Jürgen Voges

Safety and efficacy of pallidal or subthalamic nucleus stimulation in advanced PD

The authors retrospectively compared 1-year results of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN; n = 16) and internal pallidum (GPi) (n = 11) in advanced PD and found about equal improvements in “off” period motor symptoms, dyskinesias, and fluctuations. STN stimulation reduced medication requirements by 65% and required significantly less electrical power. These advantages contrasted with a need for more intensive postoperative monitoring and a higher incidence of adverse events related to levodopa withdrawal.

11C-methionine PET for differential diagnosis of low-grade gliomas

Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

Long-term results of bilateral pallidal stimulation in Parkinson's disease

We followed up 11 patients for up to 5 years after bilateral pallidal deep brain stimulation for advanced Parkinsons disease. Dyskinesias remained significantly reduced until the last assessment. The initial improvement of off‐period motor symptoms and fluctuations, however, was not sustained and gradually declined. Beneficial effects of pallidal deep brain stimulation on activities of daily living in the on‐ and off‐period were lost after the first year. Replacement of pallidal electrodes into the subthalamic nucleus in four patients could restore the initial benefit of deep brain stimulation and allowed a significant reduction of dopaminergic drug therapy.

Delineation of Brain Tumor Extent with [11C]l-Methionine Positron Emission Tomography Local Comparison with Stereotactic Histopathology

Purpose: Methyl-[11C]l-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. Experimental Design: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. Results: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). Conclusions: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery—experiences from a single centre

Objective: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. Methods: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). Results: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. Conclusions: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients’ prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

Thirty days complication rate following surgery performed for deep-brain-stimulation

Serious adverse events (SAEs) during the first 30 postoperative days after stereotactic surgery for Deep‐Brain‐Stimulation performed in 1,183 patients were retrospectively collected from five German stereotactic centers. The mortality rate was 0.4% and causes for death were pneumonia, pulmonary embolism, hepatopathy, and a case of complicated multiple sclerosis. The permanent surgical morbidity rate was 1%. The most frequently observed SAEs were intracranial hemorrhage (2.2%) and pneumonia (0.6%). Skin infection occurred in 5 of 1,183 patients (0.4%). Surgical complications caused secondary AEs (e.g. pneumonia) preferentially in older patients and in patients treated for Parkinsons disease (PD). Complication rates did not differ among the five centers.

Risk analysis of linear accelerator radiosurgery.

PURPOSE To evaluate the toxicity of stereotactic single-dose irradiation and to compare the own results with already existing risk prediction models. METHODS AND MATERIALS Computed tomography (CT) or magnetic-resonance (MR) images, and clinical data of 133 consecutive patients treated with linear accelerator radiosurgery were analyzed retrospectively. Using the Cox proportional hazards model the relevance of treatment parameters and dose-volume relationships on the occurrence of radiation-induced tissue changes (edema, localized blood-brain barrier breakdown) were assessed. RESULTS Sixty-two intraparenchymal lesions (arteriovenous malformation (AVM): 56 patients, meningioma: 6 patients) and 73 skull base tumors were selected for analysis. The median follow-up was 28.1 months (range: 9.0-58.9 months). Radiation-induced tissue changes (32 out of 135, 23.7%) were documented on CT or MR images 3.6-58.7 months after radiosurgery (median time: 17.8 months). The actuarial risk at 2 years for the development of neuroradiological changes was 25.8% for all evaluated patients, 38.4% for intraparenchymal lesions, and 14.6% for skull base tumors. The coefficient: total volume recieving a minimum dose of 10 Gy (VTREAT10) reached statistical significance in a Cox proportional hazards model calculated for all patients, intraparenchymal lesions, and AVMs. In skull base tumors, the volume of normal brain tissue covered by the 10 Gy isodose line (VBRAIN10) was the only significant variable. CONCLUSIONS These results demonstrate the particular vulnerability of normal brain tissue to single dose irradiation. Optimal conformation of the therapeutic isodose line to the 3D configuration of the target volume may help to reduce side effects.

Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial

BACKGROUND Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial. METHODS In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259). FINDINGS An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to -20·8 points (SD 17·1; -47·9%; n=40) at 6 months; -26·5 points (19·7; -61·1%; n=31) at 3 years; and -25·1 points (21·3; -57·8%; n=32). The improvement from 6 months to 3 years (-5·7 points [SD 8·4]; -34%) was significant and sustained at the 5-year follow-up (-4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae. INTERPRETATION 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. FUNDING Medtronic.

Successful treatment of chronic resistant alcoholism by deep brain stimulation of nucleus accumbens: first experience with three cases.

1 Depar tment of Psychiatry, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 2 Depar tment of Stereotaxy and Functional Neurosurgery, Univ ersity of Cologne, Cologne, Germany 3 Depar tment of Stereotactic Neurosurgery, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 4 Depar tment of Neurology, Otto-von-Guericke-University of Magdeburg, Magdeburg, Germany 5 eibni L z Institutor ef NeurobiologyMagde , burGerman g, y Treatment of alcohol dependence remains one of the biggest challenges in psychiatry, since only about half of all patients achieve long-term abstinence by the currently available thera-pies. Dysfunction of the nucleus accumbens, one of the main areas of the brain ’ s reward system, seems to play a central role in addiction and treatment resistance. Following the recent ad-vances of neuromodulation therapy by deep brain stimulation, we designed an o

Ten-Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson's disease.

Recently, a pathological oscillatory network at 10 Hz including several motor areas was described in patients with idiopathic Parkinsons disease (PD). In 7 PD patients, we tested the clinical effect of subthalamic nucleus (STN) stimulation at varying frequencies 1 to 3 years after implantation of electrodes. STN stimulation at 10 Hz induced significant worsening of motor symptoms, especially akinesia, compared with no stimulation and therapeutic stimulation (≥130 Hz). This finding indicates the clinical relevance of pathological 10 Hz synchronization in PD.