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  • 51.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    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, Radiation Physics.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, p. 297-297Article in journal (Refereed)
  • 52.
    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.
    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.Manuscript (preprint) (Other academic)
    Abstract [en]

    Communicating hydrocephalus is a disease where the cerebral ventricles are enlarged. It is characterized by the absence of 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 cerebral aqueduct (CA), with fast systolic outflow and slow diastolic inflow, can generate net pressure effects that could source the ventriculomegaly in these patients. Our hypothesis predicts a cardiac cycle averaged net pressure difference (ΔPnet) over the CA, with higher average pressure in the lateral and third ventricles. We tested the hypothesis by calculating ΔPnetacross the CA using computational fluid dynamics (CFD) based on prospectively collected high-resolution structural (FIESTA-C, resolution 0.39x0.39x0.3mm3) and velocimetric (2D-PCMRI, in-plane resolution 0.35x0.35mm2) MRI-data from 30 patients investigated for communicating hydrocephalus. The ΔPnetdue to CSF pulsations was non-zero for the study group (p=0.03) with a magnitude of 0.2±0.4 Pa, with higher pressure in the third ventricle. The maximum pressure difference over the cardiac cycle ΔPmaxwas 20.3±11.8 Pa and occurred during systole. A generalized linear model verified an association between ΔPnetand 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). The results thus supported the hypothesis with respect to the direction of ΔPnet, although the magnitude was low. This indicates that although the pulsations do generate a pressure difference across the CA it is likely too small to explain the ventriculomegaly in communicating hydrocephalus.

  • 53.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Symptoms of Depression are Common in Patients With Idiopathic Normal Pressure Hydrocephalus: The INPH-CRasH Study2016In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, no 2, p. 161-168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: If patients with idiopathic normal pressure hydrocephalus (INPH) also have depression, this could have important clinical ramifications in assessment and management of their cognitive function and response to shunting. In many dementias, depression is overrepresented, but the prevalence of depression in shunted patients with INPH is unknown.

    OBJECTIVE: The objective of this case-control study was to assess the prevalence of symptoms of depression in shunted INPH patients compared with population-based controls.

    METHODS: INPH patients consecutively shunted from 2008 to 2010 in Sweden were analyzed. Patients remaining after inclusion (within 60-85 years and not having dementia, ie, mini-mental state examination >=23) had a standardized visit to their healthcare provider and answered an extensive questionnaire. Age- and sex-matched population-based controls underwent the same procedure. Symptoms of depression were assessed using the Geriatric Depression Scale 15 (suspected depression defined as >=5 points, suspected severe depression as >=12 points). This study is part of the INPH-CRasH study.

    RESULTS: One hundred seventy-six INPH patients and 368 controls participated. After adjustment for age, sex, cerebrovascular disease, and systolic and diastolic blood pressure, patients had a higher mean depression score (patients: 4.9 ± 3.7 SD, controls: 1.9 ± 2.3 SD; OR 1.4, 95% CI 1.3-1.6, P < .001), more patients had suspected depression (46% vs 13%, OR 6.4, 95% CI 3.8-10.9, P < .001), and more patients had suspected severe depression (7.3% vs 0.6%, OR 14.4, 95% CI 3.0-68.6, P < .005).

    CONCLUSION: Symptoms of depression are overrepresented in INPH patients compared with the population, despite treatment with a shunt. Screening for depression should be done in the evaluation of INPH patients in order to find and treat a coexisting depression.

  • 54.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Ventriculomegaly and balance disturbances in patients with TIA2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, no 3, p. 163-170Article in journal (Refereed)
    Abstract [en]

    Objectives -  Dilated ventricles and gait disturbances are common in the elderly, and these are also features of the treatable syndrome idiopathic normal pressure hydrocephalus (INPH). Many studies report an association between hypertension, vascular disease and INPH. The objective of this study was to study the frequency of ventriculomegaly, with or without hydrocephalic symptoms, in patients who had suffered from a transitory ischaemic attack (TIA).

    Methods -  Gait, Romberg sign, tandem standing and one-leg stance were consecutively evaluated in elderly >24 h after a TIA. Ventricular size, white matter lesions and atrophy were assessed on computed tomography scans. Exclusion criteria were conditions possibly influencing the balance tests.

    Results -  Seventy-six patients with TIA out of 105 were included. Ventriculomegaly [Evans Index (EI) > 0.30] was observed in 19.7% and very large ventricles (EI > 0.33) in 7.9%. Ventriculomegaly was found in 58% of the patients with a previous 'history of balance or gait disturbance', but only in 12% of those without any prior disturbance (chi-square test; P = 0.0009). Three out of 76 patients with TIA (3.9%) fulfilled both radiological and clinical criteria for 'possible INPH'.

    Conclusion -  Ventriculomegaly is a common finding in elderly. One out of 20 patients with TIA may suffer from INPH, existing before and independent of the TIA diagnosis. Therefore, patients presenting with ventriculomegaly and gait/balance disturbances not attributable to other causes should be referred to a hydrocephalus centre or a neurologist with special interest in INPH.

  • 55.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wikkelsö, Carsten
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Kahlon, Babar
    Leijon, Göran
    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.
    Vascular risk factors contribute to idiopathic normal pressure hydrocephalus: the INPH-CRasH StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Objective

    The objective was to determine the complete modern vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative INPH-patients and population-based controls, in order to confirm the impact of vascular disease on INPH pathophysiology.

     

    Methods

    All shunted INPH-patients in Sweden 2008-2010 were compared to age- and gender-matched population-based controls. Inclusion criteria: 60-85 years and mini mental state estimation ³23. The ten most important modern VRFs as well as cerebrovascular and peripheral vascular disease were prospectively assessed through blood samples, by-protocol clinical examinations and standardized questionnaires. Investigated VRFs: hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking, diet, alcohol intake, cardiac disease and, physical activity.

     

    Results

    After exclusion, 176 INPH-patients and 368 controls participated. Using multivariable logistic regression, hyperlipidemia (OR: 2.380, 95%CI: 1.434-3.950), diabetes (OR: 2.169, 95%CI: 1.195-3.938), obesity (OR: 5.428, 95%CI: 2.502-11.772) and, psychosocial factors (OR: 5.343, 95%CI: 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, cerebrovascular and peripheral vascular disease were overrepresented in INPH, although not independently. The protective factors: moderate alcohol intake and physical activity were overrepresented among the controls. The population attributable risk percentage was 24%.

     

    Conclusions

    Our findings confirm that INPH-patients have a more dangerous VRF-profile and lack the protective factors present in the population. Almost one quarter of INPH could be explained by VRF, suggesting that INPH possibly may be a subgroup of vascular dementia. Targeted interventions against modifiable VRF are likely to have beneficial effects in INPH.

  • 56.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikkelsö, Carsten
    Laurell, Katarina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Kahlon, Babar
    Leijon, Göran
    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.
    Vascular risk factors in INPH A prospective case- control study (the INPH-CRasH study)2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 6, p. 577-585Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and populationbased controls to determine the extent to which vascular disease influences INPH pathophysiology. Methods: All patients with INPH who underwent shunting in Sweden in 2008-2010 were compared to age-and sex-matched population-based controls. Inclusion criteria were age 60-85 years and no dementia. The 10 most important VRFs and cerebrovascular and peripheral vascular disease were prospectively assessed using blood samples, clinical examinations, and standardized questionnaires. Assessed VRFs were hypertension, hyperlipidemia, diabetes, obesity, psychosocial factors, smoking habits, diet, alcohol intake, cardiac disease, and physical activity. Results: In total, 176 patients with INPH and 368 controls participated. Multivariable logistic regression analysis indicated that hyperlipidemia (odds ratio [OR] 2.380; 95% confidence interval [CI] 1.434-3.950), diabetes (OR 2.169; 95% CI 1.195-3.938), obesity (OR 5.428; 95% CI 2.502-11.772), and psychosocial factors (OR 5.343; 95% CI 3.219-8.868) were independently associated with INPH. Hypertension, physical inactivity, and cerebrovascular and peripheral vascular disease were also overrepresented in INPH. Moderate alcohol intake and physical activity were overrepresented among the controls. The population-attributable risk percentage was 24%. Conclusions: Our findings confirm that patients with INPH have more VRFs and lack the protective factors present in the general population. Almost 25% of cases of INPH may be explained by VRFs. This suggests that INPH may be a subtype of vascular dementia. Targeted interventions against modifiable VRFs are likely to have beneficial effects on INPH.

  • 57.
    Israelsson, Hanna
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    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.
    CSF shunting improves long-term quality of life in idiopathic normal pressure hydrocephalus: the INPH-CRasH StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction

    Measurements of quality of life (QoL) are important when evaluating a surgical method. However, QoL after shunting in idiopathic normal pressure hydrocephalus (INPH) is seldom assessed. The objective of this study was to assess QoL in a large cohort of shunted INPH patients, compared to the population, and investigate which factors influence QoL in INPH.

     

    Methods

    All INPH patients shunted in Sweden 2008-2010 were scrutinized. Population-based controls were age- and gender-matched to the patients. One hundred and seventy-six INPH patients and 368 controls were included. QoL was assessed using the EQ5D5L instrument, measuring overall QoL and health status in five dimensions. Independency, measured by accommodation and need for in-home care, and comorbidities were assessed. Patients were followed up 6-45 months after surgery (mean follow-up time: 21 months).

     

    Results

    Shunted INPH patients had lower QoL than controls (p<0.001). The patients’ health status in mobility, self-care, daily activities, and anxiety/depression was worse than the controls both before and after surgery (p<0.001). Shunting improved QoL (p<0.001) and health status in all dimensions (p<0.005). The main predictors of low QoL in INPH were depression (p<0.001) and severity of gait disturbance (p=0.001). Fewer INPH patients than controls lived independently (45% vs 85%, p<0.001) Time after shunting had no influence on QoL.

     

    Interpretation

    Improvement in QoL after shunting in INPH is long lasting, but shunted INPH patients do not reach the same level of QoL as the population. Depression and severity of gait disturbance are the strongest predictors of low QoL in INPH. 

  • 58.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters - a cross sectional study of young and old healthy subjects2015In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 56, no 7, article id Meeting Abstract: 116Article in journal (Other academic)
    Abstract [en]

    Purpose: To investigate aging effect on ocular parameters inkluding intraocular pressure (IOP) measured with different tonometry methods in healthy young (HY) and elderly (HE) subjects.

    Methods: Fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79 years of age) were included. IOP was measured with four tonometry methods in a standardized order: Ocular Response Analyser (ORA), Dynamic Contour Tonometry (DCT), Applanation Resonance Tonometry (ART) and Goldmann Applanation Tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), ocular pulse amplitude (OPA) and aqueous humor (aq).

    Results: The mean IOP (HY/HE; mmHg ± standard deviation) was 13.9 ± 2.7/16.4 ± 3.4 with ORA, 15.1 ± 2.1/16.3 ± 3.1 with DCT, 12.3 ± 2.0/13.7 ± 2.8 with GAT and 13.1 ± 2.2/12.1 ± 2.5 with ART. IOP was significantly higher (difference ± standard error) in HE compared to HY measured with ORA (+2.5 mmHg ± 0.6), GAT (+1.4 ± 0.5) and DCT (+1.2 ± 0.6). There was a trend towards lower IOP in HE when measured with ART (-1.0 ± 0.5, p=0.05). There was no difference between HE and HY in CCT, CC, AL or OPA.

    Conclusions: Tonometry methods are affected differently by age. IOP was measured higher in elderly people with ORA, DCT and GAT in this Scandinavian population. This effect was not seen in measurements with ART. Other ocular parameters did not differ between the age groups indicating that these measured parameters are not influenced by age in this population.

  • 59.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Ambarki, Khalid
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    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, Radiation Physics.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Age-dependency of ocular parameters: a cross sectional study of young and elderly healthy subjects2015In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 253, no 11, p. 1979-1983Article in journal (Refereed)
    Abstract [en]

    To investigate the effect of aging on ocular parameters, including intraocular pressure (IOP), measured with different tonometry methods in healthy young (HY) and healthy elderly (HE) subjects and to study the effect of corneal parameters on tonometry methods. In this prospective, cross-sectional study, fifty eyes of 50 HY subjects (28 females, 22-31 years of age) and 43 eyes of 43 HE subjects (22 females, 64-79) were included. IOP was measured with four tonometry methods in a standardized order: ocular response analyser (ORA), dynamic contour tonometry (DCT), applanation resonance tonometry (ART) and Goldmann applanation tonometry (GAT). Other measurements included axial length (AL), central corneal thickness (CCT), corneal curvature (CC), anterior chamber volume (ACV), corneal hysteresis (CH) and corneal resistance factor (CRF). The mean IOP (HY/HE; mmHg +/- standard deviation (SD)) was 12.2 +/- 2.2/14.1 +/- 3.5 with GAT. IOP was significantly higher (difference +/- standard error) in HE compared to HY measured with an ORA (+3.1 mmHg +/- 0.6), GAT (+1.9 +/- 0.6) and DCT (+1.6 +/- 0.6). No significant difference was found in IOP measured with ART. CH and ACV were significantly lower in HE compared to HY. There was no difference between the groups in CCT, CC, AL or CRF. No tonometry method was dependant on CCT or CC. IOP measured with an ORA and via DCT and GAT was higher in HE compared to HY Swedish subjects, while IOP measured with ART did not differ between the groups. In these homogeneous groups, tonometry methods were independent of CCT and CC.

  • 60.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Effects of topical anaesthetics and repeated tonometry on intraocular pressure2014In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 92, no 2, p. 111-115Article in journal (Refereed)
    Abstract [en]

    Purpose:

    To investigate the effects of repeated measurements of intraocular pressure (IOP) using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) to identify mechanisms contributing to the expected IOP reduction.

    Methods:

    A prospective, single-centre study with six healthy volunteers. Consecutive repeated series (six measurements/serie/method) were made alternately on both eyes for 1 hr with oxybuprocaine/fluorescein in the right eye and tetracaine in the left. The left eye was Pentacam((R)) photographed before and repeatedly for 20 min after the IOP measurements. On a separate occasion, the same volunteers received the same amount of anaesthetic drops for 1 hr but without repeated IOP measurements.

    Results:

    A significant IOP reduction occurred with both ART and GAT in the oxybuprocaine-treated eye, -4.4 mmHg and -3.8 mmHg, respectively and with ART in the tetracaine eye, -2.1 mmHg. There was a significant difference in IOP reduction between the oxybuprocaine and tetracaine eyes with ART. There was a significant drop in anterior chamber volume (ACV) immediately after the IOP measurements, -12.6 mu l that returned to pretrial level after 2 min. After 1 hr of receiving anaesthetic eye drops (without IOP measurements), the IOP decreased significantly in the oxybuprocaine eye for both ART and GAT, -3.1 and -1.7 mmHg, respectively, but not in the tetracaine eye (p = 0.72).

    Conclusion:

    The IOP reduction cannot be explained solely by aqueous humor being pressed out of the anterior chamber. While significant IOP reduction occurred with both tetracaine and oxybuprocaine after repeated mechanical applanation, the IOP reduction was significantly greater with oxybuprocaine.

  • 61.
    Johannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement 2 years after myopic laser-assisted subepithelial keratectomy2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 9, p. 1637-1642Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate intraocular pressure (IOP) measurements 24 months after laser-assisted subepithelial keratectomy (LASEK) with 3 tonometry methods-Goldmann applanation tonometry (DCT), Pascal dynamic contour tonometry (DCT), and applanation resonance tonometry (ART)-and to compare them with measurements taken preoperatively and 3 and 6 months postoperatively. SETTING: Department of Ophthalmology, Umea University, lima Sweden. DESIGN: Prospective randomized single-center. METHODS: One randomized eye per person from myopic healthy individuals who had LASEK was included. Visual acuity, central corneal thickness (CCT), corneal curvature, and IOP were measured at all time points. Six IOP measurements were performed per method, with a 5-minute lapse between methods. RESULTS: The study evaluated 38 eyes. Two years after LASEK, dynamic ART was the only method that did not measure significantly lower IOP than before LASEK (mean -0.2 mm Hg +/- 1.6 [SD]). The greatest difference was with GAT (mean -1.9 +/- 1.7 mm Hg) followed by static ART (mean -1.2 +/- 1.6 mm Hg) and then DCT (mean -0.9 +/- 1.3 mm Hg). All methods measured significantly lower IOP at 3 months and 6 months. CONCLUSIONS: Dynamic ART, which analyses IOP measurement during indentation, showed no significant difference in measured IOP after 24 months. The convex tip of the ART device and the continuous sampling of data during corneal indentation seem to be factors in why dynamic ART was less affected by corneal properties and therefore more suitable for IOP measurement in LASEK-treated eyes, although this must be confirmed in larger trials.

  • 62.
    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.

  • 63. Johansson, Staffan B.
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stemme, Göran
    Roxhed, Niclas
    A MEMS-based passive hydrocephalus shunt for body position controlled intracranial pressure regulation2014In: Biomedical microdevices (Print), ISSN 1387-2176, E-ISSN 1572-8781, Vol. 16, no 4, p. 529-536Article in journal (Refereed)
    Abstract [en]

    This paper reports a novel micro electro mechanical system (MEMS) valve with posture controlled 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 differential pressure CSF valves, the CSF valve presented here features a third port which utilizes hydrostatic pressure from a pressure compensating catheter to adapt CSF drainage to optimized levels irrespective of body position. Prototypes have 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 third port. Measured data showed that flow rate was at near ideal values at laying body position and that the flow rate can be adjusted to optimal values at standing body position by selecting an appropriate length of the pressure compensating catheter. This is the first pressure balanced CSF valve intended for body position controlled CSF pressure regulation.

  • 64.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects2018In: Current Neurology and Neuroscience Reports, ISSN 1528-4042, E-ISSN 1534-6293, Vol. 18, no 5, article id 25Article, review/survey (Refereed)
    Abstract [en]

    Purpose of Review A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD. Recent Findings For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory. Summary Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

  • 65.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement after myopic LASEK: a study evaluating Goldmann, Pascal and applanation resonance tonometry2012In: Journal of glaucoma, ISSN 1057-0829, E-ISSN 1536-481X, Vol. 21, no 4, p. 255-259Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To prospectively evaluate 3 tonometry methods-the gold standard, Goldmann applanation tonometry, a new method, Pascal dynamic contour tonometry (PDCT), and a method under development, applanation resonance tonometry (ART)-with respect to intraocular pressure (IOP) measurements before, 3 and 6 months after laser-assisted subepithelial keratectomy (LASEK).

    MATERIALS AND METHODS: One randomly assigned eye of each of 53 healthy individuals, who underwent LASEK surgery for myopia was studied. Visual acuity, central corneal thickness, corneal curvature, and IOP were measured at each visit. Six IOP measurements/methods with 5 minutes pause between methods were performed.

    RESULTS: All tonometry methods measured a significantly lower IOP after LASEK correction by a mean of -3.1 diopters. The IOP reduction was largest after 6 months for Goldmann applanation tonometry (-1.7±1.8 mm Hg) followed by ARTstat (-1.2±1.5 mm Hg), PDCT (-1.1±1.6 mm Hg), and ARTdyn (-1.0±1.5 mm Hg). The reduction of IOP did not differ significantly between different methods (P=0.11). There was a significant further reduction of measured IOP for PDCT between 3 and 6 months (-0.5±1.0 mm Hg). Uncorrected visual acuity improved significantly between 3 and 6 months postoperatively from 1.32±0.28 to 1.43±0.27.

    CONCLUSIONS: All tonometry methods measured a significant, but low, reduction of IOP 3 and 6 months after LASEK. Further change in visual acuity and IOP measurements between 3 and 6 months suggest a still ongoing postoperative process.

  • 66.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Introduction and clinical evaluation of servo-controlled applanation resonance tonometry2012In: Acta Ophthalmologica Scandinavica, ISSN 1395-3907, E-ISSN 1600-0420, Vol. 90, no 7, p. 677-682Article in journal (Refereed)
    Abstract [en]

    Purpose:  In recent years, Applanation Resonance Tonometry (ART) has been suggested for intraocular pressure (IOP) measurements. The manual version of ART (ARTmanual) has been further developed, and to improve usability, an automatic servo-controlled prototype (ARTservo) has been proposed. The aim of this study was to assess the limits of agreement (LoA) of ARTmanual and ARTservo as compared with the reference method, Goldmann Applanation Tonometry (GAT).

    Methods:  This was a prospective single-centre study on 152 eyes from 77 subjects. It was designed according to International Standard Organization’s (ISO) requirements for tonometers (ISO 2001). Intraocular pressure was measured six times/method in a standardized order. The ART technique has two available analysis procedures: a dynamic one that measures IOP during the indentation phase and a static one that causes a Goldmann-like measurement during two seconds of full applanation. The 95% LoA was defined as ±1.96 × standard deviation of difference against GAT.

    Results:  Mean IOP for GAT was 19.1 mmHg (range: 10–37 mmHg). The 95% LoA of ARTmanual was ±4.5 mmHg for both dynamic and static analyses. The 95% LoA of ARTservo was ±5.7 mmHg for dynamic and ±4.9 mmHg for static analyses.

    Conclusions:  This study confirms that the ART methodology is feasible. The further developed ARTmanual fulfilled the ISO standard with both the dynamic and the static analysis techniques. ARTservo with static analysis was close to fulfilling the standard but failed to do so in the highest IOP range. ARTservo has the potential to greatly improve usability if further development is completed.

  • 67.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Pascal, ICare and Goldmann applanation tonometry: a comparative study2008In: Acta ophthalmologica, ISSN 1755-3768, Vol. 86, no 6, p. 614-621Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To compare intraocular pressure (IOP) measurements by Pascal, ICare and Goldmann applanation tonometry (GAT), to evaluate the effects of central corneal thickness (CCT) and curvature on IOP measurement and to estimate the intra-observer variability.

    METHODS: A prospective, single-centre study of 150 eyes with a wide range of pressures. Six masked IOP measurements/method; corneal thickness and curvature were studied for each eye. GAT was the reference.

    RESULTS: IOPPascal and IOPICare correlated with IOPGAT (r = 0.91, 0.89). Mean ICare measurement exceeded GAT by 2 mmHg. Pascal measured higher than GAT at low IOPs and lower at high IOPs. For every 10 mmHg increase in IOP above 31 mmHg, Pascal measured 2 mmHg lower than GAT and vice versa. CCT was correlated significantly with IOPGAT (r = 0.23) and IOPICare (r = 0.43) but not with IOPPascal (P = 0.12). CCT was correlated with age. In a subgroup (>50 years), ICare and the difference between IOPGAT and IOPPascal were affected significantly by the CCT, whereas IOPGAT and IOPPascal were not. Corneal curvature was correlated significantly with IOPGAT (r = -0.27) and IOPPascal (r = -0.26) but not with IOPICare (P = 0.60). Intra-observer variability within each set of six measurements was approximately 2 mmHg, irrespective of method.

    CONCLUSION: This study showed a reasonable overall correlation and concordance between the IOP obtained with the three instruments. None of the methods were completely independent of the biomechanical properties of the cornea. ICare showed a significant dependency upon CCT, whereas GAT and Pascal showed a significant dependency on corneal curvature. All methods showed intra-observer variability, which leaves room for further improvement of methods.

  • 68.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskela, Timo
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Change in intraocular pressure measurement after myopic LASEK: a study evaluating Goldmann, Pascal and applanation resonance tonometryArticle in journal (Refereed)
  • 69.
    Jóhannesson, Gauti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Lindén, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Behndig, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Can we trust intraocular pressure measurements in eyes with intracameral air?2014In: Graefe's Archives for Clinical and Experimental Ophthalmology, ISSN 0721-832X, E-ISSN 1435-702X, Vol. 252, no 10, p. 1607-1610Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To evaluate the effect of intracameral air on intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) in an in-vitro porcine eye model.

    METHODS: IOP was measured on thirteen freshly enucleated eyes at three reference pressures: 20, 30, and 40 mmHg. Six measurements/method were performed in a standardized order with GAT and ART respectively. Air was injected intracamerally in the same manner as during Descemet's stripping endothelial keratoplasty (DSEK) and Descemet's membrane endothelial keratoplasty (DMEK), and the measurements were repeated.

    RESULTS: Measured IOP increased significantly for both tonometry methods after air injection: 0.7 ± 2.1 mmHg for GAT and 10.6 ± 4.9 mmHg for ART. This difference was significant at each reference pressure for ART but not for GAT.

    CONCLUSIONS: Although slightly affected, this study suggests that we can trust GAT IOP-measurements in eyes with intracameral air, such as after DSEK/DMEK operations. Ultrasound-based methods such as ART should not be used.

  • 70.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prostacyclin Influences the Pressure Reactivity in Patients with Severe Traumatic Brain Injury Treated with an ICP-Targeted Therapy2015In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 22, no 1, p. 26-33Article in journal (Refereed)
    Abstract [en]

    This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale a parts per thousand currency sign8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR a parts per thousand currency sign0. Mean PR over 96 h (PRtot) was 0.077 +/- A 0.168, in the prostacyclin group 0.030 +/- A 0.153 and in the placebo group 0.120 +/- A 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PRtot was 0.117 +/- A 0.182 in the unfavorable (GOSE 1-4) and 0.029 +/- A 0.140 in the favorable outcome group (GOSE 5-8). Area under the curve for prediction of death (ROC) was 0.742 and for favorable outcome 0.628. Prostacyclin influenced the PR in a direction of increased pressure stability and a lower PRtot was associated with improved outcome. The individual PR varied substantially over time. The predictive value of PRtot for outcome was not solid enough to be used in the clinical situation.

  • 71.
    Koskinen, Lars-Owe D.
    et al.
    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.
    Zakelis, Rolandas
    Bartusis, Laimonas
    Ragauskas, Arminas
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Can intracranial pressure be measured non-invasively bedside using a two-depth Doppler-technique?2017In: Journal of clinical monitoring and computing, ISSN 1387-1307, E-ISSN 1573-2614, Vol. 31, no 2, p. 459-467Article in journal (Refereed)
    Abstract [en]

    Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer's solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

  • 72.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hägglund, Linda
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olivecrona, Magnus
    The relation between brain interstitial clycerol and pressure reactivity in TBI is prostacyclin dependent2018In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 35, no 16, p. A185-A185Article in journal (Other academic)
  • 73.
    Kristiansen, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Linden, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hallberg, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Blood flow rate of ophthalmic artery in patients with normal tension glaucoma and healthy controls2018In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal (Other academic)
    Abstract [en]

    Purpose: To determine the blood flow rate of the ophthalmic artery (OA) in patients with Normal Tension Glaucoma (NTG) compared to age-matched healthy controls using phase-contrast magnetic resonance imaging (PCMRI).

    Methods: Seventeen patients with treated NTG (11 female; mean age: 70±9 years) and 16 age-matched healthy controls (10 female; mean age: 71±9 years) underwent PCMRI using a 3-Tesla scanner as well as ophthalmological examinations including visual acuity, Goldmann Applanation Tonometry, Humphrey perimetry and fundoscopy. Ophthalmic blood flow was acquired using a 2D PCMRI sequence set to a spatial resolution of 0.35mm/pixel. Mean flow rate and cross-sectional area was calculated using Segment Software. The eye with the most severe glaucomatous damage classified by visual field index (VFI) was chosen for comparison. The primary outcome was blood flow rate of OA.

    Results: The mean VFI was 41% ± 26 (mean±SD) for the worse NTG eyes. The intraocular pressure was 13.6±2.6 mmHg for NTG eyes and 13.8±2.1 mmHg for control eyes. The blood flow rate in the NTG group was 9.6±3.7 ml/min compared to 11.8±5.5 ml/min in the control group. The area was 1.7±0.3 mm2 and 2.0±0.6 mm2 respectively. No statistical significance was found between NTG and the control group regarding blood flow rate (p=0.07) or OA area (p=0.12).

    Conclusions: Despite OA being an anastomosis between the intracranial and extracranial circulation, possibly generating an eye unrelated variability in blood flow, we found a trend level reduction of approximately 2 ml/min in NTG. The finding warrants blood flow rate analysis of smaller arteries specifically supplying the eye, e.g. the central retinal artery.

  • 74.
    Larsson, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Israelsson, Hanna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Epilepsy, headache, and abdominal pain after shunt surgery for idiopathic normal pressure hydrocephalus: the INPH-CRasH study2018In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 128, no 6, p. 1674-1683Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Adverse events related to shunt surgery are common and might have a negative effect on outcome in patients with idiopathic normal pressure hydrocephalus (INPH). The authors' objectives were to establish the frequencies of epilepsy, headache, and abdominal pain and determine their impact on patient quality of life (QOL), in long-term follow-up after shunt surgery for INPH.

    METHODS One hundred seventy-six shunt-treated patients with INPH (mean age 74 years) and 368 age- and sex-matched controls from the population were included. The mean follow-up time after surgery was 21 months (range 6-45 months). Each participant answered a questionnaire regarding present frequency and severity of headache and abdominal pain. Confirmed diagnoses of epilepsy and all prescriptions for antiepileptic drugs (AEDs) before and after shunt surgery for INPH were gathered from national registries. Equivalent presurgical and postsurgical time periods were constructed for the controls based on the date of surgery (the division date for controls is referred to as virtual surgery). All registry data covered a mean period of 6 years (range 3-8 years) before surgery/virtual surgery and 4 years (range 2-6 years) after surgery/virtual surgery. Provoked epileptic seizures were excluded. Patient QOL was assessed with the EuroQoL 5-dimension 5-level instrument.

    RESULTS Epilepsy was more common in shunt-treated patients with INPH than in controls (4.5% vs 1.1%, respectively; p = 0.023), as was treatment with AEDs (14.8% vs 7.3%, respectively; p = 0.010). No difference was found between the populations before surgery/virtual surgery (epilepsy, 2.3% [INPH] vs 1.1% [control], p = 0.280; AED treatment, 8.5% [INPH] vs 5.4% [control], p = 0.235). New-onset epilepsy and new AED treatment after surgery/virtual surgery were more common in INPH (epilepsy, 2.3% [INPH] vs 0.0% [control], p = 0.011; AED, 8.5% [INPH] vs 3.3% [control], p = 0.015). At follow-up, more patients with INPH than controls experienced headache several times per month or more often (36.1% vs 11.6%, respectively; p < 0.001). Patients with INPH and unilateral headache had more right-sided headaches than controls (p = 0.038). Postural headache was experienced by 16% (n = 27 of 169) of the patients with INPH. Twenty percent (n = 35) of the patients with INPH had persistent abdominal pain. Headache was not correlated to lower QOL. The study was underpowered to draw conclusions regarding QOL in patients with INPH who had epilepsy and abdominal pain, but the finding of no net difference in mean QOL indicates that no correlation between them existed.

    CONCLUSIONS Epilepsy, headache, and abdominal pain are common in long-term follow-up in patients after shunt surgery for INPH and are more common among patients with INPH than in the general population. All adverse events, including mild and moderate ones, should be considered during postoperative follow-ups and in the development of new methods for shunt placement.

  • 75. Lawley, Justin S.
    et al.
    Levine, Benjamin D.
    Williams, Michael A.
    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.
    Polaner, David M.
    Subudhi, Andrew W.
    Hackett, Peter H.
    Roach, Robert C.
    Cerebral spinal fluid dynamics: effect of hypoxia and implications for high-altitude illness2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 2, p. 251-262Article, review/survey (Refereed)
    Abstract [en]

    The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial PO2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a "tight fit" brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

  • 76.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Ågren-Wilsson, Aina
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Neurokirurgi.
    Koskinen, Lars-Owe D
    Neurokirurgi.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Neurologi.
    Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves2004In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 101, no 6, p. 944-950Article in journal (Refereed)
    Abstract [en]

    Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.

    Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.

    Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.

  • 77.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hansson, William
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 3, p. 237-242Article in journal (Refereed)
    Abstract [en]

    Objective: External lumbar drainage (ELD) of CSF is a test to determine the suitability of a shunt for patients with normal pressure hydrocephalus (NPH), but its effect on ventricular volume is not known. This study investigates the effect of 3-day ELD of 500 mL on ventricular size and clinical features in patients with idiopathic NPH.

    Methods: Fifteen patients were investigated in a 1.5-T MRI scanner before and after ELD. Ventricular volume was measured manually. Clinical features involved motor and cognitive functions, testing primarily gait and attention. Reduction in ventricular volume was correlated to total drain volume and clinical parameters. Statistical tests were nonparametric, and p < 0.05 was required for significance.

    Results: Drain volume was 415 mL (median 470 mL, range 160-510 mL). Ventricular size was reduced in all patients, averaging 3.7 mL (SD 2.2 mL, p < 0.001), which corresponded to a 4.2% contraction. The ratio of volume contraction to drain volume was only 0.9%. Seven patients improved in gait and 6 in attention. Ventricular reduction and total drain volume correlated neither with improvement nor with each other. The 7 patients with the largest drain volumes (close to 500 mL), had ventricular changes varying from 1.3 to 7.5 mL.

    Conclusions: Clinical improvement occurs in patients with NPH after ELD despite unaltered ventricles, suggesting that ventricular size is of little relevance for postshunt improvement or determining shunt function. The clinical effect provided by ELD, mimicking shunting, is probably related to the recurring CSF extractions rather than to the cumulative effect of the drainage on ventricular volume. Neurology(R) 2012;79:237-242

  • 78.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Neurologi.
    Hauksson, Jón
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    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. Neurologi.
    Improvement after cerebrospinal fluid drainage is related to levels of N-acetyl-aspartate in idiopathic normal pressure hydrocephalus2008In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, no 1, p. 135-142Article in journal (Refereed)
    Abstract [en]

    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.

  • 79.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    CSF pressure assessed by lumbar puncture agrees with intracranial pressure.2007In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 68, no 2, p. 155-158Article in journal (Refereed)
  • 80.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.2008In: Brain, ISSN 1460-2156, Vol. 131, no Pt 11, p. 2904-2912Article in journal (Refereed)
    Abstract [en]

    In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function recovery in INPH patients after CSF removal is related to enhanced activity in medial parts of frontal motor areas considered crucial for motor planning; a finding consistent with INPH being a syndrome related to a reversible suppression of frontal periventricular cortico-basal ganglia-thalamo-cortical pathways.

  • 81.
    Lenfeldt, Niklas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    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, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Diffusion tensor imaging reveals supplementary lesions to frontal white matter in Idiopathic normal pressure hydrocephalus2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 68, no 6, p. 1586-1593Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:: Idiopathic normal pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:: To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:: Eighteen patients and ten controls were included. DTI was performed in a 1.5T MRI scanner before and after three-day drainage of 400 ml of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to 0.05 (Bonferroni corrected). RESULTS:: Decreased FA in patients was found in three regions (p<0.002, p<0.001 and p<0.0001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (p<0.0001) and areas of centrum semiovale associated to the precentral gyri (p<0.002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:: DTI reveals subtle injuries - interpreted as axonal loss and gliosis - to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

  • 82.
    Lindahl, O A
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Constantinou, C E
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Murayama, Y
    Hallberg, Per
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Omata, S
    Tactile resonance sensors in medicine.2009In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 33, no 4, p. 263-273Article in journal (Refereed)
    Abstract [en]

    Tactile sensors in general are used for measuring the physical parameters associated with contact between sensor and object. Tactile resonance sensors in particular are based on the principle of measuring the frequency shift, Deltaf, defined as the difference between a freely vibrating sensor resonance frequency and the resonance frequency measured when the sensor makes contact to an object. Deltaf is therefore related to the acoustic impedance of the object and can be used to characterize its material properties. In medicine, tactile resonance sensor systems have been developed for the detection of cancer, human ovum fertility, eye pressure and oedema. In 1992 a Japanese research group published a paper presenting a unique phase shift circuit to facilitate resonance measurements. In this review we summarize the current state-of-the-art of tactile resonance sensors in medicine based on the phase shift circuit and discuss the relevance of the measured parameters for clinical diagnosis. Future trends and applications enabled by this technology are also predicted.

  • 83.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    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).
    Normal-Tension Glaucoma Has Normal Intracranial Pressure: A Prospective Study of Intracranial Pressure and Intraocular Pressure in Different Body Positions2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 3, p. 361-368Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To test the hypothesis that normal-tension glaucoma (NTG) is caused by an increased pressure difference across the lamina cribrosa (LC) related to a low intracranial pressure (ICP).

    DESIGN: Prospective case-control study.

    PARTICIPANTS: Thirteen NTG patients (9 women; median 71 [range: 56-83] years) were recruited for investigation with the same protocol as 11 healthy volunteers (8 women; 47 [30-59] years). A larger control group (n = 51; 30 women; 68 [30-81] years) was used only for ICP comparison in supine position.

    METHODS: ICP and intraocular pressure (IOP) were simultaneously measured in supine, sitting, and 9° head-down tilt (HDT) positions. Trans-lamina cribrosa pressure difference (TLCPD) was calculated using ICP and IOP together with geometric distances estimated from magnetic resonance imaging to adjust for hydrostatic effects.

    MAIN OUTCOME MEASURES: ICP, IOP, and TLCPD in different body positions.

    RESULTS: Between NTG patients and healthy volunteers, there were no differences in ICP, IOP, or TLCPD in supine, sitting, or HDT (P ≥ 0.11), except for IOP in HDT (P = 0.04). There was no correlation between visual field defect and TLCPD, IOP, or ICP and in any body position (P ≥ 0.39). Mean ICP in supine was 10.3 mmHg (SD = 2.7) in the NTG group (n = 13) and 11.3 (2.2) mmHg in the larger control group (n = 51) (P = 0.24).

    CONCLUSIONS: There was no evidence of reduced ICP in NTG patients as compared with healthy controls, either in supine or in upright position. Consequently, the hypothesis that NTG is caused by an elevated TLCPD from low ICP was not supported.

  • 84.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    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).
    Re: Linden 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) REPLY2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 6, p. e43-e44Article in journal (Refereed)
  • 85.
    Lindén, Christina
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jóhannesson, Gauti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Östlund, Fanny
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Re: Linden 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) REPLY2018In: Ophthalmology (Rochester, Minn.), ISSN 0161-6420, E-ISSN 1549-4713, Vol. 125, no 10, p. E74-E75Article in journal (Refereed)
  • 86. Lundkvist, B
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, L-O D
    Malm, J
    An adjustable CSF shunt: advices for clinical use.2003In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, no 1, p. 38-42Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The opening pressure and the resistance of a CSF shunt are essential for clinical use in order to set the proper opening pressure and to determine the shunt function in vivo. We find it of vital importance to validate and supplement the product description given by the manufacturer. The in vitro properties of a newly introduced, adjustable differential pressure valve with a siphon-preventing device (Strata valve) was compared with its predecessor (Delta valve).

    METHODS: An automated, computerized experimental set-up based on regulation of pressure, built into an incubator at 37 degrees C, was used. Opening pressure, resistance and siphon preventing properties were determined. Six brand-new shunts of each type with catheters were tested. The Delta valves were at a performance level of 1.5.

    RESULTS: The hydrodynamic properties of the Strata and Delta valves were similar. The anti-siphoning device was functioning for all valves. The estimated mean resistance for Delta and Strata shunts was 2.6 +/- 0.4 and 2.2 +/- 1.0 mmHg/ml/min, respectively. The mean opening pressure for the five performance levels of the Strata shunt are: 3.3, 5.1, 7.7, 10.7 and 13.1 mmHg. There may however, be considerable variations between the shunts.

    CONCLUSIONS: The Strata shunt is a properly working adjustable valve with anti-siphoning device that showed good reproducibility concerning opening pressure and resistance. At performance level 1.5, the new Strata shunt was similar to its predecessor concerning opening pressure and resistance. The given values of the different opening pressures and resistance could be used for in vivo testing of the valve function with a standard lumbar CSF infusion test.

  • 87. Lundkvist, B
    et al.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kristensen, B
    Fagerlund, M
    Koskinen, L O
    Malm, J
    Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device: a long-term study.2001In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 94, no 5, p. 750-6Article in journal (Refereed)
    Abstract [en]

    OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt.

    METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels.

    CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.

  • 88.
    Lundkvist, Bo
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Cerebrospinal fluid dynamics and long-term survival of the Strata(®) valve in idiopathic normal pressure hydrocephalus.2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Objective -  Cerebrospinal fluid (CSF) dynamics and long-term shunt survival of the Strata(®) CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). Subjects and methods -  Seventy-two patients with INPH received a Strata(®) valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long-term shunt survivals were obtained from patient records. Results -  The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty-nine patients (72%) had an improved gait. Two patients were improved despite non-functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6-month follow-up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. Conclusions -  The long-term survival of the Strata(®) valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti-siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.

  • 89.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Idiopathic normal pressure hydrocephalus. Review2006In: Practical Neurology, Vol. 6, p. 14-27Article in journal (Refereed)
  • 90.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Reference values for CSF outflow resistance and intracranial pressure in healthy elderly2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 76, no 10, p. 903-909Article in journal (Refereed)
    Abstract [en]

    This study reports reference values for ICP and R(out) and should be used for comparison when investigating disorders with suspected CSF dynamic disturbances in the elderly. ICP was in the same range as that reported in the young and middle-aged. The upper limit of R(out) was higher than previously believed to be the upper limit of normal for this age group.

  • 91.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lundkvist, B
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Kristensen, B
    CSF outflow resistance as predictor of shunt function. A long-term study2004In: Acta Neurol Scand, ISSN 0001-6314, Vol. 110, no 3, p. 154-160Article in journal (Refereed)
    Abstract
  • 92.
    Malm, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Cesarini, Kristina G
    Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Edsbagge, Mikael
    Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden.
    Kristensen, B
    Department of Neurology, Aalborg University, Aalborg, Denmark.
    Leijon, Göran
    Division of Neurology, Faculty of Health Sciences, University Hospital, Linköping, Sweden.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Implementation of a new CSF dynamic device: a multicenter feasibility study in 562 patients2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 125, no 3, p. 199-205Article in journal (Refereed)
    Abstract [en]

    Objectives: The cerebrospinal fluid (CSF) infusion test is frequently used when selecting hydrocephalus patients for shunt surgery. Very little has been reported regarding adverse events. We present a prospective feasibility study.

    Methods: Standardized devices for measuring CSF dynamics were built and 562 patients investigated: Needles were placed by lumbar puncture (LP). An automatic CSF infusion protocol was performed. Course of events during the investigation as well as adverse events were registered.

    Results: Preoperative evaluation of normal-pressure hydrocephalus was the most common indication (63%), followed by evaluation of shunt function (23%) and intracranial pressure recordings (14%). The LP was successfully performed in all but nine cases with 24 patients (4.3%) reporting major discomfort. Ringer infusion was performed in 474 investigations, and a valid measurement of the outflow resistance was received in 439 (93%). During the infusion phase, 17 (4%) patients reported severe headache. Infusion volume was significantly higher in patients having subjective symptoms during the infusion phase compared with those without adverse events. During 269 preoperative CSF tap tests, six (2%) patients had severe headache. Post-investigational headache was reported by 83 (15%) patients at the 24-h follow-up. No serious adverse events were observed.

    Conclusion: Infusion testing was safe and without serious adverse events with a high rate of successful procedures. The investigation was associated with expected mild to moderate discomfort.

  • 93.
    Manchester, Ian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, K
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Experimental Testing of a Method for On-Line Identification of the Cerebrospinal Fluid System2007In: 29th IEEE Annual International Conference on Engineering in Medicine and Biology, Lion, France, 2007, 2007, p. 2843-2846Conference paper (Refereed)
    Abstract
  • 94.
    Manchester, Ian
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Andersson, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    A nonlinear obsever for on-line estimation of the cerebrospinal fluid outflow restistance.2008In: Automatica, ISSN 0005-1098, E-ISSN 1873-2836, Vol. 44, no 5, p. 1426-1430Article in journal (Refereed)
    Abstract [en]

    Accurate estimates of the outflow resistance of the human cerebrospinal fluid system are important for the diagnosis of a medical condition known as hydrocephalus. In this paper we design a nonlinear observer which provides on-line estimates of the outflow resistance, to the best of our knowledge the first method to do so. The output of the observer is proven to globally converge to an unbiased estimate. Its performance is experimentally verified using the same apparatus used to perform actual patient diagnoses and a specially-designed physical model of the human cerebrospinal fluid system.

  • 95.
    Manchester, Ian R
    et al.
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Andersson, Nina
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Shiriaev, Anton S
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    A nonlinear observer for on-line estimation of the cerebrospinal fluid outflow resistance2008In: Automatica, ISSN 0005-1098, E-ISSN 1873-2836, Vol. 44, p. 1426-1430Article in journal (Refereed)
  • 96. Marshall-Goebel, Karina
    et al.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Mulder, Edwin
    Gerlach, Darius
    Bershad, Eric
    Rittweger, Joern
    Effects of short-term exposure to head-down tilt on cerebral hemodynamics: a prospective evaluation of a spaceflight analog using phase-contrast MRI2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 12, p. 1466-1473Article in journal (Refereed)
    Abstract [en]

    Alterations in cerebral hemodynamics in microgravity are hypothesized to occur during spaceflight and could be linked to the Visual Impairment and Intracranial Pressure syndrome. Head-down tilt (HDT) is frequently used as a ground-based analog to simulate cephalad fluid shifts in microgravity; however, its effects on cerebral hemodynamics have not been well studied with MRI techniques. Here, we evaluate the effects of 1) various HDT angles on cerebral arterial and venous hemodynamics; and 2) exposure to 1% CO2 during an intermediate HDT angle (-12 degrees) as an additional space-related environmental factor. Blood flow, cross-sectional area (CSA), and blood flow velocity were measured with phase-contrast MRI in the internal jugular veins, as well as the vertebral and internal carotid arteries. Nine healthy male subjects were measured at baseline (supine, 0 degrees) and after 4.5 h of HDT at -6 degrees, -12 degrees (with and without 1% CO2), and -18 degrees. We found a decrease in total arterial blood flow from baseline during all angles of HDT. On the venous side, CSA increased with HDT, and outflow decreased during -12 degrees HDT (P = 0.039). Moreover, the addition of 1% CO2 to -12 degrees HDT caused an increase in total arterial blood flow (P = 0.016) and jugular venous outflow (P = 0.001) compared with -12 degrees HDT with ambient atmosphere. Overall, the results indicate decreased cerebral blood flow during HDT, which may have implications for microgravity-induced cerebral hemodynamic changes.

  • 97. Marshall-Goebel, Karina
    et al.
    Mulder, Edwin
    Bershad, Eric
    Laing, Charles
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stern, Claudia
    Rittweger, Jörn
    Intracranial and Intraocular Pressure During Various Degrees of Head-Down Tilt2017In: AEROSPACE MEDICINE AND HUMAN PERFORMANCE, ISSN 2375-6314, Vol. 88, no 1, p. 10-16Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: More than half of astronauts develop ophthalmic changes during long-duration spaceflight consistent with an abnormal intraocular and intracranial pressure (IOP, ICP) difference. The aim of our study was to assess IOP and ICP during head-down tilt (HDT) and the additive or attenuating effects of 1% CO2 and lower body negative pressure (LBNP). METHODS: In Experiment I, IOP and ICP were measured in nine healthy subjects after 3.5 h HDT in five conditions: -6 degrees, -12 degrees, and -18 degrees HDT, -12 degrees with 1% CO2, and -12 degrees with -20 mmHg LBNP. In Experiment II, IOP was measured in 16 healthy subjects after 5 min tilt at +12 degrees, 0 degrees, -6 degrees, -12 degrees, -18 degrees, and -24 degrees, with and without-40 mmHg LBNP. RESULTS: ICP was only found to increase from supine baseline during -18 degrees HDT (9.2 +/- 0.9 and 14.4 +/- 1 mmHg, respectively), whereas IOP increased from 15.7 +/- 0.3 mmHg at 0 degrees to 17.9 +/- 0.4 mmHg during -12 degrees HDT and from 15.3 +/- 0.4 mmHg at 0 degrees to 18.7 +/- 0.4 mmHg during-18 degrees HDT. The addition of -20 mmHg LBNP or 1% CO2 had no further effects on ICP or IOP. However, the use of -40 mmHg LBNP during HDT lowered IOP back to baseline values, except at 24 degrees HDT. DISCUSSION: A small, posterior intraocular-intracranial pressure difference (IOP > ICP) is maintained during HDT, and a sustained or further decreased difference may lead to structural changes in the eye in real and simulated microgravity.

  • 98.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    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).
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    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 Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Cerebrospinal fluid and blood flow patterns in idiopathic normal pressure hydrocephalus2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 135, no 5, p. 576-584Article in journal (Refereed)
    Abstract [en]

    Objectives: Increased aqueduct cerebrospinal fluid (CSF) flow pulsatility and, recently, a reversed CSF flow in the aqueduct have been suggested as hallmarks of idiopathic normal pressure hydrocephalus (INPH). However, these findings have not been adequately confirmed. Our objective was to investigate the flow of blood and CSF in INPH, as compared to healthy elderly, in order to clarify which flow parameters are related to the INPH pathophysiology.

    Materials and Methods: Sixteen INPH patients (73 years) and 35 healthy subjects (72 years) underwent phase-contrast magnetic resonance imaging (MRI). Measurements included aqueduct and cervical CSF flow, total arterial inflow (tCBF; i.e. carotid + vertebral arteries), and internal jugular vein flow. Flow pulsatility, net flow, and flow delays were compared (multiple linear regression, correcting for sex and age).

    Results: Aqueduct stroke volume was higher in INPH than healthy (148±95 vs 90±50 mL, P<.05). Net aqueduct CSF flow was similar in magnitude and direction. The cervical CSF stroke volume was lower (P<.05). The internal carotid artery net flow was lower in INPH (P<.05), although tCBF was not. No differences were found in internal jugular vein flow or flow delays.

    Conclusions: The typical flow of blood and CSF in INPH was mainly characterized by increased CSF pulsatility in the aqueduct and reduced cervical CSF pulsatility. The direction of mean net aqueduct CSF flow was from the third to the fourth ventricle. Our findings may reflect the altered distribution of intracranial CSF volume in INPH, although the causality of these relationships is unclear.

  • 99.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wåhlin, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Jacobsson, Johan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    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, Radiation Physics.
    Differences in cerebral blood flow and CSF flow between INPH and healthy elderlyManuscript (preprint) (Other academic)
    Abstract [en]

    Idiopathic normal pressure hydrocephalus (INPH) is linked to disturbance of the CSF circulation, though the exact nature of the disturbance is not clarified. Phase contrast magnetic resonance imaging (PC-MRI) allows for measurement of local CSF and blood flows, and has been applied in hydrocephalus to demonstrate changes in both cerebral blood flow and aqueduct CSF flow. Many of these studies have, however been based on small numbers of subjects, or poorly defined selection criteria. This study therefore aimed to confirm if cerebral blood flow and CSF flow between compartments differed between INPH subjects and healthy elderly.

    Forty-three healthy elderly and 22 patients diagnosed with INPH according to the INPH guidelines were investigated with PC-MRI measurements of cerebral arterial inflow (CBF) and internal jugular venous outflow, cervical CSF flow, and aqueduct CSF flow. Both net flows, pulsatile aspects of flow, and delays between flow waveforms were analysed.

    Pulsatility in the aqueduct flow was significantly higher in INPH than healthy elderly (aqueduct stroke volume: 189±184 vs. 86±46 ml, p<0.01). There was larger variation in aqueduct net flow in INPH (SD: 1.31 vs. 0.25 ml/min), but the mean net flow did not differ. Cerebral blood flow and internal jugular vein flow showed no significant differences between the groups, though there was a trend toward lower CBF in the diastolic phase and higher CBF pulsatility index. No differences were found in flow delays.

    In conclusion, cerebral in- and outflow of blood, and cervical CSF flow were similar in healthy elderly and INPH subjects. Aqueduct flow showed higher pulsatility in INPH, but there was no general reversal of the direction of aqueduct net flow. 

  • 100.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lundkvist, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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 Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, no 7, p. 735-741Article in journal (Refereed)
    Abstract [en]

    Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.

    Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.

    Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.

    Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

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