The Association between Blood-Cerebrospinal Fluid Barrier Dysfunction and the Therapeutic Effect in Tuberculous Meningitis Patients

Abstract

Objective: To explore the correlation of blood-cerebrospinal fluid (CSF) barrier (BCB) dysfunction with the therapeutic effect of antitubercular agents and their resistance, hoping to provide theoretical evidence for improvement of the therapeutic effect. Methods: Albumin in CSF and serum was assayed by IMMAGE. The CSF/serum albumin ratio (Q_ALB) was used to evaluate the permeability of the BCB. Real-time fluorescence quantitative PCR was used to detect the amount of Mycobacterium tuberculosis DNA, and an MTBDRplus reagent kit was used to determine the type of drug resistance of the M. tuberculosis.Results: The correlation analysis showed that significant correlation existed between the grade of severity of tuberculous meningitis and the Q_ALB, and the grade of severity and the total leukocyte count in the CSF, for which the correlation coefficients were 0.366 (p < 0.05) and 0.365 (p < 0.05), respectively. The Q_ALB in the group of patients who recovered was significantly higher than that in those patients who experienced disease progression (p = 0.019). Conclusions: Our study showed that the permeability of the BCB correlated with the cure rate in tuberculous meningitis. Specifically, in the treatment of tuberculous meningitis, it is of key importance to utilize the benefit of the permeability of the BCB to achieve a better outcome.

Comparison of Clinical Features and Prognostic Factors of Cryptococcal Meningitis Caused by Cryptococcus neoformans in Patients With and Without Pulmonary Nodules

“…Thus, our results showed that PN-positive patients might have more serious BCB dysfunction and weak immune function. A previous study showed that the CSF/serum albumin ratio in patients with tuberculous meningitis who recovered was higher than that in patients who experienced a progress of illness, which may have been caused by weakening of the treatment effect due to hindrance of the drug delivery by the BCB [26]. Our observations showed that PN-positive CM patients experienced worse treatment response at week 2 and were more likely to have unfavorable clinical outcome.…”

Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines

“…In a study on 83 patients with TBM, Q alb correlated with severity of disease and leucocyte counts. The patients with elevated Q alb had drug resistance [14]. This study, however, did not evaluate Q alb relationship with cytokines and MRI changes.…”

“…The infraction in TBM is usually deep seated and smaller in size. Intra parenchymal tuberculoma reveals perilesional BBB abnormality revealing ring or disc enhancement on CT or MRI scan [14,41]. The association of basal exudates with Q alb suggests focal breach of B-CSF barrier.…”

“…Intrathecal levels of TNF-α also correlated with disease severity and indicates meningeal in ammation. In TBM, there are paucities of studies on the role of CSF permeability and its association with clinical, laboratory and MRI changes [14][15][16][17]. This study is therefore undertaken to evaluate the role of B-CSF barrier permeability in the patients with TBM, and its association with clinical severity, meningeal in ammation in CSF, MRI ndings and 6 months outcome.…”

Strategies to target drugs to gliomas and CNS metastases of solid tumors

“…Another important barrier of the CNS, especially for systemic treatment of LM, is the BCSFB [59,60] (Fig. 2).…”