Neurological Sciences

, Volume 40, Issue 10, pp 2051–2063 | Cite as

No reliable gray matter changes in essential tremor

  • Rong Luo
  • PingLei Pan
  • Yun XuEmail author
  • Ling ChenEmail author
Original Article



Voxel-based morphometry (VBM) has been used to study human brain gray matter (GM) alterations in essential tremor (ET) for over one decade. However, the literature revealed heterogeneous findings.


We therefore conducted a coordinate-based meta-analysis to synthesize the VBM studies to examine which brain regions show the most reliable GM alterations in patients with ET relative to healthy controls.


A total of 16 original VBM studies, comprising 387 patients with ET and 355 healthy controls, were included in this meta-analysis. This quantitative meta-analysis revealed no evidence of robust and reliable alterations in regional brain GM structures in ET. Meta-regression analyses indicate that many moderators (e.g., MR field strength, statistical methodology, age, onset age, gender, illness severity, illness duration, and family history) account for some of the heterogeneity in GM across studies.


High heterogeneity in GM alterations across studies may reflect true heterogeneity in ET regarding the clinic, etiology, and pathology, as well as possibly the VBM methodological variations. Currently, this heterogeneity limits the use of VBM as a reliable tool to distinguish ET from healthy controls. In order to improve reproducibility of VBM results in ET, future research may benefit from increasing the sample size, comprehensively subtyping ET phenotypes, and using well-designed and standardized imaging acquisition and analytical protocols. Furthermore, data sharing should be considered as a high priority.


Essential tremor Voxel-based morphometry Gray matter Coordinate-based meta-analysis 



Anisotropic effect-size signed differential mapping


Essential tremor


Fahn-Tolosa-Marin Tremor Rating Scale


Gray matter


Montreal Neurological Institute


Magnetic resonance imaging


Preferred Reporting Items for Systematic Reviews and Meta-Analyses


Seed-based d Mapping


Voxel-based morphometry



We thank all the authors of the included studies.


This work was supported by the National Natural Science Foundation of China (81630028, 81601161), the Key Research and Development Program of Jiangsu Province of China (BE2016610), the National Key Research and Development Program of China (2016YFC1300504), and the Jiangsu Province Key Medical Discipline (ZDXKA2016020).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

10072_2019_3933_MOESM1_ESM.docx (29 kb)
ESM 1 (DOCX 28 kb)


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Department of NeurologyNanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Neurology, Affiliated Yancheng HospitalSchool of Medicine, Southeast UniversityYanchengPeople’s Republic of China
  3. 3.Department of Central Laboratory, Affiliated Yancheng HospitalSchool of Medicine, Southeast UniversityYanchengPeople’s Republic of China
  4. 4.Jiangsu Province Stroke Center for Diagnosis and TherapyNanjingPeople’s Republic of China
  5. 5.Nanjing Neuropsychiatry Clinic Medical CenterNanjingPeople’s Republic of China
  6. 6.Laboratory of Reproductive Medicine, Department of PhysiologyNanjing Medical UniversityNanjingPeople’s Republic of China

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