Dirk Hellwig

Neurostimulation for Parkinson's Disease with Early Motor Complications

BACKGROUND Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinsons disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinsons disease. METHODS In this 2-year trial, we randomly assigned 251 patients with Parkinsons disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinsons Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinsons Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS Subthalamic stimulation was superior to medical therapy in patients with Parkinsons disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

18F-Deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis

PURPOSE 18F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. METHODS AND MATERIALS Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. RESULTS In 12/34 cases, the shape and/or size of the portals were changed, primarily (n = 10) the size of the fields was reduced. The median area of CP was 182 cm2 versus 167 cm2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p = 0.03). CONCLUSION In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particularly for patients with tumor-associated dys- or atelectasis.

18F-FDG PET for Mediastinal Staging of Lung Cancer: Which SUV Threshold Makes Sense?

18F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. Methods: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after 18F-FDG PET (90–150 min after 250 MBq of 18F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (− − − through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. Results: SUVs in metastatic lymph nodes were higher (mean ± SD, 7.1 ± 4.5; range, 1.4–26.9; n = 70) than in tumor-free lymph node stations (2.4 ± 1.7; range, 0.6–14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 ± 2.0; range, 0.8–14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 ± 0.022; SUV, 0.899 ± 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. Conclusion: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on 18F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.

Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy

BACKGROUND In patients with bronchogenic carcinoma, mediastinal lymph node staging is essential for determining treatment options. In this retrospective analysis we compared the results of positron emission tomography (PET) using F-18 fluorodeoxyglucose with those of mediastinoscopy in nodal staging for suspected bronchogenic carcinoma. METHODS From March 1997 to June 2001, 102 patients (86 male,16 female, age 62 +/- 9 years) underwent both PET and mediastinoscopy for radiologically suspected mediastinal lymph node disease in bronchogenic carcinoma. Total body emission scans were acquired 90 to 150 minutes after injection of 230 MBq of F-18 fluorodeoxyglucose. Mediastinoscopic evaluation of lymph node stations was performed according to the method of Mountain and Dresler (1R, 1L, 2L, 2R, 4L, 4R,7). Patients were eligible if surgical staging was performed within 6 weeks after the PET scan. RESULTS. Of the 102 patients, benign lesions were diagnosed in 15. In 87 patients malignant disease was proven by histology, and bronchogenic carcinoma was found in 82. Of 469 nodal stations analyzed, malignancy was documented by histology in 84. In PET analysis 79 true-positive and 304 true-negative samples were found. Five lymph node stations were false negative, and 81 samples were false positive. False-positive findings in PET frequently were seen in inflammatory lung disease. The sensitivity of PET was 94.1%, specificity was 79% with a diagnostic accuracy of 81.6%. The positive predictive value of PET was 49.3%, and the negative predictive value was 98.4%. CONCLUSIONS In patients with positive PET scan results histologic verification appears necessary for exact lymph node staging. In view of the negative predictive value mediastinoscopy can be omitted in patients with bronchogenic carcinoma whose PET scan results were negative.

Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease.

Summary.In idiopathic Parkinson’s disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I-123]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p<0.01). Contralateral putamen and caudate nucleus FP-CIT uptake correlated significantly with severity of rigidity (p<0.01) and hypokinesia (p<0.01) but not with severity of resting or postural tremor (p>0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor.

Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer

PurposeThe differentiation of recurrent lung cancer and post-therapeutic changes remains a problem for radiological imaging, but FDG-PET allows biological characterisation of tissues by visualising glucose metabolism. We evaluated the diagnostic performance and prognostic impact of FDG-PET in cases of suspected relapse of lung cancer.MethodsIn 62 consecutive patients, 73 FDG-PET scans were performed for suspected recurrence after surgical therapy of lung cancer. FDG uptake by lesions was measured as the standardised uptake value (SUV). PET results were compared with the final diagnosis established by biopsy or imaging follow-up. SUV and clinical parameters were analysed as prognostic factors with respect to survival.ResultsFDG-PET correctly identified 51 of 55 relapses and gave true negative results in 16 of 18 remissions (sensitivity, specificity, accuracy: 93%, 89%, 92%). SUV in recurrent tumour was higher than in benign post-therapeutic changes (10.6±5.1 vs 2.1±0.6, p<0.001). Median survival was longer for patients with lower FDG uptake in recurrent tumour (SUV<11: 18 months, SUV≥11: 9 months, p<0.01). Long-term survival was observed mainly after surgical re-treatment (3-year survival rate 38%), even if no difference in median survival for surgical or non-surgical re-treatment was detected (11 vs 12 months, p=0.0627). For patients subsequently treated by surgery, lower FDG uptake predicted longer median survival (SUV<11: 46 months, SUV≥11: 3 months, p<0.001). SUV in recurrent tumour was identified as an independent prognostic factor (p<0.05).ConclusionFDG-PET accurately detects recurrent lung cancer. SUV in recurrent tumour is an independent prognostic factor. FDG-PET helps in the selection of patients who will benefit from surgical re-treatment.

Myocardial sympathetic degeneration correlates with clinical phenotype of Parkinson's disease

In idiopathic Parkinsons disease (PD), different clinical subtypes are distinguished due to predominant motor symptoms: a tremor‐dominant type (TDT), an akinetic rigid type (ART), and a mixed type (MT). We compared myocardial sympathetic innervation, measured by MIBG scintigraphy, in different subtypes of PD at early and advanced stages of PD. We applied MIBG scintigraphy in 102 patients with PD. About 57 patients were at Hoehn and Yahr (H&Y) stage 1, 22 at H&Y stage 2, and 23 at H&Y stages 3 and 4. For quantification of myocardial MIBG uptake, the heart‐to‐mediastinum (H/M) count‐ratio was calculated. At all H&Y stages, myocardial MIBG uptake was significantly higher in TDT patients than in ART or MT patients (P < 0.05; ANOVA). Furthermore, at each H&Y stage, myocardial MIBG uptake correlated significantly with severity of hypokinesia (P < 0.05; Spearmans correlation) and rigidity (P < 0.05), but not with severity of resting or postural tremor. The significant correlation between myocardial sympathetic degeneration and severity of hypokinesia and rigidity suggests that myocardial sympathetic degeneration and hypokinetic‐rigid symptoms develop in a closely coupled manner in early as well as advanced PD. No such correlation can be found between myocardial sympathetic degeneration and parkinsonian tremor.

Target volume definition for 18F-FDG PET-positive lymph nodes in radiotherapy of patients with non-small cell lung cancer

PurposeFDG PET is increasingly used in radiotherapy planning. Recently, we demonstrated substantial differences in target volumes when applying different methods of FDG-based contouring in primary lung tumours (Nestle et al., J Nucl Med 2005;46:1342–8). This paper focusses on FDG-positive mediastinal lymph nodes (LNPET).MethodsIn our institution, 51 NSCLC patients who were candidates for radiotherapy prospectively underwent staging FDG PET followed by a thoracic PET scan in the treatment position and a planning CT. Eleven of them had 32 distinguishable non-confluent mediastinal or hilar nodal FDG accumulations (LNPET). For these, sets of gross tumour volumes (GTVs) were generated at both acquisition times by four different PET-based contouring methods (visual: GTVvis; 40% SUVmax: GTV40; SUV=2.5: GTV2.5; target/background (T/B) algorithm: GTVbg).ResultsAll differences concerning GTV sizes were within the range of the resolution of the PET system. The detectability and technical delineability of the GTVs were significantly better in the late scans (e.g. p = 0.02 for diagnostic application of SUVmax = 2.5; p = 0.0001 for technical delineability by GTV2.5; p = 0.003 by GTV40), favouring the GTVbg method owing to satisfactory overall applicability and independence of GTVs from acquisition time. Compared with CT, the majority of PET-based GTVs were larger, probably owing to resolution effects, with a possible influence of lesion movements.ConclusionFor nodal GTVs, different methods of contouring did not lead to clinically relevant differences in volumes. However, there were significant differences in technical delineability, especially after early acquisition. Overall, our data favour a late acquisition of FDG PET scans for radiotherapy planning, and the use of a T/B algorithm for GTV contouring.

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus

Abstract.Objective: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinsons disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. Methods: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinsons disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. Results: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US

Clinical Value of Iodine-123-Alpha-Methyl-l-Tyrosine Single-Photon Emission Tomography in the Differential Diagnosis of Recurrent Brain Tumor in Patients Pretreated for Glioma at Follow-Up

20,810, EURO 20,410, GB£ 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7±21.8 (US