In the United States and in most western countries, the incidence of tuberculous meningitis, which parallels the frequency of systemic tuberculosis, has, until recently, decreased steadily and markedly since World War II. Beginning approximately 1985, there has been a moderate increase in the incidence of systemic tuberculosis (and tuberculous meningitis) in the United States—a 16 percent annual increase compared to an average annual decline of 6 percent during the preceding 30 years (Snider and Roper). This was partly due to the appearance of HIV. In fact, tuberculosis may be the first clinical manifestation of HIV infection (Barnes et al); among patients with full-blown HIV, the incidence of tuberculosis is almost 500 times the incidence in the general population (Pitchenik et al). In developing countries, particularly in sub-Saharan Africa, recent estimates of the incidence of tuberculosis suggest that it is 25 times more frequent than in the United States, again largely because of the prevalence of HIV infection. The trend of increasing incidence has recently been reversed in regions of the world where HIV has been brought under better control.
Tuberculous meningitis is usually caused by the acid-fast organism Mycobacterium tuberculosis and exceptionally, by Mycobacterium bovis, Mycobacterium avian, Mycobacterium kansasii, and Mycobacterium fortuitum (the last of these after neurosurgical procedures and cranial trauma). The emergence of HIV has led to a marked increase in cases caused by both the main organism, and also by the atypical mycobacteria. In a monograph as informative today as it was 70 years ago, Rich described two stages in the pathogenesis of tuberculous meningitis: first a bacterial seeding of the meninges and subpial regions of the brain with the formation of tubercles, followed by the rupture of one or more of the tubercles and the discharge of bacteria into the subarachnoid space. The concept that tuberculous meningitis always originates in a tubercle (i.e., part of the miliary disease) in contrast to the conventional notion of hematogenous implantation in other bacterial meningitis, has been debated.
Small, discrete white tubercles are scattered over the base of the cerebral hemispheres and to a lesser degree on the convexities. The brunt of the pathologic process falls on the basal meninges, where a thick, gelatinous exudate accumulates, obliterating the pontine and interpeduncular cisterns and extending to the meninges around the medulla, the floor of the third ventricle and subthalamic region, the optic chiasm, and the undersurfaces of the temporal lobes. There may be multiple small abscesses (Fig. 31-3) or a more uniform exudate in the leptomeninges (Fig. 31-3). By comparison, the convexities are little involved, possibly because the associated hydrocephalus obliterates the cerebral subarachnoid space. Microscopically, the meningeal tubercles are like those in other parts of the body, consisting of a central zone of caseation surrounded by epithelioid cells and some giant cells, lymphocytes, plasma cells, and connective tissue. The exudate is composed of fibrin, lymphocytes, plasma cells, other mononuclear cells, and some polymorphonuclear leukocytes. The ependyma and choroid plexus are studded with minute glistening tubercles. The exudate also surrounds the spinal cord. Unlike the typical bacterial meningitides, the disease process is not confined to the subarachnoid space but frequently penetrates the pia and ependyma and invades the underlying brain, so that the process is truly a meningoencephalitis.