[Normal pressure hydrocephalus. A condition of dementia, improved by shunt surgery].
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Biomedical subjects
C Wikkelsö
Publications and source records attributed to C Wikkelsö.
Motor performance in normal pressure hydrocephalus assessed with an optoelectronic measurement technique.
The motor performance of 10 patients with normal pressure hydrocephalus (NPH) was clinically assessed with the aid of a computer assisted optoelectronic movement analysis system (Mac Reflex). We used the Posturo Locomotion Manual (PLM) method that gives a quantitative estimation of the postural, locomotor and manual performance in freely moving humans. Measurements were done before intervention, after CSF tap test and 3 months post installation of a CSF ventriculo peritoneal shunt. Comparison was made to data from 10 matched normal subjects and 10 patients with Parkinson's disease (PD). Shunt operation of the NPH patients and l-dopa treatment of the Parkinson patients improved the motor performance to a comparable degree. However, while the NPH patients improved the speed in the PLM test after the operation, the PD patients also improved the co-ordination after l-dopa treatment. This could indicate a different mechanism behind the improvement of motor performance in NPH and PD after intervention.
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Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke.
BACKGROUND AND PURPOSE: We have previously demonstrated that stroke influences systemic immune responses. The aim of the present study was to investigate patterns of local inflammatory response as a consequence of acute stroke. METHODS: Thirty stroke patients were studied prospectively on days 0 to 3, 7 to 9, 21 to 26, and after day 90 with clinical evaluations, radiological assessments, and analysis of serum and cerebrospinal fluid cytokine levels. RESULTS: Significantly increased levels of interleukin-6 (IL-6) in cerebrospinal fluid (P < .001) were observed in virtually all patients studied compared with healthy control subjects. This increase was observed during the whole observation period but was significantly more pronounced within the first days after stroke onset, with a peak level on days 2 and 3. This initial increase was significantly correlated (r = .65, P = .002) with the volume of infarct measured by MRI 2 to 3 months later. Serum levels of IL-6 in stroke patients were significantly lower than cerebrospinal fluid levels of IL-6 (P = .013) and did not display any significant correlation to the size of the brain lesion. Also, increase in intrathecal but not systemic production of IL-1 beta was observed early during the stroke. Only minor increases of cerebrospinal fluid interferon-gamma levels were observed in two patients. CONCLUSIONS: Our study demonstrates an intrathecal production of IL-6 and IL-1 beta in patients with stroke, supporting the notion of localized inflammatory response to acute brain lesion. In addition, the significant correlation between early intrathecal production of IL-6 and the subsequent size of the brain lesion can be used as a prognostic tool, predicting the size of the brain damage before it is possible to accurately visualize it with radiological methods.
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Gait abnormality is not the only motor disturbance in normal pressure hydrocephalus.
Thirteen different motor and balance functions were examined in 76 patients age 65 +/- 13 (mean +/- SD) years with normal pressure hydrocephalus (NPH) before and 3 months after a ventriculoperitoneal shunt operation. Preoperatively, the tests were performed before and after lumbar tap of 50 cc cerebrospinal fluid. The patients showed significant improvement in all thirteen functions at the 3-month examination. The improvement was approximately 25% in all the motor functions, except for balance, in which the improvement was even more striking. Different etiological subgroups of NPH patients, including the idiopathic form, exhibited the same degree of improvement. The improvement after the lumbar tap was significant in all functions except one-legged stance, and amounted to approximately 30% of the improvement seen after the shunt operation. Our results clearly show that the impairment in motor functions in NHP patients is general, involving many motor activities performed in daily life, and is not restricted solely to the gait.
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Mercury and proteins in cerebrospinal fluid in subjects exposed to mercury vapor.
Mercury (Hg) and protein levels in cerebrospinal fluid (CSF), and mercury in plasma (P), erythrocytes (Ery), and urine (U), were determined in 10 workers exposed to mercury vapor for 2-28 (median 13) years and in 16 occupationally unexposed referents. CSF-Hg was analyzed using radiochemical neutron activation analysis and P-Hg, Ery-Hg, and U-Hg were analyzed using cold-vapor atomic absorption spectrometry. P-Hg and U-Hg were significantly higher, but Ery-Hg was similar in the exposed workers (37 nmole/liter, 16 nmole/mmole creatinine, and 56 nmole/liter, respectively) compared with the referents (7.1 nmole/liter, 1.9 nmole/mmole creatinine, and 52 nmole/liter, respectively). CSF-Hg was correlated to P-Hg, and in workers with current high exposure (P-Hg > 50 nmole/liter), the CSF-Hg was significantly higher than in the reference group (1.08 versus 0.35 nmole/liter; P = 0.002). In two individuals, studied after ceased occupational exposure, a decrease of CSF-Hg was seen. There were no indications of changes in the CSF protein pattern in the exposed workers.
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Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects.
Relative regional cerebral blood flow (rrCBF) was measured by single-photon emission tomography (SPET), using technetium-99m-d,l-hexamethylpropylene amine oxime (HMPAO) as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq 99mTc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of pathophysiological and prognostic importance in NPH.
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Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis.
There are several formulas for the quantitative determination of intrathecal IgG production: Reiber and Felgenhauer's formula (IgG(loc)), the Extended IgG index, Tourtellotte's formula (TOURT), Schuller and Sagar's formula (SCHULL), the IgG index, the Log IgG index, and Blennow and co-workers' formula (IGGPROD). To evaluate the utility of these formulas in the presence of blood-brain barrier (BBB) damage, we present the results from a study of serum and cerebrospinal fluid (CSF) samples from 125 healthy individuals, 18-88 years of age; 1072 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, 683 without BBB damage (CSF/S: albumin ratio < 9.8) and 389 with BBB damage (CSF/S albumin ratio 9.8-30); and 106 patients with definite multiple sclerosis (MS). The relation between the CSF/S albumin ratio and the CSF/S IgG ratio was remarkably linear in both healthy individuals (r = 0.95; P < 0.0001) and patients without oligoclonal bands in the CSF (r = 0.95; P < 0.0001). Therefore, IgG(loc) and the Extended IgG index, two formulas based on a nonlinear relation between the CSF/S albumin ratio and the CSF/S IgG ratio, yielded biased results (lower values) in the presence of BBB damage. TOURT and SCHULL also yielded biased (higher) values in the presence of BBB damage, probably because of incorrect constants in these formulas. There were no significant correlations between the CSF/S albumin ratio (i.e. the BBB function) and the IgG index or the Log IgG index, two dimensionless quotients for the detection of intrathecal IgG production, or between the CSF/S albumin ratio and IGGPROD, an empirical formula for the determination of intrathecal IgG production in mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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A new method for the relative quantification of rCBF examined by 99Tcm-HMPAO SPECT.
A new method for the analysis of regional cerebral blood flow (rCBF) studies, the 'Min-Max' method, was compared with the conventional method, the 'Average' method. Regional CBF was examined by single photon emission computed tomography (SPECT) using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO). The two methods were used to quantify the rCBF in a population of patients with various dementia disorders, and in healthy controls. Results from a phantom were also used. In the Average method the average counts per pixel (cp-1) within irregular manually drawn regions of interest (ROIs) was registered. In the Min-Max method the minimum cp-1 and maximum cp-1 within rectangular ROIs were registered for white and grey matter, respectively. The relative rCBF (rrCBF) was calculated as the ratio between the regional and cerebellar values. The Min-Max method gave systematically lower values for rrCBF in the white matter, in both clinical studies, and in the phantom, compared to the Average method. No difference was found in the grey matter results. The variability in rrCBF in the phantom study was greater with the Min-Max method than with the Average method, but this effect was counteracted in the clinical studies by a smaller interobserver error. The average regional differences between patients and controls appeared greater with the Min-Max method than with the Average method. The Min-Max method proved to be more simple to execute, involved a smaller observer error, and with respect to ability to distinguish patients with dementia disorders from controls, it appears to function at least as well as the accepted Average method.
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Quantitative SPECT cisternography in normal pressure hydrocephalus.
Twenty-one patients with normal pressure hydrocephalus (NPH), 8 patients with various brain diseases with an element of hydrocephalus, and 7 patients with miscellaneous dementia disorders were investigated with quantitative radionuclide cisternography (RC) using single photon emission computerized tomography (SPECT). The total intracranial counts as well as the counts in the lateral and third ventricles were measured. All 15 NPH patients accessible for postoperative examination were improved after shunt surgery. In all groups the ventricular and total intracranial counts level increased during the measurement period but remained constant in distribution in each group. The NPH patients had a higher relative count value in the lateral and third ventricles compared to the patients with miscellaneous dementia disorders. The relative values in the third and lateral ventricles were predictive for the outcome of shunt surgery. Quantitative SPECT RC appears to be a useful diagnostic procedure in NPH investigations.
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Cerebrospinal fluid monoamine metabolites in 114 healthy individuals 18-88 years of age.
Concentrations of the monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA) and 4-hydroxy-3-methoxyphenylglycol (HMPG) were determined in lumbar cerebrospinal fluid (CSF) of 114 healthy individuals, 18-88 years of age, without histories, symptoms or signs of central nervous system dysfunction. The mean values (+/- SD) were 253 +/- 109 nmol/l for HVA, 125 +/- 54 nmol/l for 5-HIAA, 47 +/- 10 nmol/l for HMPG, and 2.10 +/- 0.52 for the HVA/5-HIAA ratio. Analyses of confounding factors revealed that all metabolites correlated negatively with body height, the values being lower in taller than in shorter individuals. This is probably attributable to a larger surface area for monoamine metabolite transport from the subarachnoid space in taller than in shorter individuals. These correlations make statistical adjustment for body height important in analyses of monoamine metabolite levels. Without considering body height, all monoamine metabolites showed a positive correlation with age, and higher levels of HVA and 5-HIAA were found in women than men. After statistical adjustment for the influence of body height, no differences in CSF monoamine metabolites levels were found between the sexes, and only 5-HIAA showed a positive correlation with age. There were no significant seasonal variations for any of the monoamine metabolites.
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Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age.
Analyses of the cerebrospinal fluid (CSF) to determine the blood-CSF barrier function and to detect intrathecal IgG production are used in the diagnosis of neurological and psychiatric diseases. Therefore, accurate reference values for these parameters are of utmost importance. However, current reference values are based on 'reference groups' consisting of patients with psychiatric and/or neurological symptoms but without positive clinical findings and on groups of young students. The present study presents reference values for CSF proteins in a large sample (n = 105) of healthy individuals, with a large age-span (18-88 years of age). The parameter for the determination of the blood CSF barrier function, the CSF/serum (CSF/S) albumin ratio, was found to show an increasing variability in individuals over 45 years of age, suggesting a less stable blood-CSF barrier function than in younger individuals. The upper reference limit for the CSF/S albumin ratio was 6.8 for individuals under 45 years of age and 10.2 for individuals over 45 years of age. The IgG index, a dimensionless quotient for the determination of intrathecal IgG production, showed only a minor correlation with age and had an upper reference limit of 0.63.
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Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production.
To examine the possible influence of the blood-CSF barrier function on mathematical formulas for estimating intrathecal IgG production (IgG index, Tourtellotte's formula [TOURT], Schuller and Sagar's formula [Schull], and Reiber and Felgenhauer's formula [IgG(loc)]), we analysed serum and CSF samples from 105 healthy individuals, aged 18-88 years, and 816 consecutive patients without oligoclonal IgG bands (OCBs) in the CSF, aged 18-91 years. In healthy individuals there was no significant correlation between the CSF/serum (S) albumin ratio (i.e. blood-CSF barrier function) and the IgG index, a dimensionless quotient for determining intrathecal IgG production, and only a small correlation (r = -0.08, p < 0.05) in patients without OCBs. However, significant dependence on the blood-CSF barrier function was found, in both healthy individuals and patients without OCBs, for the formulas determining intrathecal IgG production in milligrams (per litre CSF or per day), i.e. for TOURT, SCHULL and IgG(loc). Therefore, we propose a new formula for the quantitative determination of intrathecal IgG production in mg/l, the IGGPROD, which is calculated as: CSF-IgG -[(0.51 x CSF-Alb x S-IgG)/S-Alb]. IGGPROD is an empirical formula, based on findings in 105 healthy individuals 18-88 years of age, and does not depend on the blood CSF barrier function.
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Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime.
The regional cerebral blood flow (rCBF) in 19 patients with multiple sclerosis (MS), 10 with a relapsing remitting course and 9 with a progressive course, was examined by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]-d,l-HM-PAO) as flow tracer. Nine age-matched volunteers served as controls. Low rCBF in the frontal grey matter correlated with neurological disability (p < 0.01), low frontal grey and white matter perfusion correlated with impaired cognitive functions (p < 0.02), and low rCBF in the occipital regions correlated with impaired visual functions (p < 0.03) in the MS population. A relationship was also found between reduced parietal white matter perfusion and the duration of the disease (p < 0.005). Patients with progressive MS had significantly reduced rCBF in the frontal grey matter compared with relapsing remitting MS patients and controls (p < 0.05). No other rCBF differences were found. As a diagnostic tool in MS, SPECT-[99mTc]-d,l-HM-PAO was found to be insensitive.
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Does the shunt opening pressure influence the effect of shunt surgery in normal pressure hydrocephalus?
Thirteen patients with normal pressure hydrocephalus were operated upon with an externally maneuverable shunt system (Sophy SU8) in order to investigate its influence on clinical outcome, intracranial pressure and cranial CT parameters. The opening pressure was set at high at surgery and lowered stepwise at intervals of three months to medium and low. The clinical condition, intracranial pressure and cranial CT parameters were examined at the end of the 3 months interval on each pressure level. The patients improved within the first 3 months inspite of an unchanged mean intracranial pressure and remained in a stable clinical condition during the rest of the study period. The intracranial pressure was significantly reduced at 9 months. The ventricular index, Evans index, temporal horn and third ventricle width were reduced 3 months post-operatively and did not change significantly during the rest of the study. The pre-operative third ventricle width was correlated to high psychometric test results after shunt surgery. Reduction in ventricular index, Evans index and third ventricle width after surgery correlated to improvement in psychometric scoring. The clinical improvement after shunt surgery for normal pressure hydrocephalus is seen within 3 months and is independent of the adjusted valve pressure.
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Clinical parameters in 74 consecutive patients shunt operated for normal pressure hydrocephalus.
Seventy four consecutive patients diagnosed as normal pressure hydrocephalus (NPH) and operated with a ventriculo-peritoneal shunt were followed prospectively for an average of 2.1 years. The mean age was 64 years. The effect of the operation was estimated by calculating 6 indices expression social functioning, neurological signs, gait ability, continence, psychometric performance and psychiatric condition. Ninety-six % had mental symptoms, 95% gait disturbances and 75% incontinence. Improvement was observed in 78% after shunt surgery, while 22% deteriorated. Psychiatric improvement was seen in 80% and 76% improved in gait ability. Improvement was highest in the group caused by subarachnoid hemorrhage (98%) while 73% with idiopathic NPH improved. Old age was not correlated to poorer response, while long-standing pre-operative symptoms yielded worse results. No single symptom or sign could predict a positive outcome of the operation. Eleven % of the patients could leave long-term care institutions and there was a 36% reduction of aid in daily living. Complications to shunt surgery were observed in 50% of the patients and shunt related mortality was 1%. Shunt malfunction was the most frequent complication (31%) followed by infection (19%). Epilepsy developed in 9% after surgery. All shunt complication except one appeared within the first year after surgery.
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Neuropeptides in cerebrospinal fluid in normal-pressure hydrocephalus and dementia.
Delta-sleep-inducing peptide (DSIP), vasoactive intestinal peptide (VIP), peptide YY (PYY) and somatostatin (SOM) were assayed with specific radioimmunological methods in cerebrospinal fluid (CSF) of healthy volunteers, 12 patients with Alzheimer's disease (AD), 11 patients with multi-infarct dementia (MID) and 10 patients with normal-pressure hydrocephalus (NPH). Patients with NPH were reinvestigated 3 months after a ventriculoperitoneal shunt operation. DSIP, PYY and SOM levels in CSF were decreased in patients with NPH compared to controls. The CSF concentration of SOM was also significantly reduced in patients with AD. No correlations were found between the degree of dementia in any of the illnesses and the CSF concentrations of the peptides. The concentration of DSIP, VIP and SOM increased significantly in parallel to the clinical improvement after the shunt operation in NPH patients.
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Predictive value of quantitative cisternography in normal pressure hydrocephalus.
Twenty-five patients with normal pressure hydrocephalus (NPH) and 16 patients with cerebral atrophy were investigated by quantitative cisternography using anterior images of the head 3, 6 and 24 h after a lumbar injection of 200 MBq 99mTc DTPA (diethylene-triamine-penta-acetic acid). The activity in the lateral ventricles, basal cisterns, hemispheric convexities and total intracranial region was measured. Ratios between these regions/quantities were calculated. Fifteen of the NPH patients improved while 10 were unchanged after ventriculo-peritoneal shunt surgery. The ratio between ventricular and total intracranial activity (V/T) correlated positively with the degree of improvement after shunt surgery. All NPH patients with a V/T ratio higher than 32% improved after the operation but a V/T ratio less than 32% did not exclude the possibility of improvement. With regard to quantitative measurements, the radionuclide cisternography procedure can be reduced to imaging at 24 h.
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Cerebrospinal fluid proteins in men with chronic encephalopathy after exposure to organic solvents.
Cerebrospinal fluid was examined for 23 patients with chronic toxic encephalopathy after heavy exposure to organic solvents and 23 healthy age-matched referents. No differences were found between the patients and referents with respect to the levels of albumin, immunoglobulin, prealbumin, alpha-1-antitrypsin, beta-2-microglobulin, haptoglobin, or the astroglial cell proteins S100 and glial fibrillary acidic protein in the cerebrospinal fluid. The albumin ratio was normal for both the patients and the referents. The patient group had had heavy exposure to organic solvents, but its members had not been exposed for at least one year before the study. It was concluded that, if exposure to organic solvents affects proteins in cerebrospinal fluid, such effects are probably reversible.
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