ABSTRACT
OBJECTIVE: To determine the frequency and risk factors of post-dural puncture headache (PDPH) in research volunteers. BACKGROUND: Despite increasing interest in measuring cerebrospinal fluid (CSF) biomarkers to investigate disease pathogenesis and diagnosis, previous case series have evaluated lumbar puncture (LP) safety only in clinical care. PDPH is a common complication after LP. METHODS: We determined the frequency of PDPH in neurologically unselected HIV seropositive and seronegative adults volunteering for research, as well as the variables associated with the development of PDPH. Variables studied were body mass index (BMI), HIV serostatus, volume of CSF removed, number of previous LPs, use of pre-medication, LP position, lumbar space, number of needle passes, whether or not aspiration was used, CSF white blood cell counts, CSF red blood cell counts, CD4 count, CD4 nadir, CSF HIV viral load, plasma HIV viral load, and race. RESULTS: Of 675 LPs performed over 1 year, headache developed in 38 (5.6%; 95% CI 4.2, 7.1). Most PDPH (92%) resolved spontaneously or with conservative medical management; 3 required epidural blood patch. Greater headache risk was associated with lower BMI (BMI ≤25 vs >25) (OR 3.3; CI 95% 1.5, 7.0; P = .001) and less prior LP experience (previous LPs ≤2 vs >2) (OR 2.1; CI 95% 1.1, 4.1; P = .03). PDPH was not significantly (P > .05) related to HIV serostatus, CSF volume, or gender. CONCLUSION: In this study, where tolerance to risk was low because LPs were done for research rather than clinical purposes and healthy controls were included, adverse effects were mild and self-limited.
Subject(s)
Post-Dural Puncture Headache/diagnosis , Post-Dural Puncture Headache/epidemiology , Adult , Cross-Sectional Studies , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Post-Dural Puncture Headache/etiology , Prospective Studies , Risk FactorsABSTRACT
HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched concentrations in plasma and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on the use of RAL-containing regimens and the availability of CSF and matched plasma samples. RAL was measured in 21 CSF and plasma pairs by liquid chromatography-tandem mass spectrometry, and HIV RNA was detected by reverse transcription-PCR (RT-PCR). RAL concentrations were compared to the 50% inhibitory concentration (IC(50)) for wild-type HIV-1 (3.2 ng/ml). Volunteers were predominantly middle-aged white men with AIDS and without hepatitis C virus (HCV) coinfection. The median concurrent CD4(+) cell count was 276/µl, and 28% of CD4(+) cell counts were below 200/µl. HIV RNA was detectable in 38% of plasma specimens and 4% of CSF specimens. RAL was present in all CSF specimens, with a median total concentration of 14.5 ng/ml. The median concentration in plasma was 260.9 ng/ml, with a median CSF-to-plasma ratio of 0.058. Concentrations in CSF correlated with those in with plasma (r(2), 0.24; P, 0.02) but not with the postdose sampling time (P, >0.50). RAL concentrations in CSF exceeded the IC(50) for wild-type HIV in all specimens by a median of 4.5-fold. RAL is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in all individuals. As a component of effective antiretroviral regimens or as the main antiretroviral, RAL likely contributes to the control of HIV replication in the nervous system.
