Background: The investigation of disease progression provides important information on the dynamics of cell death in Parkinson disease (PD).Objective: To determine the progression of dopaminergic impairment in PD with the use of positron emission tomography (PET).Design: Longitudinal prospective cohort study with a follow-up period of 64.5 ± 22.6 months (mean ±SD).Setting: University hospital. Patients: A consecutive sample of patients with PD (N=31; age at symptom onset, 53.6 ± 11.3 years) with a wide range of symptom duration and severity at the time of study entry. Interventions: Investigation by serial fluorodopa F 18 ([ 18 F]fluorodopa) PET as a marker for striatal dopaminergic function. Main Outcome Measures: Changes in caudate and putaminal [ 18 F]fluorodopa influx constant (K i ) values.Results: In patients with PD, the decline rate of putaminal [ 18 F]fluorodopa K i correlated inversely with disease duration before study inclusion (r=−0.46, P =.01) and positively with baseline K i values (r =0.44, P =.01), indicating a negative exponential loss of dopamine neurons. Annual disease progression rates ranged from 4.4% in the caudate nucleus to 6.3% in the putamen. A mean preclinical period of 5.6±3.2 years was calculated with symptom onset at a putaminal K i threshold of 69% from controls. Assuming nonlinear progression kinetics, the required sample size to prove neuroprotection with the use of [ 18 F]fluorodopa PET was found to increase strongly with the preceding symptom duration of study subjects. Conclusion:These data suggest that the neurodegenerative process in PD follows a negative exponential course and slows down with increasing symptom duration, contradicting the long-latency hypothesis of PD.
Thrombolysis with rtPA was effectively applied in routine management of stroke patients in a community-based approach with acceptable efforts and without additional costs. Under these circumstances, outcome and complication rates were comparable to those of multicenter trials.
Crossed cerebellar diaschisis (CCD) is well described in the chronic phase of stroke, but few data describe acute CCD and its serial changes after reperfusion. Using positron emission tomography (PET), we studied acute CCD with respect to supratentorial perfusion and outcome measures. In 19 acute stroke patients receiving intravenous thrombolysis (<3 h), 15O-water PET assessed CCD and supratentorial hypoperfusion volume before thrombolysis, 3, 24 h and 14 days later. Infarct volume at day 14 and NIHSS score at 3 months were assessed. Supratentorial hypoperfusion decreased from 25 cm3 (median) before thrombolysis to 0.1 cm3 at day 14. Baseline CCD was 13.4% and decreased continuously to 6.1% after 14 days. The NIHSS score decreased from 11 to 4 pts after 3 months. Infarct volume was 1.1 cm3. Crossed cerebellar diaschisis correlated to the hypoperfusion volume within the first 24 h after stroke, but not later. Hypoperfusion correlated to outcome measures at the early stage only. In contrast, CCD correlated to outcome values at all four measurements. Reperfusion with recovery of CCD was seen in patients with small infarcts and good clinical outcome and vice versa. Our data suggest that (i) CCD occurs as early as 3 h after stroke and might be reversible; (ii) acute CCD is closely related to the volume of supratentorial hypoperfusion. At later time points, however, CCD is disconnected from supratentorial perfusion but strongly associated to outcome measures; (iii) CCD is not susceptible to nonnutritional reperfusion and adds valuable information to interpret supratentorial reperfusion patterns.
Background and Purpose-Functional neuroimaging studies have demonstrated right inferior frontal gyrus (IFG) activation in poststroke aphasia. It remains unclear whether this activation is essential for language performance. We tested this hypothesis in a positron emission tomography (PET) activation study during a semantic task with repetitive transcranial magnetic stimulation (rTMS) on right-handed patients experiencing poststroke aphasia and examined whether rTMS stimulation over the right and left IFG would interfere with language performance. Methods-Eleven patients with left-sided middle cerebral arterial infarction, 50 to 75 years of age, were tested with the Aachen Aphasia Test Battery and underwent 15 O-H 2 O PET activation during a semantic task within 2 weeks after stroke. PET activation images were coregistered to T1-weighted MRIs. Stimulation sites were determined on renderings of head and brain over the maximum activation within left and right IFG. rTMS was performed with 20% maximum output (2.1 T), 10-s train duration, at 4Hz frequency. A positive rTMS effect was defined as an increased reaction time latency or error rate in the semantic task. Results-PET activations of the IFG were observed on the left (3 patients) and bilaterally (8 patients). Right IFG stimulation was positive in 5 patients with right IFG activation, indicating essential language function. In a verbal fluency task, these patients had a lower performance than patients without right-sided TMS effect. Conclusions-In some poststroke aphasics, right IFG activation is essential for residual language function. However, its compensatory potential seems to be less effective than in patients who recover left IFG function. These results suggest a hierarchy in recovery from poststroke aphasia and a (limited) compensatory potential of the nondominant hemisphere.
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