Topographic Mapping of the Primary Sensory Cortex Using Intraoperative Optical Imaging and Tactile Irritation.

The determination of exact tumor boundaries within eloquent brain regions is essential to maximize the extent of resection. Recent studies showed that intraoperative optical imaging (IOI) combined with median nerve stimulation is a helpful tool for visualization of the primary sensory cortex (PSC). In this technical note, we describe a novel approach of using IOI with painless tactile irritation to demonstrate the feasibility of topographic mapping of different body regions within the PSC. In addition, we compared the IOI results with preoperative functional MRI (fMRI) findings. In five patients with tumors located near the PSC who received tumor removal, IOI with tactile irritation of different body parts and fMRI was applied. We showed that tactile irritation of the hand in local and general anesthesia leads to reliable changes of cerebral blood volume during IOI. Hereby, we observed comparable IOI activation maps regarding the median nerve stimulation, fMRI and tactile irritation of the hand. The tactile irritation of different body areas revealed a plausible topographic distribution along the PSC. With this approach, IOI is also suitable for awake surgeries, since the tactile irritation is painless compared with median nerve stimulation and is congruent to fMRI findings. Further studies are ongoing to standardize this method to enable a broad application within the neurosurgical community.

Characterization of cortical hemodynamic changes following sensory, visual, and speech activation by intraoperative optical imaging utilizing phase-based evaluation methods.

Alterations within cerebral hemodynamics are the intrinsic signal source for a wide variety of neuroimaging techniques. Stimulation of specific functions leads due to neurovascular coupling, to changes in regional cerebral blood flow, oxygenation and volume. In this study, we investigated the temporal characteristics of cortical hemodynamic responses following electrical, tactile, visual, and speech activation for different stimulation paradigms using Intraoperative Optical Imaging (IOI). Image datasets from a total of 22 patients that underwent surgical resection of brain tumors were evaluated. The measured reflectance changes at different light wavelength bands, representing alterations in regional cortical blood volume (CBV), and deoxyhemoglobin (HbR) concentration, were assessed by using Fourier-based evaluation methods. We found a decrease of CBV connected to an increase of HbR within the contralateral primary sensory cortex (SI) in patients that were prolonged (30 s/15 s) electrically stimulated. Additionally, we found differences in amplitude as well as localization of activated areas for different stimulation patterns. Contrary to electrical stimulation, prolonged tactile as well as prolonged visual stimulation are provoking increases in CBV within the corresponding activated areas (SI, visual cortex). The processing of the acquired data from awake patients performing speech tasks reveals areas with increased, as well as areas with decreased CBV. The results lead us to the conclusion, that the CBV decreases in connection with HbR increases in SI are associated to processing of nociceptive stimuli and that stimulation type, as well as paradigm have a nonnegligible impact on the temporal characteristics of the following hemodynamic response.

9-Methyl-ß-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.

ß-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.

Comparison of Automatic Segmentation Algorithms for the Subthalamic Nucleus.

INTRODUCTION: Various automatic segmentation algorithms for the subthalamic nucleus (STN) have been published recently. However, most of the available software tools are not approved for clinical use. OBJECTIVE: The aim of this study is to evaluate a clinically available automatic segmentation tool of the navigation planning software Brainlab Elements (BL-E) by comparing the output to manual segmentation and a nonclinically approved research method using the DISTAL atlas (DA) and the Horn electrophysiological atlas (HEA). METHODS: Preoperative MRI data of 30 patients with idiopathic Parkinson's disease were used, resulting in 60 STN segmentations. The segmentations were created manually by two clinical experts. Automatic segmentations of the STN were obtained from BL-E and Advanced Normalization Tools using DA and HEA. Differences between manual and automatic segmentations were quantified by Dice and Jaccard coefficient, target overlap, and false negative/positive value (FNV/FPV) measurements. Statistical differences between similarity measures were assessed using the Wilcoxon signed-rank test with continuity correction, and comparison with interrater results was performed using the Mann-Whitney U test. RESULTS: For manual segmentation, the mean size of the segmented STN was 133 ± 24 mm3. The mean size of the STN was 121 ± 18 mm3 for BL-E, 162 ± 21 mm3 for DA, and 130 ± 17 mm3 for HEA. The Dice coefficient for the interrater comparison was 0.63 and 0.54 ± 0.12, 0.59 ± 0.13, and 0.52 ± 0.14 for BL-E, DA, and HEA, respectively. Significant differences between similarity measures were found for Dice and Jaccard coefficient, target overlap and FNV between BL-E and DA; and FPV between BL-E and HEA. However, none of the differences were significant compared to interrater variability. The analysis of the center of gravity of the segmentations revealed that the BL-E STN ROI was located more medially, superior and posterior compared to other segmentations. Regarding the target overlap for beta power within the STN ROI included with the HEA, the BL-E segmentation showed a significantly higher value compared to manual segmentation. CONCLUSION: Automatic image segmentation by means of the clinically approved software BL-E provides STN segmentations with similar accuracy like research tools, and differences are in the range of observed interrater variability. Further studies are required to investigate the clinical validity, for example, by comparing segmentation results of BL-E with electrophysiological data.

Parcellation of the Subthalamic Nucleus in Parkinson's Disease: A Retrospective Analysis of Atlas- and Diffusion-Based Methods.

BACKGROUND: Deep brain stimulation (DBS) is an established method of treatment for Parkinson's disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome. METHODS: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV. RESULTS: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score. CONCLUSIONS: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target ("sweet spot") for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning.

Clinical Validation of Quality Improvements Using the Six Sigma Concept: A Case Study for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: The Six Sigma concept allows for the evaluation of quality changes after the implementation of new technical equipment or adjustment of perioperative procedures. Exemplarily, we applied this method for quality assessment in deep brain stimulation surgery (DBS) for Parkinson's disease. METHODS: The medical procedure and possible errors were registered. Then, 6 critical-to-quality characteristics regarding clinical outcome, surgical precision, and the surgical process were measured. The surgical procedure was then optimized in 2 steps, and its measurement, along with the analysis, was repeated twice. RESULTS: By optimizing perioperative settings, the operation time could be reduced, and the precision of the lead placement could be increased. Clinical outcome, as measured by improvement in UPDRS-III, IV, and reduction of medication could also be improved with smaller required stimulation voltage. With directional leads considerable reduction of medication was achieved in 97% of patients (σ-value 3.39) compared to 83.7% (σ-value 2.53) with nondirectional leads. CONCLUSION: This study shows that the Six Sigma concept is a suitable quality tool to analyze and improve treatment quality of complex medical procedures such as lead positioning in DBS surgery in clinical routine. Our results suggest that directional leads in subthalamic nucleus DBS may have a favorable impact on patients' outcome.

Somatosensory functional MRI tractography for individualized targeting of deep brain stimulation in patients with chronic pain after brachial plexus injury.

BACKGROUND: The optimal targets for deep brain stimulation (DBS) in patients with refractory chronic pain are not clearly defined. We applied sensory functional MRI (fMRI)- and diffusion tensor imaging (DTI)-based DBS in chronic pain patients into 3 different targets to ascertain the most beneficial individual stimulation site. METHODS: Three patients with incapacitating chronic pain underwent DBS into 3 targets (periventricular gray (PVG), ventroposterolateral thalamus (VPL), and posterior limb of the internal capsule according to fMRI and DTI (PLIC). The electrodes were externalized and double-blinded tested for several days. Finally, the two electrodes with the best pain reduction were kept for permanent stimulation. The patients were then followed up for 12 months. Outcome measures comprised the numerical rating scale (NRS), short-form McGill's score (SF-MPQ), and health-related quality of life (SF-36). RESULTS: Continuous pain (mean NRS 6.6) was reduced to NRS 3.6 after 12 months. Only with stimulation of the PLIC pain attacks, that occurred at least 3 times a week (mean NRS 9.6) resolved in 2 patients and improved in one patient concerning both intensity (NRS 5) and frequency (twice a month). The mean SF-MPQ decreased from 92.7 to 50. The health-related quality of life improved considerably. CONCLUSION: fMRI- and DTI-based DBS to the PLIC was the only target with a significant effect on pain attacks and seems to be the most promising target in chronic pain patients after brachial plexus injury. The combination with PVG or VPL can further improve patients' outcome especially in terms of reducing the continuous pain.

Application of the Six Sigma concept for quality assessment of different strategies in DBS surgery.

BACKGROUND: For quality analysis, we applied the Six Sigma concept to define quality indicators and their boundaries as well as to compare treatment-dependent outcome data of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). METHODS: The Unified Parkinson Disease Rating Scale (UPDRS) III with on medication and on stimulation, the reduction of daily levodopa equivalence doses (LED), and the stimulation amplitude 1 year after surgery were registered. Regarding the results of the EARLYSTIM study, sigma values for applicable studies were calculated and compared. Further, the impact of perioperative conditions on patients' outcomes was analyzed. RESULTS: Forty-one studies with 2184 patients were included. The bleeding risk was 1.36%. In median, UPDRS III on/on improved by 19.9% while the LED was reduced by 45.2%. The median stimulation amplitude was 2.84 V. With the Six Sigma principle, a comparison between different centers was possible. Microelectrode recordings (MER) did not correlate with occurrence of bleedings and did not impact patient outcome. CONCLUSIONS: The Six Sigma principle can be simply used to analyze, improve and compare complex medical processes, particularly, the DBS surgery. Based on these data, higher sigma values were reached for clinical improvement in UPDRS III on/on for patients who underwent surgery in local anesthesia with intraoperative test stimulation compared to surgery in general anesthesia. However, the difference was not statistically significant. Application of MER was found to be optional with no increased bleeding risk and no improvement on patient's outcome.

Accuracy of subthalamic nucleus targeting by T2, FLAIR and SWI-3-Tesla MRI confirmed by microelectrode recordings.

BACKGROUND: Successful deep brain stimulation is mostly dependent on accurate positioning of the leads at the optimal target points. We investigated whether the identification of the subthalamic nucleus in T2-weighted 3-T MRI, fluid-attenuated inversion recovery 3-T MRI and susceptibility-weighted 3-T MRI is confirmed by intraoperative neurological microelectrode recording. METHODS: We evaluated 182 microelectrode recording leads in 21 patients with bilateral deep brain stimulation, retrospectively. Consequently, 728 electrode contact positions in T2-weighted 3-T MRI, 552 electrode contact positions in fluid-attenuated inversion recovery 3-T MRI and 490 electrode contact positions in susceptibility-weighted 3-T MRI were evaluated for a positive nucleus subthalamicus signal. RESULTS: The highest sensitivity was measured for fluid-attenuated inversion recovery 3-T MRI with 82.5 %, while the highest specificity was observed for susceptibility-weighted 3-T MRI with 90.6 %. The negative predictive value was nearly equal for susceptibility-weighted MRI and fluid-attenuated inversion recovery MRI with 87.5 % vs. 87.1 %, but the positive predictive value was higher in susceptibility-weighted 3-T MRI (86.0 %) than in the other MRI sequences. CONCLUSIONS: The susceptibility-weighted 3-T MRI-based subthalamic nucleus localization shows the best accuracy compared with T2-weighted and fluid-attenuated inversion recovery 3-T MRI. Therefore, the susceptibility-weighted 3-T MRI should be preferred for surgical planning when the operation procedure is performed under general anesthesia without microelectrode recordings.

Autologous bone flap cranioplasty following decompressive craniectomy is combined with a high complication rate in pediatric traumatic brain injury patients.

OBJECTIVE: Decompressive craniectomy (DC) is a last treatment option of refractory intracranial hypertension in traumatic brain injury (TBI) patients. Replacement of the autologous bone flap is the preferred method to cover the cranial defect after brain swelling has subsided. Long term outcomes and complications after replacement of the autologous bone flap in pediatric patients were studied in comparison to young, healthy adults. METHODS: Medical records of 27 pediatric patients who underwent DC and subsequent replacement of the bone flap between 1998 and 2011 were reviewed retrospectively. Patients were divided into two age groups (group 1: 18 children < 15 years; group 2:9 adolescents 15-18 years). For comparative reasons, a young adult control group of 39 patients between 18 and 30 years was additionally evaluated. RESULTS: With 81.8 % resorption of the bone flap, this was the major complication in young children. In up to 54.4 % of patients, a surgical revision of the osteolytic bone flap became necessary. However, in some pediatric patients, the osteolysis resolved spontaneously and further operations were not required. Probable enabling factors for bone flap resorption were young age (0-7 years), size of craniectomy, permanent shunt placement, and extent of dural opening/duraplasty. Other complications were bone flap infections, loosening of the re-inserted bone flap, and postoperative hematomas. CONCLUSION: There is an unacceptably high complication rate after reimplantation of the autologous bone following DC in pediatric TBI patients, especially in young children up to seven years of age. Artificial or synthetic cranioplasties may be considered as alternatives to initial bone flap reimplantation in the growing child. Despite the fact that DC is an effective treatment in TBI with persistent intracranial hypertension, it is important to realize that DC is not only combined with replacement of the autologous bone flap but also with a high rate of additional complications especially in pediatric patients.

[Effects of working time recording from the perspective of surgeons]. / Auswirkungen der Arbeitszeiterfassung aus Sicht der chirurgisch Tätigen.

BACKGROUND: Since 2023 the law in Germany has required that working times are recorded in the field of surgery. OBJECTIVES: The consequences of recording of the working hours in surgery are the main topic of this study. The search for ways of harmonization in the team to counteract a limited availability of personnel requires knowledge of the position of surgeons on the issue in question. MATERIAL AND METHODS: The study design is based on the situational approach of organizational research and encompasses 20 qualitative interviews and 186 datasets of an online questionnaire with 24 questions. For the evaluation group comparisons were carried out using the ANOVA analysis. The target groups were surgeons working in German hospitals. The study has an explorative character due to the targeted selection of samples. RESULTS: The results of the online survey showed a strong support for working time recording among surgeons with a general agreement of 82% and a consensus at all levels from residents to medical directors. Less than 50% of the assistants and medical specialists saw an improvement via an in-house dialogue, in comparison to senior physicians and medical directors. The right to compensatory time off by other employees represents a greater burden for senior physicians and chief physicians. DISCUSSION: The decisive result shows that there is a preference for transponder-based systems, especially among surgeons with long working hours. The problems of transparency and the right to compensatory time off, often associated with a lack of personnel, demonstrate the necessity for an improved communication and strategic personnel planning in hospitals. Surgeons have differentiated views on the transparent exchange on the topic of the working hours performed.

Resolution-enhanced multi-core fiber imaging learned on a digital twin for cancer diagnosis.

Significance: Deep learning enables label-free all-optical biopsies and automated tissue classification. Endoscopic systems provide intraoperative diagnostics to deep tissue and speed up treatment without harmful tissue removal. However, conventional multi-core fiber (MCF) endoscopes suffer from low resolution and artifacts, which hinder tumor diagnostics. Aim: We introduce a method to enable unpixelated, high-resolution tumor imaging through a given MCF with a diameter of around 0.65 mm and arbitrary core arrangement and inhomogeneous transmissivity. Approach: Image reconstruction is based on deep learning and the digital twin concept of the single-reference-based simulation with inhomogeneous optical properties of MCF and transfer learning on a small experimental dataset of biological tissue. The reference provided physical information about the MCF during the training processes. Results: For the simulated data, hallucination caused by the MCF inhomogeneity was eliminated, and the averaged peak signal-to-noise ratio and structural similarity were increased from 11.2 dB and 0.20 to 23.4 dB and 0.74, respectively. By transfer learning, the metrics of independent test images experimentally acquired on glioblastoma tissue ex vivo can reach up to 31.6 dB and 0.97 with 14 fps computing speed. Conclusions: With the proposed approach, a single reference image was required in the pre-training stage and laborious acquisition of training data was bypassed. Validation on glioblastoma cryosections with transfer learning on only 50 image pairs showed the capability for high-resolution deep tissue retrieval and high clinical feasibility.

Anticoagulation management of myocardial infarction after deep brain stimulation: a comparison of two cases.

Deep brain stimulation (DBS) is an established treatment of various diseases, particularly used for idiopathic Parkinson's disease. Frequently, DBS patients are multimorbid and managing them may be challenging, since postoperative complications can become more likely with age. In this article, we present two cases of myocardial infarction after DBS with different therapeutic strategies. Case 1 was anticoagulated with a heparin infusion with a target partial thromboplastine time (PTT) between 50 and 60 s after the myocardial infarction and showed 3 days later, after an initial postoperative inconspicuous cranial computer tomography, an intracerebral haematoma, which was evacuated without explanting the DBS lead. Case 2 was only treated with enoxaparine 40 mg s.c. twice a day after the myocardial infarction without any further complications. Both cases benefited from the DBS with respect to the motor fluctuations, but case 1 continued to suffer from psychomotor slowdown, mild hemiparesis of the left side, visual neglect and a gaze paresis. Unfortunately, there are no established guidelines or therapy recommendations for the management of such patients. An individual therapy regime is necessary for this patient population regarding the bleeding risk, the cardial risk and the symptoms of the patient. Retrospectively, the rejection of the intravenous application of heparin in case 2 seems to be the right decision. But regarding the small number of cases, it remains still an individual therapy. Further experience will help us to develop optimal therapy strategies for this patient population.

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD). The long-term benefit in PD patients with STN-DBS in comparison to medical treatment (MT) alone has not yet been demonstrated conclusively. Objectives: To judge the long-term outcome of patients with STN-DBS. Methods: To assess the evolution of PD symptoms and health-related quality of life (HRQoL) after deep brain stimulation (DBS) surgery, we conducted a cross-sectional analysis of 115 patients with STN-DBS with rater-based scales and self-reported questionnaires. In addition, we screened records of all our STN-DBS patients (2001-2019, n = 162 patients) for the onset of the morbidity milestones (falls, hallucinations, dementia, and nursing home placement) to assess disability-free life expectancy. Results: In the first year of STN-DBS, levodopa equivalent dose was reduced and motor function improved. Nonmotor symptoms and cognition remained stable. These effects were similar to previous studies. Morbidity milestones occurred 13 ± 7 years after diagnosis. Motor function, cognition, and HRQoL significantly worsened after the occurrence of any milestone, confirming the clinical relevance of these milestones. After onset of the first milestone, mean survival time was limited to 5 ± 0.8 years, which is comparable with patients with PD but without STN-DBS. Conclusions: On average, PD patients with STN-DBS live with their disease for a longer time, and morbidity milestones occur later in the disease course than in PD patients with MT. As judged by morbidity milestones, morbidity remains compressed into the final 5 years of life in PD patients with STN-DBS.

Improved efficiency of patient admission with electronic health records in neurosurgery.

BACKGROUND: Electronic health records (EHRs) may be controversial but they have the potential to improve patient care. We investigated whether the introduction of an electronic template-based admission form for the collection of information about the patient's medical history and neurological and clinical state at admission in the neurosurgical unit might have an impact on the quality of documentation in a discharge record and the amount of time taken to produce this documentation. METHOD: A new digital template-based admission form (EHR) was developed and assessed with QNOTE, an assessment tool of medical notes with standardised criteria and the possibility to benchmark the quality of documentations. This was compared to 30 prior paper-based handwritten documentations (HWD) regarding the utilisation of these medical notes for dictation of medical discharge records. RESULTS: Implementation of the EHR significantly improved the quality of patient admission documentation with a QNOTE mean grand score of 87 ± 22 (p < 0.0001) compared to prior HWD with 44 ± 30. The mean documentation time for HWD was 8.1 min ± 4.1 min and the dictation time for discharge records was 10.6 min ± 3.5 min. After implementation of EHR, the documentation time increased slightly to 9.6 min ± 2.3 min (n.s.), while the time for dictation of discharge records was reduced to 5.1 min ± 1.2 min (p < 0.0001). There was a clear correlation between a higher quality of documentation and a higher needed documentation time as well as higher quality of documentation and lower dictation times of discharge records. CONCLUSION: Implementation of the EHR improved the quality of patient admission documentation and reduced the dictation time of discharge records. IMPLICATIONS: It is crucial to involve stakeholders and users of EHRs in a timely manner during the stage of development and implementation phase to ensure optimal results and better usability.

Serum neurofilament indicates that DBS surgery can cause neuronal damage whereas stimulation itself does not.

Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson's disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not.

Prospective surgical solutions in degenerative spine: spinal simulation for optimal choice of implant and targeted device development.

OBJECTIVES: The most important goal of surgical treatment for spinal degeneration, in addition to eliminating the underlying pathology, is to preserve the biomechanically relevant structures. If degeneration destroys biomechanics, the single segment must either be surgically stabilized or functionally replaced by prosthetic restoration. This study examines how software-based presurgical simulation affects device selection and device development. METHODS: Based on videofluoroscopic motion recordings and pixel-precise processing of the segmental motion patterns, a software-based surrogate functional model was validated. It characterizes the individual movement of spinal segments relative to corresponding cervical or lumbar spine sections. The single segment-based motion of cervical or lumbar spine of individual patients can be simulated, if size-calibrated functional X-rays of the relevant spine section are available. The software plug-in "biokinemetric triangle" has been then integrated into this software to perform comparative segmental motion analyses before and after treatment in two cervical device studies: the correlation of implant-induced changes in the movement geometry and patient-related outcome was examined to investigate, whether this surrogate model could provide a guideline for implant selection and future implant development. RESULTS: For its validation in 253 randomly selected patients requiring single-level cervical (n=122) or lumbar (n=131) implant-supported restoration, the biokinemetric triangle provided significant pattern recognition in comparable investigations (p<0.05) and the software detected device-specific changes after implant-treatment (p<0.01). Subsequently, 104 patients, who underwent cervical discectomy, showed a correlation of the neck disability index with implant-specific changes in their segmental movement geometry: the preoperative simulation supported the best choice of surgical implants, since the best outcome resulted from restricting the extent of the movement of adjacent segments influenced by the technical mechanism of the respective device (p<0.05). CONCLUSIONS: The implant restoration resulted in best outcome which modified intersegmental communication in a way that the segments adjacent to the implanted segment undergo less change in their own movement geometry. Based on our software-surrogate, individualized devices could be created that slow down further degeneration of adjacent segments by influencing the intersegmental communication of the motion segments.

The exceptional properties of 9-methyl-beta-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects.

Beta-carbolines (BCs) are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease. However, we recently demonstrated protective and stimulatory effects of 9-methyl-BC (9-me-BC) in primary dopaminergic culture. In the present study, treatment with 9-me-BC unmasked a unique tetrad of effects. First, tyrosine hydroxylase (TH) expression was stimulated in pre-existing dopa decarboxylase immunoreactive neurons and several TH-relevant transcription factors (Gata2, Gata3, Creb1, Crebbp) were up-regulated. Neurite outgrowth of TH immunoreactive (THir) neurons was likewise stimulated. The interaction with tyrosine kinases (protein kinase A and C, epidermal growth factor-receptor, fibroblast growth factor-receptor and neural cell adhesion molecule) turned out to be decisive for these observed effects. Second, 9-me-BC protected in acute toxicity models THir neurons against lipopolysaccharide and 2,9-dime-BC(+) toxicity. Third, in a chronic toxicity model when cells were treated with 9-me-BC after chronic rotenone administration, a pronounced regeneration of THir neurons was observed. Fourth, 9-me-BC inhibited the proliferation of microglia induced by toxin treatment and installed an anti-inflammatory environment by decreasing the expression of inflammatory cytokines and receptors. Finally, 9-me-BC lowered the content of alpha-synuclein protein in the cultures. The presented results warrant the exploration of 9-me-BC as a novel potential anti-parkinsonian medication, as 9-me-BC interferes with several known pathogenic factors in Parkinson's disease as outlined above. Further investigations are currently under way.