Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

Sarcoidosis is a multisystem disease of unknown cause and with a worldwide distribution. Involvement of the central nervous system occurs in a relatively small number of patients with sarcoidosis. Isolated neurosarcoidosis without signs of systemic disease is a rarity. Because of its non-specific clinical presentation and neuroradiological imaging characteristics, intracranial neurosarcoidosis remains a very difficult diagnosis, particularly in the absence of systemic signs of the disease. Intracranial neurosarcoidosis has a predilection for the basal leptomeninges commonly affecting the cranial nerves, but any part of the brain may be involved, resulting in a wide spectrum of clinical syndromes. Cranial nerve involvement is the most common single symptom. Intracranial sarcoid manifests as nodular or diffuse leptomeningeal thickening and extra- or intra-axial parenchymatous lesions. Intracranial sarcoid may mimic various forms of meningitis, including carcinomatous and intracranial mass lesions such as meningioma, lymphoma and glioma, based on neuroradiological imaging. Magnetic resonance imaging is a very sensitive diagnostic tool for detecting intracranial abnormalities due to neurosarcoidosis. Lumbar puncture is useful in ruling out other neurological disorders, in particular infectious, but cerebrospinal fluid findings are not specific. Angiotensin-converting enzyme in serum and cerebrospinal fluid may be increased, decreased or normal. Therapy consists of immunosuppressive agents and should be initiated with corticosteroids. Other immunosuppressive drugs should be added in severe cases or after frequent recurrences. We review here all aspects of intracranial neurosarcoidosis from the clinical point of view, with special emphasis on presentation, diagnostic procedures, differential diagnostic considerations and treatment.

Neurosarcoidosis: a review of its intracranial manifestation

https://www.amjmed.com/article/0002-9343(92)90579-Z/pdf

Tuberculous meningitis in patients with and without human immunodeficiency virus infection

PURPOSE To evaluate the role of MR in the diagnosis and treatment of patients with neurosarcoidosis. METHODS The MR studies of 24 patients who satisfied stringent criteria for the diagnosis of sarcoid were retrospectively reviewed. All patients had signs and symptoms referable to the head and/or spine. The majority, 17 patients (71% of the total), were examined at least once with gadolinium enhancement. Fifteen of 24 patients (63%) underwent serial examinations during steroid therapy. RESULTS A wide spectrum of findings was noted: white matter and periventricular high signal intensity on long-repetition-time/long-echo-time sequences, mimicking multiple sclerosis (11 patients); leptomeningeal enhancement (11 patients); brain parenchymal mass (seven patients)--six demonstrated enhancement, one did not receive contrast; lacrimal gland mass (three patients); hydrocephalus (three patients); enlarged ventricles, apparently atrophic (one patient); periventricular enhancement (three patients); extraaxial mass, mimicking meningioma (two patients); chiasmal enhancement or swelling (one patient); enhancing nerve roots (two patients); enlarged pituitary stalk (two patients); pontine infarct (one patient); and enhancing parenchymal spinal cord mass (three patients). Partial or complete resolution of the radiographic abnormality occurred in 13 of 15 cases (87%), which paralleled clinical improvement. No response was detected in the remaining two. Abnormal enhancement was the finding that was most responsive to steroid therapy, with response seen in nine of 10 patients with leptomeningeal enhancement, in six of six patients with enhancing brain parenchymal masses, in three of three patients with enhancing cord masses, and in all three patients with periventricular enhancement. CONCLUSIONS 1) MR shows a spectrum of protean central nervous system abnormalities associated with neurosarcoidosis. 2) This high sensitivity for associated abnormalities aids in differentiating central nervous system sarcoid from the many diseases that it can mimic. In particular, enhancement was a useful clue to the diagnosis in 15 of 17 cases in which it was used (88%). 3) MR demonstrates regression of central nervous system abnormalities during steroid therapy, in particular abnormal meningeal, periventricular, and parenchymal enhancement.

http://www.ajnr.org/content/ajnr/15/5/973.full.pdf

MR of sarcoidosis in the head and spine: spectrum of manifestations and radiographic response to steroid therapy.

http://www.unilim.fr/campus-neurochirurgie/IMG/pdf/181105_dural_lesions.pdf

Dural lesions mimicking meningiomas

Twelve recent cases of Mycobacterium tuberculosis meningitis were presented, and the literature was reviewed. There are no particularly new or unique therapies or approaches to the management of this most serious disease. The major obstacle to successful diagnosis and treatment of tuberculous meningitis continues to be a lack of clinical suspicion of its presence. As illustrated in the cases presented, it has been our experience that patients already moribund or nonresponsive do not respond, regardless of the intervention undertaken. The most sensitive and economical method of detecting M. tuberculosis in the CSF may be LPA. However, this has not yet been widely validated or accepted. Larger volumes of CSF should be sent to the laboratory for testing and centifuged to about 5x concentrations before both acid-fast bacilli staining and culture are attempted. If tuberculous meningitis is suspected, three-drug therapy can be started immediately without jeopardizing subsequent culture confirmation of the presence of the TB bacillus. In addition, these patients must be followed closely to detect hydrocephalus at the earliest possible moment. When patients fail to respond to appropriate antituberculosis and pressure-reducing therapy, hydrocephalus should be actively sought by either CT or radioisotope cisternography. Although the decision to proceed to ventricular drainage or shunting must be individually made in adult patients with infection-related hydrocephalus, we agree with others that surgical intervention should be considered early and should be performed if the level of consciousness deteriorates, intracranial pressure increases, or ventricular enlargement or enhancing basal exudates are identified on CT.

Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review.

Five cases of sarcoid presenting as an intracranial tumor are reported. In one instance, the lesion presented as a tumor in the cerebellopontine angle, a site not previously reported for the initial presentation of sarcoid isolated to the central nervous system. The role of computerized tomography, surgery, and steroid therapy is discussed. In the absence of pulmonary involvement, serum angiotensin-converting enzyme levels do not appear to be helpful in predicting steroid response.

Presentation of central nervous system sarcoidosis as intracranial tumors

The third reported case of a malignant nerve sheath tumor of the facial nerve is presented. The clinical course and pathological findings are described and serve as the basis for a discussion concerning malignant nerve sheath tumors arising in the cranial nerves.

F C Dohan

Papers

Mycobacterium tuberculosis meningitis: a report of twelve cases and a literature review.

Presentation of central nervous system sarcoidosis as intracranial tumors

Malignant nerve sheath tumor of the facial nerve: case report and discussion.