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The search for reversibility of Idiopathic normal pressure hydrocephalus: Aspects on intracranial pressure measurments and CSF volume alteration
Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience.
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

BACKGROUND: Idiopathic normal pressure hydrocephalus (INPH) is still a syndrome generating more questions than answers. Today, research focuses mainly on two areas: understanding the pathophysiology – especially how the malfunctioning CSF system affects the brain parenchyma – and finding better methods to select patients benefiting from a shunt operation.

This thesis targets the aspect of finding better selection methods by investigating the measurability of intracranial pressure via lumbar space, and determining if intraparenchymal measurement of long-term ICP-oscillations (B-waves) could be replaced by short-term measurements of CSF pulse pressure waves via lumbar space. Furthermore, I look into the interaction between the CSF system and the parenchyma itself by investigating how the cortical activity of the brain changes after long-term CSF drainage, and if there is any regress in the suggested ischemia after this intervention. Finally, I examine if the neuronal integrity in the INPH brain is impaired, and if this feature is relevant for the likeliness of improvement after CSF diversion.

METHODS: The comparison of intracranial and lumbar pressure was made over a vast pressure interval using our unique CSF infusion technique, and it included ten INPH patients. Pressure was measured via lumbar space and in brain tissue, and the pressures were compared using a general linear model. Short-term lumbar pressure waves were quantified by determining the slope between CSF pulse pressure and mean pressure, defined as the relative pulse pressure coefficient (RPPC). The correlation between RPPC, B-waves and CSF outflow resistance was investigated.

In a prospective study, functional MRI was used to assess brain activity before and after long-term CSF drainage of 400 ml of CSF in eleven INPH patients. The functionalities tested included finger movement, memory, and attention. The results were benchmarked against the activity in ten healthy controls to identify the brain areas improving after drainage. The ischemia (Lactate) and neuronal integrity (NAA and Choline) were measured in a similar manner in 16 patients using proton MR spectroscopy, and the improvement of the patients after CSF drainage was based on assessment of their gait.

RESULTS: There was excellent agreement between ICP measured in brain tissue and via lumbar space (regression coefficient = 0.98, absolute difference < 1 mm Hg). Adjusting for the separation distance between the measuring devices slightly worsened the agreement, indicating other factors influencing the measured difference as well. RPPC measured via lumbar space significantly correlated to the presence of B-waves, but not to outflow resistance.

In the prospective study, controls outperformed patients on clinical tests as well as tasks related to the experiments. Improved behaviour after CSF drainage was found for motor function only, and it was accompanied by increased activation in the supplementary motor area (SMA). No lactate was detected, either before or after CSF drainage. NAA was decreased in INPH patients compared to controls, and the NAA levels were higher in the patients improving after drainage.

CONCLUSIONS: ICP can be accurately measured via lumbar space in patients with communicating CSF systems. The close relation between RPPC and B-waves indicates that B-waves are primarily related to intracranial compliance, and that measurement of RPPC via lumbar space could possibly substitute B-wave assessment as selection method for finding suitable patients for shunt surgery.

Improvement in motor function after CSF drainage was associated to enhanced activity in SMA, supporting the involvement of the cortico-basal ganglia-thalamo-cortical loop in the pathophysiology of INPH. There was no evidence indicating a widespread low-graded ischemia in INPH; however, there was a neuronal dysfunction in frontal white matter as indicated by the reduced levels of NAA. In addition, the level of neuronal dysfunction was related to the likeliness of improvement after CSF removal, normal levels of NAA predisposing for recovery.

Place, publisher, year, edition, pages
Umeå: Farmakologi och klinisk neurovetenskap , 2007. , 74 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1133
Keyword [en]
Idiopathic normal pressure hydrocephalus, intracranial pressure, subcortical ischemia, neuronal integrity, cortical activation., infusion test, cerebrospinal fluid dynamics, outflow resistance, compliance, elastance, proton spectroscopy, functional MRI, external lumbar drainage
National Category
URN: urn:nbn:se:umu:diva-1422ISBN: 978-91-7264-427-4OAI: diva2:140994
Public defence
2007-11-02, Betula, 6M, NUS, Umeå, 10:15 (English)
Available from: 2007-11-07 Created: 2007-11-07 Last updated: 2009-05-27Bibliographically approved
List of papers
1. CSF pressure assessed by lumbar puncture agrees with intracranial pressure.
Open this publication in new window or tab >>CSF pressure assessed by lumbar puncture agrees with intracranial pressure.
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2007 (English)In: Neurology, ISSN 0028-3878, Vol. 68, no 2, 155-158 p.Article in journal (Refereed) Published
urn:nbn:se:umu:diva-5749 (URN)10.1212/01.wnl.0000250270.54587.71 (DOI)17210899 (PubMedID)
Available from: 2008-10-16 Created: 2008-10-16 Last updated: 2015-10-01Bibliographically approved
2. Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves
Open this publication in new window or tab >>Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves
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2004 (English)In: Journal of Neurosurgery, ISSN 0022-3085, Vol. 101, no 6, 944-950 p.Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
American Association of Neurological Surgeons, 2004
Intracranial pressure, normal-pressure hydrocephalus, elastance, cerebrospinal fluid outflow resistance, relative pulse perssure coefficient
National Category
Radiology, Nuclear Medicine and Medical Imaging
urn:nbn:se:umu:diva-14735 (URN)000225695200009 ()15597755 (PubMedID)
Available from: 2007-11-23 Created: 2007-11-23 Last updated: 2015-10-01Bibliographically approved
3. Improvement after CSF drainage is related to levels of N-acetyl-aspartate in Idiopathic normal pressure hydrocephalus
Open this publication in new window or tab >>Improvement after CSF drainage is related to levels of N-acetyl-aspartate in Idiopathic normal pressure hydrocephalus
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In: NeurosurgeryArticle in journal (Refereed) Accepted
urn:nbn:se:umu:diva-2736 (URN)
Available from: 2007-11-07 Created: 2007-11-07Bibliographically approved
4. Supplementary motor activity accounts for recovery after CSF removal in Idiopathic normal pressure hydrocephalus
Open this publication in new window or tab >>Supplementary motor activity accounts for recovery after CSF removal in Idiopathic normal pressure hydrocephalus
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Article in journal (Refereed) Submitted
urn:nbn:se:umu:diva-2737 (URN)
Available from: 2007-11-07 Created: 2007-11-07Bibliographically approved

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