A Voxel-Based Morphometric Study of Adult Onset Primary Focal Dystonia

Nathaniel J. Killian¹, Kevin Black², Biology Department, Washington University, St. Louis, MO¹, Neuro-Imaging Laboratories, Mallickrodt Institute of Radiology, Washington University School of Medicine².

Dystonia is a neurological syndrome involving sustained or intermittent involuntary muscle contractions. These contractions usually involve twisting or turning about a joint, or abnormal postures, and may affect one or more parts of the body. Generalized dystonia typically begins at an early age, but dystonia that affects localized regions (focal dystonia), such as dystonic hand cramp or blepharospasm (involuntary eyelid contractions), typically arises in adulthood.

Idiopathic dystonia is distinguished from secondary dystonias (such as those caused by birth injury, stroke, or drug reaction) by the lack of identifiable etiology (Fahn, 1993). In other words, no obvious lesion is seen on radiological (physician) examination of magnetic resonances images (MRIs). However, visible brain lesions can cause secondary dystonia, and there is some evidence of more subtle tissue abnormalities detectable on MRI in primary focal dystonia (Schneider et al., 1994).

We hypothesized that a consistent but subtle abnormality in gray matter in a localized region of brain (most likely striatum) is present in patients with adult-onset primary focal dystonia and will be detected by appropriate analysis of MR images of brain in patients and matched controls. T1-weighted MRI images were acquired for 32 patients with adult-onset primary focal dystonia and 32 normal controls matched for sex, age (within 5 years), and handedness. The images were analyzed according to the method of Good et al. (2001) using the SPM99 software package (Wellcome Department of Cognitive Neurology) running in Matlab 5.2 (Mathworks, Natick, MA).

The analysis employs a whole-brain unbiased technique called voxel-based morphometry (VBM). VBM is used to characterize regional cerebral volume and tissue concentration differences in structural MRI (Good et al., 2001). The method has detected gray matter abnormalities in disorders without obvious radiological abnormality such as narcolepsy (B. Draganski et al., 2002), and has been validated with respect to volume measurements of specific brain regions in various studies.

Using statistical parametric mapping in SPM99 we compared the gray matter volume of our two study groups (patients and controls). We found no statistically significant abnormalities in the gray matter of patients with adult-onset primary focal dystonia after stringent correction for multiple comparisons. This suggests that adult-onset idiopathic focal dystonia may result from biochemical or other factors (Perlmutter et al., 1997). However, our findings do not rule out the possibility of abnormalities in white matter and CSF. Both of which should be the subjects of further analyses.