Frontal lobe volume in patients with Huntington's disease

Abstract

Neuropathologic and neuroimaging studies have suggested that frontal lobes are affected in Huntington's disease (HD), and that atrophy in this region may be associated with some of the cognitive impairment and clinical decline observed in patients with HD. We measured gray and white matter volumes within the frontal lobes on MRI for 20 patients with HD (10 mildly affected and 10 moderately affected) and 20 age- and sex-matched control subjects. We also correlated frontal lobe measurements with measures of symptom severity and cognitive function. Patients who were mildly affected had frontal lobe volumes (both gray and white matter) essentially identical to those of control subjects, despite clearly abnormal basal ganglia. Patients who were moderately affected demonstrated significant reductions in total frontal lobe volume (17%) and frontal white matter volume (28%). Frontal lobe white matter volume reductions, but not total frontal lobe volume reductions, were disproportionately greater than overall brain volume reductions (17%). Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after taking into account total brain volume. We conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy, but this association is not specific to the frontal lobes. Frontal lobe atrophy (like total brain atrophy) occurs in later stages of increasing HD symptom severity and this atrophy primarily involves white matter.

Regional Distribution and Clinical Correlates of White Matter Structural Damage in Huntington Disease: A Tract-Based Spatial Statistics Study

“…32 Regional atrophy of the cerebral WM in the periventricular and subinsular regions in the internal capsule and cerebellum was reported in previous volumetric MR imaging studies in presymptomatic and symptomatic HD carriers. [3][4][5][6][7][8][9] Hence the distribution of GM and WM atrophy reflecting irreversible tissue loss in our series of patients with HD is in line with prior reports.…”

“…21 This includes evaluation of motor symptoms and 3 selected timed tests, 22 namely Verbal Fluency, Stroop ColorWord Interference 23 and Symbol Digit tests, 24 which are sensitive to frontal-striatal dysfunction in HD 21 and showed correlation with cerebral WM volume. 4,7 The clinical stages as determined by their total functional capacity score were also determined by using the criteria defined by Shoulson and Fahn. 25 These 5 stages take into account an individual's engagement in an occupation; the ability to handle financial affairs, manage domestic responsibilities, and perform activities of daily living; and his or her need for care facilities.…”

“…2 However, MR imaging studies demonstrated that atrophy of the cerebral WM is already detectable in presymptomatic or early symptomatic HD carriers [3][4][5][6] and is variably advanced in symptomatic HD. [7][8][9] Moreover several diffusion-weighted imaging and DTI studies revealed microstructural damage of the residual WM in HD. [10][11][12][13][14] A role for WM damage has been proposed in explaining the varying and complex symptoms of this condition.…”

Mouse behavioral mutants have neuroimaging abnormalities

“…Certainly the increased use of diagnostic imaging tools in the clinic indicates the growing value of anatomical visualization in clinical diagnostics. Already, characteristic neuroanatomical changes in several human diseases have been demonstrated (Aylward et al, 1997(Aylward et al, , 1998Gaser et al, 1999;Giedd et al, 1994;Hynd et al, 1991;Jack et al, 1997). However, it is important to note that the genetic homogeneity in studies of inbred mice presents a unique advantage that greatly improves the statistical power of mouse studies.…”

“…Large-scale human studies of disease populations have revealed that imaging findings of this type are often characteristic of individual diseases or disease processes. Examples include schizophrenia [Gaser et al, 1999], Alzheimer disease [Jack et al, 1992[Jack et al, , 1997], Huntington's disease [Aylward et al, 1997[Aylward et al, , 1998Jernigan et al, 1991], and attention-defecit hyperactivity disorder [Giedd et al, 1994;Hynd et al, 1991]. Furthermore, symptoms detected by neuroimaging can frequently be correlated with behavioral manifestations of disease [Backman et al, 1997;Kwon et al, 2003;Hohol et al, 1997;Zivadinov et al, 2001].…”