Publications by authors named "Jan Malm"

Variations in cerebral blood flow and blood volume interact with intracranial pressure and cerebrospinal fluid dynamics, all of which play a crucial role in brain homeostasis. A key physiological modulator is respiration, but its impact on cerebral blood flow and volume has not been thoroughly investigated. Here we used 4D flow MRI in a population-based sample of 65 participants (mean age = 75 ± 1) to quantify these effects.

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Article Synopsis
  • Selective antegrade cerebral perfusion (SACP) is a technique used to maintain brain blood flow during aortic arch surgeries that require temporary stopping of blood circulation, with two methods: bilateral (bSACP) and unilateral (uSACP), each having its risks.
  • A new predictive method was developed and tested to determine cerebral perfusion pressures (CPP) during SACP, helping surgeons decide which SACP approach to use preoperatively, utilizing patient-specific imaging and simulations.
  • The study involved five patients and demonstrated that the prediction method was accurate, with minimal errors in CPP predictions, highlighting the importance of collateral artery size for accurate modeling in surgical planning.
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Higher-Level Gait Disorder (HLGD) is a type of gait disorder estimated to affect up to 6% of the older population. By definition, its symptoms originate from the higher-level nervous system, yet its association with brain morphology remains unclear. This study hypothesizes that there are patterns in brain morphology linked to HLGD.

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Background: Infusion testing is an established method for assessing CSF resistance in patients with idiopathic normal pressure hydrocephalus (iNPH). To what extent the increased resistance is related to the glymphatic system is an open question. Here we introduce a computational model that includes the glymphatic system and enables us to determine the importance of (1) brain geometry, (2) intracranial pressure, and (3) physiological parameters on the outcome of and response to an infusion test.

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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.

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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 ( ), and 4D flow MRI to assess cerebral arterial pulsatility.

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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).

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Article Synopsis
  • - The study aimed to investigate the occurrence of freezing of gait (FoG) in patients with idiopathic normal pressure hydrocephalus (iNPH), finding that 16% exhibited FoG before surgery, which decreased to 8% afterward.
  • - FoG was linked to factors such as older age, slower walking speed, lower cognitive function, and a longer disease duration; most FoG episodes happened during turning.
  • - The results suggest that FoG is a common symptom in iNPH, and shunt surgery can lead to improvements in this symptom.
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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.

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Background: Compromised cerebral blood flow can contribute to future ischemic events in patients with symptomatic carotid artery disease. However, there is limited knowledge of the effects on cerebral hemodynamics resulting from a reduced internal carotid artery (ICA) blood flow rate (BFR).

Purpose: Investigate how reduced ICA-BFR, relates to BFR in the cerebral arteries.

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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.

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Article Synopsis
  • - The study aimed to understand how certain medications affect cerebral blood flow during general anesthesia, using phase-contrast MRI for accurate measurement, instead of relying solely on blood pressure.
  • - Eighteen healthy volunteers underwent two drug interventions (noradrenaline and labetalol), which altered mean arterial pressure (MAP) while measuring changes in cerebral blood flow and cardiac output (CO).
  • - Results showed that noradrenaline infusion decreased both cerebral blood flow and cardiac output, while labetalol did not significantly change cerebral blood flow, indicating that increasing MAP might not enhance cerebral blood flow as expected.
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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.

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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.

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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).

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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).

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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.

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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.

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Article Synopsis
  • - Alterations in cerebral blood flow are common in elderly neurological diseases like stroke, small vessel disease, vascular dementia, and Alzheimer's, impacting overall brain health.
  • - 4D flow MRI is a new imaging technique that provides detailed time-resolved measurements of blood flow in the brain and identifies hemodynamic biomarkers that can track cerebrovascular health.
  • - The study focuses on how 4D flow MRI can reveal both localized and widespread blood flow issues, offering insights for early detection and monitoring interventions in cerebrovascular diseases.
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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.

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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).

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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.

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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.

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Background: Carotid stenosis can profoundly affect cerebral hemodynamics, which cannot simply be inferred from the degree of stenosis. We quantified and mapped the distribution of the blood flow rate (BFR) in the cerebral arteries before and after carotid endarterectomy using four-dimensional (4D) phase-contrast (PC) magnetic resonance imaging (MRI).

Methods: Nineteen patients (age, 71 ± 6 years; 2 women) with symptomatic carotid stenosis (≥50%) undergoing carotid endarterectomy (CEA) were investigated using 4D PC-MRI before and after surgery.

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