[SPECT. An important clinical method for brain function studies].
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Brain↗
Biomedical subjects
C Wikkelsø
Publications and source records attributed to C Wikkelsø.
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↗
Macromolecular changes in brain stem of morphinized rats.
Incorporation of [3H]valine into trichloroacetic acid-(TCA)-precipitable, water-soluble or membrane-bound material of whole brain and brain-stem did not differ significantly in morphine-intoxicated, morphine abstinent and control rats. The animals were intoxicated with morphine (final dose 340 mg/kg b.w.) for 15 days, using an ingestion method with no impairment of the caloric intake compared to controls. Abstinent rats were withdrawn from morphine for 2 days after 13 days of intoxication. Measurements of [3H]valine or [14C]valine incorporated into soluble or membrane-bound brain stem proteins failed to demonstrate any significant changes in specific protein bands from morphinized rats. Separation was achieved by polyacrylamide gel electrophoresis with or without sodium-dodecyl sulphate (SDS) or by isoelectric focusing. After immunoabsorption chromatography to remove those proteins antigenically similar to serum proteins, an increase in the staining intensity and in incorporation of [3H]valine into two protein bands (with isoelectric points (Ip:s) 5.75 and 7.7) was seen in brain stem from long-term morphine-intoxicated rats. The results show that macromolecular interactions are involved in long-term morphine actions.
Animals↗
Cerebrospinal fluid proteins and cells in normal-pressure hydrocephalus.
A total of 21 patients with normal-pressure hydrocephalus were examined. Cerebrospinal fluid (CSF) was collected before and after operation with a ventriculoperitoneal shunt. A slight plasma-like protein pattern indicating a blood-brain barrier (BBB) dysfunction was seen in 38% of the patients before operation. No characteristic changes could be found in the "CSF-specific" protein fraction. After the shunt operation 65% of the patients had a BBB dysfunction to macromolecules and 70% had two additional acidic protein bands in the CSF-specific fraction. Ventricular CSF protein content was 73% of lumbar CSF content when shunts were patent. Isotope encephalography showed a radionuclide accumulation at the intracranial part of the shunt system, indicating that the BBB damage might be located round the shunt catheter.
Blood-Brain Barrier↗
Cerebrospinal fluid "specific" proteins in various degenerative neurological diseases.
Cerebrospinal fluid (CSF) from patients suffering from various degenerative neurological diseases was fractionated into "CSF-specific" and antigenically serum-like proteins, using affinity chromatography with antihuman serum antibodies. The samples were isoelectric focused. Protein patterns were compared to similarly treated CSF from young normal volunteers and age matched controls. Several changes are described and 2 pathological patterns of the CSF-specific fraction could be identified. One pattern was characteristic for Alzheimer's dementia (AD) and senile dementia of the Alzheimer type (SDAT), but also seen in a few other diseases. The other pattern was seen in several of the investigated groups, most prominent in Huntington's chorea.
Adolescent↗
The clinical effect of lumbar puncture in normal pressure hydrocephalus.
Owing to all the difficulties involved in selecting patients with normal pressure hydrocephalus for shunt-operation, a cerebrospinal fluid-tap-test (CSF-TT) is introduced. Psychometric and motor capacities of the patients are measured before and after lumbar puncture and removal of 40-50 ml CSF. Patients fulfilling criteria for normal pressure hydrocephalus were compared to patients with dementia and atrophy shown by computed tomography. Normal pressure hydrocephalus patients showed temporary improvement after lumbar puncture. The extent of the temporary improvement appeared to be well correlated with the improvement after shunt operation. Accordingly, the CSF-TT seems to be of value when selecting those patients who will probably benefit from a shunt operation.
Adult↗
Cerebrospinal fluid specific proteins in multiinfarct and senile dementia.
Cerebrospinal fluid (CSF) from patients suffering from senile dementia (SD) and multiinfarct dementia (MID) was fractionated into CSF-specific and antigenically serum-like proteins, using affinity chromatography with antihuman serum antibodies. The samples were isoelectric focused. Protein patterns were compared to similarly treated CSF from patients suffering from transient ischemic attacks (TIA), or normal volunteers. Characteristic changes were found in the CSF-specific protein pattern from SD patients.
Adult↗
Cerebrospinal fluid investigations in multi-infarct dementia and senile dementia.
Thirty-eight demented patients were clinically investigated and classified into a multi-infarct dementia (MID) and senile dementia (SD) group. Total protein, albumin, immunoglobulin G, agar gel electrophoretic protein and iso-electric focusing pattern were determined in CSF and serum as well as the lactate dehydrogenase, LD-iso-enzyme pattern and uric acid. No significant differences were found regarding total protein, albumin and immunoglobulin G. The agar gel electrophoresis showed a tau-globulin increase in 18% of the SD-group against 6% of the MID group. The patterns were, however, plasma-like in 56% of the MID group against 23% of the SD group. The iso-electric focusing pattern showed an abnormal band in some SD-patients which was not found in the MID group. The uric acid and LD-enzyme concentration was equal in both CSF and serum. An index [Formula: see text] was calculated to give an approximate correction for the influence of different permeability of the blood-brain and CSF barrier. A significantly higher LD-index was found in the SD-group, suggesting a continuous cell degeneration.
Aged↗
A late neurologic complication of scoliosis surgery in connection with syringomyelia.
A case of scoliosis in connection with syringomyelia is described. Theories are proposed to explain the progression of the neurological symptoms after surgical correction and fusion of the deformity. Special points are emphasized that will aid in the recognition of syringomyelia in scoliosis patients. i) Abnormal neurology, in particular a dissociated disturbance of pain and temperature in the upper extremity. ii) Abnormal localization of a scoliosis curve. iii) Rapid progression of the scoliosis. iv) Bony anomalies of the upper cervical spine. v) Increased diameter of the cervical spinal canal.
Adolescent↗