UnlikeHIVencephalitis,thebrainlesionsofIRISmaybeassociatedwithaCD8+ Tcellinfiltrate,botharoundbloodvesselsanddiffuselyintheparenchyma,intheabsenceofsignificantHIVburdenormultinucleatedcells.
Progressive multifocal leukoencephalopathy (PML) is caused by JC virus, a polyomavirus, which preferentially infects oligodendrocytes, resulting in demyelination as these cells are injured and then die. Most people show serologic evidence of exposure to JC virus during childhood, and it is believed that PML results from virus reactivation, as the disease is restricted to immunosuppressed individuals. Patients develop focal and relentlessly progressive neurologic signs and symptoms, and imaging studies show extensive, often multifocal lesions in the hemispheric or cerebellar white matter.
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Fig. 23.19 Progressivemultifocalleukoencephalopathy.(A)Sectionstainedformyelinshowingirregular,poorlydefinedareasofdemyelination,whichbecomeconfluentinplaces.(B)Enlargedoligodendrocytenucleistainedforviralantigenssurroundanareaofearlymyelinloss.
MORPHOLOGYThelesionsarepatchy,irregular,ill-definedareasofwhitematterdestructionthatenlargeasthediseaseprogresses(
Fig.23.19 ).Eachlesionisanareaofdemyelination,inthecenterofwhicharescatteredlipid-ladenmacrophagesandareducednumberofaxons.Attheedgesofthelesionaregreatlyenlargedoligodendrocytenucleiwhosechromatinisreplacedbyglassy-appearingamphophilicviralinclusions.Thevirusalsoinfectsastrocytes,leadingtobizarregiantformswithirregular,hyperchromatic,sometimesmultiplenucleithatcanbemistakenforatumor.
Fungal infections usually produce parenchymal granulomas or abscesses, often associated with meningitis. The most common fungal infections have the following distinctive patterns:
Candida albicans usually produces multiple microabscesses, with or without granuloma formation.
Mucormycosis, caused by several fungi belonging to the order Mucorales, typically presents as an infection of the nasal cavity or sinuses in a diabetic patient with ketoacidosis. It may spread to the brain through vascular invasion or by direct extension through the cribriform plate. The proclivity of Mucor to invade the brain directly sets it apart from other fungi, which reach the brain by hematogenous dissemination from distant sites.
• Aspergillus fumigatus tends to cause a distinctive pattern of widespread septic hemorrhagic infarctions because of its marked predilection for blood vessel wall invasion with subsequent thrombosis.
While a wide range of other organisms can infect the nervous system and its covering, only three relatively common entities are considered here.
Cerebral infection with the protozoan Toxoplasma gondii can occur in immunosuppressed adults or in newborns who acquire the organism transplacentally from a mother with an active infection. The consequences include the triad of chorioretinitis, hydrocephalus, and intracranial calcifications. In adults, the clinical symptoms are subacute, evolving over weeks, and may be both focal and diffuse. Due to inflammation and breakdown of the blood-brain barrier at sites of infection, imaging studies often show edema associated with ring-enhancing lesions.