Case reports of chronic myeloid leukemia and tuberculosis: Is imatinib the link between the two?

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

Correlation between CNS Tuberculosis and the COVID-19 Pandemic: The Neurological and Therapeutic Insights.

The recent outbreak of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) from Wuhan, China, was caused by a single-stranded RNA virus which has kept the entire world stranded. The outbreak was first diagnosed with respiratory illness, but recent findings of acute necrotizing hemorrhage of brain, brain encephalopathy, and the presence of the virus in the cerebrospinal fluid (CSF) have unveiled its neuroinvasivness. Various clinical features related to the central nervous system (CNS) and peripheral nervous system (PNS) due to COVID-19 infection are now identified. We demonstrate here an apparent similarity in neurological disorders of COVID-19 with CNS tuberculosis, which suggests that some anti-tubercular drugs may be used as therapeutic agents against COVID-19 infection.

Intramedullary tuberculoma of the Spinal Cord, Clinical features & imaging: Possibility of early diagnosis with imaging?

Involvement of vertebral column is common in tuberculosis(TB) but intramedullary tuberculomas are rare. Spinal intramedullary tuberculoma are extremely rare, seen in only 2 of 100,000 cases of TB and 2 of 1000 cases of CNS TB. Intramedullary tuberculomas normally respond well to conventional antituberculous medications, requiring surgery only occasionally. MRI is optimal diagnostic modality in intramedullary tuberculoma as it can show specific findings. This report describes a case of Intramedullary Tuberculoma of the Spinal Cord with clinical features and specific MRI findings with review of litreture.

Extrapulmonary Tuberculosis: Pathophysiology and Imaging Findings.

Extrapulmonary tuberculosis (TB) represents approximately 15% of all TB infections. It is difficult to diagnose on the basis of imaging characteristics and clinical symptoms, and biopsy is required in many cases. Radiologists must be aware of the imaging findings of extrapulmonary TB to identify the condition in high-risk patients, even in the absence of active pulmonary infection. In extrapulmonary TB, the lymphatic system is most frequently affected. The presence of necrotic lymph nodes and other organ-specific imaging features increases the diagnostic probability of extrapulmonary TB. Disseminated infection and central nervous system involvement are the most frequent manifestations in immunosuppressed patients. Renal disease can occur in immunocompetent patients with very long latency periods between the primary pulmonary infection and genitourinary involvement. In several cases, gastrointestinal, solid-organ, and peritoneal TB show nonspecific imaging findings. Tuberculous spondylitis is the most frequent musculoskeletal manifestation. It is usually diagnosed late and affects multiple vertebral segments with extensive paraspinal abscess. Articular disease is the second most frequent musculoskeletal manifestation, and synovitis is its predominant imaging finding.©RSNA, 2019.

Clinical study of spinal tuberculosis presenting with neuro-deficits in Western India.

BACKGROUND/OBJECTIVES: Spinal tuberculosis (TB) is a destructive extra-pulmonary disease manifestation of Mycobacterium tuberculosis infection. It is responsible for many cases of paraparesis and quadriparesis in developing countries where patients seek treatment late. The aim of this study was to understand and analyze the clinical and radiological profile of patients with spinal TB and correlate it with the anatomical site affected by it. METHODS: A retrospective, observational study of 100 cases of spinal TB admitted over a period of three years. Data on demography, clinical signs and symptoms and investigations were analyzed. RESULTS: Incidence of spinal TB was found to be the highest in the third and fourth decade of life (45%). Incidence among males was 64% and females was 36%. Low socioeconomic class (72%) and past history of pulmonary TB (34%) were found to be risk factors for spinal TB. Average duration between onset of symptoms and time of presentation to the hospital was 154±15.5 days. Patients with bone involvement presented later than those without bone involvement. Paraplegia (91%) and backache (62%) were the most common clinical presentation. Thoracic spine involvement (36%) and vertebral wedging and destruction (58%) were the commonest X-ray findings. 69% patients had compressive lesion with vertebral body destruction being the commonest cause of compression. CONCLUSIONS: Spinal TB with neurological deficits affected the thoracic spine. Compressive spinal cord lesions were the common form of presentation of spinal TB. Paraplegia with backache and neurological bladder-bowel involvement were the most prevalent neuro-deficits. Magnetic resonance imaging of the spine proved to be the most useful investigation to differentiate and localize the site of tubercular lesions.

Central Nervous System Tuberculosis: An Imaging Perspective.

The increasing prevalence of tuberculosis in both immunocompetent and immunocompromised individuals in recent years makes the disease a topic of universal concern. It has insidious onset and can affect virtually any organ system in the body, including the central nervous system (CNS). CNS tuberculosis (TB) is becoming more and more complex and atypical with onset of multidrug-resistant TB. Routine diagnostic techniques using serology and body tissue are time consuming and may delay the definitive management. Hence, it is important to be familiar with various radiologic features of CNS TB to ensure early and accurate diagnosis, thereby reducing high morbidity and mortality associated with the disease. The newer imaging techniques further help to improve the characterization and diagnosis of atypical CNS TB. The authors review the imaging characteristics of different forms of CNS tuberculosis involving the brain and spine and discuss the role of advanced imaging modalities in differentiating CNS TB from other disease process.

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis.

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF(-/-)) mice and compared outcomes of disease against TNF(f/f) control and global TNF(-/-) mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF(-/-) mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF(-/-) mice were resistant to infection and presented with a phenotype similar to that in TNF(f/f) control mice. Impaired immunity in TNF(-/-) mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB.

Disseminated cerebral and spinal tuberculomas: rare cause of triparesis.

Tuberculosis continues to remain a significant public health problem in developing nations, causing substantial morbidity and mortality. Central nervous system (CNS) tuberculosis is frequently observed in endemic zones of tuberculosis including India. The emergence of infections like HIV and malnutrition ruined the public health measures to restrain tuberculosis in developing countries. The incidence of intraspinal tuberculomas is reported to be 0.2-5% among CNS tuberculomas. To date, only a few cases have been reported of mixed intraspinal and intracranial tuberculomas. The clinical outcome in CNS disseminated tuberculomas is not well described in the literature. With this view, we report a case of a 25-year-old woman who presented with neck pain, triparesis and bladder incontinence, which finally proved to be a case of multiple cerebral and spinal tuberculomas. The antitubercular treatment with steroids and other supportive measures resulted in good recovery.

Central nervous system tuberculosis: pathophysiology and imaging findings.

With the onset of the human immunodeficiency virus pandemic, the incidence of tuberculosis, including central nervous system (CNS) tuberculosis, has increased in developed countries. It is no longer a disease confined to underdeveloped and developing countries. The imaging appearance has become more complex with the onset of multidrug-resistant tuberculosis. Imaging plays an important role in the early diagnosis of CNS tuberculosis and may prevent unnecessary morbidity and mortality. This article presents an extensive review of typical and atypical imaging appearances of intracranial tuberculosis, and discusses pathogenesis, patterns of involvement, and advances in imaging of intracranial tuberculosis.

Central nervous system tuberculosis: a forgotten diagnosis.

INTRODUCTION: Early diagnosis and treatment of central nervous system (CNS) tuberculosis (TB) are very important because of its high morbidity and mortality characteristics. However, the clinical symptoms, laboratory and neuroimaging findings of CNS TB are nonspecific, no matter whether they are the common form, tuberculous meningitis (TBM), or the rare form, intracranial tuberculomas. We report a case of TBM with miliary pattern of intracranial tuberculomas, although the initial diagnosis was masked by an atypical neuropsychiatric presentation, cerebrospinal fluid (CSF) finding, and other medical comorbidity. CASE REPORT: A 51-year-old man was brought to the emergency room due to a traffic accident. The initial impression was Wernicke encephalopathy due to his alcohol use history and the clinical triad. After admission, fever and mental confusion lead to the suspicion of CNS infection. Although the initial CSF analysis was inconclusive, the miliary pattern of intracranial tuberculomas was highly suspected by brain magnetic resonance imaging finding. The diagnosis of TBM and miliary TB was finally confirmed by positive CSF and sputum culture of Mycobacterium tuberculosis. The patient had a good response to standard antituberculous therapy, although paradoxical expansion of cerebral tuberculomas occurred during treatment. CONCLUSIONS: TB is still a major public health problem in the world, and there is a rising tendency of extrapulmonary TB incidences in the developed countries. Because of the high mortality and treatable characteristics of CNS TB, physicians should be familiar with it and keep the diagnosis in mind.

Central nervous system tuberculoma.

The aim of this study was to outline the clinicoradiological features of central nervous system (CNS) tuberculoma, and highlight the importance of early treatment. We conducted a retrospective analysis between 1999 and 2008. Clinicoradiological, pathological and follow-up data of 23 patients were reviewed and analysed. The mean age at presentation was 30.3 years (range=17-43 years), and the average disease duration at presentation was six months (range=1-19 months). The tuberculoma location in the cohort was: thoracic region (10 patients); cervical region (six), cervicothoracic region (three); thoracolumbar region (one); and intracranial (six); three patients (13%) had multiple lesions. Nineteen (82.6%) and 15 (65.2%) patients had sensory-motor and bowel/bladder involvement, respectively. Two patients presented with headache and consciousness disturbance, and two patients had a history of pulmonary Koch's disease. Five patients had a history of tuberculous meningoencephalitis, and one patient had a history of enlarged cervical lymph nodes. Twenty-one patients underwent surgery, and two received conservative treatment; all patients received anti-tuberculosis therapy for 18 months. Seventeen of the 21 surgical patients and both conservatively managed patients achieved improved neurological function (with Karnofsky Performance Scale scores of 90-100). Patients presenting at an advanced disease stage had a poorer outcome. CNS tuberculoma is a benign condition with a good prognosis and effective therapy options. Enhanced brain and spine MRI should be performed to ensure the diagnosis is not missed. Early surgical decompression is recommended for intramedullary tuberculoma. Craniotomy is indicated for patients with intracranial hypertension, while more conservative therapy is appropriate for patients who have intracranial tuberculomas without intracranial hypertension.

Pathology of tropical diseases.

Tropical diseases affecting the central nervous system include infections, infestations, and nutritional deficiency disorders. This article discusses the commonly encountered diseases. The infections include bacterial, mycobacterial, fungal, parasitic, and viral infections with varied clinical manifestations. Imaging sensitivity and specificity for the prediction of the cause of infections has improved with application of advanced techniques. Microbial demonstration and histology remain the gold standard for diagnosis. Understanding the basis of imaging changes is mandatory for better evaluation of images. Nutritional disorders present with generalized and nonspecific imaging manifestations. The pathology of commonly encountered vitamin deficiencies is also discussed.

Central nervous system tuberculosis.

Central nervous system (CNS) tuberculosis is frequently encountered in tropical countries. Imaging plays an important role in its recognition and in its differentiation from other similar conditions. Specific magnetic resonance techniques, such as magnetization transfer imaging, proton magnetic resonance spectroscopy, diffusion, and perfusion imaging are useful in its characterization and management. This article reviews the various forms of CNS tuberculosis, including its complications and imaging features.

Treatment of central nervous system tuberculosis infections and neurological complications of tuberculosis treatment.

Tuberculosis (TB) with central nervous system (CNS) manifestation is a form of TB with a high mortality and morbidity. Tuberculous meningitis (TM) is the most common form of CNS-TB. Although diagnosis of CNS-TB can be challenging, early treatment of CNS-TB is related to a better outcome. If CNS-TB is suspected, even though the clinical picture is not specific, it should be immediately treated. For the treatment of CNS-TB, knowledge of the penetration across the blood-brain barrier of the various antituberculosis agents used in TB treatment is important. These will be described here in order to serve as a guide in choosing a treatment for CNS-TB. Corticosteroids have an evidence-based value in the treatment of TM and so are recommended. As for thalidomide use in CNS-TB, sound evidence is still lacking. We will also include a description of the adverse neurotoxic effects of the various other agents including their psychiatric, ototoxic and ophthalmic adverse effects.

Neurologic manifestations of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome: a case series.

BACKGROUND: Paradoxical neurologic tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a potentially life-threatening condition that occurs within 3 months after starting combination antiretroviral therapy (ART). The reports in the published literature are anecdotal, and the prevalence and outcomes of neurologic TB-IRIS are unknown. METHODS: We prospectively assessed patients with suspected TB-IRIS from June 2005 through October 2007 at our hospital in Cape Town, South Africa. We defined paradoxical TB-IRIS and paradoxical neurologic TB-IRIS with use of consensus clinical case definitions. We collected data on tuberculosis diagnosis, ART, details of TB-IRIS diagnosis, other opportunistic infections, corticosteroid use, and outcome. RESULTS: We reviewed 279 patients with suspected TB-IRIS, 54 (19%) of whom had suspected neurologic TB-IRIS, and 225 (81%) of whom had suspected non-neurologic TB-IRIS. Paradoxical TB-IRIS was diagnosed in 190 patients; 23 (12%) of these 190 patients had neurologic TB-IRIS (95% confidence interval, 7%-17%). Eight had meningitis, 7 had tuberculoma, 5 had both tuberculoma and meningitis, and 3 had radiculomyelopathy. Twenty (87%) of the 23 patients with neurologic TB-IRIS required hospital admission (median duration, 12 days; interquartile range, 6-24 days), and 21 (91%) received corticosteroids (median duration, 58 days; interquartile range, 29-86 days). Outcomes 6 months after the initial assessment for neurologic deterioration were as follows: 16 (70%) of the patients were alive (10 of these patients had documented full physical and mental recovery), 3 (13%) were dead, and 4 (17%) were lost to follow-up. CONCLUSIONS: Paradoxical neurologic TB-IRIS accounts for 12% of paradoxical TB-IRIS cases. Neurologic TB-IRIS causes considerable short-term morbidity but has reasonable long-term outcomes. Further research is needed to devise optimal diagnostic and management strategies for patients with tuberculosis who experience neurologic deterioration after starting ART.