Chronic bacterial infections and neurosarcoidosis
TUBERCULOSIS
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.
16.1 Tuberculous meningitis.(a) Thick pale yellow exudate over base of brain, particularly around the optic chiasm. (b) Nodular thickening of the lining of the lateral ventricles.
The ventricles are often moderately dilated, owing to the development of obstructive or communicating hydrocephalus. There may be infarcts.
TUBERCULOUS MENINGITIS
The human tubercle bacillus, Mycobacterium tuberculosis, is usually responsible. M. bovis only rarely causes meningitis.
Vaccination of immunosuppressed patients with the attenuated bacille Calmette–Guérin (BCG) strain occasionally produces disseminated disease, including meningitis. Immunosuppressed patients are also susceptible to infection by atypical mycobacteria, including M. avium-intracellulare, but the pattern of CNS infection in these patients is usually parenchymal rather than meningeal.
Tuberculous meningitis may complicate the initial hematogenous dissemination of a primary droplet-acquired pulmonary infection. In some cases, this complication of primary infection occurs in the context of miliary disease.
In developing countries, particularly Asia and Africa, the primary infection usually occurs in infancy or childhood.
Exposure to M. tuberculosis is much less common in developed countries, as a result of which primary infection, although infrequent, occurs at any age.
In some urban communities in developed countries, the incidence of primary tuberculosis is increasing, owing to the rising prevalence of active pulmonary tuberculosis among people with AIDS and indigent inner city inhabitants.
The growth of mycobacteria after the initial hematogenous dissemination is usually arrested by the development of cell-mediated immunity. However, dormant but viable bacilli may persist within small tubercles in the lungs (as part of the primary complex) or in other tissues. A ‘Rich’s focus’ is a persisting primary tubercle within the CNS.
Depression of cell-mediated immunity may allow reactivation of infection in primary tubercles. Rupture of a reactivated Rich’s focus into the subarachnoid space or ventricles results in tuberculous meningitis. Tuberculous meningitis may also complicate hematogenous dissemination from reactivated infection elsewhere in the body.
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.
16.3 Histology of tuberculous meningitis.(a) There is a meningeal exudate of macrophages, lymphocytes, plasma cells, and fibrin. The superficial cortex (at left) is densely gliotic. (b) Meningeal artery surrounded by lymphocytes, macrophages, and an occasional multinucleated giant cell. There is mild endarteritis, with proliferation of subintimal fibroblasts.
16.4 Part of a caseating meningeal granuloma in tuberculous meningitis.There is a characteristic infiltrate of lymphocytes, epithelioid macrophages, and Langhans’-type multinucleated giant cells.
TUBERCULOUS MENINGITIS
Initially presents over 2–3 weeks with a combination of headache, lethargy, nausea, and vomiting.
Subsequently causes a variety of neurologic signs including cranial nerve palsies, other focal neurologic deficits, epilepsy, and increasing obtundation.
May cause signs of raised intracranial pressure.
Is more commonly associated with a documented history of tuberculosis exposure or infection in children than in adults.
Examination of the cerebrospinal fluid (CSF) usually reveals lymphocytosis, a reduced concentration of glucose, and an increase in protein. M. tuberculosis can be detected in the CSF by use of polymerase chain reaction (PCR)-based techniques.
16.5 Tuberculous meningitis in an immunosuppressed patient.(a) Inflammation in the leptomeninges of a patient with AIDS. Note the absence of a typical granulomatous tissue reaction. (b) Numerous acid-fast bacilli in AIDS-associated tuberculous meningitis.
DIFFERENTIAL DIAGNOSIS OF TUBERCULOUS MENINGITIS
This includes several infectious and non-infectious disorders.
The principal infectious differential diagnoses are coccidioidomycosis (Chapter 17), particularly in the southwestern United States and Central and South America, and histoplasmosis (Chapter 17). In these, as in tuberculous meningitis, accurate diagnosis depends on identifying the relevant organisms by staining or culture of CSF or brain tissue.
Granulomatous fungal infections that are less likely to be mistaken for tuberculous meningitis include cryptococcosis, paracoccidioidomycosis and sporotrichosis (Chapter 17).
Non-infective causes of granulomatous meningeal inflammation include neurosarcoidosis, isolated (granulomatous) angiitis, idiopathic hypertrophic pachymeningitis and Wegener’s disease.
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.
16.6 Mild tuberculous endarteritis.Extension of granulomatous inflammation through the adventitia and media of a meningeal artery.
16.7 Tuberculous endarteritis.Narrowing of the lumen of an inflamed meningeal artery by accumulation of chronic inflammatory cells and proliferation of intimal connective tissue.
16.8 Acute infarction of superficial brain parenchyma in tuberculous meningitis.Several arteries in the overlying leptomeninges are occluded or severely stenosed by intimal fibroplasias (arrows). The zone of acute infarction is delineated by arrowheads.
Tuberculomas result from the growth of tubercles, which enlarge within the CNS parenchyma or remain encapsulated within the meninges, rather than rupturing into the CSF to cause meningitis (see above), except at a late stage in some cases.
Patients present with a subacute onset of focal neurologic signs and symptoms, often with evidence of raised intracranial pressure. Most have evidence of systemic tuberculosis. Tuberculomas usually respond to antibiotic therapy, although this can, very occasionally, cause central liquefaction and the formation of a tuberculous abscess. Rarely, central liquefaction occurs spontaneously.
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.
SPINAL EPIDURAL TUBERCULOSIS
This is caused by extension of tuberculous vertebral osteomyelitis into the epidural space. There is usually a history of backache and general malaise over a period of weeks or months. Compromise of the spinal cord (‘Pott’s paraplegia’) is caused by focal compression, which is often exacerbated by local vertebral collapse and kyphosis and, in some cases, spinal infarction. The thoracic cord is most often involved.
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.
SYPHILIS
The different types of CNS involvement in syphilis have been classified as:
Asymptomatic CNS involvement, associated with CSF pleocytosis and increased immunoglobulin concentration, and positive CSF syphilis serology.
Parenchymatous neurosyphilis (general paresis and tabes dorsalis).
SYPHILISSyphilis is caused by the spirochete Treponema pallidum and is usually acquired by mucous membrane or cutaneous inoculation during venereal contact. The disease is subdivided into three stages (Fig. 16.11):
16.11 Stages of syphilis.
Primary syphilis, due to proliferation of the spirochetes at the site of inoculation. This stage is characterized by the development of a chancre, which heals spontaneously after 2–6 weeks.
Secondary syphilis, due to subsequent hematogenous dissemination of spirochetes. This occurs after approximately 6 weeks in untreated patients and manifests with generalized lymphadenopathy, a maculopapular rash, condyloma lata, and mucous patches, and lasts for weeks or months after which the ‘infection’ enters a latent phase. Patients may develop latent syphilis without developing the signs and symptoms of secondary syphilis.
Months or years after the mucocutaneous lesions of secondary syphilis have resolved, approximately 30–50% of untreated patients with latent syphilis develop tertiary syphilis. There are cardiovascular (most common), ocular, neuroparenchymal, and gummatous forms, which are all associated with a chronic inflammatory process that causes progressive irreversible tissue damage.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
