The metabolic pathology of dopa‐responsive dystonia

Asanuma, Kotaro; Ma, Yilong; Huang, Chaorui; Carbon-Correll, Maren; Edwards, Christine; Raymond, Deborah; Bressman, Susan; Moeller, James R.; Eidelberg, David

doi:10.1002/ana.20442

Cited by 57 publications

(54 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have found that this disease is associated with a specific spatial covariance pattern involving metabolic abnormalities in basal ganglia thalamocortical functional/anatomic pathways (Eidelberg et al, 1994(Eidelberg et al, , 1997. Indeed, this PD-related covariance pattern (PDRP) has been detected in multiple independent patient populations scanned in the resting condition (Moeller et al, 1999;Feigin et al, 2002;Lozza et al, 2004;Asanuma et al, 2005).…”

Section: Introductionmentioning

confidence: 97%

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Tang

Spetsieris

et al. 2007

J Cereb Blood Flow Metab

Self Cite

280

385

View full text Add to dashboard Cite

Parkinson's disease (PD) is associated with an abnormal pattern of regional brain function. The expression of this PD-related covariance pattern (PDRP) has been used to assess disease progression and the response to treatment. In this study, we validated the PDRP network as a measure of parkinsonism by prospectively computing its expression (PDRP scores) in 15 O-water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans from PD patients and healthy volunteers. The reliability of this measure was also assessed within subjects using a test-retest design in mildly affected and advanced PD patients scanned at baseline and during treatment with levodopa or deep brain stimulation (DBS). We found that PDRP expression was significantly elevated in PD patients (P < 0.001) relative to controls in a prospective analysis of brain scans obtained with either H 2 15 O or FDG PET. A significant correlation (R 2 = 0.61; P < 0.001) was evident between PDRP scores computed from H 2 15 O and FDG images in PD subjects scanned with both tracers. Test-retest reproducibility was very high (intraclass correlation coefficient (ICC) > 0.92) for PDRP scores measured both within PET session and between sessions separated by up to 2 months. This high reproducibility was observed in both early stage and advanced PD patients scanned at baseline and during treatment. The within-subject variability of this measure was less than 10% for both unmedicated and treated conditions. These findings suggest that the PDRP network is a reproducible and stable descriptor of regional functional abnormalities in parkinsonism. The quantification of PDRP expression in PD patients can serve as a potential biomarker in PET intervention studies for this disorder.

show abstract

Section: Introductionmentioning

confidence: 97%

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Tang

Spetsieris

et al. 2007

J Cereb Blood Flow Metab

Self Cite

280

385

View full text Add to dashboard Cite

show abstract

“…Using this network-modeling approach, we have found that PD patients express an abnormal metabolic pattern characterized by increased pallido-thalamic and pontine activity associated with relative reductions in cortical motor regions (Eidelberg et al, 1994(Eidelberg et al, , 1997cf., Carbon et al, 2003a). To date, this PD-related pattern (PDRP) has been detected in eight independent patient populations (Moeller et al, 1999;Feigin et al, 2002;Lozza et al, 2004;Asanuma et al, 2005;Eckert et al, in press) and its expression has been found to be highly reproducible in individual subjects (Ma et al, in press). In addition to accurately discriminating between PD patients and controls (Asanuma et al, 2005;Ma et al, in press), PDRP expression has been found to correlate consistently with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores (Eidelberg et al, 1995;Lozza et al, 2004;Asanuma et al, 2006) and with clinical responses to therapy (e.g., Trošt et al, 2006;Asanuma et al, 2006;cf., Carbon et al, 2003a;Eckert and Eidelberg, 2005).…”

Section: Introductionmentioning

confidence: 99%

Metabolic brain networks associated with cognitive function in Parkinson's disease

et al. 2007

Self Cite

View full text Add to dashboard Cite

The motor manifestations of Parkinson's disease (PD) have been linked to an abnormal spatial covariance pattern involving basal ganglia thalamocortical pathways. By contrast, little is known about the functional networks that underlie cognitive dysfunction in this disorder. To identify such patterns, we studied 15 non-demented PD patients using FDG PET and a voxel-based network modeling approach. We detected a significant covariance pattern that correlated (p< 0.01) with performance on tests of memory and executive functioning. This PD-related cognitive pattern (PDCP) was characterized by metabolic reductions in frontal and parietal association areas and relative increases in the cerebellar vermis and dentate nuclei. To validate this pattern, we analyzed data from 32 subsequent PD patients of similar age, disease duration and severity. Prospective measurements of PDCP activity predicted memory performance (p<0.005), visuospatial function (p<0.01), and perceptual motor speed (p<0.005) in this validation sample. PDCP scores additionally exhibited an excellent degree of test-retest reliability (intraclass correlation coefficient, ICC=0.89) in patients undergoing repeat FDG PET at an 8-week interval. Unlike the PD-related motor pattern, PDCP expression was not significantly altered by antiparkinsonian treatment with either intravenous levodopa or deep brain stimulation (DBS). These findings substantiate the PDCP as a reproducible imaging marker of cognitive function in PD. Because PDCP expression is not altered by routine antiparkinsonian treatment, this measure of network activity may prove useful in clinical trials targeting the progression of non-motor manifestations of this disorder.

show abstract

“…In particular, network analyses of regional PET data have consistently revealed the presence of a reproducible abnormal spatial covariance pattern associated with parkinsonism (Eidelberg et al, 1994;Moeller et al, 1999;Lozza et al, 2004;Asanuma et al, 2005a). This PD-related pattern (PDRP) is characterized by pallido-thalamic and pontine hypermetabolism associated with relative metabolic decrements in premotor, prefrontal, and posterior parietal cortical regions (Carbon and Eidelberg, 2002;Asanuma et al, 2005a). We have attributed this abnormal metabolic topography to overactivity of internal pallidal (GPi) afferents from STN and consequent increases in inhibitory pallidal outflow to the ventral thalamus and pons (Eidelberg et al, 1994(Eidelberg et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

et al. 2006

Self Cite

View full text Add to dashboard Cite

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning.We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation.These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

show abstract

The metabolic pathology of dopa‐responsive dystonia

Cited by 57 publications

References 18 publications

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Abnormal Metabolic Network Activity in Parkinson'S Disease: Test—Retest Reproducibility

Metabolic brain networks associated with cognitive function in Parkinson's disease

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

Contact Info

Product

Resources

About