1,173 research outputs found

    Intracranial aneurysms in patients with Kawasaki disease or thoracic aortic aneurysms

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    Saccular intracranial aneurysm (sIA) is the most common type of IAs and characterized by outpoching sac with a neck arising from the cerebral artery wall. Pathophysiology of IAs are still poorly understood. Fusiform IA is a focal circumferential dilatation of the cerebral artery and unlike sIAs, do not have aneurysm neck, which make their treatment more complex compared to sIAs. The primary goal in the study I and II were to evaluate if Kawasaki disease (KD) is associated with increased risk for IAs (I) and white matter hyperintensities (WMH) (II); in the study III if sIAs are related with increased risk for thoracic aortic aneurysms (TAA) or dilatations (TAD); and in the study IV was to evaluate outcomes of flow diverter stent (FD) treatment of the ruptured posterior circulation fusiform IAs. In the study (I and II) 40 adults with a history of KD in a childhood were screened with brain Magnetic Resonance Imaging and Angiography for IAs and brain WMHs. No IAs were found in KD patients, which is significantly under the prevalence of 10% (95% CI 0%-8.8%, p = 0.03) that is the recommended limit for IA screening. In the study (II), we found that Kawasaki disease is related with increased WMH burden compared to age- and sex-matched migraine controls. Our study suggests that KD is not associated with IAs, but instead is associated with increased WMH burden, indicating long-term cerebrovascular involvement of KD. In the study (III) we retrospectively reviewed 411 patients with sIAs and available imaging studies (computed tomography or magnetic resonance imaging) of all thoracic aortic segments for TADs and TAAs. The prevalence of TADs and TAAs were 18% and 8%. Rheumatic disease and alcohol abuse were significant risk factors for TADs/TAAs. Our results suggests that sIAs might be associated with increased risk for TAAs and TADs. In the study (IV) five patients with ruptured posterior circulation fusiform aneurysms and treated with a FD were reviewed rertrospectively. We found that FD is a feasible treatment option for ruptured fusiform posterior circulation IAs, with a high aneurysm occlusion rate (100% at 6-months) and 80% of patients had a good outcome. However, FD treatment carries a significant risk for complications and should be considered only when other treatment options are not available.Aivovaltimoaneurysmien yhteys Kawasakin tautiin ja rinta-aortan laajentumiin. Sakkulaarinen aivovaltimoaneurysma (sIA) on yleisin aivoaneurysmatyyppi. SIA on aivovaltimoiden seinämästä työntyvä paikallinen pullistuma, joka yhdistyy aivovaltimon seinämään kaulalla. Fusiforminen IA on aivovaltimon paikallinen laajentuma ja toisin kuin sIA:ssa, fusiformisessa IA:ssa ei ole erillistä kaulaa, joka tekee hoidosta haastavaa. IA:ien syntymisen patofysiologia tunnetaan huonosti. Tutkimuksien (I) ja (II) tavoitteena oli selvittää, onko lapsuuden Kawasakin taudilla yhteyttä suurentuneeseen riskiin vuotamattomille IA:lle ja aivojen valkean aineen muutoksille. Tutkimuksen (III) tavoitteena oli selvittää ovatko sIA:t yhteydessä suurentuneeseen riskiin torakaaliaortan aneurysmille (TAA) tai dilataatioille (TAD). Tutkimuksen (IV) tarkoituksena oli selvittää flow diverter stenttihoidon (FD) tuloksia vuotaneiden takaverenkierron fusiformisten IA:ien hoidossa. Tutkimuksissa (I ja II) 40:lle lapsuudessa Kawasakin taudin sairastaneelle potilaalle suoritettiin aivojen ja aivoverisuonten magneettikuvaus IA:ien ja WMH muutosten seulomiseksi. Valkean aineen muutosten määrää verrattiin ikä- ja sukupuolivakioituihin verrokkeihin (migreenipotilaat). Kawasakin taudin sairastaneilla potilailla ei todettu IA:a ja prevalenssi oli merkittävästi alle suositellun IA:en seulontarajan 10 % (95 % CI 0 %-8.8 %, p= 0.03). Sen sijaan Kawasakin taudin sairastaneilla henkilöillä oli merkittävästi enemmän valkean aineen muutoksia verrokkeihin nähden, viitaten siihen, että Kawasakin taudilla voi olla myös aivoverisuoniin kohdistuvia vaikutuksia. Tutkimuksessa (III) analysoimme retrospektiivisetsti 411 sIA potilasta, joilla oli kuvannettu rinta-aortta tietokonetomografialla tai magneettikuvauksella. TAD:n ja TAA:n prevalenssi oli 18 % ja 8 %. Reumasairaus ja alkoholin väärinkäyttö lisäsivät merkittävästi riskiä TAD:lle/TAA:lle. SIA:iin saattaa liittyä suurentunut riski TAD:lle/TAA:lle. Tutkimuksessa (IV) analysoimme retrospektiivisesti viisi potilasta, joiden vuotanut aivojen takaverenkierron fusiforminen IA oli hoidettu FD:llä. Aneurysmien hoitotulokset olivat hyviä FD:llä ja 80 % potilaista toipuivat hyvin. FD hoitoon liittyy kuitenkin merkittäviä komplikaatioriskejä ja FD hoitoa tulisi miettiä vuotaneissa aneurysmissa vain, jos muut hoitovaihtoehdot katsotaan mahdottomiksi

    Application of Advanced MRI to Fetal Medicine and Surgery

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    Robust imaging is essential for comprehensive preoperative evaluation, prognostication, and surgical planning in the field of fetal medicine and surgery. This is a challenging task given the small fetal size and increased fetal and maternal motion which affect MRI spatial resolution. This thesis explores the clinical applicability of post-acquisition processing using MRI advances such as super-resolution reconstruction (SRR) to generate optimal 3D isotropic volumes of anatomical structures by mitigating unpredictable fetal and maternal motion artefact. It paves the way for automated robust and accurate rapid segmentation of the fetal brain. This enables a hierarchical analysis of volume, followed by a local surface-based shape analysis (joint spectral matching) using mathematical markers (curvedness, shape index) that infer gyrification. This allows for more precise, quantitative measurements, and calculation of longitudinal correspondences of cortical brain development. I explore the potential of these MRI advances in three clinical settings: fetal brain development in the context of fetal surgery for spina bifida, airway assessment in fetal tracheolaryngeal obstruction, and the placental-myometrial-bladder interface in placenta accreta spectrum (PAS). For the fetal brain, MRI advances demonstrated an understanding of the impact of intervention on cortical development which may improve fetal candidate selection, neurocognitive prognostication, and parental counselling. This is of critical importance given that spina bifida fetal surgery is now a clinical reality and is routinely being performed globally. For the fetal trachea, SRR can provide improved anatomical information to better select those pregnancies where an EXIT procedure is required to enable the fetal airway to be secured in a timely manner. This would improve maternal and fetal morbidity outcomes associated with haemorrhage and hypoxic brain injury. Similarly, in PAS, SRR may assist surgical planning by providing enhanced anatomical assessment and prediction for adverse peri-operative maternal outcome such as bladder injury, catastrophic obstetric haemorrhage and maternal death

    Intracranial hypertension in syndromic craniosynostosis:Prevalence, detection, pathophysiology and treatment

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    This thesis highlights several aspects regarding the clinical course and treatment of syndromic craniosynostosis. First, we evaluate the prevalence of (syndromic) craniosynostosis: how many children are born with this rare condition in the Netherlands? Thereafter, we focus on the detection of (risk factors for) elevated intracranial pressure: can we use the head circumference as a reliable indicator of the intracranial volume? Can we improve the detection of intracranial hypertension by adding retina scans to the follow-up protocol? Also, the consequences of raised intracranial pressure are assessed: do we see changes in brain cortical thickness? Or in the retinal thickness and/or visual acuity? Finally, we evaluated the treatment protocol for Muenke and Saehtre-Chotzen syndrome: how do we prevent and treat raised intracranial pressure in these syndromes? Should we focus on intracranial hypertension only?<br/

    Interictal Network Dynamics in Paediatric Epilepsy Surgery

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    Epilepsy is an archetypal brain network disorder. Despite two decades of research elucidating network mechanisms of disease and correlating these with outcomes, the clinical management of children with epilepsy does not readily integrate network concepts. For example, network measures are not used in presurgical evaluation to guide decision making or surgical management plans. The aim of this thesis was to investigate novel network frameworks from the perspective of a clinician, with the explicit aim of finding measures that may be clinically useful and translatable to directly benefit patient care. We examined networks at three different scales, namely macro (whole brain diffusion MRI), meso (subnetworks from SEEG recordings) and micro (single unit networks) scales, consistently finding network abnormalities in children being evaluated for or undergoing epilepsy surgery. This work also provides a path to clinical translation, using frameworks such as IDEAL to robustly assess the impact of these new technologies on management and outcomes. The thesis sets up a platform from which promising computational technology, that utilises brain network analyses, can be readily translated to benefit patient care

    Deep brain stimulation for disorders of consciousness and diminished motivation:A search for awakenings

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    This thesis deals with patients who are amongst the most severely affected after severe brain injury: those with permanent disorders of consciousness or diminished motivation. The research in this thesis is an attempt to improve consciousness and the general behavioral performance of these patients with the use of experimental interventions, including medication (such as zolpidem), and more invasive procedures, such as deep brain stimulation (DBS). The thesis contains extensive descriptions of the role of the intralaminar thalamus in the arousal regulation system, the importance of recognizing and treating secondary complications after brain injury, such as hydrocephalus, as well as a pathophysiological elaboration on akinetic mutism: a severe disorder of diminished motivation. Moreover, it describes the neurophysiological changes that accompany the paradoxical effects of zolpidem, a sleeping pill that temporarily induces ‘awakenings’ in some patients with severe brain injury. Further, it describes the first clinical and neurophysiological results of an N=6 trial of DBS in patients with a minimally conscious state and shows the importance of recognizing pathological changes from the brain’s ‘physiological baseline’ that seem to disturb normal brain functions. The thesis concludes with a description of the use of moral case deliberation in dealing with research dilemmas in patients with loss of autonomy after severe brain injury

    Intracranial Pressure Monitoring in Cerebrospinal Fluid Dynamics Disturbances

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    There are numerous gaps in the knowledge of Intracranial Pressure (ICP) physiology and Cerebrospinal Fluid (CSF) dynamics. This PhD answers some of the research questions posed by these gaps, through the use of invasive ICP monitoring in patients with suspected CSF dynamics disturbances. Research on CSF dynamics disturbances has mainly focused on conditions that cause high ICP, whilst only sparse attention has been centred on low CSF pressure/volume states. Chapter 3 and chapter 4 of this thesis are focused on Spontaneous Intracranial Hypotension (SIH). Chapter 3 is a comprehensive systematic review and meta-analysis of the clinical presentation, investigation findings and treatment outcomes of this disease. Chapter 4 is an observational study that investigated the utility of invasive ICP monitoring when there is diagnostic uncertainty for SIH. This study demonstrates that, in selected cases, ICP monitoring can be useful and confirm a low-pressure state in 8% of the patients and identify a paradoxical clinical presentation with an underlying high-pressure state in 16% of the patients. Chapters 5 and 6 provide evidence on the way that ICP and brain compliance respond to external variables, such as changes in posture and shunt setting adjustments. Chapter 5 is a retrospective observational study that describes the changes of ICP and pulse amplitude with different postures. Chapter 6 is a retrospective observational study investigating the effect of valve setting adjustments on ICP. This study demonstrates that paradoxical changes in ICP following differential pressure valves setting changes can occur. Chapters 7 and 8 investigate the possibility of replacing invasive ICP monitoring with non-invasive biomarkers of raised ICP. Chapter 7 demonstrated the association between higher ICP measurements and the absence of spontaneous retinal venous pulsations detected with infrared video recordings. Chapter 8 demonstrates the utility of integrating ophthalmic and imaging biomarkers to predict raised ICP

    Pathogenesis of Tuberculous Meningitis

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    Tuberculous Meningitis (TBM) is the most severe form of tuberculosis, affecting >100,000 people/year (Wilkinson et al., 2017, Marais et al., 2011). TBM arises when Mycobacterium tuberculosis crosses the blood-brain barrier, causing severe inflammation and tissue damage (Davis et al., 2019b). Inflammation also initiates metabolic derangement, mediating neuronal injury despite treatment (Davis et al., 2019b, Rohlwink et al., 2019, Rohlwink et al., 2017). In HIV-1 coinfection, TBM mortality is reported to be as high as 50% (Marais et al., 2011). Half of TBM survivors are affected by neurological disability (Thwaites et al., 2003). Thus, improved therapeutic strategies are needed, including targeted and nuanced modification of the injurious host inflammatory response. To develop these, we must understand the immune induced tissue damaging responses and metabolic disturbances contributing to brain damage which drive acute and long-term neurological complications. The goals of this PhD thesis were to investigate the safety of a novel drug regimen in HIV-associated TBM and through a series of nested sub-studies, understand pathogenic mechanisms of acute and long term neurological sequalae in TBM. Specifically, this thesis presents: i) A study protocol and results from a phase 2A randomised controlled trial of high dose rifampicin and adjunctive linezolid with and without aspirin in HIV-associated TBM ii) Results from a case-control study of cognitive and functional outcomes in HIV-associated TBM iiI) Results from a study investigating in vivo markers of brain injury in HIV-associated TBM via magnetic resonance spectroscopy iv) Results from a study investigating ex vivo markers of poor outcome via Luminex multiplex analysis of blood and cerebrospinal fluid. Given the timing of this PhD, this thesis also contains results of an observational case-control study to understand neurological complications of COVID-19 via systematic analysis of cerebrospinal fluid of patients presenting with neurological symptoms during the first wave of the COVID-19 pandemic in South Africa. These results are included within the appendix of the thesis

    Craniosynostosis: primary and secondary brain anomalies:A radiologic investigation

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    The Convergence of Human and Artificial Intelligence on Clinical Care - Part I

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    This edited book contains twelve studies, large and pilots, in five main categories: (i) adaptive imputation to increase the density of clinical data for improving downstream modeling; (ii) machine-learning-empowered diagnosis models; (iii) machine learning models for outcome prediction; (iv) innovative use of AI to improve our understanding of the public view; and (v) understanding of the attitude of providers in trusting insights from AI for complex cases. This collection is an excellent example of how technology can add value in healthcare settings and hints at some of the pressing challenges in the field. Artificial intelligence is gradually becoming a go-to technology in clinical care; therefore, it is important to work collaboratively and to shift from performance-driven outcomes to risk-sensitive model optimization, improved transparency, and better patient representation, to ensure more equitable healthcare for all

    High periventricular T1 relaxation times predict gait improvement after spinal tap in patients with idiopathic normal pressure hydrocephalus

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    Purpose:The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) can be challenging. Aim of this study was to use a novel T1 mapping method to enrich the diagnostic work-up of patients with suspected iNPH.Methods:Using 3T magnetic resonance imaging (MRI) we prospectively evaluated rapid high-resolution T1 mapping at 0.5 mm resolution and 4 s acquisition time in 15 patients with suspected iNPH and 8 age-matched, healthy controls.T1 mapping in axial sections of the cerebrum, clinical and neuropsychological testing were performed prior to and after cerebrospinal fluid tap test (CSF-TT). T1 relaxation times were measured in 5 predefined periventricular regions.Results:All 15 patients with suspected iNPH showed gait impairment, 13 (86.6%) showed signs of cognitive impairment and 8 (53.3%) patients had urinary incontinence. Gait improvement was noted in 12 patients (80%) after CSF-TT. T1 relaxation times in all periventricular regions were elevated in patients with iNPH compared to controls with the most pronounced differences in the anterior (1006 ± 93 ms vs. 911 ± 77 ms; p = 0.023) and posterior horns (983 ± 103 ms vs. 893 ± 68 ms; p = 0.037) of the lateral ventricles. Montreal cognitive assessment (MoCA) scores at baseline were negatively correlated with T1 relaxation times (r 0.6 and p Conclusion:In iNPH-patients, periventricular T1 relaxation times are increased compared to age-matched controls and predict gait improvement after CSF-TT. T1 mapping might enrich iNPH work-up and might be useful to indicate permanent shunting
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