Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease

We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.     

Cerebrospinal fluid levels of cyclic nucleotides in meningitis and idiopathic polyneuritis

Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were measured in cerebrospinal fluid (CSF) and plasma from 7 patients with bacterial meningitis, 9 patients with serous meningitis, 5 patients with idiopathic polyneuritis and 15 reference patients. A significantly (P less than 0.01) higher mean concentration of CSF cAMP was found in serous meningitis (33.8 +/- 12.5 nmol/l) compared to the reference group (20.2 +/- 4.0 nmol/l). No significant difference could be observed between the patients with purulent meningitis compared to the reference group. The CSF cAMP concentration (11.0 +/- 2.8 nmol/l) for idiopathic polyneuritis was significantly (P less than 0.01) lower than in the reference group. No difference in CSF levels of cGMP or in the cAMP/cGMP ratios were detected between the groups. Our data suggest that the ratio between cAMP concentrations in CSF and plasma may aid in the differential diagnosis between serous and purulent meningitis.     

Beta-2-microglobulin and ferritin in cerebrospinal fluid for evaluation of patients with meningitis of different etiologies.

To determine whether or not the beta-2-microglobulin (beta2-m) and/or ferritin levels in cerebrospinal fluid (CSF) can be used as markers for the differential diagnosis of meningitis and determination of the response to treatment, 122 subjects with etiologically well-characterized diagnoses were classified into three groups: bacterial meningitis (n = 5; mean age +/- SD. 1.0+/-1.0 year), viral meningitis (n = 39; 5.9+/-3.8 years), and a non-meningitis group (n = 78; 5.2+/-4.9 years). The levels of beta2-m and ferritin in CSF were determined by means of a latex photometric immunoassay. The statistical significance of the data was analyzed with the Mann Whitney U-test. A receiver operating characteristic curve was used to evaluate the diagnostic accuracy of each prediction marker. This study indicated that (1) the levels of beta2-m and ferritin in CSF were related with age in the non-meningitis group: subjects of up to 5 months of age exhibited higher concentrations of these proteins than ones of above 6 months of age (beta2-m, 1.89+/-1.13 vs. 0.84+/-0.65 mg/l. P < 0.01; ferritin, 2.97+/-2.04 vs. 1.81+/-1.34 microg/l, P = 0.09); (2) the beta2-m level was significantly higher in the CSF of patients with viral meningitis than in ones without meningitis (2.41+/-1.23 vs. 0.84+/-0.65 mg/l, P < 0.01): the best cut-off value was 1.2 mg/l (3) the ferritin level was significantly higher in the CSF of patients with bacterial meningitis than in ones with viral meningitis (43.24+/-39.49 vs. 6.81+/-7.41 microg/l, P < (.01): the best cut-off value was 7.5 microg/l; and (4) sequential measurement of the CSF ferritin level was of value for determination of the response to antibiotic treatment for bacterial meningitis. These results only apply to patients of greater than 6 months of age. beta2-m and ferritin in the CSF can be used as an ancillary tool for diagnostic guidance in the acute phase of meningitis and determination of the response to treatment for bacterial meningitis.     

Indole levels in human lumbar and ventricular cerebrospinal fluid and the effect of L-tryptophan administration

Levels of tryptophan (TRP), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in human lumbar and ventricular cerebrospinal fluid (CSF) were measured by reversed phase liquid chromatography (HPLC) with electrochemical detection. The levels of TRP ranged from 1593 to 4865 nmol/l in ventricular (VF) and from 1257 to 2557 nmol/l in lumbar CSF. The level of 5-HTP varied from 1.1 to 68.9 nmol/l in VF and from 5.3 to 10.8 nmol/l in lumbar CSF; no previous reports of 5-HTP levels in CSF exist. The serotonin level was 1.9-27.3 nmol/l in VF and 5.7-12.0 nmol/l in lumbar CSF. The levels of 5-HIAA were considerably higher in VF than in lumbar fluid with respective means of 498 +/- 52.4 nmol/l and 112 +/- 15.6 nmol/l (P less than 0.001). An oral dose of 2 g L-tryptophan significantly increased all indole levels except that of 5-HT, both in patients with progressive myoclonus epilepsy and in controls.     

Vasopressin in the cerebrospinal fluid of febrile children with or without seizures

Immaturity in water and electrolyte balance in the brain has been considered to increase the susceptibility of young animals and children to febrile convulsions (FCs). Arginine-vasopressin (AVP) is involved in the regulation of several centrally mediated events such as modulation of fever and the ease with which water permeates into and out of the brain. To evaluate the possible role of AVP in the control of water balance and susceptibility to convulsions during fever we measured the AVP concentration in the cerebrospinal fluid (CSF) and plasma of febrile children with or without convulsions. The febrile population consisted of 47 children, of whom 29 experienced seizures during fever. Seven children with epileptic symptoms and 18 children without seizures were included as nonfebrile controls. The CSF AVP concentration in febrile children without seizures and in nonfebrile convulsive children was significantly lower (0.60 ± 0.07 pmol / 1, mean ± SEM,P < 0.01 and 0.65 ± 0.19 pmol/l,P < 0.05, respectively) than in nonfebrile children without convulsions (0.83 ± 0.06 pmol/1). However, the levels of CSF AVP were not significantly different in children with FCs (0.71 ± 0.06 pmol/1) compared with other groups. CSF AVP correlated with the CSF osmolality (r = 0.33, P = 0.02). No statistical differences in plasma AVP levels between the groups could be found. The present data provide support for the hypothesis of synchronous regulation of osmolality and AVP concentration in CSF. During fever the concentration of CSF AVP was lower in nonconvulsive children compared with nonfebrile nonconvulsive children. CSF AVP levels were not affected in febrile children by convulsions.     

Cerebrospinal fluid neopterin in paediatric neurology: a marker of active central nervous system inflammation

Aim  Cerebrospinal fluid (CSF) neopterin production is increased by interferon-gamma stimulation and appears to act as a marker of intrathecal immune activation. We aimed to test the usefulness of elevated CSF neopterin as a biological marker of central nervous system (CNS) inflammation.
Method  We retrospectively reviewed CSF neopterin in 158 children (89 males, 69 females, mean age 4y 1mo, SD 3y 11mo, range 1mo–15y).
Results  CSF neopterin levels in children with chronic static CNS disorders ( n =105) were predominantly low, suggesting that inflammation is rare in these patients. We created an upper value of normal (chronic static group 95th centile 27.4nmol/l). CSF neopterin was elevated in all 10 patients with acute encephalitis and in 10 of 12 patients with other acute inflammatory CNS disorders (demyelination, post-infectious ataxia, myelitis). CSF neopterin was also significantly elevated in patients with chronic progressive disorders of inflammatory origin. Interestingly, CSF neopterin was elevated in four of six patients with chronic static disorders who were tested during a febrile exacerbation of seizures or dystonia, suggesting that intrathecal immune activation may be important in this setting.
Interpretation  Neopterin has a short half-life and was useful for monitoring inflammation activity in a patient with relapsing–remitting encephalitis. CSF neopterin is a useful marker of inflammation in a broad range of acute and chronic CNS disorders, and is a significantly more sensitive marker of inflammation than CSF pleocytosis.     

Glutamic acid decarboxylase in cerebrospinal fluid in infancy and childhood Part II. Glutamic acid decarboxylase activity in cerebrospinal fluid of children with neurological diseases

Glutamic acid decarboxylase (GAD) activity in cerebrospinal fluid (CSF) was determined in 53 patients with neurological diseases as follows: Epilepsy (n:17), febrile convulsions (n:3), meningoencephalitis (n:17), encephalopathies (n:10), CNS leukemia (n:3), congenital hydrocephalus (n:2) and pseudoileus neonatorum (n:1). Compared with the mean normal value (5.2 +/- 2.5 pmol CO2 formed/hr/ml) reported in Part I, a significant increase of GAD activity in CSF was demonstrated in patients with uncontrolled epileptic seizures (11.4 +/- 3.9 pmol CO2 formed/hr/ml), febrile convulsions (13.5 +/- 8.7), viral meningitis with or without encephalitis (20.3 +/- 13.6), encephalopathies (30.0 +/- 25.9), CNS leukemia (11.1 +/- 5.0), congenital hydrocephalus (20.5 +/- 7.3) and pseudoileus neonatorum (28.6). Markedly high GAD activity was found in patients with CNS leukemia several days after intrathecal injection of methotrexate (39.8 +/- 18.0). On the other hand, significantly low GAD activity was shown in patients with bacterial meningitis or brain abscess (1.3 +/- 1.2). This suggests that some bacterial factors may be inhibitory toward GAD activity in CSF. High GAD activity in CSF may be useful as an indicator of aseptic brain dysfunction, although it was not always correlated with the severity of symptoms.     

Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients

We analysed the relationship between cerebrospinal fluid (CSF) concentrations of the light subunit of the neurofilament protein (NFL, a marker of neurons, mainly axons), neopterin (a marker of immune activation), and quantitative HIV RNA levels in 47 patients with HIV-1 infection, 25 of whom had AIDS. In the AIDS patients, the mean levels of CSF NFL were high indicating neuronal destruction. The CSF NFL and the CSF neopterin concentrations were correlated in the subgroup of patients without CNS opportunistic infection (p < 0.05). There was no significant correlation between NFL and HIV RNA levels in CSF. In HIV seropositive patients without AIDS, only 3/22 had CSF NFL concentrations above the upper normal reference value. The results suggest that CNS neuronal destruction occurs frequently in patients with AIDS but rarely in those without AIDS, and that immune activation rather than the HIV viral load is associated with neurochemical signs of axonal destruction.     

Significance of CSF total neopterin and biopterin in inflammatory neurological diseases.

Total neopterin (T-N), a by-product in the biopterin biosynthesis and an indicator of activation of the cellular immune system, and total biopterin (T-B) levels in cerebrospinal fluid (CSF), were measured in patients with various inflammatory neurological diseases and Parkinson's disease, and the following results were obtained. (1) In patients with neuro-sarcoidosis, neuro-Beh?et's disease and meningitis, CSF T-N levels were markedly elevated in the exacerbation or acute stages of their neurological symptoms and remarkably decreased in the remission or chronic stages. In the neuro-sarcoidosis and neuro-Beh?et's disease patients, however, CSF T-B levels showed no substantial change. (2) There was a significant positive correlation between CSF T-N levels and CSF/serum albumin ratios only in the meningitis patients. However, increases of CSF T-N levels were not associated with those of plasma T-N levels. (3) In the Parkinson's disease patients, CSF T-N levels remained normal, although CSF T-B levels significantly decreased. (4) A gradient for the CSF T-N value (lumbar greater than ventricular CSF), being reverse to the CSF T-B value, was observed. These results indicate that the significance of CSF T-N is quite different from CSF T-B, and that CSF T-N appears to be a valuable biochemical marker for evaluating the activity of inflammation within the central nervous system. Its measurement seems useful for therapeutic monitoring, especially of patients showing the chronic exacerbating-remitting course.     

Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis

It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1-3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.     

Persistent increase of matrix metalloproteinases in cerebrospinal fluid of tuberculous meningitis

Matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by gelatin zymography and an enzyme-linked immunosorbent assay (ELISA) in a cerebrospinal fluid (CSF) from patients with tuberculous meningitis (n=24), acute aseptic meningitis (n=23) and the control (n=10). The MMP-2 and MMP-9 levels were significantly higher in the samples from the tuberculous meningitis patients than those from either the aseptic meningitis patients or the controls. In tuberculous meningitis, the patients with late neurologic complications had higher MMP-2 and MMP-9 levels than those without. The persistent increase in the MMP-2 and MMP-9 levels was associated with the development of complications following tuberculous meningitis. Inhibiting the MMPs may be an effective strategy for preventing or reducing the complications in tuberculous meningitis.     

Sulfatide as a biochemical marker in cerebrospinal fluid of patients with vascular dementia

The myelin-associated glycosphingolipid sulfatide in cerebrospinal fluid (CSF) was investigated in 20 patients with vascular dementia (VAD), 43 with Alzheimer's disease (AD) and 20 age-matched controls. The sulfatide concentration in the VAD group (307 +/- 118 nmol/l) was significantly (p less than 0.0001) higher than that in controls (145 +/- 86 nmol/l) and the AD group (178 +/- 79 nmol/l). Among the VAD patients, 8/20 had a significantly increased concentration of sulfatide (greater than mean + 2 S.D.), as compared with controls, while only 2/43 of the AD patients had a sulfatide concentration above this level. It is suggested that the elevated concentration of sulfatide in CSF from VAD patients reflects demyelination. Furthermore, sulfatide determinations, when combined with clinical findings, may be of diagnostic value, for discriminating between VAD and AD.     

Cerebrospinal fluid cyclic adenosine 3',5'-monophosphate in cases of severe cerebral ischemia and meningitis

The concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in cerebrospinal fluid was measured in 45 samples from 45 subjects, one sample per subject. 12 of the studied persons were (control group) neurologically normal, 11 were suffering from acute cerebral ischemia with deep coma, and 22 from meningitis of different types. The mean value obtained in the control group was 21.4 +/- (SEM) 3.3 nmol/l, in the group of acute cerebral ischemic attack with deep coma it was 7.00 +/- 0.81 nmol/l and in the group of meningitis 5.5 +/- 0.4 nmol/l. These values are significantly lower than the control group (p less than 0.001). These low levels, observed in the two groups of patients, may be attributed to the altered cAMP metabolism in the central nervous system because of deep coma and bacterial infections.     

Human alpha 1-microglobulin levels in neurological disorders

The concentration of alpha 1-microglobulin (alpha 1-m) in sera and cerebrospinal fluids (CSF) was measured in 121 patients with various neurological disorders. Using single radial immunodiffusion, its serum level was determined. No significant difference was found between the patients (29.1 +/- 4.3 mg/l; mean +/- 1 SD) and normal control group (23.7 +/- 4.6 mg/l). The level of CSF alpha 1-m was determined by the radioimmunoassay of solid antibody system. Its CSF level in the control group was 34.8 +/- 16.0 micrograms/l, while it was significantly increased in the patients with viral meningitis (p less than 0.01) and cerebral infarct (p less than 0.05). The level was also elevated in some cases of brain tumor, bacterial meningitis, cerebral hemorrhage, cervical spondylosis, and acute lymphocytic leukemia. There was a positive correlation between alpha 1-m and albumin levels in CSF. The analysis by CSF/serum albumin ratio and alpha 1-m ratio suggested that the increase of alpha 1-m in CSF could be explained mainly by an increase in permeability of the serum alpha 1-m through damaged blood brain barrier under these pathological conditions. Its local production within the central nervous system, however, could not be ruled out in these disorders.     

Interleukin-1β and tumor necrosis factor-α in cerebrospinal fluid of children with bacterial meningitis

Certain cytokines may contribute to the sequence of events that lead to meningeal inflammation in bacterial meningitis. The purpose of this study was to determine the levels of cytokines in the cerebrospinal fluid (CSF) of children with bacterial meningitis and aseptic meningitis of different etiologies. We determined the concentrations of interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha) in the CSF of 171 specimens of 144 patients whose cases were classified as follow: bacterial meningitis (n=23), aseptic meningitis (n=26) and non-meningitis (n=95). The detectable IL-1beta concentration (> or =20 pg/ml) in the bacterial meningitis, aseptic meningitis and non-meningitis groups were observed with 78.3%, 3.8%, and 8.4%, respectively. Significantly higher serum IL-1beta concentrations were detected in those with bacterial meningitis than those with aseptic meningitis (538.93+/-605.32 pg/ml vs 2.52+/-11.57 pg/ml; P<0.001) or among non-meningitis subjects (2.90+/-11.91 pg/ml; P<0.001). The mean TNF-alpha concentration was 148.74+/-338.77 pg/ml. There was significantly more TNF-alpha than aseptic meningitis (6.85+/-17.93 pg/ml; P<0.001) or non-meningitis (7.67+/-16.07 pg/ml; P<0.001). With regard to diagnosis, measurement of IL-1beta and TNF-alpha levels showed sensitivities of 78% and 74%, respectively; specificities of 96% and 81%, respectively. It is suggested that the levels of these cytokines, especially IL-1beta and TNF-alpha, are useful markers for distinguishing bacterial meningitis from aseptic meningitis.     

Brain function estimated from the ratio of glutamine to homocarnosine levels in cerebrospinal fluid

The ratio of glutamine to homocarnosine (G/H ratio) in CSF of children with meningeal pathology or convulsions was measured and the following results were obtained. 1. The mean G/H ratio of normal subjects was 83.0 +/- 41.4. 2. The mean G/H ratios of the patients with bacterial meningitis and meningeal leukemia were 115.9 +/- 81.9 and 115.2 +/- 49.2, respectively. Significant differences were found between those in normal subjects and these diseases. 3. The mean G/H ratio of the patients with viral meningitis was 80.0 +/- 35.1 and no significant difference was found between normal subjects and these patients. 4. The mean G/H ratios in the patients with controlled versus uncontrolled epilepsy were 130.9 +/- 67.1 and 74.8 +/- 49.4, respectively. A significant difference was found between normal subjects and the patients with controlled epilepsy. 5. The mean G/H ratio in the patients with febrile convulsions was 46.5 +/- 6.3. A significant difference was found between normal subjects and these patients. These data suggest that a high G/H ratio in CSF may indicate the excited state of the brain.     

Level of transforming growth factor beta 1 is elevated in cerebrospinal fluid of children with acute bacterial meningitis

We investigated the levels of transforming growth factor beta 1 (TGF-β1) in cerebrospinal fluid (CSF) in children with meningitis, with a view to prognostic relevance. CSF TGF-β1 levels on admission were measured by a sandwich enzyme immunoassay in children with bacterial meningitis (n = 16), aseptic meningitis (n = 12), and control subjects without evidence of central nervous system (CNS) infection (n = 16). Patients were followed up for a mean duration of 13 months, and neurodevelopmental sequelae was determined for those with bacterial meningitis. On admission, CSF TGF-β1 levels were significantly higher in children with bacterial meningitis (mean, standard error, 32.92, 2.36 pg/ml) as opposed to those with aseptic meningitis (25.26, 1.72 pg/ml) (P = 0.0155), or control subjects (20.53, 1.05 pg/ml) (P < 0.0001). The CSF TGF-β1 levels in children with aseptic meningitis were higher than those in the control group, but without significance (P = 0.02). No apparent correlation existed between CSF TGF-β1 levels and CSF protein or cell counts in patients with bacterial meningitis. No significant difference in CSF TGF-β1 levels was found between patients with or without major sequelae following bacterial meningitis. Received: 19 March 1997 Received in revised form: 24 June 1997 Accepted: 20 August 1997     

Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis

The CD14 antigen, an important cell surface molecule of monocytic cells, is involved in cellular activation: it binds lipopolysaccharide and other cellular lipid structures. Brain macrophages play a pivotal role during inflammatory reactions of the CNS parenchyma, ventricles and meninges. A soluble form of CD14 (sCD14) was measured in paired cerebrospinal fluid (CSF) and serum samples from 91 patients with different neurological diseases. Mean levels of circulating sCD14 in CSF in a control group of 22 patients with neurologic complaints but no neurological deficit on clinical examination were 0.19 +/- 0.06 (mean +/- SD) mg/l. The CSF/blood ratios of sCD14 was 49 +/- 16 x 10(-3), while those of albumin were 4.4 +/- 1.4 x 10(-3). These extremely high CSF/blood ratios of the sCD14 molecule compared to albumin indicate a local cerebral production. No significant changes in CSF sCD14 levels were found in patients with non-inflammatory neurological diseases (NID). In contrast, CSF sCD14 levels were markedly elevated during acute meningitis, but there was no direct correlation between sCD14 and monocyte count in the CSF. Thus, sCD14 could not originate in the CSF compartment from monocytes alone. The highest values for sCD14 were found in CSF during infections with various pathogens such as Staphylococcus aureus or Listeria monocytogenes. While sCD14 serum levels dramatically increased during acute bacterial meningitis, sCD14 ratios did not correlate with albumin ratios during the course of disease. Therefore, increased CSF sCD14 may originate from cerebral production by activated or infiltrated macrophages rather than passive diffusion from the blood, while elevated sCD14 serum levels resulted from enhanced local production. Increased CSF and serum sCD14 values were also observed in meningitis caused by viral infection. As in bacterial meningitis, sCD14 in CSF specimens did not correlate with the function of the blood/CSF barrier. Repeated lumbar punctures revealed a normalization of CSF sCD14 levels during clinical recovery. These results provide the first evidence for local production of sCD14 within the CNS. Our findings further indicate that sCD14 in CSF is a reliable marker for activation of macrophages within the CNS during inflammatory processes.     

Immunoreactive leukotriene C4 levels in CSF of MS patients

Using a sensitive and specific radioimmunoassay levels of leukotriene (LT)C4-like material were estimated in lumbar cerebrospinal fluid (CSF) samples from patients with multiple sclerosis (MS) in comparison to control patients with or without inflammatory processes in the central nervous system (CNS). Levels of LTC4-like material were significantly elevated (p less than 0.01) in CSF from patients with inflammatory diseases such as meningitis, polyradiculitis or meningoencephalitis (57 +/- 53 pg/ml, n = 16) as compared to those from control patients without inflammatory or immunological CNS diseases (21 +/- 16 pg/ml, n = 42). By contrast, LTC4-like material was 16 +/- 7 pg/ml in first manifestations of MS (n = 7). 21 +/- 16 pg/ml in remitting-relapsing MS (n = 15) and 10 +/- 6 pg/ml in chronic progressive MS (n = 8). These results argue against a significant pathophysiological role of cysteinyl-LT in MS.     

The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults.

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean+/-S.D. ADA activity was 12.76+/-7.53 U/l in group 1; 2.58+/-2.37 U/l in group 2; 7.38+/-3.27 U/l in group 3; 7.42+/-4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant (P<0.001), except between groups 3 and 4. The sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed in any of the non-tuberculous meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.