Temporal evolution of cerebrospinal fluid following initiation of treatment for tuberculous meningitis

Abstract

Objective: Clinicians often perform follow-up lumbar punctures (LPs) on patients with tuberculous meningitis (TBM) to document changes occurring in the cerebrospinal fluid (CSF). Normalisation of the CSF then serves as indirect confirmation of the diagnosis. However, changes occurring in CSF following the initiation of anti-tuberculosis (TB) treatment are not well described. We undertook a retrospective study to determine the temporal evolution of CSF in patients with TBM on anti-TB treatment in an attempt to provide a more rational basis for the interpretation of repeat LPs.

Methods: Patients diagnosed with TBM at King George V Hospital in Durban from 1994 to 2003 were identified. Demographic, clinical, laboratory and radiological data were recorded. We examined the change in CSF lymphocyte cell count, polymorphonuclear (PMN) cell count, glucose concentration and protein concentration. Initially, scatter plots of the data modelled over time were produced and random effects models were then used to model the predicted changes in CSF over time.

Results: Ninety-nine patients were identified, and a total of 327 LPs were done. The average number of LPs per patient was 3 (range 3 - 9). Statistically significant changes in all four variables (lymphocytes, PMN cells, glucose and protein) were demonstrated, with a p value < 0.001. The predicted models showed that lymphocyte count and protein concentration change slowly over time. PMN cells and glucose concentration changed rapidly in an exponential manner.

Conclusions: Our results demonstrate the tendency for CSF to normalise over time. The slow change in lymphocyte count and protein concentration limits clinical use. The rapid change in PMN cells and glucose concentration allows us to make reasonable clinical decisions. If a repeat LP does not show definite improvement in these two parameters, it should be considered atypical for TBM.