Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-1 | Award Amount: 16.14M | Year: 2010
There are currently no cures for Parkinsons disease (PD) but one of the most effective reparative therapies in patients to date has been with allotransplants of dopamine (DA) neuroblasts obtained from fetal ventral mesencephalic (VM) tissue. However, this cell transplantation approach has given inconsistent results, with some patients doing extremely well and coming off anti-PD medication for years, whilst others have shown no or only modest clinical improvements, and in some cases also developed severe, off-state graft-induced dyskinesias (GIDs). The reasons behind this heterogeneity of outcomes, and the emergence of GIDs in particular, need to be better understood, not least in the perspective of the rapid advances that are now being made in the development of stem-cell based therapies. There is therefore an urgent need to revisit the trials that have already been done with fetal VM tissue in PD patients, with the expectation that a critical reassessment can form the basis for an optimised and more standardised procedure that will translate into more consistently efficacious transplants with minimal side-effects. Over the last two years a group of international experts, including the key investigators of the previous European and North American trials, has been re-examining the outcome of these trials as well as reviewing the results obtained from recent and ongoing animal experimental studies, and identified a number of weaknesses that may explain the inconsistent outcome in previous trials. As a result of these discussions, the group has agreed to join forces in a new round of experimental work and cell therapy trials in PD, based on a new jointly developed protocol where all these factors are taken into account. In the first instance fetal VM tissue containing mesencephalic DA neuroblasts will be used, with the expectation that this will pave the way for bigger trials using dopaminergic neurons derived from stem cells.
Hartbauer M.,University of Graz |
Kruger T.B.,INOMED Medizintechnik GmbH |
Stieglitz T.,Albert Ludwigs University of Freiburg
Neurocomputing | Year: 2012
Recent advances in microsystems technology led to a miniaturization of cuff-electrodes, which suggests these electrodes not just for long-term neuronal recordings in mammalians, but also in medium-sized insects. In this study we investigated the possibilities offered by cuff-electrodes for neuroethology using insects as a model organism. The implantation in the neck of a tropical bushcricket resulted in high quality extracellular nerve recordings of different units responding to various acoustic, vibratory, optical and mechanical stimuli. In addition, multi-unit nerve activity related to leg movements was recorded in insects walking on a trackball. A drawback of bi-polar nerve recordings obtained during tethered flight was overlay of nerve activity with large amplitude muscle potentials. Interestingly, cuff-electrode recordings were robust to withstand walking and flight activity so that good quality nerve recordings were possible even three days after electrode implantation. Recording multi-unit nerve activity in intact insects required an elaborate spike sorting algorithm in order to discriminate neuronal units responding to external stimuli from background activity. In future, a combination of miniaturized cuff-electrodes and light-weight amplifiers equipped with a wireless transmitter will allow the investigation of neuronal processes underlying natural behavior in freely moving insects. By this means cuff-electrodes may contribute to the development of realistic neuronal models simulating neuronal processes underlying natural insect behavior, such like mate choice and predator avoidance. © 2012 Elsevier B.V.
Lopez W.O.C.,Albert Ludwigs University of Freiburg |
Lopez W.O.C.,University of Sao Paulo |
Higuera C.A.E.,Brainmee |
Fonoff E.T.,University of Sao Paulo |
And 3 more authors.
Human Movement Science | Year: 2014
Evidence supports the use of rhythmic external auditory signals to improve gait in PD patients (Arias & Cudeiro, 2008; Kenyon & Thaut, 2000; McIntosh, Rice & Thaut, 1994; McIntosh et al., 1997; Morris, Iansek, & Matyas, 1994; Thaut, McIntosh, & Rice, 1997; Suteerawattananon, Morris, Etnyre, Jankovic, & Protas, 2004; Willems, Nieuwboer, Chavert, & Desloovere, 2006). However, few prototypes are available for daily use, and to our knowledge, none utilize a smartphone application allowing individualized sounds and cadence. Therefore, we analyzed the effects on gait of Listenmee®, an intelligent glasses system with a portable auditory device, and present its smartphone application, the Listenmee app®, offering over 100 different sounds and an adjustable metronome to individualize the cueing rate as well as its smartwatch with accelerometer to detect magnitude and direction of the proper acceleration, track calorie count, sleep patterns, steps count and daily distances. The present study included patients with idiopathic PD presented gait disturbances including freezing. Auditory rhythmic cues were delivered through Listenmee®. Performance was analyzed in a motion and gait analysis laboratory. The results revealed significant improvements in gait performance over three major dependent variables: walking speed in 38.1%, cadence in 28.1% and stride length in 44.5%. Our findings suggest that auditory cueing through Listenmee® may significantly enhance gait performance. Further studies are needed to elucidate the potential role and maximize the benefits of these portable devices. © 2014 Elsevier B.V.
Kneist W.,Johannes Gutenberg University Mainz |
Kauff D.W.,Johannes Gutenberg University Mainz |
Rahimi Nedjat R.K.,Johannes Gutenberg University Mainz |
Rink A.D.,Johannes Gutenberg University Mainz |
And 6 more authors.
International Journal of Colorectal Disease | Year: 2010
Purpose: The aim of this animal study was to investigate the effect of intraoperative pelvic nerve stimulation on internal anal sphincter electromyographic signals in order to evaluate its possible use for neuromonitoring during nerve-sparing pelvic surgery. Methods: Eight pigs underwent low anterior rectal resection. The intersphincteric space was exposed, and the internal (IAS) and external anal sphincter (EAS) were identified. Electromyography of both sphincters was performed with bipolar needle electrodes. Intermittent bipolar electric stimulation of the inferior hypogastric plexus and the pelvic splanchnic nerves was carried out bilaterally. The recorded signals were analyzed in its frequency spectrum. Results: In all animals, electromyographic recordings of IAS and EAS were successful. Intraoperative nerve stimulation resulted in a sudden amplitude increase in the time-based electromyographic signals of IAS (1.0 (0.5-9.0) μV vs. 4.0 (1.0-113.0) μV) and EAS (p∈<∈0.001). The frequency spectrum of IAS in the resting state ranged from 0.15 to 5 Hz with highest activity in median at 0.77 Hz (46 cycles/min). Pelvic nerve stimulation resulted in an extended spectrum ranging from 0.15 to 20 Hz. EAS signals showed higher frequencies mainly in a range of 50 to 350 Hz. However, after muscle relaxation with pancuronium bromide, only the low frequency spectrum of the IAS signals was still present. Conclusions: Intraoperative verification of IAS function by stimulation of pelvic autonomic nerves is possible. The IAS electromyographic response could be used to monitor pelvic autonomic nerve preservation. © 2010 Springer-Verlag.
Prystaz K.,Albert Ludwigs University of Freiburg |
Prystaz K.,Inomed Medizintechnik GmbH |
Ulmer C.,Robert Bosch GmbH |
Somerlik-Fuchs K.H.,Albert Ludwigs University of Freiburg |
Krueger T.B.,Inomed Medizintechnik GmbH
Biomedizinische Technik | Year: 2013
In thyroid surgery cuff-electrodes for stimulation of the vagal nerve are used in order to prevent recurrent laryngeal nerve damage. The aim of this study was to illustrate resulting forces at application of cuff-electrodes at the vagal nerve as well as to determine electrical characteristics with impedance spectroscopy and simulation of the electrical field of cuff- electrodes. The final goal is to assure save application of cuff-electrodes at the vagal nerve for continuous stimulation by describing the physical parameters with the suggested in vitro model. © 2013 by Walter de Gruyter.
Hiebl B.,Helmholtz Center Geesthacht |
Bog S.,University of Heidelberg |
Mikut R.,Karlsruhe Institute of Technology |
Bauer C.,Karlsruhe Institute of Technology |
And 3 more authors.
Applied Cardiopulmonary Pathophysiology | Year: 2010
Minimally-invasively implantable spiral cuff electrodes coated with polyimide (PI) for insulation in combination with suitably designed amplifiers were recently reported to allow signalling of electroneurograms (ENGs). These cuff electrodes can be used to record the respiratory drive after implantation on the phrenic nerve, but PI can cause epineurial fibrosis, fiber loss, and limitedreproducibility of recordings. This study aimed to explore the tissue reaction in response to a flexible tripolar cuff electrode embedded in a thin (10 μm) PI insulating carrier after implantation around the sciatic nerves of rats (n=4) at the branching into the N. peroneus communis, the N. tibialis and N. cutaneus surae caudalis. 28 days after implantation the electrode functionality was proven and ENG signals recorded. In addition, transverse sections of the implantation site were analysed after hematoxylin-eosin (HE) and Weigert ́s fibrin staining for changes in the tissue morphology and the number of myelinated nerve fibres. 28 days after implantation the electrode contact to the nerve still was sufficient for signal recording and no changes in the nerve morphology and the number of myelinated nerve fibres could be noted. However, cuff functionality for nerve signal transfer was limited by a fibrous capsule, which covered the whole electrode and which was composed mainly of tightly packed fibroblasts and fibrin. The formation of such a fibrous capsule is known to be caused by the foreign body response and shows a limited tissue compatibility which might be mainly related to the PI insulating material. Further studies will address the investigation of alternative elastic matrix-materials to achieve a strong integration of the electrode in the nerve tissue and in this way a long term functionality of the cuff electrode.
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.3.9 | Award Amount: 11.31M | Year: 2010
The overall concept of the 48-month Integrated Project NEUWalk is focused specifically on Objective ICT-2009.3.9 Microsystems and Smart Miniaturised Systems with particular emphasis to c) Application-specific microsystems and smart miniaturised systems 1) Biomedical S&T objectives. The technological objective of NEUWalk is to develop novel microtechnology, microelectronics, brain decoding algorithms and smart control interfaces that can be flexibly assembled to address neurobiomedical issues that not only impact the quality of life in thousands of individuals throughout Europe, but also create a significant economic burden for European countries. These innovative neurotechnologies will be combined to achieve an integrated cortico-spinal neuroprosthetic interface. The underlying objective in NEUWalk is to restore motor functions in individuals with severe spinal cord injury (SCI) and to establish a more efficient, less invasive and safer strategy to alleviate Parkinsons disease (PD) syndromes. To achieve this ambitious goal, we will capitalize on recent breakthroughs that demonstrate the impressive capacity of spinal cord stimulations to promote the recovery of full weight bearing walking in paralyzed SCI rats and to alleviate severe Parkinsonian symptoms in rodents. Elaboration and validation of the NEUWalk concept will be carried out in rats with SCI and non-human primates with PD. To accelerate the translation towards efficient clinical therapies, preliminary testing will be conducted in humans with SCI. The potential impact of the microtechnology, microelectronics, and treatment paradigms developed in NEUWalk is tremendous. These advances will open avenues for revolutionary clinical applications and will contribute to fill the increasingly wider gap that separates European research on Neuroprosthetics to similar studies conducted in the United States. Beyond SCI and PD, the NEUWalk concepts will fertilize new designs for the treatment of other neurologic disorders.
Stoecklein V.M.,Ludwig Maximilians University of Munich |
Faber F.,Ludwig Maximilians University of Munich |
Koch M.,Ludwig Maximilians University of Munich |
Mattmuller R.,Inomed Medizintechnik GmbH |
And 4 more authors.
Acta Neurochirurgica | Year: 2015
Background: The use of intraoperative neurophysiological monitoring (IONM) in neurosurgery has improved patient safety and outcomes. However, a pitfall in the use of IONM remains unsolved. Currently, there is no feasible way for surgeons to interpret IONM waves themselves during operations. Instead, they have to rely on verbal feedback from a neurophysiologist. This method is prone to communication failures, which can lead to delayed or false interpretation of the data. Direct visualization of IONM waves is a way to alleviate this problem and make IONM more effective. Methods: Microscope-integrated IONM (MI-IONM) was used in 163 cranial and spinal cases. We evaluated the feasibility, system stability and how well the system integrated into the surgical workflow. We used an IONM system that was connected to a surgical microscope. All IONM modalities used at our institution could be visualized as required, superimposed on the surgical field in the eyepiece of the microscope without obstructing the surgeon’s field of vision. Results: Use of MI-IONM was safe and reliable. It furthermore provided valuable intraoperative information. The system merely required a short learning curve. Only minor system problems without impact on surgical workflow occurred. MI-IONM proved to be especially useful in surgical cases where careful monitoring of nerve function is required, e.g., cerebellopontine angle surgery. Here, direct assessment of surgical action and IONM wave change was provided to the surgeon, if necessary (on-off control). Conclusion: MI-IONM is a useful extension of conventional IONM that provides optional real-time functional information to the surgeon on demand. © 2015, Springer-Verlag Wien.
PubMed | Ludwig Maximilians University of Munich, Carl Zeiss GmbH and Inomed Medizintechnik GmbH
Type: Journal Article | Journal: Acta neurochirurgica | Year: 2015
The use of intraoperative neurophysiological monitoring (IONM) in neurosurgery has improved patient safety and outcomes. However, a pitfall in the use of IONM remains unsolved. Currently, there is no feasible way for surgeons to interpret IONM waves themselves during operations. Instead, they have to rely on verbal feedback from a neurophysiologist. This method is prone to communication failures, which can lead to delayed or false interpretation of the data. Direct visualization of IONM waves is a way to alleviate this problem and make IONM more effective.Microscope-integrated IONM (MI-IONM) was used in 163 cranial and spinal cases. We evaluated the feasibility, system stability and how well the system integrated into the surgical workflow. We used an IONM system that was connected to a surgical microscope. All IONM modalities used at our institution could be visualized as required, superimposed on the surgical field in the eyepiece of the microscope without obstructing the surgeons field of vision.Use of MI-IONM was safe and reliable. It furthermore provided valuable intraoperative information. The system merely required a short learning curve. Only minor system problems without impact on surgical workflow occurred. MI-IONM proved to be especially useful in surgical cases where careful monitoring of nerve function is required, e.g., cerebellopontine angle surgery. Here, direct assessment of surgical action and IONM wave change was provided to the surgeon, if necessary (on-off control).MI-IONM is a useful extension of conventional IONM that provides optional real-time functional information to the surgeon on demand.