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C Wikkelsø

Publications and source records attributed to C Wikkelsø.

At least 19 recordsLinked to original sources

Neurological symptoms and signs in adult aqueductal stenosis.

OBJECTIVE: To comprehensively describe and compare prospectively (pre/postoperatively) the symptomatology in aqueductal stenosis (AS) vs idiopathic normal pressure hydrocephalus (INPH). METHODS: Twenty-seven patients with AS and 39 patients with INPH were consecutively included. Postural functions, gait, wakefulness, cognitive functions, urinary continence and headache were examined before and 3 months after treatment with shunt operation or endoscopic ventriculostomy. RESULTS: The AS patients had better postural functions, walked faster, performed better cognitively and had a higher wakefulness than INPH patients, but these differences were explained by age differences between groups. The frequency of incontinence was similar in the two patients groups. Headache occurred more frequently in AS, but independently of the other symptoms. Most symptoms and signs improved after surgery. CONCLUSION: Patients with AS had a higher frequency of headaches than INPH patients, but otherwise the symptomology of the two groups was not found to differ after correcting for age differences.

Adolescent↗

White matter changes in normal pressure hydrocephalus and Binswanger disease: specificity, predictive value and correlations to axonal degeneration and demyelination.

OBJECTIVES: To analyse the diagnostic and prognostic value of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) magnetic resonance imaging (MRI) changes and their relation to symptoms and cerebrospinal fluid (CSF) markers of demyelination (sulphatide) and axonal degeneration [neurofilament triplet protein (NFL)] in a large series of patients with normal pressure hydrocephalus (NPH) and Binswanger disease (BD). MATERIALS AND METHODS: PVH and DWMH were determined by a semi-automatic segmentation method on T2-weighted images in 29 patients with NPH and 17 patients with BD. CSF analyses, psychometric testing and quantification of balance, gait and continence were performed in all patients and also postoperatively in NPH patients. RESULTS: No MRI variable could identify NPH or BD patients. Abundant PVH and DWMH preoperatively correlated with improvement in gait, balance and psychometric performance after shunt surgery (P < 0.05). CSF sulphatide correlated positively with the amount of DWMH (P < 0.05) while NFL was correlated to both PVH and DWMH (P < 0.05). Abundant PVH correlated with poor psychometric performance while DWMH correlated with gait disturbance (P < 0.05). Postoperative reduction in PVH correlated with improvement in gait, balance and psychometric performance. CONCLUSION: In spite of a refined quantification method, NPH and BD patients exhibited similar MRI changes. MRI had a predictive value in NPH patients. DWMH might relate to demyelination and PVH to neuronal axonal dysfunction. NPH and BD share the major part of symptoms and MRI changes, indicating a common pathophysiological pattern, and we raise the question of how to treat BD patients.

Aged↗

[Incidence of surgery for hydrocephalus in adults surveyed: same number afflicted by hydrocephalus as by multiple sclerosis].

The incidence of surgical treatment for adult hydrocephalus (older than 18 years) in Sweden from 1996 to 1998 was surveyed. The number of operations was 891 and the average incidence 3.36 operations per 100,000 inhabitants and year, varying regionally from 2.3 to 6.3. The mean age was 60 years (range 18-92), with no sex difference. Normal pressure hydrocephalus (47%) was most common, followed by communicating high pressure hydrocephalus (27%) and aqueductal stenosis (11%). 804 shunt operations (90%) and 67 ventriculostomies (7.5%) were performed, 2% were unclassified.

Adult↗

Tau and Abeta42 in cerebrospinal fluid from healthy adults 21-93 years of age: establishment of reference values.

BACKGROUND: Tau protein and the 42-amino acid form of beta-amyloid (Abeta42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance. METHODS: CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21-93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Abeta42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Abeta42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated. RESULTS: A correlation with age was found for CSF-tau (r = 0.60; P <0.001). Therefore, separate reference values for different age groups were established for CSF-tau: <300 ng/L in the group 21-50 years of age, <450 ng/L in the group 51-70 years of age, and <500 ng/L in the group 71-93 years of age. CSF-Abeta42 did not correlate with age (r = -0.045), and the reference value was set to >500 ng/L. No correlation was found between blood-brain barrier function and CSF-tau or CSF-Abeta42. CONCLUSIONS: These reference values can be applied when using CSF-tau and CSF-Abeta42 in clinical practice.

Adult↗

Normal pressure hydrocephalus: vascular white matter changes on MR images must not exclude patients from shunt surgery.

BACKGROUND AND PURPOSE: White matter changes such as periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) are associated with both periventricular edema and ischemic white matter degeneration. Their diagnostic and predictive value in normal pressure hydrocephalus (NPH) is unclear. To identify prognostically important changes, we classified PVH and DWMH at MR imaging in a large series of patients with NPH, before and after ventriculoperitoneal shunt surgery. METHODS: Axial proton density- and T2-weighted turbo spin-echo sequences and coronal T1-weighted sequences were performed on a 0.5-T imager in 34 patients with NPH, before and 3 months after shunt surgery. PVH at the anterior, central, and posterior thirds of the lateral ventricles was assessed on transaxial images with a semiquantitative five-step scale describing the extension (in mm) and shape of the PVH. DWMH was quantified with a four-step scale. The number of cortical and subcortical lacunar infarctions, the flow void sign, and the width of the third and lateral ventricles were registered. Gait ability, need for sleep, urinary incontinence, living conditions, and psychometric test performance were assessed pre- and postoperatively. RESULTS: After shunt surgery, 25 patients improved and nine did not. PVH, DWMH, and other MR imaging variables before shunting did not differ between groups, and no MR imaging variable could predict the clinical effect of shunt surgery. Postoperatively, the width of PVH was reduced in the improved patients, and clinical improvement correlated with reduction in PVH. Only the irregular type of PVH located at the frontal horns was reduced postoperatively. The presence of risk factors or MR imaging changes normally associated with cerebrovascular disease had no negative influence on the outcome of shunt surgery. CONCLUSION: The presence of DWMH or subcortical lacunar infarctions in NPH did not predict a poor outcome from shunt surgery and should not be used as exclusion criteria for shunting. No MR imaging findings could predict outcome of shunt surgery in patients with NPH. Clinical improvement after surgery is associated with reduction in the irregular type of PVH located around the frontal horns.

Adult↗

CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.

OBJECTIVES: To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features. METHODS: CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH. RESULTS: The CSF sulfatide concentration was markedly increased in patients with SAE (mean 766, range 300-3800 nmol/l) compared with patients with NPH (mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP in CSF were higher in patients with SAE than in patients with NPH. The patients with NPH with cerebrovascular aetiology had higher sulfatide concentrations and a poorer outcome after shunt surgery than patients with NPH with other aetiologies. CONCLUSIONS: The pathogenesis of the white matter changes in NPH and SAE is different and ischaemic white matter changes can be a part of the NPH state. The markedly increased CSF sulfatide concentrations in patients with SAE indicate ongoing demyelination as an important pathophysiological feature of SAE. The CSF sulfatide concentration distinguished between patients with SAE and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker.

Adult↗

Adult patients with "asymptomatic" and "compensated" hydrocephalus benefit from surgery.

OBJECTIVES: There exists no consensus regarding the appropriate treatment of the group of adult hydrocephalus patients often denoted as "arrested"/ "compensated", "asymptomatic" or "symptomatic congenital". Our case series describes the results of CSF diversion in these patients. MATERIAL AND METHODS: During the period of 1984 to 1994, 23 consecutive adult patients with "asymptomatic" (n = 10), "compensated" (n = 7) and "symptomatic congenital" (n = 6) hydrocephalus were prospectively evaluated. All patients showed signs of motor or psychometric impairment, had indications of an infantile or childhood debut, and had previously been ignored. In 15 patients the ventricular enlargement was a coincidental finding. Seventeen patients underwent shunt surgery or endoscopic third ventriculostomy. RESULTS: All but one operated upon improved. Six patients declined surgery, but have been followed with 1 showing deterioration, the remaining being unchanged. CONCLUSION: In addition to patients with "symptomatic congenital" most adult "asymptomatic" and "arrested"/"compensated" hydrocephalus patients can benefit from surgery despite a considerable duration of disease.

Adult↗

Patients with amyotrophic lateral sclerosis and other neurodegenerative diseases have increased levels of neurofilament protein in CSF.

In the present study we describe an ELISA to quantify the light subunit of the neurofilament triplet protein (NFL) in CSF. The method was validated by measuring CSF NFL concentrations in healthy individuals and in two well-characterized groups of patients with amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). The levels were increased in ALS (1,743 +/- 1,661 ng/L; mean +/- SD) and AD (346 +/- 176 ng/L) compared with controls (138 +/- 31 ng/L; p < 0.0001 for both). Within the ALS group, patients with lower motor neuron signs only had lower NFL levels (360 +/- 237 ng/L) than those with signs of upper motor neuron disease (2,435 +/- 1,633 ng/L) (p < 0.05). In a second study patients with miscellaneous neurodegenerative diseases were investigated (vascular dementia, olivopontocerebellar atrophy, normal pressure hydrocephalus, cerebral infarctions, and multiple sclerosis), and the CSF NFL level was found to be increased (665 +/- 385 ng/L; p < 0.0001). NFL is a main structural protein of axons, and we suggest that CSF NFL can be used to monitor neurodegeneration in general, but particularly in ALS with involvement of the pyramidal tract.

Aged↗

A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults.

The present study concerns an ELISA for glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF). The application of the method in CSF of children has previously been described in this journal. We have now adapted the technique to allow determination of the much higher GFAP concentrations found in normal and pathological CSF of adults. The assay range was extended to 16,000 pg/ml. CSF levels as high as 170,000 pg/ml could be assayed since dilution experiments indicated immunological identity between purified GFAP and GFAP in CSF. In normal controls the concentrations correlated significantly with age (P < 0.001, Spearman rank correlation test). The concentrations were less than 200 pg/ml before 20 years of age and increased to between 500 and 1300 pg/ml at approximately 75 years of age. This increase of CSF GFAP probably reflects formation of astroglial filaments in the CNS and it must be taken into consideration when determining the pathological CSF GFAP level. The method was validated using CSF samples from patients with either astrogliosis or acute tissue destruction in the CNS. Although augmented levels were observed in both groups it is quite clear that patients with acute tissue destruction may display very high CSF GFAP concentrations, whereas levels in patients with astrogliosis were only modestly increased if at all.

Adolescent↗

Normal pressure hydrocephalus: psychiatric findings before and after shunt operation classified in a new diagnostic system for organic psychiatry.

23 patients with normal pressure hydrocephalus (NPH) underwent psychiatric examinations prior to and 80 days to 10 months after a ventriculo-peritoneal shunt operation. A global evaluation of the effect of the operation on the patients' mental symptoms indicated appreciable improvement in 10 cases and slight improvement in a further 4.8 patients were assessed as unchanged, and one as mentally deteriorated. The psychiatric analyses was based on a new diagnostic system created by two of the authors (G.L., H.M.). The patients manifested varying, often complex psychiatric symptom constellations with symptomatological components from two or more organic mental disorders. Before the operation a mild or a moderately severe somnolence-sopor-coma disorder (SSCD) was diagnosed in 10 cases. After the operation all these patients became free from symptoms of SSCD. This was the most unequivocal change in connection with the operation, and the elimination of all symptoms of SSCD was the single factor which most effectively contributed to the total therapeutical result in these patients. All 23 cases were considered to have symptoms of a more or less severe astheno-emotional disorder (AED) preoperatively. The degree of severity of this disorder could not be determined with satisfactory certainty in some of the patients with complex symptoms. Amongst the 17 cases where the preoperative symptomatology allowed for a reasonably precise calculation of the degree of severity of AED, 6 were assessed as markedly improved after the operation and 10 as largely unchanged. In one patient, symptoms of the AED increased when the postoperative course was complicated by a subdural haematoma. Symptoms of an emotional-motivational blunting disorder (EMD) were diagnosed in 5 cases before the operation. After the operation 3 of these patients were symptom free in this respect while 2 unchanged. Slight or moderately severe symptoms of Korsakoff's amnestic disorder (KAD) were before the operation found in 7 cases: at the postoperative examination 6 of these cases were improved, of which 4 were free from such symptoms; one was unchanged. According to our experience, confident prognoses concerning the effect of the shunt operation on symptoms of SSCD can be made preoperatively, while, for a particular patient, the therapeutic effect on AED, EMD and KAD is often difficult, or sometimes impossible, to foresee. This article contains three case reports which represent different forms and courses of the mental symptom patterns.

Affective Symptoms↗

The contribution from the choroid plexus and the periventricular CNS to amino acids and proteins in the human CSF.

During neurosurgery the freshly secreted extracellular fluid (ECF) from the choroid plexus was sampled with small pieces of application paper in three patients with intractable epilepsy. The samples were analyzed for free amino acids and for soluble proteins. The results were compared with corresponding data on extracellular fluid from the brain surface obtained with dialysis-perfusion as well as with the cerebrospinal fluid (CSF) acquired by lumbar punction. The dialysis data were calibrated against the paper results. The choroid plexus secretion had a high concentration of transthyretin as well as of an unidentified protein with an isoelectric point of 7.4. The cortical ECF exhibited high concentrations of tau-globulin and gamma-trace protein. Among the amino acids, glutamine had lower concentration in the choroid plexus secretion and higher concentrations in the ECF of the brain compared to the CSF. The amino acid derivative ethanolamine exhibited a similar pattern. This was interpreted to demonstrate that these compounds enter the CSF from the brain tissue. In contrast, alanine, serine, and taurine had a lower concentration in the CSF than in the plexus secretion which suggests that they are removed from the CSF by brain tissue.

Adolescent↗

The S-100 protein in cerebrospinal fluid: a simple ELISA method.

A simple ELISA method is described for determinations of S-100 protein concentrations in CSF. The assay has a useful range of 200-3200 pmol/l. The precision of the ELISA was estimated using a pool of CSF. The coefficient of variation was 0.18 within assay, 0.17 between assay and 0.17 between day. The S-100 protein is stable in the CSF as no measurable differences in S-100 concentrations were observed in samples stored at room temperature for 2 days. No correlation between age and S-100 concentration was found when determinations were performed in CSF from neurologically healthy males. Furthermore, no changes of S-100 was observed in a lumbocisternal CSF gradient from patients with normal pressure hydrocephalus. Thus, the described ELISA represents an easy to handle and reliable method, well suited for routine determinations of S-100 protein concentration in the CSF.

Adult↗

Protein metabolism and electrophoretic profiles in astroglial primary cultures from different regions of newborn rat brain.

Primary astroglial cultures (14 days of age) from cerebral cortex, striatum, and hippocampus of newborn rat brain contained similar amounts of soluble proteins. Uptake and incorporation of [3H]valine into soluble protein measured after 30 and 60 min of incubation, respectively, was on a similar level in the various cultures. [3H]valine labeling of protein bands from the cell soluble fractions and incubation media of hemisphere cultures, and which were separated by isoelectric focusing (IEF) or sodium-dodecyl-sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), indicated that proteins are released to the extracellular medium after being synthesized within cultivated cells. Acidic and high molecular weight proteins were more heavily labelled in the incubation media than in the cell soluble fractions. Two-dimensional electrophoresis (IEF X SDS-PAGE) of soluble proteins from the different cultures showed similar patterns, which were quite different from the serum-free extracellular protein patterns. Both fractions were different from the pattern obtained from fetal calf-serum. In striatum and hippocampus culture media a "spot" was seen with Ip 6.0-6.8 and m.w. 105,000, and in the media from cerebellar cultures another "spot" was observed with Ip 5.2-5.6 and m.w. 55,000. The results show that the different cultures are similar in their protein synthetic capacity and protein composition. The specific differences observed in proteins obtained from the serum-free incubation media might indicate specific properties among astroglial cells from various brain regions.

Animals↗

Posttraumatic seesaw nystagmus abolished by ethanol ingestion.

We describe a patient who was left with a midchiasmal injury and bitemporal hemianopia after head trauma. Four months later, she developed typical seesaw nystagmus and moderate hydrocephalus. Lumbar punctures did not affect the nystagmus, but a temporary cessation was documented after ingestion of ethanol.

Adult↗

Dementia of different etiologies: vasoactive intestinal polypeptide in CSF.

Patients with normal-pressure hydrocephalus, multi-infarct dementia, and recent cerebral infarction had significantly lower vasoactive intestinal polypeptide (VIP) levels than age-matched controls (11 +/- 3 pmol/l, 17 +/- 4 pmol/l, 21 +/- 4 pmol/l, and 33 +/- 4 pmol/l, respectively). Three months after a shunt operation, the VIP levels had increased significantly in patients with hydrocephalus (54 +/- 13 pmol/l). VIP concentration in patients with senile dementia did not differ from that of controls.

Aged↗

Vasoactive intestinal polypeptide (VIP) in cerebrospinal fluid from men after long-term exposure to organic solvents.

Vasoactive intestinal polypeptide (VIP) is widely distributed within the central nervous system (CNS) and is thought to function as a neurotransmitter. VIP was measured in CSF from 14 men with psycho-organic syndrome occupationally exposed to organic solvents for 7-38 years and in CSF from 8 neurologically healthy male volunteers. The concentration of VIP in the exposed group, 28 +/- 15 (SD) pmol/l, did not significantly differ from that of controls, 38 +/- 14 pmol/l. Thus, determination of VIP in CSF appears to be of little value for detecting effects of long-term solvent exposure.

Humans↗

Cerebrospinal fluid proteins and cells in men subjected to long-term exposure to organic solvents.

Cerebrospinal fluid (CSF) was obtained from 17 men occupationally exposed to organic solvents and diagnosed as having a psycho-organic syndrome. Healthy volunteers and patients without neurological disorders were used as controls. The albumin ratio was increased in three heavily exposed men, indicating an increased passage of albumin over the blood-brain barrier. A slight monocytoid reaction was present in three of the subjects in the exposed group. Myelin basic protein and enolase activity were within normal limits. Isoelectric focusing of CSF-enriched proteins obtained by absorption chromatography showed alterations in nine out of 17 exposed individuals: The most prominent change was a relative increase of the protein band with Ip 4.7.

Adult↗