MACROSCOPIC APPEARANCES

Tuberculous meningitis is characterized by a gelatinous subarachnoid exudate. This may appear slightly nodular and is usually thickest in the sylvian fissures, over the base of the brain (Fig. 16.1a), and around the spinal cord. Sectioning of the brain usually reveals a similar exudate within the choroid plexus and lining the ventricles. Tubercles may be visible in the meninges, usually adjacent to sulcal veins, and in the ventricular lining (Fig. 16.1b). Small superficial tuberculomas are quite common (Fig. 16.2) and may be associated with an overlying meningeal exudate. Large tuberculomas occasionally occur, but are rare in patients with meningitis.

The ventricles are often moderately dilated, owing to the development of obstructive or communicating hydrocephalus. There may be infarcts.

MICROSCOPIC APPEARANCES

The meningeal and ventricular exudate contains lymphocytes, macrophages, and sparse plasma cells, admixed with necrotic material and fibrin (Fig. 16.3a). There may be accumulations of epithelioid cells and fibroblasts, multinucleated giant cells, and well-defined tuberculous granulomas (Figs 16.2, 16.3, 16.4) with central caseous necrosis.

Mycobacteria may be readily demonstrable or very sparse. Silver impregnation reveals a loss of reticulin in the caseous material (see Fig. 16.9 b). In immunosuppressed patients the mycobacteria are usually numerous and the inflammation less granulomatous and usually lacking multinucleated giant cells (Fig. 16.5). Parenchymal arteritis and infarcts have been reported as frequent findings in patients with AIDS.

The inflammation extends into the subpial and periventricular brain tissue, which shows reactive astrocytosis (Fig. 16.3a) and microglial proliferation. This may be associated with degeneration of white matter adjacent to the ventricles and in the spinal cord.

The inflammatory cells tend to infiltrate through the adventitia, into the media and even the intima, of blood vessels within the exudate (Figs 16.3b, 16.6). Thrombosis occurs in some blood vessels. In others, the inflammation provokes a subintimal intimal fibroblastic reaction that narrows and can occlude the lumen (Figs 16.3b, 16.7). Infarcts are therefore common (Fig. 16.8), particularly in the superficial cortex and, due to the involvement of perforating branches of the middle cerebral artery, in the basal ganglia.

MACROSCOPIC APPEARANCES

Tuberculomas appear as solitary encapsulated yellow or gray masses or multinodular aggregates of smaller masses. They are most often cerebral or cerebellar, but can occur anywhere within the neuraxis. The central tissue, though necrotic, has a firm consistency when cut.

MICROSCOPIC APPEARANCES

Histology reveals solitary or confluent tuberculous granulomas with central caseous necrosis surrounded by lymphocytes, epithelioid cells, Langhans’-type multinucleated giant cells, and an outer zone of collagen, fibroblasts, lymphocytes, and macrophages (Fig. 16.9). Older lesions may calcify. The adjacent parenchyma is usually markedly gliotic.

MACROSCOPIC APPEARANCES

There is usually extensive destruction, which may be associated with collapse of the affected vertebral bodies and intervertebral discs. This is associated with variable protrusion of gray multinodular granulomatous tissue into the epidural space (Fig. 16.10).

MICROSCOPIC APPEARANCES

The epidural mass shows typical granulomatous tuberculous inflammation with caseation. Changes in the spinal cord reflect a combination of focal compression by epidural inflammatory tissue or vertebral kyphosis, ischemia (see Chapter 9), and secondary long tract degeneration. Compression of the anterior spinal artery may produce a typical ‘watershed’ infarct (see Chapter 9) involving the upper and middle parts of the thoracic cord.

 Asymptomatic CNS involvement, associated with CSF pleocytosis and increased immunoglobulin concentration, and positive CSF syphilis serology.

 Syphilitic meningitis.

 Meningovascular syphilis.

 Parenchymatous neurosyphilis (general paresis and tabes dorsalis).

 Gummatous neurosyphilis.

MACROSCOPIC APPEARANCES

There is thickening and fibrosis of the leptomeninges, which rarely contain miliary gummas. Sectioning of the brain may reveal infarcts due to syphilitic arteritis, and hydrocephalus.

MICROSCOPIC APPEARANCES

The meninges contain scattered lymphocytes and plasma cells. The gummas, if present, resemble tubercles, but the central (gummatous) necrosis differs histologically because the reticulin is preserved. The arteritis can involve large, medium-sized, or small arteries and arterioles. It is characterized histologically by lymphocytic and plasma cell infiltration of the adventitia and media, and concentric collagenous thickening of the intima, which eventually occludes the lumen (Fig. 16.12). A chronic inflammatory infiltrate may also surround and infiltrate leptomeningeal veins, and cranial nerves. The brain and spinal parenchyma often includes foci of ischemic scarring or frank infarction, and the periventricular white matter may show perivascular inflammation and gliosis (Fig. 16.12).

MACROSCOPIC AND MICROSCOPIC APEARANCE

The meninges are thickened and fibrotic and the underlying brain is firm and atrophic. Histology reveals scanty meningeal and perivascular parenchymal aggregates of lymphocytes and plasma cells, moderate loss of neurons from the cerebral cortex, reactive gliosis, and striking proliferation of rod-shaped microglia (Fig. 16.13). Spirochetes are demonstrable in the cortex by silver impregnation in a minority of cases.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

By the time that patients come to necropsy, the degree of inflammation is often quite mild, with scattered lymphocytes and plasma cells in the fibrotic spinal leptomeninges and dorsal root ganglia (Fig. 16.14). There is moderate to marked loss of neurons from the dorsal root ganglia, with associated proliferation of satellite cells (forming nodules of Nageotte), depletion of dorsal root fibers (this may appear histologically unimpressive), and posterior column degeneration (Figs 16.15, 16.16). The changes are usually most marked in the lumbar region of the cord.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Because Lyme disease is not usually fatal, data from necropsy studies are very limited. The spirochetes are demonstrable on biopsy of the leading edge of the maculopapular skin rash, and also in the brain and other tissues by silver impregnation (using the Warthin–Starry or modified Dieterle method), immunohistochemistry, or PCR.

Perivascular inflammation and, in chronic disease, axonal degeneration, have been noted in peripheral nerve biopsies (Fig. 16.18).

The documented CNS abnormalities are quite varied: chronic meningitis, lymphoplasmacytic parenchymal brain infiltrates, microglial nodules, astrocytosis, and neuronal loss with spongiform change have all been described in case reports. Magnetic resonance imaging (MRI) may show lesions in the white matter resembling foci of demyelination. The pathologic counterpart of these imaging abnormalities has not been established.

MACROSCOPIC APPEARANCES

The distribution of lesions is variable. There is often yellowish-gray thickening of the leptomeninges over the base of the brain, particularly around the infundibular stalk and optic chiasm (Fig. 16.19). The meninges covering the brain stem, cerebellum and, less commonly, the cerebral convexities, may also show macroscopic involvement, as may those around the spinal cord and nerve roots. In some cases, sectioning of the brain reveals gelatinous gray material in the walls of the ventricles and in the choroid plexus. This may be associated with obstructive hydrocephalus.

MICROSCOPIC APPEARANCES

Histology reveals granulomatous inflammation in the meninges, ventricles, and adjacent brain or cord parenchyma (Fig. 16.20). Although the granulomas are classically noncaseating, they may show central fibrosis and, rarely, necrosis. The floor of the hypothalamus and the infundibulum are often extensively involved. There may be large granulomatous masses in the choroid plexus. The inflammatory infiltrate can involve the optic nerves and chiasm, the facial, auditory, vestibular, and other cranial nerves, and the spinal nerve roots. Small veins and arteries may be incorporated within the granulomas. Rarely, this leads to fibrinoid necrosis and even thrombosis.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The affected dura is thickened and may have a slightly nodular appearance. Microscopy reveals collagenous thickening and patchy infiltrations by a polymorphic infiltrate of lymphocytes, plasma cells, macrophages and occasional multinucleated giant cells (Fig. 16.21). Eosinophils may also be present. Granulomas and necrosis have been reported in a few cases. The diagnosis depends on excluding, as far as possible, tuberculosis, syphilis and fungal infections, lymphoma or other neoplasms, Wegener’s arteritis, rheumatoid arthritis and other systemic connective tissue/autoimmune disorders.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Foci of granular yellow or gray discoloration may be macroscopically discernible in the thalamus, hypothalamus, cerebellar dentate nuclei, and around the aqueduct. Microscopy reveals meningeal and parenchymal clusters of macrophages containing PAS-positive, diastase-resistant material (Fig. 16.22). The bacilli are Gram-positive, but this may be difficult to demonstrate because of degenerative changes. They can be demonstrated reasonably well by methenamine silver impregnation. There is usually a scanty lymphocytic infiltrate. Thickening and fibrosis of the walls of arteries and arterioles in affected parts of the brain may lead to the development of small infarcts.

Electron microscopy reveals rod-shaped intracellular bacilli (Fig. 16.22), many of which may be degenerating, as well as accumulations of membranous material.