Central Nervous System Tuberculosis Research Articles

Intracranial manifestations of central nervous system tuberculosis in children.

Tuberculosis remains a significant global health challenge, with central nervous system tuberculosis (CNS-TB) posing a substantial threat, accounting for 1-10% of all tuberculosis cases. This article explores the diverse manifestations of CNS-TB in children, with a particular focus on tuberculous meningitis and tuberculomas, as well as their associated complications. Diagnostic imaging, including CT and MRI, plays a crucial role in the early detection of CNS-TB. The article emphasizes the pivotal role of imaging in the diagnosis and management of these manifestations, underscoring the importance of early recognition by healthcare professionals. Ultimately, raising awareness among pediatric radiologists, pediatricians, and pediatric neurologists is crucial for prompt intervention and improved outcomes in cases of CNS-TB.

Modulating sonic hedgehog (SHH) pathway to create a rapid CNS-TB model: Facilitating drug discovery

Tuberculous meningitis, a severe complication of Mycobacterium tuberculosis (M. tb) infection, involves the dissemination of bacilli in the brain. This study explored the role of the sonic hedgehog (SHH) signaling pathway in regulating blood-brain barrier (BBB) integrity, M. tb invasion into the central nervous system (CNS), and disease progression of Central Nervous System Tuberculosis (CNS-TB) in a Balb/c mouse model. The modulation of the SHH pathway using agonist Purmorphamine (PUR) and antagonist Cyclopamine (CYC) revealed that CYC treatment led to a rapid and extensive invasion of M. tb in the brain, with bacterial loads increasing by 99 % compared to the untreated-infected group. In contrast, PUR reduced M. tb loads by 50 % and delayed disease progression. Histopathological analysis showed that CYC exacerbated inflammation and immune cell infiltration, while PUR mitigated these responses. Immunohistochemistry demonstrated that CYC caused severe BBB breakdown and reactive gliosis, while PUR partially attenuated this response. Further analysis revealed that CYC upregulated Matrix Metalloproteinase-9 (MMP-9) secretion, a key contributor to BBB disruption. These findings highlight the critical role of the SHH pathway in maintaining BBB integrity and regulating the immunopathological response during CNS-TB, opening up future scope for drug discovery. This Cyclopamine-induced model of rapid M. tb invasion and chronic inflammation provides a new tool for studying CNS-TB pathogenesis and evaluating potential therapeutic interventions targeting the SHH signaling axis. Significance statementUnderstanding how tuberculosis (TB) infection can spread to the brain is crucial, as this “central nervous system TB” (CNS-TB) is a serious and potentially life-threatening health complication. However, studying CNS-TB in humans is very difficult. Animal models are needed to better understand how TB gets into the brain and the resulting damage. This study in mice showed that blocking a signaling pathway called Sonic Hedgehog (SHH) allowed TB to rapidly spread to the brain, damaging the blood-brain barrier and causing severe inflammation. In contrast, activating the SHH pathway helped protect the brain from TB invasion. These findings provide important insights that could lead to new ways to prevent or treat this dangerous form of TB.

A Rare Case of Pyogenic and Tuberculous Co-Infection

CNS co-infections by pyogenic and tuberculosis are uncommon infectious processes, with few cases reported to date. These superadded bacterial infections during CNS tuberculosis present usually atypical clinical manifestations. Bacterial meningitis is a rare but severe complication of patients with spondylodiscitis. CNS tuberculosis has a broad spectrum of disease patterns and a high risk of complications and mortality. Although bacterial infection of the central nervous system (CNS) is a lifethreatening neurological emergency only few papers reported. Here We report a case of 48 year old diabetic male who was diagnosed with Neurotuberculosis with bacterial meningitis and cervical spondylodiscitis and treated with both Antibiotics and Anti-Tuberculous drugs and patient improved symptomatically. Keywords: Bacterial meningitis, TB Meningitis, Cervical Spondylodiscitis, Anti-Tuberculous drugs.

Imaging panorama of pediatric central nervous system tuberculosis.

Central nervous system tuberculosis (CNS TB) is the most dreaded manifestation of systemic tuberculosis in the pediatric age group. It is associated with high morbidity and mortality due to severe neurological complications and sequelae. Knowledge about the imaging spectrum of CNS TB will help in early presumptive diagnosis and prompt treatment, reducing the development of complications. Imaging also plays a vital role in monitoring the progression of disease after the initiation of antituberculosis therapy. Advanced magnetic resonance imaging (MRI) techniques have recently improved the diagnostic efficacy manifold.In this review, we describe the imaging characteristics, the role of advanced imaging techniques, and follow-up imaging in various types of CNS TB in the pediatric population.

An Unusual Case of CNS Tuberculoma in a 19-Year-Old Man

Background: Tuberculosis (TB) is ranked as one of the top 10 causes of death. Mycobacterium tuberculosis (M. TB) infection, the causative organism for TB affects approximately a quarter of the global population placing a burden on the healthcare system. Central nervous system tuberculosis (CNS TB) is seen in 5 to 10% of extrapulmonary TB cases and has the highest mortality. CNS tuberculoma is one of its manifestation. Clinical presentation of CNS tuberculoma depends on its location within the CNS and commonly include headache, seizures, and focal neurological deficits, due to the presence of a space occupying lesion, although patients can be asymptomatic. We report the case of a 19yr old man who had an unusual presentation of CNS tuberculoma, highlighting its clinical presentation, diagnosis and treatment. Case Presentation: Index patient is a 19-year-old male college student who resides in a city. He presented with 15 days history of fever, headache, vomiting, vertigo, ataxia, and inability to concentrate. He received antimalarial, anti typhoid and body booster medications but had no improvement and had a history of weight loss despite no dietary change. He had never been diagnosed with TB and had all his childhood vaccinations given. Plain Magnetic Resonance Imaging (MRI) brain scan done revealed a posterior fossa mass lesion with perilesional edema. Futher, a contrast MRI brain scan showed multiple ring-enhancing conglomerates of lesion around the tentorium on the posterior fossa with intense contrast enhancement. The largest of this mass measured 4.5 cm x 2.5 cm x 2.5 cm in the right superior cerebellum compressing the 4th ventricle and with effacement of the cerebellopontine angle. Lastly, an MRI spectrometry revealed elevated lipid lactate peak. His chest x-ray was unremarkable. Other blood parameters were essentially within range with the exception of Erythrocyte ESR and mantoux test. He received antitubercular drug (Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Levoflox and Streptomycin) for 18th months with complete remission. Conclusion: CNS tuberculomas are tuberculous masses that can be located anywhere from the brain to spinal cord. Advanced diagnostic modalities may guide clinicians towards making it's diagnosis. Treatment maybe medical (use of antitubercular drugs) or surgical excision with medical therapy being first choice. While the index patient had no obvious risk factors for his disease, his BCG vaccination pose a possible source of his exposure to TB infection. More research is needed on this however.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p=.014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p=.040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p=.001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p=.643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.

Thalidomide as an adjunctive therapy in complex childhood neuro-tuberculosis: a case report

BackgroundTuberculosis remains a global health challenge, with central nervous system tuberculosis (CNSTB) affecting 5–10% of extrapulmonary tuberculosis cases, leading to severe complications in children aged 2 to 4 years. Despite timely diagnosis and intervention, management of CNSTB is a challenge. Thalidomide, a TNF-α inhibitor, is a potential therapeutic option in cases resistant to adjuvant corticosteroid therapy. This case report describes the management of complicated CNSTB utilising thalidomide, a less commonly used drug, with a favourable outcome.Clinical presentationA 3-year-old boy diagnosed with CNSTB and having a ventriculoperitoneal shunt presented with left-sided hemiparesis. He was previously diagnosed with tubercular meningitis at 2.5 years of age. On anti-tubercular treatment and corticosteroid, he had a complicated course with drug-induced liver injury (DILI) and paradoxical reaction. Despite a year of anti-tubercular therapy, there was a deterioration in neurological symptoms, accompanied by an increase in the number of tuberculomas observed on MRI. Adjuvant treatment with thalidomide proved effective in suppressing immunological activation, leading to a reduction in tuberculomas.ConclusionThis case highlights the intricacies of CNSTB, including complications and refractory tuberculomas. Thalidomide was effective in managing these challenges, offering a potential therapeutic option in challenging CNSTB cases. Positive clinical and radiological responses underscore the need to further explore thalidomide as an adjunctive therapy in similar paediatric cases.

The Role of Diffusion Tensor Imaging in CNS Tuberculosis.

Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging(DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.

Outcomes of central nervous system tuberculosis in Saudi Arabia: a multi-center study

ABSTRACT Objectives Central nervous system tuberculosis (TB) (CNS-TB) can occur in several forms, including intracranial tuberculoma, tuberculous brain abscess, TB meningitis (TBM), and spinal TB. Early treatment can save lives and prevent severe neurological complications. This study aimed to describe the characteristics and post-treatment outcomes of patients with CNS-TB and identify factors associated with poor outcomes. To the best of our knowledge, this is the largest CNS-TB study till date published in Saudi Arabia. Methods This retrospective cohort study included all patients diagnosed with CNS-TB in three tertiary centers in Saudi Arabia (King Abdulaziz Medical City in Jeddah, King Abdulaziz Medical City in Riyadh, and Al-Noor Specialist Hospital in Makkah) between 2009 and 2019. Data of patients’ demographics, co-morbidities, presenting symptoms, type of CNS-TB, medical and surgical treatments, and outcome after completion of treatment were obtained from medical records. Treatment outcomes were categorized using the modified Rankin Scale for neurological disability. Results A total of 140 participants were included in this study from 2009 to 2019. Good outcomes were achieved in approximately 65% of cases, whereas 35% had poor outcomes based on the modified Rankin Scale. Glasgow Coma Scale score ≤10 at presentation and TBM/tuberculoma were significantly associated with poor outcomes. Moreover, the use of corticosteroids, more than three anti-TB medications, and surgical interventions were not significantly associated with good or poor outcomes. Discussion CNS-TB is associated with a high burden of long-term neurological morbidity. Early detection and treatment are crucial to prevent serious complications and decrease morbidity and mortality.

Clinical characteristics, radiological pointers and outcomes of central nervous system tuberculosis

BackgroundCentral nervous system tuberculosis (CNS-TB) is a severe and aggressive form of tuberculosis with a high mortality. With early identification and appropriate therapy, it carries a good outcome. Aim: To identify the clinical characteristics, radiological pointers, and outcomes of central nervous system tuberculosis. MethodsSingle-center retrospective study was conducted from January 01, 2018 to December 31, 2022 on patients diagnosed with CNS-TB.Adult patients with at least nine months of follow-up were included. Those seropositive for HIV or lost to follow-up before treatment completion were excluded. Variables were expressed as mean with standard deviation, median, and range. Chi-square and student's t-test for qualitative and quantitative variables were used. Results158 records were reviewed, and 56 were excluded. 102 patients were included with 90(88.23 %) cases of tubercular meningitis(TBM) and 12 (11.76 %) cases of isolated tuberculoma. There were 22(24.44 %) and 63(70.00%) cases of definite and probable tuberculous meningitis. Leptomeningeal enhancement (79.41%)and hydrocephalus (42.22%)were noted commonly. All cases of TBM and tuberculoma completed 9–12 months of anti-tubercular treatment. Dexamethasone was given to all patients with TBM for 6–12 weeks. One patient with biopsy-proven isolated tuberculoma received up to 24 months of ATT. Nine patients with TBM died(9/102,8.82 %). Grade III TBM, age >60 years, hydrocephalus,drug-induced hepatitis, and extra-neural tuberculosis were significant in the expired versus survivors comparison (p < 0.05). ConclusionsEarly identification, appropriate ATT regimen, and duration of treatment are associated with a good outcome in this fatal and disabling disease.

Long-term neuropsychiatric sequels in Central nervous system tuberculosis in Mexican patients

Long-term neuropsychiatric sequels in Central nervous system tuberculosis in Mexican patients

Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis

Background: Cerebrospinal fluid (CSF) Xpert MTB/RIF assay is an initial test for the diagnosis of tuberculous meningitis (TBM). Nevertheless, it is not very clear which of the factors govern CSF-Gene Xpert/MTB positivity. Objective: Hence, we aimed to assess the relationship, if any, between the clinical, laboratory and radiological parameters of the central nervous system (CNS) tuberculosis patients and the Gene Xpert study in CSF in such patients. Methods and Material: First, we studied 200 patients with CNS tuberculosis according to the case definition, and subsequently, we performed a Gene Xpert study on the CSF of these patients. Then, we correlated the clinical, radiological, and CSF criteria with the Gene Xpert positivity using the univariate binary logistic regression method via SPSS 20 (P-value &lt;0.05). Results: Seventy-five (37.5%) patients (57.3% females) of median 24 years of age, were CSF-Gene Xpert/MTB-positive and 125 (62.5%) patients were negative. The mean duration of illness (P = 0.017), weight loss or failure to thrive (P &lt; 0.001), loss of consciousness or seizure (P = 0.001), signs of meningeal irritation (P = 0.027), stage III of TBM (P &lt; 0.001), evidence of dissemination (P = 0.003), basal exudates (P = 0.004), hydrocephalus (P = 0.018), CSF lymphocytic predominance (P &lt; 0.001), and reduced CSF glucose (P = 0.011) correlated significantly with positive the Gene Xpert/MTB results. Also, Gene Xpert had a sensitivity of 80% and a specificity of 74.84% against culture Xpert. Conclusions: Xpert MTB/RIF might be more useful in the later stages of the disease and those with more severe disease.

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 &amp; 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 &amp; 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

A Complicated Case of Central Nervous System Tuberculosis in an Immuno Competent 25 year old Female with Visual Hallucinations and Blindness: Lessons Learned from a Rare Entity

Tuberculosis (TB) is a leading cause of the death in low-income countries, and central nervous system-TB (CNS-TB) is one of the most devastating variants of TB. A spectrum of symptoms can occur, ranging from nonspecific and heterogeneous to focal signs in the form of neurological complications. This case report describes a case of CNS-TB in a 25-year-old woman who presented with headache, fever, malaise, and generalized weakness of the lower extremities, followed by an unresponsive state. The patient was diagnosed with tubercular meningitis, and started on anti-tubercular therapy (ATT). Within days of inpatient treatment, the patient deteriorated rapidly, developing blindness with paraplegia and subsequently psychiatric symptoms in the form of visual hallucinations. Psychiatric symptoms were completely resolved with short-term treatment with antipsychotics. The patient had an uneventful recovery with the help of ATT and psychological support sessions, and had regular follow-ups for the next 8 months. This case focused on the differential diagnostic propensities of the index subject, who presented with CNS-TB (on ATT), visual hallucinations, and blindness during the inpatient stay. A clinician must be aware of unusual presentation of CNS-TB and other different causes of visual hallucinations for early diagnosis and prompt treatment of the patient.

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:&#x0D; 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.&#x0D; Methods:&#x0D; 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.&#x0D; Results:&#x0D; 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.&#x0D; 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.&#x0D; Conclusion:&#x0D; 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.