Cerebellar Atrophy in Cortical Myoclonic Tremor and Not in Hereditary Essential Tremor-a Voxel-Based Morphometry Study

Abstract

Essential tremor (ET) presumably has a cerebellar origin. Imaging studies showed various cerebellar and also cortical structural changes. A number of pathology studies indicated cerebellar Purkinje cell pathology. ET is a heterogeneous disorder, possibly indicating different underlying disease mechanisms. Familial cortical myoclonic tremor with epilepsy (FCMTE), with evident Purkinje cell degeneration, can be an ET mimic. Here, we investigate whole brain and, more specifically, cerebellar morphological changes in hereditary ET, FCMTE, and healthy controls. Anatomical magnetic resonance images were preprocessed using voxel-based morphometry. Study 1 included voxel-wise comparisons of 36 familial, propranolol-sensitive ET patients, with subgroup analysis on age at onset and head tremor, and 30 healthy controls. Study 2 included voxel-wise comparisons in another nine ET patients, eight FCMTE patients, and nine healthy controls. Study 3 compared total cerebellar volume between 45 ET patients, 8 FCTME patients, and 39 controls. In our large sample of selected hereditary ET patients and ET subgroups, no local atrophy was observed compared to healthy controls or FCMTE. In ET patients with head tremor, a volume increase in cortical motor regions was observed. In FCMTE, a decrease in total cerebellar volume and in local cerebellar gray matter was observed compared to healthy controls and ET patients. The current study did not find local atrophy, specifically not in the cerebellum in hereditary ET, contrary to FCMTE. Volume increase of cortical motor areas in ET patients with head tremor might suggest cortical plasticity changes due to continuous involuntary head movements.

Keywords: Cerebellum; Essential tremor; FCMTE; MRI; VBM; Volumetry.

Fig. 1

Spiral drawings from an ET and FCMTE patient. Spirals drawn with the right hand by an ET and an FCMTE patient

Fig. 2

Study 1—cortical volume increase in ET patients with head tremor. Increased volume in ET patients with head tremor compared to ET patients without head tremor. Increased volume is mainly confined to the bilateral precentral gyrus and right superior medial gyrus. Cluster-wise inference (P< 0.05 (FWE corrected), cluster-forming threshold P < 0.001). Results are projected on the ch2better template in sagittal, coronal, and axial views (MRIcroN, http://www.mccauslandcenter.sc.edu/mricro/mricron)

Fig. 3

Study 2—cerebellar volume reduction in FCMTE. Cerebellar VBM results show volume reduction in FCMTE compared to healthy controls and ET patients. Cluster-wise inference (P < 0.05 (FWE corrected), cluster-forming threshold P < 0.001). Results are projected on the SUIT atlas [42]

Fig. 4

Study 3—total cerebellar volume. Total cerebellar volume of combined subjects from studies 1 and 2. Dot plots of total cerebellar volume for ET patients, FCMTE patients, and controls, respectively. P values based on two-sided t tests