Cerebral and muscle MRI abnormalities in myotonic dystrophy.

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.

High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes.

OBJECTIVE: Previous studies have observed disruptions in brain white and gray matter structure in individuals with type 1 diabetes, and these structural differences have been associated with neurocognitive testing deficiencies. This study investigated the relationship between cerebral cortical thickness reductions and white matter microstructural integrity loss in a group of patients with type 1 diabetes and in healthy control subjects using diffusion tensor imaging (DTI). RESEARCH DESIGN AND METHODS: Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects underwent structural T1 and proton-density and DTI on a 3.0 Tesla scanner. Fractional anisotropy measurements were made on major cerebral white matter tracts, and DTI tractography was performed to identify cortical regions with high connectivity to these tracts. RESULTS: Posterior white matter tracts with reduced fractional anisotropy (optic radiations, posterior corona radiata, and the splenium region of the corpus callosum) were found to have high connectivity with a number of posterior cortical regions, including the cuneus, precuneus, fusiform, and posterior parietal cortical regions. A significant reduction in cortical thickness in the diabetic group was observed in the regions with high connectivity to the optic radiations and posterior corona radiata tracts (P < 0.05). CONCLUSIONS: The direct relationship between white and gray matter structural pathology has not been previously demonstrated in subjects with long-standing type 1 diabetes. The relationship between posterior white matter microstructural integrity disruption and lower cortical thickness demonstrated using a novel DTI connectivity technique suggests a common or interrelated pathophysiological mechanism in type 1 diabetes.

Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function.

OBJECTIVE: Long-standing type 1 diabetes is associated with deficits on neurocognitive testing that suggest central white matter dysfunction. This study investigated whether diffusion tensor imaging (DTI), a type of magnetic resonance imaging that measures white matter integrity quantitatively, could identify white matter microstructural deficits in patients with long-standing type 1 diabetes and whether these differences would be associated with deficits found by neurocognitive tests. RESEARCH DESIGN AND METHODS: Twenty-five subjects with type 1 diabetes for at least 15 years and 25 age- and sex-matched control subjects completed DTI on a 3.0 Tesla scanner and a battery of neurocognitive tests. Fractional anisotropy was calculated for the major white matter tracts of the brain. RESULTS: Diabetic subjects had significantly lower mean fractional anisotropy than control subjects in the posterior corona radiata and the optic radiation (P < 0.002). In type 1 diabetic subjects, reduced fractional anisotropy correlated with poorer performance on the copy portion of the Rey-Osterreith Complex Figure Drawing Test and the Grooved Peg Board Test, both of which are believed to assess white matter function. Reduced fractional anisotropy also correlated with duration of diabetes and increased A1C. A history of severe hypoglycemia did not correlate with fractional anisotropy. CONCLUSIONS: DTI can detect white matter microstructural deficits in subjects with long-standing type 1 diabetes. These deficits correlate with poorer performance on selected neurocognitive tests of white matter function.

Brain macrostructural and microstructural abnormalities in cocaine dependence.

RATIONALE: Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found evidence of brain abnormalities in white matter. OBJECTIVE: Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. METHODS: Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. RESULTS: DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. CONCLUSIONS: Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures.

Susceptibility of retinal vascular endothelium to infection with Toxoplasma gondii tachyzoites.

PURPOSE: Retinochoroidal infection with the protozoan parasite Toxoplasma gondii is the most common cause of posterior uveitis worldwide. Tachyzoites spread throughout the body through the blood stream and lymphatics, but preferentially encyst in the eye and other parts of the central nervous system (CNS). It is unknown whether T. gondii penetrates the CNS selectively or whether these sites of immune privilege have limited capacity to eradicate the parasite. METHODS: Human vascular endothelial cell lines, including retinal (three lines from three different donors), aortic, umbilical vein, and dermal microvascular endothelium, as well as human foreskin fibroblasts, were grown to confluence in 24-well plates. Cells were incubated with RH-strain T. gondii tachyzoites in the presence of [(3)H]-uracil. Trichloroacetic acid-insoluble radioactivity was measured as an index of T. gondii proliferation, because tachyzoites, but not human cells, incorporate uracil directly through pyrimidine salvage. RESULTS: Tachyzoites showed higher [(3)H]-uracil incorporation after incubation with retinal vascular endothelial cells in comparison with aortic (55% more), umbilical vein (33% more) and dermal (34% more) endothelial cells. In eight separate assays, significantly greater radioactivity was measured for tachyzoites cultured with retinal versus other cell subtypes (P < 0.05), except for one assay in which differences reached only borderline significance (P