MORPHOLOGYWhentheinfectionisacquiredinimmunosuppressedadults,thebrainshowsabscesses,frequentlymultiple,mostofteninvolvingthecerebralcortex(nearthegray-whitejunction)anddeepgraynuclei.Acutelesionsconsistofcentralfociofnecrosissurroundedbyacuteandchronicinflammation,macrophageinfiltration,andvascularproliferation.Bothfreetachyzoitesandencystedbradyzoitesmaybefoundattheperipheryofthenecroticfoci(
Fig.23.20
Cysticercosis is the consequence of an end-stage infection by the tapeworm Tenia solium. If ingested larval organisms leave the lumen of the gastrointestinal tract, where they would otherwise develop into mature tapeworms, they encyst. Cysts can be found throughout the body and are common within the brain and subarachnoid space. Cysticercosis typically manifests as a mass lesion and can cause seizures. Symptoms can intensify when the encysted organism dies, as occurs after therapy.
The organism is found within a cyst with a smooth lining. The body wall and hooklets from mouth parts are most commonly recognized. Death of the encysted organism may produce an intense inflammatory reaction in the surrounding brain, often including eosinophils, and marked gliosis.
Amebic meningoencephalitis manifests with different clinical syndromes, depending on the responsible pathogen. Naegleria fowleri, associated with swimming in stagnant warm fresh water ponds, causes a rapidly fatal necrotizing encephalitis. By contrast, various species of Acanthamoeba cause a chronic granulomatous meningoencephalitis.
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Fig. 23.20 Toxoplasmainfection.(A)Abscessesarepresentintheputamenandthalamus.(B)Freetachyzoitesaredemonstratedbyimmunohistochemicalstaining.Inset, Bradyzoitesarepresentasapseudocyst,againhighlightedbyimmunohistochemicalstaining.
Prion diseases are a group of infectious diseases in which the causative agent is an abnormal form of a cellular protein. These include sporadic, familial, iatrogenic, and variant forms of Creutzfeldt-Jakob disease (CJD), as well as animal diseases such as scrapie in sheep and bovine spongiform encephalopathy in cattle (“mad cow disease”). The causative protein, termed prion protein (PrP), may undergo a conformational change from its normal shape (PrPc) to an abnormal conformation called PrPsc (sc for scrapie). PrP normally is rich in α-helices, but PrPsc has a high content of β-sheets, a characteristic that makes it resistant to proteolysis (hence an alternative term for the pathogenic form, PrPres—i.e., protease-resistant). More important, when PrPsc physically interacts with PrP molecules, it induces them to adopt the PrPsc conformation (
Fig. 23.21 ), a property that accounts for the “infectious” nature of PrPsc. Over time, this self-amplifying process leads to the accumulation of a high burden of pathogenic PrPsc molecules in the brain. Certain mutations in the gene encoding PrPc (PRNP) accelerate the rate of spontaneous conformational change; these variants are associated with early-onset familial forms of prion disease (familial Creutzfeldt-Jakob disease [fCJD]). PrPc also may change its conformation spontaneously (but at an extremely low rate), accounting for sporadic cases of prion disease (sporadic Creutzfeldt-Jakob disease [sCJD]). Accumulation of PrPsc in neural tissue seems to be the cause of cell injury, but the mechanisms underlying the cytopathic changes and eventual neuronal death are still unknown.