Forschungsbereich Sahli-Haus

Transcription

1 Forschungsbereich Sahli-Haus Neurology Research Group The department of neurology has a long-standing research tradition. With the election of Prof. Claudio Bassetti as the new head of the department in 2012, clinical and translational research were both strengthened. The current main areas of research are the following: 1) stroke; neurointensive care (human and animal) 2) sleep-wake (human and animal), epilepsy (human) and consciousness (human) 3) movement and motor disorders (human and animal) 4) eye perception, cognitive neurology; neurorehabilitation; gerontotechnology (human) 3

2 In 2012 a total of 12 projects were running in the department (see below) and the following research positions were financed: 500% MD, 1200% PhD (2/3 in clinical and 1/3 in animal research), 800% study nurses, and 50% study coordinator/biostatistician. Our current efforts include the creation of: a new laboratory for animal research (ZEN, Zentrum für experimentelle Neurologie) a platform for conducting clinical studies (NKSZ, Neuroklinisches Studienzentrum) a multidisciplinary research group on the topics of epilepsy, sleep and consciousness new positions for residents interested in research (50% clinical-50% research appointments) In the following all areas of research of our department are presented, starting with the four main areas. 1) Stroke; neurointensive care s: Prof. Dr. Heinrich Mattle heinrich.mattle@insel.ch MD at the University of Zürich (1976); neurology residency in Zurich (FMH certification 1985). Fellowships in neuroradiology (Harvard University, Boston, USA, ). Venia docendi in Since 1990 vice-chairman and head of the outpatient clinics. Since 2012 co-chair of the stroke center, Department of Neurology, Inselspital. Associated professor of neurology since Human research in stroke and multiple sclerosis. Prof. Dr. Marcel Arnold marcel.arnold@insel.ch MD at the University of Berne (1994); neurology residency in Bern (FMH certification 2000). Research fellowships in clinical neurology (Hôpital Lariboisière, Université Paris 7, 2005). Venia docendi in Associate professor of neurology since Since 2012 chair of the Stroke Center, Department of Neurology, Inselspital. Human research in stroke. Prof. Dr. Werner Z Graggen werner.zgraggen@insel.ch MD at the University of Zurich (1999); neurology residency in Bern (FMH certification 2008). Fellowship in neuroscience (Brain Research Institute, University of Zurich, 1999) and in clinical neurophysiology and neurointensive care (National Hospital for Neurology and Neurosurgery, London, 2004). Venia docendi Since 2010 head of neurointensive care. Human research in stroke and neurointensive (-critical) care. Prof. C. Bassetti, PD Dr. U. Fischer, Dr. S. Jung, Dr. M. Mono, Dr. A. Galimanis, Dr. A. Weck, Dr. rer. nat. B. Gao, Dr. vet. E. Cam, M. Pace (PhD student), M. Kormann (study nurse), A. Surtmann (study nurse). The stroke group is a multidisciplinary group that aims to improve the management of acute ischemic and haemorrhagic stroke and its prevention. The studies are clinical (patient-oriented). A strong focus is on endovascular treatment of acute stroke in collaboration with our neuroradiologists. The group leads a multicentre translational Special Program University Medicine (SPUM) project investigating pathogenesis, diagnosis, imaging and treatment of dissection of cervicocerebral arteries. Long-standing collaborations with our cardiologists and with Tufts Medical School elucidate the role of patent foramen ovale in stroke and its management. Additional topics are carotid plaque characteristics, biomarkers in stroke, epilepsy in stroke victims, correlation of occlusion location of cerebral arteries and clinical signs, perfusion and diffusion weighted imaging in acute stroke, effect of collaterals in acute stroke, blood pressure in acute stroke, course of intracranial vessel stenosis, management of cerebral hemorrhage, cerebral venous and sinus thrombosis, stroke in the very old and in children, basilar artery occlusion, and outpatient rehabilitation of stroke victims, detection and treatment of cerebral misery perfusion because of vasospasms after subarachnoid haemorrhage. Stroke relevant research is conducted both in humans as well as animal models by the sleep group. 4

3 Grants Name of foundation Name of project Name(s) of PI(s) Amount allocated for 2012 Etiopathogenesis, Diagnosis M. Arnold Special Program University Medicine Imaging and Treatment of Cervicocerebral Artery Dissection (EDIT-CAD)-2 Study. PFO Konsortium M. Mono Contrast enhanced ultrasound imaging for cerebral perfusion measurement in cerebral vasospasm after subarachnoid hemorrhage J. Beck, W. Z Graggen ) Meier B, Kalesan B, Mattle HP, et al. Percutaneous Closure of Patent Foramen Ovale versus Medical Treatment in Patients With Cryptogenic Embolism. New Engl. J Med (in press) 2) Jung S, Schindler K, Findling O, et al. Adverse effect of early epileptic seizures in patients receiving endovascular treatment for ischemic stroke. Stroke 2012; 43: ) Fischer U, Mono ML, Zwahlen M, et al. Outcome of acute ischaemic stroke in the Canton of Bern, Switzerland, in The Bern Stroke Project. Stroke. 2012; 43: ) Fung C, Murek M, Z'Graggen WJ, et al. Decompressive hemicraniectomy in patients with supratentorial intracerebral hemorrhage. Stroke 2012; 43: ) Sleep-Wake, epilepsy and disorders of consciousness s Prof. Dr. Claudio Bassetti, chairman and head, clinic director, group leader claudio.bassetti@insel.ch MD at the University of Basel (1985); neurology residency in Bern/Lausanne (FMH certification 1992). Research fellowships in experimental neurophysiology (Institute of Physiology Basel, ) and sleep medicine (University of Michigan, Ann Arbor, USA, ). Venia docendi in Professor, vice-chair of neurology, University Hospital, Zurich (2001-9). Director of the Neurocenter of Southern Switzerland ( ). Since 2012 full professor of neurology, chairman, Department of Neurology, Inselspital. Human and animal research in sleep and stroke. Prof. Dr. Johannes Mathis johannes.mathis@insel.ch MD at University of Zurich (1980); neurology residency in Zürich/Bern (FMH certification 1990). Research fellowship in experimental neurophysiology (Physiological Institute, Zurich Visiting Scientist at the technical University in Munich, Germany (1991). Venia docendi in Since 1999 head of the section of clinical neurophysiology and since 2002 co-head of the sleep-wake Centre, Department of Neurology, Inselspital. Since 2008 associate Professor of Neurology. Human sleep research. PD Dr. med. Dr. sc. nat. Kaspar Schindler kaspar.schindler@insel.ch Medical School University of Bern ; National MD-PhD program, Institute of Neuroinformatics, ETH/University of Zürich ; Doctorate at the Faculty of Mathematics and Natural Sciences (PhD) and Doctorate at the Medical Faculty (MD), University of Zürich 1999; Research Fellow at the Clinic of Epileptology, University of Bonn ( ). Venia docendi Head of pre-surgical evaluation for pharmacoresistent epilepsy patients. Group leader quantitative EEG (qeeg). PD Dr. med. A. Nirkko, Dr. med. H. Gast, Dr. sc. nat. C. Roth, Dr. rer. nat. S. Palchykova, Dr. rer. nat. B. Gao, Dr. rer. nat. F. Baracchi, Dr. sc. nat. F. Zubler, O. Hodor (PhD student), B. Schneider (study nurse), M. Fuchs (technician) The main focuses in human sleep research is on the clinical significance of sleep disordered breathing in stroke patients (on clinical, cardiovascular and humoral markers of outcome, since 2009 supported by the ), on the pathophysiology of narcolepsy and its borderland (including other conditions with hypocretin deficiency), on the clinical characteristics of organic and nonorganic hypersomnias, on the clinical and pathophysiological features sleep-wake changes in patients with Parkinson s disease, on multimodal assessment of sleepiness/vigilance and ability of driving. In 2012 a new -supported project was started in collaboration with the 5

4 Neurocenter of southern Switzerland on the cardiovascular consequences of the restless legs syndrome (to be assessed in humans and in a rodent model). In 2012 a new -supported project was started in collaboration with the University of Zurich with the aim of characterizing fatigue in animal models of autoimmune disorders. The experimental sleep research addresses the impact of sleep manipulations (deprivation my gentle handling, direct current stimulation, sleep-promoting drugs) on the evolution of stroke in rodents. Our main hypothesis is that sleep deprivation may impair neuroplasticity processes involved in the recovery process, whereas sleep promotion (but also sleep deprivation before stroke) may have a beneficial effect. Functional, electrophysiological, histological, and molecular read-outs are used. The main goal of our research in human epilepsy is to quantitatively characterize peri-seizure changes of intracranial EEG signals in order to derive diagnostically and therapeutically helpful information that is complementary to classical visual EEG interpretation. In 2012 we focused on mathematical approaches derived from Information Theory and Random Matrix Theory. We demonstrated that these methods allow to delineate epileptogenic brain areas in a quantitative and objective way and to better understand the dynamics of epileptic seizures from a systems perspective. Grants Name of foundation Name of project Name(s) of PI(s) Amount allocated for 2012 Sleep apnea and stroke, C. Bassetti human Restless legs, human and M. Manconi, C. Bassetti animal research Imaging large scale M. Seeck, K. Schindler neuronal networks in epilepsy Fatigue in autoimmune diseases A. Fontana, H. Gast Cam E, Gao B, Hodor A, Bassetti CL. Sleep deprivation prior to stroke increases sleep and attenuated brain lesion in the rate. Exp Neurol (in press) 2. Ruch S, Markes O, Duss SB, et al. Sleep stage II contributes to the consolidation of declarative memories. Neuropsychology 2012; 50: Schindler K, Gast H, Goodfellow M, Rummel C. On seeing the trees and the forest: single-signal and multisignal analysis of periictal intracranial EEG. Epilepsia 2012; 53: Pizza F, Biallas M, Kallweit U, Bassetti CL. Cerebral hemodynamic changes in stroke during sleep-disordered breathing. Stroke 2012; 43: ) Movement and motor disorders Prof. Dr. Alain Kaelin, MD PhD alain.kaelin@insel.ch MD at the University of Bern (1994); neurology residency in Bern (FMH certification 1998). Fellowship in movement disorder and neurophysiological research at the National Institute of Neurological Disorders and Stroke (Bethesda, USA, Venia docendi in Senior attending, since 2008 and head, Movement Disorders Center, Department of Neurology, Inselspital. Associate professor of Neurology since Human and animal research in movement disorders. Prof. Dr. med. K. Rösler, Dr. med. M. Schüpbach, Dr. med. N. Meier, Prof. J.M. Burgunder, Prof. C. Bassetti, PD S. Bohlhalter, Dr. rer. nat. C. Capper-Loup, S. Sgroi (PhD student), U. Walker (technician) Our research aims at a better understanding of the neurophysiology of movement disorders such as Parkinson s Disease (PD), both at the clinical level and at the basic science level. In clinical research we are interested in the pathophysiological motor mechanisms occurring in PD using motor learning tasks, transcranial magnetic stimulation and clinical evaluation of patients undergoing deep brain stimulation. Our first priority remains the pathophysiology of levodopainduced dyskinesia. These disabling involuntary movements occurring in PD patients treated with levodopa are both a clinical and a research challenge. Clinical research on Deep Brain Stimulation for movement disorders is the second important topic of our group (in cooperation with the university hospital in Basel and Paris among other centers). In the field of basic research, we continued our project investigating the role of the striatal enkephalinergic system in levodopa-induced dyskinesia and finished related projects on the role 6

5 of striatal neuropeptides. For this project, we are also collaborating with Dr. Galati from the Neurocenter of Southern Switzerland. In the field of central motor disorders, we pursued our research on central motor conduction using transcranial magnetic stimulation. We finished a project about stratification of central motor conduction times in healthy volunteers and patients with multiple sclerosis, and found significant differences between these groups. Moreover, a project concerning motor fatigue in multiple sclerosis was performed. Clinical neurophysiological research concerned the use of ultrasound as an aid in nerve conduction studies and the physiology of small fibre neuropathies using analysis of skin biopsies and measurements of the cutaneous silent period. A study of small fibre neuropathy in M. Gaucher is envisaged in an international collaboration. 1. Capper-Loup C, Frey C, Rebell D, Kaelin-Lang A. Adaptive gene expression changes on the healthy side of parkinsonian rats. Neuroscience 2012; S Deuschl G, Schüpbach M, Knudsen K, et al. Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: Concept and standards of the EARLYSTIM-study. Parkinsonism Relat Disord 2012; 19: Scheidegger O, Kamm C, Humpert S, Rösler K. Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls. Mult Scler 2012; 18: Firmin L, Müller S, Rösler KM. The latency distribution of motor evoked potentials in patients with multiple sclerosis. Clin Neurophysiol 2012; 123: ) Eye perception, cognitive neurology, neurorehabilitation, gerontotechnology Prof. Dr. René Müri rene.mueri@dkf.unibe.ch MD at the University of Bern in Neurological residency in Bern and Basel (FMH certification 1991). Postdoc at INSERM U 289, Hôpital de la Salpêtrière, Paris ( ). Venia Docendi in Since 2004, head, Unit of Cognitive and Restorative Neurology, Inselspital. Since 2008 associated professor of neurology. Human research in cognitive neurology, neurorehabilitation and neuro-ophthalmology. In 2012, a new grant ( neglect and motion ) was obtained. The aim of this project is to study under which conditions motion may modulate visual hemineglect. Motion is omnipresent in daily live, and from clinical observations we know that moving objects may improve or deteriorate neglect. One aim is to find out the characteristics of these patients, who improve by motion stimuli. This will be probably a new approach for the rehabilitation of neglect. A second Project deals with bilingualism and reading strategies. The aim of this project that is in collaboration with the University of Fribourg is investigating linguistic and individual factors in bilingual language processing since reading strategies are depending not only on reading proficiency but also on language characteristics. Especially, we aim to test the hypothesis of different pattern of reading in L1 (first language) and L2. Namely, we will test equally proficient, as well as low proficient bilingual subjects mastering an opaque (like French or English) and a transparent language (like German and Italian). The project concerning aphasia and co-speech gestures. Language and co-speech gestures are closely linked, and one goal of the project is to study this interaction in healthy subjects and patients with aphasia. A special focus is on the perception of co-speech gestures. It is not clear whether aphasic patients are able to use such additional non-verbal information. To this end, we perform complex behavioural analysis during dialogues including the analysis of eye movements and fixations. In the behaviour analysis the situation during conversation between two persons will be analysed by coding speech and gestures in time. Additional information is gained by the analysis of fixation behaviour. -Grants Name of foundation Name of project Name(s) of PI(s) Amount allocated for 2012 Neural basis of praxis S. Bohlhalter CHF 110,000 production: From higherorder processing to fine motor control Aphasia and co-speech R. Müri CHF 146,000 gestures Bilingualism J.-M. Annoni CHF 100,000 Motion and spatial neglect Th. Nyffeler CHF 108,000 Enhancement of sensory processing by attention: cognitive, electrophysiological, and neuropsychological studies R. Ptak CHF 110,000 7

6 Selected Publications 1. Cazzoli D, Müri RM, Schumacher R, et al. Theta burst stimulation reduces disability during the activities of daily living in spatial neglect. Brain 2012; 135 : Kindler J, Schumacher R, Cazzoli D, et al. Theta Burst Stimulation Over the Right Broca s Homologue Induces Improvement of Naming in Aphasic Patients. Stroke. 2012; 43: Kipfer S, Pirovino C, El-Koussy M, et al. Dancing eyes and uvula after brain tumour extirpation-a sign of tumour progression? Lancet. 2012; 379: Walther S, Vanbellingen T, Müri RM, Strik WK, Bohlhalter S. Impaired pantomime in schizophrenia: association with frontal lobe function. Cortex 2012 (in press) Other areas of research in our department are whiplash injury, immune mediated neuropathies, and multiple sclerosis. 1) Whiplash injury Prof. Dr. med. Mathias Sturzenegger matthias.sturzenegger@insel.ch MD at University of Bern (1978); neurology residency in Bern (FMH certification in 1989). Cerebrovascular research Fellow at the Cerebrovascular Laboratory, Department of Neurological Surgery (University of Washington, Harborview Medical Center, Seattle, USA, 1993/94). Venia docendi in Since 2000 associate professor of Neurology. Since 1996 head of the inpatient clinic and emergencies of the Department of Neurology, Inselspital. Human research in non-atherosclerotic arteriopathies, whiplash injury, immunemediated neuropathies. Prof. R. Bingisser, PD Dr. A. Nidecker, Prof. Dr. B. Radanov, Dr. U. Pato The aim of several studies performed in this field is to evaluate the exact nature of cervical spine lesion caused by whiplash injury mechanism and responsible for the patients symptomatology. Previous research on this topic shows quite clearly, that if a method is able to delineate the pathology in the cervical spine structures, it would be high resolution MR. We therefore applied this technology in a prospective supported study in the acute setting and during follow-up. In a previous also supported study we managed to perform the first study in patients suffering from late whiplash syndrome to use randomized treatment allocation for evaluating different treatment strategies. 1. Ulbrich EJ, Aeberhard R, Wetli S, et al. Cervical muscle area measurements in whiplash patients: acute, 3 and 6 months follow-up. J Magn Reson Imaging 2012; 36: Suzanne E Anderson, Chris Boesch, et al. Are there MRI cervical spine findings specific to acute symptomatic whiplash injury? A prospective controlled study with four experienced blinded raters. Radiology, 2012, 262: ) Immune-mediated neuropathies Team Leader Prof. Dr. med. Mathias Sturzenegger matthias.sturzenegger@insel.ch 1. Jolles S, Stein MR, Hilary J, et al. How should we treat primary immunodeficiency today? New frontiers in subcutaneous immunoglobulin treatment. Biol Ther (in press) 3) Multiple sclerosis Prof. Heini Mattle henrich.mattle@insel.ch Prof. K. Rösler, Dr. C. Kamm, Dr. Ol. Findling, Dr. V. Blatter, M. Gafner (study nurse) In 2012 the results of a randomized controlled trial in Switzerland were published. The study (SWABIMS) compared the effect of atorvastatin added to bet-interferon as immunomodulatory treatment. The results were neutral. Other ongoing studies evaluate apraxia; the effect of focused treatment of ergotherapy; fatigue and eye movements in multiple sclerosis. 1. Kamm CP, El-Koussy M, Humpert S, et al. Atorvastatin added to interferon beta for relapsing remitting multiple sclerosis: a randomized controlled trial. J Neurol 2012; 259: Scheidegger O, Kamm CP, Humpert SJ, Rösler KM. Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls. Mult Scler 2012; 18: