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Idiopathic Normal Pressure Hydrocephalus: Aspects on Pathophysiology, Clinical Characteristics and Evaluation Methods
Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction. Idiopathic normal pressure hydrocephalus (iNPH) is a condition with enlargement of the cerebral ventricular system and an intracranial pressure (ICP) within normal limits. Cerebrospinal fluid circulation is disturbed but the mechanisms behind the symptoms: gait and balance difficulties, cognitive dysfunction and micturition problems, are as yet mostly unexplained.

Aim. In Studies I and II the aim was to investigate cerebral metabolism in the frontal deep white matter (FDWM) and the thalamus in iNPH using Magnetic Resonance Spectroscopy (MRS) before and after shunt surgery and to compare this with healthy individuals (HI). In Study III the aim was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in iNPH patients before and after shunt surgery, in comparison with HI. In Study IV the aim was to study postural function using computerised dynamic posturography (CDP) before and after shunt surgery as well as in comparison with HI.

Patients and Methods. In all studies the patients had a neurological examination and baseline bedside assessments of motor, balance and cognitive function were performed. Motor function was assessed using a motor score (MOS) consisting of the following items: 10 metre walk time in seconds and number of steps and TUG time in seconds and number of steps. MOS was considered significant if there was an increase of 5% or more. The HI were also tested for motor, balance and cognitive function. In Study I the patients (n=16) and the HI (n=15) were examined with MRS (absolute quantification) with voxels placed in the thalamus and in FDWM and compared with one another. In Studies III and IV the preoperative results of actigraphy and CDP respectively in patients (Study III n=33; study IV n=35) were compared with the HI: Study III, n=17; Study IV, n=16. The HI performed these examinations twice and the average was calculated. In Study II, 14 patients, and in Studies III and IV, 20 patients underwent shunt surgery and new MRS/actigraphy/CDP examinations were performed three months postoperatively and compared with the preoperative results.

Results. In the patients decreased total N-acetyl compounds (tNA) and N-acetyl aspartate (NAA) were found in the thalamus compared to the HI. No metabolic differences were seen in the FDWM between the groups. Postoperatively there were no metabolic changes in the thalamus but an increased total Choline (tCho) and a borderline significant decrease in myo-inositol (mIns).During the day the patients took fewer steps and had also lower total energy expenditure (TEE) than the HI. There was no difference concerning resting/sleeping time between patients and the HI. Postoperatively there were no differences of either number of steps, TEE or time spent resting or sleeping compared with the preoperative state. Postural function was worse in the patients compared to the HI, this difference being more pronounced in tests measuring vestibular function, where loss of balance (LOB) was frequent. There was only a slight improvement in balance after shunt surgery. A positive response to the shunt operation was seen in 86% in Study II, 85% in Study III and 90% in Study IV.

Conclusions. Our results suggest that the thalamus may be involved in the pathogenesis of iNPH. In contrast to others, we did not find any metabolic abnormalities in the FDWM, nor detect an increment of tNA or NAA postoperatively in the thalamus. The postoperative increase in tCho and borderline decrease in mIns in the FDWM might reflect a state of metabolic recovery since high tCho, a major component of the cell membrane, may be a sign of increased membrane turnover, and a decrease in mIns may indicate diminished gliosis.

The low gait capacity seen in the iNPH patients was not surprising but well that time spent resting/sleeping did not differ from the HI. Another unexpected finding was the unchanged ambulatory activity after shunt surgery despite improvement in a point test to determine capacity to walk a short distance. We believe this could be due to strong habits that are difficult to break and/or shortage of rehabilitation after surgery.

There was a profound postural dysfunction in the patients with many falls, especially in test situations intended to measure vestibular function. This implies that there is a central vestibular disturbance. The discrete improvement in postural function postoperatively was lower than previously reported.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. , 90 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1333
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84243ISBN: 978-91-7519-781-4 (print)OAI: oai:DiVA.org:liu-84243DiVA: diva2:558280
Public defence
2012-10-26, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2012-10-03 Created: 2012-10-02 Last updated: 2012-10-04Bibliographically approved
List of papers
1. Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
Open this publication in new window or tab >>Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification
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2011 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, no 7, 772-778 p.Article in journal (Refereed) Published
Abstract [en]

Introduction Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). Subjects and methods 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. 1 H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. Results INPH patients had lower NAA (p = 0.02) and lower tNA (p = 0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myoinositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Conclusion Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Place, publisher, year, edition, pages
BMJ Publishing Group, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-69842 (URN)10.1136/jnnp.2010.223529 (DOI)000291429200016 ()
Note

Original Publication: Fredrik Lundin, Anders Tisell, Olof Dahlqvist Leinhard, M. Tullberg, C. Wikkelso, Peter Lundberg and Göran Leijon, Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled (1)H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification, 2011, Journal of Neurology, Neurosurgery and Psychiatry, (82), 7, 772-778. http://dx.doi.org/10.1136/jnnp.2010.223529 Copyright: BMJ Publishing Group http://group.bmj.com/

Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08
2. Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure Hydrocephalus
Open this publication in new window or tab >>Pre-Postoperative 1H-MRS-Changes in Frontal Deep White Matter and the Thalamus in Idiopathic Normal Pressure Hydrocephalus
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

In a previous study we found a significantly decreased N-acetylaspartate (NAA) and total N-acetyl groups (tNA) in the thalamus in patients with idiopathic normal pressure hydrocephalus (iNPH) compared with healthy individuals (HI). No significant difference between the groups could be found in the frontal deep white matter (FDWM). The primary aim of this study was to investigate if these metabolites in the thalamus were normalised after shunt surgery. The secondary aim was to investigate postoperative metabolic changes in FDWM.

Subjects and Methods: Fourteen iNPH-patients, mean age 74 years, and 15 HI, also mean age 74 years, were examined. Assessment of motor scores was performed before and after shunt surgery. Absolute quantitative 1H-MRS (1.5 T, VOI 2.5-3 mL) was performed on the patients in the FDWM and in the thalamus, before and three months after shunt surgery, and also once on the HI. The following metabolites were analysed: tNA, NAA, total creatine (tCr), total choline (tCho), myo-inositol (mIns), glutamate (Glu), and lactate (Lac) concentrations. MRI volumetric calculations of the lateral ventricles were also performed.

Results: At three months postoperatively, we found no significant changes of tNA or NAA in the thalamus. In contrast, in FDWM, there was a significant increase of tCho (p=0.01) and a borderline significant decrease of mIns (p=0.06). 12/14 patients were shunt responders (motor function). Median reduction of the lateral ventricle was 16%. A weak correlation between motor score (MOS) and ventricular reduction was observed.

Conclusion: Normalisation of thalamic tNA and NAA could not be detected postoperatively. The increased tCho and decreased mIns in the FDWM postoperatively might relate to clinical improvement.

Keyword
Normal Pressure Hydrocephalus, Magnetic Resonance Spectroscopy, Postoperative, Thalamus, Frontal lobe
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-84236 (URN)
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2014-10-02Bibliographically approved
3. How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.
Open this publication in new window or tab >>How active are patients with idiopathic normal pressure hydrocephalus and does activity improve after shunt surgery? A controlled actigraphic study.
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2012 (English)In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, no 2, 192-196 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Actigraphy allows long-time evaluation of physical activity and resting behaviour in a normal environment. The aim of this study was, by use of actigraphy, to measure motor function, energy expenditure and resting/sleeping time in idiopathic normal pressure hydrocephalus (iNPH) patients before and after surgery, and compare the results with healthy individuals (HI).

SUBJECTS AND METHODS: 33 patients (mean 73 year) and 17 HI (mean 73 year) participated. Actigraphy with SenseWear (BodyMedia Inc., Pittsburgh, PA, USA) was recorded in the iNPH patients before and three months postoperatively and twice in the HI with a three-month interval. In addition, gait speed, timed up and Go (TUG) and MMSE were registered pre- and post-operatively.

RESULTS: During daytime the patients took fewer steps (p<0.001) and their total energy expenditure (TEE) was lower (p<0.01) than in the HI. Twenty patients were evaluated pre- and post-operatively and no change in either the number of steps, TEE, or time spent lying/sleeping after surgery could be detected. iNPH patients had lower gait speed, worse TUG and MMSE compared to the HI. Gait and TUG improved after surgery.

CONCLUSION: Actigraphy in iNPH patients indicated reduced ambulatory activity and lower energy expenditure compared to HI preoperatively. This did not change postoperatively in spite of improved TUG and gait speed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84239 (URN)10.1016/j.clineuro.2012.05.009 (DOI)000314447500013 ()22673042 (PubMedID)
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2017-12-07
4. Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery: A Controlled Study Using Computerised Dynamic Posturography (EquiTest)
Open this publication in new window or tab >>Postural Function in Idiopathic Normal Pressure Hydrocephalus Before and After Shunt Surgery: A Controlled Study Using Computerised Dynamic Posturography (EquiTest)
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Postural dysfunction is one of the major features of idiopathic Normal Hydrocephalus (iNPH). With computerised dynamic posturography (CDP) balance can be assessed objectively. The primary aim of this study was to describe the postural function in iNPH patients pre- and post-operatively in comparison with healthy individuals (HI) using CDP.

Subjects and methods: Thirty-five patients (16 M, 19 F) with a mean age of 73 (range 49-81) with iNPH, and sixteen HI (7 M, 9 F) aged 73 (62-89) were included. iNPH patients were operated on with a ventriculo-peritoneal shunt. Patients and HI were tested regarding motor function, balance and cognition. CDP, EquiTest (NeuroCom International, Clackamas, OR), was performed before and three months after shunt surgery and twice in HI, with a three-month interval.

Results: Pre-operatively, the 35 patients had poorer balance measured with the Sensory Organising Test (SOT) score in every condition (p= 0.01 in SOT 1 and p<0.001 in SOT 2-6) compared to the HI. The greatest difference was in test conditions measuring mainly vestibular function, where loss of balance (LOB) was frequent. Twenty patients did undergo shunt surgery and 18/20 (90%) were considered shunt responders, with a mean improvement of motor score of 26% (range 5-67 %). There was an improvement post-operatively in the weighted composite SOT score (p<0.05) but no significant change in any of the SOT conditions. LOB was not significantly reduced in any of the test conditions.

Conclusion: CDP showed that the patients had a poorer balance than the HI. The greatest difference was in SOT 5-6, indicating that the postural disturbance is of primarily central vestibular origin. There was a slight improvement of balance post-operatively.

Keyword
idiopathic Normal Pressure Hydrocephalus, Postural Function, Computerised Dynamic Posturography, Shunt surgery
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84240 (URN)
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2012-10-03Bibliographically approved

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