M-tuberculosis molecular variation in CNS infection - Evidence for strain-dependent neurovirulence

Objective: To determine the molecular diversity among Mycobacterium tuberculosis isolates associated with central nervous system tuberculosis (CNS TB) in a defined cohort of HIV uninfected patients. Design/methods: A retrospective analysis was performed of clinical and laboratory data for all patients with CNS TB diagnosed in Manitoba, Canada, between 1979 and 1996. Restriction fragment-length polymorphisms (RFLP) of archival isolates of M. tuberculosis from CNS TB patients were determined and interpreted against the frequency of different isolates from all TB patients in the years 1992 to 1996, Results: Among 2,334 patients with active TB, CNS TB was diagnosed in 42 (1.8%); meningitis with or without tuberculoma in 76%; and tuberculoma alone in 24%. CNS TB patients were significantly more likely to be young (<40 years old), female, and of Aboriginal origin. Morbidity (fixed/recurrent CNS deficit) rate was 29% and mortality rate was 26%. An adverse outcome, either morbidity or mortality, was significantly more common in those with meningitis. RFLP analysis of isolates (n = 19) from CNS TB patients revealed 13 distinct restriction patterns with a predominance of the type 1 pattern (n = 6). The frequency of type 1 restriction pattern was significantly greater in patients with CNS TB compared to all TB patients in Manitoba. Conclusions: CNS TB continues to have a high morbidity and mortality despite modern methods of detection and treatment. Although several strains of hi. tuberculosis cause CNS TB, the current study suggests that the occurrence of CNS TB may be strain-dependent.