Relationship of cerebrospinal fluid pressure, fungal burden and outcome in patients with cryptococcal meningitis undergoing serial lumbar punctures. AIDS

Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
AIDS (London, England) (Impact Factor: 5.55). 04/2009; 23(6):701-6. DOI: 10.1097/QAD.0b013e32832605fe
Source: PubMed


To assess impact of serial lumbar punctures on association between cerebrospinal fluid (CSF) opening pressure and prognosis in HIV-associated cryptococcal meningitis; to explore time course and relationship of opening pressure with neurological findings, CSF fungal burden, immune response, and CD4 cell count.
Evaluation of 163 HIV-positive ART-naive patients enrolled in three trials of amphotericin B-based therapy for cryptococcal meningitis in Thailand and South Africa.
Study protocols required four lumbar punctures with measurements of opening pressure over the first 2 weeks of treatment and additional lumbar punctures if opening pressure raised. Fungal burden and clearance, CSF immune parameters, CD4 cell count, neurological symptoms and signs, and outcome at 2 and 10 weeks were compared between groups categorized by opening pressure at cryptococcal meningitis diagnosis.
Patients with higher baseline fungal burden had higher baseline opening pressure. High fungal burden appeared necessary but not sufficient for development of high pressure. Baseline opening pressure was not associated with CD4 cell count, CSF pro-inflammatory cytokines, or altered mental status. Day 14 opening pressure was associated with day 14 fungal burden. Overall mortality was 12% (20/162) at 2 weeks and 26% (42/160) at 10 weeks, with no significant differences between opening pressure groups.
Studies are needed to define factors, in addition to fungal burden, associated with raised opening pressure. Aggressive management of raised opening pressure through repeated CSF drainage appeared to prevent any adverse impact of raised opening pressure on outcome in patients with cryptococcal meningitis. The results support increasing access to manometers in resource-poor settings and routine management of opening pressure in patients with cryptococcal meningitis.

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    • "Raised intracranial pressure is an extremely common complication of cryptococcal meningitis and is associated with sometimes profound and irreversible visual and hearing loss (Graybill et al., 2000). Whilst host factors may play a role, there is evidence for pathophysiology due to fungal factors, with a combination of a high fungal burden and infection with highly encapsulated strains obstructing CSF outflow and causing a communicating hydrocephalus (Bicanic et al., 2009; Robertson et al., 2014). Raised intracranial pressure will resolve with time, so to avert irreversible morbidity, management is by frequent, sometimes daily, large volume (up to 30–40 ml) therapeutic CSF taps or temporary diversion using lumbar or ventricular drains (Perfect et al., 2010). "
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    • "Widening access to optimal antifungal therapy requires urgent action if this high associated mortality is to be reduced to the lower levels reported from developed country settings (10 week mortality 10%–26%).60,68 Improving access to essential antifungals must be achieved alongside efforts to treat patients earlier through improved diagnostics85 and effective management of CM complications such as raised intracranial pressure.86 "
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    • "Also, our hospital does not have the equipment necessary for intensive intracranial pressure management, which has been associated with decreased mortality in cryptococcal meningitis and is recommended by the Infectious Diseases Society of America [12,22]. One possible benefit of the early, targeted screening of inpatients with the serum CRAG is that early, aggressive, empiric ICP management could be initiated on CRAG-positive patients according to the protocol recommended by Bicanic et al [23]. Finally, patients in our setting often present for medical care late in the course of their illness [24,25]. "
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