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Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus
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).
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.ORCID iD: 0000-0001-6451-1940
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2013 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, no 7, 735-741 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
BMJ Publishing Group , 2013. Vol. 84, no 7, 735-741 p.
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:umu:diva-78953DOI: 10.1136/jnnp-2012-302924ISI: 000320108200010OAI: oai:DiVA.org:umu-78953DiVA: diva2:638258
Funder
Swedish Research CouncilVinnova
Note

This project was supported by the Swedish Research Council, VINNOVA, and the Swedish Foundation for Strategic Research through their common initiative: 'Biomedical engineering for improved health' grant No VR3011-2006-7551; and by the European Union through ERDF: Objective 2, Northern Sweden grant No 158715-CMTF.

Available from: 2013-07-29 Created: 2013-07-29 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Analysis of ICP pulsatility and CSF dynamics: the pulsatility curve and effects of postural changes, with implications for idiopathic normal pressure hydrocephalus
Open this publication in new window or tab >>Analysis of ICP pulsatility and CSF dynamics: the pulsatility curve and effects of postural changes, with implications for idiopathic normal pressure hydrocephalus
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Analys av ICP-pulsationer och CSF-dynamik : pulsationskurvan och effekter av ändrad kroppsposition, med implikationer för idiopatisk normaltryckshydrocefalus
Abstract [en]

The volume defined by the rigid cranium is shared by the brain, blood and cerebrospinal fluid (CSF). With every heartbeat the arterial blood volume briefly increases and venous blood and CSF are forced out of the cranium, leading to pulsatility in CSF flow and intracranial pressure (ICP). Altered CSF pulsatility has been linked to idiopathic normal pressure hydrocephalus (INPH), which involves enlarged cerebral ventricles and symptoms of gait/balance disturbance, cognitive decline and urinary incontinence that may be improved by implantation of a shunt. The overall aim of this thesis was to investigate the fluid dynamics of the CSF system, with a focus on pulsatility, and how they relate to INPH pathophysiology and treatment.

Mathematical modelling was applied to data from infusion tests, where the ICP response to CSF volume manipulation is measured, to analyse the relationship between mean ICP and ICP pulse amplitude (AMP) before and after shunt surgery in INPH (paper I-II). The observed relationship, designated the pulsatility curve, was found to be constant at low ICP and linear at high ICP, corresponding to a shift from constant to ICP dependent compliance (paper I). Shunt surgery did not affect the pulsatility curve, but shifted baseline ICP and AMP along the curve towards lower values. Patients who improved in gait after surgery had significantly larger AMP reduction than those who did not, while ICP reduction was similar, suggesting that improving patients had baseline ICP in the linear zone of the curve before surgery. Use of this phenomenon for outcome prediction was promising (paper II). The fluid dynamics of an empirically derived pulsatility-based predictive infusion test for INPH was also investigated, with results showing strong influence from compliance (paper III).

Clinical ICP data at different body postures was used to evaluate three models describing postural effects on ICP. ICP decreased in upright positions, whereas AMP increased. The model describing the postural effects based on hydrostatic changes in the venous system, including effects of collapse of the jugular veins in the upright position, accurately predicted the measured ICP (paper IV).

Cerebral blood flow and CSF flow in the aqueduct and at the cervical level was measured with phase contrast magnetic resonance imaging, and compared between healthy elderly and INPH (paper V). Cerebral blood flow and CSF flow at the cervical level were similar in INPH patients and healthy elderly, whereas aqueductal CSF flow differed significantly. The pulsatility in the aqueduct flow was increased, and there was more variation in the net flow in INPH, but the mean net flow was normal, i.e. directed from the ventricles to the subarachnoid space (paper V).

In conclusion, this thesis introduced the concept of pulsatility curve analysis, and provided evidence that pulsatility and compliance are important aspects for successful shunt treatment and outcome prediction in INPH. It was further confirmed that enhanced pulsatility of aqueduct CSF flow was the most distinct effect of INPH pathophysiology on cerebral blood flow and CSF flow. A new model describing postural and hydrostatic effects on ICP was presented, and the feasibility and potential importance of measuring ICP in the upright position in INPH was demonstrated. 

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2013. 79 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1613
Keyword
Cerebrospinal fluid, CSF dynamics, Intracranial pressure, Pulse pressure, Normal pressure hydrocephalus, Posture, Predictive tests, Mathematical modelling, Magnetic resonance imaging, Infusion tests
National Category
Medical Engineering
Identifiers
urn:nbn:se:umu:diva-82784 (URN)978-91-7459-762-2 (ISBN)
Public defence
2013-12-06, Hörsal E 04, Unod R1, Norrlands Universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council, 221-2011-5216Swedish Research Council, VR3011-2006-7551Vinnova, VR3011-2006-7551Swedish Foundation for Strategic Research , VR3011-2006-7551
Note

Forskningsfinansiär: 

European Union, ERDF: Objective 2, Northern Sweden (grant no. 158715-CMTF). 

Available from: 2013-11-15 Created: 2013-11-11 Last updated: 2015-10-01Bibliographically approved

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