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1.	Larsson, Jenny, 1990- (författare) Population-based studies of higher-level gait disorders and hydrocephalus : focused on brain ventricular morphometry and patient outcomes following shunt surgery 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background: To study gait is of great importance for the health of the aging population. Higher-level gait disorders (HLGD) are characterized by a slow, symmetrical, unsteady gait. Its cause is most often unknown. HLGD in combination with ventriculomegaly (i.e., large brain ventricles) is obligatory for the diagnosis of Idiopathic Normal pressure hydrocephalus (INPH), a syndrome that is sometimes treatable with insertion of a CSF shunt. It is therefore important to investigate the prevalence of HLGD in the population and brain morphometry in individuals with HLGD. Further, self-perceived confidence in gait and balance among patients with HLGD and INPH is unknown and important to study as slow gait velocity is associated with falls, injuries, and death. CSF shunts in INPH are associated with adverse events and little is known about epilepsy after surgery or minor and moderate adverse events such as headache and abdominal pain.Objective: In the older population investigate the prevalence of HLGD, and its association to ventriculomegaly. To investigate quality of life (QoL), depressive symptoms, and balance confidence in an HLGD population. In patients shunted for INPH, assess falls, fear of falling, balance confidence and prevalence of the possible adverse events headache, epilepsy, and abdominal pain after shunt surgery. Methods: Two population-based case-controlled cohorts were studied. In the first study, the "Ventriculomegaly and gait disturbance in the senior population in the region of Västerbotten" (VESPR) study, individuals (65-84 years) were recruited through a questionnaire (n=6467 dispatched). The final population consisted of 798 cases with gait disorders and 249 controls without gait disorders, age- and sex-matched to individuals with HLGD. All had been examined by a physician and were categorized: 1. "HLGD"; 2. "neurological gait disorder"; 3. "non-neurological gait disorder" or; 4. "no gait disorder". Participants were assessed with: the Swedish modification of the Falls-Efficacy Scale (FES(S)), the Modified Gait-Efficacy Scale (mGES), the Euro Quality of Life 5-Dimension 5-Level (EQ5D5L) instrument (EQ5D5L index and Euro Quality of life visual analogue scale (EQ VAS)) and the Geriatric depression scale 15 (GDS-15). Cases and controls had an MRI of the brain and ventricular size was measured. The second study, the "Comorbidities and vascular risk factors associated with idiopathic normal pressure hydrocephalus" (INPH-CRasH) study, consisted of 176 shunted INPH patients and 368 age- and sex-matched controls. Mean age was 74 years in INPH and 73 in controls. All had a visit to a healthcare facility. Information regarding adverse events, falls and fear of falling were gathered through a questionnaire. Additional information on diagnoses and prescribed drugs were obtained from the Swedish national patient- and drug registries. Data was compared between the groups, and before- and after surgery for INPH. Results: In the VESPR study, 87 individuals were categorized as HLGD, corresponding to a prevalence of 5.8% (95% confidence interval (CI) 4.6-7.0) in the older population. A definite cause was found in 13% (n=11) of individuals with HLGD, but ventriculomegaly was present in 63% (n=46/73, controls: 38%, n=70/184; OR 2.8 95% CI 1.6-4.9, p<0.001). HLGD had more depressive symptoms and lower quality of life (QoL), compared with individuals without gait disorder (GDS-15: 3.9±3.4 vs. 2.5±2.8, p=0.004; EQ VAS: 63±17 vs. 71±18; p<0.001; EQ5D5L index: 0.671±0.188 vs. 0.840±0.126, p<0.001). HLGD had low confidence in gait and to avoid falls compared to those without gait disorder (mGES: 60±22 vs. 74±21; p<0.001; FES(S): 93±32 vs. 111±25 p<0.001). The INPH-CRasH study revealed that patients with INPH feared falling more often (3.3±1.1) and had lower balance confidence (78±40) than controls (fear of falling: 1.6±0.9, balance confidence: 126±14; p<0.001 in both comparisons). After surgery, the proportions were reduced in INPH (p<0.001). More INPH than controls were fallers (before surgery: 67% vs. 11% OR 15.48 95% CI 9.85-24.32; after surgery: 35% vs 11% OR 4.15 95% CI 2.65-6.50, p<0.001). The proportion was reduced after surgery (p<0.001). In shunted INPH, epilepsy, antiepileptic drug (AED) treatment and headache was more common than in controls (epilepsy: 4.5% vs. 1.1% OR 4.3, 95% CI 1.3-14.6, p=0.023; AED treatment: 14.8% vs. 7.3% OR 0.5 95% CI 0.3-0.8, p=0.010; headache: 36.1% vs 11.6% OR 0.2 95% CI 0.2-0.4, p<0.001). Forty percent INPH (n=70) had abdominal pain after surgery. Conclusions: HLGD was common in the general older population and associated to ventriculomegaly. HLGD was also associated with low quality of life and depressive symptoms. Both individuals with HLGD and patients with INPH had low confidence in their balance but it was less common after surgery for INPH. However, patients shunted for INPH still had more problems with low balance confidence, falls, and fear of falling than controls. After shunt surgery for INPH, a significant portion of patients developed epilepsy, headache, and abdominal pain. The findings motivate investigations of causal relationships between HLGD and ventriculomegaly and if treatment options exist for HLGD. The observed adverse events in patients shunted for INPH should be considered in pre- and postoperative evaluations of shunt surgery, and in the development of new techniques for shunt placement. Additional interventions directed towards low balance confidence, falls and fear of falling should be considered for patients with INPH, and for individuals with HLGD.
2.	Vikner, Tomas, 1990- (författare) Cerebral arterial pulsatility imaging using 4D flow MRI : methodological development and applications in brain aging 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract 4D flow magnetic resonance imaging (MRI) is increasingly recognizedas a versatile tool to assess arterial and venous hemodynamics. Cerebral arterial pulsatility is typically assessed by analyzing flow waveforms over the cardiac cycle, where flow amplitude is a function of cardiac output, central arterial stiffness, and cerebrovascular resistance and compliance. Excessive pulsatility may propagate to the cerebral microcirculation, and constitute a harmful mechanism for the brain. Indeed, imaging studies have linked arterial pulsatility to hippocampus volume, cerebral small vessel disease (SVD), and Alzheimer’s disease (AD). In animal models, elevated pulsatility leads to blood-brain barrier (BBB) leakage, capillary loss, and cognitive decline. However, associations to cerebrovascular lesions and brain function in the spectrum of normal aging are less investigated. Further, previous 4D flow studies have mainly assessed pulsatility in relatively large cerebral arteries. When exploring links to microvascular damage and brain function, more distal measurements, closer to the microcirculation, are desired. This thesis aimed to develop 4D flow MRI post-processing methods to obtain pulsatile waveforms in small, distal cerebral arteries with noisy velocity data and a complex vascular anatomy, and to evaluate pulsatility (primarily assessed by the pulsatility index) in relation to aging, brain function, and other imaging biomarkers of cerebrovascular damage, with particular dedication towards the hippocampus and cerebral SVD. To assess pulsatility in distal cerebral arteries, a post-processing method that automatically samples waveforms from numerous small arteries, to obtain a whole-brain representation of the distal arterial waveform, was developed (Paper I). We demonstrated the importance of averaging flow waveforms along multiple vessel segments to avoid overestimations in the pulsatility index, showed agreement with reference methods, and linked distal arterial pulsatility to age. To explore links to hippocampal function, we evaluated pulsatility in relation to cognition, hemodynamic low-frequency oscillations (LFOs), perfusion, and hippocampus volume (Paper II). We found that higher pulsatility was linked to worse hippocampus-sensitive episodic memory, weaker hippocampal LFOs, and lower whole-brain perfusion. These findings aligned with models suggesting that hippocampal microvessels could be particularly susceptible to pulsatile stress.To inform on SVD pathophysiology, we evaluated 5-year associations among pulsatility, white matter lesions (WMLs) and perivascular space (PVS) dilation, using mixed models, factor analysis, and change score models (Paper III). Lead-lag analyses indicated that, while pulsatility at baseline could not predict WML nor PVS progression, WML and PVS volumes at baseline predicted 5-year pulsatility-increases. These findings indicate that individuals with a higher load of cerebrovascular damage are more prone to see increased pulsatility over time, and suggest that high pulsatility is a manifestation, rather a risk factor, for cerebral SVD. To shed light on the potential role of BBB leakage in aging and SVD, we used dynamic contrast enhanced (DCE) MRI and intravenous gadolinium injections to quantify BBB permeability (Paper IV). We found stepwise increases in permeability from healthy white matter to WMLs, supporting that BBB leakages are implicated in SVD. However, hippocampal BBB permeability was unrelated to age, indicating that this capillary property is maintained in aging. Finally, arterial pulsatility was unrelated to BBB permeability in WMLs and in the hippocampus, providing no evidence of excessive pulsatility as a trigger of BBB leakage. In conclusion, distal arterial pulsatility measurements are reliable when averaging 4D flow waveforms over a large number of vessels. Pulsatility increases with age, and individuals with more cerebrovascular lesions are prone to see larger increases over time. Pulsatility is negatively related to perfusion and hippocampal function. However, the temporal dynamics among the SVD biomarkers, and the absence of pulsatility–permeability associations, challenge the concept of excessive pulsatility as a trigger of microvascular damage. Future studies are needed to understand whether altered cerebral hemodynamics play a causal role in cognitive decline and dementia. Meanwhile, 4D flow hemodynamic parameters could be useful as biomarkers related to vessel properties and cerebrovascular health.
3.	Birnefeld, Johan, 1989- (författare) Cerebral hemodynamics in stroke, cerebral small vessel disease and pharmacological interventions : a 4D flow MRI study 2024 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background and aim: Current cerebrovascular imaging techniques provide important information on arterial anatomy and structural pathologies, such as stenoses and occlusions, but physicians are left to infer how the blood flow is affected. In addition, the relationship between blood pressure and cerebral blood flow is complex and poorly understood. Increased transmission of cardiac pulsatility to the cerebral microvasculature has been suggested as a causative factor of cerebral small vessel disease (CSVD) but previous research have yielded conflicting results regarding this relationship. 4D flow magnetic resonance imaging (MRI) is a novel and promising technique enabling time-resolved blood flow quantification with whole-brain coverage and relatively short scan times. However, despite its obvious potential, there is not yet an evidence-based application for the use of 4D flow MRI within stroke or CSVD. This dissertation aimed to apply 4D flow MRI to describe blood flow patterns in posterior circulation stroke and cerebral blood flow responses to common pharmacological agents used to alter arterial blood pressure as well as to examine the relationship between cerebral arterial pulsatility and CSVD.Methods and Results: This doctoral dissertation consisted of four papers, referred to by roman numerals. 4D flow MRI and computed tomography angiography (CTA) were applied in 25 patients with acute ischemic stroke in the posterior circulation and a reference population of 15 healthy elderly (paper I). Individual flow profiles were created for each stroke patient and hemodynamic disturbances as well as collateral compensation were described. We show that hemodynamic findings were related to structural findings from CTA.The cross-sectional relationship between cerebral arterial pulsatility (quantified using 4D flow MRI as pulsatility index [PI] and flow volume pulsatility [FVP]) and features of CSVD were examined using regression analysis in 89 patients with acute ischemic stroke (paper II) and a population-based sample of 862 elderly (paper III). Internal carotid artery FVP was associated with increasing white matter hyperintensity (WMH) volume in patients with stroke and TIA (paper II). In addition, increasing middle cerebral artery FVP and PI were associated with worse cognitive function. In the population sample, high FVP and PI were associated with increasing WMH volume, lower brain volume and the presence of lacunes, but not the composite MRI-CSVD (paper III). Among subjects with MRI-CSVD, displaying symptoms consistent with cerebral small vessel disease was associated with higher WMH volume, lower brain volume and active smoking, but not any measure of pulsatility.Eighteen healthy volunteers were administered noradrenaline to increase mean arterial pressure by 20% above baseline, and labetalol to decrease mean arterial pressure to 15% below baseline (paper IV). Cerebral blood flow was measured using phase-contrast MRI at each blood pressure level and compared to baseline. Despite a marked increase in blood pressure, noradrenaline administration caused a reduction in cerebral blood flow and cardiac output. Meanwhile, labetalol administration caused no change in cerebral blood flow but an increased cardiac output.Conclusions: 4D flow MRI can detect hemodynamic disturbances and discriminate between hemodynamic disturbances and normal flow in patients with structural vascular pathologies. This additional information compared to structural imaging alone could potentially be used for prognosis and selection for procedures in clinical care. Cerebral arterial pulsatility is modestly associated with several MRI and clinical features of CSVD but not all. Cerebral arterial pulsatility as the main risk factor of CSVD seems unlikely but its involvement in the pathophysiology cannot be ruled out. Raising the blood pressure with noradrenaline decreases cerebral blood flow and cardiac output without any redistribution from peripheral to cerebral flow. This highlights the pitfalls of using blood pressure as a surrogate for cerebral blood flow and questions the validity of our understanding of cerebral autoregulation. Lowering the blood pressure with labetalol does not affect cerebral blood flow, reassuring its use in clinical routine. 4D flow MRI can be integrated into an in-patient work-up in selected cases of acute ischemic stroke and into the workflow of large epidemiological studies.
4.	Bäcklund, Tomas, 1958- (författare) Wearable systems and sensors for the assessment of motor control : Development and validation of methods for clinical assessment of idiopathic normal pressure hydrocephalus 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Human gait and balance are controlled by automatic processes in the central nervous system, and in sensory and proprioceptive systems. If a disturbance occurs in any of these complex structures, it may lead to balance and gait problems. Equally important are the systems controlling the upper extremity functions where reach, grasp and manipulation skills may be affected. For the neurodegenerative disease idiopathic normal pressure hydrocephalus (iNPH), balance and gait disturbances are cardinal symptoms. Motor control of the upper extremities is also affected. In clinic today, physical impairment of persons with iNPH is commonly visually assessed using subjective, course tests with ordinal scales with the risk of missing minor changes. There is a lack of objective and quantitative ways to measure motor control in daily patient care. The aim of this thesis was to develop and validate tools for objective assessment of parameters that affect motor control in persons with iNPH.Postural stability in stance and walking was assessed using gyroscopes in patients with iNPH, healthy elderly (HE) and patients with ventriculomegaly (VM). Compared to HE, patients with iNPH had reduced postural stability and relied less on vision. iNPH patients also had a lower trunk sway velocity than VM during walking. The gyroscopic system could quantitatively assess postural deficits in iNPH, making it a potentially useful tool for diagnosis and for clinical follow-up. The differences found during gait also suggests that walking, rather than quiet stance, should be further investigated for facilitating differential diagnosis compared to other patient groups with ventriculomegaly.The gait in patients with iNPH is according to guidelines defined as slow, shuffling with a low foot-lift, and wide based. To objectively quantify the latter two features, a system (Striton) was developed in-house to assess the increased distance between the feet and the peak heel-height at the push-off phase of the gait cycle. It was validated in experimental setups, compared to gold standard motion capture systems (MCS), on healthy elderly (HE), through test-retest and day-to-day evaluations, and in four patients with iNPH. Striton demonstrated high correlations, in step-width and in heel-height, compared with the MCS. The mean step-width in the HE was 5.2 ± 0.9 cm (mean±Standard Deviation) and the heel-height 16.7±0.6 cm. Test-retest and day-to-day variations were small, ±0.5 cm in step-width and ±1.2 cm in heel-height, and differences in the parameters were seen between HE and iNPH both before and after surgery. Thus, Striton has the potential of quantitatively assessing gait parameters in HE and iNPH in a valuable manner.
5.	Holmgren, Madelene, 1992- (författare) 4D flow MRI and modelling to assess cerebral arterial hemodynamics : method development and evaluation, with implementation in patients with symptomatic carotid stenosis 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Blood flow measurements are important for understanding the development of cerebrovascular diseases. With 4D flow magnetic resonance imaging (4D flow MRI), simultaneous velocity measurements are obtained in all cerebral arteries in a scan of about ten minutes. However, 4D flow MRI is a relatively new technique. For usefulness in both clinics and research, detailed knowledge is needed about its accuracy and precision for flow quantification. In patients with stroke or transient ischemic attack (TIA) from a symptomatic carotid stenosis, the stenosis may generate a difference in blood pressure and flow between the left and right cerebral hemispheres. Such a hemispheric pressure difference could be an early marker of to what extent a stenosis is affecting cerebral hemodynamics, which could be useful in the planning of carotid surgery. The overall aim of the thesis was to determine the accuracy of 4D flow MRI to measure cerebral arterial blood flow, and to develop and evaluate an approach combining 4D flow MRI and computational fluid dynamics (CFD) to characterize the cerebral arterial hemodynamics, with implementation in patients with symptomatic carotid stenosis. The thesis is based on four papers, investigating two cohorts.The first cohort consisted of 35 elderly volunteers (mean age 79 years) and was studied in paper I-II. Blood flow rates were measured in nine cerebral arteries with 4D flow MRI and 2D phase-contrast MRI as reference. Three different flow quantification methods for 4D flow MRI were evaluated and optimized: one clustering approach and two threshold-based methods. The proposed new method, based on a locally adapted threshold, outperformed the previously suggested methods in flow rate quantification. For the clustering method, flow rates were systematically underestimated. 4D flow MRI was also evaluated to assess different arterial pulsatility measures, and a Windkessel model was used to estimate reference values for cerebrovascular resistance and cerebral arterial compliance in elderly.The second cohort consisted of 28 stroke and TIA patients (mean age 73 years) with symptomatic carotid stenosis and was studied in paper III-IV. With 4D flow MRI and CFD, the preoperative hemispheric pressure laterality was quantified in the patients. The pressure laterality was compared to hemispheric flow lateralities. Estimating the hemispheric pressure laterality was a promising physiological biomarker for grading the cerebral arterial hemodynamic disturbances in patients with symptomatic carotid stenosis. A CFD model was also developed to predict carotid stump pressure, i.e., the important pressure measured in the clamped carotid artery during surgical removal of the stenosis. The predicted stump pressures were correlated with the pressures measured during surgery. Stump pressure prediction was promising and could be a potential tool in the preoperative planning in order to avoid hypoperfusion during surgery. In summary, post-processing methods were successfully developed and evaluated for accurate assessment of mean and pulsatile cerebral blood flow rates with 4D flow MRI. Thereby, this thesis provided knowledge about possibilities and limitations of how 4D flow MRI can be used with respect to cerebral arterial blood flow rate assessment. By contributing with models combining 4D flow MRI and CFD, specifically developed for analysis of pressure distributions in cerebral arteries, novel methods were proposed for assessing patients with symptomatic carotid stenosis in the planning of carotid surgery.
6.	Andersson, Johanna, 1990- (författare) Idiopathic normal pressure hydrocephalus : epidemiology and diagnostics 2021 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological condition characterized by a deterioration of gait, cognition, and continence. The diagnosis is based on a combination of enlarged ventricles seen in neuroimaging, with typical clinical findings. iNPH often affects elderly individuals (i.e., over the age of 65). Shunt insertion is the only available treatment, with an improvement rate of up to 80%.The prevalence has previously been reported to be between 0.5 and 3% among individuals over age 65. However, most previous studies have been conducted on hospital-based materials, and there is a lack of epidemiological studies based on the general population. One of the challenges of diagnosing iNPH is that there are no common, widely accepted diagnostic criteria. There are currently two different diagnostic guidelines: the American-European guidelines and the Japanese ones, which makes it harder to compare different studies.The aim of this thesis was to determine the prevalence of iNPH in population-based materials and to evaluate the differences between the diagnostic guidelines. Furthermore, we wanted to assess the quality of life and depressive symptoms among individuals with iNPH compared to those without. In addition, we assessed longitudinal changes in the clinical and radiological findings of iNPH.We asked 1,000 individuals aged 65 and older to participate in the study by answering a questionnaire containing typical iNPH symptoms. We invited all participants who had marked at least two symptoms on the questionnaire for further investigation, in addition to a randomly selected group with fewer than two symptoms. A total of 168 participants underwent clinical examinations and computed tomography (CT) of the brain. We followed up with the same cohort two years later with repeated testing, with the addition of questionnaires on depressive symptoms and quality of life. A total of 122 individuals remained in the 2-year follow-up cohort. The clinical examinations included an iNPH-specific grading scale for symptoms and neurological examinations.The prevalence of iNPH for those 65 years and older was 3.7% according to the American-European guidelines and 1.5% according to the Japanese guidelines. The prevalence was higher for those over age 80, with no differences between the sexes. Furthermore, participants with iNPH had more depressive symptoms and lower quality of life than those without iNPH. Radiological findings and symptoms progressed slightly over two years, and those with symptom deterioration had an even higher degree of radiological progress compared to those with stationary or improved symptoms.This thesis shows that iNPH is fairly common in a normal population of elderly individuals. There is disagreement between the current diagnostic guidelines, which underscores the need for revisions, preferably into one common diagnostic system. In this thesis, individuals with iNPH had a lower functional status, more depressive symptoms, and lower quality of life than those without iNPH.Moreover, iNPH progresses slightly in both symptoms and radiological signs over two years, which underlines the value of clinical follow-up for asymptomatic individuals with radiological signs of iNPH. Finally, iNPH is probably underdiagnosed and an important diagnosis to consider in an elderly person with gait and balance impairments.
7.	Behrens, Anders, 1979- (författare) Measurements in Idiopathic Normal Pressure Hydrocephalus : Computerized neuropsychological test battery and intracranial pulse waves 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients.Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility.In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation.One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.
8.	Björnfot, Cecilia, et al. (författare) Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study 2024 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. Tidskriftsartikel (refereegranskat)abstract White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
9.	Gasslander, Johan, et al. (författare) Risk factors for developing subdural hematoma : a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus 2021 Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 134:2, s. 668-677 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH.METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs.RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups.CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.
10.	Larsson, Jenny, et al. (författare) Higher-level gait disorder and its association with ventriculomegaly: A population-based case-control study Annan publikation (övrigt vetenskapligt/konstnärligt)
11.	Larsson, Jenny, et al. (författare) Higher-level gait disorders - quality of life, balance confidence, and depression: The VESPR cohort, a population-based study on gait disorders Annan publikation (övrigt vetenskapligt/konstnärligt)
12.	Malm, Jan, Professor, 1957-, et al. (författare) Cerebrospinal fluid shunt dynamics in patients with idiopathic adult hydrocephalus syndrome. 1995 Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 58:6, s. 715-723 Tidskriftsartikel (refereegranskat)abstract The objective was to assess CSF dynamics of different shunt constructions in patients with adult hydrocephalus syndrome and correlate these findings to clinical outcome, neuroradiology, and the specifications of the shunts provided by the manufacturer. Thirty four patients with idiopathic adult hydrocephalus (normal pressure hydrocephalus) syndrome were included in a prospective, consecutive case series. A differential pressure valve (Cordis Hakim standard system) was used in 28 patients and a variable resistance valve (Cordis Orbis-Sigma) in six. A constant pressure infusion method was used; CSF pressure and conductance were determined before surgery. Three months after shunt placement CSF pressure, the "pressure v flow" curve, and gravity induced flow were measured. There was no difference between mean preoperative and postoperative resting CSF pressures in patients with Hakim shunts. The opening pressures of the Hakim shunts were higher than the value proposed by the manufacturer. A pronounced gravity effect induced CSF flow and decrease of the CSF pressure. In functioning variable resistance valves, CSF dynamics normalised postoperatively. There was no gravity effect and the characteristics shaped "pressure v flow" curve was sometimes seen. Six patients (three differential pressure valves, three variable resistance valves) had non-functioning shunts. Four of these patients were improved after the operation but improvement was transient in three. In all patients, there was no relation between the width of the ventricles and clinical improvement or CSF pressure. In conclusion, the differential pressure valve system does not behave according to the specifications provided by the manufacturer. A decrease in CSF pressure in patients with this shunt was solely due to the effect of gravity. Eleven percent of the differential pressure valves and 50% of the variable resistance valves were non-functioning. In the functioning variable resistance valves, the antisiphon system seems to be effective.
13.	Ryska, Pavel, et al. (författare) Radiological markers of idiopathic normal pressure hydrocephalus : Relative comparison of their diagnostic performance 2020 Ingår i: Journal of the Neurological Sciences. - : Elsevier. - 0022-510X .- 1878-5883. ; 408 Tidskriftsartikel (refereegranskat)abstract PURPOSE: Numerous radiological measures have been proposed as imaging biomarkers of idiopathic normal pressure hydrocephalus (iNPH), however, the number of studies systematically comparing their diagnostic values remains limited. The study objective was to compare the diagnostic performance of fifteen cross-sectional imaging iNPH biomarkers.MATERIALS AND METHODS: Eighty subjects were prospectively enrolled in the study: 35 subjects with clinically confirmed iNPH and 45 matched healthy controls (HC). Values of linear, angular and index measurements including three newly proposed biomarkers were obtained from 3T brain MRI studies by two independent readers. Diagnostic performance of biomarkers was studied by using receiver operating characteristic (ROC) analysis and t-statistic.RESULTS: All biomarkers studied were able to reliably differentiate iNPH subjects from HC (p < .001) except for cella media-to-temporal horn ratio. Z-Evans index, vertical cella media and vertical frontal horn diameters showed the highest discriminatory power between iNPH and HC groups (area under curve >0.99). Simple linear measurements of vertical (0.99) or horizontal (0.95) frontal horn diameters showed results comparable to calculated ratios, i.e. z-Evans (0.99) and Evans (0.96) indexes, respectively.CONCLUSION: The best diagnostic performance among fifteen radiological iNPH biomarkers was found in linear measurements referring to caudocranial alterations of the ventricular geometry, outweighing those referring to laterolateral ventricular enlargement (as e.g. commonly used Evans index). Simple linear measurements of vertical or horizontal frontal horn diameters showed comparable results to calculated, more time-consuming z-Evans or Evans indexes, respectively.
14.	Vikner, Tomas, et al. (författare) 5-year associations among cerebral arterial pulsatility, perivascular space dilation, and white matter lesions 2022 Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 92:5, s. 871-881 Tidskriftsartikel (refereegranskat)abstract Objective: High cerebral arterial pulsatility index (PI), white matter lesions (WMLs), enlarged perivascular spaces (PVSs), and lacunar infarcts are common findings in the elderly population, and considered indicators of small vessel disease (SVD). Here, we investigate the potential temporal ordering among these variables, with emphasis on determining whether high PI is an early or delayed manifestation of SVD.Methods: In a population-based cohort, 4D flow MRI data for cerebral arterial pulsatility was collected for 159 participants at baseline (age 64–68), and for 122 participants at follow-up 5 years later. Structural MRI was used for WML and PVS segmentation, and lacune identification. Linear mixed-effects (LME) models were used to model longitudinal changes testing for pairwise associations, and latent change score (LCS) models to model multiple relationships among variables simultaneously.Results: Longitudinal 5-year increases were found for WML, PVS, and PI. Cerebral arterial PI at baseline did not predict changes in WML or PVS volume. However, WML and PVS volume at baseline predicted 5-year increases in PI. This was shown for PI increases in relation to baseline WML and PVS volumes using LME models (R (Formula presented.) 0.24; p < 0.02 and R (Formula presented.) 0.23; p < 0.03, respectively) and LCS models ((Formula presented.) = 0.28; p = 0.015 and (Formula presented.) = 0.28; p = 0.009, respectively). Lacunes at baseline were unrelated to PI.Interpretation: In healthy older adults, indicators of SVD are related in a lead–lag fashion, in which the expression of WML and PVS precedes increases in cerebral arterial PI. Hence, we propose that elevated PI is a relatively late manifestation, rather than a risk factor, for cerebral SVD.
15.	Vikner, Tomas, et al. (författare) Cerebral arterial pulsatility is linked to hippocampal microvascular function and episodic memory in healthy older adults 2021 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:7, s. 1778-1790 Tidskriftsartikel (refereegranskat)abstract Microvascular damage in the hippocampus is emerging as a central cause of cognitive decline and dementia in aging. This could be a consequence of age-related decreases in vascular elasticity, exposing hippocampal capillaries to excessive cardiac-related pulsatile flow that disrupts the blood-brain barrier and the neurovascular unit. Previous studies have found altered intracranial hemodynamics in cognitive impairment and dementia, as well as negative associations between pulsatility and hippocampal volume. However, evidence linking features of the cerebral arterial flow waveform to hippocampal function is lacking. We used a high-resolution 4D flow MRI approach to estimate global representations of the time-resolved flow waveform in distal cortical arteries and in proximal arteries feeding the brain in healthy older adults. Waveform-based clustering revealed a group of individuals featuring steep systolic onset and high amplitude that had poorer hippocampus-sensitive episodic memory (p = 0.003), lower whole-brain perfusion (p = 0.001), and weaker microvascular low-frequency oscillations in the hippocampus (p = 0.035) and parahippocampal gyrus (p = 0.005), potentially indicating compromised neurovascular unit integrity. Our findings suggest that aberrant hemodynamic forces contribute to cerebral microvascular and hippocampal dysfunction in aging.
16.	Birnefeld, Johan, et al. (författare) Associations of cerebral arterial pulsatility, clinical symptoms and imaging features of cerebral small vessel disease Annan publikation (övrigt vetenskapligt/konstnärligt)
17.	Birnefeld, Johan, et al. (författare) Cerebral arterial pulsatility is associated with features of small vessel disease in patients with acute stroke and TIA : a 4D flow MRI study 2020 Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 267:3, s. 721-730 Tidskriftsartikel (refereegranskat)abstract Cerebral small vessel disease (SVD) is a major cause of stroke and cognitive impairment. However, the underlying mechanisms behind SVD are still poorly understood. High cerebral arterial pulsatility has been suggested as a possible cause of SVD. In population studies, arterial pulsatility has been linked to white matter hyperintensities (WMH), cerebral atrophy, and cognitive impairment, all features of SVD. In stroke, pulsatility data are scarce and contradictory. The aim of this study was to investigate the relationship between arterial pulsatility and SVD in stroke patients. With a cross-sectional design, 89 patients with acute ischemic stroke or TIA were examined with MRI. A neuropsychological assessment was performed 1 year later. Using 4D flow MRI, pulsatile indices (PI) were calculated for the internal carotid artery (ICA) and middle cerebral artery (M1, M3). Flow volume pulsatility (FVP), a measure corresponding to the cyclic expansion of the arterial tree, was calculated for the same locations. These parameters were assessed for associations with WMH volume, brain volume and cognitive function. ICA-FVP was associated with WMH volume (β = 1.67, 95% CI: [0.1, 3.24], p = 0.037). M1-PI and M1-FVP were associated with decreasing cognitive function (β = - 4.4, 95% CI: [- 7.7, - 1.1], p = 0.009 and β = - 13.15, 95% CI: [- 24.26, - 2.04], p = 0.02 respectively). In summary, this supports an association between arterial pulsatility and SVD in stroke patients, and provides a potential target for further research and preventative treatment. FVP may become a useful biomarker for assessing pulsatile stress with PCMRI and 4D flow MRI.
18.	Birnefeld, Johan, et al. (författare) Cerebral blood flow assessed with phase-contrast magnetic resonance imaging during blood pressure changes with noradrenaline and labetalol : a trial in healthy volunteers 2024 Ingår i: Anesthesiology. - : Wolters Kluwer. - 0003-3022 .- 1528-1175. ; 140:4, s. 669-678 Tidskriftsartikel (refereegranskat)abstract Background: Adequate cerebral perfusion is central during general anesthesia. However, perfusion is not readily measured bedside. Clinicians currently rely mainly on MAP as a surrogate even though the relationship between blood pressure and cerebral blood flow is not well understood. The aim of this study was to apply phase contrast MRI to characterize blood flow responses in healthy volunteers to commonly used pharmacological agents that increase or decrease arterial blood pressure.Methods: Eighteen healthy volunteers aged 30-50 years were investigated with phase contrast MRI. Intraarterial blood pressure monitoring was used. First, intravenous noradrenaline was administered to a target MAP of 20% above baseline. After a wash-out period, intravenous labetalol was given to a target MAP of 15% below baseline. Cerebral blood flow was measured using phase contrast MRI and defined as the sum of flow in the internal carotid arteries and vertebral arteries. CO was defined as the flow in the ascending aorta.Baseline median cerebral blood flow was 772 ml/min (interquartile range, 674 to 871), and CO was 5,874 ml/min (5,199 to 6,355). The median dose of noradrenaline was 0.17 µg · kg−1 · h−1 (0.14 to 0.22). During noradrenaline infusion, cerebral blood flow decreased to 705 ml/min (606 to 748; P = 0.001), and CO decreased to 4,995 ml/min (4,705 to 5,635; P = 0.01). A median dose of labetalol was 120 mg (118 to 150). After labetalol boluses, cerebral blood flow was unchanged at 769 ml/min (734 to 900; P = 0.68). CO increased to 6,413 ml/min (6,056 to 7,464; P = 0.03).Conclusion: In healthy awake subjects, increasing MAP using intravenous noradrenaline decreased cerebral blood flow and CO. This data does not support inducing hypertension with noradrenaline to increase cerebral blood flow. Cerebral blood flow was unchanged when decreasing MAP using labetalol.
19.	Björnfot, Cecilia, et al. (författare) Assessing cerebral arterial pulse wave velocity using 4D flow MRI 2021 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 41:10, s. 2769-2777 Tidskriftsartikel (refereegranskat)abstract Intracranial arterial stiffening is a potential early marker of emerging cerebrovascular dysfunction and could be mechanistically involved in disease processes detrimental to brain function via several pathways. A prominent consequence of arterial wall stiffening is the increased velocity at which the systolic pressure pulse wave propagates through the vasculature. Previous non-invasive measurements of the pulse wave propagation have been performed on the aorta or extracranial arteries with results linking increased pulse wave velocity to brain pathology. However, there is a lack of intracranial “target-organ” measurements. Here we present a 4D flow MRI method to estimate pulse wave velocity in the intracranial vascular tree. The method utilizes the full detectable branching structure of the cerebral vascular tree in an optimization framework that exploits small temporal shifts that exists between waveforms sampled at varying depths in the vasculature. The method is shown to be stable in an internal consistency test, and of sufficient sensitivity to robustly detect age-related increases in intracranial pulse wave velocity.
20.	Bluett, Brent, et al. (författare) Clinical features of idiopathic normal pressure hydrocephalus : critical review of objective findings 2023 Ingår i: Movement Disorders Clinical Practice. - : John Wiley & Sons. - 2330-1619. ; 10:1, s. 9-16 Forskningsöversikt (refereegranskat)abstract Background: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic clinical triad of gait, cognitive, and urinary dysfunction, albeit incomplete in a relevant proportion of patients. The clinical findings and evolution of these symptoms have been variably defined in the literature.Objectives: To evaluate how the phenomenology has been defined, assessed, and reported, we performed a critical review of the existing literature discussing the phenomenology of iNPH. The review also identified the instrumental tests most frequently used and the evolution of clinical and radiologic findings.Methods: The review was divided into 3 sections based on gait, cognitive, and urinary dysfunction. Each section performed a literature search using the terms “idiopathic normal pressure hydrocephalus” (iNPH), with additional search terms used by each section separately. The number of articles screened, duplicates, those meeting the inclusion criteria, and the number of articles excluded were recorded. Findings were subsequently tallied and analyzed.Results: A total of 1716 articles with the aforementioned search criteria were identified by the 3 groups. A total of 81 full-text articles were reviewed after the elimination of duplicates, articles that did not discuss phenomenological findings or instrumental testing of participants with iNPH prior to surgery, and articles with fewer than 10 participants.Conclusions: “Wide-based gait” was the most common gait dysfunction identified. Cognitive testing varied significantly across articles, and ultimately a specific cognitive profile was not identified. Urodynamic testing found detrusor overactivity and “overactive bladder” as the most common symptom of urinary dysfunction.
21.	Eklund, Sanna, et al. (författare) 10-year mortality, causes of death and cardiovascular comorbidities in idiopathic normal pressure hydrocephalus 2024 Ingår i: Journal of Neurology. - : Springer Nature. - 0340-5354 .- 1432-1459. ; 271, s. 1311-1319 Tidskriftsartikel (refereegranskat)abstract Objective: The objective was to investigate 10-year mortality, causes of death and cardiovascular comorbidity in idiopathic normal pressure hydrocephalus (iNPH) and to evaluate their mutual associations.Methods: This prospective cohort study included 176 CSF-shunted iNPH patients, and 368 age- and sex-matched controls. At inclusion, participants were medically examined, had blood analyzed and answered a questionnaire. The vascular comorbidities investigated were smoking, diabetes, body mass index, blood pressure (BP), hyperlipidemia, kidney function, atrial fibrillation and, cerebro- and cardiovascular disease.Results: Survival was observed for a mean period of 10.3 ± 0.84 years. Shunted iNPH patients had an increased risk of death compared to controls (hazard ratio (HR) = 2.5, 95% CI 1.86–3.36; p < 0.001). After 10 years, 50% (n = 88) of iNPH patients and 24% (n = 88) of the controls were dead (p < 0.001). The risk of dying from cardiovascular disease, falls and neurological diseases were higher in iNPH (p < 0.05). The most common cause of death in iNPH was cardiovascular diseases (14% vs 7% for controls). Seven out of nine iNPH dying from falls had subdural hematomas. Systolic BP (HR = 0.985 95% CI 0.972–0.997, p = 0.018), atrial fibrillation (HR = 2.652, 95% CI 1.506–4.872, p < 0.001) and creatinine (HR = 1.018, 95% CI 1.010–1.027, p < 0.001) were independently associated with mortality for iNPH.Discussion: This long-term and population-matched cohort study indicates that in spite of CSF-shunt treatment, iNPH has shorter life expectancy. It may be important to treat iNPH in supplementary ways to reduce mortality. Both cardiovascular comorbidities and lethal falls are contributing to the excess mortality in iNPH and reducing these preventable risks should be an established part of the treatment plan.
22.	Eklund, Sanna A., et al. (författare) Vascular risk profiles for predicting outcome and long-term mortality in patients with idiopathic normal pressure hydrocephalus : comparison of clinical decision support tools 2023 Ingår i: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 138:2, s. 476-482 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Vascular risk factors (VRFs) may act synergistically, and clinical decision support tools (CDSTs) have been developed that present vascular risk as a summarized score. Because VRFs are a major issue in patients with idiopathic normal pressure hydrocephalus (INPH), a CDST may be useful in the diagnostic workup. The objective was to compare 4 CDSTs to determine which one most accurately predicts short-term outcome and 10-year mortality after CSF shunt surgery in INPH patients.METHODS: One-hundred forty INPH patients who underwent CSF shunt surgery were included. For each patient, 4 CDST scores (Systematic Coronary Risk Evaluation–Older Persons [SCORE-OP], Framingham Risk Score [FRS], Revised Framingham Stroke Risk Profile, and Kiefer’s Comorbidity Index [KCI]) were estimated. Short-term outcome (3 months after CSF shunt surgery) was defined on the basis of improvements in gait, Mini-Mental State Examination score, and modified Rankin Scale score. The 10-year mortality rate after surgery was noted. The CDSTs were compared by using Cox regression analysis, receiver operating characteristic curve analysis, and the chi-square test.RESULTS: For 3 CDSTs, increased score was associated with increased risk of 10-year mortality. A 1-point increase in the FRS indicated a 2% higher risk of death within 10 years (HR 1.02, 95% CI 1.003–1.035, p = 0.021); SCORE-OP, 5% (HR 1.05, 95% CI 1.019–1.087, p = 0.002); and KCI, 12% (HR 1.12, 95% CI 1.03–1.219, p = 0.008). FRS predicted short-term outcome of surgery (p = 0.024). When the cutoff value was set to 32.5%, the positive predictive value was 80% and the negative predictive value was 48% (p = 0.012).CONCLUSIONS: The authors recommend using FRS to predict short-term outcome and 10-year risk of mortality in INPH patients. The study indicated that extensive treatment of the risk factors of INPH may decrease risk of mortality.
23.	Hansson, William, et al. (författare) Cerebral Microbleeds-Long-Term Outcome After Cerebrospinal Fluid Shunting in Idiopathic Normal Pressure Hydrocephalus 2023 Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 93:2, s. 300-308 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cerebral microbleeds (CMBs) are common in idiopathic normal pressure hydrocephalus (INPH) and have been suggested as radiological markers of a brain prone to bleeding. The presence of CMBs might be relevant when selecting patients for shunt surgery.OBJECTIVE: To evaluate whether CMBs increases long-term risk of hemorrhagic complications and mortality or affects outcomes after cerebrospinal fluid shunt surgery in a cohort of patients with INPH.METHODS: One hundred and forty nine shunted patients with INPH (mean age, 73 years) were investigated with MRI (T2* or susceptibility-weighted imaging sequences) preoperatively. CMBs were scored with the Microbleed Anatomic Rating Scale. Patients were observed for a mean of 6.5 years (range 2 weeks to 13 years) after surgery. Hemorrhagic events and death were noted. Improvement in gait was evaluated 3 to 6 months after surgery.RESULTS: At baseline, 74 patients (50%) had CMBs. During follow-up, 7 patients (5%) suffered a hemorrhagic stroke and 43 (29%) suffered a subdural hematoma/hygroma with a median time from surgery of 30.2 months (IQR 50). Overall, having CMBs was not associated with suffering a subdural hematoma/hygroma or hemorrhagic stroke during follow-up with 1 exception that an extensive degree of CMBs (≥50 CMB) was more common in patients suffering a hemorrhagic stroke ( P = .03). CMBs were associated with increased mortality ( P = .02, Kaplan-Meier, log-rank test). The presence of CMBs did not affect gait outcome ( P = .28).CONCLUSION: CMBs were associated with hemorrhagic stroke and mortality. CMBs do not seem to reduce the possibility of gait improvement after shunt surgery or contribute to the risk of hemorrhagic complications regarding subdural hematoma or hygroma.
24.	Holmgren, Madelene, et al. (författare) Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI 2020 Ingår i: Journal of Magnetic Resonance Imaging. - : Wiley-Blackwell. - 1053-1807 .- 1522-2586. ; 51:5, s. 1516-1525 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Four-dimensional flow magnetic resonance imaging (4D flow MRI) enables efficient investigation of cerebral blood flow pulsatility in the cerebral arteries. This is important for exploring hemodynamic mechanisms behind vascular diseases associated with arterial pulsations.PURPOSE: To investigate the feasibility of pulsatility assessments with 4D flow MRI, its agreement with reference two-dimensional phase-contrast MRI (2D PC-MRI) measurements, and to demonstrate how 4D flow MRI can be used to assess cerebral arterial compliance and cerebrovascular resistance in major cerebral arteries.STUDY TYPE: Prospective.SUBJECTS: Thirty-five subjects (20 women, 79 ± 5 years, range 70-91 years).FIELD STRENGTH/SEQUENCE: 4D flow MRI (PC-VIPR) and 2D PC-MRI acquired with a 3T scanner.ASSESSMENT: Time-resolved flow was assessed in nine cerebral arteries. From the pulsatile flow waveform in each artery, amplitude (ΔQ), volume load (ΔV), and pulsatility index (PI) were calculated. To reduce high-frequency noise in the 4D flow MRI data, the flow waveforms were low-pass filtered. From the total cerebral blood flow, total PI (PItot ), total volume load (ΔVtot ), cerebral arterial compliance (C), and cerebrovascular resistance (R) were calculated.STATISTICAL TESTS: Two-tailed paired t-test, intraclass correlation (ICC).RESULTS: There was no difference in ΔQ between 4D flow MRI and the reference (0.00 ± 0.022 ml/s, mean ± SEM, P = 0.97, ICC = 0.95, n = 310) with a cutoff frequency of 1.9 Hz and 15 cut plane long arterial segments. For ΔV, the difference was -0.006 ± 0.003 ml (mean ± SEM, P = 0.07, ICC = 0.93, n = 310) without filtering. Total R was 11.4 ± 2.41 mmHg/(ml/s) (mean ± SD) and C was 0.021 ± 0.009 ml/mmHg (mean ± SD). ΔVtot was 1.21 ± 0.29 ml (mean ± SD) with an ICC of 0.82 compared with the reference. PItot was 1.08 ± 0.21 (mean ± SD).DATA CONCLUSION: We successfully assessed 4D flow MRI cerebral arterial pulsatility, cerebral arterial compliance, and cerebrovascular resistance. Averaging of multiple cut planes and low-pass filtering was necessary to assess accurate peak-to-peak features in the flow rate waveforms.LEVEL OF EVIDENCE: 2Technical Efficacy Stage: 2
25.	Holmgren, Madelene, et al. (författare) Middle cerebral artery pressure laterality in patients with symptomatic ICA stenosis 2021 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:1 Tidskriftsartikel (refereegranskat)abstract An internal carotid artery (ICA) stenosis can potentially decrease the perfusion pressure to the brain. In this study, computational fluid dynamics (CFD) was used to study if there was a hemispheric pressure laterality between the contra- and ipsilateral middle cerebral artery (MCA) in patients with a symptomatic ICA stenosis. We further investigated if this MCA pressure laterality (ΔPMCA) was related to the hemispheric flow laterality (ΔQ) in the anterior circulation, i.e., ICA, proximal MCA and the proximal anterior cerebral artery (ACA). Twenty-eight patients (73±6 years, range 59–80 years, 21 men) with symptomatic ICA stenosis were included. Flow rates were measured using 4D flow MRI data (PC-VIPR) and vessel geometries were obtained from computed tomography angiography. The ΔPMCA was calculated from CFD, where patient-specific flow rates were applied at all input- and output boundaries. The ΔPMCA between the contra- and ipsilateral side was 6.4±8.3 mmHg (p<0.001) (median 3.9 mmHg, range -1.3 to 31.9 mmHg). There was a linear correlation between the ΔPMCA and ΔQICA (r = 0.85, p<0.001) and ΔQACA (r = 0.71, p<0.001), respectively. The correlation to ΔQMCA was weaker (r = 0.47, p = 0.011). In conclusion, the MCA pressure laterality obtained with CFD, is a promising physiological biomarker that can grade the hemodynamic disturbance in patients with a symptomatic ICA stenosis.
26.	Holmgren, Madelene, et al. (författare) Prediction of cerebral perfusion pressure during carotid surgery : A computational fluid dynamics approach 2022 Ingår i: Clinical Biomechanics. - : Elsevier BV. - 0268-0033 .- 1879-1271. ; 100 Tidskriftsartikel (refereegranskat)abstract Background: Maintaining cerebral perfusion pressure in the brain when a carotid artery is closed during vascular surgery is critical for avoiding intraoperative hypoperfusion and risk of ischemic stroke. Here we propose and evaluate a method based on computational fluid dynamics for predicting patient-specific cerebral perfusion pressures at carotid clamping during carotid endarterectomy.Methods: The study consisted of 22 patients with symptomatic carotid stenosis who underwent carotid endarterectomy (73 ± 5 years, 59–80 years, 17 men). The geometry of the circle of Willis was obtained preoperatively from computed tomography angiography and corresponding flow rates from four-dimensional flow magnetic resonance imaging. The patients were also classified as having a present or absent ipsilateral posterior communicating artery based on computed tomography angiography. The predicted mean stump pressures from computational fluid dynamics were compared with intraoperatively measured stump pressures from carotid endarterectomy.Findings: On group level, there was no difference between the predicted and measured stump pressures (−0.5 ± 13 mmHg, P = 0.86) and the pressures were correlated (r = 0.44, P = 0.039). Omitting two outliers, the correlation increased to r = 0.78 (P < 0.001) (−1.4 ± 8.0 mmHg, P = 0.45). Patients with a present ipsilateral posterior communicating artery (n = 8) had a higher measured stump pressure than those with an absent artery (n = 12) (P < 0.001).Interpretation: The stump pressure agreement indicates that the computational fluid dynamics approach was promising in predicting cerebral perfusion pressures during carotid clamping, which may prove useful in the preoperative planning of vascular interventions.
27.	Holmlund, Petter, 1988-, et al. (författare) Author Response: Posture-Dependent Collapse of the Optic Nerve Subarachnoid Space : A Combined MRI and Modeling Study 2021 Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 62:15 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
28.	Holmlund, Petter, 1988-, et al. (författare) Posture-dependent collapse of the optic nerve subarachnoid space : A combined MRI and modeling study 2021 Ingår i: Investigative Ophthalmology and Visual Science. - : Association for Research in Vision and Ophthalmology. - 0146-0404 .- 1552-5783. ; 62:4 Tidskriftsartikel (refereegranskat)abstract PURPOSE: We hypothesize that a collapse of the optic nerve subarachnoid space (ONSAS) in the upright posture may protect the eyes from large translamina cribrosa pressure differences (TLCPD) believed to play a role in various optic nerve diseases (e.g., glaucoma). In this study, we combined magnetic resonance imaging (MRI) and mathematical modeling to investigate this potential ONSAS collapse and its effects on the TLCPD.METHODS: First, we performed MRI on six healthy volunteers in 6° head-down tilt (HDT) and 13° head-up tilt (HUT) to assess changes in ONSAS volume (measured from the eye to the optic canal) with changes in posture. The volume change reflects optic nerve sheath (ONS) distensibility. Second, we used the MRI data and mathematical modeling to simulate ONSAS pressure and the potential ONSAS collapse in a 90° upright posture.RESULTS: The MRI showed a 33% decrease in ONSAS volume from the HDT to HUT (P < 0.001). In the upright posture, the simulations predicted an ONSAS collapse 25 mm behind lamina cribrosa, disrupting the pressure communication between the ONSAS and the intracranial subarachnoid space. The collapse reduced the simulated postural increase in TLCPD by roughly 1 mm Hg, although this reduction was highly sensitive to ONS distensibility, varying between 0 and 4.8 mm Hg when varying the distensibility by ± 1 SD.CONCLUSIONS: The ONSAS volume along the optic nerve is posture dependent. The simulations supported the hypothesized ONSAS collapse in the upright posture and showed that even small changes in ONS stiffness/distensibility may affect the TLCPD.
29.	Israelsson, Hanna, 1983-, et al. (författare) Cerebrospinal Fluid Shunting Improves Long-Term Quality of Life in Idiopathic Normal Pressure Hydrocephalus 2020 Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 86:4, s. 574-582 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The short- and long-term impact of cerebrospinal fluid shunting on quality of life (QoL) in idiopathic normal pressure hydrocephalus (INPH) is poorly understood.OBJECTIVE: To investigate QoL in shunted INPH patients compared to the population and to investigate which factors influence QoL in INPH.METHODS: INPH patients consecutively shunted in Sweden during 2008-2010 were scrutinized. Population-based controls were age- and sex-matched to the patients. Included participants were the following: 176 INPH patients and 368 controls. QoL was assessed using the EuroQol 5-dimension 5-level (EQ5D5L) instrument, which measures overall QoL and health status in 5 dimensions. Independency (accommodation and/or need for in-home care) and comorbidities were assessed. Patients were followed up 6-45 mo after surgery (mean follow-up time: 21 mo).RESULTS: Shunting improved QoL (P < .001) and health status in all dimensions (P < .005). Shunted INPH patients had lower QoL than controls (P < .001). The patients' health status in mobility, self-care, daily activities, and anxiety/depression was worse than the controls both before and after surgery (P < .001). The main predictors of low QoL in INPH were symptoms of depression (P < .001) and severity of gait disturbance (P = .001). Fewer INPH patients than controls lived independently (45% vs 85%, P < .001). Time after shunting had no influence on QoL.CONCLUSION: QoL remains improved in shunted INPH patients at a mean follow-up time of 21 mo, but the patients do not reach the same QoL as the population. Symptoms of depression and severity of gait disturbance are the strongest predictors of low QoL in INPH.
30.	Israelsson Larsen, Hanna, 1983-, et al. (författare) Risk factors, comorbidities, quality of life, and complications after surgery in idiopathic normal pressure hydrocephalus : review of the INPH-CRasH study 2020 Ingår i: Neurosurgical Focus. - Rolling Meadows : American Association of Neurological Surgeons. - 1092-0684. ; 49:4 Forskningsöversikt (refereegranskat)abstract OBJECTIVE: Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a shunt that drains CSF. The cause of the disease is unknown, but a vascular pathway has been suggested. The INPH-CRasH (Comorbidities and Risk Factors Associated with Hydrocephalus) study was a modern epidemiological case-control study designed to prospectively assess parameters regarding comorbidities and vascular risk factors (VRFs) for INPH, quality of life (QOL), and adverse events in patients with shunted INPH. The objective of this review was to summarize the findings of the INPH-CRasH study.METHODS: VRFs, comorbidities, QOL, and adverse events were analyzed in consecutive patients with INPH who underwent shunt placement between 2008 and 2010 in 5 of 6 neurosurgical centers in Sweden. Patients (n = 176, within the age span of 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n = 368, same inclusion criteria as for the patients with INPH). Assessed parameters were as follows: hypertension; diabetes; obesity; hyperlipidemia; psychosocial factors (stress and depression); smoking status; alcohol intake; physical activity; dietary pattern; cerebrovascular, cardiovascular, or peripheral vascular disease; epilepsy; abdominal pain; headache; and clinical parameters before and after surgery. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG studies, and blood samples.RESULTS: Four VRFs were independently associated with INPH: hyperlipidemia, diabetes, obesity, and psychosocial factors. Physical inactivity and hypertension were also associated with INPH, although not independently from the other risk factors. The population attributable risk percent for a model containing all of the VRFs associated with INPH was 24%. Depression was overrepresented in patients with INPH treated with shunts compared to the controls (46% vs 13%, p < 0.001) and the main predictor for low QOL was a coexisting depression (p < 0.001). Shunting improved QOL on a long-term basis. Epilepsy, headache, and abdominal pain remained common for a mean follow-up time of 21 months in INPH patients who received shunts.CONCLUSIONS: The results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for QOL should probably be included in the workup of patients with INPH. The effect of targeted interventions against modifiable VRFs and antidepressant treatment in INPH patients should be evaluated. Seizures, headache, and abdominal pain should be inquired about at postoperative follow-up examinations.
31.	Jacobsson, Johan, et al. (författare) Comparison of the CSF dynamics between patients with idiopathic normal pressure hydrocephalus and healthy volunteers 2019 Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 131:4, s. 1018-1023 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Intracranial pressure (ICP), outflow resistance (Rout), and amplitude of cardiac-related ICP pulsations (AMPs) are established parameters to describe the CSF hydrodynamic system and are assumed, but not confirmed, to be disturbed in idiopathic normal pressure hydrocephalus (INPH). The aim of this study was to compare the CSF hydrodynamic profile between patients with INPH and healthy volunteers.METHODS: Sixty-two consecutive INPH patients (mean age 74 years) and 40 healthy volunteers (mean age 70 years) were included. Diagnosis was made by two independent neurologists who assessed patients’ history, neurological status, and MRI studies. A CSF dynamic investigation through the lumbar route was performed: ICP and other CSF dynamic variables were blinded to the neurologists during the diagnostic process and were not used for establishing the diagnosis of INPH.RESULTS: Rout was significantly higher in INPH (Rout 17.1 vs 11.1; p < 0.001), though a substantial number of INPH subjects had normal Rout. There were no differences between INPH patients and controls regarding ICP (mean 11.5 mm Hg). At resting pressure, there was a trend that AMP in INPH was increased (2.4 vs 2.0 mm Hg; p = 0.109). The relationship between AMP and ICP was that they shared the same slope, but the curve was significantly shifted to the left for INPH (reduced P0 [p < 0.05]; i.e., higher AMP for the same ICP).CONCLUSIONS: This study established that the CSF dynamic profile of INPH deviates from that of healthy volunteers and that INPH should thus be regarded as a disease in which intracranial hydrodynamics are part of the pathophysiology.Clinical trial registration no.: NCT01188382 (clinicaltrials.gov)
32.	Johansson, Elias, et al. (författare) Diagnosing carotid near-occlusion with phase-contrast MRI 2021 Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 42:5, s. 927-929 Tidskriftsartikel (refereegranskat)abstract Carotid near-occlusion is a frequently overlooked diagnosis when CTA examinations are assessed in routine practice. To evaluate the potential value of phase-contrast MR imaging in identifying near-occlusion, we examined 9 carotid near-occlusions and 20 cases of conventional $50% carotid stenosis (mean stenosis degree, 65%) with phase-contrast MR imaging. Mean ICA flow was lower in near-occlusions (52 mL/min) than in conventional $50% stenosis (198 mL/min, P, .001). ICA flow of #110 mL/min was 100% sensitive and specific for near-occlusion. Phase-contrast MR imaging is a promising tool for diagnosing carotid near-occlusion.
33.	Johansson, Staffan, 1978-, et al. (författare) A MEMS-based passive hydrocephalus shunt with adaptive flow characteristics 2013 Ingår i: 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII). - : IEEE conference proceedings. - 9781467359818 ; , s. 1671-1674 Konferensbidrag (refereegranskat)abstract This paper reports a novel MEMS valve with adaptive flow characteristics for improved treatment of hydrocephalus, a disease that is characterized by elevated pressure in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. In contrast to conventional valves with two ports, the valve presented here features a third port, called compensation port, which utilizes hydrostatic pressure to adapt CSF drainage based on body position. A prototype has been fabricated using standard MEMS manufacturing processes and the experimental evaluation successfully showed that the flow rate was adjustable with a varying hydrostatic pressure on the compensation port. Extracted data shows that flow rate was at near ideal values at both standing and laying body position showing an effective adaptation to body position. This is the first passive hydrocephalus valve intended for body position dependent CSF pressure regulation.
34.	Kihlstedt, Carl-Johan, et al. (författare) Freezing of gait in idiopathic normal pressure hydrocephalus 2024 Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background: Reports of freezing of gait (FoG) in idiopathic normal pressure hydrocephalus (iNPH) are few and results are variable. This study's objective was to evaluate the frequency of FoG in a large cohort of iNPH patients, identify FoG-associated factors, and assess FoG’s responsiveness to shunt surgery.Methods: Videotaped standardized gait protocols with iNPH patients pre- and post-shunt surgery (n = 139; median age 75 (71–79) years; 48 women) were evaluated for FoG episodes by two observers (Cohens kappa = 0.9, p < 0.001). FoG episodes were categorized. Mini-mental state examination (MMSE) and MRI white matter hyperintensities (WMH) assessment using the Fazekas scale were performed. CSF was analyzed for Beta-amyloid, Tau, and Phospho-tau. Patients with and without FoG were compared.Results: Twenty-two patients (16%) displayed FoG at baseline, decreasing to seven (8%) after CSF shunt surgery (p = 0.039). The symptom was most frequently exhibited during turning (n = 16, 73%). Patients displaying FoG were older (77.5 vs. 74.6 years; p = 0.029), had a slower walking speed (0.59 vs. 0.89 m/s; p < 0.001), a lower Tinetti POMA score (6.8 vs. 10.8; p < 0.001), lower MMSE score (21.3 vs. 24.0; p = 0.031), and longer disease duration (4.2 vs. 2.3 years; p < 0.001) compared to patients not displaying FoG. WMH or CSF biomarkers did not differ between the groups.Conclusions: FoG is occurring frequently in iNPH patients and may be considered a typical feature of iNPH. FoG in iNPH was associated with higher age, longer disease duration, worse cognitive function, and a more unstable gait. Shunt surgery seems to improve the symptom.
35.	Larsson, Jenny, et al. (författare) Falls and Fear of Falling in Shunted Idiopathic Normal Pressure Hydrocephalus : The Idiopathic Normal Pressure Hydrocephalus Comorbidity and Risk Factors Associated With Hydrocephalus Study 2021 Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 89:1, s. 122-128 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Gait and balance impairment are typical symptoms of idiopathic normal pressure hydrocephalus (INPH), implicating that falls may afflict these patients.OBJECTIVE: To investigate falls, related injuries, and associated psychological features, before and after shunt surgery for INPH and compared to the general population.METHODS: The study included 176 patients shunted for INPH and 368 age- and sex-matched controls. Falls, fear of falling (FOF), fall-related injuries (mild-severe), confidence in avoiding falls (Swedish Falls Efficacy Scale (FES(S)), quality of life (QoL; EuroQoL 5-dimension 5 level instrument), and symptoms of depression (Geriatric Depression Scale 15) were investigated. Pre- and postoperative observational times were 12 mo before surgery and 21 mo after (mean). Recurrent fallers fell ≥2 times.RESULTS: More INPH patients than controls were recurrent fallers (67% vs 11%; P < .001). They feared falling more often (FOF, mean ± standard deviation: 3.3 ± 1.1 vs 1.6 ± 0.9; P < .001) and had lower confidence in avoiding falls (FES(S) 78 ± 40 vs 126 ± 14; P < .001). After surgery, INPH patients improved in all parameters but they did not reach the levels of the controls. Among fallers there was no difference between patients and controls in the severity of injuries suffered. Low QoL and symptoms of depression were more common among recurrent fallers than one-time or nonfallers in both shunted patients and controls (P ≤ .001).CONCLUSION: Falls, FOF, and low confidence in avoiding falls are considerable problems in INPH that may be reduced by shunt surgery. We suggest that remaining risk of falling and preventative measures are routinely considered in postoperative follow-ups and rehabilitation planning.
36.	Lenfeldt, Niklas, et al. (författare) Improvement after cerebrospinal fluid drainage is related to levels of N-acetyl-aspartate in idiopathic normal pressure hydrocephalus 2008 Ingår i: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 62:1, s. 135-142 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: This study uses proton magnetic resonance spectroscopy to investigate whether or not idiopathic normal pressure hydrocephalus is associated with neuronal dysfunction or ischemia in the brain. We evaluate whether or not proton magnetic resonance spectroscopy is useful for predicting improvement after long-term external lumbar drainage (ELD) of cerebrospinal fluid.METHODS: Eighteen patients (mean age, 73 yr; six women) and 10 matching controls participated. Participants were characterized by clinical features, cognitive and motor function tests, and cerebrospinal fluid hydrodynamics (patients only). Signals from N-acetyl-aspartate (NAA), choline, lactate, and creatine (Cr) (reference) were sampled once in controls and twice in patients (before and after a 3-day ELD of approximately 135 mL/24 h) by proton magnetic resonance spectroscopy (1.5 T) from a 7.2-mL volume in the frontal white matter. Improvement was defined by video recordings of the patients' gait.RESULTS: Sixteen patients finished the ELD (one patient had meningitis, and one patient had catheter insertion failure) with a mean drain volume of 395 mL. NAA/Cr ratios were lower in patients than in controls (1.60 versus 1.84, P = 0.02), but no difference was found for choline/Cr ratios. No lactate signals were detected. Fifty percent of patients improved after ELD. They had higher NAA/Cr ratios than nonimproved patients (1.70 versus 1.51, P = 0.01), but no differences were found in choline/Cr ratios or drain volume.CONCLUSION: NAA/Cr ratios were decreased in patients with idiopathic normal pressure hydrocephalus, which is consistent with neuronal dysfunction in the frontal white matter. Improved patients had NAA/Cr ratios close to normal, indicating that enough functional neurons are a prerequisite for the cerebrospinal fluid drainage to have an effect.
37.	Lindén, Christina, et al. (författare) Re: Lindén et al.: Normal-tension glaucoma has normal intracranial pressure: a prospective study of intracranial pressure and intraocular pressure in different body positions (Ophthalmology.2018;125:361-368) REPLY 2018 Ingår i: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 125:10, s. e74-e75 Tidskriftsartikel (refereegranskat)
38.	Luciano, Mark, et al. (författare) Placebo-controlled effectiveness of idiopathic normal pressure hydrocephalus shunting : a randomized pilot trial 2023 Ingår i: Neurosurgery. - : Wolters Kluwer. - 0148-396X .- 1524-4040. ; 92:3, s. 481-489 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Multiple prospective nonrandomized studies have shown 60% to 70% of patients with idiopathic normal pressure hydrocephalus (iNPH) improve with shunt surgery, but multicenter placebo-controlled trial data are necessary to determine its effectiveness.OBJECTIVE: To evaluate the effectiveness of cerebrospinal fluid shunting in iNPH through comparison of open vs placebo shunting groups at 4 months using a pilot study.METHODS: Patients were randomized to a Codman Certas Plus valve (Integra LifeSciences) set at 4 (open shunt group) or 8 (“virtual off”; placebo group). Patients and assessors were blinded to treatment group. The primary outcome measure was 10-m gait velocity. Secondary outcome measures included functional scales for bladder control, activities of daily living, depression, and quality of life. Immediately after 4-month evaluation, all shunts were adjusted in a blinded fashion to an active setting and followed to 12 months after shunting.RESULTS: A total of 18 patients were randomized. At the 4-month evaluation, gait velocity increased by 0.28 ± 0.28 m/s in the open shunt group vs 0.04 ± 0.17 m/s in the placebo group. The estimated treatment difference was 0.22 m/s ([P = .071], 95% CI −0.02 to 0.46). Overactive Bladder Short Form symptom bother questionnaire significantly improved in open shunt vs placebo (P = .007). The 4-month treatment delay did not reduce the subsequent response to active shunting, nor did it increase the adverse advents rate at 12 months.CONCLUSION: This multicenter, randomized pilot study demonstrates the effectiveness, safety, and feasibility of a placebo-controlled trial in iNPH, and found a trend suggesting gait velocity improves more in the open shunt group than in the placebo group.
39.	Malm, Jan, Professor, 1957-, et al. (författare) Hemodynamic Disturbances in Posterior Circulation Stroke : 4D Flow Magnetic Resonance Imaging Added to Computed Tomography Angiography 2021 Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 15 Tidskriftsartikel (refereegranskat)abstract Objective: A clinically feasible, non-invasive method to quantify blood flow, hemodynamics, and collateral flow in the vertebrobasilar arterial tree is missing. The objective of this study was to evaluate the feasibility of quantifying blood flow and blood flow patterns using 4D flow magnetic resonance imaging (MRI) in consecutive patients after an ischemic stroke in the posterior circulation. We also explore if 4D-flow, analyzed in conjunction with computed tomography angiography (CTA), has potential as a diagnostic tool in posterior circulation stroke.Methods: Twenty-five patients (mean age 62 years; eight women) with acute ischemic stroke in the posterior circulation were investigated. At admission, all patients were examined with CTA followed by MRI (4D flow MRI and diffusion-weighted sequences) at median 4 days after the presenting event. Based on the classification of Caplan, patients were divided into proximal/middle (n = 16) and distal territory infarcts (n = 9). Absolute and relative blood flow rates were calculated for internal carotid arteries (ICA), vertebral arteries (VA), basilar artery (BA), posterior cerebral arteries (P1 and P2), and the posterior communicating arteries (Pcom). In a control group consisting of healthy elderly, the 90th and 10th percentiles of flow were calculated in order to define normal, increased, or decreased blood flow in each artery. “Major hemodynamic disturbance” was defined as low BA flow and either low P2 flow or high Pcom flow. Various minor hemodynamic disturbances were also defined. Blood flow rates were compared between groups. In addition, a comprehensive analysis of each patient’s blood flow profile was performed by assessing relative blood flow rates in each artery in conjunction with findings from CTA.Results: There was no difference in total cerebral blood flow between patients and controls [604 ± 117 ml/min vs. 587 ± 169 ml/min (mean ± SD), p = 0.39] or in total inflow to the posterior circulation (i.e., the sum of total VA and Pcom flows, 159 ± 63 ml/min vs. 164 ± 52 ml/min, p = 0.98). In individual arteries, there were no significant differences between patients and controls in absolute or relative flow. However, patients had larger interindividual relative flow variance in BA, P1, and P2 (p = 0.01, <0.01, and 0.02, respectively). Out of the 16 patients that had proximal/middle territory infarcts, nine had CTA findings in VA and/or BA generating five with major hemodynamic disturbance identified with 4D flow MRI. For those without CTA findings, seven had no or minor 4D flow MRI hemodynamic disturbance. Among nine patients with distal territory infarcts, one had major hemodynamic disturbances, while the remaining had minor disturbances.Conclusion: 4D flow MRI contributed to the identification of the patients who had major hemodynamic disturbances from the vascular pathologies revealed on CTA. We thus conclude that 4D flow MRI could add valuable hemodynamic information when used in conjunction with CTA.
40.	Malm, Jan, Professor, 1957-, et al. (författare) Influence of comorbidities in idiopathic normal pressure hydrocephalus - research and clinical care : A report of the ISHCSF task force on comorbidities in INPH 2013 Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Idiopathic normal pressure hydrocephalus (INPH) is a syndrome of ventriculomegaly, gait impairment, cognitive decline and incontinence that occurs in an elderly population prone to many types of comorbidities. Identification of the comorbidities is thus an important part of the clinical management of INPH patients. In 2011, a task force was appointed by the International Society for Hydrocephalus and Cerebrospinal Fluid Disorders (ISHCSF) with the objective to compile an evidence-based expert analysis of what we know and what we need to know regarding comorbidities in INPH. This article is the final report of the task force. The expert panel conducted a comprehensive review of the literature. After weighing the evidence, the various proposals were discussed and the final document was approved by all the task force members and represents a consensus of expert opinions. Recommendations regarding the following topics are given: I. Musculoskeletal conditions; II. Urinary problems; III. Vascular disease including risk factors, Binswanger disease, and white matter hyperintensities; IV. Mild cognitive impairment and Alzheimer disease including biopsies; V. Other dementias (frontotemporal dementia, Lewy body, Parkinson); VI. Psychiatric and behavioral disorders; VII. Brain imaging; VIII. How to investigate and quantify. The task force concluded that comorbidity can be an important predictor of prognosis and post-operative outcome in INPH. Reported differences in outcomes among various INPH cohorts may be partly explained by variation in the rate and types of comorbidities at different hydrocephalus centers. Identification of comorbidities should thus be a central part of the clinical management of INPH where a detailed history, physical examination, and targeted investigations are the basis for diagnosis and grading. Future INPH research should focus on the contribution of comorbidity to overall morbidity, mortality and long-term outcomes.
41.	Qvarlander, Sara, Teknisk doktor, 1982-, et al. (författare) CSF formation rate : a potential glymphatic flow parameter in hydrocephalus? 2024 Ingår i: Fluids and Barriers of the CNS. - : BioMed Central (BMC). - 2045-8118. ; 21:1 Tidskriftsartikel (refereegranskat)abstract Background: Studies indicate that brain clearance via the glymphatic system is impaired in idiopathic normal pressure hydrocephalus (INPH). This has been suggested to result from reduced cerebrospinal fluid (CSF) turnover, which could be caused by a reduced CSF formation rate. The aim of this study was to determine the formation rate of CSF in a cohort of patients investigated for INPH and compare this to a historical control cohort.Methods: CSF formation rate was estimated in 135 (75 ± 6 years old, 64/71 men/women) patients undergoing investigation for INPH. A semiautomatic CSF infusion investigation (via lumbar puncture) was performed. CSF formation rate was assessed by downregulating and steadily maintaining CSF pressure at a zero level. During the last 10 min, the required outflow to maintain zero pressure, i.e., CSF formation rate, was continuously measured. The values were compared to those of a historical reference cohort from a study by Ekstedt in 1978.Results: Mean CSF formation rate was 0.45 ± 0.15 ml/min (N = 135), equivalent to 27 ± 9 ml/hour. There was no difference in the mean (p = 0.362) or variance (p = 0.498) of CSF formation rate between the subjects that were diagnosed as INPH (N = 86) and those who were not (N = 43). The CSF formation rate in INPH was statistically higher than in the reference cohort (0.46 ± 0.15 vs. 0.40 ± 0.08 ml/min, p = 0.005), but the small difference was probably not physiologically relevant. There was no correlation between CSF formation rate and baseline CSF pressure (r = 0.136, p = 0.115, N = 135) or age (-0.02, p = 0.803, N = 135).Conclusions: The average CSF formation rate in INPH was not decreased compared to the healthy reference cohort, which does not support reduced CSF turnover. This emphasizes the need to further investigate the source and routes of the flow in the glymphatic system and the cause of the suggested impaired glymphatic clearance in INPH.
42.	Ryska, P., et al. (författare) Variability of Normal Pressure Hydrocephalus Imaging Biomarkers with Respect to Section Plane Angulation : How Wrong a Radiologist Can Be? 2021 Ingår i: American Journal of Neuroradiology. - : American Society of Neuroradiology. - 0195-6108 .- 1936-959X. ; 42:7, s. 1201-1207 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND PURPOSE: Systematic analysis of angulation-related variability of idiopathic normal pressure hydrocephalus imaging biomarkers has not been published yet. Our aim was to evaluate the variability of these radiologic biomarkers with respect to imaging plane angulation.MATERIALS AND METHODS: Eighty subjects (35 with clinically confirmed idiopathic normal pressure hydrocephalus and 45 age- and sex-matched healthy controls) were prospectively enrolled in a 3T brain MR imaging study. Two independent readers assessed 12 radiologic idiopathic normal pressure hydrocephalus biomarkers on sections aligned parallel or perpendicular to the bicallosal, bicommissural, hypophysis-fastigium, and brain stem vertical lines, respectively.RESULTS: Disproportionately enlarged subarachnoid space hydrocephalus, simplified callosal angle, frontal horn diameter, z-Evans Index, and cella media vertical width did not show significant systematic differences in any of 6 section plane combinations studied. The remaining 7 biomarkers (including the Evans Index and callosal angle) showed significant differences in up to 4 of 6 mutually compared section plane combinations. The values obtained from sections aligned with the brain stem vertical line (parallel to the posterior brain stem margin) showed the most deviating results from other section angulations.CONCLUSIONS: Seven of 12 idiopathic normal pressure hydrocephalus biomarkers including the frequently used Evans Index and callosal angle showed statistically significant deviations when measured on sections whose angulations differed or did not comply with the proper section definition published in the original literature. Strict adherence to the methodology of idiopathic normal pressure hydrocephalus biomarker assessment is, therefore, essential to avoid an incorrect diagnosis. Increased radiologic and clinical attention should be paid to the biomarkers showing low angulation-related variability yet high specificity for idiopathic normal pressure hydrocephalus-related morphologic changes such as the z-Evans Index, frontal horn diameter, or disproportionately enlarged subarachnoid space hydrocephalus.
43.	Vikner, Tomas, et al. (författare) Blood-brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly 2024 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Blood-brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68-84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume ( formula presented ), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10-3 min-1) and formula presented from 0.79 to 1.78%. Cognition was related to PS (·10-3 min-1) in hippocampus (β = - 2.9; p = 0.006), basal ganglia (β = - 2.3; p = 0.04), white matter (β = - 2.6; p = 0.04), whole-brain (β = - 2.7; p = 0.04) and borderline-related for cortex (β = - 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS-cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.
44.	Vikner, Tomas, et al. (författare) Blood-brain barrier permeability, vascular density, and cerebral 4D flow MRI hemodynamics in a population-based elderly cohort Annan publikation (övrigt vetenskapligt/konstnärligt)
45.	Vikner, Tomas, et al. (författare) Characterizing pulsatility in distal cerebral arteries using 4D flow MRI 2020 Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016. ; 40:12, s. 2429-2440 Tidskriftsartikel (refereegranskat)abstract Recent reports have suggested that age-related arterial stiffening and excessive cerebral arterial pulsatility cause blood-brain barrier breakdown, brain atrophy and cognitive decline. This has spurred interest in developing non-invasive methods to measure pulsatility in distal vessels, closer to the cerebral microcirculation. Here, we report a method based on four-dimensional (4D) flow MRI to estimate a global composite flow waveform of distal cerebral arteries. The method is based on finding and sampling arterial waveforms from thousands of cross sections in numerous small vessels of the brain, originating from cerebral cortical arteries. We demonstrate agreement with internal and external reference methods and show the ability to capture significant increases in distal cerebral arterial pulsatility as a function of age. The proposed approach can be used to advance our understanding regarding excessive arterial pulsatility as a potential trigger of cognitive decline and dementia.
46.	Vikström, Axel, et al. (författare) Establishing the distribution of cerebrovascular resistance using computational fluid dynamics and 4D flow MRI 2024 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Cerebrovascular resistance (CVR) regulates blood flow in the brain, but little is known about the vascular resistances of the individual cerebral territories. We present a method to calculate these resistances and investigate how CVR varies in the hemodynamically disturbed brain. We included 48 patients with stroke/TIA (29 with symptomatic carotid stenosis). By combining flow rate (4D flow MRI) and structural computed tomography angiography (CTA) data with computational fluid dynamics (CFD) we computed the perfusion pressures out from the circle of Willis, with which CVR of the MCA, ACA, and PCA territories was estimated. 56 controls were included for comparison of total CVR (tCVR). CVR were 33.8 ± 10.5, 59.0 ± 30.6, and 77.8 ± 21.3 mmHg s/ml for the MCA, ACA, and PCA territories. We found no differences in tCVR between patients, 9.3 ± 1.9 mmHg s/ml, and controls, 9.3 ± 2.0 mmHg s/ml (p = 0.88), nor in territorial CVR in the carotid stenosis patients between ipsilateral and contralateral hemispheres. Territorial resistance associated inversely to territorial brain volume (p < 0.001). These resistances may work as reference values when modelling blood flow in the circle of Willis, and the method can be used when there is need for subject-specific analysis.
47.	Wahlin, Anders, et al. (författare) Re: Wahlin et al. : Optic nerve length before and after spaceflight [REPLY] 2021 Ingår i: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 128:5, s. E28-E28 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
48.	Williams, Michael A., et al. (författare) Mischaracterization of Spaceflight-Associated Neuro-ocular Syndrome 2019 Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 76:10, s. 1258-1259 Tidskriftsartikel (refereegranskat)
49.	Wåhlin, Anders, et al. (författare) 4D flow MRI hemodynamic biomarkers for cerebrovascular diseases 2022 Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:2, s. 115-127 Forskningsöversikt (refereegranskat)abstract Alterations in cerebral blood flow are common in several neurological diseases among the elderly including stroke, cerebral small vessel disease, vascular dementia, and Alzheimer's disease. 4D flow magnetic resonance imaging (MRI) is a relatively new technique to investigate cerebrovascular disease, and makes it possible to obtain time-resolved blood flow measurements of the entire cerebral arterial venous vasculature and can be used to derive a repertoire of hemodynamic biomarkers indicative of cerebrovascular health.The information that can be obtained from one single 4D flow MRI scan allows both the investigation of aberrant flow patterns at a focal location in the vasculature as well as estimations of brain-wide disturbances in blood flow. Such focal and global hemodynamic biomarkers show the potential of being sensitive to impending cerebrovascular disease and disease progression and can also become useful during planning and follow-up of interventions aiming to restore a normal cerebral circulation.Here, we describe 4D flow MRI approaches for analyzing the cerebral vasculature. We then survey key hemodynamic biomarkers that can be reliably assessed using the technique. Finally, we highlight cerebrovascular diseases where one or multiple hemodynamic biomarkers are of central interest.
50.	Wåhlin, Anders, et al. (författare) Optic Nerve Length before and after Spaceflight 2021 Ingår i: Ophthalmology. - : Elsevier. - 0161-6420 .- 1549-4713. ; 128:2, s. 309-316 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The spaceflight-associated neuro-ocular syndrome (SANS) affects astronauts on missions to the International Space Station (ISS). The SANS has blurred vision and ocular changes as typical features. The objective of this study was to investigate if microgravity can create deformations or movements of the eye or optic nerve, and if such changes could be linked to SANS.DESIGN: Cohort study.PARTICIPANTS: Twenty-two astronauts (age 48 ± 4 years).METHODS: The intervention consisted of time in microgravity at the ISS. We co-registered pre- and postspaceflight magnetic resonance imaging (MRI) scans and generated centerline representations of the optic nerve. The coordinates for the optic nerve head (ONH) and optic chiasm (OC) ends of the optic nerve were recorded along with the entire centerline path.MAIN OUTCOME MEASURES: Optic nerve length, ONH movement, and OC movement after time in microgravity.RESULTS: Optic nerve length increased (0.80 ± 0.74 mm, P < 0.001), primarily reflecting forward ONH displacement (0.63 ± 0.53 mm, P < 0.001). The forward displacement was positively related to mission duration, preflight body weight, and clinical manifestations of SANS. We also detected upward displacement of the OC (0.39 ± 0.50 mm, P = 0.002), indicative of brain movement, but this observation could not be linked to SANS.CONCLUSIONS: The spaceflight-induced optic nerve lengthening and anterior movement of the ONH support that SANS is caused by an altered pressure difference between the brain and the eye, leading to a forward push on the posterior of the eye. Body weight is a potential contributing risk factor. Direct assessment of intracranial pressure in space is required to verify the implicated mechanism behind the ocular findings in SANS.

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