Neurol. 1994;36:636–42.
Jenkins IH, Bain PG, Colebatch JG, Thompson PD, Findley LJ, Frackowiak RS, et al. A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections. Ann Neurol. 1993;34:82–90.
Wills AJ, Jenkins IH, Thompson PD, Findley LJ, Brooks DJ. A positron emission tomography study of cerebral activation associated with essential and writing tremor. Arch Neurol. 1995;52:299–305.
Boecker H, Wills AJ, Ceballos-Baumann A, Samuel M, Thompson PD, Findley LJ, et al. The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study. Ann Neurol. 1996;39:650–8.
Boecker H, Weindl A, Brooks DJ, Ceballos-Baumann AO, Liedtke C, Miederer M, et al. GABAergic dysfunction in essential tremor: an 11C-flumazenil PET study. J Nucl Med. 2010;51:1030–5.
Czarnecki K, Jones DT, Burnett MS, Mullan B, Matsumoto JY. SPECT perfusion patterns distinguish psychogenic from essential tremor. Parkinsonism Relat Disord. 2011;17(5):328–32.
Bucher SF, Seelos KC, Dodel RC, Reiser M, Oertel WH. Activation mapping in essential tremor with functional magnetic resonance imaging. Ann Neurol. 1997;41:32–40.
Neely KA, Kurani AS, Shukla P, Planetta PJ, Wagle Shukla A, Goldman JG, et al. Functional brain activity relates to 0–3 and 3–8 Hz force oscillations in essential tremor. Cereb Cortex. 2015;25(11):4191–202.
Raethjen J, Deuschl G. The oscillating central network of essential tremor. Clin Neurophysiol. 2012;123:61–4.
Buijink AW, Broersma M, van der Stouwe AM, van Wingen GA, Groot PF, Speelman JD, et al. Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor. Parkinsonism Relat Disord. 2015;21(4):383–8.
Deco G, Jirsa VK, McIntosh AR. Emerging concepts for the dynamical organization of resting-state activity in the brain. Nat Rev Neurosci. 2011;12(1):43–56.
Fang W, Lv F, Luo T, Cheng O, Liao W, Sheng K, et al. Abnormal regional homogeneity in patients with essential tremor revealed by resting-state functional MRI. PLoS One. 2013;8(7):e69199.
Fang W, Chen H, Wang H, Zhang H, Puneet M, Liu M, et al. Essential tremor is associated with disruption of functional connectivity in the ventral intermediate nucleus-motor cortex-cerebellum circuit. Hum Brain Mapp. 2015. doi:10.1002/hbm.23024.
Fang W, Chen H, Wang H, Zhang H, Liu M, Puneet M, et al. Multiple resting-state networks are associated with tremors and cognitive features in essential tremor. Mov Disord. 2015. doi:10.1002/mds.26375.
Cerasa A, Passamonti L, Novellino F, Salsone M, Gioia MC, Morelli M, et al. Fronto-parietal overactivation in patients with essential tremor during Stroop task. Neuroreport. 2010;21:148–51.
Passamonti L, Novellino F, Cerasa A, Chiriaco C, Rocca F, Matina MS, et al. Altered cortical-cerebellar circuits during verbal working memory in essential tremor. Brain. 2011;134:2274–86.
Janicki SC, Cosentino S, Louis ED. The cognitive side of essential tremor: what are the therapeutic implications? Ther Adv Neurol Disord. 2013;6(6):353–68.
Passamonti L, Cerasa A, Quattrone A. Neuroimaging of essential tremor: what is the evidence for cerebellar involvement? Tremor Other Hyperkinet Mov (N Y). 2012;2. pii: 02-67-421-3.
Tedesco AM, Chiricozzi FR, Clausi S, Lupo M, Molinari M, Leggio MG. The cerebellar cognitive profile. Brain. 2011;134(Pt 12):3672–86.
Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009;44:489–501.
Cerasa A, Quattrone A, Gioia MC, Magariello A, Muglia M, Assogna F, et al. MAO A VNTR polymorphism and amygdala volume in healthy subjects. Psychiatry Res. 2011;191(2):87–9.
Eckert MA, Tenforde A, Galaburda AM, et al. To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains. Neuroimage. 2006;32:1001–7.
Thawani SP, Schupf N, Louis ED. Essential tremor is associated with dementia: prospective population-based study in New York. Neurology. 2009;73:621–5.
Cerasa A, Nisticò R, Salsone M, Bono F, Salvino D, Morelli M, et al. Neuroanatomical correlates of dystonic tremor: a cross-sectional study. Parkinsonism Relat Disord. 2014;20(3):314–7.
Orrù G, Pettersson-Yeo W, Marquand AF, Sartori G, Mechelli A. Using support vector machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review. Neurosci Biobehav Rev. 2012;36(4):1140–5.
Cherubini A, Nisticó R, Novellino F, Salsone M, Nigro S, Donzuso G, et al. Magnetic resonance support vector machine discriminates essential tremor with rest tremor from tremor-dominant Parkinson disease. Mov Disord. 2014;29(9):1216–9.
Schmahmann JD, Doyon J, Toga A, Petrides M, Evans A. MRI Atlas of the Human Cerebellum. San Diego: Academic; 2000.
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Cerasa, A., Quattrone, A. Linking Essential Tremor to the Cerebellum—Neuroimaging Evidence. Cerebellum 15, 263–275 (2016). https://doi.org/10.1007/s12311-015-0739-8
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DOI: https://doi.org/10.1007/s12311-015-0739-8