Inositol in the cerebrospinal fluid in various nervous system diseases

The authors studied the changes of inositol concentration in the cerebrospinal fluid in 97 neurological patients. The highest values were found in cases of chronic ischalgia or brachial plexus painful syndromes and in multiple sclerosis, and the lowest ones in patients with generalized epileptic seizures. Intermediate values were observed in cases of headaches of different aetiology, in painful spinal syndromes without radiological changes, epidemic vertigo and craniocerebral injuries with brain commotion.     

Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients

OBJECTIVE: To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients. DESIGN: CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings. METHODS: Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DNA. Histopathological examination of CNS tissue obtained at autopsy or on brain biopsy. RESULTS: DNA of one or more viruses was found in CSF in 181 out of 500 patients (36%; HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%, and JCV 9%). Among the 219 patients with histological CNS examination, HSV-1 or 2 was detected in CSF in all six patients (100%) with HSV infection of the CNS, CMV in 37 out of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36 (97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%) with progressive multifocal leukoencephalopathy. Furthermore, HSV-1 was found in one, VZV in four, CMV in three, EBV in three, HHV-6 in seven, and JCV in one patient without histological evidence of the corresponding CNS disease. CONCLUSIONS: CSF PCR has great relevance for diagnosis of virus-related opportunistic CNS diseases in HIV-infected patients as demonstrated by its high sensitivity, specificity, and the frequency of positive findings.     

Cerebrospinal fluid proteins in the diagnosis of disorders of the blood-cerebrospinal fluid barrier in central nervous system diseases

BACKGROUND: Many neurological diseases are connected with the dysfunction of blood-CSF barrier. The quantitative determination of CSF proteins has already been used in the diagnosis of barrier impairments and inflammatory diseases of the central nervous system. PATIENTS: Serum and CSF, totaling 264 samples, were obtained from 15 controls and 117 patients with various diseases of the nervous system. Laurell's electroimmunoassay was used for estimation of albumin and IgG levels in serum and CSF. CSF-protein profile was evaluated according to Reiber's graph for the evaluation of the CSF-protein profile. RESULTS: The graph for the protein profile can be divided into 5 functionally different parts (1--normal range, 2, 3, 4--different types of barrier dysfunctions and 5--local humoral response in CNS without any barrier impairment). There was a good correlation of CSF-protein profiles and neurological diseases in our group of patients. CONCLUSIONS: According to our results, Reiber's graph was helpful for the diagnosis of blood-CSF-barrier dysfunctions. The graph has the following advantages: a) possibility of simultaneous assessment of the functional state of blood-CSF-barrier and the inflammatory response of the CNS, b)sensitivity for the determination of pathological local IgG-production in CNS and c) minimal number of protein assays necessary.     

Quantitation of human cytomegalovirus (HCMV) DNA in cerebrospinal fluid by competitive PCR in AIDS patients with different HCMV central nervous system diseases

The current study was designed to quantitate human cytomegalovirus (HCMV) DNA in cerebrospinal fluid (CSF) of persons with AIDS with specific HCMV-related CNS disease. DNA present in CSF obtained from AIDS patients was initially detected by a qualitative PCR procedure and then quantitated using a competitive PCR assay. In a group of 21 AIDS patients with HCMV-related CNS disease, 12 patients with HCMV polyradiculopathy had a mean +/- SEM of 11,982 +/- 4,480 copies/microliters in their CSF compared to 1,747 +/- 929 for 9 patients with HCMV encephalitis p = 0.017). Of the 14 patients with > 1,000 copies/microliters of HCMV DNA in CSF, 11(79%) had HCMV polyradiculopathy including all 3 with > 10,000 copies/microliters. Ganciclovir treatment of 3 patients with HCMV-related CNS disease was associated with a decline in HCMV DNA detectable within CSF. These data indicate that quantities of HCMV DNA in CSF are higher in persons with HCMV-related polyradiculopathy than encephalitis, and that quantitation of HCMV DNA can be useful in monitoring antiviral therapy.     

Evidence for low molecular weight, non-transferrin-bound iron in rat brain and cerebrospinal fluid

Extrapolation to humans from experimental radioimmunotherapy in nude mouse xenograft models is confounded by large relative tumour size and small volume of distribution in mice allowing tumour uptake of radiolabelled antibodies unattainable in patients. Our large animal model of human tumours in cyclosporin-immunosuppressed sheep demonstrated tumour uptake of targeted radiolabelled monoclonal antibodies comparable with uptakes reported in clinical trials. Sheep immunosuppression with daily intravenous cyclosporin augmented by oral ketoconazole maintained trough blood levels of cyclosporin within the range 1000-1500 ng ml(-1). Human tumour cells were transplanted orthotopically by inoculation of 10(7) cells: SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into ovary and peritoneum. Tumour xenografts grew at all sites within 3 weeks of inoculation, preserving characteristic morphology without evidence of necrosis or host rejection. Lymphatic metastasis was demonstrated in regional nodes draining xenografts of melanoma and ovarian carcinoma. Colonic LS1 74T xenografts produced mucin and carcinoembryonic antigen (CEA). The anti-CEA IgG1 monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% DI g(-1) (percentage of injected dose per gram) and 0.034% DI g(-1) in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% DI g(-1). Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy.     

Cerebrospinal fluid lysozyme activity in patients with central nervous system tumours

The presence of lysozyme in the CSF is considered with regard to its value in the early diagnosis of primary or secondary CNS Tumours. Since the appearance of this enzyme in the CSF is secondary to the increase of protein in the fluid, the search for lysozyme in the CSF is of no practical help in the diagnosis of CNS tumours.     

The central nervous system and the lymphatic system. Lymphatic drainage of the cerebrospinal fluid

BACKGROUND: Recent evidence suggests that transient neurologic symptoms commonly follow lidocaine spinal anesthesia. However, information concerning factors that affect their occurrence is limited. Accordingly, to evaluate many potential risk factors, the authors undertook a prospective, multicenter, epidemiologic study. METHODS: On a voluntary basis, anesthetists at 15 participating centers forwarded a data sheet on patients who had spinal anesthesia to a research nurse blinded to the details of anesthesia and surgery. A subset was randomly selected for follow-up. The pressure [corrected] of transient neurologic symptoms, defined as leg or buttock pain, was the principal outcome variable. Logistic regression was used to control for potential confounders, and adjusted odds ratios and confidence intervals were used to estimate relative risk. RESULTS: During a 14-month period, 1,863 patients were studied, of whom 47% received lidocaine, 40% bupivacaine, and 13% tetracaine. Patients given lidocaine were at higher risk for symptoms compared with those receiving bupivacaine (relative risk, 5.1; 95% CI, 2.5 to 10.2) or tetracaine (relative risk, 3.2; 95% CI, 1.04 to 9.84). For patients who received lidocaine, the relative risk of transient neurologic symptoms was 2.6 (95% CI, 1.5 to 4.5) with the lithotomy position compared with other positions, 3.6 (95% CI, 1.9 to 6.8), for outpatients compared with inpatients, and 1.6 (95% CI, 1 to 2.5) for obese (body mass index >30) compared with nonobese patients. CONCLUSIONS: These results indicate that transient neurologic symptoms commonly follow lidocaine spinal anesthesia but are relatively uncommon with bupivacaine or tetracaine. The data identify lithotomy position and outpatient status as important risk factors in patients who receive lidocaine. Among other factors postulated to increase risk, obesity had an effect of borderline statistical significance, whereas age, sex, history of back pain, needle type, and lidocaine dose and concentration failed to affect risk.     

Immunofixation electrophoretic techniques applied to identification of proteins in serum and cerebrospinal fluid

We describe the application of immunofixation staining of agarose-gel electrophoretograms in areas where its use in the clinical laboratory is appropriate. Immunofixation electrophoresis consists of an electrophoretic phase followed by a fixation phase in which antiserum is used to precipitate the protein. As long as the antibody is in slight excess or near equivalency, the antigen/antibody complex remains insoluble. The reaction can be detected by visual inspection in indirect light, by protein staining, or by use of antibodies labeled with fluorescein, enzyme, or isotope. In the method described here we primarily have used protein staining (Coomassie Blue) to accentuate the proteins fixed by antisera. All unreacted proteins are removed by pressing with filter paper and saline washing. In the clinical laboratory, this method expedites immunochemical evaluation of samples and may also supplement immunoelectrophoresis. It has been applied successfully in identifying small obscure monoclonal proteins in the serum and cerebrospinal fluid of patients with multiple sclerosis, subacute sclerosing panencephalitis, biclonal gammopathies, serum monoclonal light chains, and mobility shifts of certain proteins, particularly of the complement series. Immunofixation demonstrates that the protein bands present in spinal fluid from multiple sclerosis and subacute sclerosing panencephalitis patients are of the IgG class of immunoglobulins; and non-IgG protein, such as beta and gamma trace proteins, are not detected. We also comment on reverse immunofixation with labeled antigen as a branch of the procedure that allows detection of function of the immunoglobulins separated by electrophoresis.     

Detection of rifampin resistance by single-strand conformation polymorphism analysis of cerebrospinal fluid of patients with tuberculosis of the central nervous system

Mutations in a 69-bp region of the rpoB gene of Mycobacterium tuberculosis are associated with rifampin resistance (Rif[r]). These have been detected with mycobacterial DNA extracted from bacterial suspensions or respiratory specimens that were acid-fast smear positive. We experimented with a strategy for the rapid detection of Rif(r) in cerebrospinal fluid (CSF) samples. The strategy involves the amplification of the 69-bp region of rpoB by means of PCR and the identification of nucleotide mutations by single-strand conformation polymorphism (SSCP) analysis of the amplification products. Sixty-five CSF specimens collected from 29 patients (19 patients were coinfected with human immunodeficiency virus) with culture or autopsy-confirmed (22 patients) or highly probable (7 patients) tuberculosis of the central nervous system (CNS-TB) were processed. Amplified products suitable for evaluation by SSCP analysis were obtained from 37 CSF specimens from 25 subjects (86.2%). PCR-SSCP of CSF correctly identified the rifampin susceptibility phenotype of isolates from all 17 patients for whom the results of susceptibility tests carried out with strains cultured from CSF or respiratory samples were available. Moreover, this assay revealed the rifampin susceptibility genotype of isolates from the eight patients (three patients with culture-confirmed CNS-TB and five patients in whom CNS-TB was highly probable) for whom no susceptibility test results were available; the PCR-SSCP data obtained for these patients were concordant with the outcome after a standard antituberculosis treatment. The evolution of a mutation in the rpoB gene was documented in a patient during the course of treatment. PCR-SSCP analysis of CSF seems to be an efficacious method of predicting Rif(r) and would reduce the time required for susceptibility testing from approximately 4 to 8 weeks to a few days.     

D-dimer levels in the cerebrospinal fluid: a marker of central nervous system involvement in neoplastic disease

D-dimer assay was performed on 145 cerebrospinal fluid (CSF) samples from patients with or without neoplastic diseases. Levels of D-dimers were significantly higher in carcinoma and lymphoid malignancies with clinical or biological evidence of central nervous system (CNS) involvement than in diseases without such complications. In one patient, serial determinations of D-dimers were well correlated with the appearance and disappearance of CNS involvement. Although this test is not specific for neoplastic affections, our data suggest that the measurement of D-dimers in CSF may be useful in the diagnosis of CNS involvement of neoplastic cells and in monitoring intrathecal therapy in patients with lymphoma, acute lymphoblastic leukaemia or carcinoma. In this study, the D-dimer assay was also positive in some non neoplastic diseases, but failed to differentiate subarachnoid haemorrhage from traumatic lumbar puncture.     

Marker proteins in cerebrospinal fluid of patients with grave craniocerebral injury

The permeability of the blood-brain barrier for the cerebrospinal fluid marker proteins has been assessed in patients with grave craniocerebral injuries. The content of albumin and alpha 2-macroglobulin in the survivors decreased with time and by day 7 after the injury was virtually normal. In patients who died the content of these proteins was reliably increased starting from day 1. By day 7 the content of albumin in the cerebrospinal fluid approached the norm in this group, whereas the content of alpha 2-macroglobulin remained increased. The level of IgG surpassed the normal value on day 1 only in the patients who died, and later it did not differ from the norm in both groups.     

Autonomic nervous system in patients with cochleovestibular diseases

Clinical, electrophysiological investigations, evaluation of autonomic nervous system reactivity with estimation of Kerdo vegetative and stability indices were carried out in 58 patients with cochleovestibulopathy (CVP) and 10 normal controls. CVP patients with compensated disease had sympathicotonia, those with decompensated CVP exhibited parasympathicotonia. Functional loading tests and the stability index values revealed compensatory nature of sympathicotonia. Quantitative and qualitative characteristics of the compensation were related to age (under 40, over 41) and pathogenesis of the disease (central or peripheral). In CVP decompensation poor tolerance of mental work load was reported.     

Antibodies to the axolemma-enriched fraction in the cerebrospinal fluid and serum of patients with multiple sclerosis and other neurological diseases

Antibodies to an axolemma-enriched fraction (AEF) antigen have been detected in the cerebrospinal fluid (CSF) and serum of patients with Multiple Sclerosis (MS) using an enzyme-linked immunosorbent assay (ELISA). A marginal elevation (P < 0.08) of anti-AEF IgG was found in MS CSF when compared with OND samples. When CSF was diluted to a standardized IgG concentration, the anti-AEF IgG level in MS CSF was significantly elevated (P=0.007) when compared to OND CSF. MS serum was also found to contain a significantly higher level (P < 0.001) of anti-AEF IgG when compared to OND serum using the ELISA technique.     

Angiitis of the central nervous system in systemic diseases

PURPOSE: This review is aimed at presenting classification and diagnosis criteria of isolated central nervous system (CNS) angiitis, and at proposing guidelines for diagnosis and management of this disease. CURRENT KNOWLEDGE AND KEY POINTS: Isolated CNS angiitis are rare and most information has been provided by studies of very small series. Angiitis can be primitive or secondary to infectious, neoplastic diseases, or toxics. Clinical manifestations and radiologic abnormalities are not specific. A brain biopsy is therefore often required to confirm the diagnosis, as numerous non-inflammatory vascular diseases can mimic both clinically and radiologically isolated CNS angiitis. PERSPECTIVES AND PROJECTS: To help guide the diagnosis and therapeutical management of patients with CNS angiitis, strict classification criteria should be used: 1) rule out the various diseases that can mimic clinical and radiological CNS aspects related to isolated angiitis and differentiate "isolated CNS angiitis" from "CNS angiitis associated with systemic diseases"; 2) search for factors associated with the development of a "secondary CNS angiitis"; 3) check presumed mechanism at the origin of the cerebral vascular disease: "angiitis" versus "angiopathy"; 4) if the diagnosis of "primary CNS angiitis" is still suspected, it seems reasonable to perform cerebral and leptomeningeal biopsies. Treatment is still unknown and has to be discussed on a case by case basis according to the severity and progression of symptoms.     

Inflammatory diseases of the central nervous system in dogs

Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.     

Fractional clearances of low molecular weight proteins in lead workers

The phenomenon of wanting to help another is a universal human experience. Individuals reach out to others in order to fulfill personal commitments, to assist loved ones, or to meet professional obligations. The purpose of this research using Parse's method was to generate the structure of this experience as lived by nurses. Findings indicate that the lived experience of wanting to help another is directing nurturing intentions amidst uplifting affirmations with others while dissonant constraints unfold new possibilities. Findings are discussed in light of Parse's theory in order to expand the knowledge base of nursing. Similarities and differences with research findings on the experiences of nurturance and caring are presented. Implications for practice and further research are specified for nurses encountering persons who express their desire to help another.     

Central nervous system infections in patients with malignant diseases

Infections of the nervous system remain a significant source of morbidity and mortality in patients with cancer. This paper reviews the main pathogens and emphasizes some of the principles of diagnosis and management of nervous system infections in cancer patients. Due to immunosuppression, diagnosis is more difficult in this group, secondary to the multitude of potential pathogens, and often by their atypical presentations. Fever or headache are often the only symptoms. Clinical history and general examination should guide appropriate studies such as neuroimaging. CSF analysis, cultures, and brain biopsy. Diagnostic evaluation should be pursued rapidly and aggressively since specific treatments can often reduce morbidity and mortality. Bacterial infections are generally due to break-down of the natural barriers and neutropenia. In neutropenia, Pseudomonas aeruginosa, and Enterobacteriae are the most frequent etiology. If all causes of immunodepression are included, Listeria monocytogenes meningitis is the main bacterial infection encountered. Fungal infections have emerged as a major cause of death among cancer patients. The prognosis of cryptococcosis and histoplasmosis meningitis are markedly improved with new antifungal therapy. Aspergillosis and Mucormycosis, which may cause cerebral abcesses and secondary vascular complications, are almost always fatal. The incidence of meningo-cerebral Candidiasis is often underestimated. Similar to Histoplasmosis, it is frequently disseminated. Viral infections are mainly seen in patients with T-lymphocyte defects. Herpes-simplex virus and Varicella-Zoster virus encephalitis should quicky lead to intravenous treatment with Acyclovir. As in AIDS patients, cerebral toxoplasmosis is the most frequent parasitic infection and appropriate therapy greatly reduces morbidity. It should be emphasized that multitude pathogens are often seen in cancer patients. Despite development of new therapeutic agents, central nervous system infections should still be considered life-threatening. Therefore, antibacterial, antifungal, and antiviral prophylaxis should be the rule for all cancer patients.     

Interventional use of plasminogen activators in central nervous system diseases

Still an experimental approach, the direct intra-arterial infusion of plasminogen activators in the setting of acute thrombotic stroke has received impetus from successful clinical trials of intravenous infusion therapy. Direct therapy, employing catheter delivery, has successfully produced evidence of recanalization in carotid artery territory and vertebrobasilar artery territory thrombotic occlusions. One very recent prospective randomized study has demonstrated the success and limitations of this approach. Attention to safety concerns will be important to the future success of direct intra-arterial delivery of plasminogen activators in acute thrombotic stroke.