95 results on '"ANS - Systems '
Search Results
2. ALL-tRNAseq enables robust tRNA profiling in tissue samples
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Chantal Scheepbouwer, Ernesto Aparicio-Puerta, Cristina Gomez-Martin, Heleen Verschueren, Monique van Eijndhoven, Laurine E. Wedekind, Stavros Giannoukakos, Nathalie Hijmering, Lisa Gasparotto, Hilde T. van der Galien, Roos S. van Rijn, Eleonora Aronica, Robby Kibbelaar, Vivi M. Heine, Pieter Wesseling, David P. Noske, W. Peter Vandertop, Daphne de Jong, D. Michiel Pegtel, Michael Hackenberg, Tom Wurdinger, Alan Gerber, Danijela Koppers-Lalic, Pathology, AII - Inflammatory diseases, ANS - Cellular & Molecular Mechanisms, Child and Adolescent Psychiatry & Psychosocial Care, Neurosurgery, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life, Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, AII - Cancer immunology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, and AII - Infectious diseases
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tissue samples ,Genetics ,cancer ,high-throughput sequencing ,transfer RNA ,Developmental Biology - Abstract
Transfer RNAs (tRNAs) are small adaptor RNAs essential for mRNA translation. Alterations in the cellular tRNA population can directly affect mRNA decoding rates and translational efficiency during cancer development and progression. To evaluate changes in the composition of the tRNA pool, multiple sequencing approaches have been developed to overcome reverse transcription blocks caused by the stable structures of these molecules and their numerous base modifications. However, it remains unclear whether current sequencing protocols faithfully capture tRNAs existing in cells or tissues. This is specifically challenging for clinical tissue samples that often present variable RNA qualities. For this reason, we developed ALL-tRNAseq, which combines the highly processive MarathonRT and RNA demethylation for the robust assessment of tRNA expression, together with a randomized adapter ligation strategy prior to reverse transcription to assess tRNA fragmentation levels in both cell lines and tissues. Incorporation of tRNA fragments not only informed on sample integrity but also significantly improved tRNA profiling of tissue samples. Our data showed that our profiling strategy effectively improves classification of oncogenic signatures in glioblastoma and diffuse large B-cell lymphoma tissues, particularly for samples presenting higher levels of RNA fragmentation, further highlighting the utility of ALL-tRNAseq for translational research.
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- 2023
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3. Quantitative Assessment of the Apical and Basolateral Membrane Expression of VEGFR2 and NRP2 in VEGF-A-stimulated Cultured Human Umbilical Vein Endothelial Cells
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Esmeralda K. Bosma, Shahan Darwesh, Jia Y. Zheng, Cornelis J.F. van Noorden, Reinier O. Schlingemann, Ingeborg Klaassen, Ophthalmology, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ANS - Cellular & Molecular Mechanisms, ANS - Systems & Network Neuroscience, Medical Biology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and ACS - Microcirculation
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Vascular Endothelial Growth Factor A ,Histology ,apicobasal ,endothelial barrier ,Cell Membrane ,receptors ,Vascular Endothelial Growth Factor Receptor-2 ,Retina ,Neuropilin-2 ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,Cattle ,Anatomy ,membrane microdomains ,Cells, Cultured ,vascular endothelial growth factor receptor - Abstract
Endothelial cells (ECs) form a precisely regulated polarized monolayer in capillary walls. Vascular endothelial growth factor-A (VEGF-A) induces endothelial hyperpermeability, and VEGF-A applied to the basolateral side, but not the apical side, has been shown to be a strong barrier disruptor in blood–retinal barrier ECs. We show here that VEGF-A presented to the basolateral side of human umbilical vein ECs (HUVECs) induces higher permeability than apical stimulation, which is similar to results obtained with bovine retinal ECs. We investigated with immunocytochemistry and confocal imaging the distribution of VEGF receptor-2 (VEGFR2) and neuropilin-2 (NRP2) in perinuclear apical and basolateral membrane domains. Orthogonal z-sections of cultured HUVECs were obtained, and the fluorescence intensity at the apical and basolateral membrane compartments was measured. We found that VEGFR2 and NRP2 are evenly distributed throughout perinuclear apical and basolateral membrane compartments in unstimulated HUVECs grown on Transwell inserts, whereas basolateral VEGF-A stimulation induces a shift toward basolateral VEGFR2 and NRP2 localization. When HUVECs were grown on coverslips, the distribution of VEGFR2 and NRP2 across the perinuclear apical and basolateral membrane domains was different. Our findings demonstrate that HUVECs dynamically regulate VEGFR2 and NRP2 localization on membrane microdomains, depending on growth conditions and the polarity of VEGF-A stimulation.
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- 2023
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4. Protocol of a randomized controlled trial investigating Deep Brain Stimulation for MOtor symptoms in patients with Parkinson's disease DEmentia (DBS-MODE)
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V. Sisodia, B. E. K. S. Swinnen, J. M. Dijk, E. Verwijk, G. van Rooijen, A. W. Lemstra, P. R. Schuurman, R. M. A. de Bie, Graduate School, Neurology, ANS - Neurodegeneration, Medical Psychology, APH - Mental Health, Neurosurgery, ANS - Systems & Network Neuroscience, APH - Aging & Later Life, Brein en Cognitie (Psychologie, FMG), and Amsterdam Neuroscience - Neurodegeneration
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Randomized controlled trial ,Deep brain stimulation ,Parkinson’s disease ,Dementia ,Neurology (clinical) ,General Medicine - Abstract
Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for disabling motor symptoms of Parkinson’s disease (PD) that persist despite optimal pharmacological treatment. Currently, DBS is not performed if there is concomitant significant cognitive impairment based on concerns of cognitive deterioration, higher complication rate and less functional improvement. However, this has not been investigated so far. Methods A single center, prospective, randomized, open-label, blinded end-point (PROBE design) pilot clinical trial is being performed. Patients are eligible for the trial if they have PD dementia (PDD), are able to provide informed consent, and experience disabling motor response fluctuations, bradykinesia, dyskinesia, or painful dystonia, despite optimal pharmacological treatment. In total 44 patients will be randomized to either STN-DBS accompanied by best medical treatment (DBS group) or to best medical treatment alone (BMT group). The primary outcome measure is the change from baseline to 30 weeks on the Movement Disorder Society—Unified Parkinson’s Disease Rating Scale part III score in a standardized off-drug phase. The main secondary outcome measures consist of scales assessing cognitive aspects of daily living, neuropsychiatric symptoms and impulsive compulsive disorders. Additional secondary outcome measures include motor signs during on-drug phase, dyskinesia, motor fluctuations, cognitive performance, (severe) adverse events, treatment satisfaction, and caregiver burden. Patients will be followed during 52 weeks after randomization. Discussion The Deep Brain Stimulation for MOtor symptoms in patients with Parkinson’s disease DEmentia (DBS-MODE) trial directly compares the effectiveness and safety of DBS with BMT in patients with PDD. Trial registration The DBS-MODE trial has been registered in the International Clinical Trial Registry Platform (NL9361) on the 24th of March 2021 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL9361).
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- 2023
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5. Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor
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Andreas Nowacki, Sabry Barlatey, Bassam Al‐Fatly, Till Dembek, Maarten Bot, Alexander L. Green, Dorothee Kübler, M. Lenard Lachenmayer, Ines Debove, Alba Segura‐Amil, Andreas Horn, Veerle Visser‐Vandewalle, Rick Schuurman, Michael Barbe, Tipu Z. Aziz, Andrea A. Kühn, T. A. Khoa Nguyen, Claudio Pollo, Neurosurgery, ANS - Neurodegeneration, and ANS - Systems & Network Neuroscience
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Treatment Outcome ,Neurology ,Deep Brain Stimulation ,Essential Tremor ,Tremor ,Humans ,570 Life sciences ,biology ,610 Medicine & health ,Prospective Studies ,Neurology (clinical) ,Retrospective Studies - Abstract
OBJECTIVE To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data was used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement greater than 50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural-connectivity-based cerebello-thalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a greater than 50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION Our multicentre ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of deep brain stimulation in the future. This article is protected by copyright. All rights reserved.
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- 2022
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6. Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study
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Maud A. Tjerkstra, Marcella C. A. Müller, Bert A. Coert, Friso W. A. Hoefnagels, Mervyn D. I. Vergouwen, Peter van Vliet, Lizzy Ooms, Gabriël J. E. Rinkel, Arjen J. C. Slooter, Wouter A. Moojen, Korné Jellema, W. Peter Vandertop, Dagmar Verbaan, Graduate School, ANS - Neurovascular Disorders, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, Neurosurgery, CCA - Cancer Treatment and Quality of Life, ANS - Systems & Network Neuroscience, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, and CCA - Imaging and biomarkers
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Neurology ,delayed cerebral ischemia ,intracranial vasospasm ,Neurology (clinical) ,aneurysmal subarachnoid hemorrhage ,hypertension induction - Abstract
Background: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3−/6-month clinical efficacy of HTI in aSAH patients with clinical DCI. Methods: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4–6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses. Results: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17–2.27) and at day 5 after DCI 1.04 (95% CI 0.84–1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results. Conclusions: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3−/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.
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- 2023
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7. Long-term Outcome of Deep Brain Stimulation of the Ventral Part of the Anterior Limb of the Internal Capsule in a Cohort of 50 Patients With Treatment-Refractory Obsessive-Compulsive Disorder
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Pelle de Koning, Roel J. T. Mocking, Damiaan Denys, Pepijn van den Munckhof, Ilse Graat, Pieter Ooms, Martijn Figee, Rick Schuurman, Mariska Mantione, Nienke Vulink, Graduate School, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ANS - Amsterdam Neuroscience, Neurosurgery, ANS - Neurodegeneration, and ANS - Systems & Network Neuroscience
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0301 basic medicine ,medicine.medical_specialty ,Deep brain stimulation ,Internal capsule ,Hamilton Anxiety Rating Scale ,medicine.medical_treatment ,Global Assessment of Functioning ,Anxiety ,behavioral disciplines and activities ,Long-term effectiveness ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Rating scale ,Internal Capsule ,Obsessive-compulsive disorder ,Medicine ,Humans ,Side effects ,Biological Psychiatry ,Depression (differential diagnoses) ,business.industry ,030104 developmental biology ,Treatment Outcome ,Tolerability ,Physical therapy ,Quality of Life ,business ,030217 neurology & neurosurgery - Abstract
Background: Deep brain stimulation (DBS) is an effective intervention for patients with severe treatment-refractory obsessive-compulsive disorder (OCD). Our aim was to examine long-term effectiveness and tolerability of DBS and its impact on functioning and well-being. Methods: Fifty patients with severe treatment-refractory OCD received DBS of the ventral part of the anterior limb of the internal capsule and were followed for at least 3 years following implantation (mean 6.8 ± 3 years). Primary effectiveness was assessed by change in Yale-Brown Obsessive Compulsive Scale scores. Secondary effectiveness measures included Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, World Health Organization Quality of Life Scale–Brief Version, Global Assessment of Functioning, and a scale assessing functioning in work, family, and social life. Adverse effects of DBS were examined with a structured interview (n = 38). Results: At long-term follow-up, OCD symptoms decreased by 39% (p < .001), and half of the patients were responders (≥35% decrease of Yale-Brown Obsessive Compulsive Scale score). Anxiety and depressive symptoms decreased significantly, with reductions of 48% and 50%, respectively. The World Health Organization Quality of Life Scale–Brief Version general score improved significantly, as did 3 of 4 subdomains. Both clinician- and patient-rated functioning improved substantially (p < .001). The unemployment rate decreased from 78% at baseline to 58% at last follow-up (z = −1.90, p = .058), and 21 patients stopped or decreased psychotropic medication (z = −2.887, p = .004). Long-term adverse effects included cognitive complaints and fatigue. Serious adverse events included 1 suicide attempt, related to comorbid depression. Conclusions: Our results provide evidence that DBS of the ventral part of the anterior limb of the internal capsule is effective and tolerable for treatment-refractory OCD in the long term and improves functioning and overall well-being.
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- 2021
8. Tractography-based versus anatomical landmark-based targeting in vALIC deep brain stimulation for refractory obsessive-compulsive disorder
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Ilse Graat, Roel J. T. Mocking, Luka C. Liebrand, Pepijn van den Munckhof, Maarten Bot, P. Rick Schuurman, Isidoor O. Bergfeld, Guido van Wingen, Damiaan Denys, Graduate School, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, ANS - Cellular & Molecular Mechanisms, Biomedical Engineering and Physics, ANS - Brain Imaging, ANS - Neurovascular Disorders, AMS - Amsterdam Movement Sciences, Neurosurgery, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, ACS - Diabetes & metabolism, and ACS - Microcirculation
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Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,Molecular Biology - Abstract
Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is effective for refractory obsessive-compulsive disorder (OCD). Retrospective evaluation showed that stimulation closer to the supero-lateral branch of the medial forebrain bundle (slMFB), within the vALIC, was associated with better response to DBS. The present study is the first to compare outcomes of DBS targeted at the vALIC using anatomical landmarks and DBS with connectomic tractography-based targeting of the slMFB. We included 20 OCD-patients with anatomical landmark-based DBS of the vALIC that were propensity score matched to 20 patients with tractography-based targeting of electrodes in the slMFB. After one year, we compared severity of OCD, anxiety and depression symptoms, response rates, time to response, number of parameter adjustments, average current, medication usage and stimulation-related adverse effects. There was no difference in Y-BOCS decrease between patients with anatomical landmark-based and tractography-based DBS. Nine (45%) patients with anatomical landmark-based DBS and 13 (65%) patients with tractography-based DBS were responders (BF10 = 1.24). The course of depression and anxiety symptoms, time to response, number of stimulation adjustments or medication usage did not differ between groups. Patients with tractography-based DBS experienced fewer stimulation-related adverse effects than patients with anatomical landmark-based DBS (38 vs 58 transient and 1 vs. 17 lasting adverse effects; BF10 = 14.968). OCD symptoms in patients with anatomical landmark-based DBS of the vALIC and tractography-based DBS of the slMFB decrease equally, but patients with tractography-based DBS experience less adverse effects.
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- 2022
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9. The continued need for animals to advance brain research
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Paul J. Lucassen, Kate Jeffrey, Antonis Asiminas, Heidi M. B. Lesscher, Jos Prickaerts, Gertjan van Dijk, Amanda J. Kiliaan, Daniela Jezova, Carlos P. Fitzsimons, Klaus-Peter Lesch, S. Mechiel Korte, Ulrich L. M. Eisel, Roger A.H. Adan, Tamas Kozicz, Liset Menendez de la Prida, Joanes Grandjean, Marloes J. A. G. Henckens, Corette J. Wierenga, Vladyslav V. Vyazovskiy, Cyriel M. A. Pennartz, Marten P. Smidt, Ype Elgersma, Anne S. Mallien, Sharon M. Kolk, Liya Ma, Kirk Leech, Ingo Willuhn, Jorge F. Mejias, Maximilian Wiesmann, Frank J. Meye, Louk J. M. J. Vanderschuren, Marilise Escobar Burger, Sidarta Ribeiro, August B. Smit, Peter Meerlo, Robbert Havekes, Eddy A. van der Zee, Rixt van der Veen, Regien G. Schoemaker, Massimo Pasqualetti, Andries Kalsbeek, Martien J H Kas, Michael Bader, Joram D. Mul, Bernhard Englitz, Janine I. Rossato, Denovan P. Begg, Tomonori Takeuchi, Markus Wöhr, Antonio Fernández-Ruiz, Bella Williams, Nael Nadif Kasri, Aniko Korosi, Judith R. Homberg, Tom Beckers, Maarten Kamermans, Piotr Popik, Peter Gass, Umberto Olcese, Anna S. Mitchell, Christiane Herden, Jocelien D A Olivier, Monique Wolvekamp, Arjan Blokland, Azahara Oliva González, Natalia Alenina, Lisa Genzel, Wendy Jarrett, Ali-Akbar Salari, Roelof A. Hut, Anne-Marie van Dam, Anita Lüthi, Benno Roozendaal, Steven A. Kushner, Medicinal chemistry, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Neurodegeneration, Netherlands Institute for Neuroscience (NIN), Clinical Genetics, Psychiatry, Afd Pharmacology, AISS Behaviour Neuroscience, dASS BW-1, Sub Cell Biology, Pharmacology, Celbiologie, Structural and Functional Plasticity of the nervous system (SILS, FNWI), Cognitive and Systems Neuroscience (SILS, FNWI), Molecular Neuroscience (SILS, FNWI), Section Psychopharmacology, RS: FPN NPPP II, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, University of Toronto, Endocrinology, Endocrinology Laboratory, ANS - Cellular & Molecular Mechanisms, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Biomedical Engineering and Physics, Paediatrics, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, ANS - Systems & Network Neuroscience, Van Dijk lab, Eisel lab, Havekes lab, Hut lab, Kas lab, Meerlo lab, Olivier lab, Schoemaker lab, and Van der Zee lab
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Animal Experimentation ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Science & Technology ,Animals ,Brain ,Neurosciences ,General Neuroscience ,Neuroscience(all) ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,MEDLINE ,Neurophysiology ,Brain research ,Taverne ,Engineering ethics ,Neurosciences & Neurology ,Neuroscience research ,Animal testing ,Psychology ,Life Sciences & Biomedicine ,Value (mathematics) ,Molecular Neurobiology - Abstract
Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised., We would like to thank Loren Frank, UCSF, USA; Sheena Josselyn, Hospital for Sick Children, University of Toronto, Canada; Shantanu Jadhav, Brandeis University, USA; the European Animal Research Association (EARA); the Federation of European Neuroscience Societies Committee on Animals in Research (CARE); the Swiss Society for Neuroscience; the Society for Neuroscience Committee on Animals in Research (CAR); and Stichting Informatie Dierproeven (the Dutch foundation for public information on animal testing: SID) for input on and support for this article.
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- 2021
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10. Nucleus accumbens dopamine tracks aversive stimulus duration and prediction but not value or prediction error
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Jessica N Goedhoop, Bastijn JG van den Boom, Rhiannon Robke, Felice Veen, Lizz Fellinger, Wouter van Elzelingen, Tara Arbab, Ingo Willuhn, Netherlands Institute for Neuroscience (NIN), Graduate School, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, and ANS - Systems & Network Neuroscience
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Nucleus Accumbens/physiology ,prediction error ,General Immunology and Microbiology ,behavior ,General Neuroscience ,Dopamine ,Hominidae ,General Medicine ,General Biochemistry, Genetics and Molecular Biology ,Nucleus Accumbens ,Rats ,neuroscience ,Rats, Sprague-Dawley ,motivation ,Reward ,aversive stimuli ,Animals ,rat ,Sprague-Dawley ,Cues - Abstract
There is active debate on the role of dopamine in processing aversive stimuli, where inferred roles range from no involvement at all, to signaling an aversive prediction error (APE). Here, we systematically investigate dopamine release in the nucleus accumbens core (NAC), which is closely linked to reward prediction errors, in rats exposed to white noise (WN, a versatile, underutilized, aversive stimulus) and its predictive cues. Both induced a negative dopamine ramp, followed by slow signal recovery upon stimulus cessation. In contrast to reward conditioning, this dopamine signal was unaffected by WN value, context valence, or probabilistic contingencies, and the WN dopamine response shifted only partially toward its predictive cue. However, unpredicted WN provoked slower post-stimulus signal recovery than predicted WN. Despite differing signal qualities, dopamine responses to simultaneous presentation of rewarding and aversive stimuli were additive. Together, our findings demonstrate that instead of an APE, NAC dopamine primarily tracks prediction and duration of aversive events.
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- 2022
11. Deep brain stimulation for obsessive–compulsive disorder: a crisis of access
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Veerle Visser-Vandewalle, Pablo Andrade, Philip E. Mosley, Benjamin D. Greenberg, Rick Schuurman, Nicole C. McLaughlin, Valerie Voon, Paul Krack, Kelly D. Foote, Helen S. Mayberg, Martijn Figee, Brian H. Kopell, Mircea Polosan, Eileen M. Joyce, Stephan Chabardes, Keith Matthews, Juan C. Baldermann, Himanshu Tyagi, Paul E. Holtzheimer, Chris Bervoets, Clement Hamani, Carine Karachi, Damiaan Denys, Ludvic Zrinzo, Patric Blomstedt, Matilda Naesström, Aviva Abosch, Steven Rasmussen, Volker A. Coenen, Thomas E. Schlaepfer, Darin D. Dougherty, Philippe Domenech, Peter Silburn, James Giordano, Andres M. Lozano, Sameer A. Sheth, Terry Coyne, Jens Kuhn, Luc Mallet, Bart Nuttin, Marwan Hariz, Michael S. Okun, Neurosurgery, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, Adult Psychiatry, and ANS - Compulsivity, Impulsivity & Attention
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General Medicine ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
12. A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings
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M.J. Stam, B.C.M. van Wijk, P. Sharma, M. Beudel, D.A. Piña-Fuentes, R.M.A. de Bie, P.R. Schuurman, W.-J. Neumann, A.W.G. Buijink, Coordination Dynamics, IBBA, AMS - Rehabilitation & Development, Graduate School, Neurology, ANS - Neurodegeneration, Neurosurgery, and ANS - Systems & Network Neuroscience
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Local field potentials ,Neurology ,ECG ,Physiology (medical) ,Parkinson's disease ,Beta ,Neurology (clinical) ,Artifacts ,Sensory Systems - Abstract
ObjectiveSensing-enabled neurostimulators for deep brain stimulation (DBS) therapy record neural activity directly from the stimulating electrodes in the form of local field potentials (LFPs). However, these LFPs are often contaminated with electrocardiographic (ECG) artifacts that impede the detection of physiomarkers for adaptive DBS research. This study systematically compared the ability of different ECG suppression methods to recover disease-specific electrical brain activity from ECG-contaminated LFPs.ApproachThree ECG suppression methods were evaluated: (1) QRS interpolation of the Perceive toolbox, (2) four variants of a template subtraction method, and (3) sixteen variants of a singular value decomposition (SVD) method. The performance of these methods was examined using LFPs recorded with the Medtronic PerceptTM PC system from the subthalamic nucleus in nine patients with Parkinson’s disease while stimulation was turned off (“OFF-DBS”; anode disconnected) and while stimulation was turned on at 0 mA (“ON-DBS 0 mA”; anode connected). In addition, ECG-contaminated LFPs were simulated by scaling a co-recorded external ECG signal and adding it to the OFF-DBS LFPs.Main ResultsECG artifacts were present in 10 out of 18 ON-DBS 0 mA recordings. All ECG suppression methods were able to drastically reduce the percent difference of beta band (13 – 35 Hz) spectral power and at least partly recover the beta peak and beta burst dynamics. Using predetermined R-peaks improved the performance of the ECG suppression methods. Lengthening the time window around the R-peaks resulted in stronger reduction in artifact-induced beta band power but at an increased risk of flattening the beta peak and loss of beta burst dynamics.SignificanceThe SVD method formed the preferred trade-off between artifact cleaning and signal loss, as long as its parameter settings (time window around the R-peaks; number of components) are adequately chosen.
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- 2022
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13. Body mass index at diagnosis of a childhood brain tumor; a reflection of hypothalamic-pituitary dysfunction or lifestyle?
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I. M. A. A. van Roessel, J. van Schaik, A. Y. N. Schouten-van Meeteren, A. M. Boot, H. L. Claahsen-van der Grinten, S. C. Clement, L. van Iersel, K. S. Han, A. S. P. van Trotsenburg, W. P. Vandertop, L. C. M. Kremer, H. M. van Santen, Faculteit Medische Wetenschappen/UMCG, Paediatric Oncology, General Paediatrics, Paediatric Endocrinology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Neurosurgery, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life, ARD - Amsterdam Reproduction and Development, Paediatrics, and Amsterdam Neuroscience - Neurovascular Disorders
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Childhood brain tumor ,BMI ,Oncology ,nutritional and metabolic diseases ,Obesity ,Hypothalamic-pituitary dysfunction ,Lifestyle ,Hypopituitarism - Abstract
Purpose Childhood brain tumor survivors (CBTS) are at risk of becoming overweight, which has been shown to be associated with hypothalamic-pituitary (HP) dysfunction during follow-up. Body mass index (BMI) at diagnosis is related to BMI at follow-up. It is uncertain, however, whether aberrant BMI at brain tumor diagnosis reflects early hypothalamic dysfunction or rather reflects genetic and sociodemographic characteristics. We aimed to examine whether BMI at childhood brain tumor diagnosis is associated with HP dysfunction at diagnosis or its development during follow-up. Methods The association of BMI at diagnosis of a childhood brain tumor to HP dysfunction at diagnosis or during follow-up was examined in a Dutch cohort of 685 CBTS, excluding children with craniopharyngioma or a pituitary tumor. Individual patient data were retrospectively extracted from patient charts. Results Of 685 CTBS, 4.7% were underweight, 14.2% were overweight, and 3.8% were obese at diagnosis. Being overweight or obese at diagnosis was not associated with anterior pituitary deficiency or diabetes insipidus at diagnosis or during follow-up. In children with suprasellar tumors, being obese at diagnosis was associated with central precocious puberty. Conclusion Overweight or obesity at diagnosis of a childhood brain tumor seems not to be associated with pituitary deficiencies. These results suggest that genetics and lifestyle may be more important etiologic factors for higher BMI at diagnosis in these children than hypothalamic dysfunction. To improve the long-term outcome of CBTS with regards to overweight and obesity, more attention should be given to lifestyle already at the time of brain tumor treatment.
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- 2022
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14. Quantifying eloquent locations for glioblastoma surgery using resection probability maps
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Wim Bouwknegt, Georg Widhalm, Frederik Barkhof, Lorenzo Bello, Domenique M J Müller, Michiel Wagemakers, Shawn L. Hervey-Jumper, W. Peter Vandertop, Wimar A. van den Brink, Marnix G. Witte, Pierre A. Robe, Tommaso Sciortino, Seunggu J. Han, Barbara Kiesel, Marco Conti Nibali, Julia Furtner, Philip C. De Witt Hamer, Marco Rossi, Roelant S Eijgelaar, Hilko Ardon, Martin Visser, Jan C. de Munck, Alfred Kloet, Albert J S Idema, Mitchel S. Berger, Aeilko H. Zwinderman, Neurosurgery, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life, Epidemiology and Data Science, APH - Methodology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, Amsterdam Neuroscience - Neurovascular Disorders, and Amsterdam Neuroscience - Systems & Network Neuroscience
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Male ,Neoplasm, Residual ,Biopsy ,Kaplan-Meier Estimate ,Logistic regression ,Neurosurgical Procedures ,0302 clinical medicine ,glioma ,Medicine ,neurosurgery ,BRAIN ,Brain Mapping ,medicine.diagnostic_test ,Brain Neoplasms ,General Medicine ,Middle Aged ,extent of resection ,GLIOMAS ,Treatment Outcome ,030220 oncology & carcinogenesis ,oncology ,Female ,NEWLY-DIAGNOSED GLIOBLASTOMA ,Adult ,medicine.medical_specialty ,WHITE-MATTER TRACTS ,residual volume ,Extent of resection ,Resection ,MULTIFORME ,03 medical and health sciences ,Glioma ,Humans ,Karnofsky Performance Status ,Grading (tumors) ,Aged ,Probability ,Receiver operating characteristic ,business.industry ,EXTENT ,medicine.disease ,Survival Analysis ,Surgery ,ROC Curve ,PREDICTS SURVIVAL ,PATTERNS ,reproducibility of results ,Glioblastoma ,business ,030217 neurology & neurosurgery ,RESPONSE ASSESSMENT - Abstract
OBJECTIVE Decisions in glioblastoma surgery are often guided by presumed eloquence of the tumor location. The authors introduce the “expected residual tumor volume” (eRV) and the “expected resectability index” (eRI) based on previous decisions aggregated in resection probability maps. The diagnostic accuracy of eRV and eRI to predict biopsy decisions, resectability, functional outcome, and survival was determined. METHODS Consecutive patients with first-time glioblastoma surgery in 2012–2013 were included from 12 hospitals. The eRV was calculated from the preoperative MR images of each patient using a resection probability map, and the eRI was derived from the tumor volume. As reference, Sawaya’s tumor location eloquence grades (EGs) were classified. Resectability was measured as observed extent of resection (EOR) and residual volume, and functional outcome as change in Karnofsky Performance Scale score. Receiver operating characteristic curves and multivariable logistic regression were applied. RESULTS Of 915 patients, 674 (74%) underwent a resection with a median EOR of 97%, functional improvement in 71 (8%), functional decline in 78 (9%), and median survival of 12.8 months. The eRI and eRV identified biopsies and EORs of at least 80%, 90%, or 98% better than EG. The eRV and eRI predicted observed residual volumes under 10, 5, and 1 ml better than EG. The eRV, eRI, and EG had low diagnostic accuracy for functional outcome changes. Higher eRV and lower eRI were strongly associated with shorter survival, independent of known prognostic factors. CONCLUSIONS The eRV and eRI predict biopsy decisions, resectability, and survival better than eloquence grading and may be useful preoperative indices to support surgical decisions.
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- 2021
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15. Optimizing Deep Brain Stimulation Parameters in Obsessive–Compulsive Disorder
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Nienke Vullink, Pepijn van den Munckhof, Rick Schuurman, Isidoor O. Bergfeld, Damiaan Denys, Erik Rietveld, Pieter Ooms, Ilse Graat, Maarten van Westen, Pelle de Koning, Luka C. Liebrand, Graduate School, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, ANS - Amsterdam Neuroscience, Biomedical Engineering and Physics, ACS - Diabetes & metabolism, ACS - Microcirculation, ANS - Brain Imaging, ANS - Neurovascular Disorders, AMS - Amsterdam Movement Sciences, and Neurosurgery
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Obsessive-Compulsive Disorder ,medicine.medical_specialty ,Deep brain stimulation ,medicine.medical_treatment ,Stimulation Parameter ,Stimulation ,Electrode Contact ,behavioral disciplines and activities ,03 medical and health sciences ,0302 clinical medicine ,Physical medicine and rehabilitation ,obsessive–compulsive disorder ,Clinical Research ,Obsessive compulsive ,mental disorders ,Humans ,Medicine ,Effective treatment ,In patient ,Cognitive Behavioral Therapy ,business.industry ,General Medicine ,Symptom reduction ,stimulation parameters ,3. Good health ,Editor's Choice ,Treatment Outcome ,Anesthesiology and Pain Medicine ,Neurology ,neuromodulation ,Neurology (clinical) ,business ,optimization ,030217 neurology & neurosurgery - Abstract
Objectives Deep brain stimulation (DBS) is an innovative and effective treatment for patients with therapy‐refractory obsessive–compulsive disorder (OCD). DBS offers unique opportunities for personalized care, but no guidelines on how to choose effective and safe stimulation parameters in patients with OCD are available. Our group gained relevant practical knowledge on DBS optimization by treating more than 80 OCD patients since 2005, the world's largest cohort. The article's objective is to share this experience. Materials and Methods We provide guiding principles for optimizing DBS stimulation parameters in OCD and discuss the neurobiological and clinical basis. Results Adjustments in stimulation parameters are performed in a fixed order. First, electrode contact activation is determined by the position of the electrodes on postoperative imaging. Second, voltage and pulse width are increased stepwise, enlarging both the chance of symptom reduction and of inducing side effects. Clinical evaluation of adjustments in stimulation parameters needs to take into account: 1) the particular temporal sequence in which the various OCD symptoms and DBS side‐effects change; 2) the lack of robust response predictors; 3) the limited sensitivity of the Yale‐Brown Obsessive–Compulsive Scale to assess DBS‐induced changes in OCD symptoms; and 4) a patient's fitness for additional cognitive‐behavioral therapy (CBT). Conclusions Decision‐making in stimulation parameter optimization needs to be sensitive to the particular time‐courses on which various symptoms and side effects change.
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- 2021
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16. Flexible Working Memory Through Selective Gating and Attentional Tagging
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Sander M. Bohte, Wouter Kruijne, Christian N. L. Olivers, Pieter R. Roelfsema, Artificial Intelligence, Astronomy, Adult Psychiatry, ANS - Systems & Network Neuroscience, Netherlands Institute for Neuroscience (NIN), Cognitive Psychology, Integrative Neurophysiology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and IBBA
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NEURAL BASIS ,Computer science ,Cognitive Neuroscience ,Models, Neurological ,Control (management) ,Sensory system ,PREFRONTAL CORTEX ,050105 experimental psychology ,Task (project management) ,03 medical and health sciences ,0302 clinical medicine ,Arts and Humanities (miscellaneous) ,Human–computer interaction ,Encoding (memory) ,Animals ,Humans ,Learning ,Reinforcement learning ,Attention ,0501 psychology and cognitive sciences ,NETWORK ,Focus (computing) ,Artificial neural network ,Working memory ,business.industry ,05 social sciences ,MONKEY ,Cognition ,DECISION ,Sensory Gating ,REPRESENTATIONS ,MODEL ,Task (computing) ,Memory, Short-Term ,Key (cryptography) ,TASK ,Neural Networks, Computer ,Artificial intelligence ,EYE-MOVEMENTS ,business ,LSTM ,Reinforcement, Psychology ,030217 neurology & neurosurgery - Abstract
Working memory is essential for intelligent behavior as it serves to guide behavior of humans and nonhuman primates when task-relevant stimuli are no longer present to the senses. Moreover, complex tasks often require that multiple working memory representations can be flexibly and independently maintained, prioritized, and updated according to changing task demands. Thus far, neural network models of working memory have been unable to offer an integrative account of how such control mechanisms are implemented in the brain and how they can be acquired in a biologically plausible manner. Here, we present WorkMATe, a neural network architecture that models cognitive control over working memory content and learns the appropriate control operations needed to solve complex working memory tasks. Key components of the model include a gated memory circuit that is controlled by internal actions, encoding sensory information through untrained connections, and a neural circuit that matches sensory inputs to memory content. The network is trained by means of a biologically plausible reinforcement learning rule that relies on attentional feedback and reward prediction errors to guide synaptic updates. We demonstrate that the model successfully acquires policies to solve classical working memory tasks, such as delayed match-to-sample and delayed pro-saccade/antisaccade tasks. In addition, the model solves much more complex tasks including the hierarchical 12-AX task or the ABAB ordered recognition task, which both demand an agent to independently store and updated multiple items separately in memory. Furthermore, the control strategies that the model acquires for these tasks subsequently generalize to new task contexts with novel stimuli. As such, WorkMATe provides a new solution for the neural implementation of flexible memory control.Author SummaryWorking Memory, the ability to briefly store sensory information and use it to guide behavior, is a cornerstone of intelligent behavior. Existing neural network models of Working Memory typically focus on how information is stored and maintained in the brain, but do not address how memory content is controlled: how the brain can selectively store only stimuli that are relevant for a task, or how different stimuli can be maintained in parallel, and subsequently replaced or updated independently according to task demands. The models that do implement control mechanisms are typically not trained in a biologically plausible manner, and do not explain how the brain learns such control. Here, we present WorkMATe, a neural network architecture that implements flexible cognitive control and learns to apply these control mechanisms using a biologically plausible reinforcement learning method. We demonstrate that the model acquires control policies to solve a range of both simple and more complex tasks. Moreover, the acquired control policies generalize to new situations, as with human cognition. This way, WorkMATe provides new insights into the neural organization of Working Memory beyond mere storage and retrieval.
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- 2021
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17. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial
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René Post, Menno R Germans, Maud A Tjerkstra, Mervyn D I Vergouwen, Korné Jellema, Radboud W Koot, Nyika D Kruyt, Peter W A Willems, Jasper F C Wolfs, Frits C de Beer, Hans Kieft, Dharmin Nanda, Bram van der Pol, Gerwin Roks, Frank de Beer, Patricia H A Halkes, Loes J A Reichman, Paul J A M Brouwers, Renske M van den Berg-Vos, Vincent I H Kwa, Taco C van der Ree, Irene Bronner, Janneke van de Vlekkert, Henri P Bienfait, Hieronymus D Boogaarts, Catharina J M Klijn, René van den Berg, Bert A Coert, Janneke Horn, Charles B L M Majoie, Gabriël J E Rinkel, Yvo B W E M Roos, W Peter Vandertop, Dagmar Verbaan, Menno R. Germans, Maud A. Tjerkstra, Mervyn D.I. Vergouwen, Radboud W. Koot, Nyika D. Kruyt, Peter W.A. Willems, Jasper F.C. Wolfs, Frits C. de Beer, Patricia H.A. Halkes, Loes J.A. Reichman, Paul J.A.M. Brouwers, Renske M. van den Berg-Vos, Vincent I.H. Kwa, Taco C. van der Ree, Henri P. Bienfait, Hieronymus D. Boogaarts, Catharina J.M. Klijn, Martine van Bilzen, H.J.G. Dieks, Koen de Gans, J.B.M. ten Holter, Jelle R. de Kruijk, Charlie T.J.M. Leijzer, Delmar Molenaar, Robbert J. van Oostenbrugge, Jeske van Pamelen, Fianne H.M. Spaander, Sarah E. Vermeer, J. Manuela Voorend, Bert A. Coert, Charles B.L.M. Majoie, Gabriël J.E. Rinkel, Yvo B.W.E.M. Roos, W. Peter Vandertop, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, Neurology, Radiology and nuclear medicine, VU University medical center, ACS - Atherosclerosis & ischemic syndromes, Graduate School, ANS - Systems & Network Neuroscience, ANS - Neurovascular Disorders, Experimental Vascular Medicine, Radiology and Nuclear Medicine, and ACS - Microcirculation
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Intention-to-treat analysis ,Antifibrinolytic ,business.industry ,medicine.drug_class ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] ,General Medicine ,Odds ratio ,030204 cardiovascular system & hematology ,Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,All institutes and research themes of the Radboud University Medical Center ,Randomized controlled trial ,law ,Modified Rankin Scale ,Anesthesia ,Clinical endpoint ,Medicine ,030212 general & internal medicine ,Prospective cohort study ,business ,Tranexamic acid ,medicine.drug - Abstract
BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups.INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale.FUNDING: Fonds NutsOhra.
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- 2021
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18. Efficacy and quality of life after 6-9 years of deep brain stimulation for depression
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Isidoor O. Bergfeld, Pieter Ooms, Anja Lok, Lara de Rue, Pieter Vissers, Dirk de Knijff, Ferdinand Horst, Guus Beute, Pepijn van den Munckhof, P. Richard Schuurman, Damiaan Denys, Netherlands Institute for Neuroscience (NIN), Neurosurgery, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, ANS - Neurodegeneration, and ANS - Systems & Network Neuroscience
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Adult ,Clinical trial ,Quality of life ,Depressive Disorder, Treatment-Resistant ,Depression ,General Neuroscience ,Biophysics ,Deep brain stimulation ,Humans ,Major depression ,Neurology (clinical) ,Treatment outcome ,Treatment-resistant depression - Abstract
Background: Given the invasiveness of deep brain stimulation (DBS), the effect should prove to be stable over the long-term and translate into an improvement of quality of life (QOL). Objective: To study the effectiveness and QOL up to nine years after the DBS surgery. Methods: We treated 25 adult patients with major depression with DBS of the ventral anterior limb of the internal capsule (vALIC). We followed them up naturalistically for 6–9 years after surgery (mean: 7.7 [SD:1.5] years), including a randomized crossover phase after the first year comparing sham with active DBS. Symptom severity was quantified using the Hamilton Depression Scale with response defined as a ≥50% decrease of the score compared to baseline. Quality of life was measured using the WHOQOL-BREF, assessing 5 domains (general, physical, psychological, social, environmental). Results: Intention-to-treat response rates remained mostly stable from Year 3 to last follow-up (Year 3, 5 and 6: 40%; Year 4: 36%; Last observation: 44%). General, physical, psychological (all P < 0.001) and the environmental (P = 0.02) domain scores increased during DBS optimization and remained stable over the long term. No statistically significant changes were detected on the social domain. Patients scored significantly higher during active than sham DBS on the psychological, social and environmental domains, and trended towards a higher score on the general and physical domains. Conclusion: This study shows continued efficacy of vALIC DBS in depression, which translates into an improvement of QOL providing further support for DBS as a durable treatment for TRD.
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- 2022
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19. A unidirectional but not uniform striatal landscape of dopamine signaling for motivational stimuli
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Wouter van Elzelingen, Jessica Goedhoop, Pascal Warnaar, Damiaan Denys, Tara Arbab, Ingo Willuhn, Netherlands Institute for Neuroscience (NIN), Graduate School, Adult Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, and ANS - Systems & Network Neuroscience
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Multidisciplinary ,Reward ,motivation ,behavior ,striatum ,Learning ,Pavlovian conditioning ,dopamine ,Corpus Striatum - Abstract
Dopamine signals in the striatum are critical for motivated behavior. However, their regional specificity and precise information content are actively debated. Dopaminergic projections to the striatum are topographically organized. Thus, we quantified dopamine release in response to motivational stimuli and associated predictive cues in six principal striatal regions of unrestrained, behaving rats. Absolute signal size and its modulation by stimulus value and by subjective state of the animal were interregionally heterogeneous on a medial to lateral gradient. In contrast, dopamine-concentration direction of change was homogeneous across all regions: appetitive stimuli increased and aversive stimuli decreased dopamine concentration. Although cues predictive of such motivational stimuli acquired the same influence over dopamine homogeneously across all regions, dopamine-mediated prediction-error signals were restricted to the ventromedial, limbic striatum. Together, our findings demonstrate a nuanced striatal landscape of unidirectional but not uniform dopamine signals, topographically encoding distinct aspects of motivational stimuli and their prediction.
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- 2022
20. Large practice variations in diagnosis and treatment of delayed cerebral ischemia after subarachnoid hemorrhage
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Maud A. Tjerkstra, Dagmar Verbaan, Bert A. Coert, René Post, René van den Berg, Jonathan M. Coutinho, Janneke Horn, W. Peter Vandertop, Neurosurgery, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, Graduate School, Neurology, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Radiology and Nuclear Medicine, ACS - Microcirculation, ACS - Atherosclerosis & ischemic syndromes, Intensive Care Medicine, and ANS - Neuroinfection & -inflammation
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Treatment ,Diagnosis ,Humans ,Vasospasm, Intracranial ,Surgery ,Nimodipine ,Subarachnoid hemorrhage ,Neurology (clinical) ,Cerebral Infarction ,Survey ,Delayed cerebral ischemia ,Brain Ischemia - Abstract
Background: Delayed cerebral ischemia (DCI) contributes to poor outcomes after subarachnoid hemorrhage (SAH). The pathophysiology of DCI is not fully understood, which has hindered the adoption of a uniform definition. Furthermore, a reliable diagnostic test and an effective evidence-based treatment are lacking. This could lead to variations in care. Methods: A web-based survey on the variations in the definition, diagnosis, and treatment of DCI was designed and sent to 314 intensivists, neurologists, and neurosurgeons of all 9 hospitals in the Netherlands who care for patients with SAH. The responders were categorized into physicians responsible for the coordination of SAH care and those who were not. For questions on the definition and diagnosis, only the responses from the coordinating physicians were evaluated. For the treatment questions, all the responses were evaluated. Results: The response rate was 34% (106 of 314). All 9 hospitals were represented. Of the responses, 27 did not provide answers for the definition, diagnosis, or treatment questions; 79 responses were used for analysis. Signs of vasospasm were required by 21 of the 47 coordinating physicians (44%) when considering DCI. Of the 47 coordinating physicians, 24 (51%) did not use a diagnostic test results for a positive diagnosis of DCI. When patients were discharged within 21 days, 33 of the 73 responders (45%) did not provide a prescription for nimodipine continuation. Finally, all but one hospital had treated DCI with hypertension induction. Conclusions: We found large variations in the definition, diagnosis, and treatment of DCI in the Netherlands. In the absence of evidence-based treatment, standardization of management seems warranted in an effort to optimize DCI care.
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- 2022
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21. Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex
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Feng Wang, Pieter R. Roelfsema, Xing Chen, Eduardo Fernández, Netherlands Institute for Neuroscience (NIN), Integrative Neurophysiology, Amsterdam Neuroscience - Systems & Network Neuroscience, and ANS - Systems & Network Neuroscience
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Male ,Neuroprosthetics ,Neural Prostheses ,genetic structures ,Computer science ,media_common.quotation_subject ,Phosphenes ,Visual Physiology ,Stimulation ,Blindness ,03 medical and health sciences ,0302 clinical medicine ,Perception ,medicine ,Animals ,030304 developmental biology ,media_common ,Visual Cortex ,0303 health sciences ,Multidisciplinary ,Neural Prosthesis ,Macaca mulatta ,Electric Stimulation ,Phosphene ,Visual cortex ,medicine.anatomical_structure ,Pattern Recognition, Visual ,Receptive field ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Restoring vision by stimulating the brain Electrical stimulation of the visual cortex has long been proposed as an approach to restoring vision in blind people. Previous studies positioned electrodes on the surface of the brain and thus required delivery of relatively high currents. However, this approach limits the number of electrodes that can be safely stimulated simultaneously, and such surface electrodes activate several millimeters of cortex, which results in a low spatial resolution. Chen et al. demonstrated that the simultaneous stimulation of multiple intracortical electrodes in the monkey primary visual cortex gives rise to the perception of shape and successive stimulation to the perception of motion (see the Perspective by Beauchamp and Yoshor). This major improvement provides proof of concept for the use of electrical microstimulation to create a form of artificial vision in the blind. Science , this issue p. 1191 ; see also p. 1165
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- 2020
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22. Object selection by automatic spreading of top-down attentional signals in V1
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Floris P. de Lange, Pieter R. Roelfsema, Matthias Ekman, Adult Psychiatry, ANS - Systems & Network Neuroscience, Amsterdam Neuroscience - Systems & Network Neuroscience, Integrative Neurophysiology, and Netherlands Institute for Neuroscience (NIN)
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Male ,genetic structures ,Computer science ,0302 clinical medicine ,Orientation (geometry) ,Premovement neuronal activity ,Computer vision ,Attention ,Object-based attention ,Research Articles ,education.field_of_study ,Brain Mapping ,medicine.diagnostic_test ,General Neuroscience ,05 social sciences ,Representation (systemics) ,180 000 Predictive Brain ,Top-down and bottom-up design ,Magnetic Resonance Imaging ,Visual field ,medicine.anatomical_structure ,FMRI ,Visual Perception ,Female ,Cues ,Adult ,Population ,050105 experimental psychology ,03 medical and health sciences ,Young Adult ,medicine ,Reaction Time ,Humans ,0501 psychology and cognitive sciences ,Visual cortex ,education ,Cued speech ,V1 ,Action, intention, and motor control ,business.industry ,Hemodynamics ,Object (computer science) ,Receptive field ,Space Perception ,Gestalt psychology ,Artificial intelligence ,Visual Fields ,Functional magnetic resonance imaging ,business ,030217 neurology & neurosurgery ,Photic Stimulation - Abstract
What is selected when attention is directed to a specific location of the visual field? Theories of object-based attention have suggested that when spatial attention is directed to part of an object, attention does not simply enhance the attended location but automatically spreads to enhance all locations that comprise the object. Here, we tested this hypothesis by reconstructing the distribution of attention from primary visual cortex (V1) population neuronal activity patterns in 24 human adults (17 female) using functional magnetic resonance imaging (fMRI) and population-based receptive field (prf) mapping. We find that attention spreads from a spatially cued location to the underlying object, and enhances all spatial locations that comprise the object. Importantly, this spreading was also evident when the object was not task relevant. These data suggest that attentional selection automatically operates at an object level, facilitating the reconstruction of coherent objects from fragmented representations in early visual cortex.SIGNIFICANCE STATEMENTObject perception is an astonishing feat of the visual system. When visual information about orientation, shape, and color enters through our eyes, it has yet to be integrated into a coherent representation of an object. But which visual features constitute a single object and which features belong to the background? The brain mechanisms underpinning object perception are yet to be understood. We now demonstrate that one candidate mechanism, the successive activation of all parts of an object, occurs in early visual cortex and results in a detailed representation of the object following Gestalt principles. Furthermore, our results suggest that object selection occurs automatically, without involving voluntary control.
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- 2020
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23. High recurrence rate in patients with choroidal hemangioma treated with limited single spot photodynamic therapy during long-term follow-up
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Frank D. Verbraak, Reinier O. Schlingemann, M Stehouwer, Graduate School, ACS - Atherosclerosis & ischemic syndromes, Ophthalmology, ANS - Systems & Network Neuroscience, and Amsterdam Neuroscience - Systems & Network Neuroscience
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Male ,Time Factors ,Visual acuity ,genetic structures ,medicine.medical_treatment ,Visual Acuity ,Photodynamic therapy ,long-term follow-up ,0302 clinical medicine ,Medicine ,Fluorescein Angiography ,Netherlands ,Photosensitizing Agents ,Choroid Neoplasms ,Incidence ,General Medicine ,Middle Aged ,Treatment Outcome ,medicine.anatomical_structure ,photodynamic therapy ,Original Article ,Female ,medicine.symptom ,Hemangioma ,Choroidal hemangioma ,Tomography, Optical Coherence ,Adult ,recurrence ,Fundus Oculi ,Long term follow up ,03 medical and health sciences ,Humans ,In patient ,Circumscribed choroidal hemangioma ,Aged ,Retrospective Studies ,Choroid ,business.industry ,Verteporfin ,Original Articles ,eye diseases ,Ophthalmology ,Cross-Sectional Studies ,Photochemotherapy ,long‐term follow‐up ,030221 ophthalmology & optometry ,Neoplasm Recurrence, Local ,business ,Nuclear medicine ,030217 neurology & neurosurgery ,High recurrence rate ,circumscribed choroidal hemangioma ,Follow-Up Studies - Abstract
Purpose: To evaluate the long-term follow-up of patients with a circumscribed choroidal hemangioma (CCH) treated with limited single spot photodynamic therapy (PDT) at the Amsterdam University Medical Center, location AMC (AUMC). Methods: This cross-sectional study included 17 patients, treated between 2001 and 2012. Evaluation included best corrected visual acuity, slitlamp examination, fundoscopy, ophthalmic ultrasonography (USG), fluorescein/indocyanine green angiography (FA/ICG), fundus autofluorescence (FAF) and optical coherence tomography (OCT). Primary outcome: recurrence rate, secondary outcomes: long-term functional and structural changes. Results: An unexpected high recurrence rate of 35% (n6) was found with a mean follow-up time between treatment and recurrence of almost 6 years, range 2.8–10.7 years. With a recurrence, the classical CCH pattern was no longer recognizable on FA or ICG. Signs of leakage were best observed with OCT, and the recurrence could be confirmed with USG. Retreatment with PDT of all recurrences was successful. After a successful initial PDT, the achieved visual acuity (VA) showed a small decrease over time, median VA from 0.10 LogMar to 0.15 LogMar (p 0.09) after a mean follow-up of 11.36 years (range 5.1–15.5 years). During follow-up study visit, the OCT revealed a slightly increased thickness of the choroid in 86% of cases at the site of the original tumour, without a clear correlation to the recurrences. Conclusion: Limited single spot PDT is a safe and effective treatment for CCH preserving a good VA. However, because of the relatively high recurrence rate found in this study, we recommend regular follow-up with OCT every 6 months.
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- 2020
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24. Procedures performed during neurosurgery residency in Europe
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Stienen, M. N., Freyschlag, C. F., Schaller, K., Meling, T., Al-Amin, A., Al-Mahfoudh, R., Amelot, A., Arvidsson, L., Athanasiou, A., Avellan, C. I. A., Bauchet, L., Berilazic, L., Bolger, C., Bourdillon, P., Boviatsis, S., Bozinov, O., Branco, P., Braunsdorf, W., Cahill, J., Clusmann, H., Conrad, J., Cordier, D., Cristino, N., Djilvesi, D., Duerinck, J., Dumot, C., Durak, M. A., Eisenring, C. V., Esposito, G., Finiels, P. -J., Flaskas, T., Fuentes, S., Ganau, M., Georgiadis, I., Georgiopoulos, M., Giakoumettis, D., Gilis, N., Gradil, C., Grau, S. J., Grin, A., Hadjigeorgiou, G., Halatsch, M. -E., Hecht, N., Holling, M., Ilic, R., Iken, L., Santos, N. I., Jacquesson, T., Jalloh, I., Jelaca, B., Kaestner, S., Kalasauskas, D., Kaliyev, A., Kleiber, J. -C., Konczalla, J., Kothbauer, K. F., Kovacevic, V., Krajcinovic, N., Krieg, S. M., Kamarainen, O. -P., Lapcic, M., Lapras, C., Ljungqvist, J., W. B., Lo, Lubrano, V., Majovsky, M., Manet, R., Marchi, F., Medetov, Y., Meling, T. R., Melloni, I., Melot, A., Mertens, P., Metcalfe, S., Moerkve, S. H., Mora, A. R., Musabelliu, E., Naushahi, M. J., Nurzhan, A., Omerhodzic, I., Paldor, I., Pallud, J., Papanastassiou, V., Papic, V., Paschalis, T., Payer, M., Peerdeman, S. M., Peruzzi, P., Segerlind, J. P., Posti, J. P., Proust, F., Regli, L., Rinne, J., Roche, P. -H., Rocka, S., Rotermund, R., Rutherford, S. A., Ratsep, T., Ruter, A., Saarenpaa, I. M., Samanci, M. Y., Samardzic, M., Sampron, N., Sandvik, U., Scerrati, A., Schneider, M., Schul, D. B., Sengul, G., Simon, E., Sinha, S., Solheim, O., Spatola, G., Spektor, S., Sundblom, J., Syrmos, N. C., Teo, M., Thomson, S., Tonchev, N., Tosic, L., Vandertop, W. P., von der Brelie, C., Vuk, A., Walkden, J., Wendel, C., Yaqout, M., Yusupova, M., Zollino, G., University of Zurich, Surgical clinical sciences, Neuroprotection & Neuromodulation, Neurosurgery, IOO, and ANS - Systems & Network Neuroscience
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Adult ,Male ,Neurosurgery/education ,medicine.medical_specialty ,Certification ,Caseload ,Europe ,Neurosurgery ,Residency ,Training program ,Working hour restriction ,610 Medicine & health ,Neurosurgical Procedures ,NO ,03 medical and health sciences ,10180 Clinic for Neurosurgery ,0302 clinical medicine ,Surveys and Questionnaires ,Germany ,Medicine ,Humans ,Child ,Greece ,business.industry ,Female sex ,Internship and Residency ,Mean age ,Surgical procedures ,Middle Aged ,Current analysis ,United Kingdom ,Original Article - Neurosurgery Training ,ddc:616.8 ,030220 oncology & carcinogenesis ,Surgery ,Female ,Neurology (clinical) ,France ,business ,030217 neurology & neurosurgery ,Switzerland ,Demography - Abstract
Background In a previous article (10.1007/s00701-019-03888-3), preliminary results of a survey, aiming to shed light on the number of surgical procedures performed and assisted during neurosurgery residency in Europe were reported. We here present the final results and extend the analyses. Methods Board-certified neurosurgeons of European Association of Neurosurgical Societies (EANS) member countries were asked to review their residency case logs and participate in a 31-question electronic survey (SurveyMonkey Inc., San Mateo, CA). The responses received between April 25, 2018, and April 25, 2020, were considered. We excluded responses that were incomplete, from non-EANS member countries, or from respondents that have not yet completed their residency. Results Of 430 responses, 168 were considered for analysis after checking in- and exclusion criteria. Survey responders had a mean age of 42.7 ± 8.8 years, and 88.8% were male. Responses mainly came from surgeons employed at university/teaching hospitals (85.1%) in Germany (22.0%), France (12.5%), the United Kingdom (UK; 8.3%), Switzerland (7.7%), and Greece (7.1%). Most responders graduated in the years between 2011 and 2019 (57.7%). Thirty-eight responders (22.6%) graduated before and 130 responders (77.4%) after the European WTD 2003/88/EC came into effect. The mean number of surgical procedures performed independently, supervised or assisted throughout residency was 540 (95% CI 424–657), 482 (95% CI 398–568), and 579 (95% CI 441–717), respectively. Detailed numbers for cranial, spinal, adult, and pediatric subgroups are presented in the article. There was an annual decrease of about 33 cases in total caseload between 1976 and 2019 (coeff. − 33, 95% CI − 62 to − 4, p = 0.025). Variables associated with lesser total caseload during residency were training abroad (1210 vs. 1747, p = 0.083) and female sex by trend (947 vs. 1671, p = 0.111), whereas case numbers were comparable across the EANS countries (p = 0.443). Conclusion The final results of this survey largely confirm the previously reported numbers. They provide an opportunity for current trainees to compare their own case logs with. Again, we confirm a significant decline in surgical exposure during training between 1976 and 2019. In addition, the current analysis reveals that female sex and training abroad may be variables associated with lesser case numbers during residency.
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- 2020
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25. Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma
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van Linde, Myra E., Labots, Mariette, Brahm, Cyrillo G., Hovinga, Koos E., de Witt Hamer, Philip C., Honeywell, Richard J., de Goeij-de Haas, Richard, Henneman, Alex A., Knol, Jaco C., Peters, Godefridus J., Dekker, Henk, Piersma, Sander R., Pham, Thang V., Vandertop, William P., Jiménez, Connie R., Verheul, Henk M. W., ANS - Systems & Network Neuroscience, ANS - Neurovascular Disorders, Neurosurgery, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, Internal medicine, CCA - Treatment and quality of life, Amsterdam Neuroscience - Systems & Network Neuroscience, Clinical pharmacology and pharmacy, Medical oncology laboratory, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Neurodegeneration, and CCA - Cancer Treatment and quality of life
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Proteomics ,Cancer Research ,Indoles ,Brain Neoplasms ,urologic and male genital diseases ,female genital diseases and pregnancy complications ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,All institutes and research themes of the Radboud University Medical Center ,Oncology ,Cell Line, Tumor ,Sunitinib ,Humans ,Pyrroles ,Glioblastoma - Abstract
Purpose: Tyrosine kinase inhibitors (TKI) have poor efficacy in patients with glioblastoma (GBM). Here, we studied whether this is predominantly due to restricted blood–brain barrier penetration or more to biological characteristics of GBM. Patients and Methods: Tumor drug concentrations of the TKI sunitinib after 2 weeks of preoperative treatment was determined in 5 patients with GBM and compared with its in vitro inhibitory concentration (IC50) in GBM cell lines. In addition, phosphotyrosine (pTyr)-directed mass spectrometry (MS)-based proteomics was performed to evaluate sunitinib-treated versus control GBM tumors. Results: The median tumor sunitinib concentration of 1.9 μmol/L (range 1.0–3.4) was 10-fold higher than in concurrent plasma, but three times lower than sunitinib IC50s in GBM cell lines (median 5.4 μmol/L, 3.0–8.5; P = 0.01). pTyr-phosphoproteomic profiles of tumor samples from 4 sunitinib-treated versus 7 control patients revealed 108 significantly up- and 23 downregulated (P < 0.05) phosphopeptides for sunitinib treatment, resulting in an EGFR-centered signaling network. Outlier analysis of kinase activities as a potential strategy to identify drug targets in individual tumors identified nine kinases, including MAPK10 and INSR/IGF1R. Conclusions: Achieved tumor sunitinib concentrations in patients with GBM are higher than in plasma, but lower than reported for other tumor types and insufficient to significantly inhibit tumor cell growth in vitro. Therefore, alternative TKI dosing to increase intratumoral sunitinib concentrations might improve clinical benefit for patients with GBM. In parallel, a complex profile of kinase activity in GBM was found, supporting the potential of (phospho)proteomic analysis for the identification of targets for (combination) treatment.
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- 2022
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26. European Academy of Neurology/Movement Disorder Society-European Section Guidelines on Pallidotomy for Parkinson's Disease: Let's Be Accurate
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Hariz, Marwan, Bronstein, Jeff M, Cosgrove, G Rees, de Bie, Rob M A, DeLong, Mahlon R, Gross, Robert E, Krack, Paul, Krauss, Joachim K, Lang, Anthony E, Lees, Andrew J, Lozano, Andres M, Obeso, José A, Schuurman, P Richard, Vitek, Jerold L, Neurosurgery, Neurology, ANS - Neurodegeneration, and ANS - Systems & Network Neuroscience
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610 Medicine & health ,610 Medizin und Gesundheit - Published
- 2022
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27. Thalamic local field potentials recorded using the deep brain stimulation pulse generator
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Buijink, A. W. G., Piña-Fuentes, D. A., Stam, M. J., Bot, M., Schuurman, P. R., van den Munckhof, P., van Rootselaar, A. F., de Bie, R. M. A., Beudel, M., Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurosurgery, Neurology, Graduate School, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, ANS - Brain Imaging, and APH - Aging & Later Life
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Neurology ,Physiology (medical) ,Tremor ,Deep brain stimulation ,Essential tremor ,Closed-loop ,Neurology (clinical) ,Adaptive ,nervous system diseases - Abstract
Background: Essential tremor (ET) is one of the most common movement disorders, and continuous deep brain stimulation (DBS) is an established treatment for medication-refractory cases. However, the need for increasing stimulation intensities, with unpleasant side effects, and DBS tolerance over time can be problematic. The advent of novel DBS devices now provides the opportunity to longitudinally record LFPs using the implanted pulse generator, which opens up possibilities to implement adaptive DBS algorithms in a real-life setting. Methods: Here we report a case of thalamic LFP activity recorded using a commercially available sensing-enabled DBS pulse generator (Medtronic Percept PC). Results: In the OFF-stimulation condition, a peak tremor frequency of 3.8 Hz was identified during tremor evoking movements as assessed by video and accelerometers. Activity at the same and supraharmonic frequency was seen in the frequency spectrum of the LFP data from the left vim nucleus during motor tasks. Coherence analysis showed that peripherally recorded tremor was coherent with the LFP signal at the tremor frequency and supraharmonic frequency. Conclusion: This is the first report of recorded tremor-related thalamic activity using the electrodes and pulse generator of an implanted DBS system. Larger studies are needed to evaluate the clinical potential of these fully implantable systems, and ultimately pulse generators with sensing-coupled algorithms driving stimulation, to really close the loop.
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- 2022
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28. Subthalamic deep brain stimulation for advanced Parkinson’s disease: Optimizing localization and stimulation of the target area
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Verhagen, Rens, van Schaik, I.N., Schuurman, P.R., Bour, L.J., Heida, T., Faculteit der Geneeskunde, van Schaik, Ivo, Schuurman, Rick, Bour, Lodewijk, ANS - Neuroinfection & -inflammation, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, ANS - Amsterdam Neuroscience, and Graduate School
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surgical procedures, operative ,nervous system ,nervous system diseases - Abstract
Deep brain stimulation (DBS) is an effective surgical treatment for advanced Parkinson’s Disease (PD). Continuous electrical stimulation within the subthalamic nucleus (STN), one of the basal ganglia, can successfully alleviate PD motor symptoms. However, the success of STN-DBS can be limited by side effects which can occur when unwanted neuronal areas or connections are stimulated. Therefore, it is important that the stimulation is targeted at the right location as specifically as possible. In this thesis we have studied several aspects of STN-DBS and how they contribute to optimal localization and stimulation of the preferred target area. We have used conventional imaging and electrode technology to study how the target area can be optimally located. Additionally, we have studied developments in imaging techniques and electrode design, i.e., the steering DBS electrode, to investigate how future technology can be used to further optimize both localization and stimulation of the most effective target area. We conclude that a continuous effort should be made to critically review DBS targeting considering the evolving clinical and technological possibilities. We argue that targeting and steering stimulation are inseparable in optimizing DBS results. When targeting is inaccurate, steering stimulation might compensate for some of the lost potential benefit. However, the current preoperative planning with high field MRI and verification by intraoperative measurements and imaging make the targeting so accurate that it could perhaps be adapted specifically to the steering electrode. This thesis suggests that the full potential of steering electrodes could possibly be unleashed by targeting more specifically aimed at the dorsolateral motor segment of the STN.
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- 2022
29. Cerebral circulation time on DSA during endovascular treatment in WFNS grade I aneurysmal SAH patients—a predictor of DCI?
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W. Peter Vandertop, Bart J. Emmer, René van den Berg, Dagmar Verbaan, Charles B. L. M. Majoie, Bert A Coert, Mark Schembri, Neurosurgery, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Systems & Network Neuroscience, ACS - Atherosclerosis & ischemic syndromes, Radiology and nuclear medicine, and Amsterdam Neuroscience - Neurovascular Disorders
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medicine.medical_specialty ,Subarachnoid hemorrhage ,medicine.diagnostic_test ,genetic structures ,business.industry ,Angiography ,Vasospasm ,Odds ratio ,Digital subtraction angiography ,medicine.disease ,Logistic regression ,Aneurysm ,Exact test ,Internal medicine ,medicine ,Cardiology ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Delayed cerebral ischemia ,Neuroradiology - Abstract
PURPOSE: Delayed cerebral ischemia (DCI) remains a contributor to poor outcome following aneurysmal subarachnoid hemorrhage (aSAH). We evaluated cerebral circulation time (CCT) on digital subtraction angiography (DSA) during endovascular treatment (EVT) in WFNS grade I aSAH patients as a predictor of DCI.METHODS: Of 135 consecutive WNFS grade I aSAH patients, 90 were included. Age, gender, time of DSA from ictus ( 72 h), Fisher scale, severe vasospasm, development of DCI, EVD-dependent hydrocephalus, re-bleeding, and procedural complications were recorded. CCT was calculated retrospectively from multiphase DSA. Association with DCI was established through univariate and, subsequently, multivariable logistic regression. An optimal threshold value was identified using ROC curve analysis. Patient groups defined by threshold CCT value, DCI, and, subsequently, time of DSA from ictus were analyzed using χ2 and Fisher's exact test.RESULTS: CCT was the only significant factor in the multivariable logistic regression for the outcome development of DCI (OR/second increase in CCT = 1.46 [95% CI 1.14-1.86, p = .003]). When CCT was dichotomized at 8.5 s, the odds ratio for developing DCI was 7.12 (95% CI 1.93-26.34, p = .003) for CCT > 8.5 s compared with 8.5 s (all patients, p = .001; patients imaged before and after 72 h of ictus, p = .024 and p = .034, respectively).CONCLUSION: A CCT > 8.5 s on DSA during EVT in WFNS grade I aSAH patients is associated with an increased risk of developing DCI and may aid in the management of high-risk patients.
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- 2021
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30. The PRolaCT studies — a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma
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Zandbergen, I.M., Najafabadi, A.H.Z., Pelsma, I.C.M., Akker-van Marle, M.E. van den, Bisschop, P.H.L.T., Boogaarts, H.D.J., Bon, A.C. van, Burhani, B., Cessie, S. le, Dekkers, O.M., Drent, M.L., Feelders, R.A., Graaf, J.P. de, Hoogmoed, J., Kapiteijn, K.K., Klauw, M.M. van der, Nieuwlaat, W.A.C.M., Pereira, A.M., Stades, A.M.E., Ven, A.C. van de, Wakelkamp, I.M.M.J., Furth, W.R. van, Biermasz, N.R., Dutch Prolactinoma Study Grp, Internal Medicine, Endocrinology, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Neurosurgery, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Amsterdam Gastroenterology Endocrinology Metabolism
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Pediatrics ,medicine.medical_specialty ,Medicine (General) ,Adenoma ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Medicine (miscellaneous) ,Randomised clinical trial ,Cohort Studies ,Study Protocol ,R5-920 ,All institutes and research themes of the Radboud University Medical Center ,Quality of life ,Medicine ,Humans ,Pharmacology (medical) ,Pituitary Neoplasms ,Prolactinoma ,Observational cohort ,Randomized Controlled Trials as Topic ,Retrospective Studies ,Protocol (science) ,business.industry ,Dopamine agonist ,Pituitary tumour ,Hyperprolactinaemia ,medicine.disease ,Clinical trial ,Observational Studies as Topic ,Treatment Outcome ,Endoscopic transsphenoidal resection ,Quality of Life ,Observational study ,business ,Cohort study ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Background First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. Methods We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4–6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. Discussion Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. Trial registration US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480. Registered on 27 September 2019, registered retrospectively (by 2 months).
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- 2021
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31. Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex
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John D. Rolston, Richard A. Normann, Alfonso Rodil, Tyler S. Davis, Pieter R. Roelfsema, Maria Dolores Grima, Antonio M. Lozano Ortega, Xing Chen, Bernardeta Gómez, Arantxa Alfaro, Cristina Soto-Sánchez, Pablo González-López, Eduardo Fernández, Sebastian Peña, Adult Psychiatry, ANS - Systems & Network Neuroscience, Departamentos de la UMH::Medicina Clínica, Integrative Neurophysiology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and Netherlands Institute for Neuroscience (NIN)
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medicine.medical_specialty ,SDG 16 - Peace ,genetic structures ,Phosphenes ,Stimulation ,Audiology ,Blindness ,Simultaneous stimulation ,Retina ,Cortex (anatomy) ,Optic Nerve Diseases ,medicine ,Complete Blindness ,Humans ,Vision, Ocular ,Visual Cortex ,business.industry ,SDG 16 - Peace, Justice and Strong Institutions ,General Medicine ,Multielectrode array ,Middle Aged ,Justice and Strong Institutions ,Electric Stimulation ,Electrodes, Implanted ,Visual Prosthesis ,6 - Ciencias aplicadas::61 - Medicina [CDU] ,medicine.anatomical_structure ,Visual cortex ,Phosphene ,Treatment Outcome ,Visual prosthesis ,Visual Perception ,Commentary ,Female ,Occipital Lobe ,business ,Microelectrodes - Abstract
BACKGROUND: A long-held dream of scientists is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists. METHODS: We implanted an intracortical microelectrode array consisting of 96 electrodes in the visual cortex of a 57-year-old person with complete blindness for a six- month period. We measured thresholds and the characteristics of the visual percepts elicited by intracortical microstimulation. RESULTS: Implantation and subsequent explantation of intracortical microelectrodes were carried out without complications. The mean stimulation threshold for single electrodes was 66.8 ± 36.5 μA. We consistently obtained high-quality recordings from visually deprived neurons and the stimulation parameters remained stable over time. Simultaneous stimulation via multiple electrodes were associated with a significant reduction in thresholds (p
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- 2021
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32. Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses
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Robert A. Schoevers, Mohsen Ghanbari, Annemarie I. Luik, Bastiaan T. Heijmans, Nienke R. Biermasz, Brenda W.J.H. Penninx, Carisha S. Thesing, Aeilko H. Zwinderman, Ruifang Li-Gao, Kaitlin H Wade, Frits R. Rosendaal, Dorret I. Boomsma, M. Arfan Ikram, Marian Beekman, Dennis O. Mook-Kanamori, Lisanne S. Vijfhuizen, P. Eline Slagboom, Debbie A Lawlor, Matthew Lee, Naveed Sattar, Matt J. Neville, Stella Trompet, J. Wouter Jukema, L.H. Lumey, Diana van Heemst, Ian Ford, Renée de Mutsert, Rima Mustafa, Patrick C.N. Rensen, Xiang Zhang, M.M. Bos, Abbas Dehghan, Carolien A. Wijsman, Gonneke Willemsen, Gisela M. Terwindt, Irene de Boer, Raymond Noordam, Ko Willems van Dijk, René Pool, Fredrik Karpe, Arn M. J. M. van den Maagdenberg, Neil Goulding, Rebecca C Richmond, Simon P. Mooijaart, Amy Hofman, Constantinos Christodoulides, Chihua Li, Mariska Bot, Neurosurgery, ANS - Neurodegeneration, ANS - Systems & Network Neuroscience, Epidemiology and Data Science, APH - Methodology, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Epidemiology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, and APH - Personalized Medicine
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medicine.medical_specialty ,Epidemiology ,lcsh:Medicine ,Physiology ,Coronary Artery Disease ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolic Diseases ,SDG 3 - Good Health and Well-being ,Risk Factors ,Mendelian randomization ,medicine ,Insomnia ,Humans ,Metabolomics ,Isoleucine ,sleep ,Aged ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,Creatinine ,business.industry ,lcsh:R ,Chronotype ,General Medicine ,Mendelian Randomization Analysis ,R1 ,Confidence interval ,3. Good health ,Cross-Sectional Studies ,Phenotype ,chemistry ,Human and Animal Physiology ,Cohort ,Fysiologie van Mens en Dier ,medicine.symptom ,business ,Sleep ,Body mass index ,030217 neurology & neurosurgery ,Research Article ,Genome-Wide Association Study - Abstract
Background Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease. Methods We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions. Results We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (− 0.08 standard deviation (SD)[95% confidence interval (CI) − 0.12, − 0.03] in AMV and − 0.03SD [− 0.07, − 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (− 0.04SD [− 0.08, 0.00] in AMV and − 0.05SD [− 0.09, − 0.02] in MR), and lower phospholipids in very large HDL particles (− 0.04SD [− 0.08, 0.002] in AMV and − 0.05SD [− 0.08, − 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures. Conclusions Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
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- 2021
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33. Spatial concordance of DNA methylation classification in diffuse glioma
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Philip C. De Witt Hamer, Petra J. W. Pouwels, W Pieter Vandertop, Frederik Barkhof, Otto S. Hoekstra, Kevin J. Anderson, Sunit Das, Annemieke J.M. Rozemuller, Niels Verburg, Pieter Wesseling, Ronald Boellaard, Michael D. Taylor, Jeroen A.M. Beliën, Jaap C. Reijneveld, Roel G.W. Verhaak, Maqsood Yaqub, Joseph F. Costello, Kevin C. Johnson, Adriaan A. Lammertsma, Floris P. Barthel, Thomas Koopman, Neurosurgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, CCA - Imaging and biomarkers, AMS - Tissue Function & Regeneration, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pathology, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, CCA - Cancer Treatment and Quality of Life, ANS - Neurovascular Disorders, and ANS - Systems & Network Neuroscience
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Adult ,0301 basic medicine ,DNA methylation classification ,Cancer Research ,Oligodendroglioma ,Intratumoral heterogeneity ,Biology ,Imaging ,03 medical and health sciences ,Diffuse Glioma ,0302 clinical medicine ,Diffuse Astrocytoma ,glioma ,Glioma ,medicine ,Humans ,AcademicSubjects/MED00300 ,Epigenetics ,epigenetics ,Brain Neoplasms ,Genetic heterogeneity ,imaging ,Methylation ,DNA Methylation ,medicine.disease ,Isocitrate Dehydrogenase ,030104 developmental biology ,Oncology ,Mutation ,Basic and Translational Investigations ,intratumoral heterogeneity ,DNA methylation ,Cancer research ,AcademicSubjects/MED00310 ,Neurology (clinical) ,030217 neurology & neurosurgery - Abstract
Background Intratumoral heterogeneity is a hallmark of diffuse gliomas. DNA methylation profiling is an emerging approach in the clinical classification of brain tumors. The goal of this study is to investigate the effects of intratumoral heterogeneity on classification confidence. Methods We used neuronavigation to acquire 133 image-guided and spatially separated stereotactic biopsy samples from 16 adult patients with a diffuse glioma (7 IDH-wildtype and 2 IDH-mutant glioblastoma, 6 diffuse astrocytoma, IDH-mutant and 1 oligodendroglioma, IDH-mutant and 1p19q codeleted), which we characterized using DNA methylation arrays. Samples were obtained from regions with and without abnormalities on contrast-enhanced T1-weighted and fluid-attenuated inversion recovery MRI. Methylation profiles were analyzed to devise a 3-dimensional reconstruction of (epi)genetic heterogeneity. Tumor purity was assessed from clonal methylation sites. Results Molecular aberrations indicated that tumor was found outside imaging abnormalities, underlining the infiltrative nature of this tumor and the limitations of current routine imaging modalities. We demonstrate that tumor purity is highly variable between samples and explains a substantial part of apparent epigenetic spatial heterogeneity. We observed that DNA methylation subtypes are often, but not always, conserved in space taking tumor purity and prediction accuracy into account. Conclusion Our results underscore the infiltrative nature of diffuse gliomas and suggest that DNA methylation subtypes are relatively concordant in this tumor type, although some heterogeneity exists.
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- 2021
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34. Mouse visual cortex contains a region of enhanced spatial resolution
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Enny H. van Beest, Rob. R.M. Teeuwen, Areg Barsegyan, Ulf H. Schnabel, Sreedeep Mukherjee, Matthew W. Self, Chris van der Togt, Arne F. Meyer, Pieter R. Roelfsema, Jasper Poort, Lisa Kirchberger, Adult Psychiatry, ANS - Systems & Network Neuroscience, Integrative Neurophysiology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, van Beest, Enny H [0000-0002-2454-0445], Kirchberger, Lisa [0000-0001-6837-5210], Roelfsema, Pieter R [0000-0002-1625-0034], Self, Matthew W [0000-0001-5731-579X], Apollo - University of Cambridge Repository, van Beest, Enny H. [0000-0002-2454-0445], Roelfsema, Pieter R. [0000-0002-1625-0034], Self, Matthew W. [0000-0001-5731-579X], and Netherlands Institute for Neuroscience (NIN)
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Male ,0301 basic medicine ,Visual perception ,Visual acuity ,Eye Movements ,genetic structures ,Striate cortex ,631/378/2649/1723 ,General Physics and Astronomy ,Extrastriate cortex ,Visual processing ,Mice ,0302 clinical medicine ,Mapping techniques ,Image resolution ,Visual resolution ,Visual Cortex ,Physics ,education.field_of_study ,Multidisciplinary ,631/378/3920 ,article ,Computer Science::Graphics ,medicine.anatomical_structure ,Head Movements ,Visual Perception ,Sensory processing ,64/60 ,Female ,medicine.symptom ,631/378/2613/2614 ,Quantitative Biology::Tissues and Organs ,Science ,Population ,631/378/3917 ,Neural circuits ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,medicine ,Animals ,631/378/2613/1875 ,education ,Quantitative Biology::Neurons and Cognition ,business.industry ,9/97 ,Eye movement ,Pattern recognition ,General Chemistry ,eye diseases ,Mice, Inbred C57BL ,030104 developmental biology ,Visual cortex ,Receptive field ,Retinotopy ,14/63 ,Perception ,Artificial intelligence ,Visual Fields ,14/69 ,business ,Neuroscience ,Photic Stimulation ,030217 neurology & neurosurgery - Abstract
Funder: The work was supported by NWO (ALW grant 823-02-010) and the European Union’s Horizon 2020 and FP7 Research and Innovation Program (grant agreement 7202070 ‘Human Brain Project SGA1, SGA2 and SGA3’’, ERC grant agreement 339490 ‘Cortic_al_gorithms’’ and the Erasmus Mundus “NeuroTime” program) and the Stichting Vrienden van het Herseninstituut. A.F.M. was supported by the Radboud Excellence Initiative. J.P. is a Wellcome Trust and Royal Society Sir Henry Dale Fellow (211258/Z/18/Z)., The representation of space in mouse visual cortex was thought to be relatively uniform. Here we reveal, using population receptive-field (pRF) mapping techniques, that mouse visual cortex contains a region in which pRFs are considerably smaller. This region, the “focea,” represents a location in space in front of, and slightly above, the mouse. Using two-photon imaging we show that the smaller pRFs are due to lower scatter of receptive-fields at the focea and an over-representation of binocular regions of space. We show that receptive-fields of single-neurons in areas LM and AL are smaller at the focea and that mice have improved visual resolution in this region of space. Furthermore, freely moving mice make compensatory eye-movements to hold this region in front of them. Our results indicate that mice have spatial biases in their visual processing, a finding that has important implications for the use of the mouse model of vision.
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- 2021
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35. Theta-phase dependent neuronal coding during sequence learning in human single neurons
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Benedikt Zoefel, Sander Idema, Marlène Poncet, Matthew W. Self, Judith C. Peters, Pieter R. Roelfsema, Leila Reddy, Johannes C. Baayen, Rufin VanRullen, Jessy K. Possel, Adult Psychiatry, ANS - Systems & Network Neuroscience, Integrative Neurophysiology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), ANR-18-CE37-0007,AI-REPS,Intelligence Artificielle et Humaine: des représentations sémantiques communes?(2018), ANR-19-NEUC-0004,OsCiDeep,US-France Research Proposal: Oscillatory processes for visual reasoning in deep neural networks(2019), ANR-19-P3IA-0004,ANITI,Artificial and Natural Intelligence Toulouse Institute(2019), Neurosurgery, Amsterdam Neuroscience - Systems & Network Neuroscience, University of St Andrews. School of Psychology and Neuroscience, RS: FPN CN 1, Vision, and Netherlands Institute for Neuroscience (NIN)
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Male ,[SDV]Life Sciences [q-bio] ,General Physics and Astronomy ,Hippocampus ,Action Potentials ,Local field potential ,0302 clinical medicine ,Premovement neuronal activity ,Theta Rhythm ,Physics ,Neurons ,0303 health sciences ,Multidisciplinary ,Cognition ,Human brain ,Temporal Lobe ,medicine.anatomical_structure ,CELL ASSEMBLIES ,Female ,Sequence learning ,RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry ,Adult ,Adolescent ,TOOLBOX ,Quantitative Biology::Tissues and Organs ,Science ,Models, Neurological ,Stimulus (physiology) ,General Biochemistry, Genetics and Molecular Biology ,Article ,Temporal lobe ,Neuronal coding ,PRECESSION ,03 medical and health sciences ,Young Adult ,WORKING-MEMORY ,Encoding (memory) ,medicine ,OSCILLATIONS ,Humans ,Learning ,030304 developmental biology ,Sequence (medicine) ,Epilepsy ,Quantitative Biology::Neurons and Cognition ,Working memory ,RECOGNITION ,DAS ,Cognitive neuroscience ,MEDIAL TEMPORAL-LOBE ,General Chemistry ,nervous system ,RC0321 ,HIPPOCAMPUS ,Neuron ,Neuroscience ,030217 neurology & neurosurgery ,Photic Stimulation - Abstract
The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory., Previous work has shown that in rodents phase precession – the phase of action potentials relative to the theta oscillation – is associated with the representation of sequential locations. Here the authors demonstrate that phase precession also occurs in the human hippocampus using single neuron and LFP recordings.
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- 2021
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36. General Anesthesia vs Local Anesthesia in Microelectrode Recording–Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial
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Joke M. Dijk, Pepijn van den Munckhof, Rozemarije A. Holewijn, Vincent J. J. Odekerken, Martijn Beudel, Maarten Bot, Gert J. Geurtsen, Dagmar Verbaan, Rob M.A. de Bie, P. Rick Schuurman, Graduate School, Neurosurgery, ANS - Neurodegeneration, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Neurology, APH - Mental Health, and APH - Aging & Later Life
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Male ,Movement disorders ,Deep brain stimulation ,medicine.medical_treatment ,Deep Brain Stimulation ,Anesthesia, General ,behavioral disciplines and activities ,law.invention ,Randomized controlled trial ,Rating scale ,law ,Subthalamic Nucleus ,medicine ,Humans ,Local anesthesia ,Original Investigation ,Aged ,business.industry ,Parkinson Disease ,Middle Aged ,nervous system diseases ,Clinical trial ,Subthalamic nucleus ,Mood ,Treatment Outcome ,Anesthesia ,Female ,Neurology (clinical) ,medicine.symptom ,business ,Microelectrodes ,Anesthesia, Local - Abstract
Importance It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease. Objective To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study. Design, setting, and participants This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS. Interventions Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead. Main outcomes and measures The primary outcome variable was the between-group difference in cognitive, mood, and behavioral adverse effects as measured by a composite score. The secondary outcomes included the Movement Disorders Society Unified Parkinson's Disease Rating Scale, the patient assessment of surgical burden and operative time. Results A total of 110 patients were randomized to awake (local anesthesia; n = 56; mean [SD] age, 60.0 (7.4) years; 40 [71%] male) or to asleep (general anesthesia; n = 54; mean [SD] age, 61.3 [7.9] years; 38 [70%] male) DBS surgery. The 6-month follow-up visit was completed by 103 participants. The proportion of patients with adverse cognitive, mood, and behavioral effects on the composite score was 15 of 52 (29%) after awake and 11 of 51 (22%) after asleep DBS (odds ratio, 0.7 [95% CI, 0.3-1.7]). There was no difference in improvement in the off-medication Movement Disorders Society Unified Parkinson's Disease Rating Scale Motor Examination scores between groups (awake group: mean [SD], -27.3 [17.5] points; asleep group: mean [SD], -25.3 [14.3] points; mean difference, -2.0 [95% CI, -8.1 to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery. Conclusions and relevance There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures. Trial registration trialregister.nl Identifier: NTR5809.
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- 2021
37. Defining the Dorsal STN Border Using 7.0-T MRI: A Comparison to Microelectrode Recordings and Lower Field Strength MRI
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Joke M. Dijk, Rob M.A. de Bie, Okker Verhagen, Matthan W.A. Caan, Vincent J. J. Odekerken, Y Dilai, Maarten Bot, Wouter V. Potters, Pepijn van den Munckhof, P. Richard Schuurman, Graduate School, Neurosurgery, ANS - Systems & Network Neuroscience, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Microcirculation, AMS - Restoration & Development, Neurology, APH - Aging & Later Life, and APH - Methodology
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Male ,Dorsum ,Deep brain stimulation ,Deep Brain Stimulation ,medicine.medical_treatment ,T2 imaging ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Imaging, Three-Dimensional ,0302 clinical medicine ,Subthalamic Nucleus ,medicine ,Humans ,In patient ,Aged ,business.industry ,Parkinson Disease ,Middle Aged ,Magnetic Resonance Imaging ,nervous system diseases ,Subthalamic nucleus ,Microelectrode ,surgical procedures, operative ,nervous system ,Clinical Study ,Female ,Surgery ,Neurology (clinical) ,Lower field ,Nuclear medicine ,business ,Microelectrodes ,therapeutics ,030217 neurology & neurosurgery - Abstract
Background: 7.0-T T2-weighted MRI offers excellent visibility of the subthalamic nucleus (STN), which is used as a target for deep brain stimulation (DBS) in Parkinson’s disease (PD). A comparison of 7.0-T MRI to microelectrode recordings (MER) for STN border identification has not been performed. Objective: To compare representation of STN borders on 7.0-T T2 MRI with the borders identified during MER in patients undergoing DBS for PD and to evaluate whether STN identification on 7.0-T T2 MRI leads to alterations in stereotactic target planning. Design/Methods: STN border identification was done using volumetric 7.0-T T2 MRI acquisitions. This was compared to the STN borders identified by MER. STN target planning was independently performed by 3 DBS surgeons on T2 imaging using 1.5-, 3.0-, and 7.0-T MRI. Results: A total of 102 microelectrode tracks were evaluated in 19 patients. Identification of the dorsal STN border was well feasible on 7-T T2, whereas the ventral STN was undistinguishable from the substantia nigra. The dorsal STN border on MRI was located more dorsal than MER in 73% of trajectories. The average distance from MRI to MER border was 0.9 mm (range –4.4 to +3.5 mm). STN target planning showed high correspondence between the 3 field strengths. Conclusion: 7.0-T T2 MRI offers the possibility of easy identification of the dorsal border of the STN. However, higher field strength MRI does not change the planning of the target. Compared to MER, the dorsal border on MRI was located more dorsal in the majority of cases, situating MER activity within STN representation.
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- 2019
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38. Dragon 1 Protocol Manuscript
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R. Korenblik, B. Olij, L. A. Aldrighetti, M. Abu Hilal, M. Ahle, B. Arslan, L. J. van Baardewijk, I. Baclija, C. Bent, C. L. Bertrand, B. Björnsson, M. T. de Boer, S. W. de Boer, R. P. H. Bokkers, I. H. M. Borel Rinkes, S. Breitenstein, R. C. G. Bruijnen, P. Bruners, M. W. Büchler, J. C. Camacho, A. Cappelli, U. Carling, B. K. Y. Chan, D. H. Chang, J. choi, J. Codina Font, M. Crawford, D. Croagh, E. Cugat, R. Davis, D. W. De Boo, F. De Cobelli, J. F. De Wispelaere, O. M. van Delden, M. Delle, O. Detry, R. Díaz-Nieto, A. Dili, J. I. Erdmann, O. Fisher, C. Fondevila, Å. Fretland, F. Garcia Borobia, A. Gelabert, L. Gérard, F. Giuliante, P. D. Gobardhan, F. Gómez, T. Grünberger, D. J. Grünhagen, J. Guitart, J. Hagendoorn, J. Heil, D. Heise, E. Herrero, G. F. Hess, M. H. Hoffmann, R. Iezzi, F. Imani, J. Nguyen, E. Jovine, J. C. Kalff, G. Kazemier, T. P. Kingham, J. Kleeff, O. Kollmar, W. K. G. Leclercq, S. Lopez Ben, V. Lucidi, A. MacDonald, D. C. Madoff, S. Manekeller, G. Martel, A. Mehrabi, H. Mehrzad, M. R. Meijerink, K. Menon, P. Metrakos, C. Meyer, A. Moelker, S. Modi, N. Montanari, J. Navines, U. P. Neumann, P. Peddu, J. N. Primrose, X. Qu, D. Raptis, F. Ratti, F. Ridouani, C. Rogan, U. Ronellenfitsch, S. Ryan, C. Sallemi, J. Sampere Moragues, P. Sandström, L. Sarriá, A. Schnitzbauer, M. Serenari, A. Serrablo, M. L. J. Smits, E. Sparrelid, E. Spüntrup, G. A. Stavrou, R. P. Sutcliffe, I. Tancredi, J. C. Tasse, V. Udupa, D. Valenti, Y. Fundora, T. J. Vogl, X. Wang, S. A. White, W. A. Wohlgemuth, D. Yu, I. A. J. Zijlstra, C. A. Binkert, M. H. A. Bemelmans, C. van der Leij, E. Schadde, R. M. van Dam, UCL - SSS/IREC/IMAG - Pôle d'imagerie médicale, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de chirurgie, UCL - (MGD) Service de radiologie - résonance magnétique, Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), RS: GROW - R2 - Basic and Translational Cancer Biology, Surgery, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: DA BV Medisch Specialisten Radiologie (9), RS: Carim - B06 Imaging, MUMC+: MA Heelkunde (9), CCA - Cancer Treatment and quality of life, Radiology and nuclear medicine, ACS - Pulmonary hypertension & thrombosis, Radiology & Nuclear Medicine, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, CCA - Cancer Treatment and Quality of Life, ANS - Cellular & Molecular Mechanisms, ANS - Neuroinfection & -inflammation, ACS - Microcirculation, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Korenblik, R, Olij, B, Aldrighetti, L A, Hilal, M Abu, Ahle, M, Arslan, B, van Baardewijk, L J, Baclija, I, Bent, C, Bertrand, C L, Björnsson, B, de Boer, M T, de Boer, S W, Bokkers, R P H, Rinkes, I H M Borel, Breitenstein, S, Bruijnen, R C G, Bruners, P, Büchler, M W, Camacho, J C, Cappelli, A, Carling, U, Chan, B K Y, Chang, D H, Choi, J, Font, J Codina, Crawford, M, Croagh, D, Cugat, E, Davis, R, De Boo, D W, De Cobelli, F, De Wispelaere, J F, van Delden, O M, Delle, M, Detry, O, Díaz-Nieto, R, Dili, A, Erdmann, J I, Fisher, O, Fondevila, C, Fretland, Å, Borobia, F Garcia, Gelabert, A, Gérard, L, Giuliante, F, Gobardhan, P D, Gómez, F, Grünberger, T, Grünhagen, D J, Guitart, J, Hagendoorn, J, Heil, J, Heise, D, Herrero, E, Hess, G F, Hoffmann, M H, Iezzi, R, Imani, F, Nguyen, J, Jovine, E, Kalff, J C, Kazemier, G, Kingham, T P, Kleeff, J, Kollmar, O, Leclercq, W K G, Ben, S Lopez, Lucidi, V, Macdonald, A, Madoff, D C, Manekeller, S, Martel, G, Mehrabi, A, Mehrzad, H, Meijerink, M R, Menon, K, Metrakos, P, Meyer, C, Moelker, A, Modi, S, Montanari, N, Navines, J, Neumann, U P, Peddu, P, Primrose, J N, Qu, X, Raptis, D, Ratti, F, Ridouani, F, Rogan, C, Ronellenfitsch, U, Ryan, S, Sallemi, C, Moragues, J Sampere, Sandström, P, Sarriá, L, Schnitzbauer, A, Serenari, M, Serrablo, A, Smits, M L J, Sparrelid, E, Spüntrup, E, Stavrou, G A, Sutcliffe, R P, Tancredi, I, Tasse, J C, Udupa, V, Valenti, D, Fundora, Y, Vogl, T J, Wang, X, White, S A, Wohlgemuth, W A, Yu, D, Zijlstra, I A J, Binkert, C A, Bemelmans, M H A, van der Leij, C, Schadde, E, and van Dam, R M
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Liver hypertrophy ,Portal vein embolization (PVE) ,Hepatic Veins ,Accreditation ,MAJOR HEPATECTOMY ,SDG 3 - Good Health and Well-being ,Combined portal- and hepatic vein embolization (PVE ,MULTIPLE ,Hepatectomy ,Humans ,Multicenter Studies as Topic ,Radiology, Nuclear Medicine and imaging ,Cardiac and Cardiovascular Systems ,Prospective Studies ,HEPATOBILIARY SCINTIGRAPHY ,Combined portal- and hepatic vein embolization (PVE/HVE) ,Kardiologi ,Portal Vein ,Liver Neoplasms ,Colorectal cancer liver metastases (CRLM) ,Hepatic vein embolization (HVE) ,HVE) ,Future liver remnant (FLR) ,Hypertrophy ,Embolization, Therapeutic ,2-STAGE HEPATECTOMY ,VENOUS DEPRIVATION ,Treatment Outcome ,Liver ,COMPLETE RESECTION ,Cardiology and Cardiovascular Medicine ,Hepatomegaly - Abstract
Study Purpose The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. Methods The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. Results Not applicable. Conclusion DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. Trial Registration Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).
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- 2022
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39. Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study
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Frederik Barkhof, Marnix G. Witte, Merijn E De Swart, Barbara Kiesel, Roelant S Eijgelaar, Wimar A. van den Brink, Alfred Kloet, Philip C. De Witt Hamer, Emmanuel Mandonnet, Marjolein Visser, Hilko Ardon, Marco Conti Nibali, Shawn L. Hervey-Jumper, Wim Bouwknegt, Marco Rossi, L Bello, Georg Widhalm, Tommaso Sciortino, W. Peter Vandertop, Mitchel S. Berger, Albert J S Idema, Domenique M J Müller, Michiel Wagemakers, Julia Furtner, Pierre A. Robe, Seunggu J. Han, Neurosurgery, Surgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, CCA - Cancer Treatment and quality of life, Amsterdam Neuroscience - Neurovascular Disorders, Amsterdam Neuroscience - Systems & Network Neuroscience, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, and CCA - Cancer Treatment and Quality of Life
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medicine.medical_specialty ,time-to-treatment ,Clinical Investigations ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,AcademicSubjects/MED00300 ,Medicine ,Doubling time ,Survival analysis ,medicine.diagnostic_test ,Performance status ,business.industry ,Hazard ratio ,glioblastoma ,waiting list ,medicine.disease ,neurosurgical procedures ,Confidence interval ,Surgery ,Oncology ,030220 oncology & carcinogenesis ,treatment outcome ,AcademicSubjects/MED00310 ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Glioblastoma ,Cohort study - Abstract
BackgroundThe impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery.MethodsAdults with first-time surgery in 2012–2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers.ResultsIncluded were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893–0.994) and larger tumor volume (HR 1.012, 95% CI 1.010–1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery.ConclusionsWith current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.
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- 2021
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40. A phase I/II study of bevacizumab, irinotecan and erlotinib in children with progressive diffuse intrinsic pontine glioma
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Fatma E El-Khouly, Sophie E. M. Veldhuijzen van Zanten, Esther Sanchez Aliaga, W. Peter Vandertop, Dannis G. van Vuurden, N. Harry Hendrikse, Dewi P. Bakker, Gertjan J.L. Kaspers, Marc H. A. Jansen, Pediatric surgery, ACS - Diabetes & metabolism, Amsterdam Neuroscience - Neuroinfection & -inflammation, Radiology and nuclear medicine, CCA - Cancer Treatment and quality of life, Clinical pharmacology and pharmacy, Amsterdam Neuroscience - Neurovascular Disorders, Neurosurgery, Radiology & Nuclear Medicine, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, and CCA - Cancer Treatment and Quality of Life
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,Astrocytoma ,Irinotecan ,Targeted therapy ,Erlotinib Hydrochloride ,Diffuse intrinsic pontine glioma (DIPG) ,SDG 3 - Good Health and Well-being ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Brain Stem Neoplasms ,Humans ,Progression-free survival ,Child ,EGFR inhibitors ,business.industry ,Diffuse Intrinsic Pontine Glioma ,Radiation therapy ,Erlotinib ,Neurology ,Tolerability ,Cohort ,Disease Progression ,Quality of Life ,Clinical Study ,Neurology (clinical) ,business ,medicine.drug - Abstract
Introduction This study investigates the safety, tolerability, and preliminary efficacy of combined treatment with VEGF inhibitor bevacizumab, topoisomerase I inhibitor irinotecan, and EGFR inhibitor erlotinib in children with progressive diffuse intrinsic pontine glioma (DIPG). Methods Biweekly bevacizumab (10 mg/kg) and irinotecan (125 mg/m2) were combined with daily erlotinib. Two cohorts received increasing doses of erlotinib (65 and 85 mg/m2) following a 3 + 3 dose-escalation schedule, until disease progression with a maximum of one year. Dose-limiting toxicities (DLT) were monitored biweekly. Secondary progression free survival (sPFS) and overall survival (OS) were determined based on clinical and radiological response measurements. Quality of life (QoL) during treatment was also assessed. Results Between November 2011 and March 2018, nine patients with disease progression after initial radiotherapy were enrolled. Median PFS at start of the study was 7.3 months (range 3.5–10.0). In the first dose cohort, one patient experienced a DLT (grade III acute diarrhea), resulting in enrollment of three additional patients in this cohort. No additional DLTs were observed in consecutive patients receiving up to a maximum dose of 85 mg/m2. Median sPFS was 3.2 months (range 1.0–10.9), and median OS was 13.8 months (range 9.3–33.0). Overall QoL was stable during treatment. Conclusions Daily erlotinib is safe and well tolerated in doses up to 85 mg/m2 when combined with biweekly bevacizumab and irinotecan in children with progressive DIPG. Median OS of the study patients was longer than known form literature.
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- 2021
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41. The Role of Heparan Sulfate and Neuropilin 2 in VEGFA Signaling in Human Endothelial Tip Cells and Non-Tip Cells during Angiogenesis In Vitro
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Cornelis J.F. Van Noorden, Marchien G. Dallinga, Ingeborg Klaassen, Alinda W. M. Schimmel, Geesje M. Dallinga-Thie, Reinier O. Schlingemann, Yasmin Habani, ACS - Atherosclerosis & ischemic syndromes, ANS - Cellular & Molecular Mechanisms, ANS - Systems & Network Neuroscience, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Diabetes & metabolism, Medical Biology, Ophthalmology, and ACS - Microcirculation
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Vascular Endothelial Growth Factor A ,VEGFA ,Very low-density lipoprotein ,endocrine system ,Angiogenesis ,QH301-705.5 ,Neovascularization, Physiologic ,Apoptosis ,SULF2 ,Lipoproteins, VLDL ,Article ,Extracellular matrix ,chemistry.chemical_compound ,angiogenesis ,Human Umbilical Vein Endothelial Cells ,Humans ,NRP2 ,Biology (General) ,Sprouting angiogenesis ,Gene knockdown ,Chemistry ,General Medicine ,Heparan sulfate ,tip cells ,Vascular Endothelial Growth Factor Receptor-2 ,endothelial cells ,Cell biology ,Neuropilin-2 ,Endothelial stem cell ,Vascular endothelial growth factor A ,cardiovascular system ,HSPG ,Heparitin Sulfate ,Sulfatases ,Signal Transduction - Abstract
During angiogenesis, vascular endothelial growth factor A (VEGFA) regulates endothelial cell (EC) survival, tip cell formation, and stalk cell proliferation via VEGF receptor 2 (VEGFR2). VEGFR2 can interact with VEGFR2 co-receptors such as heparan sulfate proteoglycans (HSPGs) and neuropilin 2 (NRP2), but the exact roles of these co-receptors, or of sulfatase 2 (SULF2), an enzyme that removes sulfate groups from HSPGs and inhibits HSPG-mediated uptake of very low density lipoprotein (VLDL), in angiogenesis and tip cell biology are unknown. In the present study, we investigated whether the modulation of binding of VEGFA to VEGFR2 by knockdown of SULF2 or NRP2 affects sprouting angiogenesis, tip cell formation, proliferation of non-tip cells, and EC survival, or uptake of VLDL. To this end, we employed VEGFA splice variant 121, which lacks an HSPG binding domain, and VEGFA splice variant 165, which does have this domain, in in vitro models of angiogenic tip cells and vascular sprouting. We conclude that VEGFA165 and VEGFA121 have similar inducing effects on tip cells and sprouting in vitro, and that the binding of VEGFA165 to HSPGs in the extracellular matrix does not seem to play a role, as knockdown of SULF2 did not alter these effects. Co-binding of NRP2 appears to regulate VEGFA–VEGFR2-induced sprout initiation, but not tip cell formation. Finally, as the addition of VLDL increased sprout formation but not tip cell formation, and as VLDL uptake was limited to non-tip cells, our findings suggest that VLDL plays a role in sprout formation by providing biomass for stalk cell proliferation.
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- 2021
42. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study
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Michela Botta, Anissa M Tsonas, Janesh Pillay, Leonoor S Boers, Anna Geke Algera, Lieuwe D J Bos, Dave A Dongelmans, Marcus W Hollmann, Janneke Horn, Alexander P J Vlaar, Marcus J Schultz, Ary Serpa Neto, Frederique Paulus, Jesse P. van Akkeren, Cheetel K. Algoe, Rombout B. van Amstel, Onno L. Baur, Pablo van de Berg, Alida E. van den Berg, Dennis C.J.J. Bergmans, Dido I. van den Bersselaar, Freke A. Bertens, Alexander J.G.H. Bindels, Milou M. de Boer, Sylvia den Boer, Leonoor S. Boers, Margriet Bogerd, Lieuwe D.J. Bos, Jennifer S. Breel, Hendrik de Bruin, Sanne de Bruin, Caro L. Bruna, Laura A. Buiteman-Kruizinga, Olaf L. Cremer, Rogier M. Determann, Willem Dieperink, Dave A. Dongelmans, Hildegard S. Franke, Michal S. Galek-Aldridge, Mart J. de Graaff, Laura A. Hagens, Jasper J. Haringman, Sebastiaan T. van der Heide, Pim L.J. van der Heiden, Nanon F.L. Heijnen, Stephan J.P. Hiel, Lotte L. Hoeijmakers, Liselotte Hol, Markus W. Hollmann, Marga E. Hoogendoorn, Robrecht van der Horst, Evy L.K. Ie, Dimitri P. Ivanov, Nicole Juffermans, Eline Kho, Eline S. de Klerk, Ankie W.M.M. Koopman-van Gemert, Matty Koopmans, Songul Kucukcelebi, Michael A. Kuiper, Dylan W. de Lange, Niels van Mourik, Sunny G.L.H. Nijbroek, Marisa Onrust, Evelien A.N. Oostdijk, Charlotte J. Pennartz, Luigi Pisani, Ilse M. Purmer, Thijs C.D. Rettig, Jan-Paul Roozeman, Michiel T.U. Schuijt, Marcus J. Schultz, Mengalvio E. Sleeswijk, Marry R. Smit, Peter E. Spronk, Willemke Stilma, Aart C. Strang, Anissa M. Tsonas, Pieter R. Tuinman, Christel M.A. Valk, Felicia L. Veen-Schra, Lars I. Veldhuis, Patricia van Velzen, Ward H. van der Ven, Alexander P.J. Vlaar, Peter van Vliet, Peter H.J. van der Voort, Louis van Welie, Henrico J.F.T. Wesselink, Hermien H. van der Wier-Lubbers, Bas van Wijk, Tineke Winters, Wing Yi Wong, Arthur R.H. van Zanten, Intensive Care Medicine, Graduate School, AII - Inflammatory diseases, Pulmonology, ACS - Pulmonary hypertension & thrombosis, Anesthesiology, ANS - Neuroinfection & -inflammation, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Nursing, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, AMS - Amsterdam Movement Sciences, AMS - Sports, AMS - Musculoskeletal Health, Orthopedic Surgery and Sports Medicine, General Paediatrics, APH - Aging & Later Life, APH - Personalized Medicine, APH - Quality of Care, APH - Global Health, ACS - Microcirculation, ACS - Heart failure & arrhythmias, ACS - Diabetes & metabolism, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Critical Care, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Urban Vitality, Lectoraat Critical Care, Faculteit Gezondheid, Public and occupational health, Pulmonary medicine, and Intensive care medicine
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,artificial ,RESPIRATORY-DISTRESS-SYNDROME ,netherlands ,respiration, artificial ,nederland ,03 medical and health sciences ,0302 clinical medicine ,cohort studies ,Intensive care ,Heart rate ,middle aged ,covid-19/therapy ,Medicine ,EPIDEMIOLOGY ,030212 general & internal medicine ,kunstmatige beademing ,Tidal volume ,business.industry ,Retrospective cohort study ,Articles ,INTENSIVE-CARE UNITS ,Prone position ,retrospective studies ,030228 respiratory system ,covid-19 ,Emergency medicine ,Breathing ,PATTERNS ,treatment outcome ,Observational study ,ARDS ,business ,respiration ,Cohort study - Abstract
Background: Little is known about the practice of ventilation management in patients with COVID-19. We aimed to describe the practice of ventilation management and to establish outcomes in invasively ventilated patients with COVID-19 in a single country during the first month of the outbreak. Methods: PRoVENT-COVID is a national, multicentre, retrospective observational study done at 18 intensive care units (ICUs) in the Netherlands. Consecutive patients aged at least 18 years were eligible for participation if they had received invasive ventilation for COVID-19 at a participating ICU during the first month of the national outbreak in the Netherlands. The primary outcome was a combination of ventilator variables and parameters over the first 4 calendar days of ventilation: tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and ICU complications. Patient-centred outcomes were ventilator-free days at day 28, duration of ventilation, duration of ICU and hospital stay, and mortality. PRoVENT-COVID is registered at ClinicalTrials.gov (NCT04346342). Findings: Between March 1 and April 1, 2020, 553 patients were included in the study. Median tidal volume was 6·3 mL/kg predicted bodyweight (IQR 5·7–7·1), PEEP was 14·0 cm H2O (IQR 11·0–15·0), and driving pressure was 14·0 cm H2O (11·2–16·0). Median respiratory system compliance was 31·9 mL/cm H2O (26·0–39·9). Of the adjunctive treatments for refractory hypoxaemia, prone positioning was most often used in the first 4 days of ventilation (283 [53%] of 530 patients). The median number of ventilator-free days at day 28 was 0 (IQR 0–15); 186 (35%) of 530 patients had died by day 28. Predictors of 28-day mortality were gender, age, tidal volume, respiratory system compliance, arterial pH, and heart rate on the first day of invasive ventilation. Interpretation: In patients with COVID-19 who were invasively ventilated during the first month of the outbreak in the Netherlands, lung-protective ventilation with low tidal volume and low driving pressure was broadly applied and prone positioning was often used. The applied PEEP varied widely, despite an invariably low respiratory system compliance. The findings of this national study provide a basis for new hypotheses and sample size calculations for future trials of invasive ventilation for COVID-19. These data could also help in the interpretation of findings from other studies of ventilation practice and outcomes in invasively ventilated patients with COVID-19. Funding: Amsterdam University Medical Centers, location Academic Medical Center.
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- 2021
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43. Risk of Rupture After Intracranial Aneurysm Growth
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Jill Abrigo, Johanna Kuhmonen, Yoshiaki Shiokawa, Ido R. van den Wijngaard, Timo Koivisto, Akio Morita, René van den Berg, Hieronymus D. Boogaarts, Toshihiro Ishibashi, Gabriel J.E. Rinkel, Ronit Agid, Mario Teo, Jaakko Rinne, Junta Moroi, Keiji Igase, Mervyn D.I. Vergouwen, Nima Etminan, Melissa Rahi, Antti E. Lindgren, Laura T. van der Kamp, Nicolaas P.A. Zuithoff, Katharina A. M. Hackenberg, Irene C. van der Schaaf, Jerome St George, W. Peter Vandertop, Ivan Radovanovic, Yuichi Murayama, Dagmar Verbaan, George K.C. Wong, Neurosurgery, ANS - Neurovascular Disorders, Radiology and Nuclear Medicine, ACS - Microcirculation, ANS - Systems & Network Neuroscience, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, and Amsterdam Neuroscience - Systems & Network Neuroscience
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Adult ,Male ,Risk ,medicine.medical_specialty ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Kaplan-Meier Estimate ,Aneurysm, Ruptured ,Aneurysm rupture ,Cohort Studies ,Aneurysm ,medicine.artery ,Cox proportional hazards regression ,medicine ,Anterior cerebral artery ,Humans ,Posterior communicating artery ,Aged ,Retrospective Studies ,business.industry ,Hazard ratio ,Absolute risk reduction ,Correction ,Intracranial Aneurysm ,Middle Aged ,medicine.disease ,Surgery ,Middle cerebral artery ,Female ,Neurology (clinical) ,business - Abstract
Item does not contain fulltext IMPORTANCE: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear. OBJECTIVE: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth. EXPOSURES: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging. MAIN OUTCOMES AND MEASURES: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. RESULTS: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%. CONCLUSION AND RELEVANCE: Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth.
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- 2021
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44. Tranexamic acid for chronic subdural hematoma
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Lucas G Westerink, Rob Nabuurs, Steven Immenga, René van den Berg, Roger Lodewijkx, Dagmar Verbaan, René Post, Anil Can, William P. Vandertop, Neurosurgery, Graduate School, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Radiology and Nuclear Medicine, ACS - Microcirculation, Radiology and nuclear medicine, Amsterdam Neuroscience - Neurovascular Disorders, and Amsterdam Neuroscience - Systems & Network Neuroscience
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medicine.medical_specialty ,Weakness ,law.invention ,Hematoma ,Chronic subdural hematoma ,Randomized controlled trial ,law ,Trephining ,medicine ,Humans ,neurosurgery ,business.industry ,General Medicine ,medicine.disease ,Surgery ,Volume measurements ,Treatment Outcome ,Tranexamic Acid ,Radiological weapon ,Hematoma, Subdural, Chronic ,Drainage ,Neurology (clinical) ,Neurosurgery ,medicine.symptom ,business ,Tranexamic acid ,medicine.drug - Abstract
Background There is no consensus on optimal treatment for a chronic subdural hematoma (cSDH). In patients with only moderate symptoms treatment with tranexamic acid (TXA) has been suggested. We report off-label use of TXA in seven patients. Methods Between August 2016 and May 2018 we identified seven patients for primary conservative treatment with TXA until satisfactory clinical and radiological status was achieved. Primary outcome was surgery for cSDH evacuation. Radiological follow-up was performed at regular intervals for hematoma volume measurements. Results Five patients experienced complete resolution of symptoms, one patient had a burr-hole craniostomy five days after initiation of TXA treatment due to an increase of left-sided weakness and dysarthria and in one patient symptoms did not improve. Median follow-up was 15 weeks (range 6-25, without the operated patient). The median total volume before start of treatment was 83 mL (range 11-137) for all patients. At the last follow-up, the median total volume in the non-operated patients decreased by 73% to 33 mL (range 0-77). Conclusions TXA could be considered as primary medical treatment in patients with a cSDH and mild symptoms. The results of current randomized clinical trials must be awaited.
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- 2021
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45. Treatment of symptomatic postoperative pelvic lymphoceles: A systematic review
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Ijsbrand A.J. Zijlstra, Anne S. ten Hove, Ming Y. Tjiong, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), Radiology and nuclear medicine, Graduate School, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, and ACS - Microcirculation
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medicine.medical_specialty ,Percutaneous ,medicine.medical_treatment ,Lymphocele ,030218 nuclear medicine & medical imaging ,Pelvis ,03 medical and health sciences ,Embolization ,0302 clinical medicine ,Postoperative Complications ,Sclerotherapy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Percutaneous catheter drainage ,Interventional radiology ,medicine.diagnostic_test ,business.industry ,General Medicine ,medicine.disease ,Confidence interval ,Surgery ,Fine-needle aspiration ,030220 oncology & carcinogenesis ,Relative risk ,Drainage ,Neoplasm Recurrence, Local ,Percutaneous fine needle aspiration ,business - Abstract
Purpose: A broad range of therapeutic options exists for symptomatic postoperative lymphoceles. However, no consensus exists on what is the optimal therapy. In this study, we aimed to compare the efficacy of currently available radiologic interventions in terms of number of successful interventions, number of recurrences, and number of complications. Methods: A systematic review was conducted with a pre-defined search strategy for PubMed, EMBASE, and Cochrane databases from inception until September 2019. Quality assessment was performed using the ‘Risk Of Bias In Non-randomized Studies - of Interventions’ tool. Statistical heterogeneity was assessed using the I2 and χ2 test and a meta-analysis was considered for studies reporting on multiple interventions. Results: 37 eligible studies including 732 lymphoceles were identified. Proportions of successful interventions for percutaneous fine needle aspiration, percutaneous catheter drainage, percutaneous catheter drainage with delayed or instantaneous addition of sclerotherapy, and embolization were as follows: 0.341 (95% confidence interval [CI]: 0.185−0.542), 0.612 (95% CI: 0.490−0.722), 0.890 (95% CI: 0.781−0.948), 0.872 (95% CI: 0.710−0.949), 0.922 (95% CI: 0.731−0.981). Random-effects meta-analysis of seven studies revealed a pooled relative risk for percutaneous catheter drainage with delayed addition of sclerotherapy of 1.57 (95% CI: 1.17–2.10) when compared to percutaneous catheter drainage alone. The risk of bias in this study was severe. Conclusions: This systematic review demonstrates that the success rates of percutaneous catheter drainage with sclerotherapy are more favorable when compared to percutaneous catheter drainage alone in the treatment of postoperative pelvic lymphoceles. Overall, percutaneous catheter drainage with delayed addition of sclerotherapy, and embolization showed the best outcomes.
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- 2021
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46. Biliopancreatic and biliary leak after pancreatoduodenectomy treated by percutaneous transhepatic biliary drainage
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A.C. Henry, Olivier R. Busch, Jan A. Vos, Marc van Leersum, Ijsbrand A.J. Zijlstra, Armand B. Lamers, Marco J. L. van Strijen, Hjalmar C. van Santvoort, Marc G. Besselink, Krijn P. van Lienden, I. Quintus Molenaar, Lieke Hofman, Daniel A. F. van den Heuvel, F. Jasmijn Smits, Sanne M. Schreuder, Otto M. van Delden, Wouter W. te Riele, Surgery, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, CCA -Cancer Center Amsterdam, ACS - Microcirculation, ANS - Neurovascular Disorders, ANS - Systems & Network Neuroscience, Graduate School, and CCA - Imaging and biomarkers
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Leak ,medicine.medical_specialty ,Biliary drainage ,Percutaneous ,Hepatology ,business.industry ,Biliary Tract Diseases ,Technical success ,Gastroenterology ,Biliary leak ,medicine.disease ,Surgery ,Pancreaticoduodenectomy ,Biliary Tract Surgical Procedures ,Pancreatic fistula ,Anastomotic leakage ,medicine ,Drainage ,Humans ,Percutaneous transhepatic biliary drainage ,business ,Retrospective Studies - Abstract
Background Complementary to percutaneous intra-abdominal drainage, percutaneous transhepatic biliary drainage (PTBD) might ameliorate healing of pancreatic fistula and biliary leakage after pancreatoduodenectomy by diversion of bile from the site of leakage. This study evaluated technical and clinical outcomes of PTBD for this indication. Methods All patients undergoing PTBD for leakage after pancreatoduodenectomy were retrospectively evaluated in two tertiary pancreatic centers (2014–2019). Technical success was defined as external biliary drainage. Clinical success was defined as discharge with a resolved leak, without additional surgical interventions for anastomotic leakage other than percutaneous intra-abdominal drainage. Results Following 822 pancreatoduodenectomies, 65 patients (8%) underwent PTBD. Indications were leakage of the pancreaticojejunostomy (n = 25; 38%), hepaticojejunostomy (n = 15; 23%) and of both (n = 25; 38%). PTBD was technically successful in 64 patients (98%) with drain revision in 40 patients (63%). Clinical success occurred in 60 patients (94%). Leakage resolved after median 33 days (IQR 21–60). PTBD related complications occurred in 23 patients (35%), including cholangitis (n = 14; 21%), hemobilia (n = 7; 11%) and PTBD related bleeding requiring re-intervention (n = 4; 6%). In hospital mortality was 3% (n = 2). Conclusion Although drain revisions and complications are common, PTBD is highly feasible and appears to be effective in the treatment of biliopancreatic leakage after pancreatoduodenectomy.
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- 2021
47. Invasive and Non-invasive Neurostimulation for OCD
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Pelle de Koning, Damiaan Denys, Ingo Willuhn, Ilse Graat, Roel J. T. Mocking, Eva Dijkstra, Nienke Vulink, Bastijn J.G. van den Boom, Isidoor O. Bergfeld, Tara Arbab, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Graduate School, ANS - Cellular & Molecular Mechanisms, ANS - Systems & Network Neuroscience, APH - Mental Health, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Deep brain stimulation ,medicine.medical_treatment ,behavioral disciplines and activities ,03 medical and health sciences ,0302 clinical medicine ,Neuroimaging ,medicine ,Effective treatment ,Treatment outcome ,Neurostimulation ,030304 developmental biology ,0303 health sciences ,business.industry ,Neuromodulation ,Non invasive ,Ventral striatum ,Working mechanisms ,Neuromodulation (medicine) ,Transcranial magnetic stimulation ,medicine.anatomical_structure ,nervous system ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
It becomes increasingly clear that (non-)invasive neurostimulation is an effective treatment for obsessive-compulsive disorder (OCD). In this chapter we review the available evidence on techniques and targets, clinical results including a meta-analysis, mechanisms of action, and animal research. We focus on deep brain stimulation (DBS), but also cover non-invasive neurostimulation including transcranial magnetic stimulation (TMS). Data shows that most DBS studies target the ventral capsule/ventral striatum (VC/VS), with an overall 76% response rate in treatment-refractory OCD. Also TMS holds clinical promise. Increased insight in the normalizing effects of neurostimulation on cortico-striatal-thalamic-cortical (CSTC) loops – through neuroimaging and animal research – provides novel opportunities to further optimize treatment strategies. Advancing clinical implementation of neurostimulation techniques is essential to ameliorate the lives of the many treatment-refractory OCD patients.
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- 2021
48. Structural and functional correlates of subthalamic deep brain stimulation-induced apathy in Parkinson's disease
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P. Richard Schuurman, Anne-Fleur van Rootselaar, Lennard I. Boon, Arjan Hillebrand, Gert J. Geurtsen, Wouter V. Potters, Henk W. Berendse, Cornelis J. Stam, Rob M.A. de Bie, Thomas J.C. Zoon, Naomi Prent, Maarten Bot, Odile A. van den Heuvel, Pepijn van den Munckhof, Neurology, ANS - Neurodegeneration, Neurosurgery, ANS - Systems & Network Neuroscience, Medical Psychology, APH - Mental Health, ANS - Brain Imaging, APH - Aging & Later Life, Amsterdam Neuroscience - Systems & Network Neuroscience, Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Neurodegeneration, and Amsterdam Neuroscience - Brain Imaging
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medicine.medical_specialty ,Parkinson's disease ,Deep brain stimulation ,medicine.medical_treatment ,Apathy ,Biophysics ,Stimulation ,050105 experimental psychology ,lcsh:RC321-571 ,03 medical and health sciences ,Functional connectivity ,0302 clinical medicine ,Subthalamic Nucleus ,Internal medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Anterior cingulate cortex ,business.industry ,General Neuroscience ,05 social sciences ,Dopaminergic ,Magnetoencephalography ,Parkinson Disease ,medicine.disease ,Dorsolateral prefrontal cortex ,Subthalamic nucleus ,Treatment Outcome ,medicine.anatomical_structure ,nervous system ,Parkinson’s disease ,Cardiology ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Background: Notwithstanding the large improvement in motor function in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS), apathy may increase. Postoperative apathy cannot always be related to a dose reduction of dopaminergic medication and stimulation itself may play a role. Objective: We studied whether apathy in DBS-treated PD patients could be a stimulation effect. Methods: In 26 PD patients we acquired apathy scores before and >6 months after DBS of the subthalamic nucleus (STN). Magnetoencephalography recordings (ON and OFF stimulation) were performed ≥6 months after DBS placement. Change in apathy severity was correlated with (i) improvement in motor function and dose reduction of dopaminergic medication, (ii) stimulation location (merged MRI and CT-scans) and (iii) stimulation-related changes in functional connectivity of brain regions that have an alleged role in apathy. Results: Average apathy severity significantly increased after DBS (p < 0.001) and the number of patients considered apathetic increased from two to nine. Change in apathy severity did not correlate with improvement in motor function or dose reduction of dopaminergic medication. For the left hemisphere, increase in apathy was associated with a more dorsolateral stimulation location (p = 0.010). The increase in apathy severity correlated with a decrease in alpha1 functional connectivity of the dorsolateral prefrontal cortex (p = 0.006), but not with changes of the medial orbitofrontal or the anterior cingulate cortex. Conclusions: The present observations suggest that apathy after STN-DBS is not necessarily related to dose reductions of dopaminergic medication, but may be an effect of the stimulation itself. This highlights the importance of determining optimal DBS settings based on both motor and non-motor symptoms.
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- 2021
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49. Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
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François Rustenburg, Cyra E. Leurs, Bakhos A. Tannous, Maud Tjerkstra, Farrah J. Mateen, Sander Idema, Bauke Ylstra, W. Peter Vandertop, Laurine E. Wedekind, Nik Sol, Adrienne Vancura, Edward Post, William P.J. Leenders, R. Jonas A. Nilsson, B. Moraal, Jip Ramaker, Anna C. Navis, Kenn Zwaan, Ann Hoeben, Sjors G J G In 't Veld, Jihane Tannous, Joep Killestein, Philip C. De Witt Hamer, Jaap C. Reijneveld, Thomas Wurdinger, Heleen Verschueren, Pieter Wesseling, Pepijn Schellen, David P. Noske, Myron G. Best, Interne Geneeskunde, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Neurology, Neurosurgery, Pathology, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Systems & Network Neuroscience, Radiology and nuclear medicine, CCA - Cancer Treatment and Quality of Life, ANS - Neurovascular Disorders, Graduate School, and ANS - Systems & Network Neuroscience
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Oncology ,blood platelets ,NEUROONCOLOGY ,liquid biopsies ,0302 clinical medicine ,Tumor Microenvironment ,Platelet ,RNA, Neoplasm ,Neoplasm Metastasis ,Aged, 80 and over ,lcsh:R5-920 ,0303 health sciences ,Brain Neoplasms ,swarm intelligence ,Middle Aged ,CANCER ,3. Good health ,machine learning ,030220 oncology & carcinogenesis ,Disease Progression ,medicine.symptom ,POOR SURVIVAL ,lcsh:Medicine (General) ,MESSENGER-RNA ,Algorithms ,Adult ,medicine.medical_specialty ,Pseudo progression ,Multiple Sclerosis ,RNA Splicing ,EANO GUIDELINE ,Asymptomatic ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Aged ,Monitoring, Physiologic ,030304 developmental biology ,Cancer och onkologi ,business.industry ,Multiple sclerosis ,glioblastoma ,Cancer ,RNA ,BLOOD-PLATELETS ,medicine.disease ,ADJUVANT TEMOZOLOMIDE ,Survival Analysis ,tumor-educated platelets ,ROC Curve ,Case-Control Studies ,Cancer and Oncology ,CELLS ,business ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,RESPONSE ASSESSMENT ,LUNG ,Glioblastoma ,Brain metastasis - Abstract
Summary Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74–0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95–0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70–1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients., Graphical Abstract, Highlights TEP RNA enables blood-based brain tumor diagnostics TEP RNA is dynamic throughout anti-tumor treatment TEP RNA may be employed for therapy monitoring, Sol et al. show that tumor-educated platelets (TEPs) can be employed for detection of glioblastoma. Glioblastoma TEP RNA profiles can be differentiated from patients with metastatic brain cancer or MS. Furthermore, the tumor signals in TEPs are dynamic, indicating that TEPs can be employed for blood-based therapy monitoring.
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- 2020
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50. Magnetic resonance imaging-based synthetic computed tomography of the lumbar spine for surgical planning: a clinical proof-of-concept
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W. Peter Vandertop, Peter R. Seevinck, Victor E. Staartjes, Marijn van Stralen, Marc L. Schröder, MOVE Research Institute, Neurosurgery, ANS - Neurovascular Disorders, and ANS - Systems & Network Neuroscience
- Subjects
Neuronavigation ,Computed tomography ,image conversion ,Surgical planning ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Pedicle screw ,Lumbar Vertebrae ,medicine.diagnostic_test ,business.industry ,lumbar spine ,deep learning ,imaging ,Magnetic resonance imaging ,General Medicine ,Cone-Beam Computed Tomography ,artificial intelligence ,Magnetic Resonance Imaging ,Acquisition Protocol ,machine learning ,Proof of concept ,Surgery ,Lumbar spine ,Neurology (clinical) ,Neural Networks, Computer ,business ,Nuclear medicine ,Tomography, X-Ray Computed ,030217 neurology & neurosurgery - Abstract
OBJECTIVEComputed tomography scanning of the lumbar spine incurs a radiation dose ranging from 3.5 mSv to 19.5 mSv as well as relevant costs and is commonly necessary for spinal neuronavigation. Mitigation of the need for treatment-planning CT scans in the presence of MRI facilitated by MRI-based synthetic CT (sCT) would revolutionize navigated lumbar spine surgery. The authors aim to demonstrate, as a proof of concept, the capability of deep learning–based generation of sCT scans from MRI of the lumbar spine in 3 cases and to evaluate the potential of sCT for surgical planning.METHODSSynthetic CT reconstructions were made using a prototype version of the “BoneMRI” software. This deep learning–based image synthesis method relies on a convolutional neural network trained on paired MRI-CT data. A specific but generally available 4-minute 3D radiofrequency-spoiled T1-weighted multiple gradient echo MRI sequence was supplemented to a 1.5T lumbar spine MRI acquisition protocol.RESULTSIn the 3 presented cases, the prototype sCT method allowed voxel-wise radiodensity estimation from MRI, resulting in qualitatively adequate CT images of the lumbar spine based on visual inspection. Normal as well as pathological structures were reliably visualized. In the first case, in which a spiral CT scan was available as a control, a volume CT dose index (CTDIvol) of 12.9 mGy could thus have been avoided. Pedicle screw trajectories and screw thickness were estimable based on sCT findings.CONCLUSIONSThe evaluated prototype BoneMRI method enables generation of sCT scans from MRI images with only minor changes in the acquisition protocol, with a potential to reduce workflow complexity, radiation exposure, and costs. The quality of the generated CT scans was adequate based on visual inspection and could potentially be used for surgical planning, intraoperative neuronavigation, or for diagnostic purposes in an adjunctive manner.
- Published
- 2020
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