Neurotuberculosis (clinical pathological and imaging correlations with scientific basis)

The neurotuberculosis has emerged with new and/or modified clinical entities particularly in BCG vaccinated children. The paper describes these entities based on clinical data, pathology findings, neuroimaging,(CT Scan of brain and/or MRI of brain and spinal cord, DSA), often positive PCR for TB, TB antigen or antibody in a routine normal or mildly abnormal CSF. It also deals with scientific basis to appreciate the newly emerging pictures. Because of partial immunity given by BCG there are large number of localised lesions in different parts of the brain and/or meninges with protean clinical manifestations depending upon the site of the lesions. To mention a few of them are Serous Tuberculous Meningitis (S.TBM), TB Encephalopathy (TBE) isolated or combination of several manifestations like development of multiple intracranial tuberculoma during or without treatment, manifestations due to development of infarctions in the territory of large intracranial arteries and/or small arteries with lacunar infarcts with resultant large number of syndromes. Some of the examples are due to involvement of Internal Capsule, Basal Ganglia, Thalami, Hypothalami, Cerebellum, Brainstem, Cranial nerves, Locked-in Syndrome, MRI findings of Leigh's Disease, Moyamoya, Frontal lobe signs, POST TBM Demyelination of the brain and/or long tracts of spinal cord, Steroid dependent and steroid withdrawal syndromes, Behaviour disorder by antineuronal antibody with neuronal damage. and recently Neuro-TB manifestations with HIV infection. This paper will describe several brain damaging mechanism. Tuberculo-protein is responsible for initiating pathological damage (Burn and Finlay 1932, Udani 1958, Dastur and Udani 1965 -1966) but progressive or recurrent autoimmune disease is due to T-cells entering into CNS which are specific to Epitopes Myelin Basic Protein (MBP) and Myelin Oligodendrocyte Protein (MOGP) which cause focal or generalised demyelination as proved in Experimental Allergic Encephalitis (EAE). However,damage is caused by Nitric Oxide (NO) and Oxygen radicals which are cytotoxic to MBP and MOGP,'NO' is a neuromodulator but in excess is neurotoxic and also damages the brain microvasculature causing oedema, myelin loss, ischemic infarction and haemorrhages and/or recurrent autoimmune disease. Excess 'NO' is mainly produced by activated macrophages through T-cells induced cytokines (Kilbane and Sharf 1992). However the role of amoeboid microglia in endothelial cell damage produced by antibodies to addressins and/or by perforins, cytotoxic lymphotoxins to MOGP which directly kills oligedendrocytes. However the humoral mechanisms probably also plays an important role in the damage to myelin. Human and experimental studies as in Gullain Barre' syndrome (Gheramann et al 1993, Dawson et al 1992 Leishmann and Hicky 1993). The whole concept of Neuro-TB with newly emerging clinical pictures with normal CSF but positive PCR for TB and/or TB Antigen by Elisa has to be changed as supported by recent neuroimmunological studies.