Central Nervous System Tuberculosis Research Articles

Neuroimaging Changes and Treatment Outcome of Tubercular Meningitis- Experiences 22 Cases in a Tertiary Care Center

Background: Tuberculous meningitis (TBM) is caused by Mycobacterium tuberculosis (M. tuberculosis) and is the most common form of central nervous system (CNS) tuberculosis (TB).The prevalence of TB meningitis remains largely underestimated because clinical manifestations are nonspecific in early stages of the disease. Prompt diagnosis is critical for initiating appropriate therapy, facilitating measures to prevent dissemination of this highly contagious disease and to combat fatal complication in children Aims: To evaluate the role of neuroimaging changes and treatment outcome of tubercular meningitis. Methods: This prospective hospital-based cohort study was conducted in Department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during January 2022 to December 2022. Children age belonged to 1 month to 10 year diagnosed as TBM during study period were enrolled in this study. Detailed history, clinical examination, CSF analysis and other relevant investigations were done. Data were recorded in standard questionnaire. Statistical analyses of the results were obtained by using window-based computer software devised with Statistical Packages for Social Sciences (SPSS-22). Results: Total 22 diagnosed case of TBM was enrolled and evaluated. Among them two third (63.63%) children were in 5-10 year age group. Male (59%) were outnumbered than female (36.36 %).Male female ratio was 1.6:1. More than half (59%) of patients came from urban area. All of the patients were vaccinated. Cent percent (100%) patients were presented with fever followed by headache (77.27%), sign of meningeal irritation (54.54%), vomiting (54.54%) and seizures (50%). Most common complication was hemiparesis (45.45%) followed by cranial nerve palsy (40.90%), visual problem (9.09%) and hydrocephalus (4.54%). Abnormal neuroimaging changes were found in 100% cases. Common findings were hydrocephalus (40.90%), tubercloma (36.36%), basilar enhancement (18.18%), Benign enlargement of subdural space & cerebellar hyperintensity (9%) and thalamic infract was present in 4.54% cases. Anti TB and steroid treatment were given in 100% cases and among them18.18% cases were required shunt procedure. More than one-third cases (40.90%) were completely normal without any no sequelae. Among abnormal sequelae found in two third (59%) cases. Speech impairment (36.36%) was most common followed by GDD (18.18%), hemiparesis (13.63%), quadriparesis (9.09%) and epilepsy in 9.09% cases. Conclusion: In our study all children of TBM were presented with fever followed by other predominant clinical features headache, vomiting, seizures and   sign of meningeal irritation.  Abnormal neuroimaging changes were found in all cases. Common findings were  basilar enhancement, hydrocephalus, tubercloma, benign enlargement of subdural space & cerebellar hyper intensity and thalamic infract. After treatment more than one-third cases were completely normal without any no sequelae. J Bangladesh Coll Phys Surg 2024; 42: 214-218

Concomitant bedaquiline and delamanid therapy in patients with drug-resistant extra-pulmonary tuberculosis in Mumbai, India

BackgroundWorld Health Organization suggests concurrent bedaquiline-delamanid (BDQ-DLM) as part of individualised regimens for eligible patients with pulmonary drug-resistant tuberculosis (DR-TB); however, data for patients with drug-resistant extrapulmonary tuberculosis (EPTB) is extremely limited. This study documents the treatment outcomes and adverse events associated with concurrent BDQ-DLM-based regimens in patients with drug-resistant EPTB at a Médecins Sans Frontières clinic in Mumbai, India. MethodsRetrospective cohort study based on routinely collected programmatic data. Individualised regimens were based on drug-susceptibility testing and previous drug exposure. Drug-resistant EPTB patients initiated on regimens containing concurrent BDQ and DLM from April 2016 to October 2019 were included.Patients who completed treatment were followed up at 12 months. ResultsOf 17 patients, median age was 23 years (IQR = 21–30 years) and 12/17 (71 %) were female. Pre-extensively drug-resistant tuberculosis and extensively drug-resistant TB was reported in 13/17 (76.4 %) and 2/17 (11.7 %) patients respectively. Microbiological reports were unavailable for two patients with central nervous system TB. Lymph node TB was the commonest form of EPTB in 9/17 (53 %) of patients. Median duration of treatment was 18.9 months. At least one grade three or four severe adverse event (SAE) was reported by 13/17 (76.4 %) patients. Thirteen (76.4 %) patients had favourable outcomes. None of the patients relapsed or died in the one-year period of post-treatment follow-up. ConclusionConcurrent BDQ-DLM-based regimens in drug-resistant EPTB were effective and associated with manageable adverse events.

Tongue tremor: A rare manifestation of disseminated central nervous system tuberculosis

Tongue tremor: A rare manifestation of disseminated central nervous system tuberculosis

Posterior fossa tuberculosis: Unusual presentations of a common disease and literature review

The burden of tuberculosis is very high in our country and though the number of deaths due to tuberculosis has drastically reduced, still the associated morbidities caused by the disease can be very debilitating.1 Central nervous system tuberculosis is a rare and serious presentation of tuberculosis, the general presentation being hydrocephalus, meningitis, and disseminated miliary lesions.2 More often than not tuberculosis is associated with immunocompromised status and central nervous system tuberculosis in immunocompetent young individuals with no evidence of systemic tuberculosis is very rare.3Association of tuberculosis with ocular manifestations and even blindness is not uncommon, the causes of blindness being causes like uveitis, retinitis, interstitial keratitis, ophthalmitis, and even orbital tuberculosis.4 Classical teaching in neurosurgery is that a posterior fossa lesion unless proven otherwise is a metastasis. Therefore, here we are discussing three cases of central nervous system tuberculosis in isolation, without any systemic involvement in immunocompetent adults in the posterior fossa region as well as a literature review of cases from across the globe of posterior fossa tuberculosis in immunocompetent adults. The first case is regarding a treatable cause like tuberculoma in an immunocompetent young adult causing blindness which is rare as well as unfortunate. The other two cases highlight the need to keep tuberculosis as a differential even when the clinical features, radiological features, and blood and other investigations are not suggestive.

Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients

BackgroundEarly and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR).MethodsThis study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization.Results53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0–63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 − 84.1%), 76.0% (95%CI: 56.6 − 88.5%), 77.8% (59.2 − 89.4%) and 85.2% (95%CI: 67.5 − 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay.ConclusionsNTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.

Clinical manifestations and prognosis of tuberculous spondylitis in an adolescent with disseminated tuberculosis: a case report

Indonesia is one of the countries with the highest number of tuberculosis (TB) cases globally. Around 10-20% of adolescents with TB infection progress to pulmonary TB, and less than 0.5% develop miliary or central nervous system TB. TB spondylitis occurs in only 5.6% of extrapulmonary TB patients. The clinical manifestations of disseminated and TB spondylitis are heterogeneous and insidious, with several potential risk- and prognostic factors. We report the case of a 16-year-old male admitted with abdominal distension, paraplegia, and urinary retention. He was diagnosed with disseminated TB with TB spondylitis. This case was unique because the patient had no classic symptoms of pulmonary TB. This report focuses on the diagnosis, comprehensive management, and prognosis of TB spondylitis, as well as the risk factors for disseminated TB. The management consisted of antituberculous agents and surgery. The prognosis is influenced by the patient’s age, severity of kyphosis deformity, number of vertebrae involved, lesion site, and patient’s health status, including nutritional status.

Neuroimaging of tuberculosis- modalities, imaging protocols and radiomics: a review

Background and Objective:
 A large number of review and research articles exists in literature which describe the radiological appearance of various manifestations of nervous system tuberculosis, however there is paucity of text which describes the application of each and every imaging modality in the workup of the entire spectrum of this pathology. The intent of this article is to review the existing literature on the role of different radiological modalities in the stepwise work up of CNS TB. The article focuses on the role of plain radiograph, fluoroscopy, computed tomography, magnetic resonance imaging along with its advanced sequences and nuclear medicine in imaging of the many faces of tuberculosis in CNS. The article also aims to review the existing literature on the role of MR based textural analysis (Radiomics) as a problem-solving tool in various nervous system pathologies.
 Methods:
 We searched PubMed central databases for articles published in English from January 1 2000 to February 28 2021 along with references from the relevant articles. The search terms included “imaging in central nervous system tuberculosis” “Radiomics in tuberculosis “, “Radomics in central nervous system ”. In total 95 articles including case reports, case series, original articles and review articles were included in this review.
 Results:
 Conventional imaging modalities including radiograph and fluoroscopy are becoming extinct in work up of tuberculosis in the nervous system itself, however a plain radiograph still holds a key position in screening the chest for presence of subclinical respiratory tract infection in patients presenting with brain tuberculosis. In addition, it is a sensitive tool as baseline investigation in workup of spinal tuberculosis (T.B). Fluoroscopy is a useful tool in image guided procedures for collection of samples for histopathology and CSF analysis.
 Cross sectional imaging modalities including computed tomography and magnetic resonance imaging have revolutionized imaging of central nervous system pathologies in particular tuberculosis. Computed tomography acts as a screening tool to identify the presence of intracranial tuberculosis and recognize its complications. In addition it is an important tool to determine the extent of spinal T.B. Magnetic Resonance Imaging (MRI) along with its advanced sequences including spectroscopy, Magnetization transfer T1 sequence (MT T1), perfusion imaging, and magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) is an ideal imaging method to work up CNS TB. It can identify numerous manifestations of tuberculosis in the brain, work up its associated complication, and explain the extent of neurological symptoms. Moreover, it has the capability to differentiate TB from other nervous system infections. Furthermore, it can differentiate neoplastic and inflammatory brain disorders from CNS TB. Radiomics, particularly the textural features based on MR imaging is the future of neuroimaging. Its role is getting established in the work up of several intracranial pathologies including brain tumors and neurodegenerative disorders. Certainly, it has significant potential in the imaging work up of CNS tuberculosis, which is underexplored and therefore requires the central attention of upcoming researchers focusing on this topic.
  Conclusion:
 Cross sectional imaging is the mainstay of imaging workup. Nuclear imaging is becoming an essential adjuvant to determine the burden of the disease. Role of radiomics is evolving in intracranial pathologies and certainly needs the central attention of future researches to establish its role in CNS TB imaging.

Clinical presentation, management, and outcome of suspected central nervous system infections in Indonesia: a prospective cohort study

BackgroundLittle is known about the etiology, clinical presentation, management, and outcome of central nervous system (CNS) infections in Indonesia, a country with a high burden of infectious diseases and a rising prevalence of HIV.MethodsWe included adult patients with suspected CNS infections at two referral hospitals in a prospective cohort between April 2019 and December 2021. Clinical, laboratory, and radiological assessments were standardized. We recorded initial and final diagnoses, treatments, and outcomes during 6 months of follow-up.ResultsOf 1051 patients screened, 793 were diagnosed with a CNS infection. Patients (median age 33 years, 62% male, 38% HIV-infected) presented a median of 14 days (IQR 7–30) after symptom onset, often with altered consciousness (63%), motor deficits (73%), and seizures (21%). Among HIV-uninfected patients, CNS tuberculosis (TB) was most common (60%), while viral (8%) and bacterial (4%) disease were uncommon. Among HIV-infected patients, cerebral toxoplasmosis (41%) was most common, followed by CNS TB (19%), neurosyphilis (15%), and cryptococcal meningitis (10%). A microbiologically confirmed diagnosis was achieved in 25% of cases, and initial diagnoses were revised in 46% of cases. In-hospital mortality was 30%, and at six months, 45% of patients had died, and 12% suffered from severe disability. Six-month mortality was associated with older age, HIV, and severe clinical, radiological and CSF markers at presentation.ConclusionCNS infections in Indonesia are characterized by late presentation, severe disease, frequent HIV coinfection, low microbiological confirmation and high mortality. These findings highlight the need for earlier disease recognition, faster and more accurate diagnosis, and optimized treatment, coupled with wider efforts to improve the uptake of HIV services.

Tubercular Meningitis Mimicking Acute Disseminated Encephalomyelitis (ADEM)- A Case Report

Tuberculosis remains endemic in India, and its manifestation in the central nervous system (CNS) poses significant challenges in diagnosis and management. We present a rare case of a 65-year-old male with tubercular meningitis exhibiting atypical features of acute disseminated encephalomyelitis (ADEM). The patient presented with a month-long history of fever, severe headache, altered sensorium, and neurological signs including brisk reflexes, neck rigidity, and bilateral motor weakness. Initial investigations revealed elevated inflammatory markers and abnormal cerebrospinal fluid (CSF) findings consistent with tubercular meningitis. Despite negative CSF culture and nucleic acid amplification tests (NAATs) for Mycobacterium tuberculosis, the patient displayed characteristic asymmetrical bilateral cerebral lesions on MRI suggestive of ADEM. Given the diagnostic ambiguity and a high suspicion of CNS tuberculosis with concurrent ADEM, the patient was treated with anti-tubercular therapy (ATT) and a course of intravenous methylprednisolone followed by oral prednisolone. Subsequent clinical improvement prompted gradual tapering of prednisolone, leading to a full recovery at discharge. This case highlights the complexity of diagnosing CNS tuberculosis coexisting with ADEM, emphasizing the importance of a comprehensive clinical assessment and tailored therapeutic interventions in managing such intricate neurological presentations.

Revisiting the tubercular zone: A poor prognostic finding on neuroimaging

Central nervous system tuberculosis accounts for approximately 1–2% of cases but with a high morbidity and mortality burden. A 37-year-old female presented with fever and headache for 15 days followed by altered sensorium with associated dystonic posturing of both upper limbs and lower limbs (left>right side). The patient’s condition deteriorated despite optimal antitubercular treatment and other supportive measures for two weeks. An MRI brain was suggestive of areas of diffusion restriction in the right caudate nucleus, anterior limb of internal capsule, genu, and anteromedial thalamus. The patient ultimately succumbed to death. Tubercular zone infarctions carry an ominous prognosis and can be considered an indicator of morbidity and mortality in patients with tuberculous meningitis (TBM).

Surgery for Central Nervous System Tuberculosis in Children.

Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Central nervous system tuberculosis is widely prevalent in the world, especially in the developing countries and continues to be a socioeconomic problem. It is highly devastating form of tuberculosis leading to unacceptable levels of morbidity and mortality despite appropriate antitubercular therapy. The clinical symptoms are varied and nonspecific. They can be easily overlooked. Tuberculous meningitis is the most common presentation and its sequelae viz. vasculitis, infarction and hydrocephalus can be devastating. The ensuing cognitive, intellectual, and endocrinological outcome can be a significant source of morbidity and mortality, especially in resource constrained countries. Early diagnosis and treatment of tuberculous meningitis and institution of treatment is helpful in limiting the course of disease process. The diagnosis of CNS tuberculosis remains a formidable diagnostic challenge. The microbiological methods alone cannot be relied upon. CSF diversion procedures need to be performed at the appropriate time in order to achieve good outcomes. Tuberculous pachymeningitis and arachnoiditis are morbid sequelae of tuberculous meningitis. Tuberculomas present as mass lesions in the craniospinal axis. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Tuberculosis of the spinal cord is seen similar to intracranial tuberculosis in pathogenesis but with its own unique clinical manifestations and management. Multidrug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted. The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized. Heightened clinical suspicion is paramount to ensure prompt investigation. Early diagnosis and treatment are essential to a gratifying outcome and prevent complications.

Contact screening of children exposed to active pulmonary tuberculosis: A hospital-based study in Navi Mumbai, India

Abstract Background: Contact investigation is a proactive method employed for active case-finding to improve the detection of active tuberculosis (TB) cases, constituting a crucial component of National TB Programs. Household contacts face a higher exposure risk than individuals in the general population. Although integrated into national policy, the execution of contact investigations is not regularly undertaken, and the outcomes of these investigations are inadequately characterized. Objective: To evaluate risk factors and determine the occurrence of TB disease among household contacts of individuals diagnosed with sputum smear-positive TB in Kamothe, Navi Mumbai, India. Materials and Methods: From December 2018 to November 2020, active screening was carried out for 120 household contact children aged up to 18 years, linked to 52 index cases receiving care at MGM Medical College and Hospital in Navi Mumbai, India. Results: Out of the 120 screened children, 10 (8.3%) showed symptoms, whereas 110 (91.6%) were asymptomatic. Among those exhibiting symptoms, 5 (50%) had abnormal chest X-ray findings. The diagnosis of TB was established in eight cases, including five with pulmonary TB, two with lymph node TB, and one with central nervous system TB. All confirmed TB-positive cases underwent antitubercular treatment, with children under 5 years receiving Isoniazid Preventive Therapy. Conclusion: The study resulted in a 6.67% incidence rate, offering an opportunity to initiate chemoprophylaxis among children. This research identified risk factors associated with the development of TB disease, encompassing female gender, underweight status, residing in crowded conditions, prolonged contact, and extended duration of exposure.

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review.

Neurotuberculosis is defined as a tuberculous infection of the meninges, brain parenchyma, vessels, cranial and spinal nerves, spinal cord, skull, and spine that can occur either in a localized or in a diffuse form. It is a heterogeneous disease characterized by many imaging appearances and it has been defined as "the great mimicker" due to similarities with many other conditions. The diagnosis of central nervous system (CNS)tuberculosis (TB) is based on clinical presentation, neuroimaging findings, laboratory and microbiological findings, and comprehensive evaluation of the response to anti-TB drug treatment. However, the absence of specific symptoms, the wide spectrum of neurological manifestations, the myriad of imaging findings, possible inconclusive laboratory results, and the paradoxical reaction to treatment make the diagnosis often challenging and difficult, potentially delaying adequate treatment with possible devastating short-term and long-term neurologic sequelae. Familiarity with the imaging characteristics helps in accurate diagnosis and may prevent or limit significantly morbidity and mortality. The goal of this review is to provide a comprehensive up-to-date overview of the conventional and advanced imaging features of CNS TB for radiologists, neuroradiologists, and pediatric radiologists. We discuss the most typical neurotuberculosis imaging findings and their differential diagnosis in children and adults with the goal to provide a global overview of this entity.

Effect of continuation of intensive phase on poor responders of antituberculosis treatment on morbidity and mortality in central nervous system tuberculosis (CNS-TB)

Effect of continuation of intensive phase on poor responders of antituberculosis treatment on morbidity and mortality in central nervous system tuberculosis (CNS-TB)

Central nervous system tuberculosis causing motor tractopathy-a case report

Central nervous system tuberculosis causing motor tractopathy-a case report

Central nervous system tuberculosis. Magnetic resonance imaging as the first line diagnostic tool

Central nervous system tuberculosis. Magnetic resonance imaging as the first line diagnostic tool

Central nervous system tuberculosis in patients with systemic rheumatic disease that were receiving immunosuppresive therapy

Central nervous system tuberculosis in patients with systemic rheumatic disease that were receiving immunosuppresive therapy

Longterm magnetic resonance imaging surveillance in central nervous system tuberculosis patients with anti-tuberculosis treatment success

Longterm magnetic resonance imaging surveillance in central nervous system tuberculosis patients with anti-tuberculosis treatment success

Differences in brain volume and thickness in patients with pulmonary or spine tuberculosis (TB) compared to non-TB individuals: A cross-sectional retrospective study

IntroductionThere is evidence showing that central nervous system TB (CNS-TB) causes meningitis, pachymeningitis, tuberculomas, and granulomas. However, the impact of pulmonary or spine TB on brain morphology and thickness is yet to be documented. TB is associated with increased levels of inflammatory biomarkers in specific brain regions. ObjectivesThe primary aim of this study was to compare cortical-brain volume and thickness between patients with pulmonary or spine TB and non-TB individuals and investigate the association between inflammatory biomarkers and brain volume or thickness among patients with pulmonary or spine TB. MethodsParticipants ranging in age from 18 to 65 years (23 TB patients and 50 healthy controls), who were scanned using 1.5-T MRI at Jazan Hospital, were compared in terms of brain volumes and thicknesses. Brain volume and thickness were measured using FreeSurfer. ResultsThere were significant differences in the volumes of the bilateral and total amygdala and accumbens areas, right hippocampus and cerebellum, and CSF, and in the thickness of the right pericalcarine area between patients with pulmonary or spine TB and healthy controls. We also found significant associations between inflammatory biomarkers (CRP, WBC, and platelets) and brain volume but not thickness in patients with TB, p < .05. ConclusionsThis study is the first to show that pulmonary or spine TB reduces brain size and thickness and suggests that TB may be better understood by considering the correlation between inflammatory biomarkers and brain volumes.