Figure 1.
Spatial Location of the Structural Cerebellar Abnormalities in Essential Tremor (ET) Patients Relative to Healthy Controls.
(A) Evidence for gray matter abnormalities in ET patients relative to controls as detected by voxel-based morphometry (VBM) studies. (B) Evidence for white matter changes as obtained with diffusion imaging techniques. Abbreviations: FA, fractional anisotropy.
Table 1.
Structural Neuroimaging Studies Reporting Anatomical Neurodegenerative Processes in ET
| Reference | Sample | Neuroimaging Method | Main Finding |
| Daniels et al.12 | 27 patients (14 with ET-PT; 13 with ET-IT) 27 HC | VBM | ET<HC: No significant GM loss ET-IT > HC: GM increase in the temporal and occipital cortex |
| Martinelli et al.13 | 10 ET 10 HC | DWI (ADC) | ET<HC: No significant differences in ADC values |
| Shin et al.14 | 10 ET 8 HC | DTI (FA) | ET<HC: Reduced FA in pons, cerebellum, midbrain, orbitofrontal cortex, lateral frontal cortex, parietal cortex and temporal cortex |
| Quattrone et al.15 | 50 patients (30 ET arm; 20 ET head) 32 HC | VBM Manual volumetry | ET<HC: No significant GM loss ET head<HC: GM loss in the cerebellar vermis |
| Cerasa et al.16 | 46 ET (27 ET arm; 19 ET head) 28 HC | Automated subcortical Segmentation | ET<HC: No significant GM loss ET head<HC: GM volumetric atrophy of the entire cerebellum |
| Benito-Léon et al.17 | 19 ET 20 HC | VBM | ET<HC: GM/WM losses in the bilateral cerebellum, right frontal lobe, left medulla, parietal lobes, right insula and right limbic lobe |
| Nicoletti et al.18 | 25 FET 15 PD 15 HC | DTI (FA/MD) | FET<PD<HC: Reduced FA of dentate nucleus and superior cerebellar peduncle FET<PD<HC: Increased MD of superior cerebellar peduncle. |
| Jia et al.19 | 15 ET 15 HC | DTI (FA/ADC) | ET<HC: Increased ADC of red nucleus |
| Bagepally et al.20 | 20 ET 17 HC | VBM | ET<HC: GM loss in bilateral cerebellum, vermis, bilateral frontal and occipital lobes |
| Klein et al.21 | 14 ET 20 HC | DTI (FA/ADC) - TBSS VBM | DTI-TBSS: ET<HC: Increased MD of inferior cerebellar peduncle bilaterally, left parietal WM; reduced FA in the right inferior cerebellar peduncle. VBM: ET,HC: No significant GM or WM losses |
Abbreviations: VBM, voxel based morphometry; GM, gray matter; WM, white matter; DTI, diffusion tensor imaging; MD, mean diffusivity; FA, fractional anisotropy; TBSS, tract-based spatial statistics; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient; ET, essential tremor; ET-IT, essential tremor patients with intentional tremor; ET-PT, essential tremor patients with postural tremor; ET arm, essential tremor with arm tremor; ET head: essential tremor with head tremor; FET, familial essential tremor; PD, Parkinson's disease; HC, healthy controls.
DTI provides estimation of GM/WM tissue composition by using two distinct MRI measures (MD, FA). VBM provides a probabilistic intensity value of GM/WM volume/density voxel by voxel in the entire brain. Increased water in brain areas (where neuronal/axonal loss occurs) corresponds to increased ADC values. TBSS is a technique for analyzing group effects in diffusion-based imaging voxel by voxel in the entire brain.
Figure 2.
Summary of A Number of Positron Emission Tomography (PET) and Functional Magnetic Resonance Imaging Studies Demonstrating A Key Involvement of the Cerebellum in the Pathophysiology of Essential Tremor (ET) While Participants Executed A Specific Motor Task (i.e., Holding A Posture) or A Cognitive Paradigm (i.e., Keeping in the Working Memory A Series of Letters).
A PET study (Boecker et al.27) that employed a specific gamma-aminobutyric-acid radioligand is also reported to further display the key role of functional abnormalities in the cerebellar circuits in ET patients.
Table 2.
Functional Neuroimaging Studies in ET
| Reference | Sample | Neuroimaging Method | Main Finding |
| Colebatch et al.22 | 4 ET patients with postural tremor, 4 controls | PET | ET> HC: increased activation in sensorimotor cortex contralateral to the side of tremor and in both lateral premotor regions, and in cerebellar hemispheres when holding a posture (arms outstretched) vs. a rest condition. |
| Jenkins I H et al.23 | 6 ET with postural tremor, 6 controls | PET | Involuntary postural tremor in ET was associated with bilateral cerebellar activation, and contralateral striatal, thalamic, and sensorimotor cortex activation. |
| Wills AJ et al.24 | 6 ET with postural tremor, 6 controls | PET | ET patients > HC: during arm extension ET patients displayed abnormal increases in bilateral cerebellar and abnormal red nuclear activation. |
| Wills AJ et al.25 | 7 ET patients, 6 patients with writing tremor, and 6 controls | PET | ET patients > HC: abnormally increased bilateral cerebellar, red nuclear, and thalamic activation. Writing tremor was associated with abnormal bilateral cerebellar activation. |
| Boecker H et al.26 | 6 ET with postural tremor, 6 controls during administration of alcohol | PET | ET patients > HC: increased bilateral cerebellar activation including the cerebellar vermis. Ethanol ingestion: bilateral decreases of cerebellar blood flow in both ET patients and controls. In contrast, alcohol ingestion increased the activity in the inferior olivary nuclei in ET but not controls. |
| Boecker H et al.27 | 8 ET with postural tremor, 8 controls | PET with GABA radioligand | ET vs. controls: reduced GABAA receptor binding in the cerebellum, the ventrolateral thalamus, and the lateral premotor cortex. |
| Bucher SF et al.28 | 12 ET with postural tremor, 15 controls | fMRI | ET patients > HC: increased activation of the primary sensory motor areas, the globus pallidus, and the thalamus, contralaterally to the side of tremor. Bilateral increased activation of the nucleus dentate, the cerebellar hemispheres, and the red nucleus. |
| Cerasa et al.29 | 12 ET, 12 controls | fMRI | ET > HC: increased activation in the parietal cortex and dorsolateral prefrontal cortex during the execution of a Stroop task > a sensory motor baseline. |
| Passamonti et al.30 | 15 ET, 15 controls (different sample from that included in Cerasa et al. 2010) | fMRI | ET > HC: increased activation in the cerebellum during the execution of working memory trials with high attentional load. Functional connectivity: abnormalities were detected in the executive control circuit and in the default mode network of ET vs. controls. Patients with high cognitive scores also showed increased neural abnormalities. |