Glucosephosphate isomerase as a CSF marker for leptomeningeal metastasis.

Glucosephosphate isomerase (GPI), also known as phosphohexoisomerase, is a glycolytic enzyme whose activity is elevated in serum and CSF of patients with primary and metastatic CNS tumors. To improve the diagnostic accuracy of leptomeningeal metastasis (LM), we measured GPI levels in CSF of 66 patients with CNS or systemic malignancies with suspected LM. We determined GPI kinetically using a coupled enzyme reaction assay. There were 31 males and 35 females, aged 1 to seventy-six. Thirty-one had primary brain tumors, and 35 had systemic cancer with suspected CNS metastasis. We analyzed 95 samples; GPI values ranged from 0.85 to 329.0 U/l (normal, less than 20 U/l). Compared with positive CSF cytology and myelography, GPI sensitivity was 53.5% and specificity 92.1% for the group as a whole. There was a highly significant association between elevated CSF GPI (greater than 20 U/l) and LM. The results were similar for both primary CNS and systemic malignancies. Although not very sensitive, an elevated CSF GPI strongly suggests LM and may aid in early diagnosis of this serious complication of cancer.

Identification of autotaxin as a neurite retraction-inducing factor of PC12 cells in cerebrospinal fluid and its possible sources.

Abstract Cerebrospinal fluid (CSF) induced neurite retraction of differentiated PC12 cells; the action was observed in 15 min (a rapid response) and the activity further increased until 6 h (a long-acting response) during exposure of CSF to the cells. The CSF action was sensitive to monoglyceride lipase and diminished by homologous desensitization with lysophosphatidic acid (LPA) and by pretreatment with an LPA receptor antagonist Ki16425. Although fresh CSF contains LPA to some extent, the LPA content in the medium was increased during culture of PC12 cells with CSF. The rapid response was mimicked by exogenous LPA, and a long-acting response was duplicated by a recombinant autotaxin, lysophospholipase D (lyso-PLD). Although the lyso-PLD substrate lysophosphatidylcholine (LPC) was not detected in CSF, lyso-PLD activity and an approximately 120-kDa autotaxin protein were detected in CSF. On the other hand, LPC but not lyso-PLD activity was detected in the conditioned medium of a PC12 cell culture without CSF. Among neural cells examined, leptomeningeal cells expressed the highest lyso-PLD activity and autotaxin protein. These results suggest that leptomeningeal cells may work as one of the sources for autotaxin, which may play a critical role in LPA production and thereby regulate axonal and neurite morphological change.

Phosphohexose isomerase in cerebrospinal fluid in meningitis.

The diagnostic value of determining phosphohexose isomerase (PHI, E.C. 5.3.1.9) activity in the CSF for differential diagnosis of bacterial and viral meningitis was investigated. In 29 patients with untreated bacterial meningitis, a mean enzyme activity of 511 U/1 was found, whereas a value 19 U/1 was found in 61 cases of viral meningitis. The reference range with an upper limit of 6 U/1 was determined from CSF samples from 163 "healthy" children. The high diagnostic sensitivity and specificity of 100% and 99.5% respectively make PHI a sensitive differential diagnostic parameter in meningitis.

[Significance of lactate level, lysozyme concentration and phosphohexose isomerase activity in the cerebrospinal fluid in the differential diagnosis of meningitis]. / Die Bedeutung des Laktatspiegels, der Lysozymkonzentration und der Phosphohexose-Isomerase-Aktivität im zerebrospinalen Liquor für die Differentialdiagnose der Meningitis.

The significance of the measurement of lactate, lysozyme and PHI in CSF for differential diagnosis of meningitis was examined in 58 cases of viral, 36 of bacterial and 5 of tuberculous etiology. In the early phase of the illness CSF lactate was found to be the most sensitive parameter for distinction of viral from bacterial or tuberculous meningitis respectively. Except for one case CSF lactate exceeded 3.8 mmol/l in all cases of bacterial etiology, whereas this value was never reached in any case of viral meningitis. While lactate concentration was maximal on the day of admission and declined continuously thereafter, PHI activity reached its maximum on the third day after beginning of the therapy. At this time all patients with a bacterial or tuberculous meningitis had PHI activities about 50 U/l. This value wasn't exceeded in any case of viral meningitis. In a few cases some days after onset of therapy a distinction of bacterial meningitis from viral forms was still possible by PHI determination but not by lactate measurement. Determination of lysozyme also could be helpful in the later phase of the disease.

Clinical significance and source of raised catalytic activities of phosphohexose isomerase in the CSF in meningitis.

The value of phosphohexose isomerase (EC 5.3.1.9) determination in the CSF in the diagnosis of meningitis was tested under routine conditions. In 48 patients with untreated bacterial meningitis, enzyme activity concentrations between 40 and 2335 U/l were measured, whereas the highest phosphohexose isomerase activity concentration in 92 patients with viral meningitis was 34 U/l. Lysis of the CSF leukocytes with Triton X-100 resulted in a substantial increase of phosphohexose isomerase activity. In bacterial meningitis these values increased to 200 to 7000 U/l, but remained under 150 U/l in viral meningitis. The raised enzyme activities are derived from the leukocytes and appear to reflect their functional and metabolic state. The information provided by the leukocyte morphology can thus be appreciably extended by phosphohexose isomerase determination.