Brain structural changes in essential tremor: Voxel-based morphometry at 3-Tesla

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Abstract

Background

Abnormalities in cerebello-thalamo-cortical pathways have been suggested as a basis for essential tremor (ET). Two voxel-based morphometry (VBM) studies, each using a 1.5-T magnet, evaluated ET patients, leading to contradictory results. Using a 3-T magnet, we assessed whether white or gray matter changes occurred in ET patients vs. controls.

Methods

We recruited 19 ET patients (mean age 69.8 ± 9.4 years) and 20 age and gender-matched controls. 3-T MRI data were analyzed using the Statistical Parametric Mapping (SPM) 5 package.

Results

In case–control comparisons, white matter changes were seen in several areas (right cerebellum, left medulla, right parietal lobe, and right limbic lobe); gray matter changes were seen in several areas as well (bilateral cerebellum, bilateral parietal lobes, right frontal lobe, and right insula) (p < 0.001, uncorrected at a voxel level). Compared with controls, ET patients with severe tremor had white matter changes in the midbrain, both occipital lobes, and right frontal lobe, and gray matter changes bilaterally in the cerebellum (p < 0.001, uncorrected at a voxel level).

Conclusions

Structural white and gray abnormalities may be detected in ET patients using VBM and a high-field MRI scanner. Such changes may be related to the pathological substrates associated with this disease.

Introduction

Essential tremor (ET) is one of the most common adult neurological disorders [1], [2] yet its pathogenesis is not well understood [3], [4]. Clinical and imaging studies point to cerebellar involvement and the tremor is thought to be mediated by a neuronal loop involving cerebello-thalamo-cortical pathways [3], [4]. Moreover, recent post-mortem studies provide evidence of degenerative changes in the cerebellum in many cases [5], [6], [7], with a six-fold increase in Purkinje cell axonal swellings (torpedoes) and an approximately 40% reduction in the number of Purkinje cells [7]. In contrast to post-mortem studies, magnetic resonance imaging (MRI) studies provide a non-invasive method to examine structural changes in living patients who have not yet arrived at an end-stage of disease. Yet brain structural changes in this disease have not been studied in great detail using new MRI sequences.

Voxel-based morphometry (VBM) is a fully automated and unbiased whole-brain method, which assesses regional differences between subjects in white matter and gray matter [8]. Two VBM studies, each using a 1.5-T magnet, evaluated ET patients, and these lead to contradictory results [9], [10]. In one, the authors did not demonstrate cerebellar gray or white matter changes [9]. In contrast, a more recent VBM study showed marked atrophy of the cerebellar vermis in ET patients with head tremor [10].

The introduction of 3-T magnets to the clinical arena has improved the ability to detect central nervous system disturbances; this is due to an increased signal-to-noise ratio. This gain in signal-to-noise ratio, in contrast to that of 1.5 T imaging, may also be used to decrease scan times [11], [12], [13]. Decreased scan times in 3 T MR can reduce data artifacts related to patient motion in subjects who are unable to or who have difficulty holding still during the MRI process. Early concerns that field strength may decrease contrast-to-noise ratio are unfounded when using axial 3D T1-weighted inversion-recovery fast gradient echo sequences [13].

In the present study, we applied VBM analysis to brain images acquired with a 3-T magnet to investigate whether changes in white or gray matter are present in ET patients compared with matched controls.

Section snippets

Participants and evaluation

ET patients were recruited consecutively in the month of October 2006 from two outpatient neurology clinics in Madrid: Móstoles General Hospital and University Hospital “Príncipe de Asturias”. A 10 to 20 minute, semi-structured tremor interview was conducted in which demographic information and data on tremor (e.g., age of onset) were collected. Each patient was examined using a standardized tremor examination [14]. This examination included one test of postural tremor and five tests of kinetic

Results

Of 21 eligible ET patients, two were excluded because they refused. None were excluded because of neurological comorbidities or structural abnormalities on conventional MRI images. Of the 24 eligible controls, four were excluded prior to VBM analyses because they had pathological findings on MRI, including low-grade glioma (one control), bilateral subdural hygromas (one control), severe cerebellar atrophy in the setting of chemotherapy (one control), and multiple white matter hyperintense

Discussion

Using VBM analysis on brain images obtained with a 3-T magnet, our ET patients had significant changes in white or gray matter when compared with matched controls.

Such changes were primarily located bilaterally in the cerebellum, right frontal lobe, left medulla, parietal lobes, right insula, and right limbic lobe. In additional analyses of the subgroup of ET patients with severe tremor, bilateral changes in the cerebellum and the right frontal lobe were again observed.

Clinical, neuroimaging

Acknowledgments

The authors would like to thank Pablo García-Polo for his technical assistance.

Dr. Benito-León is supported by an educational grant from Fundación Mutua Madrileña. Dr. Louis is supported by NIH R01 NS042859 and R01 NS039422 from the National Institutes of Health, Bethesda, MD.

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