Paretic neurosyphilis stems from parenchymal involvement by spirochetes and is associated with neuronal loss and marked proliferation of microglial cells. Clinically, this form of the disease causes an insidious progressive loss of mental and physical functions, mood alterations (including delusions of grandeur), and eventually severe dementia.
Tabes dorsalis results from damage to the sensory nerves in the dorsal roots. Consequences include impaired joint position sense and ataxia; loss of pain sensation, leading to skin and joint damage (Charcot joints); other sensory disturbances, particularly characteristic “lightning pains”; and the absence of deep tendon reflexes.
Neuroborreliosis refers to involvement of the nervous system by the spirochete Borrelia burgdorferi, the causative agent of Lyme disease. Neurologic signs and symptoms are highly variable and include aseptic meningitis, facial nerve palsies, mild encephalopathy, and polyneuropathies.
Fungal infection of the nervous system can give rise to chronic meningitis and, as with other pathogens, this can be associated at times with parenchymal infection. Immunosuppression increases the risk for these diseases, but it is not a requirement for infection to occur. Several fungal pathogens cause CNS disease:
Cryptococcus neoformans can cause both meningitis and meningoencephalitis, often in the setting of immunosuppression. It may be fulminant and fatal in as little as 2 weeks or may be indolent, evolving over months or years. The CSF may have few cells but elevated protein, and the mucoid encapsulated yeasts can be visualized on India ink preparations. Extension into the brain follows vessels in the Virchow-Robin spaces. As organisms proliferate, these spaces expand, giving rise to a “soap bubble”–like appearance (
Fig. 23.17
Histoplasma capsulatum commonly involves the nervous system in the setting of disseminated infection. There is an increased risk for disease in the setting of HIV infection. Histoplasmosis typically causes a basilar meningitis, with elevated CSF protein, mildly decreased glucose, and mild lymphocytic pleocytosis. Parenchymal lesions can occur, mostly from tracking of organisms along Virchow-Robin spaces.
Coccidioides immitis, a fungus endemic to desert regions of the American Southwest, most commonly causes meningitis in the setting of disseminated infection. Diagnosis can be made by examining the CSF for specific antibody. Without treatment, coccidioidal meningitis has a high fatality.
The entire gamut of infectious pathogens (viruses to parasites) can infect the brain, often in characteristic patterns. In general, viral infections are diffuse, bacterial infections (when not associated with meningitis) are localized, while other organisms produce mixed patterns. In immunosuppressed hosts, more widespread involvement with any agent is typical.
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Fig. 23.17 Cryptococcalinfection.(A)Whole-brainsectionshowingthenumerousareasoftissuedestructionassociatedwiththespreadoforganismsintheperivascularspaces.(B)Athighermagnification,itispossibletoseethecryptococciinthelesions.
Brain abscesses are most often caused by bacterial infections. These can arise by direct implantation of organisms, local extension from adjacent foci (mastoiditis, paranasal sinusitis), or hematogenous spread (usually from a primary site in the heart, lungs, or distal bones, or after tooth extraction). Predisposing conditions include acute bacterial endocarditis, from which septic emboli are released that may produce multiple abscesses; cyanotic congenital heart disease, associated with a right-to-left shunt and loss of pulmonary filtration of organisms; and chronic pulmonary infections, as in bronchiectasis, which provide a source of microbes that spread hematogenously.