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  • 1.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Blekinge Centre of Competence, Blekinge Hospital Karlskrona, Karlskrona, Sweden.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Elgh, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Smith, Cynthia
    Williams, Michael A
    Malm, Jan
    A computerized neuropsychological test battery designed for idiopathic normal pressure hydrocephalus2014In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 11, article id 22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A tool for standardized and repeated neuropsychological assessments in patients with idiopathic normal pressure hydrocephalus (INPH) is needed. The objective of this study was to develop a computerized neuropsychological test battery designed for INPH and to evaluate its reliability, validity and patient's ability to complete the tests.

    METHODS: Based on a structured review of the literature on neuropsychological testing in INPH, the eight tests most sensitive to the INPH cognitive profile were implemented in a computerized format. The Geriatric Depression Scale (GDS) was also included. Tests were presented on a touch-screen monitor, with animated instructions and speaker sound. The battery was evaluated with the following cohorts: A. Test-retest reliability, 44 healthy elderly; B. Validity against standard pen and pencil testing, 28 patients with various cognitive impairments; C. Ability to complete test battery, defined as completion of at least seven of the eight tests, 40 investigated for INPH.

    RESULTS: A. All except the figure copy test showed good test-retest reliability, r = 0.67-0.90; B. A high correlation was seen between conventional and computerized tests (r = 0.66-0.85) except for delayed recognition and figure copy task; C. Seventy-eight percent completed the computerized battery; Patients diagnosed with INPH (n = 26) performed worse on all tests, including depression score, compared to healthy controls.

    CONCLUSIONS: A new computerized neuropsychological test battery designed for patients with communicating hydrocephalus and INPH was introduced. Its reliability, validity for general cognitive impairment and completion rate for INPH was promising. After exclusion of the figure copy task, the battery is ready for clinical evaluation and as a next step we suggest validation for INPH and a comparison before and after shunt surgery.

    TRIAL REGISTRATION: ClinicalTrials.org NCT01265251.

  • 2.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation2017In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 14, article id 17Article in journal (Refereed)
    Abstract [en]

    Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

  • 3.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Can pulsatile CSF flow across the cerebral aqueduct cause ventriculomegaly?: A prospective study of patients with communicating hydrocephalus.2019In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 16, no 1, article id 40Article in journal (Refereed)
    Abstract [en]

    Background: Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of detectable cerebrospinal fluid (CSF) outflow obstructions and often with increased CSF pulsatility measured in the cerebral aqueduct (CA). We hypothesize that the cardiac-related pulsatile flow over the CA, with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. This would require a non-zero cardiac cycle averaged net pressure difference (ΔPnet) over the CA, with higher average pressure in the lateral and third ventricles.

    Methods: We tested the hypothesis by calculating ΔPnet across the CA using computational fluid dynamics based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39 × 0.39 × 0.3 mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35 × 0.35 mm2) MRI-data from 30 patients investigated for communicating hydrocephalus.

    Results: The ΔPnet due to CSF pulsations was non-zero for the study group (p = 0.03) with a magnitude of 0.2 ± 0.4 Pa (0.001 ± 0.003 mmHg), with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔPmax was 20.3 ± 11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔPnet and CA cross-sectional area (p = 0.01) and flow asymmetry, described by the ratio of maximum inflow/outflow (p = 0.04), but not for aqueductal stroke volume (p = 0.35).

    Conclusions: The results supported the hypothesis with respect to the direction of ΔPnet, although the magnitude was low. Thus, although the pulsations may generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.

  • 4.
    Johansson, Elias
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bahrami, Nazila
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cerebral microbleeds in idiopathic normal pressure hydrocephalus2016In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 13, article id UNSP 4Article in journal (Refereed)
    Abstract [en]

    Background: A vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH.

    Methods: In this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence. The MRI exams were reviewed by two neuroradiologists for the presence of CMBs; the prevalence of findings of two or more CMBs was compared between INPH group and control group. After investigation, INPH patients underwent shunt surgery.

    Results: Two or more CMB were detected more frequently in the INPH group compared to HeCo (n = 6, 43 % vs. n = 4, 10 %; p = 0.01). Among the participants where MRI revealed CMB, the number of CMB was higher among the INPH patients than the HeCo (median 8; IQR 2-34 vs. median 1; IQR 1-2; p = 0.005).

    Conclusions: This study supports a vascular component to the pathophysiology of INPH.

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