Bio

Bio


Dr. Stienen obtained his medical degree at the Ruhr-University Bochum (Germany), where he also earned his doctoral degree (MD) with highest honors (Summa Cum Laude) for experimental studies dealing with the conductivity of potassium channels of glial cells. He undertook his neurosurgical training at the Cantonal Hospital St.Gallen, and at the University Hospitals of Geneva and Zürich (Switzerland). Dr. Stienen has obtained the Swiss board certification for Neurosurgery (FMH) in 01/2018, and was nominated “Fellow of the European Board of Neurological Surgeons” (FEBNS) in 03/2018. He has been appointed consultant neurosurgeon at the University Hospital Zürich in 01/2018 and has achieved the rank of a private docent (venia legendi) at the University of Zürich with a habilitation thesis on “The Assessment of Complications and Outcomes in Modern Neurosurgical Patient Care”.

Dr. Stienen’s primary interest is caring for patients, and he is constantly motivated to bring out the best by seeing them recover well and getting back to their daily lives. Besides the clinical work, he has long-standing interest in research, focusing mainly on the three topics 1) Subjective and objective outcome assessment of patients with diseases of the spine, 2) Multi-dimensional assessment of patients after aneurysmal subarachnoid hemorrhage and 3) Training and education in Neurosurgery. Dr. Stienen has conducted studies and led research groups. He has published extensively in those fields, and is frequently invited as reviewer for international highly ranked academic journals.

As Clinical Instructor at Stanford, Dr. Stienen is currently concentrating on the treatment of complex diseases of the spine (Complex Spine Fellowship). After this, he will travel to South Korea for an additional spine fellowship, having been awarded with a travel grant from the Swiss Society of Neurosurgery. He will then continue to pursue a clinical academic career in neurosurgery as attending neurosurgeon at the University Hospital Zürich.

Academic Appointments


Administrative Appointments


  • Junior Resident, Department of Neurosurgery, Kantonsspital St.Gallen, Switzerland (Prof. Gerhard Hildebrandt) (2012 - 2014)
  • Senior Resident, Department of Neurosurgery, Hôpitaux Universitaires de Genève, Switzerland (Prof. Karl Schaller) (2014 - 2016)
  • Chief Resident, Department of Neurosurgery, University Hospital Zurich, Switzerland (Prof. Luca Regli) (2017 - 2017)
  • Attending Neurosurgeon, Department of Neurosurgery, University Hospital Zurich, Switzerland (Prof. Luca Regli) (2018 - 2018)
  • Clinical Instructor & Complex Spine Fellow, Department of Neurosurgery, Stanford University Hospital (Prof. Jon Park & Prof. John Ratliff) (2018 - 2019)

Professional Education


  • Priv.-Doz., University of Zurich, Zurich, Switzerland, Neurosurgery (2019)
  • FEBNS, European Association of Neurosurgical Societies (EANS), Neurosurgery (2018)
  • FMH, Foederatio Medicorum Helveticorum, Neurosurgery (2018)
  • MD, Ruhr-University Bochum, Bochum, Germany, Medicine (2011)

Research & Scholarship

Clinical Trials


  • A Patient Registry at the Neurosurgery Department Recruiting

    The investigators record all indications, treatments and outcomes from patients treated at the Neurosurgery Department. - Trial with surgical intervention

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  • Covers to Improve Esthetic Outcome After Surgery for Chronic Subdural Hematoma Recruiting

    The clinical-functional result after frontal and parietal burr-hole trepanation for the treatment of chronic subdural hematoma (cSDH) is effective with regards to control of the hematoma and regression of symptoms (headache, decreased vigilance and neurological deficits). However, in patients the treatment may leave visible depressions of the scalp, just above the trepanation sites, that typically develop gradually after weeks - months after the procedure. A considerable proportion of patients find this aesthetically, functionally and psychologically disturbing; the skin depressions may even cause pain or interfere with activities of daily living, such as combing, etc. An effective method would exist to avoid this undesired treatment effect: Before the skin is closed, a permeable titanium burr-hole plate could be attached above the trepanation site in order to prevent the skin from sinking into the bony defect. However, this is rarely done today, likely because there is no evidence that this treatment modification is effective and safe. Moreover, as material is implanted, this causes additional costs. The primary aim of this study is to evaluate whether the application of burr-hole plates on both the frontal and parietal burr-hole in the context of burr-hole trepanation for the treatment of cSDH can improve patient satisfaction with the aesthetic result of the surgery. In addition, the study is intended to demonstrate that this additional measure will not result in poorer hematoma control, poorer clinical/neurological outcomes, or additional complications for the patient. In a prospective, single-blind and controlled approach, we randomize 80 patients with uni- or bilateral cSDH into an intervention group (with burr-hole plates) or into a control group (without burr-hole plates). The primary end result of the study is the patient's reported satisfaction with the aesthetic outcome of the surgical scar. Secondary results are pain, functionality, neurological status, health-related quality of life, residual hematoma volume, and complications (according to Clavien-Dindo scale; especially re-operation rate for recurring cSDH and infections). The study corresponds to a modern approach, since today's patients not only expect favorable treatment results for their disease, but the therapy should also avoid permanent undesired side-effects, if possible.

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  • Linking Digital Smartphone Behaviour With Brain Function Recruiting

    This study will thus examine daily behaviour based on smartphone use and link it to the neurological and neuropsychological status as well as to neuroradiological studies that are part of the clinical routine. The study will examine behaviour changes before and after surgery, and how this change in measured behaviour with the smartphone relates to today's "gold standard", namely professional neuropsychological examination and quantification of brain damage on imaging studies (MRI). This study is a proof-of-principle study that intends to build the basis for larger future observational studies on patients with focal or diffuse brain pathologies.

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  • Swiss SOS MoCA - DCI Study Recruiting

    The primary objective of this multicenter observational study is to determine the effect size of the relationship between DCI and neuropsychological impairment 14-28 days and 3 months after aSAH. Secondary objectives are the feasibility to administer and the validity of the MoCA in an intensive care unit setting, as well as the test/retest reliability of the MoCA in patients with acute brain damage in absence of aSAH.

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  • Swiss Study on Subarachnoid Hemorrhage Recruiting

    This registry was created to assess management parameters of patients treated for aneurysmal subarachnoid hemorrhage in Switzerland. All Swiss hospitals with a neurosurgery department, an intensive care unit and an interventional neuroradiology team that treat neurovascular emergencies participate in the registry. Clinical parameters are entered into a common database. This database will provide (1) a nationwide assessment of the current standard of care and (2) the outcomes for patients in Switzerland including neuropsychological assessments.

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  • The Pathogenesis of Terson Syndrome and the Role of CSF Tau / Amyloid-ß 40 and 42 in Patients With Aneurysmatic Subarachnoid Hemorrhage Not Recruiting

    Prospective clinical study to investigate the pathogenesis of Terson syndrome and the prognostic value of the CSF-biomarkers tau-protein and amyloid-β 40 and 42 in patients with aneurysmatic subarachnoid hemorrhage. Our two hypotheses are as follows: 1. The incidence of Terson syndrome correlates with the initial intracranial opening pressure (measured with extra ventricular drain) 2. The CSF-biomarkers correlate with the outcome assessed at discharge, 3-, 6- and 12-months postictally using Glasgow-Outcome-Scale-Extended (GOSE) and Euro-Qol-5 as well as with complications related to aneurysmatic subarachnoid hemorrhage such as cerebral vasospasm, delayed cerebral ischemia and re-bleed.

    Stanford is currently not accepting patients for this trial.

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  • The Value of Short-term Pain Relief for the Prediction of Long-term Outcome After Cervical or Lumbar Nerve Root Infiltration Not Recruiting

    The purpose if this study is to assess the response to nerve root infiltration therapy in patients with cervical or lumbar disc herniations.

    Stanford is currently not accepting patients for this trial.

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Publications

All Publications


  • Objective measures of functional impairment for degenerative diseases of the lumbar spine: a systematic review of the literature. The spine journal : official journal of the North American Spine Society Stienen, M. N., Ho, A. L., Staartjes, V. E., Maldaner, N., Veeravagu, A., Desai, A., Gautschi, O. P., Bellut, D., Regli, L., Ratliff, J. K., Park, J. 2019

    Abstract

    BACKGROUND CONTEXT: The accurate determination of a patient's functional status is necessary for therapeutic decision-making and to critically appraise treatment efficacy. Current subjective patient-reported outcome measure (PROM)-based assessments have limitations and can be complimented by objective measures of function.PURPOSE: To systematically review the literature and provide an overview on the available objective measures of function for patients with degenerative diseases of the lumbar spine.STUDY DESIGN/SETTING: Systematic review of the literature.METHODS: The PRISMA guidelines were followed. Two reviewers independently searched the PubMed, Web of Science, EMBASE and SCOPUS databases for permutations of the words "objective", "assessment", "function", "lumbar" and "spine", including articles on human subjects with degenerative diseases of the lumbar spine that reported on objective measures of function, published until September 2018. No funding was received. The authors report no conflicts of interest.RESULTS: Of 2389 identified articles, 82 were included in the final analysis. There was a significant increase of 0.12 per year in the number of publications dealing with objective measures of function since 1989 (95% CI 0.08-0.16, p<0.001). Some publications studied multiple diagnoses and objective measures. The US was the leading nation in terms of scientific output for objective outcome measures (n=21; 25.6%), followed by Switzerland (n=17; 20.7%), Canada, Germany and the United Kingdom (each n=6; 7.3%). Our search revealed 21 different types of objective measures, predominantly applied to patients with lumbar spinal stenosis (n=67 publications; 81.7%), chronic/unspecific low back pain (n=28; 34.2%) and lumbar disc herniation (n=22; 26.8%). The Timed-Up-and-Go (TUG) test was the most frequently applied measure (n=26 publications; 31.7%; cumulative number of reported subjects: 5181), followed by the Motorized Treadmill Test (MTT; n=25 publications; 30.5%, 1499 subjects) and with each n=9 publications (11.0%) the Five-Repetition Sit-To-Stand test (5R-STS; 955 subjects), as well as accelerometry analyses (336 subjects). The reliability and validity of many of the less-applied objective measures was uncertain. There was profound heterogeneity in their application and interpretation of results. Risk of bias was not assessed.CONCLUSIONS: Clinical studies on patients with lumbar degenerative diseases increasingly employ objective measures of function, which offer high potential for improving the quality of outcome measurement in patient-care and research. This review provides an overview on available options. Our findings call for an agreement and standardization in terms of test selection, conduction and analysis to facilitate comparison of results across cohorts.

    View details for DOI 10.1016/j.spinee.2019.02.014

    View details for PubMedID 30831316

  • Reversible Paraplegie - erfreulicher Ausgang bei verzogert gestellter Diagnose. Praxis Stienen, M. N., Bellut, D., Stojanov, D., Eriks-Hoogland, I., Regli, L., Oertel, M. F. 2019; 108 (5): 341–45

    Abstract

    Reversible Paraplegia - Favorable Outcome After Delayed Diagnosis Abstract. A 74-year-old woman was referred for progressive gait disturbances. On presentation, she had a complete paraplegia (wheelchair-bound for 19 months) and bladder sphincter dyssynergia with sensory sacral sparing. Magnetic resonance imaging studies revealed a 24 * 13 * 17 mm intradural mass with compression of the spinal cord and myelomalacia between C6 and Th1. We performed unilateral laminectomies of C6-Th1 and microsurgical resection of a meningioma. Under intensive rehabilitation, the patient regained independent walking ability and recovery of bladder function and continence within six months postoperatively.

    View details for DOI 10.1024/1661-8157/a003205

    View details for PubMedID 30940039

  • Posterior open reduction and internal fixation of C1 fractures: the C-clamp technique. Acta neurochirurgica Gelinas-Phaneuf, N., Stienen, M. N., Park, J. 2018

    Abstract

    BACKGROUND: The treatment of isolated atlas (C1) fractures is still controversial. The surgical management usually involves an arthrodesis of the atlanto-axial (C1-C2) joint with or without occipital fixation. We reviewed the senior author's series of posterior only open reduction and internal fixation (ORIF) of isolated C1 fractures.METHODS: Retrospective analysis of consecutive patients with isolated C1 fractures, treated in one institution by posterior only ORIF between 2005 and 2017. All fractures of C1 with concomitant C2 or occipital condyle fractures were excluded. The C1 arch was reduced with C1 lateral mass screws, connected with a transverse rod in a C-clamp fashion. We analyzed neck pain on the visual analog scale (VAS) and imaging signs of instability on follow-up.RESULTS: We identified eight patients, six males, and two females with a mean age of 37.9years (range 20-71years). All were neurologically intact before surgery, none had a documented transverse ligament disruption, and the mean gap between the fractured pieces was 5.3mm. Five patients were treated <72h of injury, two patients had failed halo vest for 8-10weeks, and one patient was operated after 6months because of painful pseudarthrosis despite wearing a hard collar. One patient developed a transient neurological deficit due to vertebral artery dissection that had resolved completely at time of follow-up. The mean follow-up after surgery was 12.6months (range 1-49months) and mean preoperative neck pain (VAS 5.1) was significantly decreased (VAS 0.8; p<0.001). On follow-up radiological evaluation, no instability was noted in any patient.CONCLUSIONS: Posterior ORIF of C1 fractures may be an option for patients who fail or do not wish to pursue conservative management. The particular advantage of this technique over C1-C2 arthrodesis is the preserved range of rotational motion. Mono-axial screws seem to provide better reduction capacity.

    View details for DOI 10.1007/s00701-018-3710-x

    View details for PubMedID 30393819

  • Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study. BMJ (Clinical research ed.) Jaja, B. N., Saposnik, G., Lingsma, H. F., Macdonald, E., Thorpe, K. E., Mamdani, M., Steyerberg, E. W., Molyneux, A., Manoel, A. i., Schatlo, B., Hanggi, D., Hasan, D., Wong, G. K., Etminan, N., Fukuda, H., Torner, J., Schaller, K. L., Suarez, J. I., Stienen, M. N., Vergouwen, M. D., Rinkel, G. J., Spears, J., Cusimano, M. D., Todd, M., Le Roux, P., Kirkpatrick, P., Pickard, J., van den Bergh, W. M., Murray, G., Johnston, S. C., Yamagata, S., Mayer, S., Schweizer, T. A., Macdonald, R. L. 2018; 360: j5745

    Abstract

    To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).Cohort study with logistic regression analysis to combine predictors and treatment modality.Subarachnoid Haemorrhage International Trialists' (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a "neuroimaging model," with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

    View details for DOI 10.1136/bmj.j5745

    View details for PubMedID 29348138

  • UniversitätsSpital Zürich: 80 years of neurosurgical patient care in Switzerland. Acta neurochirurgica Stienen, M. N., Serra, C., Stieglitz, L. H., Krayenbühl, N., Bozinov, O., Regli, L. 2018; 160 (1): 3–22

    Abstract

    The predecessor of today's Department of Neurosurgery, UniversitätsSpital Zürich (USZ), was founded 80 years ago as the first independent Swiss clinic dedicated to neurosurgical patient care. On the occasion of this anniversary, we aimed to highlight the history of neurosurgery as a specialty at the USZ, and to put it into the historical context of Swiss and European Neurosurgery.A literature review was conducted and we searched the archives of the USZ and the city of Zurich, as well as those of Swiss journals to extract relevant published articles, books, historical reports and pictures. The USZ Department of Medical History, the Museum of Medical History and the Swiss National Library were contacted to provide source material. To further verify the content, (emeritus) faculty from the USZ and external experts on the history of Swiss neurosurgery reviewed the manuscript.Surgeries of the head and spine had occasionally been conducted in Zurich by the general surgeons, Rudolf Ulrich Krönlein and Paul Clairmont, before an independent neurosurgical clinic was founded by Hugo Krayenbühl on 6 July 1937. This was the first Swiss department dedicated to neurosurgical patient care. Besides providing high-quality medicine for both the local and wider population, the department was chaired by eminent leaders of neurosurgery, who influenced the scientific and clinical neurosurgery of their time. As such, it has long been regarded as one of the top teaching and research hospitals in Switzerland and in Europe.On the occasion of its 80th anniversary, we have performed an in-depth review of its development, successes and challenges, with a special focus on the early decades. Reflecting on the past, we have identified common denominators of success in neurosurgery that remain valid today.

    View details for DOI 10.1007/s00701-017-3357-z

    View details for PubMedID 29134341

    View details for PubMedCentralID PMC5735218

  • Predictors of In-Hospital Death After Aneurysmal Subarachnoid Hemorrhage: Analysis of a Nationwide Database (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]). Stroke Stienen, M. N., Germans, M., Burkhardt, J. K., Neidert, M. C., Fung, C., Bervini, D., Zumofen, D., Röthlisberger, M., Marbacher, S., Maduri, R., Robert, T., Seule, M. A., Bijlenga, P., Schaller, K., Fandino, J., Smoll, N. R., Maldaner, N., Finkenstädt, S., Esposito, G., Schatlo, B., Keller, E., Bozinov, O., Regli, L. 2018; 49 (2): 333–40

    Abstract

    To identify predictors of in-hospital mortality in patients with aneurysmal subarachnoid hemorrhage and to estimate their impact.Retrospective analysis of prospective data from a nationwide multicenter registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal Subarachnoid Hemorrhage]; 2009-2015). Both clinical and radiological independent predictors of in-hospital mortality were identified, and their effect size was determined by calculating adjusted odds ratios (aORs) using multivariate logistic regression. Survival was displayed using Kaplan-Meier curves.Data of n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%), active treatment was discontinued after hospital admission (no aneurysm occlusion attempted), and this cohort was excluded from analysis of the main statistical model. In the remaining n=1669 patients, the rate of in-hospital mortality was 13.9% (n=232). Strong independent predictors of in-hospital mortality were rebleeding (aOR, 7.69; 95% confidence interval, 3.00-19.71; P<0.001), cerebral infarction attributable to delayed cerebral ischemia (aOR, 3.66; 95% confidence interval, 1.94-6.89; P<0.001), intraventricular hemorrhage (aOR, 2.65; 95% confidence interval, 1.38-5.09; P=0.003), and new infarction post-treatment (aOR, 2.57; 95% confidence interval, 1.43-4.62; P=0.002).Several-and among them modifiable-factors seem to be associated with in-hospital mortality after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming to reduce the risk of rebleeding are most promising in patients where active treatment is initially pursued.URL: http://www.clinicaltrials.gov. Unique identifier: NCT03245866.

    View details for DOI 10.1161/STROKEAHA.117.019328

    View details for PubMedID 29335333

  • The Barrow Neurological Institute Grading Scale as a Predictor for Delayed Cerebral Ischemia and Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From a Nationwide Patient Registry (Swiss SOS). Neurosurgery Neidert, M. C., Maldaner, N., Stienen, M. N., Roethlisberger, M., Zumofen, D. W., D'Alonzo, D., Marbacher, S., Maduri, R., Hostettler, I. C., Schatlo, B., Schneider, M. M., Seule, M. A., Schöni, D., Goldberg, J., Fung, C., Arrighi, M., Valsecchi, D., Bijlenga, P., Schaller, K., Bozinov, O., Regli, L., Burkhardt, J. K. 2018

    Abstract

    The Barrow Neurological Institute (BNI) scale is a novel quantitative scale measuring maximal subarachnoid hemorrhage (SAH) thickness to predict delayed cerebral ischemia (DCI). This scale could replace the Fisher score, which was traditionally used for DCI prediction.To validate the BNI scale.All patient data were obtained from the prospective aneurysmal SAH multicenter registry. In 1321 patients, demographic data, BNI scale, DCI, and modified Rankin Scale (mRS) score up to the 1-yr follow-up (1FU) were available for descriptive and univariate statistics. Outcome was dichotomized in favorable (mRS 0-2) and unfavorable (mRS 3-6). Odds ratios (OR) for DCI of Fisher 3 patients (n = 1115, 84%) compared to a control cohort of Fisher grade 1, 2, and 4 patients (n = 206, 16%) were calculated for each BNI grade separately.Overall, 409 patients (31%) developed DCI with a high DCI rate in the Fisher 3 cohort (34%). With regard to the BNI scale, DCI rates went up progressively from 26% (BNI 2) to 38% (BNI 5) and corresponding OR for DCI increased from 1.9 (1.0-3.5, 95% confidence interval) to 3.4 (2.1-5.3), respectively. BNI grade 5 patients had high rates of unfavorable outcome with 75% at discharge and 58% at 1FU. Likelihood for unfavorable outcome was high in BNI grade 5 patients with OR 5.9 (3.9-8.9) at discharge and OR 6.6 (4.1-10.5) at 1FU.This multicenter external validation analysis confirms that patients with a higher BNI grade show a significantly higher risk for DCI; high BNI grade was a predictor for unfavorable outcome at discharge and 1FU.

    View details for DOI 10.1093/neuros/nyx609

    View details for PubMedID 29351673

  • The influence of preoperative dependency on mortality, functional recovery and complications after microsurgical resection of intracranial tumors. Journal of neuro-oncology Stienen, M. N., Zhang, D. Y., Broggi, M., Seggewiss, D., Villa, S., Schiavolin, S., Bozinov, O., Krayenbühl, N., Sarnthein, J., Ferroli, P., Regli, L. 2018

    Abstract

    The decision whether to operate on patients with intracranial tumors is complex and influenced by patient-specific factors, including the preoperative functional status. This work assesses the risks for mortality and complications, and post-operative recovery in functionally dependent patients undergoing microsurgical resection of intracranial tumors.Observational two-center study, analyzing institutional registry data. Dependency was defined as admission Karnofsky Performance Scale (KPS) of ≤ 50. The primary endpoint was in-hospital mortality. Secondary endpoints were rate and type [Clavien-Dindo grade (CDG)] of complications, as well as postoperative change in KPS until the 3-month follow-up (M3).Of n = 1951 patients, n = 98 (5.0%) were dependent. Mortality rates were 2.0% for dependent and 0.4% for independent patients (p = 0.018). In univariable analysis, dependent patients were more likely than independent patients to die in hospital (OR 5.49, 95% CI 1.12-26.8, p = 0.035). In a multivariable model, the effect was slightly attenuated (OR 4.75, 95% CI 0.91-24.7, p = 0.064). Dependent patients tended to experience more postoperative complications. They were more likely to suffer from a severe complication (CDG 4 and 5; OR 3.55, 95% CI 1.49-8.46, p = 0.004). In 40.8 and 52.4% of cases, dependent patients regained functional independence at discharge and M3, respectively.In operated patients with intracranial tumors presenting functionally dependent at admission, the risk for in-hospital mortality and complications is elevated. However, if conducted successfully, surgery may lead to regain of independence in every second patient within 3 months.

    View details for DOI 10.1007/s11060-018-2882-9

    View details for PubMedID 29721751

  • Measuring the Impact of Delayed Cerebral Ischemia on Neuropsychological Outcome After Aneurysmal Subarachnoid Hemorrhage-Protocol of a Swiss Nationwide Observational Study (MoCA-DCI Study). Neurosurgery Stienen, M. N., Fung, C., Bijlenga, P., Zumofen, D. W., Maduri, R., Robert, T., Seule, M. A., Marbacher, S., Geisseler, O., Brugger, P., Gutbrod, K., Chicherio, C., Monsch, A. U., Beaud, V., Rossi, S., Früh, S., Schmid, N., Smoll, N. R., Keller, E., Regli, L. 2018

    Abstract

    The exact relationship between delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and neuropsychological impairment remains unknown, as previous studies lacked a baseline examination after aneurysm occlusion but before the DCI-period. Neuropsychological evaluation of acutely ill patients is often applied in a busy intensive care unit (ICU), where distraction represents a bias to the obtained results.To evaluate the relationship between DCI and neuropsychological outcome after aSAH by comparing the Montreal Cognitive Assessment (MoCA) results in aSAH patients with and without DCI at 3 mo with a baseline examination before the DCI-period (part 1). To determine the reliability of the MoCA, when applied in an ICU setting (part 2).Prospective, multicenter, and observational study performed at all Swiss neurovascular centers. For part 1, n = 240 consecutive aSAH patients and for part 2, n = 50 patients with acute brain injury are recruited.Part 1: Effect size of the relationship between DCI and neuropsychological outcome (MoCA). Part 2: Reliability measures for the MoCA.The institutional review boards approved this study on July 4, 2017 under case number BASEC 2017-00103. After completion, the results will be offered to an international scientific journal for peer-reviewed publication. This study determines the exact impact of DCI on the neuropsychological outcome after aSAH, unbiased by confounding factors such as early brain injury or patient-specific characteristics. The study provides unique insights in the neuropsychological state of patients in the early period after aSAH.

    View details for DOI 10.1093/neuros/nyy155

    View details for PubMedID 29762759

  • Efficacy of intraoperative epidural triamcinolone application in lumbar microdiscectomy: a matched-control study. Journal of neurosurgery. Spine Stienen, M. N., Joswig, H., Chau, I., Neidert, M. C., Bellut, D., Wälchli, T., Schaller, K., Gautschi, O. P. 2018; 28 (3): 291–99

    Abstract

    OBJECTIVE The purpose of this study was to investigate whether the intraoperative application of an epidural steroid (ES) on the decompressed nerve root improves short- and midterm subjective and objective clinical outcomes after lumbar microdiscectomy. METHODS This study was a retrospective analysis of a 2-center database including consecutive cases in which patients underwent lumbar microdiscectomy. All patients who received ES application (40 mg triamcinolone, ES group) were matched by age and sex to patients who had not received ES application (control group). Objective functional impairment (OFI) was determined using age- and sex-adjusted T-scores of the Timed Up and Go (TUG) test. Back and leg pain (visual analog scale), functional impairment (Oswestry Disability Index [ODI], Roland-Morris Disability Index [RMDI], and health-related quality of life (hrQoL; 12-Item Short Form Health Survey [SF-12] physical component summary [PSC] score and EuroQol [EQ-5D index]) were measured at baseline, on postoperative day 3, and at postoperative week 6. RESULTS Fifty-three patients who received ES application were matched with 101 controls. There were no baseline demographic or disease-specific differences between the study groups, and preoperative pain, functional impairment, and hrQoL were similar. On postoperative day 3, the ES group had less disability on the RMDI (mean 7.4 vs 10.3, p = 0.003) and higher hrQoL as determined by the SF-12 PCS (36.5 vs 32.7, p = 0.004). At week 6, the ES group had less disability on the RMDI (3.6 vs 5.7, p = 0.050) and on the ODI by trend (17.0 vs 24.4, p = 0.056); better hrQoL, determined by the SF-12 PCS (44.3 vs 39.9, p = 0.018); and lower OFI (TUG test T-score 100.5 vs 110.2, p = 0.005). The week 6 responder status based on the minimum clinically important difference (MCID) was similar in the ES and control groups for each metric. The rates and severity of complications were similar, with a 3.8% and 4.0% reoperation rate in the ES group and control group, respectively (p = 0.272). There was a tendency for shorter hospitalization in the ES group (5.0 vs 5.8 days, p = 0.066). CONCLUSIONS Intraoperative ES application on the decompressed nerve root is an effective adjunct treatment that may lower subjective and objective functional impairment and increase hrQoL in the short and intermediate term after lumbar microdiscectomy. However, group differences were lower than the commonly accepted MCIDs for each metric, indicating that the effect size of the benefit is limited. ■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: retrospective cohort trial; evidence: Class II.

    View details for DOI 10.3171/2017.6.SPINE161372

    View details for PubMedID 29243999

  • Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease JOURNAL OF NEUROSURGERY-SPINE Stienen, M. N., Smoll, N. R., Joswig, H., Corniola, M. V., Schaller, K., Hildebrandt, G., Gautschi, O. P. 2017; 26 (5): 598-604

    Abstract

    OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p < 0.001). Patients with mild, moderate, and severe OFI had increased leg pain by 0.90 (p = 0.044), 1.54 (p < 0.001), and 1.94 (p < 0.001); increased ODI by 7.99 (p = 0.004), 12.64 (p < 0.001), and 17.13 (p < 0.001); and decreased SF-12 PCS by -2.57 (p = 0.049), -3.63 (p = 0.003), and -6.23 (p < 0.001), respectively. CONCLUSIONS The OFI BSS is a valid measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.

    View details for DOI 10.3171/2016.11.SPINE16683

    View details for Web of Science ID 000400041700009

    View details for PubMedID 28291406

  • Assessment of the Minimum Clinically Important Difference in the Timed Up and Go Test After Surgery for Lumbar Degenerative Disc Disease. Neurosurgery Gautschi, O. P., Stienen, M. N., Corniola, M. V., Joswig, H., Schaller, K., Hildebrandt, G., Smoll, N. R. 2017; 80 (3): 380-385

    Abstract

    The Timed Up and Go Test (TUG Test) has previously been described as a reliable tool to evaluate objective functional impairment in patients with degenerative disc disease.The aim of this study was to assess the minimum clinically important difference (MCID) of the TUG Test.The TUG Test (measured in seconds) was correlated with validated patient-reported outcome measures (PROs) of pain intensity (Visual Analog Scale for back and leg pain), functional impairment (Oswestry Disability Index, Roland Morris Disability Index), and health-related quality of life measures (Short Form-12 and EuroQol 5D). Three established methods were used to establish anchor-based MCID values using responders of the following PROs (Visual Analog Scale back and leg pain, Oswestry Disability Index, Roland Morris Disability Index, EuroQol 5D index, and Short Form-12 Physical Component Summary) as anchors: (1) average change, (2) minimum detectable change, and (3) change difference approach.One hundred patients with a mean ± SD age of 56.2 ± 16.1 years, 57 (57%) male, 45 patients undergoing microdiscectomy, 35 undergoing lumbar decompression, and 20 undergoing fusion surgery were studied. The 3 MCID computation methods revealed a range of MCID values according to the PRO used from 0.9 s (Oswestry Disability Index based on the change difference approach) to 6.0 s (EuroQol 5D index based on the minimum detectable change approach), with a mean MCID of 3.4 s for all measured PROs.The MCID for the TUG Test time is highly variable depending on the computation technique used. The average TUG Test MCID was 3.4 s using all 3 methods and all anchors.

    View details for DOI 10.1227/NEU.0000000000001320

    View details for PubMedID 27352275

  • Influence of the mental health status on a new measure of objective functional impairment in lumbar degenerative disc disease. The spine journal : official journal of the North American Spine Society Stienen, M. N., Smoll, N. R., Joswig, H., Snagowski, J., Corniola, M. V., Schaller, K., Hildebrandt, G., Gautschi, O. P. 2016

    Abstract

    The Timed Up and Go (TUG) test has recently been proposed as a simple and standardized measure for objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD).The study aimed to explore the relationship between a patient's mental health status and both patient-reported outcome measures (PROMs) and TUG test results.This is a prospective institutional review board-approved two-center study.The sample was composed of 375 consecutive patients scheduled for lumbar spine surgery and a healthy cohort of 110 control subjects.Patients and control subjects were assessed with the TUG test and a comprehensive panel of subjective PROMs of pain intensity (visual analog scale [VAS]), functional impairment (Roland-Morris Disability Index [RMDI]), Oswestry Disability Index [ODI]), as well as health-related quality of life (hrQoL; Euro-Qol [EQ]-5D).Standardized age- and sex-adjusted TUG test T-scores were calculated. The dependent variable was the short-form (SF)-12 mental component summary (MCS) quartiles, and the independent variables were the TUG T-scores and PROMs. Direct and adjusted analyses of covariance were performed to estimate the interaction between the SF-12 MCS quartiles and the independent variables.In patients, there was a significant decrease in the subjective PROMs, notably the VAS back pain (p=.001) and VAS leg pain (p=.035), as well as significant increase in the RMDI (p<.001), ODI (p<.001), and the EQ-5D index (p<.001) with every increase in the quartile of the SF-12 MCS. There were no significant group differences of OFI as measured by the TUG T-scores across the SF-12 MCS quartiles (p=.462). In the healthy control group, a significant decrease in VAS leg pain (p=.028), RMDI (p=.013), and ODI (p<.001), as well as a significant increase in the EQ-5D index (p<.001), was seen across the SF-12 MCS quartiles, whereas TUG T-scores remained stable (p=.897).There are significant influences of mental hrQoL on subjective measures of pain, functional impairment, and hrQoL that might lead to bias when evaluating patients with lumbar DDD who suffer from reduced mental hrQoL. The TUG test appears to be a stable instrument and especially helpful in the evaluation of patients with lumbar DDD and mental health problems.

    View details for DOI 10.1016/j.spinee.2016.12.004

    View details for PubMedID 27988343

  • Letter to the Editor: Training and career aspects of female neurosurgical residents in Europe. Journal of neurosurgery Stienen, M. N., Gautschi, O. P., Schaller, K., Netuka, D., Demetriades, A. K., Ringel, F., Gempt, J., Kuhlen, D. 2016; 125 (5): 1317-1320

    View details for PubMedID 27540901

  • Residency program trainee-satisfaction correlate with results of the European board examination in neurosurgery ACTA NEUROCHIRURGICA Stienen, M. N., Netuka, D., Demetriades, A. K., Ringel, F., Gautschi, O. P., Gempt, J., Kuhlen, D., Schaller, K. 2016; 158 (10): 1823-1830

    Abstract

    Substantial country differences in neurosurgical training throughout Europe have recently been described, ranging from subjective rating of training quality to objective working hours per week. The aim of this study was to analyse whether these differences translate into the results of the written and oral part of the European Board Examination in Neurological Surgery (EBE-NS).Country-specific composite scores for satisfaction with quality of theoretical and practical training, as well as working hours per week, were obtained from an electronic survey distributed among European neurosurgical residents between June 2014 and March 2015. These were related to anonymous country-specific results of the EBE-NS between 2009 and 2016, using uni- and multivariate linear regression analysis.A total of n = 1025 written and n = 63 oral examination results were included. There was a significant linear relationship between the country-specific EBE-NS result in the written part and the country-specific composite score for satisfaction with quality of theoretical training [adjusted regression coefficient (RC) -3.80, 95 % confidence interval (CI) -5.43-7 -2.17, p < 0.001], but not with practical training or working time. For the oral part, there was a linear relationship between the country-specific EBE-NS result and the country-specific composite score for satisfaction with quality of practical training (RC 9.47, 95 % CI 1.47-17.47, p = 0.021), however neither with satisfaction with quality of theoretical training nor with working time.With every one-step improvement on the country-specific satisfaction score for theoretical training, the score in the EBE-NS Part 1 increased by 3.8 %. With every one-step improvement on the country-specific satisfaction score for practical training, the score in the EBE-NS Part 2 increased by 9.47 %. Improving training conditions is likely to have a direct positive influence on the knowledge level of trainees, as measured by the EBE-NS. The effect of the actual working time on the theoretical and practical knowledge of neurosurgical trainees appears to be insignificant.

    View details for DOI 10.1007/s00701-016-2917-y

    View details for Web of Science ID 000383703400001

    View details for PubMedID 27517689

  • Validity and Reliability of a Measurement of Objective Functional Impairment in Lumbar Degenerative Disc Disease: The Timed Up and Go (TUG) Test NEUROSURGERY Gautschi, O. P., Smoll, N. R., Corniola, M. V., Joswig, H., Chau, I., Hildebrandt, G., Schaller, K., Stienen, M. N. 2016; 79 (2): 270-278

    Abstract

    There are few objective measures of functional impairment to support clinical decision making in lumbar degenerative disc disease (DDD).We present the validation (and reliability measures) of the Timed Up and Go (TUG) test.In a prospective, 2-center study, 253 consecutive patients were assessed using the TUG test. A representative cohort of 110 volunteers served as control subjects. The TUG test values were assessed for validity and reliability.The TUG test had excellent intra- (intraclass correlation coefficient: 0.97) and interrater reliability (intraclass correlation coefficient: 0.99), with a standard error of measurement of 0.21 and 0.23 seconds, respectively. The validity of the TUG test was demonstrated by a good correlation with the Visual Analog Scale (VAS) back (Pearson's correlation coefficient [PCC]: 0.25) and VAS (PCC: 0.29) leg pain, functional impairment (Roland-Morris Disability Index [PCC: 0.38] and Oswestry Disability Index [PCC: 0.34]), as well as with health-related quality of life (Short Form-12 Mental Component Summary score [PCC: -0.25], Short Form-12 Physical Component Summary score [PCC: -0.32], and EQ-5D [PCC: -0.28]). The upper limit of "normal" was 11.52 seconds. Mild (lower than the 33rd percentile), moderate (33rd to 66th percentiles), and severe objective functional impairment (higher than the 66th percentile) as determined by the TUG test was <13.4 seconds, 13.4 to 18.4 seconds, and >18.4 seconds, respectively.The TUG test is a quick, easy-to-use, valid, and reliable tool to evaluate objective functional impairment in patients with lumbar degenerative disc disease. In the clinical setting, patients scoring a TUG test time of over 12 seconds can be considered to have functional impairment.BMI, body mass indexDDD, degenerative disc diseaseHRQOL, health-related quality of lifeICC, intraclass correlationLDH, lumbar disc herniationLSS, lumbar spinal stenosisODI, Oswestry Disability IndexOFI, objective functional impairmentPCC, Pearson's correlation coefficientPCS, Physical Component SummaryRMDI, Roland-Morris Disability IndexSF, Short FormVAS, visual analog scale.

    View details for DOI 10.1227/NEU.0000000000001195

    View details for Web of Science ID 000382335100037

    View details for PubMedID 26702840

  • Sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life in patients with lumbar degenerative disc disease PAIN Gautschi, O. P., Corniola, M. V., Smoll, N. R., Joswig, H., Schaller, K., Hildebrandt, G., Stienen, M. N. 2016; 157 (5): 1065-1071

    Abstract

    Sex differences in pain perception are known to exist; however, the exact pathomechanism remains unclear. This work aims to elucidate sex differences in subjective and objective measures of pain, functional impairment, and health-related quality of life (HRQoL) in patients with lumbar degenerative disc disease. In a prospective 2-center study, back and leg pain (visual analogue scale [VAS]), functional disability (Oswestry Disability Index and Roland-Morris Disability Index), and HRQoL (EuroQol-5D and Short Form [SF12]) were collected for consecutive patients undergoing lumbar spine surgery. Objective functional impairment (OFI) was estimated using age-adjusted and sex-adjusted cutoff values for the timed-up-and-go (TUG) test. A healthy cohort of n = 110 subjects served as the control group. Univariate and multivariate analyses were performed to test the association between sex and pain, subjective and OFIs, and HRQoL. The study comprised n = 305 patients (41.6% females). Female patients had more VAS back pain (P = 0.002) and leg pain (P = 0.014). They were more likely to report higher functional impairment in terms of Oswestry Disability Index (P = 0.005). Similarly, HRQoL measured with the EuroQol-5D index (P = 0.012) and SF12 physical composite score (P = 0.005) was lower in female patients. Female patients reported higher VAS back and leg pain, functional impairment, and reduced HRQoL than male patients. However, there were no sex differences with respect to the presence and degree of OFI measured by the TUG test using age-adjusted and sex-adjusted cutoff values. As such, the TUG may be a good test to overcome sex bias for the clinical assessment of patients with degenerative disc disease.

    View details for DOI 10.1097/j.pain.0000000000000480

    View details for Web of Science ID 000378875600011

    View details for PubMedID 26761383

  • Catheter-tip Granulomas Associated with Intrathecal Drug Delivery - A Two-Center Experience Identifying 13 Cases PAIN PHYSICIAN Kratzsch, T., Stienen, M. N., Reck, T., Hildebrandt, G., Hoederath, P. 2015; 18 (5): E831-E840

    Abstract

    Intrathecal (IT) drug therapy with implanted pumps is an effective treatment modality for chronic pain and/or spasticity, especially after non-invasive treatment has failed. Long-term use of intrathecal opioids may cause formation of inflammatory masses at the tip of intrathecal catheters, possibly leading to neurological deficits and/or catheter revision.We aimed to identify risk factors for catheter-tip granuloma (CG) formation.Retrospective study.Tertiary Spine Centers in Germany and Switzerland.We retrospectively reviewed data at 2 Swiss centers (Kantonsspital St. Gallen, Swiss Paraplegic Centre Nottwil) between 01/1994 and 10/2013. Collected data were age at operation, gender, smoking status, previous spinal operations, spinal level of catheter-tip, clinical symptoms, catheter testing with contrast agent, applied drugs, drug concentration, as well as cumulative daily drug dosages.Thirteen patients with a mean age of 52.6 years and CG formation after a mean of 6.9 years of follow-up were identified and compared to 54 patients of similar age and length of follow-up (48.6 years, P = 0.535; follow-up 5.3 years, P = 0.236) without CG. In the analysis of risk factors, catheter ending in the middle thoracic spine (Th4-8; 38.5 vs. 6.5%; P = 0.010), previous spinal surgery (75 vs. 41%; P = 0.051), and chronic pain as an underlying primary symptom for IT drug therapy (100 vs. 56%, P = 0.003) were associated with CG formation. IT drug therapy for spasticity appeared to be much less associated with CG formation (0 vs. 44%, P = .0003). As the symptomatology is closely related to the medical treatment applied, patients with CG were more likely to be treated with IT morphine (77 vs. 20%; P < 0.001), and as tendency with IT clonidine (54 vs. 26%; P = 0.092) and IT bupivacaine (46 vs. 20%; P = 0.077). Average in-pump morphine concentration (30.3 vs. 19.5 mg/mL; P = 0.05) as well as average daily dose of morphine (12.5 vs. 6.2 mg/d; P = 0.037) were significantly higher in the CG group. Smoking could not be identified as risk factor for CG formation.Limitations include the retrospective approach, the limited group size of granuloma patients, as well as missing data in the investigated patient groups.Our patient cohort with CG differed in some features, of which some like catheter localization, choice, dosage, and the concentration of drugs are potentially modifiable. These results could contribute to the prevention of CG in the future.

    View details for Web of Science ID 000367524400010

    View details for PubMedID 26431137

  • Sentinel Headache: A Warning Sign Preceding Every Fourth Aneurysmal Subarachnoid Hemorrhage AMERICAN JOURNAL OF NEURORADIOLOGY Joswig, H., Fournier, J. Y., Hildebrandt, G., Stienen, M. N. 2015; 36 (9): E62-E63

    View details for DOI 10.3174/ajnr.A4467

    View details for Web of Science ID 000361044500003

    View details for PubMedID 26185328

  • Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations ACTA NEUROCHIRURGICA Zweifel-Zehnder, A. E., Stienen, M. N., Chicherio, C., Studerus-Germann, A., Blaesi, S., Rossi, S., Gutbrod, K., Schmid, N., Beaud, V., Mondadori, C., Brugger, P., Sacco, L., Mueri, R., Hildebrandt, G., Fournier, J., Keller, E., Regli, L., Fandino, J., Mariani, L., Raabe, A., Daniel, R. T., Reinert, M., Robert, T., Schatlo, B., Bijlenga, P., Schaller, K., Monsch, A. U. 2015; 157 (9): 1449-1458

    Abstract

    In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines.To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized.We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed.This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

    View details for DOI 10.1007/s00701-015-2480-y

    View details for Web of Science ID 000359862500001

    View details for PubMedID 26179382

  • The need for an objective outcome measurement in spine surgery-the timed-up-and-go test SPINE JOURNAL Gautschi, O. P., Corniola, M. V., Schaller, K., Smoll, N. R., Stienen, M. N. 2014; 14 (10): 2521-2522

    View details for DOI 10.1016/j.spinee.2014.05.004

    View details for Web of Science ID 000343100600037

    View details for PubMedID 25256899

  • Glia and epilepsy: Experimental investigation of antiepileptic drugs in an astroglia/microglia co-culture model of inflammation EPILEPSIA Dambach, H., Hinkerohe, D., Prochnow, N., Stienen, M. N., Moinfar, Z., Haase, C. G., Hufnagel, A., Faustmann, P. M. 2014; 55 (1): 184-192

    Abstract

    The contribution of glial cells, mainly astrocytes and microglia, to the pathophysiology of epilepsy is increasingly appreciated. Glia play a pivotal role in the initiation and maintenance of the central nervous system (CNS) immune response and neuronal metabolic and trophic supply. Recent clinical and experimental evidence suggests a direct relationship between epileptic activity and CNS inflammation, which is characterized by accumulation, activation, and proliferation of microglia and astrocytes. Concomitant glia-mediated mechanisms of action of several antiepileptic drugs (AEDs) have been proposed. However, their direct effects on glial cells have been rarely investigated. We aimed to investigate the effect of commonly used AEDs on glial viability, the gap junctional network, the microglial activation, and cytokine expression in an in vitro astroglia/microglia co-culture model.Primary astrocytic cultures were prepared from brains of postnatal (P0-P2) Wistar rats and co-cultured with a physiologic amount of 5%, as well as 30% microglia in order to mimic inflammatory conditions. Co-cultures were treated with valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHE), and gabapentin (GBT). Viability and proliferation were measured using the tetrazolium (MTT) assay. The microglial activation state was determined by immunocytochemical labeling. The astroglial connexin 43 (Cx43) expression was measured by Western blot analysis. The transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) cytokine levels were measured by the quantitative sandwich enzyme immunosorbent assay (ELISA).Astrocytes, co-cultured with 5% microglia (M5 co-cultures), showed a dose-dependent, significant reduction in glial viability after incubation with PHE and CBZ. Furthermore, VPA led to highly significant microglial activation at all doses examined. The antiinflammatory cytokine TGF-β1 release was induced by high doses of GBT and PHE. Astrocytes co-cultured with 30% microglia (M30 co-cultures) revealed a dose-dependent significant reduction in glial viability after incubation with PHE, accompanied by increased TGF-β1 and TNF-α levels. However, CBZ significantly reduced the amount of activated microglial cells and increased the total number of inactivated microglia. Finally, CBZ resulted in reduced viability at all doses examined.CNS inflammation is characterized by a disturbance of glial cell functions. Strong microglial activation, a typical hallmark of inflammation, was induced by VPA in M5 and continued in M30 co-cultures. With regard to the direct relation between CNS inflammation and seizures, VPA seems to be unsuitable for reducing inflammatory conditions. The reverse effect was achieved after CBZ. We noticed significant microglial inactivation, after incubation of the M30 co-cultures. In conclusion, we suggest that AEDs with antiinflammatory glial features are beneficial for seizures caused by persistent brain inflammation.

    View details for DOI 10.1111/epi.12473

    View details for Web of Science ID 000329893900023

    View details for PubMedID 24299259

  • Little-known Swiss contributions to the description, diagnosis, and surgery of lumbar disc disease before the Mixter and Barr era JOURNAL OF NEUROSURGERY-SPINE Stienen, M. N., Surbeck, W., Troehler, U., Hildebrandt, G. 2013; 19 (6): 767-773

    Abstract

    The understanding of lumbar spine pathologies made substantial progress at the turn of the twentieth century. The authors review the original publication of Otto Veraguth in 1929 reporting on the successful resection of a herniated lumbar disc, published exclusively in the German language. His early report is put into the historical context, and its impact on the understanding of pathologies of the intervertebral disc (IVD) is estimated. The Swiss surgeon and Nobel Prize laureate Emil Theodor Kocher was among the first physicians to describe the traumatic rupture of the IVD in 1896. As early as 1909 Oppenheim and Krause published 2 case reports on surgery for a herniated lumbar disc. Goldthwait was the first physician to delineate the etiopathogenes is between annulus rupture, symptoms of sciatica, and neurological signs in his publication of 1911. Further publications by Middleton and Teacher in 1911 and Schmorl in 1929 added to the understanding of lumbar spinal pathologies. In 1929, the Swiss neurologist Veraguth (surgery performed by Hans Brun) and the American neurosurgeon Walter Edward Dandy both published their early experiences with the surgical therapy of a herniated lumbar disc. Veraguth's contribution, however, has not been appreciated internationally to date. The causal relationship between lumbar disc pathology and sciatica remained uncertain for some years to come. The causal relationship was not confirmed until Mixter and Barr's landmark paper in 1934 describing the association of sciatica and lumbar disc herniation, after which the surgical treatment became increasingly popular. Veraguth was among the first physicians to report on the clinical course of a patient with successful resection of a herniated lumbar disc. His observations should be acknowledged in view of the limited experience and literature on this ailment at that time.

    View details for DOI 10.3171/2013.8.SPINE121008

    View details for Web of Science ID 000327367400017

    View details for PubMedID 24074509

  • Current practice in neuropsychological outcome reporting after aneurysmal subarachnoid haemorrhage ACTA NEUROCHIRURGICA Stienen, M. N., Weisshaupt, R., Fandino, J., Fung, C., Keller, E., Hildebrandt, G., Studerus-Germann, A., Muri, R., Gutbrod, K., Blasi, S., Monsch, A. U., Brugger, P., Mondadori, C., Sailer, M., Bijlenga, P., Schaller, K., Schatlo, B. 2013; 155 (11): 2045-2051

    Abstract

    Neuropsychological deficits (NPD) are common in patients with aneurysmal subarachnoid haemorrhage (aSAH). NPD are one of the major limiting factors for patients with an otherwise acceptable prognosis for sustained quality of life. There are only a few studies reporting outcome after aSAH, which used a standardized neuropsychological test battery as a primary or secondary outcome measure. Aim of this study was to determine the current practice of reporting NPD following aSAH in clinical studies.A MEDLINE analysis was performed using the search term "subarachnoid haemorrhage outcome". The latest 1,000 articles were screened. We recorded study design, number of patients, and the presence of neuropsychological outcome report. Additionally, the time of testing after aSAH, the neuropsychological tests administered, as well as the percentage of patients with NPD were analyzed.A total of 324 publications between 2009 and 2012 were selected for further review. Of those, 21 studies (6.5%) reported neuropsychological outcome, in 2,001 of 346,666 patients (0.6%). The assessment of NPD differed broadly using both subjective and objective cognitive evaluation, and a large variety of tests were used.Neuropsychological outcome is underreported, and there is great variety in assessment in currently published clinical articles on aSAH. Prospective randomized trials treating aSAH may benefit from implementing more comprehensive and standardized neuropsychological outcome measures. This approach might identify otherwise unnoticed treatment effects in future interventional studies of aSAH patients.

    View details for DOI 10.1007/s00701-013-1823-9

    View details for Web of Science ID 000325815600006

    View details for PubMedID 23887856

  • Introducing a nationwide registry: the Swiss study on aneurysmal subarachnoid haemorrhage (Swiss SOS) ACTA NEUROCHIRURGICA Schatlo, B., Fung, C., Fathi, A., Sailer, M., Winkler, K., Daniel, R. T., Bijlenga, P., Ahlborn, P., Seule, M., Zumofen, D., Reinert, M., Woernle, C., Stienen, M., Levivier, M., Hildebrandt, G., Mariani, L., Bernays, R., Fandino, J., Raabe, A., Keller, E., Schaller, K. 2012; 154 (12): 2173-2178

    Abstract

    Aneurysmal subarachnoid haemorrhage (aSAH) is a haemorrhagic form of stroke and occurs in a younger population compared with ischaemic stroke or intracerebral haemorrhage. It accounts for a large proportion of productive life-years lost to stroke. Its surgical and medical treatment represents a multidisciplinary effort. Due to the complexity of the disease, the management remains difficult to standardise and quality of care is accordingly difficult to assess.To create a registry to assess management parameters of patients treated for aSAH in Switzerland.A cohort study was initiated with the aim to record characteristics of patients admitted with aSAH, starting January 1st 2009. Ethical committee approval was obtained or is pending from the institutional review boards of all centres. In the study period, seven Swiss hospitals (five university [U], two non-university medical centres) harbouring a neurosurgery department, an intensive care unit and an interventional neuroradiology team so far agreed to participate in the registry (Aarau, Basel [U], Bern [U], Geneva [U], Lausanne [U], St. Gallen, Zürich [U]). Demographic and clinical parameters are entered into a common database.This database will soon provide (1) a nationwide assessment of the current standard of care and (2) the outcomes for patients suffering from aSAH in Switzerland. Based on data from this registry, we can conduct cohort comparisons or design diagnostic or therapeutic studies on a national level. Moreover, a standardised registration system will allow healthcare providers to assess the quality of care.

    View details for DOI 10.1007/s00701-012-1500-4

    View details for Web of Science ID 000311359500006

    View details for PubMedID 23053275

  • Emil Theodor Kocher-Valve surgery for epilepsy EPILEPSIA Surbeck, W., Stienen, M. N., Hildebrandt, G. 2012; 53 (12): 2099-2103

    Abstract

    Emil Theodor Kocher (1841-1917) was a pioneering and versatile Swiss surgeon who played a decisive role in the surgical evolution on the threshold to the 20th century. Apart from conducting intense research and fostering the development of the surgical treatment of thyroid gland diseases (honored with a Nobel Prize in 1909), he remained a generalist and was active in orthopedic, genitourinary, and neurologic surgery. Even today, many surgical techniques and instruments are still named after him, thus providing evidence of his great impact. His neurosurgical ambitions included, in particular, cerebral and spinal trauma, the pathophysiology of elevated intracranial pressure, as well as etiological considerations and the operative treatment of epilepsy. This article aims to shed light on Kocher's work on epilepsy, published exclusively in German, and illustrates the development of his idea on valve surgery for recurrent general convulsions.

    View details for DOI 10.1111/j.1528-1167.2012.03663.x

    View details for Web of Science ID 000312218000011

    View details for PubMedID 22967053

  • Emil Theodor Kocher: the first Swiss neurosurgeon ACTA NEUROCHIRURGICA Hildebrandt, G., Surbeck, W., Stienen, M. N. 2012; 154 (6): 1105-1115

    Abstract

    Emil Theodor Kocher (1841-1917) was elected as head of the university clinic for surgery in Berne, Switzerland at the age of 31 years. During the 45 years of his professorship he became one of the outstanding surgeons of Europe by using surgical techniques based predominately on physiological and biological ideas. The aim of this article was to highlight his neurosurgical achievements published in the German language.The illustrations of Kocher's works in the field of neurosurgery are exclusively based on his publications and works published by his co-workers.Kocher received the Nobel Prize in Physiology or Medicine in 1909 because he devoted himself to intense research and development in the pathophysiology and surgical treatment of diseases of the thyroid gland. His particular neurosurgical interests were in cerebral and spinal trauma, operative treatment of epilepsy and the pathophysiology of elevated intracranial pressure.Studies of Kocher's contributions, published exclusively in the German language, lead to the conclusion that Kocher must be designated as the first Swiss neurosurgeon.

    View details for DOI 10.1007/s00701-012-1341-1

    View details for Web of Science ID 000304113800022

    View details for PubMedID 22492296

  • Anti-inflammatory effects of the anticonvulsant drug levetiracetam on electrophysiological properties of astroglia are mediated via TGF beta 1 regulation BRITISH JOURNAL OF PHARMACOLOGY Stienen, M. N., Haghikia, A., Dambach, H., Thoene, J., Wiemann, M., Gold, R., Chan, A., Dermietzel, R., Faustmann, P. M., Hinkerohe, D., Prochnow, N. 2011; 162 (2): 491-507

    Abstract

    The involvement of astrocytes as immune-competent players in inflammation and the pathogenesis of epilepsy and seizure-induced brain damage has recently been recognized. In clinical trials and practice, levetiracetam (LEV) has proven to be an effective antiepileptic drug (AED) in various forms of epileptic seizures, when applied as mono- or added therapy. Little is known about the mechanism(s) of action of LEV. Evidence so far suggests a mode of action different from that of classical AEDs. We have shown that LEV restored functional gap junction coupling and basic membrane properties in an astrocytic inflammatory model in vitro.Here, we used neonatal rat astrocytes co-cultured with high proportions (30%) of activated microglia or treated with the pro-inflammatory cytokine interleukin-1β to provoke inflammatory responses. Effects of LEV (50 µg·mL⁻¹) on electrophysiological properties of astrocytes (by whole cell patch clamp) and on secretion of TGFβ1 (by (ELISA)) were studied in these co-cultures.LEV restored impaired astrocyte membrane resting potentials via modification of inward and outward rectifier currents, and promoted TGFβ1 expression in inflammatory and control co-cultures. Furthermore, LEV and TGFβ1 exhibited similar facilitating effects on the generation of astrocyte voltage-gated currents in inflammatory co-cultures and the effects of LEV were prevented by antibody to TGFβ1.Our data suggest that LEV is likely to reduce the harmful spread of excitation elicited by seizure events within the astro-glial functional syncytium, with stabilizing consequences for neuronal-glial interactions.

    View details for DOI 10.1111/j.1476-5381.2010.01038.x

    View details for Web of Science ID 000285305900015

    View details for PubMedID 20955362

    View details for PubMedCentralID PMC3031068