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Biomedical subjects

V Sturm

Publications and source records attributed to V Sturm.

At least 19 recordsLinked to original sources

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.

Adolescent↗

Deep brain stimulation of the subthalamic nucleus reversibly deteriorates stuttering in advanced Parkinson's disease.

The etiology of developmental stuttering is still unknown. In some patients, stuttering re-emerges or is aggravated with the onset of Parkinson's disease (PD). We here report on a patient with PD treated by deep brain stimulation of the subthalamic nucleus and severe deterioration of stuttering under effective stimulation. Positron emission tomography (PET) of regional cerebral blood flow (rCBF) in stimulation on- and off-conditions showed overactivation of cerebral and cerebellar motor systems during speech activation and was in line with recent PET studies investigating brain activation during stuttering. The abnormal rCBF pattern increased in the stimulation on-condition and was associated with a marked worsening of stuttering. Clinical and imaging findings in this patient support the hypothesis that the basal ganglia circuitry plays an important role in the pathophysiology of stuttering.

Antiparkinson Agents↗

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.

Acoustic Stimulation↗

Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation.

OBJECTIVES: Glutamate mediated excitotoxicity of the hyperactive subthalamic nucleus (STN) has been reported to contribute to nigral degeneration in Parkinson's disease (PD). Deep brain stimulation of the STN (STN DBS), in its role as a highly effective treatment of severe PD motor complications, has been thought to inhibit STN hyperactivity and therefore decrease progression of PD. METHODS: In a prospective two centre study, disease progression was determined by means of serial (18)F-fluorodopa (F-dopa) positron emission tomography (PET) in 30 patients with successful STN DBS over the first 16 (SD 6) months after surgery. RESULTS: Depending on the method of PET data analysis used in the two centres, annual progression rates relative to baseline were 9.5-12.4% in the caudate and 10.7-12.9% in the putamen. CONCLUSIONS: This functional imaging study is the first to demonstrate a continuous decline of dopaminergic function in patients with advanced PD under clinically effective bilateral STN stimulation. The rates of progression in patients with STN DBS were within the range of previously reported data from longitudinal imaging studies in PD. Therefore this study could not confirm the neuroprotective properties of DBS in the STN target.

Aged↗

The influence of head frame distortions on stereotactic localization and targeting.

A strong attachment of a stereotactic head frame to the patient's skull may cause distortions of the head frame. The aim of this work was to identify possible distortions of the head frame, to measure the degree of distortion occurring in clinical practice and to investigate its influence on stereotactic localization and targeting. A model to describe and quantify the distortion of the Riechert-Mundinger (RM) head frame was developed. Distortions were classified as (a) bending and (b) changes from the circular ring shape. Ring shape changes were derived from stereotactic CT scans and frame bending was determined from intraoperative stereotactic x-ray images of patients with implanted 125I-seeds acting as landmarks. From the examined patient data frame bending was determined to be 0.74 mm+/-0.32 mm and 1.30 mm in maximum. If a CT-localizer with a top ring is used, frame bending has no influence on stereotactic CT-localization. In stereotactic x-ray localization, frame bending leads to an overestimation of the z-coordinate by 0.37 mm+/-0.16 mm on average and by 0.65 mm in maximum. The accuracy of patient positioning in radiosurgery is not affected by frame bending. But in stereotactic surgery with an RM aiming bow trajectory displacements are expected. These displacements were estimated to be 0.36 mm+/-0.16 mm (max. 0.74 mm) at the target point and 0.65 mm+/-0.30 mm (max. 1.31 mm) at the entry point level. Changes from the circularring shape are small and do not compromise the accuracy of stereotactic targeting and localization. The accuracy of CT-localization was found to be close to the resolution limit due to voxel size. Our findings for frame bending of the RM frame could be validated by statistical analysis and by comparison with an independent patient examination. The results depend on the stereotactic system and details of the localizers and instruments and also reflect our clinical practice. Therefore, a generalization is not possible. Preliminary experience with a new MR-compatible RM head frame made of ceramics shows no frame distortions as with the conventional frame made of an Al-Cu-Mg alloy.

Algorithms↗

Radiosurgery for cerebral arteriovenous malformations in hereditary hemorrhagic telangiectasia.

The authors evaluated the efficacy of radiosurgery (RS) for cerebral arteriovenous malformations in hereditary hemorrhagic telangiectasia (HHT AVMs). Two patients with seven HHT AVMs were treated by linear accelerator-RS. Complete obliteration was achieved 18 to 24 months post-treatment without side effects. Because HHT AVMs are small and multiple, RS is superior to microsurgery because it is noninvasive and all AVMs can be treated in one session regardless of their location.

Adult↗

MR-guided stereotactic neurosurgery--comparison of fiducial-based and anatomical landmark transformation approaches.

For application in magnetic resonance (MR) guided stereotactic neurosurgery, two methods for transformation of MR-image coordinates in stereotactic, frame-based coordinates exist: the direct stereotactic fiducial-based transformation method and the indirect anatomical landmark method. In contrast to direct stereotactic MR transformation, indirect transformation is based on anatomical landmark coregistration of stereotactic computerized tomography and non-stereotactic MR images. In a patient study, both transformation methods have been investigated with visual inspection and mutual information analysis. Comparison was done for our standard imaging protocol, including t2-weighted spin-echo as well as contrast enhanced t1-weighted gradient-echo imaging. For t2-weighted spin-echo imaging, both methods showed almost similar and satisfying performance with a small, but significant advantage for fiducial-based transformation. In contrast, for t1-weighted gradient-echo imaging with more geometric distortions due to field inhomogenities and gradient nonlinearity than t2-weighted spin-echo imaging, mainly caused by a reduced bandwidth per pixel, anatomical landmark transformation delivered markedly better results. Here, fiducial-based transformation yielded results which are intolerable for stereotactic neurosurgery. Mean Euclidian distances between both transformation methods were 0.96 mm for t2-weighted spin-echo and 1.67 mm for t1-weighted gradient-echo imaging. Maximum deviations were 1.72 mm and 3.06 mm, respectively.

Algorithms↗

Iris pigment epithelial cells: a possible cell source for the future treatment of neurodegenerative diseases.

For the treatment of neurodegenerative disorders such as Parkinson's disease cell or gene therapeutical options are increasingly verified. For such approaches, neural stem cells or astrocytes are discussed as possible cell candidates. As also fetal retinal pigment epithelial cells have been successfully tested for such therapeutical options, we investigated the potential of iris pigment epithelial cells as an autologous source for future cell replacement therapies. Using the ELISA technique, we looked for the secretion of neurotrophic factors under basal and stimulated conditions by iris pigment epithelial cells (IPE) cells and compared them with the secretion of retinal pigment epithelial cells (RPE) cells. As iron plays a causative role in cell death during Parkinson's disease, the iron-binding capacity by IPE cells was investigated. Furthermore, we checked the integrative capacity of IPE cells after transplantation into the striatum of adult rats. Our data reveal that IPE cells produce and secrete a variety of neurotrophic factors which can be stimulated after treatment with cytokines. Following transplantation, the cells can be easily detected by their pigmentation, survive for at least 8 weeks and as shown by electron microscopy integrate within the host tissue. Moreover, cells can be transduced with high efficiency using a third generation adenoviral vector, making them promising vehicles to locally deliver therapeutic proteins for the treatment of neurodegenerative diseases in a combined cell and gene therapeutical approach.

Animals↗

Geometrical and dosimetrical characterization of the photon source using a micro-multileaf collimator for stereotactic radiosurgery.

A micro-multileaf collimator (microMLC) for stereotactic radiosurgery is used for determination of the spatial intensity distribution of the photon source of a linear accelerator. The method is based on grid field dose measurements using film dosimetry and is easy to perform. Since the microMLC does not allow 'direct' imaging of the photon source, special software has been developed to analyse grid field measurements. Besides the source-density function, grid field analysis yields the position of the focal spot in the room laser coordinate system of the linear accelerator and the position of the treatment head rotation axis and the inclination angle of the leaf bank. Thus the method can be used for base dosimetry and for quality assurance in radiosurgery using a microMLC.

Algorithms↗

Acute demyelination: diagnostic difficulties and the need for brain biopsy.

BACKGROUND: Despite the rapid development in neuro-imaging over the past two decades, ring like contrast-enhancing lesions on CCT or MRI still may pose a diagnostic challenge. The main differential diagnoses of these lesions include metastatic carcinoma, high-grade glioma and brain abscess. Acute demyelination seldom turns out to be the underlying pathology. METHOD: Retrospective analysis was done on six patients with acute demyelination treated at our neurosurgical department between 1990 and 2001. Clinical, radiological, PET, intra-operative and histological findings were evaluated. FINDINGS: In five patients, the diagnosis of acute demyelination was established by histopathological evaluation of stereotactic biopsy specimen, in the sixth patient following microsurgical extirpation of the lesion. Neuropathology revealed demyelination with the presence of myelin-phagocytosing macrophages. In addition, lymphocytic infiltrates were present. Symptoms and signs improved significantly after high-dose steroid therapy. CONCLUSIONS: Despite CNS tissue destruction, necrosis and cyst formation are not usually found in demyelinating disease, being rather more common in young patients with ring-like contrast-enhancing lesions on CCT and MRI. Though an incorrect diagnosis can lead to a potentially fatal therapeutic intervention, histological diagnosis should be made in all cases. Due to minimum morbidity, stereotactic biopsy is the method of choice to obtain representative specimens for histological diagnosis. Open microsurgery of these lesions is not indicated since conservative medical treatment with steroids results in a favourable outcome in most cases.

Acute Disease↗

Effects of pallidal deep brain stimulation and levodopa treatment on reaction-time performance in Parkinson's disease.

Basal ganglia-thalamocortical circuits play an important role in movement preparation and execution. Tracer, single-cell, and lesion studies in monkeys suggest the existence of topologically segregated motor and nonmotor basal ganglia cortical circuits. In this study we used deep brain stimulation (DBS) of the posteroventrolateral globus pallidus internus (GPi) in patients with Parkinson's disease to elucidate the function of the GPi in human sensorimotor behavior. This question was investigated by comparing the influence of DBS on patients' performance in various reaction-time tasks that differed with respect to cognitive but not motor requirements. As a main result, DBS improved performance on the different tasks independently of the complexity of the involved cognitive processing functions. Furthermore, the observed effects did not depend on the modality of the processed information. These results suggest that the functional state of the posteroventrolateral GPi selectively affects the motor stage in simple sensorimotor acts, because this stage was the only stage involved in all investigated tasks. In addition to DBS, we manipulated the levodopa medication state of the PD patients. In contrast to DBS, levodopa effects on reaction times were less consistent. Levodopa improved reaction times in choice reaction tasks significantly, while affecting reaction times in a simple reaction task to a lesser extent. Error analysis revealed that the medication-dependent reaction-time improvement in the choice reaction tasks was accompanied by an increase in errors, suggesting a shift of the speed-accuracy criteria of the patients. A similar pattern of results was not observed for the DBS effects. Taken together, our data are in agreement with recent findings in monkeys that indicate a topological organization of the GPi in which motor functions are localized in posterolateral regions apart from cognitive regions. Furthermore, our data show a way to uncover the subcortical-cortical circuitry serving human sensorimotor behavior.

Acoustic Stimulation↗

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

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 Parkinson's 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 Parkinson's 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 dollars 20,810, EURO 20,410, GB pounds 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 dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Aged↗

Deep brain stimulation of the subthalamic nucleus versus levodopa challenge in Parkinson's disease: measuring the on- and off-conditions with FDG-PET.

In order to compare the effects of high-frequency stimulation of the subthalamic nucleus (STN-DBS) and a levodopa-challenge on cerebral metabolic activity, we conducted PET scans with [(18)F]2-fluoro-2-deoxyglucose (FDG) in the drug- and stimulation- on- and off-condition in a single patient suffering from advanced PD. Our data revealed evidence for improved thalamocortical processing released from inhibition by overactive basal ganglia output nuclei in both on-conditions. While levodopa also led to a reduction of lentiform hyperactivity, effective STN stimulation seemed to interfere with distinct cerebellar and limbic circuits.

Aged↗

Intracerebral transplantation and successful integration of astrocytes following genetic modification with a high-capacity adenoviral vector.

To investigate the ability of genetically modified astrocytes to integrate into adult rat brain, two spontaneously immortalized cell lines and the allogenic nontumorigenic glioma cell line F98 were transduced with a high-capacity adenoviral vector (HC-Adv) expressing the EGFP gene from the hCMV promoter. In organotypic slice cultures the transduced astrocytes were shown to integrate into the brain tissue. Following transplantation of the transduced astrocytes into the striatum of adult rats, the transplanted cells survived at least for 6 weeks, continuously expressed the EGFP transgene, in close neighborhood with cells of the recipient tissue executing their differentiation capacity along the glial lineage. Thus, HC-Adv transduced astrocytes are promising vehicles to locally deliver therapeutic proteins for the treatment of neurodegenerative diseases.

Adenoviridae↗

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.

Activities of Daily Living↗

Effects of bilateral pallidal or subthalamic stimulation on gait in advanced Parkinson's disease.

Bilateral high-frequency stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) both alleviate akinesia, rigidity, and tremor in idiopathic Parkinson's disease. To test the specific effect of these procedures on gait, we used quantitative gait analysis in addition to relevant subscores of the Unified Parkinson's Disease Rating Scale in a group of 10 patients with advanced Parkinson's disease treated by GPi stimulation and eight patients treated by STN stimulation. Patients were assessed before and 3 months after surgery. Thirty age-matched healthy subjects served as controls. The non-random selection allowed a descriptive but no direct statistical comparison of the respective procedure. Gait analysis showed significant stimulation-induced improvements of spatiotemporal gait and step parameters in both patient groups. Moreover, the effects on step length and cadence suggested a differential effect of both basal ganglia targets. Hence, the increase in gait velocity in the STN group was almost exclusively due to a significant increase in step length, while in the GPi group statistically non-significant increases in both step length and cadence contributed.

Aged↗

Brachytherapy: Results of two different therapy strategies for patients with primary glioblastoma multiforme.

BACKGROUND: In the current study, the authors describe and compare two different strategies of brachytherapy for the treatment of patients with primary glioblastoma multiforme (GBM). METHODS: The study was comprised of 84 patients. Forty-five patients were implanted with permanent or temporary low activity iodine-125 ((125)I) seeds in Cologne and 21 patients were implanted with temporary iridium-192 ((192)Ir) wires in Amsterdam. Both groups received external beam radiation therapy (EBRT); the (125)I group received 10-30 grays (Gy) with the implant in situ and the (192)Ir group received 60 Gy before implantation. In Cologne, implantation was performed after a diagnostic stereotactic biopsy whereas in Amsterdam implantation took place after cytoreductive diagnostic surgery. In addition, 18 patients in Amsterdam served as a control group. This group received only EBRT after cytoreductive surgery. RESULTS: In both groups the mean age of the patients was between 50-55 years, with 80% of the patients age > 45 years. The mean implantation volume encompassed by the referenced isodose was 23 cm(3) for (125)I and 48 cm(3) for (192)Ir. Initial dose rates were 2. 5-2.9 centigrays (cGy)/hour for permanent (125)I, 4.6 cGy/hour for temporary (125)I, and 44-100 cGy/hour (mean, 61 cGy) for (192)Ir. A total dose of 50-60 Gy, 60-80 Gy, and 40 Gy, respectively, was administered at the outer margins of the tumor. The median survival was approximately 16 months for both the (125)I group and the (192)Ir group. This was 6 months longer than the median survival in the control group. Reoperations were performed in 4 patients in the (125)I group (9%) versus 7 patients in the (192)Ir group (33%). No complications or late reactions were reported in the (125)I group, whereas one case of hemorrhage and three cases of delayed stroke were observed in the (192)Ir group. CONCLUSIONS: The equal median survival times in these two brachytherapy groups with such different dose rate radiation schedules support the hypothesis that dose rate does not play a major role in the survival of patients with primary GBM.

Adult↗