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Background: High-frequency stimulation of the subthalamic nucleus (STN-DBS) improves motor symptoms in advanced Parkinson's disease (PD), but the mechanisms are still unclear. Functional imaging evidenced pathological overactivity in motor cortical areas in advanced PD that can be normalized by effective therapies., Patients and Methods: We studied resting state cerebral blood flow pre-operatively and 12 months after surgery in 40 patients with advanced PD using ECD-SPECT. SPECT scans were also acquired 1 year apart in 21 matched PD controls who did not undergo surgery. Statistical analysis was performed using statistical parametric mapping (SPM2) software. In addition, we correlated brain perfusion changes after surgery with clinical improvement, assessed using the unified PD rating scale motor score (UPDRS-III)., Results: Patients showed marked motor improvement and medication reduction after surgery. Stimulated PD patients revealed bilateral rCBF decrements in motor cortical areas and prefrontal cortex bilaterally compared to pre-surgical condition as well as versus PD controls (p<.01 FDR corrected). Perfusion increases were found in cerebellum, temporal and occipital lobes. Clinical improvement was associated with perfusion decrements in primary motor and premotor cortices., Conclusions: Effective STN-DBS is associated with neuronal activity changes in brain regions implicated in movement programming and performance. We hypothesize that clinical benefit might be associated with stimulation-induced normalization of the abnormal overactivity within the cortico-basal ganglia-thalamo-cortical motor loop in advanced PD.

Background and Methods: We used (123)I-Ioflupane SPECT to study 32 unrelated patients with essential tremor (16 with positive familial history), 47 sporadic tremor dominant patients with Parkinson's disease and 31 healthy control subjects. Discriminant analysis was used to categorize healthy subjects and patients with Parkinson's disease or essential tremor., Results: Patients with essential tremor had higher uptake values (50% putamen and 21% caudate, P<0.001) compared to those with Parkinson's disease but lower than healthy subjects (15% putamen and 21% caudate, P<0.05). Discriminant analysis classified seven essential tremor patients in the healthy subjects cohort (22%) and two as Parkinson's disease (6%)., Conclusions: Our results show that some essential tremor patients may present mild abnormalities of striatal dopamine transporters and a typical Parkinson's disease-like pattern of uptake loss. These findings suggest a link between the two disorders.

Extradural motor cortex stimulation (EMCS) has been proposed as alternative to deep brain stimulation (DBS) in the treatment of Parkinson's disease (PD). Its mechanisms of action are still unclear. Neuroimaging evidenced motor cortical dysfunction in PD that can be reversed by therapy. We performed left hemisphere EMCS surgery in six advanced PD patients fulfilling CAPSIT criteria for DBS with the exception of age >70 years. After 6 months, we measured regional cerebral blood flow (rCBF) at rest with SPECT and Tc-99m cysteinate dimer bicisate off-medication with stimulator off and on. Clinical assessment included Unified Parkinson's Disease Rating Scale part II and III, Abnormal Involuntary Movement Scale and mean dopaminergic medication dosage. We used statistical parametric mapping for imaging data analysis. Clinically we observed no mean changes in motor scales, although blinded evaluation revealed some benefit in individual patients. We found significant rCBF decrements in the pre-central gyrus, pre-motor cortex and caudate nucleus bilaterally, left prefrontal areas and right thalamus. Perfusion increments were found in cerebellum bilaterally. EMCS determined significant modulation of neuronal activity within the cortico-basal ganglia-thalamo-cortical motor loop in our cohort of advanced PD patients. However, these effects were paralleled by mild and variable clinical efficacy.

We performed [123I]FP-CIT/SPECT in 20 drug-naive Parkinson's disease (PD) patients, 10 with unilateral akinesia/rigidity at onset (arPD) and 10 with additional tremor-at-rest (tPD), to evaluate whether resting tremor at onset is associated with differences in striatal dopamine transporter binding. Patients of the two cohorts were matched for age, disease duration (<3 years) and severity of non-tremor motor symptoms; 31 healthy participants served as controls. Mean striatal dopamine transporter binding reduction in PD patients vs. controls was 42% for arPD and 50% for tPD; mean ipsilateral striatum and caudate nucleus uptake values were lower by 12 and 24%, respectively, in tPD than arPD. We conclude that widespread degeneration of the nigrostriatal dopaminergic pathway might be necessary for the development of parkinsonian tremor-at-rest.

We prospectively evaluated 20 patients with Parkinson's disease (PD) preoperatively and 12 months after subthalamic nucleus-deep brain stimulation (STN-DBS). All patients had clinical (UPDRS III) and neuropsychological evaluations as well as brain perfusion SPECT-ECD. Clinical and cognitive data were compared with 12 matched PD patients who had not undergone surgery. STN-DBS patients improved in motor symptoms and reduced medications but selectively declined in category fluency (p<0.01). No clinical and cognitive changes were found in the control group at follow-up. Worsening fluency was associated with perfusion decrements in left dorsolateral prefrontal cortex, anterior cingulate cortex and ventral caudate nucleus (p<.001).

We used 123I-Ioflupane SPECT to study striatal dopamine transporter (DAT) binding in 36 Parkinson's disease (PD) patients with history of severe occupational exposure to hydrocarbons. Data were compared with 38 PD patients without exposure history as well as healthy controls. Both PD cohorts showed significant striatal uptake decrements compared with controls. We found significantly lower values in the whole striatum of exposed compared with non-exposed patients (0.83 +/- 0.25 vs. 1.05 +/- 0.39; P = 0.004), more pronounced in the putamen (0.61 +/- 0.24 vs. 0.85 +/- 0.42; P = 0.004). We conclude that severe occupational exposure to hydrocarbons may modify disease course and ultimately accelerate nigro-striatal denervation.

We measured striatal dopamine transporter binding using [(123)I]ioflupane and SPECT in patients with Parkinson's disease associated with the LRRK2 (PARK8) Gly2019Ser gene mutation (LRRK2-PD) and in gene-negative patients with idiopathic Parkinson's disease (IPD) of comparable disease duration and severity. The LRRK2-PD group consisted of a total of 10 patients (3 sporadic) with mean age 62 +/- 14 years, disease duration 9 +/- 3 years, and UPDRS III motor score 21.60 +/- 6.65. The control IPD group consisted of 15 patients with mean age 59 +/- 9 years, disease duration 9 +/- 5 years, and UPDRS III motor score 23.80 +/- 8.69. [(123)I]ioflupane-specific uptake ratios were calculated for caudate nucleus and putamen using the occipital cortex as reference region. We found no differences between the LRRK2-PD group and IPD in all items studied. In particular, putamen and caudate uptake values as well as side asymmetry indexes and putamen/caudate ratios all revealed comparable between-group values. We conclude that in these patients carrying the LRRK2 Gly2019Ser mutation, the neurodegenerative process results in a pattern of nigrostriatal dopaminergic dysfunction similar to that observed in IPD., ((c) 2006 Movement Disorder Society)

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.

Deep brain Stimulation (DBS) is an effective treatment for patients with advanced Parkinson's disease (PD) and motor complications who can no longer be improved by adjustment of medical therapy. Selection of surgery candidates and follow-up after surgery are critical for good outcome. Functional neuroimaging can help in the clinical assessment of these patients. We have used single photon emission computed tomography (SPECT) and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the subthalamic nucleus (STN) in 20 patients with advanced PD. We found a significant increase in the anterior cingulate/supplementary motor cortex in the 12 good responders (change in off unified UPDRS >50%). Conversely, patients with poor response (n=8; change in off UPDRS-III <50% following DBS) revealed a significant worsening of cortical hypoperfusion particularly in the prefrontal areas. No flow decrements were detected in the basal ganglia and in the thalamus in both groups during DBS stimulation suggesting that DBS does not have a "lesion like" effect. If DBS stimulates and does not inactivate STN projection neurons, flow reduction in the poor responders may be secondary to increased inhibitory basal ganglia output.

Positron emission tomography (PET) and network analysis have been used to identify a reproducible pattern of regional metabolic covariation that is associated with idiopathic Parkinson's disease (PD). The activity of this PD-related pattern can be quantified in individual subjects and used to discriminate PD patients from atypical parkinsonians. Because PET is not commonly available, we sought to determine whether similar discrimination could be achieved using more routine single photon emission computed tomography (SPECT) perfusion methods. Twenty-three subjects with PD (age, 63 +/- 9 years), 22 subjects with multiple system atrophy (MSA; age, 64 +/- 7 years), and 20 age-matched healthy controls (age, 62 +/- 13 years) underwent SPECT imaging of regional cerebral perfusion with Tc-99m ethylene cysteinate dimer (ECD). Using network analysis, we determined whether a PD-related pattern existed in the SPECT data, and whether its expression discriminated PD from MSA patients. Additionally, we compared the accuracy of group discrimination achieved by this pattern with that of the PET-derived PD-related pattern applied to the SPECT data. Network analysis of the SPECT data identified a significant pattern characterized by relative increases in cerebellar, lentiform, and thalamic perfusion covarying with decrements in the frontal operculum and in the medial temporal cortex. Subject scores for this pattern discriminated PD patients from controls (P < 0.01) and from MSA patients (P < 0.03). Subject scores for the PET-derived PD-related pattern computed in the individual SPECT scans more accurately distinguished PD patients from controls (P < 0.005) and from MSA patients (P = 0.0002). A significant PD-related covariance pattern can be identified in SPECT perfusion data. Moreover, the disease related pattern identified previously with PET can be applied to individual SPECT perfusion scans to provide group discrimination between PD patients, healthy controls, and individuals with MSA. Because of significant individual subject overlap between groups, however, the clinical utility of this method in the differential diagnosis of Parkinsonism remains uncertain., (Copyright 2002 Movement Disorder Society)

Cognitive abnormalities have been reported in a large percentage of patients with Parkinson's disease (PD). Often cognitive changes are sub-clinical and involve frontal lobe function. In other occasions they develop into full dementia. Functional neuroimaging may help characterize these abnormalities. We have studied brain perfusion with SPECT and the tracer ECD in 44 PD patients, 22 presenting with normal cognitive function and 22 with clinical and neuropsychological signs of dementia. Compared with 21 healthy controls, demented PD patients showed significant perfusion decrements in all cortical areas, particularly temporal and parietal regions; in the non-demented cohort reductions were limited to the frontal lobe area. These results suggest that brain perfusion abnormalities are present in PD patients. It is speculated that different pathological mechanisms underlie perfusion differences.