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Cerebrospinal fluid infusion methods: development and validation on patients with idiopathic normal pressure hydrocephalus
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebrospinal fluid (CSF) infusion tests can be used to estimate the dynamic properties of the CSF system. Idiopathic normal pressure hydrocephalus (INPH) is a syndrome signified by a disturbance to the CSF system, where the cause is unknown and the diagnosis is difficult to determine. As an aid in identifying patients with INPH who will improve after shunt surgery, infusion tests are commonly used to determine the outflow conductance (Cout), or outflow resistance (Rout=1/Cout), of the CSF system. The tests are also used to determine shunt function in vivo. The general aim of this thesis was to develop and validate CSF infusion methods, to investigate the dynamics of the CSF system. The methods should be applicable to patients with INPH, to aid in the quest to further improve the diagnosis and management of this syndrome.

An existing mathematical model describing the dynamics of the CSF system was further developed. The characteristics of the model were verified and the effect of expanding intracranial air on the intracranial pressure (ICP) was simulated. The simulations supported the recommendation to maintain sea-level pressure during air ambulance transportation of patients with suspected intracranial air.

A recently developed infusion apparatus was evaluated, on an experimental model as well as on a patient material. The repetitiveness in estimating Cout was found to be good. A statistically significant difference was found between the repeated Cout estimations in the patient group, indicating that there might have been a small physiological change introduced during the infusion test. A parameter, ∆Cout, was proposed and evaluated. It proved to reflect the reliability of individual Cout investigations in a clinically useful way, as well as to provide easily interpreted information.

An adaptive algorithm for assessment of Cout was developed and evaluated on a patient group. The new algorithm was shown to reduce the investigation time, from 60 minutes, by 14.3 ± 5.9 minutes (mean ± SD), p<0.01, without reducing the reliability of the estimated Cout below clinically relevant levels.

The relationship between ICP and CSF outflow was studied in a group of patients investigated for INPH. It was found that in the range of moderate increase from baseline pressure, the assumption of a pressure independent Rout was confirmed (p=0.5). However, at larger pressure increments, the relationship had a non-linear tendency (p<0.05). This indicates that the traditional view of a pressure independent Rout might have to be questioned in the region where ICP exceeds baseline pressure too much.

Infusion tests can be performed in different ways, where three main categories may be distinguished. The bolus infusion method was compared to the constant pressure and constant flow infusion methods, on an experimental model as well as on a patient material. When physiological pressure fluctuations were added to the model, significant differences were found in the determination of Cout in the range of clinical importance, i.e. low Cout (p<0.05). The finding was supported by the patient investigations, the difference was however not significant.

With the application of the new methods developed in this thesis, and the increased knowledge concerning relationships between CSF dynamic parameters, the CSF infusion test was further improved with the ability to increase measurement reliability in a reduced time. This constitutes a good basis to perform a large multi-centre study with the main goal to determine the predictive value of the parameter Cout.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2007. , 74 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1116
Keyword [en]
Infusion test, idiopathic normal pressure hydrocephalus, outflow conductance, outflow resistance, intracranial pressure, cerebrospinal fluid dynamics
National Category
Medical Engineering
Research subject
medicinsk informatik
Identifiers
URN: urn:nbn:se:umu:diva-1367OAI: oai:DiVA.org:umu-1367DiVA: diva2:140775
Public defence
2007-10-12, Betula, 6M, NUS, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2008-09-02 Created: 2008-09-02 Last updated: 2014-05-16Bibliographically approved
List of papers
1. Air transport of patients with intracranial air: computer model of pressure effects
Open this publication in new window or tab >>Air transport of patients with intracranial air: computer model of pressure effects
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2003 (English)In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, Vol. 74, no 2, 138-144 p.Article in journal (Refereed) Published
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-2573 (URN)
Available from: 2008-09-02 Created: 2008-09-02 Last updated: 2015-10-01Bibliographically approved
2. Assessment of cerebrospinal fluid outflow conductance using constant-pressure infusion - a method with real time estimation of reliability
Open this publication in new window or tab >>Assessment of cerebrospinal fluid outflow conductance using constant-pressure infusion - a method with real time estimation of reliability
2005 (English)In: Physiological Measurement, ISSN 0967-3334, E-ISSN 1361-6579, Vol. 26, no 6, 1137-1148 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:umu:diva-13949 (URN)doi:10.1088/0967-3334/26/6/022 (DOI)16311460 (PubMedID)
Available from: 2007-11-29 Created: 2007-11-29 Last updated: 2015-10-01Bibliographically approved
3. Adaptive method for assessment of cerebrospinal fluid outflow conductance.
Open this publication in new window or tab >>Adaptive method for assessment of cerebrospinal fluid outflow conductance.
2007 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 45, no 4, 337-343 p.Article in journal (Refereed) Published
Abstract [en]

Outflow conductance (C out) is important for predicting shunt responsiveness in patients with suspected idiopathic adult hydrocephalus syndrome (IAHS). C out is determined by performing an infusion test into the cerebrospinal fluid system, and the reliability of the test is dependent on the measurement time. The objective of this study was to develop an adaptive signal analysis method to reduce the investigation time, by taking the individual intracranial pressure variations of the patient into consideration. The method was evaluated on 28 patients with suspected IAHS. The results from full time investigations (60 min) were compared to the results of the new algorithm. Applying the new adaptive method resulted in a reduction of mean investigation time by 14.3 ± 5.9 min (mean ± SD), p < 0.01. The reduction of reliability in the C out estimation was found clinically negligible. We thus recommend this adaptive method to be used when performing constant pressure infusion tests.

Keyword
Intracranial pressure, Idiopathic adult hydrocephalus syndrome, Normal pressure hydrocephalus, Outflow conductance, Outflow resistance, Cerebrospinal fluid dynamics, Infusion test
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-12425 (URN)10.1007/s11517-006-0157-7 (DOI)000245298000002 ()17323083 (PubMedID)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2015-10-01Bibliographically approved
4. Dependency of cerebrospinal fluid outflow resistance on intracranial pressure
Open this publication in new window or tab >>Dependency of cerebrospinal fluid outflow resistance on intracranial pressure
2008 (English)In: Journal of Neurosurgery, ISSN 0022-3085, Vol. 109, no 5, 918-922 p.Article in journal (Refereed) Published
Abstract [en]

OBJECT: The outflow resistance (Rout) of the cerebrospinal fluid (CSF) system has generally been accepted by most investigators as independent of intracranial pressure (ICP), but there are also those claiming that it is not. The general belief is that this question has been investigated numerous times in the past, but few studies have actually been specifically aimed at looking at this relationship, and no study has been able to provide scientific evidence to elucidate fully this fundamental and important issue. The objective of this study was to investigate the relationship between ICP and CSF outflow in 30 patients investigated for idiopathic normal-pressure hydrocephalus. METHODS: Lumbar infusion tests with constant pressure levels were performed, and ICP and corresponding flow were measured on 6 pressure levels for each patient. All data were standardized for comparison. RESULTS: In the range of moderate increases from baseline pressure (approximately 5-12 mm Hg, mean baseline pressure 11.7 mm Hg), the assumption of a pressure-independent Rout was confirmed (p = 0.5). However, when the pressure increment from baseline pressure was larger (approximately 15-22 mm Hg), the relationship had a nonlinear tendency (p < 0.05). CONCLUSIONS: The results of this study support the classic textbook theory of a pressure-independent Rout in the normal ICP range, where the CSF system is commonly operating. However, the theory might have to be questioned in regions where ICP exceeds baseline pressure by too much.

Keyword
infusion test, intracranial pressure, linearity, normal-pressure hydrocephalus, outflow resistance
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-20833 (URN)10.3171/JNS/2008/109/11/0918 (DOI)000260362100020 ()18976085 (PubMedID)2-s2.0-58149168576 (Scopus ID)
Funder
Swedish Research Council, 621-2005-304-7
Available from: 2009-03-26 Created: 2009-03-26 Last updated: 2015-02-12Bibliographically approved
5. Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance
Open this publication in new window or tab >>Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance
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2010 (English)In: Journal of Neurosurgery, ISSN 0022-3085, Vol. 113, no 6, 1294-1303 p.Article in journal (Refereed) Published
Abstract [en]

Object There are several infusion methods available to estimate the outflow conductance (Cout) or outflow resistance (Rout = 1/Cout) of the CSF system. It has been stated that for unknown reasons, the bolus infusion method estimates a higher Cout than steady-state infusion methods. The aim of this study was to compare different infusion methods for estimation of Cout.

Methods The following 3 different infusion methods were used: the bolus infusion method (Cout bol); the constant flow infusion method, both static (Cout stat) and dynamic (Cout dyn) analyses; and the constant pressure infusion method (Cout cpi). Repeated investigations were performed on an experimental model with well-known characteristics, with and without physiological pressure variations (B-waves, breathing, and so on). All 3 methods were also performed in a randomized order during the same investigation in 20 patients with probable or possible idiopathic normal-pressure hydrocephalus; 6 of these patients had a shunt and 14 did not.

Results Without the presence of physiological pressure variations, the concordance in the experimental model was good between all methods. When they were added, the repeatability was better for the steady-state methods and a significantly higher Cout was found with the bolus method in the region of clinically relevant Cout (p < 0.05). The visual fit for the bolus infusion was dependent on subjective assessment by the operator. This experimental finding was confirmed by the clinical results, where significant differences were found in the investigations in patients without shunts between Cout of the visual bolus method and Cout stat, Cout dyn, and Cout cpi (4.58, 4.18, and 6.12 μl/[second × kPa], respectively).

Conclusions This study emphasized the necessity for standardization of Cout measurements. An experienced operator could partly compensate for difficulties in correctly estimating the pressure parameters for the bolus infusion method, but for the general user this study suggests a steady-state method for estimating Cout.

Place, publisher, year, edition, pages
American Association of Neurological Surgeons, 2010
Keyword
normal-pressure hydrocephalus; steady-state infusion; intracranial-pressure; csf outflow; resistance; system; shunt; management; diagnosis; dementia
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:umu:diva-2577 (URN)10.3171/2010.8.JNS10157 (DOI)000284565500034 ()
Note

Publicerades i Nina Anderssons (=Nina Sundströms) avhandling som ett manuskript med titel:

Does the cerebrospinal fluid outflow conductance determined by steady state infusion methods differ from that of the bolus infusion method?

Available from: 2008-09-02 Created: 2008-09-02 Last updated: 2015-10-01Bibliographically approved

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