Voxel-based comparison of regional cerebral glucose metabolism between PSP and corticobasal degeneration

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Abstract

Objectives: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders that may be accompanied by dementia and parkinsonism as clinical symptoms. The purpose of this study was to elucidate cerebral metabolic differences of these two diseases with cognitive impairments by [18F] fluorodeoxyglucose (FDG) and positron emission tomography (PET). Methods: A total of 12 patients with PSP (age: 62.8±6.0 years old, m: 7, f: 5, Mini-Mental State Examination (MMSE): 23.4±2.6), 12 patients with CBD (age: 64.8±6.3 years old, m: 6, f: 6, MMSE: 22.9±4.5), and age-matched healthy subjects (normal control (NC)) (age: 63.8±7.7 years old, m: 7, f: 5) were subjected to FDG-PET to obtain glucose metabolic images. We compared regional cerebral metabolic images by a voxel-by-voxel analysis with statistical parametric mapping (SPM) among PSP, CBD, and NC subjects, and evaluated differences of hypometabolic regions. Results: The patients with PSP showed reduced cerebral glucose metabolism in the medial and lateral frontal gyri, basal ganglia, and midbrain compared with NC, whereas the patients with CBD showed significant reduction in the parietal lobes (p<0.001). SPM also revealed parietal hypometabolism in CBD patients compared with PSP patients (p<0.001). Conclusions: The predominant parietal glucose metabolic reduction in CBD patients was different from previously reported findings. This finding would be the characteristic substance of patients with CBD accompanying cognitive impairments. Our findings suggest that measurement of glucose metabolism by PET and a voxel-based analysis is useful to understand the pathophysiology of these two diseases with cognitive impairments.

Introduction

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative disorders of middle and late age presenting with dementia and parkinsonism. The neurological features of PSP included impaired ocular motility, pseudobulbar palsy, and axial dystonia, while those of CBD include asymmetric rigidity of the limbs, myoclonus, alien limb sign, and localized cortical signs such as apraxia or cortical sensory loss. The clinical syndromes of typical cases of PSP and CBD are distinct, although atypical cases are described that have overlapping clinical and pathologic features. Several pathologic features, such as astrocytic lesions and ballooned neurons, differentiate PSP from CBD, although both diseases share several neuropathological features including filamentous tau inclusions in neurons and glia and biochemical alterations in the tau protein. Several clinical, pathological, and molecular features rationalize the concept of sporadic form of tauopathy. Nevertheless, there are sufficient differences to continue the present-day trend to consider PSP and CBD as separate disorders [1], [2].

These two diseases are sometimes difficult to distinguish on clinical grounds. Functional neuroimagings such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) may help to differentiate CBD from PSP. A number of studies with PET and SPECT have demonstrated cerebral metabolism or perfusion abnormalities in PSP and CBD, separately. CBD patients are characterized by an asymmetric hypometabolism mainly in the sensorimotor and parietal cortices and the thalamus, while PSP patients are characterized by a global metabolic reduction mainly in the frontal lobes and the basal ganglia. However, only a few studies have made direct comparisons of the two diseases [3], [4], [5], [6], and there are some discrepancies in the results of these studies. The disagreement among the studies may be due to the use of groups of patients that were not matched in terms of age, cognitive impairment, or hemisphere that was most affected. The purpose of the present study was to delineate the pathophysiological difference between PSP and CBD by using fluorodeoxyglucose (FDG)-PET. By a voxel-by-voxel analysis, we compared two groups equivalent for age, gender, cognitive impairment, and hemisphere that was most affected.

Section snippets

Subjects

A total of 12 patients with probable PSP diagnosed by NINDS-SPSP International Workshop [7] and 12 patients with probable CBD that fulfilled the criteria of the CBD Multicenter Case-Control Study (CBDMCCS) [8] were selected from patients who were admitted to our hospital for examination of cognitive impairment. The two groups were matched for age and scores on the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale (ADAS). The PSP patients consisted of seven males and

Results

Asymmetry was positive in 10 of the 12 patients with CBD, and mirror PET images were made for 5 CBD patients with a right predominance. Of the 12 patients with PSP, 1 had a left predominance and, as a result, there was no need for preparing mirror images. None of the healthy controls had hemispheric asymmetry.

In the PSP group, cerebral glucose metabolism was significantly decreased in the anterior cingulate gyrus, inferior frontal gyrus, caudate nucleus, and midbrain compared with the control

Discussion

In patients with PSP, glucose metabolism was decreased in the lateral and medial frontal lobes, caudate nucleus, and midbrain as compared with age-matched healthy controls. These findings were consistent with those of previous ROI-based studies and a voxel-based study. In PSP, the basal ganglia and brain stem are the main loci of pathological changes, while the cortical regions have only a slight pathological involvement [22]. However, there seems to be agreement among previous functional

Conclusions

In PSP patients, the metabolic reduction is dominant in the frontal lobe, while in CBD patients, the metabolic reduction is dominant in the parietal lobe. These differences in glucose metabolism appear to reflect the pathological and clinical differences between these two diseases that are especially characterized by cognitive impairments. These findings suggest that measurement of glucose metabolism by PET followed by a voxel-based analysis is useful to understand pathophysiology of these two

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