Mycobacterial Infections

Mycobacterial infections, always prevalent in developing countries, are now reappearing in the United States and Europe, especially in immunodeficient persons. During hematogenous dissemination of tuberculosis, small caseating lesions (tubercles) develop in the meninges and in brain tissue. Mycobacteria can survive in these lesions for a long time. When tubercles rupture, mycobacteria are discharged into the CSF causing tuberculous meningitis. This may happen in the course of disseminated miliary tuberculosis, or sometimes years later. The focus of the initial infection in the lungs may be undetected. In some cases, tuberculous meningitis has a fulminant presentation, similar to bacterial meningitis. In other cases, it presents insidiously and progresses slowly over weeks or months, causing headache, confusion and cranial nerve deficits. Infection of the CSF causes initially acute inflammation. Mycobacteria are not eliminated because they have components in their cell walls that enable them to survive in macrophages. Two to three weeks after the onset of the infection, sooner in sensitized hosts, a cell-mediated immune reaction develops. This enhances intracellular killing of mycobacteria by macrophages. However, enzymes released by dying macrophages cause necrosis of infected tissue. Necrotic tissue is yellowish and has a cheesy consistency, hence caseous (L. caseus. cheese) necrosis.

Tb meningitis

Tb meningitis

The histological findings in tuberculous meningitis are the same as those of mycobacterial infections elsewhere, namely epithelioid cell granulomas with Langhans giant cells, lymphocytic infiltrates, and caseous necrosis. Epithelioid cells are macrophages engaged in mycobacterial killing. They aggregate in clusters (granulomas) or fuse, forming giant cells. These changes involve the arachnoid membrane and subarachnoid space diffusely. Acid fast organisms can be demonstrated in necrotic tissue and in the granulomas. Mycobacteria produce no exotoxins. Inflammation gradually kills the organisms. However, its destructive force causes also severe damage to vessels, nerves, and the arachnoid membrane with complications (vasculitis, cerebral infarction, hydrocephalus, nerve damage) even more serious than those of suppurative meningitis. Also, unlike suppurative meningitis in which the exudate is usually confined to the subarachnoid space, epithelioid cell granulomas destroy the pia and invade the brain. The CSF in tuberculous meningitis shows pleocytosis with a predominance of mononuclear cells, high protein and low glucose.


Tuberculous infection of the brain sometimes results in formation of a tumor-like mass (tuberculoma) that consists of caseous necrotic material surrounded by epithelioid cell granulomas and mononuclear cells. Rupture of the tuberculoma and release of mycobacteria into the subarachnoid space cause meningitis.

Infections caused by Spirochetes

Tertiary syphilis has protean neurological manifestations which are caused by meningovascular and parenchymal lesions. The meningovascular lesions are a lymphoplasmacytic meningitis and intimal thickening of small and medium-size leptomeningeal and parenchymal arteries (endarteritis obliterans- Heubner arteritis). The parenchymal lesions are tabes dorsalis (rot of the spinal cord), characterized by inflammation and degeneration of dorsal roots and posterior columns, and general paresis of the insane (dementia paralytica), an encephalitis due to invasion of the brain by spirochetes. In addition, syphilis can cause gummas in the brain. A gumma (L gummi. gum) is a rubberry necrotic and inflammatory mass which contains spirochetes and acts like a space-occupying lesion. Syphilis can also cause an acute meningitis during its secondary stage.

Lyme disease is caused by the tick-borne spirochete Borrelia Burgdorferi. In its second and third stages, it can cause meningitis, radiculitis, neuropathy, and encephalitis, leading to ataxia, paralysis, dementia, and other neurological manifestations. The CSF shows mononuclear pleocytosis and mild protein elevation. The pathology is not well studied. Presumably, there are lymphoplasmacytic infiltrates and vasculitis in the meninges and brain, similar to changes that have been observed in other tissues.

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