A5078150048- Sleep and Wakefulness Research
- Sleep and related disorders
- Migraine and Headache Studies
- Circadian rhythm and melatonin
- Trigeminal Neuralgia and Treatments
- Regulation of Appetite and Obesity
- Sympathectomy and Hyperhidrosis Treatments
- Sleep and Work-Related Fatigue
- Systemic Lupus Erythematosus Research
- Restless Legs Syndrome Research
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Mind wandering and attention
- Obstructive Sleep Apnea Research
- Neuroscience of respiration and sleep
- Peripheral Neuropathies and Disorders
- EEG and Brain-Computer Interfaces
- Zebrafish Biomedical Research Applications
- Sphingolipid Metabolism and Signaling
- Neuroscience and Neuropharmacology Research
- Advanced Neuroimaging Techniques and Applications
- Epilepsy research and treatment
- Vascular Malformations Diagnosis and Treatment
- Intensive Care Unit Cognitive Disorders
- Hormonal and reproductive studies
- Atherosclerosis and Cardiovascular Diseases
Leiden University Medical Center
2016-2025
Stichting Epilepsie Instellingen Nederland
2017-2025
Leiden University
2006-2024
Western Digital (Netherlands)
2023
Klinik Barmelweid
2022
John Wiley & Sons (United States)
2021
Hudson Institute
2021
Loyola University Medical Center
2020
California Center for Sleep Disorders
2018
Netherlands Institute for Neuroscience
2005-2011
The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake and metabolism. There is growing interest function Parkinson's disease (PD), given high prevalence non-motor symptoms such as sleep disturbances this disorder. However, studies measuring CSF levels have yielded contradictory results. In PD patients matched controls, we (i) estimated number neurons post-mortem hypothalami using immunocytochemistry an image analysis...
The changes in brain function that perpetuate opiate addiction are unclear. In our studies of human narcolepsy, a disease caused by loss immunohistochemically detected hypocretin (orexin) neurons, we encountered control (from an apparently neurologically normal individual) with 50% more neurons than other brains had studied. We discovered this individual was heroin addict. Studying five postmortem from addicts, report the tissue had, on average, 54% producing did subjects. Similar increases...
The classification of the central disorders hypersomnolence has undergone multiple iterations in an attempt to capture biologically meaningful disease entities absence known pathophysiology. Accumulating data suggests that further refinements may be necessary. At 7th International Symposium on Narcolepsy, a group clinician-scientists evaluated support keeping or changing classifications, and as result suggest several changes. First, idiopathic hypersomnia with long sleep durations appears...
Purpose: Narcolepsy type-1 (NT1) is a rare chronic neurological sleep disorder with excessive daytime sleepiness (EDS) as usual first and cataplexy pathognomonic symptom. Shortening the NT1 diagnostic delay key to reduce disease burden related low quality of life. Here we investigated changes over years (1990– 2018) factors associated in Europe. Patients Methods: We analyzed 580 patients (male: 325, female: 255) from 12 European countries using Network database. combined machine learning...
Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT can also occur secondary forms narcolepsy and be only temporary, suggesting it without irreversible neuronal loss. The recent discovery that patients show loss (corticotropin-releasing hormone) CRH-producing neurons suggests other mechanisms than cell-specific attack, are...
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms interactions environmental triggers in multi-ethnic sample 6,073 cases 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 DPB1*04:02) discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant at TRA DQB1*06:02 loci...
To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin MCH neurons estimated their total numbers the lateral hypothalamus of both HD matched controls. In addition, levels were determined prefrontal cortical tissue post-mortem ventricular cerebrospinal fluid (CSF) using a radioimmunoassay. The number was significantly reduced by 30% brains (P =...
Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations have so far not been studied the human brain. We explored system changes hypothalamus cortex depression from male female subjects.We quantified differences between patients well-matched controls, terms of hypothalamic hypocretin-1 immunoreactivity (ir) receptors (Hcrtr-receptors)-mRNA anterior cingulate (ACC) dorsolateral prefrontal cortex. In addition, we...
Aim To determine whether our E-diary can be used to diagnose migraine and provide more reliable migraine-related frequency numbers compared patients’ self-reported estimates. Methods We introduced a self-developed including automated algorithms differentiating headache days, indicating patient has migraine. Reliability of the diagnosis in combination with two previously validated E-questionnaires was physician’s as gold standard patients referred Leiden Headache Clinic (n = 596). In subset...
Recent studies fueled doubts as to whether all currently defined central disorders of hypersomnolence are stable entities, especially narcolepsy type 2 and idiopathic hypersomnia. New reliable biomarkers needed, the question arises current diagnostic criteria should be reassessed. The main aim this data-driven observational study was see algorithms would segregate 1 identify more subgrouping individuals without cataplexy with new clinical biomarkers.We used agglomerative hierarchical...
Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration neurons. In addition excessive daytime sleepiness, Prader-Willi syndrome (PWS) may show narcolepsy-like symptoms, such as sleep-onset rapid eye movement sleep and cataplexy, independent obesity-related disturbances, which suggests disorder We hypothesized that symptoms PWS are caused by decline number estimated neurons postmortem...
In healthy subjects, sleep propensity increases when the distal skin temperature relative to proximal temperature. This increase results from increased blood flow in of extremities and is, among other factors, controlled by hypotha-lamic circadian clock, as is sleep. Because narcolepsy characterized hypothalamic alterations, we studied narcoleptic patients relation their characteristically during day. Distal gradient (DPG) were measured a Multiple Sleep Latency Test. allowed be wakefulness,...
The sustained attention to response task comprises withholding key presses one in nine of 225 target stimuli; it proved be a sensitive measure vigilance small group narcoleptics. We studied results 96 patients from tertiary narcolepsy referral centre. Diagnoses according ICSD-2 criteria were with (n=42) and without cataplexy (n=5), idiopathic hypersomnia long sleep time (n=37), obstructive apnoea syndrome (n=12). was administered prior each five multiple latency test sessions. Analysis...
The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy cataplexy have low levels, we hypothesized that they may be less prone to risk- reward-seeking behaviors, including substance abuse.Endpoints were performance on an array of psychometric tests (including Eysenck Impulsiveness Scale, Zuckerman Sensation Seeking Gormally Binge Eating Beck Depression Anxiety Inventory) Balloon Analogue Risk Task...
Objective Identifying common genetic variants that confer risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro‐Analysis program (LUCA) population (n = 840) and unselected controls from Netherlands Epidemiology of Obesity Study (NEO; n 1,457). Replication was performed Norwegian sample 144 cases Trondheim 1,800 Nord‐Trøndelag Health Survey (HUNT). Gene set tissue enrichment analyses, blood cell‐derived RNA‐sequencing genes...
Narcolepsy type 1 (NT1) is a chronic sleep disorder correlated with loss of hypocretin(orexin). In NT1 post‐mortem brains, we observed 88% reduction in corticotropin‐releasing hormone (CRH)‐positive neurons the paraventricular nucleus (PVN) and significantly less CRH‐positive fibers median eminence, whereas CRH‐neurons locus coeruleus thalamus, other PVN neuronal populations were spared: that is, vasopressin, oxytocin, tyrosine hydroxylase, thyrotropin releasing hormone‐expressing neurons....