Idiopathic Normal Pressure Hydrocephalus Aspects on Pathophysiology, Clinical Characteristics and Evaluation Methods

Sammanfattning: 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.