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On the pathophysiology of idiopathic adult hydrosephalus syndrome: energy metabolism, protein patterns, and intracranial pressure
Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurology. Umeå University, Faculty of Medicine, Radiation Sciences.
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The symptoms in Idiopathic Adult Hydrocephalus Syndrome (IAHS) – gait disturbance, incontinence, and cognitive deficit – correlate anatomically to neuronal dysfunction in periventricular white matter. The pathophysiology is considered to include a cerebrospinal fluid (CSF) hydrodynamic disturbance, including pressure oscillations (“B waves”), in combination with cerebrovascular disease. IAHS and Subcortical Arteriosclerotic Encephalopathy (SAE) show clinical similarities, which constitutes a diagnostic problem. The aim of this thesis was to investigate biochemical markers in CSF, possibly related to the pathophysiology, and their usefulness in diagnosis, to investigate the effect of ICP changes on glucose supply and metabolism in periventricular deep white matter, and to present criteria for objective, computerised methods for evaluating the content of B waves in an intracranial pressure (ICP) registration. CSF samples from 62 IAHS patients, 26 SAE patients, and 23 controls were analysed for sulfatide, total-tau (T-tau) hyperphosphorylated tau (P-tau), neurofilament protein light (NFL), and beta-amyloid-42 (Aß42). In ten IAHS patients, recordings of ICP, brain tissue oxygen tension (PtiO2), and samplings of brain extracellular fluid from periventricular white matter by way of microdialysis were performed, at rest and during a CSF infusion and tap test. Microdialysis samples were analysed for glucose, lactate, pyruvate, glutamate, glycerol, and urea. Patterns before and after spinal tap were analysed and changes from increasing ICP during the infusion test were described. The long term ICP registration was used to evaluate two computerised methods according to optimal amplitude threshold, monitoring time, and correlation to the manual visual method. In CSF, NFL was elevated in both IAHS and SAE patients, reflecting the axonal damage. In a multinominal logistic regression model, the combined pattern of high NFL, low P-tau and low Aß42 in CSF was shown to be highly predictive in distinguishing between IAHS, SAE and controls. Analysis of microdialysis samples for glucose, lactate, and pyruvate showed, in combination with PtiO2, a pattern of low-grade ischemia. After the spinal tap of CSF, the pattern changed, indicating increased glucose metabolic rate. During the infusion test, there were prompt decreases in the microdialysis values of glucose, lactate and pyruvate during ICP increase, but no sign of hypoxia. The values normalised immediately when ICP was lowered, indicating that the infusion test is not causing damage. One of the computerised methods, with an amplitude threshold set to 1 mm Hg, was shown robust in evaluating B wave content in an ICP registration. At least 5 hours registration time was needed. The highly predictive pattern of biochemical markers in CSF indicates a possibility of identifying simple tests in diagnosing and selecting patients for surgical treatment. The results of microdialysis and PtiO2 indicate low-grade ischemia in the periventricular white matter, which is ameliorated from CSF removal, and that glucose supply and metabolism are sensitive to short-term ICP elevations, thus proposing a link between ICP oscillations and symptoms from neuronal disturbance. A computerised method for evaluation of B waves is a prerequisite for evaluating the impact of pressure oscillations in the pathophysiology of IAHS.

Place, publisher, year, edition, pages
2005. , 64 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 955
Keyword [en]
hydrocephalus, biochemical markers, microdialysis, cerebrospinal fluid, B waves, brain tissue oxygen tension
Research subject
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-520ISBN: 91-7305-852-1 (print)OAI: oai:DiVA.org:umu-520DiVA: diva2:143688
Public defence
2005-04-29, Sal Betula, by 6 M, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Available from: 2005-04-28 Created: 2005-04-28 Last updated: 2009-11-17Bibliographically approved
List of papers
1. Cerebrospinal fluid biochemical markers in the evaluation of Idiopathic Adult Hydrocephalus Syndrome.
Open this publication in new window or tab >>Cerebrospinal fluid biochemical markers in the evaluation of Idiopathic Adult Hydrocephalus Syndrome.
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Manuscript (Other academic)
Identifiers
urn:nbn:se:umu:diva-4541 (URN)
Available from: 2005-04-28 Created: 2005-04-28 Last updated: 2010-01-13Bibliographically approved
2. Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome
Open this publication in new window or tab >>Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome
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2003 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 74, no 2, 217-221 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: In idiopathic adult hydrocephalus syndrome (IAHS), a pathophysiological model of "chronic ischaemia" caused by an arteriosclerotic process in association with a CSF hydrodynamic disturbance has been proposed. OBJECTIVE: To investigate whether CSF hydrodynamic manipulation has an impact on biochemical markers related to ischaemia, brain tissue oxygen tension (PtiO(2)), and intracranial pressure. METHODS: A microdialysis catheter, a PtiO(2) probe, and an intracerebral pressure catheter were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. A subcutaneous microdialysis probe was used as reference. Intracranial pressure and intracerebral PtiO(2) were recorded continuously. Samples were collected for analysis between 2 and 4 pm on day 1 (baseline) and at the same time on day 2, two to four hours after a lumbar CSF hydrodynamic manipulation. The concentrations of glucose, lactate, pyruvate, and glutamate on day 1 and 2 were compared. RESULTS: After CSF drainage, there was a significant rise in the intracerebral concentration of lactate and pyruvate. The lactate to pyruvate ratio was increased and remained unchanged after drainage. There was a trend towards a lowering of glucose and glutamate. Mean intracerebral PtiO(2) was higher on day 2 than on day 1 in six of eight patients. CONCLUSIONS: There is increased glucose metabolism after CSF drainage, as expected in a situation of postischaemic recovery. These new invasive techniques are promising tools in the future study of the pathophysiological processes in IAHS.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-4542 (URN)10.1136/jnnp.74.2.217 (DOI)12531954 (PubMedID)
Available from: 2005-04-28 Created: 2005-04-28 Last updated: 2017-05-19
3. Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome
Open this publication in new window or tab >>Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome
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2005 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, no 8, 1088-1093 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-14111 (URN)10.1136/jnnp.2004.042838 (DOI)16024885 (PubMedID)
Available from: 2007-11-29 Created: 2007-11-29 Last updated: 2017-05-19
4. Two computerized methods used to analyze intracranial pressure B waves: comparison with traditional visual interpretation
Open this publication in new window or tab >>Two computerized methods used to analyze intracranial pressure B waves: comparison with traditional visual interpretation
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2001 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 94, no 3, 392-396 p.Article in journal (Refereed) Published
Abstract [en]

OBJECT: Slow and rhythmic oscillations in intracranial pressure (ICP), also known as B waves, have been claimed to be one of the best preoperative predictive factors in idiopathic adult hydrocephalus syndrome (IAHS). Definitions of B waves vary widely, and previously reported results must be treated with caution. The aims of the present study were to develop a definition of B waves, to develop a method to estimate the B-wave content in an ICP recording by using computer algorithms, and to validate these procedures by comparison with the traditional visual interpretation. METHODS: In eight patients with IAHS, ICP was continuously monitored for approximately 20 hours. The ICP B-wave activity as a percentage of total monitoring time (B%) was estimated by using visual estimation according to the definition given by Lundberg, and also by using two computer algorithms (Methods I and II). In Method I each individual wave was classified as a B wave or not, whereas Method II was used to estimate the B-wave content by evaluating the B-wave power in 10-minute blocks of ICP recordings. CONCLUSIONS: The two computerized algorithms produced similar results. However, with the amplitude set to 1 mm Hg, Method I yielded the highest correlation with the visual analysis (r = 0.74). At least 5 hours of monitoring time was needed for an acceptable approximation of the B% in an overnight ICP recording. The advantages of using modern technology in the analysis of B-wave content of ICP are obvious and these methods should be used in future studies.

Identifiers
urn:nbn:se:umu:diva-4544 (URN)10.3171/jns.2001.94.3.0392 (DOI)11235941 (PubMedID)
Available from: 2005-04-28 Created: 2005-04-28 Last updated: 2017-12-14Bibliographically approved

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