Cerebral and muscle MRI abnormalities in myotonic dystrophy

Abstract

Pathophysiological mechanisms underlying the clinically devastating CNS features of myotonic dystrophy (DM) remain more enigmatic and controversial than do the muscle abnormalities of this common form of muscular dystrophy. To better define CNS and cranial muscle changes in DM, we used quantitative volumetric and diffusion tensor MRI methods to measure cerebral and masticatory muscle differences between controls (n=5) and adults with either congenital (n=5) or adult onset (n=5) myotonic dystrophy type 1 and myotonic dystrophy type 2 (n=5). Muscle volumes were diminished in DM1 and strongly correlated with reduced white matter integrity and gray matter volume. Moreover, correlation of reduced fractional anisotropy (white matter integrity) and gray matter volume in both DM1 and DM2 suggests that these abnormalities may share a common underlying pathophysiological mechanism. Further quantitative temporal and spatial characterization of these features will help delineate developmental and progressive neurological components of DM, and help determine the causative molecular and cellular mechanisms.

Figure 1. Automated segmentation of white and gray matter and cerebrospinal fluid

Images from a single control subject illustrate the automated segmentation technique (FMRIB’s Automated Segmentation Tool or FAST) used in the calculation of cerebral volumes by tissue type: White matter is yellow, grey matter is blue, and CSF is red. This segmentation method was used for volumetric measurements, and to identify white matter in diffusion tensor imaging studies, which was then subsequently evaluated for fractional anisotropy as a measure of tissue integrity.

Figure 2. Cerebral compartments for white and gray matter analyses

Regions of interest (ROIs) defined by the investigators for the purpose of comparing cerebral volumes and regional white matter integrity across subjects. The pre-defined ROIs are shown overlaid on a T1-weighted image of a control subject for reference. The ROIs are as follows: superior frontal (SUP), inferior frontal (INF), superior to corpus callosum (ACC) and occipital (OCC).

Figure 3. Sample segmentation of lateral and medial pterygoid, masseter and temporalis muscles

Manual segmentation of lateral and medial pterygoid muscles (left), masseter (center), and temporalis (right) muscles in a sample subject.

Figure 4. Pairwise analysis of FA in four cerebral compartments

Significantly lower FA was observed in the DM1 adult onset and DM1 congenital onset groups in the cerebral, supra-callosal, inferior frontal and occipital compartments.

Figure 5. Scatterplot of FA and combined medial and lateral pterygoid muscle volumes for all subjects

The correlation between the combined medial and lateral pterygoid volume and total cerebral FA across all subjects; the Spearman’s rho statistic is 0.654 over all subjects.