Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis: Alterations with penicillin and methylprednisolone

W. M. Scheld, R. G. Dacey, H. R. Winn, J. E. Welsh, J. A. Jane, M. A. Sande

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Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increased in acute pneumococcal meningitis when compared to control, uninfected animals (6.77±3.52 vs 0.26±0.04 mm Hg/μl per min, P<0.001). Similar elevations (8.93±4.15 mm Hg/μl per min) were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07±4.68 mm Hg/μl per min) and had not returned to normal up to 15 days later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/μl per min) and no 'rebound' effect was apparent 24 hr later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the brain to compensate for changes in intracranial volume and pressure.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalJournal of Clinical Investigation
Issue number2
StatePublished - 1980


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