MACROSCOPIC APPEARANCES

The brain is swollen and congested. Hemorrhagic infarcts are common and may be extensive (Fig. 15.1), and a purulent exudate is seen over the cerebral hemispheres or the base of the brain or both (Fig. 15.2). The ventricles may appear compressed by the swollen cerebral hemispheres, or distended if the aqueduct has been obstructed by purulent material. There may be coexistent cerebral abscesses, particularly in association with Citrobacter diversus or Proteus mirabilis meningitis.

MICROSCOPIC APPEARANCES

The meningeal exudate contains large numbers of neutrophils, scattered macrophages, fibrin, and necrotic cellular debris. The exudate may be particularly prominent over the base of the brain. It extends along perivascular spaces into the brain parenchyma. Bacteria are usually demonstrable within the exudate.

Inflammatory cells tend to infiltrate the walls of leptomeningeal and cortical arteries and veins (Fig. 15.3). Intimal accumulations of inflammatory cells may be a prominent feature. Venous thrombosis and infarction are often evident (Figs 15.1, 15.3) and may be extensive.

Purulent material is usually seen in the choroid plexus and may also adhere to ventricular walls. An acute, predominantly perivascular, inflammatory infiltrate is present in the adjacent tissue.

COMPLICATIONS

Complications of acute meningitis are:

MACROSCOPIC APPEARANCES

The brain is swollen and the leptomeninges are congested. A purulent exudate is seen in the subarachnoid space over the cerebral hemispheres and the base of the brain (Fig. 15.5a), and accumulating in the basal cisterns and cerebral sulci. The exudate associated with pneumococcal infections is often particularly prominent over the cerebral convexities (Fig. 15.5b). There may be little or no macroscopically discernible exudate in patients dying very acutely or those who have been partially treated with antibiotics. Sectioning of the brain may reveal edematous white matter and compressed ventricles or ventricular enlargement due to obstructive hydrocephalus. There is usually purulent fluid within the ventricles. The ventricular exudate may be pronounced in patients with ventricular shunt infection (Fig. 15.6), in whom the leptomeninges appear remarkably clear. Occasionally, the coagulopathy associated with meningococcal septicemia is complicated by ventricular hemorrhage. Small infarcts may result from thrombosis of penetrating arteries (Fig. 15.7). Venous thrombosis and hemorrhagic infarcts are less common than in neonatal meningitis.

Subdural effusions are an occasional complication of meningitis in children and appear as accumulations of clear fluid over the cerebral convexities or in the interhemispheric fissure.

MICROSCOPIC APPEARANCES

During the first few days, the subarachnoid (Fig. 15.8) and ventricular (Fig. 15.9) exudate contains large numbers of neutrophils and necrotic debris. Intracellular and extracellular bacteria can usually be demonstrated. The exudate extends along perivascular spaces into the cerebral cortex (Fig. 15.10), cerebellum, brain stem, and spinal cord. There is usually purulent material in the choroid plexus (Fig. 15.11). Perivascular inflammation and fibrinoid necrosis of blood vessels may be seen in the periventricular white matter (Figs 15.9, 15.12). With time, the numbers of lymphocytes and macrophages increase, and by the end of the first week these predominate. There is usually some proliferation of fibroblasts.

Inflammatory cells tend to infiltrate the walls of leptomeningeal and cortical arteries and veins and may accumulate in the intima (Fig. 15.13). Thrombosis of small meningeal and cortical blood vessels (Fig. 15.14) with associated focal infarction is relatively common in cases coming to necropsy (Figs 15.5b, 15.7, 15.14). Meningitis due to B. anthracis is often hemorrhagic (Fig. 15.15).

COMPLICATIONS

As noted above, these include:

MACROSCOPIC APPEARANCES

As would be expected, abscesses caused by direct spread of local infection tend to be located in the frontal (Fig. 15.18) or temporal lobes or the anterior parietal region, adjacent to the source of infection. Less commonly, otogenic infection may be complicated by a cerebellar abscess. Abscesses caused by hematogenous spread of infection tend to occur at junctions between gray and white matter and are often multiple (Fig. 15.19). They may be situated in any part of the brain, although the perfusion territory of the middle cerebral arteries is usually involved. Listeria monocytogenes has a predilection for the brain stem and tends to cause a purulent rhombencephalitis (Fig. 15.20), with or without an associated meningitis.

The earliest stage of focal cerebritis appears macroscopically as an ill-defined region of hyperemia with surrounding white matter edema. It takes about 1–3 weeks for an abscess with a visible capsule and purulent center to become macroscopically discernible. Over weeks and months, the abscess enlarges by expanding into the white matter. The capsule gradually thickens, although this occurs to a greater extent in the subcortical region than in the deep white matter, where the capsule tends to remain relatively thin. Abscesses caused by hematogenous spread of infection tend to be less well encapsulated than those caused by local spread. Abscesses occasionally rupture into the ventricular system, causing a purulent ventriculitis, or into the leptomeninges (Fig. 15.21).

MICROSCOPIC APPEARANCES

The evolution of a cerebral abscess can be subdivided into the following four stages:

Focal suppurative encephalitis lasts 1–2 days and is characterized by swelling of endothelial cells, and perivascular and parenchymal infiltration by neutrophils (Figs 15.22, 15.23). Small foci of necrosis develop rapidly. Only occasional mononuclear inflammatory cells are present at this stage.

Focal suppurative encephalitis with confluent central necrosis is characterized by adjacent foci of necrosis, which soon enlarge and become confluent (Fig. 15.24). By day 3 or 4, foamy macrophages are much more numerous and the infiltrate includes lymphocytes and some plasma cells. Bacterial brain abscesses associated with septicemia in immunocompromised patients may show extensive necrosis with little or no encapsulation (Fig. 15.25). Multiple, poorly encapsulated cerebral microabscesses are a frequent feature of septicemia due to Staph. aureus, particularly in the immunosuppressed, elderly or debilitated.

Early encapsulation is seen by days 5–7: an early granulation tissue response is evident around the margin of the necrotic tissue, with newly formed capillaries and scattered fibroblasts (Fig. 15.26). Over the next few days, the fibroblasts proliferate and deposit reticulin (Fig. 15.27). The surrounding brain tissue is edematous and contains swollen reactive astrocytes. Parenchymal blood vessels have plump endothelial cells and tend to be surrounded by small aggregates of lymphocytes.

Late encapsulation is seen from about day 14 when most abscesses have a clearly defined structure consisting of:

Progressive collagen deposition over subsequent weeks thickens the capsule. The thickness varies at different points, tending to be greater on the cortical than on the ventricular aspect (Fig. 15.29). Occasionally, the infection in a chronic abscess resolves in the absence of treatment, leaving a dense fibrous capsule lined by sparse macrophages and amorphous material.

MACROSCOPIC AND MICROSCOPIC FEATURES

In most cases, an empyema is situated above the tentorium (Fig. 15.30), occasionally adjacent to the falx cerebri. Empyema occurs less commonly in the posterior fossa or, rarely, in the spinal canal (Fig. 15.30). Subdural empyema consists of pus surrounded by granulation tissue and a mixed inflammatory infiltrate.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

A spinal epidural abscess usually extends over several vertebral levels (Fig. 15.31). Intracranial epidural abscesses tend to be biconvex in shape, sharply delimited by the skull and the displaced dura.

Histology reveals extradural purulent material (Fig. 15.32) surrounded by inflamed granulation tissue. Osteomyelitis involving the vertebrae adjacent to a spinal epidural abscess may also be evident.