Research & Development Kempenhaeghe. March 2015

Transcription

1 Research & Development Kempenhaeghe March 05

2 Kempenhaeghe is a leading center of medical expertise, offering diagnosis and treatment to adults and children who suffer from a complex form of epilepsy, a sleeping disorder or neurological learning disabilities. Research & Development of Kempenhaeghe is aimed at development and transfer of expertise. Research questions for our studies originate directly from patient care and are focused on innovation of patient care. Since 00, a strategic collaboration was started with in order to develop novel technologies to improve quality, efficiency, and safety of care in epilepsy, sleep medicine, and neuro-cognitive disorders. And since 04, the Academic Center of Epileptology was set up with Maastricht University Medical Center (Maastricht UMC+). In this overview, examples of innovation projects of Kempenhaeghe with other partners are provided. In addition, a publication list of 04/5 and an overview of ongoing PhD projects are shown. Brain mechanisms of language problem in children with rolandic epilepsy Rolandic epilepsy (RE) is one of the most common childhood epilepsies, and is characterized by relatively mild seizures which typically occur during sleep. In addition, the seizures spontaneously stop before adolescence, and RE has long been considered a benign disease. However, epilepsy is often not only a disease associated with seizures, and in RE children often develop learning difficulties, especially language problems. These language impairments are known from clinical practice and also surface in neuropsychological testing, but it is not clear how this works on the level of the brain. The goal of this project was to find brain abnormalities which might explain these language problem using advanced neuroimaging. Functional and diffusion weighted MRI was used to study functional and structural connectivity of the brain network. dr. ir. René Besseling, assistant lecturer Eindhoven University of Technology, R.M.H.Besseling@tue.nl Promotores: prof. dr. Bert Aldenkamp,,3,4, prof. dr. ir. Walter Backes 4 Copromotor: dr. Jaap Jansen 4 3 Ghent University Hospital, Belgium 4 Maastricht University Medical Center Functional MRI (fmri) is a way to study synchronicity of brain activity in distributed brain regions. Classically it is used to see which region(s) activate under a certain task, but it may also be used to investigate which regions are in synch (and thus functionally connected) during rest. We found that the motor areas of the brain are functionally connected with language areas in the left half of the brain. Since in RE the seizures actually originate in these motor areas, this may represent a pathway along which RE can impact language. Indeed, this functional connection between motor and language areas was impaired in children with RE compared to healthy control children. In addition, we used diffusion weighted MRI (DWI) to study structural brain connectivity. DWI exploits the fact that in brain nerve fibers, transport of water occurs primarily along the fibers (and not in perpendicular directions). DWI can be used to reconstruct the course of nerve fibers within the brain (tractography), but also to quantify their microstructural integrity. In line with our functional findings, we found reduced structural connectivity between the motor areas and left lateralized language areas in children with RE. Furthermore, lower microstructural integrity of these connections was associated with reduced language performance in these children. These studies shed light on the brain mechanisms underlying language impairments in children with RE, and provide starting points for therapy development. This work has been published in leading clinical as well as technical journals and has resulted in a PhD thesis Brain wiring and neuronal dynamcics advances in MR imaging of focal epilepsy Figure: fmri of the brain Neurostimulation: towards a deeper insight into the mechanism of action Nowadays, different methods of neurostimulation exist which have shown to be valuable in cognitive neuroscience, neurophysiology, psychiatry and neurology. An example of probably one of the most familiar results is the relief of tremor in patients with Parkinson s disease after deep brain stimulation. Although the clinical benefits have been proven in some disorders, not all patients respond well to neurostimulation. The mechanism of action of different stimulation techniques, and the influence of the stimulation parameters, such as the stimulation frequency, intensity, or location, are not yet known. This knowledge is crucial for further improvement of stimulation techniques in clinical practice, to learn what type of patient responds best to a certain stimulation technique, and to be able to tune the stimulation parameters specifically per patient. This PhD project, started halfway 04, aims at improving the knowledge about the mechanism of action of neurostimulation. Protocols for pilot studies will be conducted in the coming months with the collaborating institutes: Kempenhaeghe, Eindhoven University of Technology, University Hospital Ghent, and the University Hospital Maastricht. Results from the first pilot studies are expected in the beginning of 06.

3 Within Kempenhaeghe, the final, long-term, goal with respect to neurostimulation is to apply the knowledge in a clinical project called NEU3-CA (Neurodegeneration, Neuronal Networks and Neuromodulation in Epilepsy-induced Accelerated Cognitive Ageing). A part of NEU3-CA focuses on the question whether neurostimulation may improve cognitive decline in patients with epilepsy and signs of accelerated cognitive ageing. The results of the PhD project will be helpful to determine the stimulation protocol for NEU3-CA but are definitely applicable beyond this scope, i.e. may be helpful for healthy ageing. ir. Debby Klooster,, PhD student Kempenhaeghe/ kloosterd@kempenhaeghe.nl/d.c.w.klooster@tue.nl One of the core research lines of the Center for Sleep Medicine at Kempenhaeghe is therefore aimed at developing advanced, minimally-intrusive methods to measure sleep and sleep disorders, preferably over longer periods of time in the home environment. Tools will be developed to assess aspects of breathing disorders in sleep (sleep apnea) as well as subjective symptoms in insomnia patients. Research also focuses on using these long term measurements as a feedback for therapy, so highly personalized treatment strategies will become within reach. This research is performed in close collaboration with the faculties of Industrial Design and Electrical Engineering of the Eindhoven University of Technology, as well as several departments at Philips. Recently, funding for 7 PhD s was obtained in this collaboration through an Impulse- grant called Advanced Sleep Monitoring. Collaborators: dr. Anton de Louw,, prof. dr. Bert Aldenkamp,,3,4, dr. ir. Sveta Zinger,, prof. dr. ir. Jan Bergmans, prof. dr. Werner Mess 4, dr. ir. René Besseling, prof. dr. Kristl Vonck 3, dr. Evelien Carrette 3, drs. Sofie Carrette 3, drs. Pieter van Mierlo 3, prof. dr. Chris Baeken 3, drs. Lisanne Breuer, prof. dr. Anton Tijhuis, prof. dr. Paul Boon,3 dr. Sebastiaan Overeem,, Scientific coordinator Center for Sleep Medicine Kempenhaeghe OvereemS@kempenhaeghe.nl 3 Ghent University Hospital, Belgium 4 Maastricht University Medical Center Eye tracking in children with neurological learning disabilities Sleep: how we spend one third of our lifetime Sleep is a fascinating and essential behavior, in which we spend about one third of our lifetime. Given this timespan, it is not surprising that many things can go wrong with our sleep. There are many different sleep disorders - about 85 have currently been described - and many people are afflicted by disturbed sleep: up to 0% of the population is estimated to suffer from a sleep disorder. Sleep disorders are typically characterized by subjective symptoms that change over time and under the influence of external behaviors. Objective parameters of sleep - such as sleep depth or sleep efficiency - fluctuate as well. In current clinical practice, these temporal aspects are almost completely ignored. Moreover, the current diagnostic techniques capture only a very limited part of the underlying pathophysiology. In the outpatient Center for Neurological Learning Disorders children (in the range from toddlers to adolescents) with learning problems due to a neurological cause are assessed for a multidisciplinary perspective. Diverse neurocognitive problems are seen e.g., attentional problems as in acquired ADHD but also, problems in information processing, memory or motor function. Since one year we use eye tracking technology alongside neurological and neuropsychological assessment. We use Tobii eye tracking and collaborate in this with Erasmus Medical Center where there is a lot of expertise with this technology. An eye-tracker is a tool that can be attached to a computer screen and measures where and how long a child is looking at the screen. Because the eye-tracker is attached to the screen, the child can move its head unimpeded and is not aware that eyes are being tracked. Data allow analyses of information processing as measured by for example eye movements, duration of looking time, pupil diameter.

4 Together with the department of industrial design of University of Technology in Eindhoven, we developed a diagnostic computer game named Timo s Adventure for a touch screen computer. The game consists of six tasks for children aged 4-8 years to measure different neurocognitive functions, primarily attention, working memory, planning skills, reaction times and time estimation. During the game the child s reactions on pushbuttons and eye tracking data are measured and can be analyzed in collaboration. Besides the results of the different tasks, we collect information on visual search strategies, attention and distraction parameters (e.g., how long does it take for a child to go back to target after being distracted). Eye tracking is a safe and non-invasive method to collect valuable information from scientific and clinical perspective. This information helps in the diagnosis of neurocognitive problems children with neurological learning disabilities. We currently refine the eye tracking technology for example in assessment procedures for evaluating the effect of ADHD medication. drs. Janneke Peijnenborgh, PhD student/psychologist peijnenborghj@kempenhaeghe.nl Collaborators: dr. Jos Hendriksen,4, prof. dr. Bert Aldenkamp,,3,4, prof. dr. Hans Vles,4, Pongpanote Gongsook, dr. Jun Hu, prof. dr. Matthias Rauterberg, dr. Petra Hurks 5, drs. Marlou Kooiker 5, dr. Johan Pel 6 3 Ghent University Hospital, Belgium 4 Maastricht University Medical Center 5 Maastricht University 6 Erasmus Medical Center, Rotterdam Ongoing PhD-projects Home-based, multimodal detection of nocturnal seizures Study on working memory in adolescents with autism in the Netherlands Effects of long term use of anti-epileptic drugs on bone metabolism MRI based analysis of neurodegeneration in epilepsy Adaptation, standardization and validation of the Dutch version of the Wechsler Memory Scale - fourth edition Neurodegeneration and accelerated cognitive ageing in epilepsy MMIND-E: MEG and MRI in diagnosis of epilepsy Interictal epileptiform activity as a marker for clinical outcome Transition to adult medical care for adolescents with epilepsy Mitochondrial dysfunction in refractory epilepsy Pre-surgical functional mapping in epilepsy using EEG and fmri Cognitive effects of anti-epileptic drug treatment Health technology assessment in epilepsy - Economic evaluations and preference studies Neurostimulation: towards a deeper insight into the mechanism of action Psychological factors and individual differences in insomnia: Implications for theory and treatment Ketogenic diet. Treatment for children and adults with refractory epilepsy Self-management in people with epilepsy On the analysis and classification of sleep stages from cardiorespiratory signals Thalamo-cortical circuit identification using structural and functional connectivity analysis Neuropsychiatric comorbidities in chronic epilepsy patients with an intellectual disability * Time awareness and working memory in children with neurological learning disabilities: diagnostic and therapeutic implications Intelligent systems in the diagnosis and behavioral change in narcolepsy Epileptic seizure detection Neuropsychiatric comorbidities in chronic epilepsy patients with an intellectual disability * Post-stroke epilepsy Assessment of respiratory effort during sleep: esophageal pressure versus noninvasive techniques Neurotransmitter metabolism of cognitive adverse events of antiepileptic drugs Monitoring of non-convulsive seizure states of epilepsy Economic-evaluation and patient-based preference in epilepsy * twin study Judith van Andel Evelien Barendse Kim Beerhorst Antoine Bernas Zita Bouman Lisanne Breuer Albert Colon Saskia Ebus Rianne Geerlings Nienke Gosens Kees Hermans Dominique Ijff Reina de Kinderen Debby Klooster Merijn van de Laar Daniëlle Lambrechts Loes Leenen Xi Long Stephan Meesters Jans van Ool Janneke Peijnenborgh Laury Quaedackers Andrei Sazonov Francesca Snoeijen- Schouwenaars Jordie van Tuijl Nele Vandenbussche Tamar van Veenendaal Lei Wang Ben Wijnen PhD theses defended in Brain wiring and neuronal dynamics advances in MR imaging of focal epilepsy VNS in children; more than just seizure reduction Psychogenic non-epileptic seizures the identification of neuropsychological correlates Sleep in Parkingson s disease a focus on nocturnal movements René Besseling Sylvia Klinkenberg Sylvie Kolfschotenvan der Kruijs Maartje Louter

5 List of publications 04 and 05 (/05) Author is affiliated with Kempenhaeghe Aalbers MW, Rijkers K, Majoie HJ, Dings JT, Schijns OE, Schipper S, De Baets MH, Kessels A, Vles JS, Hoogland G. The influence of neuropathology on brain inflammation in human and experimental temporal lobe epilepsy. J Neuroimmunol 04; 7(-): doi: 0.06/j. jneuroim Baumann CR, Mignot E, Lammers GJ, Overeem S, Arnulf I, Rye D, Dauvilliers Y, Honda M, Owens JA, Plazzi G, Scammell TE. Challenges in Diagnosing Narcolepsy without Cataplexy: A Consensus Statement. Sleep 04; 37(6): doi: /sleep.3756 Besseling RM, Jansen JF, Overvliet GM, van der Kruijs SJ, Ebus S, de Louw AJ, Hofman PA, Aldenkamp AP, Backes WH. Delayed convergence between brain network structure and function in rolandic epilepsy. Frontiers in Human Neuroscience 04; 8: 704. doi: / fnhum Bickerstaffe A, Beelen A, Zwarts MJ, Nollet F, van Dijk JP. Quantitative muscle ultrasound and quadriceps strength in patients with post-polio syndrome. Muscle Nerve 05; 5(): 4-9. doi: 0.00/mus.47 Bickerstaffe A, van Dijk JP, Beelen A, Zwarts MJ, Nollet F. Loss of motor unit size and quadriceps strength over 0years in post-polio syndrome. Clin Neurophysiol 04; 5(6): doi: 0.06/j.clinph Blanchard MG, Willemsen MH, Walker JB, Dib-Hajj SD, Waxman SG, Jongmans MC, Kleefstra T, van de Warrenburg BP, Praamstra P, Nicolai J, Yntema HG, Bindels RJ, Meisler MH, Kamsteeg EJ. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy. J Med Genet 05. doi: 0.36/jmedgenet Boets B, Verhoeven J, Wouters J, Steyaert J. Fragile Spectral and Temporal Auditory Processing in Adolescents with Autism Spectrum Disorder and Early Language Delay. J Autism Dev Disord 04; (Dec 4). doi: 0.007/s Bouman Z, Hendriks MP, Aldenkamp AP, Kessels RP. Clinical validation of the WMS-IV-NL brief cognitive status exam (BCSE) in older adults with MCI or dementia. Int Psychogeriatr 04; (Jul 3): -9. doi: 0.07/s Braakman HM, Vaessen MJ, Jansen JF, Debeij-van Hall MH, de Louw A, Hofman PA, Vles JS, Aldenkamp AP, Backes WH. Aetiology of cognitive impairment in children with frontal lobe epilepsy. Acta Neurol Scand 05; 3(): 7-9. doi: 0./ane.83 Braakman HMH, Vaessen MJ, Jansen JFA, Debeij-van Hall MHJA, de Louw A, Hofman PAM, Vles JS, Aldenkamp AP, Backes WH. Pediatric frontal lobe epilepsy: white matter abnormalities and cognitive impairment Acta Neurol Scand 04; 9(4): 5-6. doi: 0./ane.83 Braams O, Meekes J, Braun K, Schappin R, van Rijen PC, Hendriks MP, Jennekens-Schinkel A, van Nieuwenhuizen O. Parenting stress does not normalize after child s epilepsy surgery. Epilepsy & Behavior 05; 4: doi: 0.06/j.yebeh Buffel I, Meurs A, Portelli J, Raedt R, De Herdt V, Sioncke L, Wadman W, Bihel F, Schmitt M, Vonck K, Bourguignon JJ, Simonin F, Smolders I, Boon P. Neuropeptide FF and proloactinrelaesing peptide decrease cortical excitability through activation of NPFF receptors. Epilepsia 05 (epub) Cernat RA, Ungureanu C, Ungureanu GM, Aarts R, Arends J. Real-time extraction of the respiratory rate from photoplethysmographic signal using wearable devices. Proceedings AMI 4, European Conference on Ambient Intelligence, Chen YH, De Beeck MO, Vanderheyden L, Carrette E, Mihajlovic V, Vanstreesl K, Grundlehner B, Gadeyne S, Boon P, Van Hoof C. Soft, comfortable polymer dry electrodes for high quality ECG and EEG recording. Sensors 04;4() van der Corput P, Arends J, van Wijk JJ. Visualization of Medicine Prescription Behavior. Computer Graphics Forum 04; 33(3): doi: 0./cgf.37 Cuperus J, Vugs B, Scheper A, Hendriks M. Executive function behaviours in children with specific language impairment (SLI). International Journal of Developmental Disabilities 04; 60(3): doi: 0.79/ Y De Letter M, Aarts A, Van Borsel J, Vanhoutte S, De Taeye L, Raedt R, Van Mierlo P, Boon P, Van Roost D, Santens P. Electrophysiological registration of phonological perception in the subthalamic nucleus of patients with Parkinson s disease. Brain Lang 04;38:9-6 De Taeye L, Vonck K, van Bochove M, Boon P, Van Roost D, Mollet L, Meurs A, De Herdt V, Carrette E, Dauwe I, Gadeyne S, van Mierlo P, Verguts T, Raedt R. The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy. Neurotherapeutics 04; (3): 6-6. doi: 0.007/s De Taeye L, Pourtois G, Meurs A, Boon P, Vonck K, Carrette E, Raedt R. Event-related potentials reveal preserved attention allocation but impaired emotion regulation in patients with epilepsy and comorbid negative affect. PLoS One 05 (epub) Donjacour CE, Aziz NA, Overeem S, Kalsbeek A, Pijl H, Lammers GJ. Glucose and fat metabolism in narcolepsy and the effect of sodium oxybate: a hyperinsulinemic-euglycemic clamp study. Sleep 04; 37(4): doi: /sleep.359 Doorenweerd N, Straathof CS, Dumas EM, Spitali P, Ginjaar IB, Wokke BH, Schrans DG, van den Bergen JC, van Zwet EW, Webb A. Reduced cerebral grey matter and altered white matter in boys with Duchenne muscular dystrophy. Annals of Neurology 04; 76(3): doi: 0.00/ana.4 Drost G, Stunnenberg BC, Trip J, Borm G, McGill KC, Ginjaar I, van der Kooi AW, Zwarts MJ, van Engelen BG, Faber CG. Myotonic discharges discriminate chloride from sodium muscle channelopathies. Neuromuscular Disorders 05; 5(): doi: 0.06/j.nmd Ebus SC, IJff DM, den Boer JT, van Hall MJ, Klinkenberg S, van der Does A, Boon PJ, Arends JB, Aldenkamp AP. Changes in the frequency of benign focal spikes accompany changes in central information processing speed: A prospective -year follow-up study. Epilepsy Behav 04; 43: 8-5. doi: 0.06/j.yebeh Ebus SC, Lambrechts D, Herraets I, Majoie MH, de Louw A, Boon PJ, Aldenkamp A, Arends J. Can an early 4-hour EEG predict the response to the ketogenic diet? A prospective study in 34 children and adults with refractory epilepsy treated with the ketogenic diet. Seizure 04; 3(6): doi: 0.06/j.seizure Fürbass F, Ossenblok P, Hartmann M, Perko H, Skupch A, Lindinger G, Elezi L, Pataraia E, Colon A, Baumgartner C. Prospective Multi-Center Study of an Automatic Online Seizure Detection System for Epilepsy Monitoring Units. Clinical Neurophysiology 04; (Oct ). doi: 0.06/j.clinph Geerlings RPJ, Aldenkamp AP, de With PHN, Zinger S, Gottmer-Welschen LMC, de Louw AJA. Transition to adult medical care for adolescents with epilepsy. Epilepsy & Behavior 05; 44: doi: 0.06/j.yebeh van Geldorp B, Bouman Z, Hendriks MP, Kessels RP. Different types of working memory binding in epilepsy patients with unilateral anterior temporal lobectomy. Brain Cogn 04; 85: doi: 0.06/j.bandc van Gilst MM, Bloem BR, Overeem S. Prospective assessment of subjective sleep benefit in Parkinson inverted question marks disease. BMC Neurol 05; 5():. doi: 0.86/ s Grimonprez A, Raedt R, Dauwe I, Mollet L, Larsen LE, Meurs A, De Herdt V, Wadman W, Delbeke J, Vonck K, Boon P. Vagus nerve stimulation has antidepressant effects in kainic acid model for temporal lobe epilepsy. Brain Stimul 05;8:3-0 Gongsook P, Peijnenborgh J, Sallustro C, Van der Spek E, Hu J, Bellotti F, Rauterberg M & Hendriksen J. A diagnostic tool on time perception of children with ADHD, Springer International Publishing, 04. Groot LJ, Gosens N, Vles JS, Hoogland G, Aldenkamp AP, Rouhl RP. Inter- and intraobserver agreement of seizure behavior scoring in the amygdala kindled rat. Epilepsy Behav 04; 4: 0-3. doi: 0.06/j.yebeh Gupta L, Besseling RM, Overvliet GM, Hofman PA, de Louw A, Vaessen MJ, Aldenkamp AP, Ulman S, Jansen JF, Backes WH. Spatial heterogeneity analysis of brain activation in fmri. Neuroimage Clin 04; 5: doi: 0.06/j.nicl Halma E, de Louw AJA, Klinkenberg S, Aldenkamp AP, IJff DM, Majoie M. Behavioral side-effects of levetiracetam in children with epilepsy: a systematic review. Seizure 04; 3(9): doi: 0.06/j.seizure Helmstaedter C, Aldenkamp AP, Baker GA, Mazarati A, Ryvlin P, Sankar R. Disentangling the relationship between epilepsy and its behavioral comorbidities - The need for prospective studies in new-onset epilepsies. Epilepsy Behav 04; 3: doi: 0.06/j.yebeh Hendriksen RG, Hoogland G, Schipper S, Hendriksen JG, Vles JS, Aalbers MW. A Possible Role of dystrophin in neuronal excitability: a review of the current literature. Neurosci Biobehav Rev 05; (Feb 9). doi: 0.06/j.neubiorev van Houdt PJ, Ossenblok PP, Colon AJ, Hermans KH, Verdaasdonk RM, Boon PA, de Munck JC. Are Epilepsy-Related fmri Components Dependent on the Presence of Interictal Epileptic Discharges in Scalp EEG? Brain Topogr 04; (Oct 6). doi: 0.007/s IJff DM, van Veenendaal TM, Majoie HJ, de Louw AJ, Jansen JF, Aldenkamp AP. Cognitive effects of lacosamide as adjunctive therapy in refractory epilepsy. Acta Neurol Scand 05; (Jan 8). doi: 0./ane.37 Jansen JF, van der Kruijs SJ, Vlooswijk MC, Majoie HM, Hofman PA, Aldenkamp AP, Backes WH. Quantitative MR and cognitive impairment in cryptogenic localisation-related epilepsy. Epileptic Disord 04; 6(3): doi: 0.684/epd de Kinderen RJ, Evers SM, Rinkens R, Postulart D, Vader CI, Majoie MH, Aldenkamp AP. Side-effects of antiepileptic drugs: The economic burden. Seizure 04; 3(3): doi: 0.06/j.seizure de Kinderen RJ, Postulart D, Aldenkamp AP, Evers SM, Lambrechts DA, de Louw AJ, Majoie MH, Grutters JP. Cost-effectiveness of the ketogenic diet and vagus nerve stimulation for the treatment of children with intractable epilepsy. Epilepsy Research 05; 0: 9-3. doi: 0.06/j. eplepsyres Klinkenberg S, Ubbink S, Vles J, de Louw A, Debeij-van Hall M, Scheijen D, Brokx J. Noninvasive treatment alternative for intractable startle epilepsy. Epilepsy & Behavior Case Reports 04; : doi: 0.06/j.ebcr Klinkenberg S, van den Borne C, Aalbers M, Verschuure P, Kessels A, Leenen L, Rijkers K, Aldenkamp A, Vles J, Majoie H. The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy. Epilepsy & Behavior 04; 37: doi: 0.06/j. yebeh van der Kruijs SJ, Bodde NM, Carrette E, Lazeron RH, Vonck KE, Boon PA, Langereis GR, Cluitmans PJ, Feijs LM, Hofman PA, Backes WH, Jansen JF, Aldenkamp AP. Neurophysiological correlates of dissociative symptoms. J Neurol Neurosurg Psychiatry 04; 85(): doi: 0.36/jnnp van der Kruijs SJ, Jagannathan SR, Bodde NM, Besseling RM, Lazeron RH, Vonck KE, Boon PA, Cluitmans PJ, Hofman PA, Backes WH, Aldenkamp AP, Jansen JF. Resting-state networks and dissociation in psychogenic non-epileptic seizures. J Psychiatr Res 04; 54: doi: 0.06/j.jpsychires

6 van de Laar M, Pevernagie D, van Mierlo P, Overeem S. Subjective sleep characteristics in primary insomnia versus insomnia with comorbid anxiety or mood disorder. Sleep and Biological Rhythms 05; 3(): doi: 0./sbr.00 van de Laar M, Pevernagie D, van Mierlo P, Overeem S. Psychiatric Comorbidity and Aspects of Cognitive Coping Negatively Predict Outcome in Cognitive Behavioral Treatment of Psychophysiological Insomnia. Behav Sleep Med 04; (Apr 7). doi: 0.080/ Leenen LA, Wijnen BF, de Kinderen RJ, Majoie MH, van Heugten CM, Evers SM. (Cost)- effectiveness of a multi-component intervention for adults with epilepsy: study protocol of a Dutch randomized controlled trial (ZMILE study). BMC Neurology 04; 4: 55. doi: 0.86/ s Louter M, Arends JB, Bloem BR, Overeem S. Actigraphy as a diagnostic aid for REM sleep behavior disorder in Parkinson s disease. BMC Neurol 04; 4(): 76. doi: 0.86/ Louter M, Maetzler W, Prinzen J, van Lummel RC, Hobert M, Arends JB, Bloem BR, Streffer J, Berg D, Overeem S, Liepelt-Scarfone I. Accelerometer-based quantitative analysis of axial nocturnal movements differentiates patients with Parkinson s disease, but not high-risk individuals, from controls. J Neurol Neurosurg Psychiatry 05; 86(): doi: 0.36/ jnnp Maes J, Verbraecken J, Willemen M, De Volder I, van Gastel A, Michiels N, Verbeek I, Vandekerckhove M, Wuyts J, Haex B, Willemen T, Exadaktylos V, Bulckaert A, Cluydts R. Sleep misperception, EEG characteristics and Autonomic Nervous System activity in primary insomnia: A retrospective study on polysomnographic data. Int J Psychophysiol 04; 9(3): doi: 0.06/j.ijpsycho Meekes J, Braams OB, Braun KPJ, Jennekens-Schinkel A, Van Rijen PC, Alpherts WCJ, Hendriks MPH, Van Nieuwenhuizen O. Visual memory after epilepsy surgery in children: A standardized regression-based analysis of group and individual outcomes. Epilepsy Behav 04; 36: doi: 0.06/j.yebeh Meesters S, Ossenblok P, Colon A, Schijns O, Florack L, Boon P, Wagner L, Fuster A, Automated identification of intracranial depth electrodes in computed tomography data. Conf Proc IEEE International Symposium on Biomedical Imaging, 05 Mu J, Rampp S, Carrette E, Roessler K, Sommer B, Schmitt FC, De Tiege X, Hamer H, Boon P, Pauli E, Bluemcke I, Zhou D, Buchfelder M, Stefan H. Clinical relevance of source location in frontal lobe epilepsy and prediction of postoperative long-term outcome. Seizure 04; 3(7): doi: 0.06/j.seizure Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M, Claassen JA. Effect of Night of Total Sleep Deprivation on Cerebrospinal Fluid beta-amyloid 4 in Healthy Middle-Aged Men: A Randomized Clinical Trial. JAMA Neurol 04; 7(8): doi: 0.00/ jamaneurol Orosz I, Mccormic D, Zamponi N, Varadkar S, Feucht M, Parain D, Griens R, Vallee L, Boon P, Rittey C, Jayewardene AK, Bunker M, Arzimanoglou A, Lagae L. Vagus nerve stimulation for drug-resistant epilepsy: A European long-term study up to 4 months in 347 children. Epilepsia 04;55: Penzel T, Pevernagie D, Dogas Z, Grote L, de Lacy S, Rodenbeck A, Bassetti C, Berg S, Cirignotta F, d Ortho MP, Garcia-Borreguero D, Levy P, Nobili L, Paiva T, Peigneux P, Pollmacher T, Riemann D, Skene DJ, Zucconi M, Espie C. Catalogue of knowledge and skills for sleep medicine. J Sleep Res 04; 3(): -38. doi: 0./jsr.095 Peijnenborgh J, Hurks P, Aldenkamp A, Vles J, Hendriksen J. Efficacy of working memory training in children and adolescents with learning disabilities. Neuropsychological Rehabilitation, 05. Rossi S, Patki S, Passoni M, Perko H, Gritsch G, Ossenblok P, Yazicioglu RF. High density wireless EEG prototype: Design and evaluation against reference equipment. 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