Directional DBS leads show large deviations from their intended implantation orientation.

OBJECTIVE: Lead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. METHODS: The Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. RESULTS: Deviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DISCUSSION: Our results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Adverse events associated with deep brain stimulation in patients with childhood-onset dystonia.

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Voxel-based dose calculation in radiocolloid therapy of cystic craniopharyngiomas.

Very high doses are administered in radiocolloid therapy of cystic craniopharyngiomas. However individual dose planning is not common yet mainly due to insufficient image resolution. Our aim was to investigate whether currently available high-resolution image data can be used for voxel-based dose calculation for short-ranged ß-emitters ((32)P,(90)Y,(186)Re) and to assess the achievable accuracy. We developed a convolution algorithm based on voxelized dose activity distributions and dose-spread kernels. Results for targets with 5-40 mm diameter were compared with high-resolution Monte Carlo calculations in spherical phantoms. Voxel size was 0.35 mm. Homogeneous volume and surface activity distributions were used. Dose-volume histograms of targets and shell structures were compared and γ index (dose tolerance 5%, distance to agreement 0.35 mm) was calculated for dose profiles along the principal axes. For volumetric activity distributions 89.3% ± 11.9% of all points passed the γ test (mean γ 0.53 ± 0.16). For surface distributions 33.6% ± 14.8% of all points passed the γ test (mean γ 2.01 ± 0.60). The shift of curves in dose-volume histograms was -1.7 Gy ± 7.6 Gy (-4.4 Gy ± 24.1 Gy for (186)Re) in volumetric distributions and 46.3% ± 32.8% in surface distributions. The results show that individual dose planning for radiocolloid therapy of cystic craniopharyngiomas based on high-resolution voxelized image data is feasible and yields highly accurate results for volumetric activity distributions and reasonable dose estimates for surface distributions.

Whole-body kinetics and dosimetry of L-3--123I-iodo-alpha-methyltyrosine.

The synthetic amino acid L-3--123I-iodo-alpha-methyltyrosine (IMT) is currently under clinical evaluation as a single-photon emission tomography (SPET) tracer of amino acid uptake in brain tumours. So far, dosimetric data in respect of IMT are not available. Therefore we investigated the whole-body distribution of IMT in six patients with cerebral gliomas and the radiation doses were estimated. Whole-body scans were acquired at 1.5, 3 and 5 h after i.v. injection of 370-550 MBq IMT. The bladder was voided prior to each scan and the radioactivity excreted in the urine was measured. Based on the MIRD-11 method and the updated MIRDOSE3, the mean absorbed doses for various organs and the effective dose were calculated from geometric means of the anterior and posterior whole-body scans using seven source organs and the residence time. IMT was predominantly excreted by the kidneys (52.8%+/-11.5% at 1.5 h p.i., 63.0%+/-15.7% at 3 h p.i. and 74.6%+/-9.8% at 5 h p.i.). No organ system other than the urinary tract showed significant retention of the tracer. Early whole-body scans revealed slightly increased tracer uptake in the liver and in the bowel. Highest absorbed doses were found for the urinary bladder wall (0.047 mGy/MBq), the kidneys (0.010 mGy/MBq), the lower large intestinal wall (0.011 mGy/MBq) and the upper large intestinal wall (0.008 mGy/MBq). The effective dose according to ICRP 60 was estimated to be 0.0073 mSv/MBq for adults. This leads to an effective dose of 3.65 mSv in a typical brain SPET study using 500 MBq IMT. The MIRDOSE3 scheme yielded similar results. Thus, in spite of the relatively high tracer dose required for optimal brain scanning, radiation exposure in SPET studies with IMT is in the normal range of routine nuclear medicine investigations.

[Alleles in chromosome 10p21-26 in malignant gliomas]. / Allelieuntersuchungen auf Chromosom 10q21-26 in malignen Gliomen.

Loss of genetic material on chromosome 10 is regarded as a prominent feature in the genesis of glioblastomas. To use chromosome 10 deletions as diagnostic markers for glioblastomas we investigated, if the loss of chromosome 10 material could be restricted on the region 10q21-26. By PCR microsatellite analysis on frozen tissue and paraffin material from the ZULCH brain tumor collection we found (1) loss of heterozygosity in 10q21-26 in 75% of the investigated DNA from frozen tissue and (2) an interstitial loss in the region of the microsatellite marker D10S186. The combined immunohistochemical analysis of overexpression of EGFR, EGF and TGF alpha with LOH on chromosome 10 showed that chromosome 10 deletions are not exclusively bound to EGFR overexpression.

[The effect of cytokines on regeneration results of compressed nerve roots and transsected peripheral nerves]. / Die Wirkung von Zytokinen auf das Regenerationsergebnis komprimierter Nervenwurzeln und durchtrennter peripherer Nerven.

The possible beneficial effect of Interleukin-1 (IL-1) on nerve regeneration was studied using clinical, neurophysiological and histomorphological methods. The sciatic nerves of Wistar rats were transsected and the severed ends abutted, sewn together and covered with fibrin adhesive. In a second group the lumbar-sacral nerve roots were exposed, IL-1 was injected and compression of the nerve roots was carried out. The region surrounding the lesion was infused with either saline (controls) or IL-1 (treatment group) in both groups. Compared to the controls, the treated animals showed a significant improvement of nerve regeneration as measured by clinical and neurophysiological parameters. After 3 months of observation, the total number of myelinated axons distal to the site of lesion was increased, while the fiber diameter distribution was unchanged. It is likely that cloned IL-1 will soon become available for human treatment. The present results indicate that it may be worthwhile to investigate its usefulness in the treatment of peripheral nerve injury in primates and humans.