Paroxysmal Cerebral Disorders (PaCD)

The LUMC Paroxysmal Cerebral Disorders research group is focused at important and prevalent paroxysmal cerebral disorders, foremost migraine, cluster headache, narcolepsy, syncope and epilepsy, to unravel the spectrum of neurobiological causes and consequences of these brain disorders. The aim is to understand disease mechanisms, to predict and prevent attacks, to identify targets for drug treatment, to develop tailored (including sex-specific) treatments, and to test novel treatment modalities.

Headache

The headache research group focuses on neurobiological and molecular triggering mechanisms that lead up to migraine and cluster headache attacks to identify treatment targets for prediction and prevention of attacks and disease progression. The Leiden Headache group is also studying pathogenesis of monogenic disorders such as Hemiplegic Migraine and Cerebral Hereditary Angiopathies, which serve as models for migraine pathogenesis and help improve insight into the pathophysiology of common neurovascular disorders, including stroke and vascular dementia. The group is also involved in exploring the migraine–stroke relationship, with a special focus on female-specific triggers for migraine and stroke.

Syncope

The research aims to delineate the clinical spectrum and to unravel the role of the autonomic nervous system in  various disorders that cause transient loss of consciousness (TLOC) such as reflexsyncope, psychogenic pseudosyncope and (pure) autonomic failure. Main focus of research is the coupling of clinical features to neurophysiological measurements, thereby increasing insight in underlying pathophysiological mechanisms of syncope and autonomic failure. In addition, we aim to improve treatment for subjects with autonomic failure and co-initiated the HEADS up trial, investigating the effect of sleeping in head-up tilt on symptoms of autonomic failure in subjects with Parkinson’s disease.   

Epilepsy

Epilepsy and migraine are common disabling brain conditions with abrupt changes in cortical excitability at the core of the problem. The unpredictable attacks have a major impact on the lives of patients and families. Clinical management is fraught by the lack of reliable biomarkers for attack occurrence and treatment efficacy. Evaluation of treatment still relies on inaccurate patient event diaries that are evaluated with hindsight (“trial and error” approach). Conventional short-term hospital observations fail to identify biomarkers, as they provide a snapshot in time of the patient’s brain state without capturing day-to-day fluctuations. As a consequence most detailed knowledge on disease mechanisms still comes from experimental animals even though translation to clinical biomarkers and patient care may be limited. Our translational team, therefore, aims to unravel disease mechanisms and to develop biomarkers to predict treatment response, with parallel preclinical and clinical studies. 

Sleep

Sleep plays a major role in many neurological disorders. There are also primary sleep disorders, in which disturbed sleep is the core feature of the disease. Sleep research in the LUMC traditionally has a focus on Central Nervous System (CNS) Hypersomnolence Disorders, such as narcolepsy. In collaboration with Sleep-Wake Centre SEIN we aim to unravel the auto-immune pathophysiology of CNS Hypersomnolence to develop new treatments.

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Sleep

Sleep plays a major role in many neurological disorders. There are also primary sleep disorders, in which disturbed sleep is the core feature of the disease. Sleep research in the LUMC traditionally has a focus on Central Nervous System (CNS) Hypersomnolence Disorders, such as narcolepsy. In collaboration with Sleep-Wake Centre SEIN we aim to unravel the auto-immune pathophysiology of CNS Hypersomnolence to develop new treatments.

Thanks to the PaCD research line and the collaboration between the LUMC and SEIN, there is a unique opportunity to study sleep in relation to paroxysmal disorders. For example, together with the headache group, research was started into the relationship between sleep and headache disorders. Especially in hypnic headache and cluster headache there is a clear and strong link between sleep and attacks. Also in migraine the relation with sleep is intriguing, yet still poorly understood. Another example is research into how sleep affects brain clearance in neurodegenerative disorders, a collaboration with the neuroradiology department of the LUMC and the LUMC amyloid research group.

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Themes for Innovation

Team

Clinical Principal Investigators

  • G.M. Terwindt, MD, PhD
    Professor of Neurology
    Consultant Neurologist
    Focus: Migraine, Cluster headache, Cerebral Hereditary Angiopathies
  • R. Fronczek, MD, PhD
    Consultant Neurologist
    Focus: Cluster headache, Sleep
  • R.D. Thijs, MD, PhD
    Consultant Neurologist
    Focus: Syncope and Autonomic failure, Epilepsy
  • I.A. van Rossum, MD, PhD
    Consultant Neurologist
    Focus: Syncope and Autonomic failure
  • G.J. Lammers, MD, PhD
    Professor of Neurology
    Consultant Neurologist
    Focus: Sleep
…

Clinical Principal Investigators

  • G.M. Terwindt, MD, PhD
    Professor of Neurology
    Consultant Neurologist
    Focus: Migraine, Cluster headache, Cerebral Hereditary Angiopathies
  • R. Fronczek, MD, PhD
    Consultant Neurologist
    Focus: Cluster headache, Sleep
  • R.D. Thijs, MD, PhD
    Consultant Neurologist
    Focus: Syncope and Autonomic failure, Epilepsy
  • I.A. van Rossum, MD, PhD
    Consultant Neurologist
    Focus: Syncope and Autonomic failure
  • G.J. Lammers, MD, PhD
    Professor of Neurology
    Consultant Neurologist
    Focus: Sleep

Non-clinical Principal Investigators

  • A. van den Maagdenberg, PhD
    Professor of Functional and Molecular Neurogenetics
    Focus: Migraine, Epilepsy
  • E.A. Tolner, PhD
    Focus: Migraine, Epilepsy

Key publication