Research & Development Kempenhaeghe

March 2015

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 spontane-

ously 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 connec-

tivity of the brain network.

Functional MRI (fMRI) is a way to study synchronicity of brain activ-

ity 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 per-

pendicular 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 lan-

guage 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

Contact person:

dr. ir. René Besseling2, assistant lecturer Eindhoven University of

Technology, R.M.H.Besseling@tue.nl

Promotores:

prof. dr. Bert Aldenkamp1,2,3,4, prof. dr. ir. Walter Backes4

Copromotor:

dr. Jaap Jansen4

1 Kempenhaeghe, Heeze 2 Eindhoven University of Technology3 Ghent University Hospital, Belgium 4 Maastricht University Medical Center

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 stimula-

tion 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 stimu-

lation 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 2014, 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 2016.

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 disa-bilities. 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 2010, a strategic collaboration was started with Eindhoven University of Technology in order to develop novel technologies to improve quality, efficiency, and safety of care in epilepsy, sleep medicine, and neuro-cognitive disorders. And since 2014, 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 2014/15 and an overview of ongoing PhD projects are shown.

Figure: fMRI of the brain

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.

Contact person:

ir. Debby Klooster1,2, PhD student Kempenhaeghe/

Eindhoven University of Technology

kloosterd@kempenhaeghe.nl/d.c.w.klooster@tue.nl

Collaborators:

dr. Anton de Louw1,2, prof. dr. Bert Aldenkamp1,2,3,4, dr. ir. Sveta

Zinger1,2, prof. dr. ir. Jan Bergmans2, prof. dr. Werner Mess4,

dr. ir. René Besseling2, prof. dr. Kristl Vonck3, dr. Evelien Carrette3,

drs. Sofie Carrette3, drs. Pieter van Mierlo3, prof. dr. Chris Baeken3,

drs. Lisanne Breuer1, prof. dr. Anton Tijhuis2, prof. dr. Paul Boon1,3

1 Kempenhaeghe, Heeze2 Eindhoven University of Technology3 Ghent University Hospital, Belgium4 Maastricht University Medical Center

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 surpri-

sing 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 10% of the

population is estimated to suffer from a sleep disorder.

Sleep disorders are typically characterized by subjective symp-

toms 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.

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 measure-

ments 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-2 grant called Advanced Sleep Monitoring.

Contact person:

dr. Sebastiaan Overeem1,2, Scientific coordinator Center for

Sleep Medicine Kempenhaeghe

OvereemS@kempenhaeghe.nl

1 Kempenhaeghe, Heeze2 Eindhoven University of Technology

Eye tracking in children with neurological learning disabilities

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 per-

spective. 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 neurologi-

cal 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 in-

formation processing as measured by for example eye movements,

duration of looking time, pupil diameter.

Ongoing PhD-projects

Home-based, multimodal detection of nocturnal seizures Judith van Andel

Study on working memory in adolescents with autism in the Netherlands

Evelien Barendse

Effects of long term use of anti-epileptic drugs on bone metabolism

Kim Beerhorst

MRI based analysis of neurodegeneration in epilepsy Antoine Bernas

Adaptation, standardization and validation of the Dutch version of the Wechsler Memory Scale - fourth edition

Zita Bouman

Neurodegeneration and accelerated cognitive ageing in epilepsy Lisanne Breuer

MMIND-E: MEG and MRI in diagnosis of epilepsy Albert Colon

Interictal epileptiform activity as a marker for clinical outcome Saskia Ebus

Transition to adult medical care for adolescents with epilepsy Rianne Geerlings

Mitochondrial dysfunction in refractory epilepsy Nienke Gosens

Pre-surgical functional mapping in epilepsy using EEG and fMRI Kees Hermans

Cognitive effects of anti-epileptic drug treatment Dominique Ijff

Health technology assessment in epilepsy - Economic evaluations and preference studies

Reina de Kinderen

Neurostimulation: towards a deeper insight into the mechanism of action

Debby Klooster

Psychological factors and individual differences in insomnia: Implications for theory and treatment

Merijn van de Laar

Ketogenic diet. Treatment for children and adults with refractory epilepsy

Daniëlle Lambrechts

Self-management in people with epilepsy Loes Leenen

On the analysis and classification of sleep stages from cardiorespiratory signals

Xi Long

Thalamo-cortical circuit identification using structural and functional connectivity analysis

Stephan Meesters

Neuropsychiatric comorbidities in chronic epilepsy patients with an intellectual disability *

Jans van Ool

Time awareness and working memory in children with neurological learning disabilities: diagnostic and therapeutic implications

Janneke Peijnenborgh

Intelligent systems in the diagnosis and behavioral change in narcolepsy

Laury Quaedackers

Epileptic seizure detection Andrei Sazonov

Neuropsychiatric comorbidities in chronic epilepsy patients with an intellectual disability *

Francesca Snoeijen-Schouwenaars

Post-stroke epilepsy Jordie van Tuijl

Assessment of respiratory effort during sleep: esophageal pressure versus noninvasive techniques

Nele Vandenbussche

Neurotransmitter metabolism of cognitive adverse events of antiepileptic drugs

Tamar van Veenendaal

Monitoring of non-convulsive seizure states of epilepsy Lei Wang

Economic-evaluation and patient-based preference in epilepsy Ben Wijnen

* twin study

PhD theses defended in 2014 - 2015

Brain wiring and neuronal dynamics – advances in MR imaging of focal epilepsy

René Besseling

VNS in children; more than just seizure reduction Sylvia Klinkenberg

Psychogenic non-epileptic seizures – the identification of neuropsychological correlates

Sylvie Kolfschoten-van der Kruijs

Sleep in Parkingson’s disease – a focus on nocturnal movements Maartje Louter

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 estima-

tion. During the game the child’s reactions on pushbuttons and

eye tracking data are measured and can be analyzed in col-

laboration. 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 pro-

blems children with neurological learning disabilities. We currently

refine the eye tracking technology for example in assessment

procedures for evaluating the effect of ADHD medication.

Contact person:

drs. Janneke Peijnenborgh, PhD student/Psychologist

peijnenborghj@kempenhaeghe.nl

Collaborators:

dr. Jos Hendriksen1,4, prof. dr. Bert Aldenkamp1,2,3,4,

prof. dr. Hans Vles1,4, Pongpanote Gongsook2, dr. Jun Hu2, prof.

dr. Matthias Rauterberg2, dr. Petra Hurks5, drs. Marlou Kooiker5,

dr. Johan Pel6

1 Kempenhaeghe, Heeze2 Eindhoven University of Technology3 Ghent University Hospital, Belgium4 Maastricht University Medical Center5 Maastricht University6 Erasmus Medical Center, Rotterdam

List of publications 2014 and 2015 (2/2015)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 2014; 271(1-2): 36-42. doi: 10.1016/j.jneuroim.2014.03.016

• 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 2014; 37(6): 1035-1042. doi: 10.5665/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 2014; 8: 704. doi: 10.3389/fnhum.2014.00704.

• 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 2015; 51(1): 24-29. doi: 10.1002/mus.24272

• Bickerstaffe A, van Dijk JP, Beelen A, Zwarts MJ, Nollet F. Loss of motor unit size and quadriceps strength over 10years in post-polio syndrome. Clin Neurophysiol 2014; 125(6): 1255-1260. doi: 10.1016/j.clinph.2013.11.003

• 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 2015. doi: 10.1136/jmedgenet-2014-102813

• 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 2014; (Dec 14). doi: 10.1007/s10803-014-2341-1

• 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 2014; (Jul 31): 1-9. doi: 10.1017/s1041610214001471

• 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 2015; 131(1): 17-29. doi: 10.1111/ane.12283

• 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 2014; 129(4): 252-262. doi: 10.1111/ane.12183

• 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 2015; 42: 147-152. doi: 10.1016/j.yebeh.2014.10.034

• 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 proloactin-relaesing peptide decrease cortical excitability through activation of NPFF receptors. Epilepsia 2015 (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’14, European Conference on Ambient Intelligence, 2014 2014.

• 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 2014;14(12)

• van der Corput P, Arends J, van Wijk JJ. Visualization of Medicine Prescription Behavior. Computer Graphics Forum 2014; 33(3): 161-170. doi: 10.1111/cgf.12372

• Cuperus J, Vugs B, Scheper A, Hendriks M. Executive function behaviours in children with specific language impairment (SLI). International Journal of Developmental Disabilities 2014; 60(3): 132-143. doi: 10.1179/2047387714Y.0000000049

• 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 2014;138:19-26

• 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. Neurothera-peutics 2014; 11(3): 612-622. doi: 10.1007/s13311-014-0272-3

• 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 2015 (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 2014; 37(4): 795-801. doi: 10.5665/sleep.3592

• 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 2014; 76(3): 403-411. doi: 10.1002/ana.24222

• 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 2015; 25(1): 73-80. doi: 10.1016/j.nmd.2014.09.014

• 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 2-year follow-up study. Epilepsy Behav 2014; 43: 8-15. doi: 10.1016/j.yebeh.2014.11.027

• Ebus SC, Lambrechts D, Herraets I, Majoie MH, de Louw A, Boon PJ, Aldenkamp A, Arends J. Can an early 24-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 2014; 23(6): 468-474. doi: 10.1016/j.seizure.2014.03.008

• 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 2014; (Oct 2). doi: 10.1016/j.clinph.2014.09.023

• 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 2015; 44: 127-135. doi: 10.1016/j.yebeh.2014.12.041

• 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 2014; 85: 231-238. doi: 10.1016/j.bandc.2013.12.009

• van Gilst MM, Bloem BR, Overeem S. Prospective assessment of subjective sleep benefit in Parkinson inverted question marks disease. BMC Neurol 2015; 15(1): 2. doi: 10.1186/s12883-014-0256-2

• 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 2015;8:13-20

• 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, 2014.

• 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 2014; 42: 10-13. doi: 10.1016/j.yebeh.2014.10.030

• 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 2014; 5: 266-276. doi: 10.1016/j.nicl.2014.06.013

• 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 2014; 23(9): 685-691. doi: 10.1016/j.seizure.2014.06.004

• 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 2014; 31: 43-47. doi: 10.1016/j.yebeh.2013.11.010

• 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 2015; (Feb 9). doi: 10.1016/j.neubiorev.2015.01.023

• 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 2014; (Oct 16). doi: 10.1007/s10548-014-0407-1

• 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 2015; (Jan 28). doi: 10.1111/ane.12372

• 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 2014; 16(3): 318–327. doi: 10.1684/epd.2014.0665

• de Kinderen RJ, Evers SM, Rinkens R, Postulart D, Vader CI, Majoie MH, Aldenkamp AP. Side-effects of antiepileptic drugs: The economic burden. Seizure 2014; 23(3): 184-190. doi: 10.1016/j.seizure.2013.11.009

• 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 2015; 110: 119-131. doi: 10.1016/j.eplepsyres.2014.12.005

• 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 2014; 2: 49-53. doi: 10.1016/j.ebcr.2014.02.002

• 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 2014; 37: 133-138. doi: 10.1016/j.yebeh.2014.06.001

• 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 2014; 85(2): 174-179. doi: 10.1136/jnnp-2012-302905

• 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 2014; 54: 126-133. doi: 10.1016/j.jpsychires.2014.03.010

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Research and Development Board

prof. dr. Paul Boon, director

prof. dr. Bert Aldenkamp, executive secretary

prof. dr. Johan Arends, chair Medical Ethical Committee

dr. Laura Gottmer-Welschen, manager

dr. Anton de Louw, medical director Academic Center for Epileptology

prof. dr. Dirk Pevernagie, medical head Center for Sleep Medicine

Sterkselseweg 65

5591 VE HEEZE

Postbus 61

5590 AB HEEZE

T (040) 227 90 22

E info@kempenhaeghe.nl

W www.kempenhaeghe.nl

• 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 Biologi-cal Rhythms 2015; 13(1): 41-48. doi: 10.1111/sbr.12100

• 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 Psychop-hysiological Insomnia. Behav Sleep Med 2014; (Apr 7). doi: 10.1080/15402002.2013.845781

• 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 2014; 14: 255. doi: 10.1186/s12883-014-0255-3

• Louter M, Arends JB, Bloem BR, Overeem S. Actigraphy as a diagnostic aid for REM sleep behavior disorder in Parkinson’s disease. BMC Neurol 2014; 14(1): 76. doi: 10.1186/1471-2377-14-76

• 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 2015; 86(1): 32-37. doi: 10.1136/jnnp-2013-306851

• 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 2014; 91(3): 163-171. doi: 10.1016/j.ijpsycho.2013.10.012

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