Department of Neurology
Paroxysmal cerebral disorders (PaCD)
Programme leader: Prof. Dr. M.D. Ferrari
Principal investigators: Prof. Dr. M.D. Ferrari, Prof. Dr. J.G. van Dijk, Prof. Dr. A.M. van den Maagdenberg, Dr. G.J. Lammers, Dr. G.M. Terwindt, and Dr. M.J.H. Wermer
Projects & Mission: There are four main translational research lines studying highly disabling and mechanistically partly related brain disorders that are primarily characterized by recurring attacks of disease-specific transient brain dysfunction:
- Migraine and related headache and pain disorders (Ferrari, Terwindt, Van den Maagdenberg, and Wermer) "Headache research LUMC"
- Narcolepsy and other excessive daytime sleepiness disorders (Lammers, Van Dijk)
- Syncope transient global cerebral hypoperfusion and other autonomic disorders (Van Dijk)
- Pathogenesis and treatment of cerebral ischaemia related to migraine, subarachnoid hemorrhage, and rare monogenic neurovascular disorders (Wermer, Terwindt, Ferrari, and Van den Maagdenberg).
Neurological motor disorders (NMD)
Programme leader: Prof. Dr. R.A.C. Roos
Principal investigators: Prof. Dr. J.J.G.M. Verschuuren, Prof. Dr. J.J. van Hilten, Prof. Dr. R.A.C. Roos, and Dr. J. Plomp
Projects & Mission: There are three complementary lines of research each studying diseases of the motor system:
- Peripheral Motor System: Duchenne muscular dystrophy and myasthenic syndromes (Verschuuren, Niks, Straathof, Plomp) "Neuromuscular research LUMC"
- Both peripheral and central: Complex Regional Pain Syndrome (CRPS) (Van Hilten) "Trend Consortium"
- Central Motor System: Parkinson’s disease and Huntington’s disease (Van Hilten, Roos). "TRACK Huntington research"
"European Huntington network"
Aim and focus paroxysmal cerebral disorders
The programme consists of translational research lines, studying the diagnosis, clinical aspects, epidemiology, socio-economic-impact, structural and functional cerebral consequences, pathophysiology, and treatment of three highly disabling and mechanistically related episodic brain disorders that are primarily characterised by recurring attacks of transient dysfunction of disease-specific parts of the brain which may last from several minutes to several days.
Cohesion within LUMC
PaCD is very well embedded within the “Leiden Centre for Translational Neuroscience (LCTN)”, one of the six LUMC priority research theme’s, and within two of the recently recognized University Priority Profiles: Brain function and dysfunction over the lifespan and The Leiden Centre for Translational Drug Discovery & Development (LCTD3). There are much excellent, and often longstanding, clinical and scientific collaboration with other LUMC departments, including Human Genetics, Radiology, Molecular Cell Biology, Parasitology (Biomolecular Mass Spectrometry Unit), General Physician, Psychiatry, Bioinformatics, Clinical Genetics, Vascular Medicine, Nephrology, Thrombosis and Hemostasis, Anaesthesiology, Rheumatology, Immunohematology, and the Blood bank.
Position in international context
The PIs of the main PaCD research lines act at the forefront of the international scientific arena and are leading participants in the most important international scientific consortia and professional organisations of their research field. There is extensive clinical and scientific collaboration and even partnership with internationally leading research institutes; these include prestigious institutes such as Harvard, MIT, Stanford, Cambridge, Lausanne, University College London, University of California at San Francisco and at Los Angeles, University of Munich, and the University of Zurich and ETH.
The Leiden Migraine Team is globally among the premier research groups in (i) the genetics and molecular neurobiology of migraine and migraine attack-triggering mechanisms; and (ii) the neuroimaging analysis of structural cerebral consequences of migraine. It also is among the leading groups world-wide in the clinical evaluation of new migraine treatments.
The Leiden Narcolepsy Group, though relatively small, has played an important role in discovering and unravelling the causal role of hypocretin in narcolepsy and, most recently, in studying how immunological processes against hypothalamic hypocretin cells are likely to trigger the disease. Dr. Lammers is the current President of the European Narcolepsy Network (EU-NN).
The Leiden Syncope Researchers have been instrumental in developing a new classification of transient loss of consciousness, which was adopted in 2009 by the European Society of Cardiology, making it the current world standard for this field.
Aim and focus neurological motor disorders
The “Neurological Motor Disorders (NMDs)” is a collaborative effort of our clinical team supported by basic science research groups focusing on chronic conditions of the motor system from muscle to cortex. Healthy muscle, efficient neuromuscular transmission, and optimal brain function are all essential to produce and control movements.
The focus for all these disorders is to elucidate the pathophysiology and to study the efficacy of new drugs or modification of existing treatment strategies in order to improve the course of disease. Detailed clinical profiling, study of the natural history, web-based patient databases, and new outcome measures are all used to develop new treatments for these NMDs.
Biological or radiological (MRI) biomarkers or new outcome measures are being developed for the whole range of peripheral as well as central motor disorders, including Duchenne muscular dystrophy, myasthenia gravis, CRPS, Parkinson and Huntington disease
Detailed knowledge of the course of disease is essential for the development of sensitive outcome measures or interventions with “end of life” stage problems of several of these severely invalidating NMDs and is an important topic of study
New therapies include antisense oligonucleotide therapy for Duchenne muscular dystrophy or Huntington, new immunomodulating drugs for myasthenic syndromes, intrathecal drugs for CRPS and palliative care interventions for Huntington’s disease.
Cohesion within LUMC
NMD is very well embedded within the “Leiden Centre for Translational Neuroscience (LCTN)”, one of the six LUMC priority research theme’s, and within two of the recently recognized University Priority Profiles: Brain function and dysfunction over the lifespan and The Leiden Centre for Translational Drug Discovery & Development (LCTD3). There are many excellent, and often longstanding, clinical and scientific collaborations with other LUMC departments, including (in alphabetical order): Anaesthesiology, Bioinformatics, Blood bank, Cardiology, Clinical Genetics, Clinical Chemistry, Endocrinology, Human Genetics, Immunohematology, Infectious diseases, Medical Statistics and Leiden Institute of Advanced Computer Science, Medical Psychology, Molecular Cell Biology, Neurosurgey, Parasitology (Biomolecular Mass Spectrometry Unit), Pharmacy, Pathology, Pediatrics, Psychiatry, Radiology, Rehabilitation, and Rheumatology.
Position in international context
The Leiden Neuromuscular Team
The LUMC has a world leading position in the development of the antisense oligonucleotide medication for Duchenne muscular dystrophy (www.lumc.nl/duchenne and www.dmd.nl). It has a close collaboration with many internationally renowned neuromuscular experts. We are an active member of the EU-funded TREAT-NMD project (2006-2011). TREAT-NMD involves 22 European and 8 non-European partner countries, including USA, Australia and Turkey (www.treat-nmd.eu).
The LUMC is an internationally recognized referral center for myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). It has the world-largest data collection on patients with LEMS (Lancet Neurology, 2011). We participate in the Euromyasthenia project, with partners in 16 European countries, and the EU-project FIGHT-MG which is analysing 1000 MG patients from Norway and the Netherlands (www.euromyasthenia.org). In search for new antigens for seronegative MG we have a longstanding collaboration with the University of Philadelphia, USA (prof. J. Dalmau), and of Barcelona, Spain (prof. F. Graus, and prof. I.Illa). Prof. Verschuuren is president of the Dutch Neuromuscular Research Center (www.isno.nl) and the Neuroimmunology panel of the European Federation of Neurological Societies (www.efns.nl).
The clinical team actively supports the basic science research activities on facioscapulo humeral muscle dystrophy (FSHD), oculopharyngeal muscular dystrophy (OPMD) and inclusion body myositis (IBM). Prof. Van der Maarel is leading the neuroscientist research group working on neuromuscular disorders (www.humgen.nl/lab-frants/FSHDresearch).
Our research on Complex Regional Pain Syndrome (CRPS) is embedded in the National consortium on CRPS: Trauma RElated Neuronal Dysfunction (TREND), which is chaired by Van Hilten (scientific director) (www.trendconsortium.nl). Firm collaborations have been established between TREND and international partners worldwide (Germany, UK, Switzerland, Denmark, USA, and Australia) to participate in joint research and grant applications. We were involved in the international revalidation study of new and improved diagnostic criteria, which have now been accepted by the International Association for the Study of Pain as the new global standard to diagnose the condition. Two of our researchers rank among the top 3 of authors who published most on CRPS in the past 5 years (positions 2, 3).
In Parkinson’s disease (PD) we have set-up one of the most extensively characterized cohorts of PD patients worldwide (the PROPARK-cohort), which is the reason why we participate in the International Parkinson Disease Genomics Consortium. The measurement instruments developed by our group to assess PD, are used globally in a range of different studies. Most instruments (SCOPA-rating scales) have been translated into multiple languages. We also collaborate in EUROPARK, a European consortium to investigate the non-motor symptoms of PD.
In Huntington’s disease we participate in two large international consortia (European Huntington’s Disease Network (EHDN) and the Track-HD study Collaboration London, Paris, and Vancouver). In Europe the LUMC is the biggest centre for HD. In the European network Roos is member of the executive committee of the EHDN as well as member of the steering committee of Registry, which is the largest study of the EHDN. He is also secretary general of the research committee of Huntington’s disease of the world federation of neurology.