Frank Hertel

Implantation of electrodes for deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease with the aid of intraoperative microrecording under general anesthesia.

OBJECTIVEDeep brain stimulation (DBS) is widely accepted in the treatment of advanced Parkinsons disease (PD) and other movement disorders. The standard implantation procedure is performed under local anesthesia (LA). Certain groups of patients may not be eligible for surgery under LA because of clinical reasons, such as massive fear, reduced cooperativity, or coughing attacks. Microrecording (MER) has been shown to be helpful in DBS surgery. The purpose of this study was to evaluate the feasibility of MER for DBS surgery under general anesthesia (GA) and to compare the data of intraoperative MER as well as the clinical data with that of the current literature of patients undergoing operation under LA. CLINICAL PRESENTATIONThe data of nine patients with advanced PD (mean Hoehn and Yahr status, 4.2) who were operated with subthalamic nucleus (STN) DBS under GA, owing to certain clinical circumstances ruling out DBS under LA, were retrospectively analyzed. All operations were performed under analgosedation with propofol or remifentanil and intraoperative MER. For MER, remifentanil was ceased completely and propofol was lowered as far as possible. INTERVENTIONThe STN could be identified intraoperatively in all patients with MER. The typical bursting pattern was identified, whereas a widening of the baseline noise could not be as adequately detected as in patients under LA. The daily off phases of the patients were reduced from 50 to 17%, whereas the Unified Parkinsons Disease Rating Scale III score was reduced from 43 (preoperative, medication off) to 19 (stimulation on, medication off) and 12 (stimulation on, medication on). Two patients showed a transient neuropsychological deterioration after surgery, but both also had preexisting episodes of disorientation. One implantable pulse generator infection was noticed. No further significant clinical complications were observed. CONCLUSIONSTN surgery for advanced PD with MER guidance is possible with good clinical results under GA. Intraoperative MER of the STN region can be performed under GA with a special anesthesiological protocol. In this setting, the typical STN bursting pattern can be identified, whereas the typical widening of the background noise baseline while entering the STN region is obviously absent. This technique may enlarge the group of patients eligible for STN surgery. Although the clinical improvements and parameter settings in this study were within the range of the current literature, further randomized controlled studies are necessary to compare the results of STN DBS under GA and LA, respectively.

Perfusion-weighted Magnetic Resonance Imaging in Patients with Vasospasm: A Useful New Tool in the Management of Patients with Subarachnoid Hemorrhage

OBJECTIVE:Cerebral vasospasm (VSP) is one of the most important risk factors for the development of a delayed neurological deficit after subarachnoid hemorrhage (SAH). Perfusion-weighted magnetic resonance imaging (pwMRI) provides the possibility of detecting tissue at risk for infarction. The objective of our study was to evaluate the feasibility and impact of pwMRI in the management of SAH patients. METHODS:From a consecutive series of 180 patients experiencing SAH and treated at our institution over a 3-year period, we identified 20 who underwent pwMRI during their acute illness. For these 20 patients, the results of pwMRI were compared with the results of diffusion-weighted MRI, transcranial Doppler sonography, and neurological examinations performed at the same time and with repeated pwMRI examinations of the same patient at different times. RESULTS:Nineteen of 20 patients showed perfusion changes predominantly in the time maps. Fifteen of 19 patients with changes in pwMRI had a neurological deficit at the same time. In 7 of 15 patients with neurological deterioration, transcranial Doppler sonography showed signs of VSP, whereas all 15 patients showed alterations in pwMRI. The areas of perfusion changes in pwMRI correlated well with the neurological deficits of the patients and were larger than the areas of changed diffusion in diffusion-weighted MRI performed at the same time. There were no clinical complications with regard to the pwMRI examinations. CONCLUSION:pwMRI is safe and helpful in the management of patients with VSP after SAH. The sensitivity of pwMRI is higher than that of transcranial Doppler sonography in the detection of decreased perfusion as a result of VSP. pwMRI can detect tissue at risk before definitive infarction occurs and therefore may lead to a change of therapy in those patients.

Side population in human glioblastoma is non-tumorigenic and characterizes brain endothelial cells

The identification and significance of cancer stem-like cells in malignant gliomas remains controversial. It has been proposed that cancer stem-like cells display increased drug resistance, through the expression of ATP-binding cassette transporters that detoxify cells by effluxing exogenous compounds. Here, we investigated the ‘side population’ phenotype based on efflux properties of ATP-binding cassette transporters in freshly isolated human glioblastoma samples and intracranial xenografts derived thereof. Using fluorescence in situ hybridization analysis on sorted cells obtained from glioblastoma biopsies, as well as human tumour xenografts developed in immunodeficient enhanced green fluorescence protein-expressing mice that allow an unequivocal tumour-stroma discrimination, we show that side population cells in human glioblastoma are non-neoplastic and exclusively stroma-derived. Tumour cells were consistently devoid of efflux properties regardless of their genetic background, tumour ploidy or stem cell associated marker expression. Using multi-parameter flow cytometry we identified the stromal side population in human glioblastoma to be brain-derived endothelial cells with a minor contribution of astrocytes. In contrast with their foetal counterpart, neural stem/progenitor cells in the adult brain did not display the side population phenotype. Of note, we show that CD133-positive cells often associated with cancer stem-like cells in glioblastoma biopsies, do not represent a homogenous cell population and include CD31-positive endothelial cells. Interestingly, treatment of brain tumours with the anti-angiogenic agent bevacizumab reduced total vessel density, but did not affect the efflux properties of endothelial cells. In conclusion our findings contribute to an unbiased identification of cancer stem-like cells and stromal cells in brain neoplasms, and provide novel insight into the complex issue of drug delivery to the brain. Since efflux properties of endothelial cells are likely to compromise drug availability, transiently targeting ATP-binding cassette transporters may be a valuable therapeutic strategy to improve treatment effects in brain tumours.

A new rechargeable device for deep brain stimulation: a prospective patient satisfaction survey.

Background: Deep brain stimulation (DBS) is highly successful in treating Parkinson’s disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3–5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. Methods: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. Results: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. Conclusions: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.

Advanced Methods for Target Navigation using Microelectrode Recordings in Stereotactic Neurosurgery for Deep Brain Stimulation

This study describes novel methods for navigating and placing of electrodes into specific structures in the basal ganglia for deep brain stimulation (DBS), as it is common in the treatment of Parkinsons disease. Critical to these procedures in neurosurgery is the localization and identification of different target structures such as subthalamic nucleus (STN) along the electrodes trajectory and finding the best position for the stimulating electrode. Typically, microelectrode recordings (MER) of local neural activity along up to five parallel trajectories are used by neurosurgeons for detecting the target region and creating the anatomic positions of the electrodes by imagination. We developed a method for automatic classification of the MER signals, which provides an electrode model with patient specific borders of the STN. In addition, a method is provided for finding the best matching of the electrode model with a 3D model of the STN. As a result, a 2.5D visualization of the target region is produced with the most probable positions of the electrodes and their intersections.

Alteration of cerebral perfusion in patients with idiopathic normal pressure hydrocephalus measured by 3D perfusion weighted magnetic resonance imaging

AbstractObjectiveIt is controversial whether alteration of cerebral perfusion plays an important role in the pathophysiology of patients with idiopathic normal pressure hydrocephalus (NPH) and can help to predict the outcome after shunt surgery.Materials and Methods28 patients with suspected NPH were examined clinically (Homburg Hydrocephalus Scale, walking test, incontinence protocol) and by 3D dynamic susceptibility based perfusion weighted magnetic resonance imaging (PWI–MRI) before and after cerebrospinal fluid release (spinal tap test, STT). The perfusion parameters (negative integral (NI), time of arrival (T0), time to peak (TTP), mean transit time, and the difference TTP—T0 were analysed.ResultsThree different groups of patients were identified preoperatively: In group 1 seven patients showed an increase in the cerebral perfusion and a clinical improvement after STT. The second group (9 patients) also revealed an increase of the cerebral perfusion, but no significant alteration of the clinical assessment could be found. In the third group neither the cerebral perfusion nor the clinical assessment changed. 14 of the 16 patients (group 1 and 2) were examined three months after shunt placement. 11 patients showed a good or excellent result, 2 patients revealed a fair assessment, and only 1 patient had transiently improved. No patient was downgraded after shunting. In the patient group 1 and 2 the NI increased significantly (effect size: 34%), whereas in group 3 no significant alteration of NI was observed.ConclusionPWI–MRI improves the prediction of outcome after shunt placement in patients with NPH and can offer new insights into the pathophysiology.

A solution for multi-alignment by transformation synchronisation

The alignment of a set of objects by means of transformations plays an important role in computer vision. Whilst the case for only two objects can be solved globally, when multiple objects are considered usually iterative methods are used. In practice the iterative methods perform well if the relative transformations between any pair of objects are free of noise. However, if only noisy relative transformations are available (e.g. due to missing data or wrong correspondences) the iterative methods may fail. Based on the observation that the underlying noise-free transformations can be retrieved from the null space of a matrix that can directly be obtained from pairwise alignments, this paper presents a novel method for the synchronisation of pairwise transformations such that they are transitively consistent. Simulations demonstrate that for noisy transformations, a large proportion of missing data and even for wrong correspondence assignments the method delivers encouraging results.

Stabilization with the Dynamic Cervical Implant: a novel treatment approach following cervical discectomy and decompression

OBJECT Although cervical total disc replacement (TDR) has shown equivalence or superiority to anterior cervical discectomy and fusion (ACDF), potential problems include nonphysiological motion (hypermobility), accelerated degeneration of the facet joints, particulate wear, and compromise of the mechanical integrity of the endplate during device fixation. Dynamic cervical stabilization is a novel motion-preserving concept that facilitates controlled, limited flexion and extension, but prevents axial rotation and lateral bending, thereby reducing motion across the facet joints. Shock absorption of the Dynamic Cervical Implant (DCI) device is intended to protect adjacent levels from accelerated degeneration. METHODS The authors conducted a prospective evaluation of 53 consecutive patients who underwent DCI stabilization for the treatment of 1-level (n = 42), 2-level (n = 9), and 3-level (n = 2) cervical disc disease with radiculopathy or myelopathy. Forty-seven patients (89%) completed all clinical and radiographic outcomes at a minimum of 24 months. Clinical outcomes consisted of Neck Disability Index (NDI) and visual analog scale (VAS) scores, neurological function at baseline and at latest follow-up, as well as patient satisfaction. Flexion-extension radiography was evaluated for device motion, implant migration, subsidence, and heterotopic ossification. Cervical sagittal alignment (Cobb angle), functional spinal unit (FSU) angle, and range of motion (ROM) at index and adjacent levels were evaluated with WEB 1000 software. RESULTS The NDI score, VAS neck and arm pain scores, and neurological deficits were significantly reduced at each postoperative time point compared with baseline (p < 0.0001). At 24 months postoperatively, 91% of patients were very satisfied and 9% somewhat satisfied, while 89% would definitely and 11% would probably elect to have the same surgery again. In 47 patients with 58 operated levels, the radiographic assessment showed good motion (5°-12°) of the device in 57%, reduced motion (2°-5°) in 34.5%, and little motion (0-2°) in 8.5%. The Cobb and FSU angles improved, showing a clear tendency for lordosis with the DCI. Motion greater than 2° of the treated segment could be preserved in 91.5%, while 8.5% had a near segmental fusion. Mean ROM at index levels demonstrated satisfying motion preservation with DCI. Mean ROM at upper and lower adjacent levels showed maintenance of adjacent-level kinematics. Heterotopic ossification, including 20% minor and 15% major, had no direct impact on clinical results. There were 2 endplate subsidences detected with an increased segmental lordosis. One asymptomatic anterior device migration required reoperation. Three patients underwent a secondary surgery in another segment during follow-up, twice for a new disc herniation and once for an adjacent degeneration. There was no posterior migration and no device breakage. CONCLUSIONS Preliminary results indicate that the DCI implanted using a proper surgical technique is safe and facilitates excellent clinical outcomes, maintains index-and adjacent-level ROM in the majority of cases, improves sagittal alignment, and may be suitable for patients with facet arthrosis who would otherwise not be candidates for cervical TDR. Shock absorption together with maintained motion in the DCI may protect adjacent levels from early degeneration in longer follow-up.

Purification of Small Interfering RNA Using Nondenaturing Anion-Exchange Chromatography

A manufacturing and purification process for duplex oligonucleotides was established, which shortens and simplifies currently used procedures, yielding a product of higher purity. The reported procedure is based on nondenaturing anion-exchange (AEX) chromatography, which is performed on the annealed duplex rather than the individual single strands. The duplex is formed early in the process by annealing of the crude single strands directly after solid-phase synthesis. Two 30 μmol manufacturing runs using duplex purification were performed on 2 different AEX resins and compared with a manufacturing run of the same scale using conventional single-strand chromatography. The same pooling strategy was employed for all purifications. Content of optimal duplex (duplex exclusively comprising full-length single strands) was 90.5% and 90.2% for the batches obtained by duplex purification and 86.1% for the batch obtained by single-strand purification. Maximum chromatographic recoveries were 67% for the duplex purification and 68% for the single-strand purification. Hence, the manufacture of small interfering RNA (siRNA) using duplex purification was simpler and faster than conventional single-strand purification and provided better purity and similar yield of final siRNA.

Fast correspondences for statistical shape models of brain structures

Statistical shape models based on point distribution models are powerful tools for image segmentation or shape analysis. The most challenging part in the generation of point distribution models is the identification of corresponding landmarks among all training shapes. Since in general the true correspondences are unknown, correspondences are frequently established under the hypothesis that correct correspondences lead to a compact model, which is mostly tackled by continuous optimisation methods. In favour of the prospect of an efficient optimisation, we present a simplified view of the correspondence problem for statistical shape models that is based on point-set registration, the linear assignment problem and mesh fairing. At first, regularised deformable point-set registration is performed and combined with solving the linear assignment problem to obtain correspondences between shapes on a global scale. With that, rough correspondences are established that may not yet be accurate on a local scale. Then, by using a mesh fairing procedure, consensus of the correspondences on a global and local scale among the entire set of shapes is achieved. We demonstrate that for the generation of statistical shape models of deep brain structures, the proposed approach is preferable over existing population-based methods both in terms of a significantly shorter runtime and in terms of an improved quality of the resulting shape model.