Decrease in Gray Matter in ET

A clinical investigative study of cerebral and cerebellar gray matter in patients with essential tremor (ET) using voxel-based morphometric (VBM) analysis supports the concept of ET as progressive and diffuse in nature.

Think of a voxel, an element on a grid that indicates volume, as a cube in three dimensions rather than a pixel (or dot) in two dimensions. With VBM, the neuroimaging analysis uses magnetic resonance imaging (MRI) scans to generate data and compare statistics in order to identify volume differences in brain anatomy between groups of subjects. The data can be used to infer the presence of atrophy or, less commonly, tissue expansion in subjects with disease.

The study, published in the Journal of Neuroimaging, was developed and administered by a team of doctors from the Department of Neuroimaging and Interventional Radiology and Department of Neurology, National Institute of Mental Health & Neurosciences, Bangalore, India.

Evidence suggests that the cerebellum, a region of the brain that controls coordination of voluntary motor movement, balance and equilibrium, is involved in the generation of tremor in ET. Using VBM analysis, researchers studied the pattern of morphological changes in the brain of ET patients and evaluated structural differences between subtypes of ET.

Once the patients were scanned, their data was evaluated using VBM analysis. Differences in cerebral gray matter were compared in the following groups: Between ET patients and controls, ET patients with and without head tremor, and familial and non-familial ET patients. All patients had limb tremor with or without head or voice tremor.

After studying the images and comparing them between ET patients and controls, researchers found gray matter (GM) atrophy in multiple areas of the cerebellar and cerebral hemispheres.

A subgroup comparison between ET patients with and without head tremor revealed significant areas of GM atrophy in multiple areas, but no differences in cerebellar GM was evident. The findings state:

If head tremor patients are considered [an] advanced form of ET then our result shows that head tremor patients do not harbor significant cerebellar changes when compared to those without head tremor. In other words, there is no relationship between head tremor and cerebellar GM loss.

The report suggests that ET patients with head tremor may represent a distinct clinical phenotype of ET.

No areas of significant difference were found between ET patients with and without family history of the condition. The findings note that this result has limitations given that it was “difficult to evaluate all the family members of ET patients and reservations of patients in accepting their illness as familial.”

The doctors conclude in the study that VBM analysis of patients with ET showed extensive cortical GM and cerebellar atrophy, which supports the neurodegenerative nature of the disease. Further, more extensive cortical degenerative changes were found in patients with head tremor in addition to limb tremor, which suggests that this subgroup may represent a distinct subtype of ET.

The significance of these findings needs to be determined by revalidation of the findings using a larger study group.