Paroxysmal Cerebral Disorders (PaCD)
Aim and focus
The research programme is focused at the most relevant and prevalent paroxysmal cerebral disorders: migraine, cluster headache, narcolepsy, syncope and epilepsy to unravel the spectrum of neurobiological causes and consequences of these episodic brain disorders. The aim is to predict and prevent attacks, to unravel targets for drug treatment, to develop tailored (including sex-specific) treatments and to test novel treatment modalities.
Migraine and Cluster headache
The LUMC has the only academic headache research and referral centre in The Netherlands and is globally recognized as one of the premier headache centres for genetics, molecular neuroscience, neuroimaging, and clinical assessment of new treatments. Main assets are extensive local and (inter)national collaborations between clinical and fundamental research groups, with ample access to state-of-the-art technology platforms (genetics, transgenic animal models, stem cell generation & differentiation, neuroimaging, neurophysiology, bioinformatics) and some of the world largest and best pheno- and genotyped patient cohorts for migraine (> 8,000), monogenic migraine-subtype syndromes (> 600), and cluster headache (> 2,000). The Leiden Headache Centre is well embedded within international consortia. Our research is primarily aimed at unravelling the pathogenesis of migraine and cluster headache and to dissect molecular and neurobiological mechanisms for the triggering, initiation, recurrence and chronification of attacks. Furthermore, we focus on sex-specific features of headaches and aim to identify and validate treatment targets for the acute and prophylactic treatment of attacks and chronification and to decipher the underlying mechanisms for the bidirectional comorbidity of migraine, depression, and epilepsy. Last but not least, we focus on uncovering the mechanisms and to test novel treatment modalities for migraine-related cerebral ischemia, with a special focus on female-specific triggers for migraine and stroke.
Our research programme has been instrumental in developing the international classification of 'transient loss of consciousness'. There are strong links with the international cardiological and neurological communities.
Our programme aims to delineate the clinical spectrum and to unravel the role of the autonomic nervous system in reflex syncope, pure autonomic failure, psychogenic pseudo-syncope. We also aim to unravel the mechanisms for how orthostatic hypotension may lead to brain dysfunction and damage and to improve the diagnosis and clinical care of patients with “transient loss of consciousness” (TLOC).
It is our mission to bring research closer to our clinical services by fostering multidisciplinary approaches to react to our practice's pressing questions. To do so we have built a strong network with SEIN, the largest epilepsy center in the Netherlands and University College London (UCL) as key collaborators. A major theme in our epilepsy programme is the unravelling of Sudden Unexpected Death in Epilepsy (SUDEP) a tragic complication of epilepsy. It typically affects young adults thus explaining why epilepsy represents the second main neurologic cause of years of potential life lost. Evidence points strongly to seizure-induced autonomic shutdown as the key SUDEP mechanism. We build on our expertise in autonomic signals to conduct preclinical studies and translate these to in vivo biomarkers. While targeted interventions are still lacking, the best way to prevent SUDEP is to improve seizure control. Epilepsy management is however fraught by a trial-and-error approach. Our translational team therefore aims to develop novel biomarkers to predict treatment response, with parallel preclinical and clinical studies.
Our institute provides access to one of the largest and clinically best characterised narcolepsy patient cohorts in the world. We were instrumental in the seminal discoveries that narcolepsy is caused by loss of hypocretin/orexin cells in the hypothalamus and that this might be triggered by immunological processes.
Our research programme aims to unravel the etiology and pathophysiology of narcolepsy, with a focus on autoimmune aspects and to validate easy-to-perform objective measurements of vigilance as a marker for disease severity. Moreover, we assess the impact of sleep disturbance on metabolic and endocrine function, using narcolepsy as a model and study the borderland of narcolepsy, including behaviourally-induced sleep complaints.