CSF Protein Concentration Research Articles

Cerebrospinal fluid protein and opening pressure in idiopathic intracranial hypertension (pseudotumor cerebri)

We studied the relationship between the CSF protein concentration and the degree of elevation of the CSF opening pressure in 177 patients with idiopathic intracranial hypertension (pseudotumor cerebri). There was no linear correlation between the CSF protein and opening pressure. In addition, low CSF protein (less than 20 mg/dl) was present in only 26% of the patients. Our findings fail to confirm previous reports of an inverse relationship between the CSF opening pressure and CSF protein as well as low CSF protein in these patients.

SPINAL CORD SCHISTOSOMIASIS

Fourteen patients with schistosomiasis of the spinal cord are described. They fall into two groups: 7 patients had clinical and computer-assisted myelographic evidence of lesions in the conus medullaris or cauda equina, or both. The clinical picture in the remaining 7 patients was usually that of acute or subacute transverse myelitis with normal or equivocal CT myelographic appearances. Granulomas containing bilharzial ova were found in 2 female patients with conus swelling subjected to laminectomy and biopsy. In 1 of these the ova were identified as S. haematobium while in the second, unidentified bilharzial ova were found. A presumptive diagnosis of spinal cord schistosomiasis was made in the remaining 12 patients based on characteristic clinical and investigative profiles. All 13 patients tested showed evidence of bilharzial infection based on positive blood serology or the detection of bilharzial ova, or both. All but 1 patient showed at least one of the following abnormalities on CSF examination: pleocytosis, an elevated protein content and as indicated by the presence of oligoclonal IgG bands, an elevated IgG index and an increased CSF IgG synthesis rate. A CSF bilharzia enzyme-linked immunosorbent assay (ELISA) test, developed to indicate the presence of schistosomal infection within the theca, was found to be sensitive although not entirely specific for the diagnosis of spinal cord schistosomiasis. Eleven of the 14 patients showed rapid clinical improvement, 8 after praziquantel and corticosteroid treatment, 2 after operation and 1 spontaneously. Significant reductions in the CSF cell count, protein concentration and bilharzia ELISA titre, and in intrathecal antibody production, occurred following praziquantel and corticosteroid therapy. The CSF sugar level showed a significant rise. A reduction in conus size was observed in 3 patients when CT myelography was repeated after medical therapy. The normalization of most of the laboratory parameters after combined medical treatment with praziquantel and corticosteroids, together with clinical and radiological improvement, strengthened the presumptive diagnosis of cord schistosomiasis and supports the policy of early intensive medical treatment (as opposed to surgical therapy) for this condition when diagnosed on indirect evidence.

P.O.E.M.S. syndrome with complete recovery after treatment of a solitary plasmocytoma

The P.O.E.M.S. syndrome is a rare clinical entity that has been described mainly in Japan. It is characterized by a progressive polyneuropathy with raised CSF protein content, organomegaly, endocrinopathy, skin changes and plasma cell dyscrasia. We report a new documented case associated with a solitary plasmocytoma of the 12th thoracic vertebra. Immunopathological and ultrastructural studies of the peripheral nerve did not disclose any immunespecific changes. Surgery and radiation therapy of the plasmocytoma allowed a complete recovery, with a 5-year follow-up. This case report illustrates the need for serial full skeletal survey, including scintigraphy, in middleaged patients with progressive polyneuropathy of obscure origin.

Can late relapse be predicted at initial diagnosis in childhood acute lymphoblastic leukemia?

We have investigated whether any prognostic factor can be used to identify those children who have a relapse after discontinuation of therapy for acute lymphoblastic leukemia (ALL). Our population-based series comprised 167 children with newly diagnosed ALL. The 3-year event-free survival rate in these children was 65%. Maintenance therapy was electively discontinued for 120 patients, 20 of whom have subsequently had a relapse 1 to 27 months later. In multivariate analysis the risk of late relapse in the 15 patients with initially enlarged kidneys was 4.5-fold (95% confidence limits 1.7-11.8) that of the others (p less than 0.01). The risk in the 18 patients with initially elevated CSF protein concentration (greater than 0.4 g/l) or leukocyte count (greater than 5 x 10(6)/l), but with no blasts in the CSF, was 3.8-fold (1.5-9.6) that of the others (p less than 0.01). Our results indicate that enlarged kidneys or abnormal CSF findings at initial diagnosis are associated with an increased risk of late relapse in children with ALL.

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.

Ocular manifestations of tubercular meningitis: a clinico-biochemical study.

Forty-eight children with tubercular meningitis were observed and followed up for development of ocular sequelae over a period of four months. Commonest ocular abnormality encountered in this condition was optic disc change (62%) of which papillitis was the most frequent. The incidence of pupillary change and cranial nerve paralysis was seen to be 48% and 28% respectively. Anisocoria and mydriasis were commonly observed pupillary changes. The third cranial nerve was the most frequent nerve involved in this condition. It was observed that patients who had high CSF protein content (greater than 75 mg%) showed more chances of development of primary optic atrophy (P value 0.001). Choroidal tubercle and papilledema were found to be signs of grave prognostic significance.

Treatment of Kearns-Sayre syndrome with coenzyme Q10.

We studied the metabolism of coenzyme Q10 (CoQ) and the effects of CoQ therapy in five patients with Kearns-Sayre syndrome (KSS). Although the mitochondrial fraction was increased in muscles from KSS patients, CoQ content was slightly low. CoQ synthesis was normal in fibroblasts from KSS patients. Administration of 120 to 150 mg/d of CoQ improved abnormal metabolism of pyruvate and NADH oxidation in skeletal muscle. CoQ therapy decreased CSF protein concentration and CSF lactate/pyruvate ratio. ECG abnormalities and neurologic symptoms also improved.

Autonomic dysfunction, peripheral neuropathy, and depression

A 15-year-old boy with diarrhea, dizziness, dysesthesias, and depression is described. On admission, his blood pressure was 110/84 reclining but < 40 systolic while standing. Vibratory sensation and nerve conduction velocities were decreased in his lower extremities. CSF protein concentration was normal but sural nerve biopsy demonstrated generalized demyelination. Extensive toxicologic and metabolic screening proved unremarkable. Norepinephrine concentrations in plasma and urine, and CSF concentration of 3-methoxy-4-hydroxy phenylglycol (MHPG) were markedly reduced. The patient demonstrates a combination of autonomic dysfunction, peripheral neuropathy, and affective disorder. This collection of clinical and neurochemical findings represents a previously unreported entity involving a defect of both central and peripheral noradrenergic systems.

CSF protein, albumin and IgG concentrations in elderly male patients

CSF protein, albumin and IgG concentrations in elderly male patients

Multiple sclerosis co-existent with myxedema: An autopsy case report

A 64-year-old woman developed impaired consciousness and vision, sensorimotor paresis, hypothermia, bradycardia, and edema. Symptoms fluctuated with seasonal exacerbations in winter and terminated in coma with respiratory insufficiency at age 69. High CSF protein content and low serum T 4 and TSH levels were noted. Treatment with prednisolone and thyroxin considerably improved her consciousness and edema. The patient suddenly expired of pulmonary embolism. Postmortem examination revealed a marked atrophy of pituitary and thyroid glands, while multiple demyelinating plaques were disclosed in the optic tract and cervical cord. A review of the literature indicates that this is the first report of the co-existence of two such disorders.

Comparison of proteins in CSF of lateral and IVth ventricles during early development of fetal sheep

This study examines the relationship between plasma proteins in blood and in CSF in the developing brain of sheep fetuses between 30 and 60 days gestation. Five proteins account for the very high concentration of protein in fetal CSF (over 1000 mg/100 ml at 30 days); α-feto-protein, fetuin, albumin, α 1-antitrypsin and transferrin; the concentration of each protein is similar in lateral and IVth ventricular CSF at 30 days. By 40 days there is considerable decrease in protein concentration in lateral ventricular CSF. At this age in the IVth ventricle the overall total was unchanged, although there were changes in concentration of individual proteins. At 60 days the concentration of each protein in both compartments had fallen below that at 40 days; the marked concentration difference between lateral and IVth ventricular CSF was still present. Experiments using i.v. [ 125I]- or [ 3H] labeled plasma proteins in 30–40-day fetuses showed that very little protein penetrated into lateral ventricular CSF by 3–5 h after injection; in the same experiments [ 125I]albumin reached a CSF/plasma ratio of about 15% in the IVth ventricle (compared with 55% for the natural steady state). Autoradiographic studies carried out on material from the same animals did not give evidence for transfer of labeled protein across the choroid plexuses although any such penetration may have been below the threshold of the method. Other explanations for the high concentration of protein in CSF that were considered include penetration via cerebral vessels and synthesis of plasma proteins by choroid plexus epithelial cells or neurons within the brain.

Experience with iohexol in lumbar myelography.

An open phase II clinical trial of iohexol for lumbar myelography in 17 patients is reported. The overall frequency of adverse reactions was exceedingly low. Special attention was paid to psychic reactions and no such were recorded. The CSF analyses and EEG recordings before and after myelography did not differ significantly. The CSF protein content could not be evaluated as the contrast medium interfered with the reagents.

Neuropathologic evaluation of 40 confirmed cases of Legionella pneumonia.

Autopsy examination of the brain was performed in 40 cases of Legionella pneumonia. Thirty-nine of 40 patients had underlying chronic or acute medical problems. Sixteen patients (40%) had neurologic signs or symptoms that were not explained by preexisting disease. CSF was normal in six of seven patients examined; CSF protein content was 66 mg/100 ml in one patient. Neuropathologic examination in all 40 patients demonstrated no lesions attributable to disseminated Legionella pneumophila. Mechanisms other than direct cerebral invasion by the causative organism must be sought to explain the neurologic manifestations of Legionella pneumonia.

Bacterial meningitis in Nottingham.

Records of 171 cases of bacterial meningitis admitted to Nottingham hospitals from January 1974 to June 1980 were reviewed. The distribution of organisms producing meningitis and the factors influencing mortality in different age groups were assessed. Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae accounted for 69% of all proven cases. The overall mortality was 26% being lowest in patients with meningococcal meningitis (0%) and highest in those with pneumococcal meningitis (53%). The following factors were associated with a poor prognosis: age more than 40 years, or less than 2 months; state of consciousness on admission; high CSF protein concentration; and a positive blood culture. There was no evidence that antibiotic therapy prior to admission affected prognosis. Although many laboratory findings were altered by prior treatment with antibiotics, this did not prevent the establishment of a diagnosis in the individual patient.

Glutathione peroxidase in human cerebrospinal fluid

Glutathione peroxidase activity was investigated in human cerebrospinal fluid. CSF was obtained from 23 male adult patients with dementia, cerebrovascular disease and multiple sclerosis. The mean glutathione peroxidase activity in the CSF was 6.2 nmol NADPH oxidized min −1·mg −1 protein ± 0.6S.E.M.. No differences in the activities were observed in these neurological diseases suggesting that this value may reflect normal glutathione peroxidase activity in human CSF. The age or the protein concentration in CSF did not correlate significantly with glutathione peroxidase activity in CSF.

Zinc concentrations in the cerebrospinal fluid of normal adults and patients with neurological diseases.

Zinc concentrations in CSF were determined with flame atomic absorption spectrophotometry in patients assumed to have a normal CSF. No sex difference was found. There was a correlation between zinc, protein and albumin concentrations in CSF. In patients with increased protein levels in CSF or subarachnoid haemorrhage increased zinc concentrations were found.

Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis.

Entry of proteins into the cerebrospinal (CSF) from the blood is partially determined by the size of the protein. To determine whether other characteristics of proteins influence CSF entry, proteins or protein fragments were iodinated, inoculated intravenously, and serum and CSF were sampled at later times. The Fc fragment of immunoglobulin G (IgG) did not enter the CSF significantly better than the Fab fragment suggesting that choroidal Fc receptors are not of importance for selective immunoglobulin entry. To determine the role of protein charge on entry, bovine serum albumin [isoelectric point (pI) = 3.9] was chemically altered to provide an albumin with an average pI of 6 (A-6) and another with a pI of 8.5 (A-8). All albumins were of the same size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A-8 entered the CSF approximately 10-fold better than the native albumin. A-6 was intermediate, entering approximately twofold better. At the time of increased CSF protein concentration during an acute viral encephalitis these differences were narrowed but not eliminated. It is concluded that charge is an important determinant of protein entry into the CSF.

Relation of concentrations of Haemophilus influenzae type b in cerebrospinal fluid to late sequelae of patients with meningitis

Forty-four patients with Haemophilus influenzae type b meningitis had follow-up evaluations approximately one year after hospital discharge. Patients with greater than or equal to 10(7) colony-forming units of H. influenzae type b per milliliters CSF had significantly greater frequencies of speech impairment (P less than 0.001), hearing loss (P = 0.04), and moderate or severe neurologic sequelae (P less than 0.01). Patients with greater than or equal to 1 microgram H. influenzae b antigen/ml CSF had a greater incidence of hearing loss (P = 0.03) but not of speech abnormalities (P = 0.06) or other neurologic sequelae (P = 0.64). Glucose concentrations less than 10 mg/dl correlated with the incidence of hearing loss (P = 0.02) and speech impairment (P = 0.02). "Partial" antibiotic therapy, CSF protein concentrations, and number of CSF polymorphonuclear leukocytes did not correlate well with sequelae. These data indicate that pretreatment concentrations of H. influenzae b and glucose concentrations in CSF were the best predictors of late sequelae of patients with H. influenzae b meningitis.

Clinicopathological Study and Clinical Significance of ‘Silent’ Hemorrhage in Arteriovenous Malformations of the Brain

Operative procedures for cerebral arteriovenous malformations (AVMs) and histological study of the specimens may reveal old hemorrhage in some cases of AVMs with no clinical history of hemorrhage. Such asymptomatic hemorrhage has been reported as ‘silent’ hemorrhage. The authors analysed the incidence of silent hemorrhage of cerebral AVMs and its correlation with: patient's age, sex, location and size of AVMs, type of symptoms, number of attacks, interval from the onset to operation, CSF protein content, and CT scan findings. The clinical material consisted of 16 cases of supratentorial AVMs without evidence of a clinical history of hemorrhage. They had histories of either epilepsy or transient hemiparesis. All AVMs were totally excised microsurgically and the specimens were examined histologically for detection of iron containing granule cells. Silent hemorrhage was confirmed either surgically or histologically in 5 cases (31%). Presence or absence of silent hemorrhage had a tendency to be correlated with the location, size of AVMs, interval from clinical onset to operation, CSF protein content, and CT scan findings. However, statistical significance was not seen except in CSF protein content. Therefore, preoperative prediction of the presence of silent hemorrhage was not possible. This investigation indicated that the incidence of silent hemorrhage of cerebral AVMs was unexpectedly high. Since it was not possible to diagnose preoperatively, the possibility of silent hemorrhage should be kept in mind in determining the indication of surgical management for unruptured AVMs. Surgical management of unruptured AVMs should be justified in patients who have small or mediumsized AVMs mainly situated in silent areas.

Diffusion of moxalactam into the cerebrospinal fluid in children with bacterial meningitis

We studied the penetration of moxalactam into the cerebrospinal fluid of 16 children (age range one month to 4 1/2 years) who were being treated for bacterial meningitis. Two hours after single intravenous doses of 15 or 25 mg/kg, moxalactam was detectable in the CSF in only one of 11 instances; however, following three doses (50 mg/kg each) moxalactam was detectable in eight of 17 instances. In these eight instances CSF concentrations of moxalactam ranged between 1.5 and 18.9 micrograms/ml (mean 7.7) and the CSF/plasma ratio ranged from 2.6 to 36% (mean 17.7). There was no relation between the stage of meningitis or the CSF cell count and the diffusion of the drug into the CSF. However, the diffusion of the drug significantly correlated with the CSF protein content. In view of the unpredictability of moxalactam penetration into CSF, caution should be exercised in using it alone in the treatment of meningitis.