The phenomenon of PR is frequently observed in TB patients co-infected with HIV after the commencement of Highly Active Antiretroviral Therapy (HAART) where patients experience temporary exacerbation or worsening of symptoms, signs, and/or radiographic manifestations of TB disease.[6
] But such phenomenon is also described in TB patients without HIV infection after the starting of ATD in 2–23%;[7
] however, the frequency of PR is much lower in these groups compared with patients receiving HAART.[8
] It manifests clinically as worsening of fever, cough, chest infiltrates, or increased lymphadenopathy or symptomatic tuberculoma. A tuberculoma results when intracranial tubercles enlarge without rupturing into the subarachnoid space. Development of symptomatic intracranial tuberculomas while on therapy was first described in 1974 by Thrush and Barwick.[9
] When tuberculomas occur as PR, original sites of infections could be pulmonary, meningeal, or miliary.[10
] The latent period between start of chemotherapy and development of intracranial tuberculoma is between 10 days and 5 months,[10
] but it may be delayed up to 18 months.[11
] Most adult patients present with seizures, while constitutional symptoms are less. Focal weakness and papilledema are most frequent signs. Sizes of the tuberculomas vary from a few millimeters to 4 cm. They are found in cerebral hemisphere, basal ganglia, brain stem, cerebellum, and spinal cord. They are usually infratentorial in children and supratentorial in adults. Solitary lesions are more frequent than multiple lesions. The CT and MRI have revolutionized the diagnosis of intracranial tuberculomas. The characteristic CT and MRI findings are nodular enhancing lesions with a central hypointensity. The enhancement may be homogenous, patchy, serpentine, or ring enhancing. Perilesional edema is often marked. Similar CT findings are also seen in glioma, metastasis, abscess, neurocysticercosis, and fungal granuloma. Angiographically tuberculoma appears as an avascular mass, sometimes with a faint tumor blush. Demonstration of caseating granuloma or AFB in stereotactic biopsy of the lesion is gold standard for the diagnosis.
Adjunctive corticosteroid treatment improves the symptoms and seizure control and reduces tuberculoma size and perilesional edema radiographically. Thalidomide has been used successfully in a few patients to reduce the size of tuberculomas.[12
] Similarly, infliximab, a tumor necrosis factor-α blocker, was used to control severe paradoxical reaction of brain and lymph nodes.[13
] Surgical therapy for intracranial tuberculoma is usually considered only when medical therapy fails, when decompression is necessary, or when the diagnosis is uncertain. The outcome of most patients is favorable, but few cases may end with residual disability, even death.[14
] The cause of the PR in immunocompetent person is not yet known, but is supposed to be having immunological basis. The pathogenesis has been attributable to several factors like persistence of lipid-rich insoluble cell wall antigen infected tissue, exposure and release of new antigen targets during mycobacterial killing, hypersensitivity to tuberculoprotein, and exaggerated immune restoration (following TB-induced immunosuppression) occurring on TB treatment.[7
In the present study, there were five patients, all immunocompetent and compliant with their antituberculous therapy. One patient was suffering from miliary TB, one patient from miliary TB with destructive vertebral lesions, two patients from TB meningitis, and one patient from pulmonary TB. They all developed PR mainly in the central nervous system after commencement of ATD. The latent period between commencement of ATD and development of PR was between 1 and 4 months. PR may involve the initial site of the disease manifestation, but sometimes may appear in distant site which may lead to diagnostic confusion. It is important to recognize these clinically frustrating but benign PR, which usually does not require change in therapy. We should be aware of these events and at the same time consider other causes of inadequate response such as wrong diagnosis, inadequate drug regimen, multi-drug resistant TB, atypical mycobacterial disease, complication of drug therapy, or progression of the disease itself before attributing their signs and symptoms to PR.[16
] So, a high index of suspicion is needed for the diagnosis of PR. In fact, an initial improvement followed by deterioration despite firm diagnosis and adequate therapy are strong evidence to suspect PR on clinical grounds. These reactions can be effectively managed with continuation of ATD. Systemic corticosteroid is probably indicated for most of the neurological PR to manage symptoms and cerebral edema.[17
] This is well evident from the present study, as all our patients improved with the above treatment.