MACROSCOPIC APPEARANCES

The cerebral lesion is usually single and located in the cortical gray matter, basal ganglia, or at the junction between cortex and white matter. Early lesions appear as small foci of hemorrhagic softening. These become necrotic, with yellow–green centers, and later cavitate. The walls are irregular and there is no evidence of encapsulation. Occasionally there are multiple abscesses.

MICROSCOPIC APPEARANCES

Cerebral amebic abscesses contain inflamed necrotic tissue and it may be difficult to distinguish E. histolytica trophozoites within this tissue from macrophages. The trophozoites are spherical or oval, 15–25 μm in diameter, and have vacuolated cytoplasm and a single nucleus. Occasionally pseudopodia can be seen. In routinely stained sections, the nuclei are round and have a small central karyosome and peripheral chromatin (Fig. 18.1). The cytoplasm contains abundant glycogen.

Trophozoites can usually be identified in the abscess wall, which has an inner zone of necrotic tissue and a broad outer zone with prominent congestion and vascular proliferation. Reactive gliosis and an infiltrate of lymphocytes, plasma cells, macrophages, and some neutrophils are seen in the surrounding brain.

MACROSCOPIC APPEARANCES

The brain is swollen and there is a hemorrhagic exudate in the meninges over the cerebrum, brain stem, and cerebellum. The olfactory bulbs and tracts and the adjacent parts of the frontal and temporal lobes contain areas of hemorrhagic necrosis (Fig. 18.2).

MICROSCOPIC APPEARANCES

A scanty mononuclear inflammatory infiltrate (Fig. 18.2) with focal hemorrhage is seen in the meninges, and there is usually extensive necrosis of brain parenchyma. N. fowleri amebae are present in the subarachnoid space and around vessels in the necrotic parenchyma (Fig. 18.3). Their diameter, of 8–15 μm, is slightly less than that of E. histolytica. They resemble macrophages, but can be distinguished from them by their vesicular nucleus with its large central nucleolus.

MACROSCOPIC APPEARANCES

The brain is usually swollen, covered by a diffuse leptomeningeal exudate, and includes foci of softening, hemorrhage, and necrosis, particularly in the anterior part of the cerebral hemispheres, the thalamus (Fig. 18.4), brain stem, and cerebellum (Fig. 18.5).

MICROSCOPIC APPEARANCES

The brain shows foci of chronic inflammation centered around arteries and veins. The inflammation is typically granulomatous and includes lymphocytes, macrophages, plasma cells, and multinucleated giant cells, but may be necrotizing. There is also a chronic inflammatory infiltrate in the meninges (Fig. 18.6). Acanthamoeba or Balamuthia trophozoites and cysts may be found in and around the walls of affected blood vessels (Fig. 18.6), and also in areas relatively free of inflammation (Fig. 18.6). The amebae are 15–40 μm in diameter and have a prominent vesicular nucleus with a dense central nucleolus. The cysts are surrounded by a double membrane (Fig. 18.6).

MACROSCOPIC APPEARANCES

The brain is usually swollen with congested leptomeninges. The cerebral cortex may appear dusky pink color due to marked congestion, or slate gray due to the presence of abundant malarial pigment (Fig. 18.8). The white matter often contains petechial hemorrhages.

MICROSCOPIC APPEARANCES

The small vessels are engorged by red blood cells, which may have a ghost-like appearance with poor staining of hemoglobin (Fig. 18.9). Many of these cells, particularly in the gray matter, contain malaria parasites and/or granules of dark malarial pigment, which is related to hematin. Marginated aggregates of red blood cells may appear to be adherent to the vascular endothelium (Fig. 18.10).

Edema, capillary necrosis, and perivascular hemorrhages are usually evident, and there may be parenchymal and meningeal infiltration by lymphocytes and macrophages. Petechial or larger hemorrhages can occur in any part of the brain, but are most common in the white matter and may surround necrotic arterioles and veins (Fig. 18.11). Patients with longer survival may harbor foci of softening and gliosis. Collections of microglia and astrocytes, the so-called Dürck granulomas, are probably related to resorption of ring hemorrhages (Fig. 18.11). The microglia contain iron pigment and lipid.

MACROSCOPIC APPEARANCES

The brain typically contains multifocal necrotic lesions of variable size (Fig. 18.12). There may be associated hemorrhage. Older lesions are cystic due to resorption of necrotic material. The basal ganglia are often involved, but any part of the brain may be affected. Occasionally brain involvement results in an encephalitic process without obvious focal lesions on macroscopic examination.

MICROSCOPIC APPEARANCES

Necrotizing abscesses or foci of coagulative necrosis are surrounded by mononuclear and polymorphonuclear inflammatory cells, newly formed capillaries, reactive astrocytes, and microglia (Fig. 18.13). Infiltrates of lymphocytes and macrophages surround the blood vessels. Scanty fibrous encapsulation may be evident. Other findings include intimal proliferation and thrombosis, fibrinoid necrosis (Fig. 18.13), and perivascular hemorrhage. The pathological findings depend partly on the degree of impairment of immune function: inflammation is less prominent and fibrosis usually absent in patients whose immune function is severely compromised.

Intracellular and extracellular Toxoplasma tachyzoites (also known as endozoites or trophozoites) are usually abundant. They are oval- or crescent-shaped and measure 2–4 μm by 4–8 μm (Fig. 18.14). Those within cells may be clustered together (in vacuoles or larger pseudocysts) or may appear to lie free in the cell cytoplasm. They can be seen reasonably well when stained with hematoxylin and eosin, but are more readily identified and distinguished from other protozoa immunohistochemically (Fig. 18.15). Cysts measuring 20–100 μm in diameter and containing large numbers of bradyzoites (also known as cystozoites) may occur within, or at the periphery of, the necrotic areas (Figs 18.15, 18.16).

Chronic lesions consist of cystic spaces containing macrophages and only very rare tachyzoites. Cerebral toxoplasmosis occasionally causes a diffuse non-necrotizing inflammatory process with scattered microglial nodules and astrocytic gliosis involving both gray and white matter. In HIV patients who have received cART, end-stage (burnt out) lesions are common: foci of cavitation and gliosis without a surrounding tissue reaction. However, in patients who develop IRIS, there may be florid inflammation.

MACROSCOPIC APPEARANCES

Macroscopic abnormalities occur in the more severe cases and include:

MICROSCOPIC APPEARANCES

Active lesions in congenital toxoplasmosis show extensive coagulative necrosis. They are usually associated with lipid-laden macrophages, lymphocytes, and a few neutrophils, which are also present in the leptomeninges (Fig. 18.18). The adjacent brain tissue may contain microglial nodules. Toxoplasma tachyzoites and cysts can be seen in the meningeal exudate, around (rather than within) the necrotic lesions, and are particularly numerous near the ventricular cavities (Fig. 18.18).

The foci of necrosis eventually tend to undergo mineralization (Fig. 18.18, see also Fig. 18.17). Residual Toxoplasma cysts can usually be found (Fig. 18.18). Ependymal granulations and gliosis may lead to aqueduct stenosis and obstructive hydrocephalus.

MACROSCOPIC APPEARANCES

The leptomeninges may be cloudy and the brain swollen and congested. Sometimes the brain is macroscopically normal. Patients who have been treated with melarsoprol may develop acute hemorrhagic leukoencephalopathy (Fig. 18.19) (see Chapter 20).

MICROSCOPIC APPEARANCES

Lymphocytes, macrophages, and plasma cells surround the cerebral blood vessels and infiltrate the subarachnoid space (Fig. 18.20). Some of the plasma cells contain multiple intracytoplasmic globules of immunoglobulin. These ‘morular cells’ (Fig. 18.20) are characteris tic, but not specific. Other features include a reactive gliosis, and clusters of mononuclear inflammatory cells (Fig. 18.20). Typical microglial nodules may be abundant, especially in T. b. rhodesiense encephalitis, and are often associated with lymphophagocytosis. Trypanosomes are rarely demonstrable in the histologic sections.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Acute phase: The brain appears swollen and congested, with scattered petechial hemorrhages. Amastigote (Leishmania-like) forms of the parasites are present within glial cells (Fig. 18.21) or less frequently at the center of microglial nodules, which are scattered within the brain parenchyma (Fig. 18.21).

Chronic phase: The brain usually appears normal. A few glial nodules and aggregates of lymphoid cells may be found, but no parasites.

Reactivated disease takes the form of granulomatous or multifocal necrotizing encephalitis (Figs 18.22, 18.23) with abundant amastigote parasites (Fig. 18.23). The identity of the parasite can be confirmed immunohistochemically.

 Microsporidia are single-celled, obligate intracellular parasites.

 More than 20 genera of microsporidium are pathogenic in mammals, but Encephalitozoon spp. affect immunosuppressed populations more commonly than other species.

 In humans, microsporidium can be transmitted via contaminated water or air droplets and via the fecal–oral route. Sexual transmission of Encephalitozoon spp. may also occur.

 The parasites have an internal coiled tube through which sporoplasm is extruded to pierce and inject infectious sporoplasm into the cytoplasm of the host cell.

 Disseminated infection with CNS involvement has been reported following kidney, pancreas, and bone marrow transplantation.

 CNS involvement has, very rarely, been reported in immunocompetent hosts.

MACROSCOPIC APPEARANCES

External examination of the brain may show mild meningeal opacity. Sectioning of the brain reveals multiple soft nodules in the gray and white matter, some with obvious central necrosis. The lesions can mimic those of cerebral toxoplasmosis.

MICROSCOPIC APPEARANCES

Histology reveals foci of necrosis with surrounding astrocytosis and microglial proliferation. Parasites may be detected within astrocytes, appearing as clusters of hematoxyphilic dots (the nuclei of the microsporidia) within refractive clear cytoplasm, often Gram- and Ziehl–Neelsen-positive. Electron microscopy is helpful to identify the organisms. Diagnosis by PCR on tissue biopsy samples is highly sensitive but not widely available.

During CNS infection, spores are often present in the peripheral blood.

INTRODUCTION

The cestodes (tapeworms) and the trematodes (flukes) are two major groups of Platyhelminthes (flatworms) and may cause serious neurologic disease. A wide variety of nematodes (roundworms) can occasionally also involve the nervous system and produce disease.

Invasion of the central nervous system by parasitic worms is usually the most worrying clinical complication of human helminthiasis. The pathways from the portal of entry to the CNS are manifold and differ from species to species.

A brief classification of the major helminthic infections of the CNS is presented in Table 18.2.

CYSTICERCOSIS

In global terms, cysticercosis is the commonest parasitic infection of the CNS and a leading cause of epilepsy worldwide. It is a major public health concern in the developing world, but the number of cases is also increasing in affluent countries, particularly among immigrants from endemic regions. Although relatively uncommon in most parts of the United States, it is an important infection in California and states bordering Mexico, as well as in other parts of the world, such as Central and South America, India, sub-Saharan Africa, China, and certain European countries.

MACROSCOPIC APPEARANCES

The number of cysts within the CNS varies from one to several hundred (Fig. 18.25). They occur in the parenchyma (especially the gray matter), meninges, or ventricles (Fig. 18.25). The viable intraparenchymal cysticerci are usually 1–2 cm in diameter and contain a single invaginated scolex. After degeneration they become fibrotic and represented by a firm white nodule (Fig. 18.25), which eventually calcifies. The spinal cord is rarely involved.

The meningeal cysts are small and colorless. They adhere to the pia or float freely in the subarachnoid space (Fig. 18.25), particularly in the sylvian fissure. With time, basal cysts tend to shrink, and the meninges become thickened and fibrotic.

Racemose cysticerci are large multiloculated grape-like clusters of cysts that lack an invaginated scolex. They are usually found in the basilar cisterns or within the ventricular system (Fig. 18.25), especially the fourth ventricle.

MICROSCOPIC APPEARANCES

Each scolex has a rostellum with four suckers and a double row of 22–32 hooklets (Fig. 18.26). The cyst wall is sparsely cellular and consists of three histologically distinct layers (Fig. 18.26):

While encysted larvae are viable, the surrounding parenchyma shows minimal reaction. Shortly after the cysticerci die, they are surrounded by neutrophils, lymphocytes, macrophages, foreign body giant cells, and eosinophils (Fig. 18.27), and then enclosed by a zone of granulation tissue, which eventually produces a dense collagenous capsule (Fig. 18.27). The lesion may include necrotic tissue and cholesterol clefts. Old nodules may be entirely fibrotic. Eventually some of the cysts become mineralized (Fig. 18.27).

Ventricular cysticerci usually cause a granular ependymitis. Degeneration of racemose cysticerci in the ventricles or subarachnoid space may provoke a florid granulomatous inflammatory reaction (Fig. 18.27).

HYDATID DISEASE (ECHINOCOCCOSIS)

MACROSCOPIC APPEARANCES

Hydatid cysts in the CNS are usually solitary, spherical, and unilocular. They may grow very large. The commonest location is in the perfusion territory of the middle cerebral artery. Skull and vertebral involvement has been reported. The cysts contain clear colorless fluid and a granular deposit of protoscolices, the so-called hydatid sand.

MICROSCOPIC APPEARANCES

The wall of the cyst (Fig. 18.28) consists of:

The interior of the cyst contains numerous small protoscolices in brood capsules (Fig. 18.28). Apart from mild gliosis and occasional lymphocytic cuffing of blood vessels in the immediate vicinity, there is little other reaction to the cysts.

The pattern of growth of E. multilocularis differs from that of E. granulosus or E. vogeli in that it lacks an encapsulating cyst and grows invasively by external budding of protoscolices.

COENUROSIS

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The cysts are usually unilocular and measure up to 5 cm in diameter. They are found in the ventricles, usually the fourth, or in the subarachnoid space. Unlike hydatid cysts, the walls of a coenurus cyst are thin and milky-white and are not laminated. There is no surrounding fibrous capsule. The cysts contain multiple scolices, which project from the inner surface into the lumen. The head of each scolex carries a rostellum armed with a double row of hooklets. There is reactive gliosis and chronic inflammation with occasional giant cells in the adjacent brain tissue.

SPARGANOSIS

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The ‘sparganum’ comprises a central, usually degenerating, worm and a surrounding collagenous capsule. A dense infiltrate of mononuclear inflammatory cells is present in the surrounding tissue, which also shows edema and reactive gliosis. There may be evidence of larval migration, in the form of tunnel-like cavities containing granulation tissue.

ANGIOSTRONGYLIASIS

TRICHINOSIS

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Reported lesions include:

STRONGYLOIDIASIS

VISCERAL LARVA MIGRANS

MACROSCOPIC AND MICROSCOPIC APPEARANCES

In the brain the larvae produce small necrotic and inflammatory lesions containing macrophages, lymphocytes, neutrophils, and eosinophils. Dead larvae are usually surrounded and partly engulfed by giant cells (Fig. 18.30).

SCHISTOSOMIASIS

MACROSCOPIC APPEARANCES

Miliary granulomas may be seen scattered throughout the brain, but are most numerous in the cerebral and cerebellar cortex and the deep gray matter. Sometimes the lesions are solitary and mimic a tumor. Spinal schistosomiasis can cause marked swelling of the affected cord segments (Fig. 18.32). Granulomas may be studded over the surface of the brain or cord, or agglomerated to form nodules, which protrude from the surface and occasionally invade the dura

MICROSCOPIC APPEARANCES

The histologic reaction to the ova varies from nothing to florid granulomatous inflammation with multinucleated giant cells, marked fibrosis, and adjacent gliosis (Fig. 18.33). Eosinophils are usually present. Some patients develop focal arteritis.