Increased serum concentrations of tissue plasminogen activator correlate with an adverse clinical outcome in patients with bacterial meningitis.
نویسندگان
چکیده
Increased serum concentrations of tissue plasminogen activator correlate with an adverse clinical outcome in patients with bacterial meningitis Bacterial meningitis is the most common serious infection of the central nervous system. It is still characterised by high mortality and morbidity in adults. In this disease extensive perpetuated inflammation with leucocyte invasion into the central nervous system (CNS) results in breakdown of the blood–brain barrier and promotes neuronal damage. 1 Tissue type plasminogen activator (tPA) has been shown to have various biological effects that could have an impact on the pathophysi-ological changes observed in bacterial meningitis. In the CNS, endothelial cells, microglia, astrocytes, and neurones can produce the 70 kDa protein tPA, which normally does not cross the blood–brain barrier. 2 Raised tPA levels in the cerebrospinal fluid (CSF) have previously been reported for certain CNS diseases such as multiple sclerosis, leukaemia, and encephalitis, 3 and raised serum tPA levels for patients with sepsis. 4 tPA converts plasminogen into plasmin, a rate limiting step in the proteolysis of fibrin, but also in the degradation of extracellular matrix, matrix metalloproteinase activation, and the processing of growth factors and cytokines. 2 Further, tPA has been shown to increase neuronal cell death during excitotox-icity and cerebral ischaemia. 2 Thus tPA may promote blood–brain barrier disruption, proinflammatory signalling, and neuronal damage, and so be involved in the pathophysi-ology of bacterial meningitis. We studied the expression of tPA in the CSF and serum of 12 patients with bacterial meningitis (causative pathogens: Str pneumoniae (8); S aureus (3); H influenzae (1)) who had been admitted to our hospital (median age 63 years; range 29 to 78). Clinical outcome was measured according to the Glasgow outcome scale (GOS; 1, death; 2, persistent vegetative state; 3, severe disability; 4, moderate disability ; 5, good recovery). Ten patients with non-inflammatory neurological diseases (median age 37 years; range 23 to 81) and 10 patients with Guillain-Barré syndrome, an inflammatory demyelinating polyradicu-loneuropathy in which blood–CSF barrier breakdown occurs without CSF pleocytosis, served as controls (median age 59 years; range 34 to 84). A lumbar puncture was done and venous blood collected for diagnostic purposes after the patient's informed consent had been obtained. CSF and serum concentrations of tPA were measured by a specific enzyme linked immunosorbent assay (TintElize®, USA; detection limit 1.5 ng/ml). Immunoreac-tive tPA concentrations are expressed as ng/ml of biological fluid. Blood and CSF variables for the three patient groups …
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عنوان ژورنال:
- Journal of neurology, neurosurgery, and psychiatry
دوره 73 4 شماره
صفحات -
تاریخ انتشار 2002