Publications by authors named "Hans von Holst"

34 Publications

Learning through a virtual patient vs. recorded lecture: a comparison of knowledge retention in a trauma case.

Int J Med Educ 2018 Mar 28;9:86-92. Epub 2018 Mar 28.

Department of Clinical Science, Intervention and Technology, Division of Orthopaedics and Biotechnology, Karolin-ska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.

Objectives: To compare medical students' and residents' knowledge retention of assessment, diagnosis and treatment procedures, as well as a learning experience, of patients with spinal trauma after training with either a Virtual Patient case or a video-recorded traditional lecture.

Methods: A total of 170 volunteers (85 medical students and 85 residents in orthopedic surgery) were randomly allocated (stratified for student/resident and gender) to either a video-recorded standard lecture or a Virtual Patient-based training session where they interactively assessed a clinical case portraying a motorcycle accident. The knowledge retention was assessed by a test immediately following the educational intervention and repeated after a minimum of 2 months. Participants' learning experiences were evaluated with exit questionnaires. A repeated-measures analysis of variance was applied on knowledge scores. A total of 81% (n = 138) of the participants completed both tests.

Results: There was a small but significant decline in first and second test results for both groups (F = 18.154, p = 0.00). However, no significant differences in short-term and long-term knowledge retention were observed between the two teaching methods. The Virtual Patient group reported higher learning experience levels in engagement, stimulation, general perception, and expectations.

Conclusions: Participants' levels engagement were reported in favor of the VP format. Similar knowledge retention was achieved through either a Virtual Patient or a recorded lecture.
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http://dx.doi.org/10.5116/ijme.5aa3.ccf2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951773PMC
March 2018

A National Survey of Traumatic Brain Injuries Admitted to Hospitals in Sweden from 1987 to 2010.

Neuroepidemiology 2015 18;45(1):20-7. Epub 2015 Jul 18.

Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.

Background: With an increasing and aging population, there is a global demand for improving the primary prevention strategies aimed at reducing traumatic brain injuries (TBIs). The objective of the present epidemiological study was to evaluate the pattern of TBI in Sweden over a 24 years period (1987-2010).

Methods: The Swedish Hospital Discharge Register was used, where in-patient care with a main diagnosis of TBI according to ICD9/10 was included. External factors, age and gender distribution was evaluated.

Results: A decreasing number of annual incidence was observed, that is, from 230 to 156 per 100,000 inhabitants. A steady decrease of concussion was observed while other intracranial injuries increased especially traumatic subdural hemorrhage and subarachnoid hemorrhage. The study identified 3 groups of patients - young, adults and elderly. The highest incidence and the largest increase of incidence were seen in the oldest age group (85+ years) while the population under 65 years had a decreasing incidence of TBI. The most frequent etiology was fall accidents (57%) with a relative constant trend over the study period.

Conclusions: More effort should be focused on different strategies for different age groups, especially the elderly group. A well-planned strategy for primary prevention guidelines for different age groups will have the chance to further reduce not only the health-care costs but also complications among elderly care.
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http://dx.doi.org/10.1159/000381780DOI Listing
May 2016

Higher impact energy in traumatic brain injury interferes with noncovalent and covalent bonds resulting in cytotoxic brain tissue edema as measured with computational simulation.

Acta Neurochir (Wien) 2015 Apr 17;157(4):639-48; discussion 648. Epub 2015 Feb 17.

Section of Neurosurgery, Division of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden,

Background: Cytotoxic brain tissue edema is a complicated secondary consequence of ischemic injury following cerebral diseases such as traumatic brain injury and stroke. To some extent the pathophysiological mechanisms are known, but far from completely. In this study, a hypothesis is proposed in which protein unfolding and perturbation of nucleotide structures participate in the development of cytotoxic edema following traumatic brain injury (TBI).

Methods: An advanced computational simulation model of the human head was used to simulate TBI. The consequences of kinetic energy transfer following an external dynamic impact were analyzed including the intracranial pressure (ICP), strain level, and their potential influences on the noncovalent and covalent bonds in folded protein structures.

Results: The result shows that although most of the transferred kinetic energy is absorbed in the skin and three bone layers, there is a substantial amount of energy reaching the gray and white matter. The kinetic energy from an external dynamic impact has the theoretical potential to interfere not only with noncovalent but also covalent bonds when high enough. The induced mechanical strain and pressure may further interfere with the proteins, which accumulate water molecules into the interior of the hydrophobic structures of unfolded proteins. Simultaneously, the noncovalent energy-rich bonds in nucleotide adenosine-triphosphates may be perturbed as well.

Conclusions: Based on the analysis of the numerical simulation data, the kinetic energy from an external dynamic impact has the theoretical potential to interfere not only with noncovalent, but also with covalent bonds when high enough. The subsequent attraction of increased water molecules into the unfolded protein structures and disruption of adenosine-triphosphate bonds could to some extent explain the etiology to cytotoxic edema.
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http://dx.doi.org/10.1007/s00701-015-2368-xDOI Listing
April 2015

Decompressive craniectomy (DC) at the non-injured side of the brain has the potential to improve patient outcome as measured with computational simulation.

Acta Neurochir (Wien) 2014 Oct 8;156(10):1961-7; discussion 1967. Epub 2014 Aug 8.

Division of Neuronic Engineering, School of Technology and Health, Royal Institute of Technology (KTH), Stockholm, Sweden,

Objective: Decompressive craniectomy (DC) is efficient in reducing the intracranial pressure in several complicated disorders such as traumatic brain injury (TBI) and stroke. The neurosurgical procedure has indeed reduced the number of deaths. However, parallel with the reduced fatal cases, the number of vegetative patients has increased significantly. Mechanical stretching in axonal fibers has been suggested to contribute to the unfavorable outcome. Thus, there is a need for improving treatment procedures that allow both reduced fatal and vegetative outcomes. The hypothesis is that by performing the DC at the non-injured side of the head, stretching of axonal fibers at the injured brain tissue can be reduced, thereby having the potential to improve patient outcome.

Methods: Six patients, one with TBI and five with stroke, were treated with DC and where each patient's pre- and postoperative computerized tomography (CT) were analyzed and transferred to a finite element (FE) model of the human head and brain to simulate DC both at the injured and non-injured sides of the head. Poroelastic material was used to simulate brain tissue.

Results: The computational simulation showed slightly to substantially increased axonal strain levels over 40 % on the injured side where the actual DC had been performed in the six patients. However, when the simulation DC was performed on the opposite, non-injured side, there was a substantial reduction in axonal strain levels at the injured side of brain tissue. Also, at the opposite, non-injured side, the axonal strain level was substantially lower in the brain tissue. The reduced axonal strain level could be verified by analyzing a number of coronal sections in each patient. Further analysis of axial slices showed that falx may tentatively explain part of the different axonal strain levels between the DC performances at injured and opposite, non-injured sides of the head.

Conclusions: By using a FE method it is possible to optimize the DC procedure to a non-injured area of the head thereby having the potential to reduce axonal stretching at the injured brain tissue. The postoperative DC stretching of axonal fibers may be influenced by different anatomical structures including falx. It is suggested that including computational FE simulation images may offer guidance to reduce axonal strain level tailoring the anatomical location of DC performance in each patient.
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http://dx.doi.org/10.1007/s00701-014-2195-5DOI Listing
October 2014

Multipurpose heterofunctional dendritic scaffolds as crosslinkers towards functional soft hydrogels and implant adhesives in bone fracture applications.

J Mater Chem B 2013 Nov 10;1(44):6015-6019. Epub 2013 Oct 10.

KTH Royal Institute of Technology, Polymer and Fiber Technology, Division of Coating Technology, Stockholm, Sweden.

Two sets of heterofunctional dendritic frameworks displaying an inversed and exact number of ene and azide groups have successfully been synthesized and post-functionalized with biorelevant molecules. Their facile scaffolding ability enabled the fabrication of soft and azide functional dendritic hydrogels with modulus close to muscle tissue. The dendritic scaffolds are furthermore shown to be promising primers for the development of novel bone fracture stabilization adhesives with shear strengths succeeding commercial Histroacryl®.
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http://dx.doi.org/10.1039/c3tb21061hDOI Listing
November 2013

A pilot evaluation of an educational program that offers visualizations of cervical spine injuries: medical students' self-efficacy increases by training.

Inform Health Soc Care 2014 Jan 9;39(1):33-46. Epub 2013 Oct 9.

Department of Clinical Science, Intervention and Technology, Division of Orthopaedics and Biotechnology, Karolinska Institutet, Karolinska University Hospital , Huddinge, Stockholm , Sweden and.

In this pilot study, a new method for visualization through imaging and simulation (VIS-Ed) for teaching diagnosis and treatment of cervical spine trauma was formatively evaluated. The aims were to examine if medical students' self-efficacy would change by training using VIS-Ed, and if so these changes were related to how they evaluated the session, and the user interface (UI) of this program. Using a one-group, pre-post course test design 43 Swedish medical students (4th year, 17 males, 26 females) practiced in groups of three participants. Overall the practice and the UI were considered as positive experiences. They judged VIS-Ed as a good interactive scenario-based educational tool. All students' self-efficacy increased significantly by training (p < 0.001). Spearman's rank correlation tests revealed that increased self-efficacy was only associated with: how the session was compared to as expected (p < 0.007). Students' self-efficacy increased significantly by training, but replication studies should determine if this training effect is gender-related.
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http://dx.doi.org/10.3109/17538157.2013.834343DOI Listing
January 2014

Heating during infrared neural stimulation.

Lasers Surg Med 2013 Sep 7;45(7):469-81. Epub 2013 Jul 7.

Royal Institute of Technology, School of Technology and Health, Alfred Nobels Allé 10, 14152, Huddinge, Sweden.

Background And Objective: Infrared neural stimulation (INS) has recently evoked interest as an alternative to electrical stimulation. The mechanism of activation is the heating of water, which induces changes in cell membrane potential but may also trigger heat sensitive receptors. To further elucidate the mechanism, which may be dependent on cell type, a detailed description of the temperature distribution is necessary. A good control of the resulting temperature during INS is also necessary to avoid excessive heating that may damage the cells. Here we present a detailed model for the heating during INS and apply it for INS of in vitro neural networks of rat cerebral cortex neurons.

Study Design/materials And Methods: A model of the heating during INS of a cell culture in a non-turbid media was prepared using multiphysics software. Experimental parameters such as initial temperature, beam distribution, pulse length, pulse duration, frequency and laser-cell distance were used. To verify the model, local temperature measurements using open pipette resistance were conducted. Furthermore, cortical neurons in culture were stimulated by a 500  mW pulsed diode laser (wavelength 1,550  nm) launched into a 200  µm multimodal optical fiber positioned 300  µm from the glass surface. The radiant exposure was 5.2 J/cm(2) .

Results: The model gave detailed information about the spatial and temporal temperature distribution in the heated volume during INS. Temperature measurements using open pipette resistance verified the model. The peak temperature experienced by the cells was 48°C. Cortical neurons were successfully stimulated using the 1,550  nm laser and single cell activation as well as neural network inhibition were observed.

Conclusion: The model shows the spatial and temporal temperature distribution in the heated volume and could serve as a useful tool for future studies of the heating during INS.
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http://dx.doi.org/10.1002/lsm.22158DOI Listing
September 2013

The dynamic triple peak impact factor in traumatic brain injury influences native protein structures in gray and white matter as measured with computational simulation.

Neurol Res 2013 Oct 29;35(8):782-9. Epub 2013 May 29.

Karolinska Institutet, Stockholm, Sweden.

Background: Traumatic brain injuries (TBIs) cause a substantial burden to the patient, relatives, and the society as a whole. Much experience and knowledge during the last two decades have improved the neurosurgical treatment as well as the outcome. However, there is still much debate on what actually happens when external kinetic energy is transferred to the head immediately after a TBI. Better knowledge about the cascades of mechanical events at the time of accident is a prerequisite to further reduce the burden in all categories and improve the neurosurgical care of TBI patients.

Methods: In the present study, we use the finite element modeling of the human brain to numerically simulate impact velocities of 10, 6, and 2 m/s to clarify some of the immediate consequences of the external kinetic energy transfer focusing on the gray (GM) and white matters (WM).

Results: The numerical simulation was focused on the external kinetic energy transfer with a level of 227·3 J reaching the head, intracranial pressure (ICP), strain energy density, 1st principal strain level, and their respective impacts on the brain tissue. The results show that, for a 10 m/s impact, a total internal potential energy of 208·6 J was absorbed, of which 14·3% (29·81 J) was absorbed by the scalp, 22·05% (46·0 J) by the outer compact bone, 17·12% (35·72 J) by the porous bone, 27·44% (57·23 J) by the inner compact bone, and 7·31% (15·24 J) by the facial bone. The rest of the internal potential energy was defined to reach the GM (3·6%, 7·51 J) and the WM 1·59% (3·31 J). Also, the ICP, strain energy density, and 1st principal strain levels, defined as the dynamic triple peak impact factor, influenced the GM and WM with their own impact peaks during the first 10 ms after the accident and were the highest for the 10 and 6 m/s impacts, while the 2 m/s impact had only a slight influence on the GM and WM structures.

Conclusions: The present study shows for the first time that following an impact of 10 m/s, 88·31% of the calculated external kinetic energy was absorbed by the external parts of the head before the remaining energy of 5·19% reached the GM and WM. GM absorbed about twice as much of the energy compared to the WM. It is suggested that the dynamic triple peak impact factor may have a profound effect on native protein structures in the cerebral metabolism after a TBI.
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http://dx.doi.org/10.1179/1743132813Y.0000000227DOI Listing
October 2013

Consequences of the dynamic triple peak impact factor in Traumatic Brain Injury as Measured with Numerical Simulation.

Front Neurol 2013 12;4:23. Epub 2013 Mar 12.

Section of Neurosurgery, Division of Clinical Neuroscience, Karolinska Institutet Stockholm, Sweden ; Division of Neuronic Engineering, School of Technology and Health, Royal Institute of Technology (KTH) Stockholm, Sweden.

There is a lack of knowledge about the direct neuromechanical consequences in traumatic brain injury (TBI) at the scene of accident. In this study we use a finite element model of the human head to study the dynamic response of the brain during the first milliseconds after the impact with velocities of 10, 6, and 2 meters/second (m/s), respectively. The numerical simulation was focused on the external kinetic energy transfer, intracranial pressure (ICP), strain energy density and first principal strain level, and their respective impacts to the brain tissue. We show that the oblique impacts of 10 and 6 m/s resulted in substantial high peaks for the ICP, strain energy density, and first principal strain levels, however, with different patterns and time frames. Also, the 2 m/s impact showed almost no increase in the above mentioned investigated parameters. More importantly, we show that there clearly exists a dynamic triple peak impact factor to the brain tissue immediately after the impact regardless of injury severity associated with different impact velocities. The dynamic triple peak impacts occurred in a sequential manner first showing strain energy density and ICP and then followed by first principal strain. This should open up a new dimension to better understand the complex mechanisms underlying TBI. Thus, it is suggested that the combination of the dynamic triple peak impacts to the brain tissue may interfere with the cerebral metabolism relative to the impact severity thereby having the potential to differentiate between severe and moderate TBI from mild TBI.
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http://dx.doi.org/10.3389/fneur.2013.00023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594920PMC
March 2013

Decompressive craniectomy causes a significant strain increase in axonal fiber tracts.

J Clin Neurosci 2013 Apr 9;20(4):509-13. Epub 2013 Feb 9.

Division of Neuronic Engineering, School of Technology and Health, Royal Institute of Technology (KTH), Alfred Nobels Allé 10, SE-141 52 Huddinge, Stockholm, Sweden.

Decompressive craniectomy (DC) allows for the expansion of a swollen brain outside the skull and has the potential to reduce intracranial pressure. However, the stretching of axons may contribute to an unfavorable outcome in patients treated with DC. In this study, we present a method for quantifying and visualizing axonal fiber deformation during both the pre-craniectomy and post-craniectomy periods to provide more insight into the mechanical effects of this treatment on axonal fibers. The deformation of the brain tissue in the form of a Lagrangian finite strain tensor for the entire brain was obtained by a non-linear image registration method based on the CT scanning data sets of the patient. Axonal fiber tracts were extracted from diffusion-weighted images. Based on the calculated brain tissue strain tensor and the observed axonal fiber tracts, the deformation of axonal fiber tracts in the form of a first principal strain, axonal strain and axonal shear strain were quantified. The greatest axonal fiber displacement was predominantly located in the treated region of the craniectomy, accompanied by a large axonal deformation close to the skull edge of the craniectomy. The distortion (stretching or shearing) of axonal fibers in the treated area of the craniectomy may influence the axonal fibers in such a way that neurochemical events are disrupted. A quantitative model may clarify some of the potential problems with this treatment.
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http://dx.doi.org/10.1016/j.jocn.2012.04.019DOI Listing
April 2013

Numerical impact simulation of gradually increased kinetic energy transfer has the potential to break up folded protein structures resulting in cytotoxic brain tissue edema.

J Neurotrauma 2013 Jul;30(13):1192-9

Section of Neurosurgery, Division of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Although the consequences of traumatic brain injury (TBI) and its treatment have been improved, there is still a substantial lack of understanding the mechanisms. Numerical simulation of the impact can throw further lights on site and mechanism of action. A finite element model of the human head and brain tissue was used to simulate TBI. The consequences of gradually increased kinetic energy transfer was analyzed by evaluating the impact intracranial pressure (ICP), strain level, and their potential influences on binding forces in folded protein structures. The gradually increased kinetic energy was found to have the potential to break apart bonds of Van der Waals in all impacts and hydrogen bonds at simulated impacts from 6 m/s and higher, thereby superseding the energy in folded protein structures. Further, impacts below 6 m/s showed none or very slight increase in impact ICP and strain levels, whereas impacts of 6 m/s or higher showed a gradual increase of the impact ICP and strain levels reaching over 1000 KPa and over 30%, respectively. The present simulation study shows that the free kinetic energy transfer, impact ICP, and strain levels all have the potential to initiate cytotoxic brain tissue edema by unfolding protein structures. The definition of mild, moderate, and severe TBI should thus be looked upon as the same condition and separated only by a gradual severity of impact.
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http://dx.doi.org/10.1089/neu.2012.2730DOI Listing
July 2013

Organic bioelectrodes in clinical neurosurgery.

Authors:
Hans von Holst

Biochim Biophys Acta 2013 Sep 24;1830(9):4345-52. Epub 2012 Oct 24.

Department of Neurosurgery, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Background: Clinical neurosurgery deals with surgical procedures and intensive care of illnesses in the human central and peripheral nervous system. Neurosurgery should be looked upon as a high-tech specialty and very much dependent on new technological innovations aiming at improvements of patient's treatment and outcome. During the last decades neurosurgery has improved substantially thanks to the introduction of applied imaging technologies such as computerized tomography and magnetic resonance tomography, and new surgical modalities such as the microscope, brain navigation and neuroanesthesiology. Neurosurgical disorders, which should have the potential to benefit from conductive organic bioelectrodes, include traumatic brain and spinal cord injury and peripheral nerve injuries due to external violence in the restoration of healthy communication. This holds true also for cerebral nerves altered in their functions due to benign and malignant brain and spinal cord tumors. Further, new innovative devices in the field of functional nervous tissue disorders make the use of organic conductive electrodes attractive by considering the electrical neurochemical properties of neural interfaces.

Conclusions: Although in its infancy, conducting organic polymers as bioelectrodes have several potential applications in clinical neurosurgery. The time it takes for new innovations and basic research to be transferred into clinical neurosurgery should not take too long. However, a prerequisite for successful implementation is the close interdisciplinary collaboration between engineers and clinicians. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.
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http://dx.doi.org/10.1016/j.bbagen.2012.10.013DOI Listing
September 2013

Increased strain levels and water content in brain tissue after decompressive craniotomy.

Acta Neurochir (Wien) 2012 Sep 1;154(9):1583-93. Epub 2012 Jun 1.

Section of Neurosurgery, Division of Clinical Neuroscience, Karolinska Institutet, SE-171 76, Stockholm, Sweden.

Background: At present there is a debate on the effectiveness of the decompressive craniotomy (DC). Stretching of axons was speculated to contribute to the unfavourable outcome for the patients. The quantification of strain level could provide more insight into the potential damage to the axons. The aim of the present study was to evaluate the strain level and water content (WC) of the brain tissue for both the pre- and post-craniotomy period.

Methods: The stretching of brain tissue was quantified retrospectively based on the computerised tomography (CT) images of six patients before and after DC by a non-linear image registration method. WC was related to specific gravity (SG), which in turn was related to the Hounsfield unit (HU) value in the CT images by a photoelectric correction according to the chemical composition of brain tissue.

Results: For all the six patients, the strain level showed a substantial increase in the brain tissue close to the treated side of DC compared with that found at the pre-craniotomy period and ranged from 24 to 55 % at the post-craniotomy period. Increase of strain level was also observed at the brain tissue opposite to the treated side, however, to a much lesser extent. The mean area of craniotomy was found to be 91.1 ± 12.7 cm(2). The brain tissue volume increased from 27 to 127 ml, corresponding to 1.65 % and 8.13 % after DC in all six patients. Also, the increased volume seemed to correlate with increased strain level. Specifically, the overall WC of brain tissue for two patients evaluated presented a significant increase after the treatment compared with the condition seen before the treatment. Furthermore, the Glasgow Coma Scale (GCS) improved in four patients after the craniotomy, while two patients died. The GCS did not seem to correlate with the strain level.

Conclusions: We present a new numerical method to quantify the stretching or strain level of brain tissue and WC following DC. The significant increase in strain level and WC in the post-craniotomy period may cause electrophysiological changes in the axons, resulting in loss of neuronal function. Hence, this new numerical method provides more insight of the consequences following DC and may be used to better define the most optimal size and area of the craniotomy in reducing the strain level development.
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http://dx.doi.org/10.1007/s00701-012-1393-2DOI Listing
September 2012

Influences of brain tissue poroelastic constants on intracranial pressure (ICP) during constant-rate infusion.

Comput Methods Biomech Biomed Engin 2013 28;16(12):1330-43. Epub 2012 Mar 28.

a Division of Neuronic Engineering, School of Technology and Health (STH), Royal Institute of Technology (KTH) , Stockholm , Sweden.

A 3D finite element (FE) model has been developed to study the mean intracranial pressure (ICP) response during constant-rate infusion using linear poroelasticity. Due to the uncertainties in the poroelastic constants for brain tissue, the influence of each of the main parameters on the transient ICP infusion curve was studied. As a prerequisite for transient analysis, steady-state simulations were performed first. The simulated steady-state pressure distribution in the brain tissue for a normal cerebrospinal fluid (CSF) circulation system showed good correlation with experiments from the literature. Furthermore, steady-state ICP closely followed the infusion experiments at different infusion rates. The verified steady-state models then served as a baseline for the subsequent transient models. For transient analysis, the simulated ICP shows a similar tendency to that found in the experiments, however, different values of the poroelastic constants have a significant effect on the infusion curve. The influence of the main poroelastic parameters including the Biot coefficient α, Skempton coefficient B, drained Young's modulus E, Poisson's ratio ν, permeability κ, CSF absorption conductance C(b) and external venous pressure p(b) was studied to investigate the influence on the pressure response. It was found that the value of the specific storage term S(ε) is the dominant factor that influences the infusion curve, and the drained Young's modulus E was identified as the dominant parameter second to S(ε). Based on the simulated infusion curves from the FE model, artificial neural network (ANN) was used to find an optimised parameter set that best fit the experimental curve. The infusion curves from both the FE simulation and using ANN confirmed the limitation of linear poroelasticity in modelling the transient constant-rate infusion.
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http://dx.doi.org/10.1080/10255842.2012.670853DOI Listing
June 2014

Training diagnosis and treatment of cervical spine trauma using a new educational program for visualization through imaging and simulation (VIS): a first evaluation by medical students.

Stud Health Technol Inform 2012 ;173:171-4

Department of Psychology, Umeå University, Umeå, Sweden.

In this pilot study we investigated how medical students evaluated a VIS practice session. Immediately after training 43 students answered a questionnaire on the training session. They evaluated VIS as a good interactive scenario based educational tool.
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May 2012

Influence of gravity for optimal head positions in the treatment of head injury patients.

Acta Neurochir (Wien) 2011 Oct 8;153(10):2057-64; discussion 2064. Epub 2011 Jul 8.

Division of Neuronic Engineering, KTH-Royal Institute of Technology, Alfred Nobels Allé 10, 141 52, Huddinge, Sweden.

Background: Brain edema is a major neurological complication of traumatic brain injury (TBI), commonly including a pathologically increased intracranial pressure (ICP) associated with poor outcome. In this study, gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue and the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a finite element (FE) model.

Methods: A detailed FE model including the meninges, brain tissue and a fully connected cerebrospinal fluid (CSF) system was used in this study. Brain tissue was modelled as a poroelastic material consisting of an elastic solid skeleton composed of neurons and neuroglia, permeated by interstitial fluid. The effect of head positions (supine and prone position) due to gravity was investigated for a localized brain edema at the posterior part of the brain.

Results: The water content increment at the edema zone remained nearly identical for both positions. However, the interstitial fluid pressure (IFP) inside the edema zone decreased around 15% by having the head in a prone position compared with a supine position.

Conclusions: The decrease of IFP inside the edema zone by changing patient position from supine to prone has the potential to alleviate the damage to central nervous system nerves. These observations indicate that considering the patient's head position during intensive care and at rehabilitation might be of importance to the treatment of edematous regions in TBI patients.
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http://dx.doi.org/10.1007/s00701-011-1078-2DOI Listing
October 2011

Spinal cord injury worldwide.

Authors:
Hans von Holst

Neuroepidemiology 2010 2;34(3):192. Epub 2010 Feb 2.

Karolinska Institutet and Royal Institute of Technology, Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden. hans.vonholst @ karolinska.se

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http://dx.doi.org/10.1159/000279336DOI Listing
December 2010

Stability of poly(3,4-ethylene dioxythiophene) materials intended for implants.

J Biomed Mater Res B Appl Biomater 2010 May;93(2):407-15

Division of Neuronic Engineering, School of Technology and Health, Royal Institute of Technology, Huddinge, Sweden.

This study presents experiments designed to study the stability of the conducting polymer poly(3,4-ethylene dioxythiophene) (PEDOT), under simulated physiological conditions using phosphate-buffered saline (PBS) and hydrogen peroxide (H(2)O(2)) (0.01 M) at 37 degrees C over a 5- to 6-week period. Voltage pulsing in PBS was used as an additional test environment. The influence of switching the counter ion used in electropolymerization from polystyrene sulphonate (PSS) to heparin was investigated. Absorbance spectroscopy and cyclic voltammetry were used to evaluate the material properties. Most of the samples in H(2)O(2) lost both electroactivity and optical absorbance within the study period, but PEDOT:PSS was found slightly more stable than PEDOT:heparin. Polymers were relatively stable in PBS throughout the study period, with around 80% of electroactivity remaining after 5 weeks, disregarding delamination, which was a significant problem especially for polymer on indium tin oxide substrates. Voltage pulsing in PBS did not increase degradation. The counter ion influenced the time course of degradation in oxidizing agents.
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http://dx.doi.org/10.1002/jbm.b.31597DOI Listing
May 2010

Incidence of traumatic peripheral nerve injuries and amputations in Sweden between 1998 and 2006.

Neuroepidemiology 2009 28;32(3):217-28. Epub 2009 Jan 28.

Division of Neuronic Engineering, School of Technology and Health, Royal Institute of Technology, Huddinge, Sweden.

Background: To define the epidemiological pattern of nerve injuries and traumatic amputations in Sweden, 1998-2006, and investigate possible targets for emerging neural engineering and neuroprosthetic technologies.

Methods: The Swedish Hospital Discharge Register was used as the information base, including data from all public inpatient care, excluding outpatient data. ICD-10 codes were used to classify nerve injuries and traumatic amputations of high incidence levels or inpatient care time. Selected codes, causative factors, age and gender distribution were discussed in detail, and potential targets for tailored solutions were identified.

Results: Incidence rate was determined as 13.9 for nerve injuries and 5.21 for amputations per 100,000 person-years. The majority of injuries occurred at the wrist and hand levels, although it could be concluded that these are often minor injuries requiring less than a week of hospitalization. The single most care-consuming nerve injury was brachial plexus injury, constituting on average 68 injuries and 960 hospital days annually. When minor amputations of fingers and toes were disregarded, the most frequent site of amputation was between the knee and ankle (24 patients/year).

Conclusions: Based on an analysis of incidence and care time, we find that brachial plexus injuries and lower leg amputations should be the primary targets of new technologies.
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http://dx.doi.org/10.1159/000197900DOI Listing
December 2009

Bifunctional dendrimers: from robust synthesis and accelerated one-pot postfunctionalization strategy to potential applications.

Angew Chem Int Ed Engl 2009 ;48(12):2126-30

Royal Institute of Technology, School of Chemistry and Chemical Science, Division of Coating Technology, Teknikringen 56-58, 10044 Stockholm, Sweden.

A fourth wheel: Two sets of bifunctional AB(2)C dendrimers having internal acetylene/azides and external hydroxy groups were constructed utilizing benign synthetic protocols. An in situ postfunctionalization strategy was successfully carried out to illustrate the chemoselective nature of these dendrimers. The dendrimers were also transformed into dendritic nanoparticles or utilized as dendritic crosslinkers for the fabrication hydrogels.
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http://dx.doi.org/10.1002/anie.200804987DOI Listing
May 2009

Composite biomolecule/PEDOT materials for neural electrodes.

Biointerphases 2008 Sep;3(3):83-93

School of Technology and Health, Royal Institute of Technology, Alfred Nobels Allé 10, SE-14152 Huddinge, Sweden.

Electrodes intended for neural communication must be designed to meet both the electrochemical and biological requirements essential for long term functionality. Metallic electrode materials have been found inadequate to meet these requirements and therefore conducting polymers for neural electrodes have emerged as a field of interest. One clear advantage with polymer electrodes is the possibility to tailor the material to have optimal biomechanical and chemical properties for certain applications. To identify and evaluate new materials for neural communication electrodes, three charged biomolecules, fibrinogen, hyaluronic acid (HA), and heparin are used as counterions in the electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT). The resulting material is evaluated electrochemically and the amount of exposed biomolecule on the surface is quantified. PEDOT:biomolecule surfaces are also studied with static contact angle measurements as well as scanning electron microscopy and compared to surfaces of PEDOT electrochemically deposited with surfactant counterion polystyrene sulphonate (PSS). Electrochemical measurements show that PEDOT:heparin and PEDOT:HA, both have the electrochemical properties required for neural electrodes, and PEDOT:heparin also compares well to PEDOT:PSS. PEDOT:fibrinogen is found less suitable as neural electrode material.
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http://dx.doi.org/10.1116/1.2998407DOI Listing
September 2008

Critical evaluation of the existing guidelines on mild traumatic brain injury.

J Rehabil Med 2004 Feb(43 Suppl):106-12

Department of Internal Medicine, University of Iowa Health Center, Iowa City, Iowa 52242, USA.

The purpose of guidelines is to reduce practice variability, but they need to be evidence-based. We examine current mild traumatic brain injury guidelines, critique their basis in evidence and examine their variability in recommendations. A systematic search of the literature found 38,806 abstracts, with 41 guidelines. There were 18 sports-related guidelines, 13 related to admission policies, 12 related to imaging and 5 related to neuropsychological assessment. Some guidelines addressed several areas. Only 5 guidelines reported a methodology for the assembly of evidence used to develop the guideline. After appraising the guidelines against a validated index, we found that 3 of the 41 guidelines could be categorized as evidence-based. Two of these focused on paediatric patients and 1 on adult patients. Limited methodological quality in the current guidelines results in conflicting recommendations amongst them.
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http://dx.doi.org/10.1080/16501960410023868DOI Listing
February 2004

Prognosis for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

J Rehabil Med 2004 Feb(43 Suppl):84-105

Alberta Centre for Injury Control and Research, Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada.

We searched the literature on the epidemiology, diagnosis, prognosis, treatment and costs of mild traumatic brain injury. Of 428 studies related to prognosis after mild traumatic brain injury, 120 (28%) were accepted after critical review. These comprise our best-evidence synthesis on prognosis after mild traumatic brain injury. There was consistent and methodologically sound evidence that children's prognosis after mild traumatic brain injury is good, with quick resolution of symptoms and little evidence of residual cognitive, behavioural or academic deficits. For adults, cognitive deficits and symptoms are common in the acute stage, and the majority of studies report recovery for most within 3-12 months. Where symptoms persist, compensation/litigation is a factor, but there is little consistent evidence for other predictors. The literature on this area is of varying quality and causal inferences are often mistakenly drawn from cross-sectional studies.
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http://dx.doi.org/10.1080/16501960410023859DOI Listing
February 2004

Non-surgical intervention and cost for mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

J Rehabil Med 2004 Feb(43 Suppl):76-83

Department of Neuroscience, Rehabilitation Medicine, Uppsala University Hospital, Uppsala, Sweden.

We examined the evidence for non-surgical interventions and for economic costs for mild traumatic brain injury patients by a systematic search of the literature and a best-evidence synthesis. After screening 38,806 abstracts, we critically reviewed 45 articles on intervention and accepted 16 (36%). We reviewed 16 articles on economic costs and accepted 7 (44%). We found some evidence that early educational information can reduce long-term complaints and that this early intervention need not be intensive. Most cost studies were performed more than a decade ago. Indirect costs are probably higher than direct costs. Studies comparing costs for routine hospitalized observation vs the use of computerized tomography scan examination for selective hospital admission indicate that the latter policy reduces costs, but comparable clinical outcome of these policies has not been demonstrated. The sparse scientific literature in these areas reflects both conceptual confusion and limited knowledge of the natural history of mild traumatic brain injury.
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http://dx.doi.org/10.1080/16501960410023840DOI Listing
February 2004

Diagnostic procedures in mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

J Rehabil Med 2004 Feb(43 Suppl):61-75

Department of Neuroscience, Rehabilitation Medicine, Uppsala University Hospital, Uppsala, Sweden.

We examined diagnostic procedures in mild traumatic brain injury by a systematic literature search. After screening 38,806 abstracts, we critically reviewed 228 diagnostic studies and accepted 73 (32%). The estimated prevalence of intracranial CT scan abnormalities is 5% in patients presenting to hospital with a Glasgow Coma Scale score of 15 and 30% or higher in patients presenting with a score of 13. About 1% of all treated patients with mild traumatic brain injury require neurosurgical intervention. There is strong evidence that clinical factors can predict computerized tomography scan abnormalities and the need for intervention in adults, but no such evidence for mild traumatic brain injury in children. We found evidence that skull fracture is a risk factor for intracranial lesions, but the diagnostic accuracy of radiologically diagnosed skull fracture as an indication of intracranial lesions is poor. There is only a little evidence for the diagnostic validity of cognitive testing and other diagnostic tools for mild traumatic brain injury.
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http://dx.doi.org/10.1080/16501960410023822DOI Listing
February 2004

Incidence, risk factors and prevention of mild traumatic brain injury: results of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

J Rehabil Med 2004 Feb(43 Suppl):28-60

Alberta Centre for Injury Control and Research, Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada.

Objective: We undertook a best-evidence synthesis on the incidence, risk factors and prevention of mild traumatic brain injury.

Methods: Medline, Cinahl, PsycINFO and Embase were searched for relevant articles. After screening 38,806 abstracts, we critically reviewed 169 studies on incidence, risk and prevention, and accepted 121 (72%).

Results: The accepted articles show that 70-90% of all treated brain injuries are mild, and the incidence of hospital-treated patients with mild traumatic brain injury is about 100-300/100,000 population. However, much mild traumatic brain injury is not treated at hospitals, and the true population-based rate is probably above 600/100,000. Mild traumatic brain injury is more common in males and in teenagers and young adults. Falls and motor-vehicle collisions are common causes.

Conclusion: Strong evidence supports helmet use to prevent mild traumatic brain injury in motorcyclists and bicyclists. The mild traumatic brain injury literature is of varying quality, and the studies are very heterogeneous. Nevertheless, there is evidence that mild traumatic brain injury is an important public health problem, but we need more high-quality research into this area.
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http://dx.doi.org/10.1080/16501960410023732DOI Listing
February 2004

Mild traumatic brain injuries presenting to Swedish hospitals in 1987-2000.

J Rehabil Med 2004 Feb(43 Suppl):22-7

Department of Internal Medicine, University of Iowa Health Center, Iowa City, Iowa, USA.

Objective: To evaluate the incidence and causes of mild traumatic brain injury in Sweden.

Design: Retrospective, population-based incidence cohort study.

Subjects: All persons presenting to hospitals in Sweden between 1987 and 2000 with a discharge diagnosis of ICD-9 code 850 and ICD-10 code S0.60.

Methods: Data source was the Hospital Discharge Register at the National Board of Health and Welfare (Sweden). Incidence rates are stratified by age, gender, mechanism of injury and length of hospital stay.

Results: Men had a mean of 209 mild traumatic brain injuries per 100,000 inhabitants and women averaged 148 per 100,000. Men had more mild traumatic brain injury than women at all ages. There were 2 incidence peaks, in the age strata 16-20 years and those over 65 years. Falls were the most common cause of mild traumatic brain injury overall and occurred commonly under the age of 10 years and over the age of 65 years. Motor vehicle and bicycle injuries were the second and third most common causes of mild traumatic brain injury, and had their peak incidence in those aged 16-35 years.

Conclusion: Preventative strategies for mild traumatic brain injury should be age and gender specific.
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http://dx.doi.org/10.1080/16501960410023714DOI Listing
February 2004

Mandate of the WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury.

J Rehabil Med 2004 Feb(43 Suppl):8-10

Department of Neurosurgery and the WHO Collaborating Centre for Neurotrauma, Karolinska Institutet, Stockholm, Sweden.

In collaboration with outside experts, the WHO Collaborating Centre for Neurotrauma at the Karolinska Institute, Stockholm, Sweden, has assembled a task force to undertake a best-evidence synthesis of the literature on mild traumatic brain injury. The task force has addressed the epidemiology, diagnosis, prognosis, treatment and economic costs of mild traumatic brain injury in order to make recommendations to reduce the medical as well as the social consequences of mild traumatic brain injury.
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http://dx.doi.org/10.1080/16501960410023633DOI Listing
February 2004

Transsphenoidal surgery in Cushing disease: 10 years of experience in 34 consecutive cases.

J Neurosurg 2004 Apr;100(4):634-8

Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden.

Object: Cushing disease is a rare disorder. Because of their small size the adrenocorticotropic hormone (ACTH)-producing tumors are often not detectable on neuroimaging studies. To obtain a cure with transsphenoidal surgery (TSS) may therefore be difficult. In this report the authors present 10 years of experience in the treatment of patients with Cushing disease who were followed up with the same protocol and treated by the same surgeon.

Methods: Thirty-four patients, 26 of them female and eight of them male (mean age 40 years, range 13-74 years) were studied. All had obvious clinical signs and symptoms of Cushing syndrome. Magnetic resonance (MR) imaging was performed in all patients, and inferior petrosal sinus (IPS) sampling was done in 14. In 12 patients MR imaging indicated a pituitary tumor; 10 were microadenomas and two were macroadenomas. In six patients with no visible tumor, the results of IPS sampling supported the diagnosis. All patients underwent TSS; the mean follow-up duration was 6 +/- 0.5 years. Selective adenomectomy was performed in 32 and hemihypophysectomy in the other two patients. A cure was obtained in 31 patients (91%) after one TSS and in two more patients after further TSS; one patient was not cured despite two TSSs and one underwent bilateral adrenalectomy. Disease recurrence was seen in two patients after 3 years, and they were successfully treated with stereotactic gamma knife surgery. Half of the patients had an ACTH deficiency postoperatively, whereas one third had other pituitary hormone insufficiencies. There were no serious complications attributable to the surgical intervention.

Conclusions: Transsphenoidal surgery with selective adenomectomy is an effective and safe treatment for Cushing disease. In the patients presented in this study, the surgical outcome seemed to depend on careful preoperative evaluation and the surgeon's experience. For optimal results in this rare disease the authors therefore suggest that the endocrinological, radiological, and surgical procedures be coordinated in a specialized center.
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http://dx.doi.org/10.3171/jns.2004.100.4.0634DOI Listing
April 2004
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