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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Paradoxical deterioration in patients with tuberculous meningitis is a significant diagnostic and treatment challenge. We present the case of a 55-year-old previously healthy male, human immunodeficiency virus (HIV)-negative, presenting with headache, fever, agitation and slurred speech, who was ultimately diagnosed with tuberculous meningoencephalitis confirmed by cerebrospinal fluid polymerase chain reaction positive for Mycobacterium tuberculosis complex. After initiation of a standard antitubercular therapy combined with glucocorticoids, the patient experienced an initial neurological improvement. However, after 3 months of therapy, he had a major stroke with neurological deterioration, clinically and radiologically attributable to a paradoxical deterioration or an immune reconstruction syndrome as described in HIV-positive patients. Due to the persistence of inflammatory symptoms and radiological evidence of worsening tuberculomas despite ongoing antituberculosis therapy, off-label use of the tumour necrosis factor (TNF) inhibitor infliximab was initiated. The patient received three doses of infliximab at 5 mg/kg at monthly intervals, which led to marked clinical and radiological improvement. Follow-up magnetic resonance imaging showed regression of lesions, and the patient was eventually discharged with a significant recovery of motor and speech functions. This case underscores the potential of TNF inhibitors in managing severe cases of paradoxical deterioration in patients with tuberculous meningitis, challenging existing treatment paradigms and suggesting a need for further research into the pathophysiology and treatment of this condition.

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. [ABSTRACT FROM AUTHOR]

Background Despite advancements in tuberculosis (TB) control and treatment in the United States (US), patients with central nervous system TB (CNS-TB) continue to experience significantly higher mortality rates than those without CNS-TB. This raises concerns regarding clinical management and the need for a deeper understanding of the risk factors contributing to these deaths. This study aimed to determine the predictors of mortality in patients with CNS-TB. Methods We conducted a retrospective 1:2 propensity score–matched case-control study. Cases were TB patients diagnosed with TB of the meninges, brain, spinal cord, or peripheral nerves, as documented in the Florida Department of Health (FDOH) TB registry, between 2009 and 2021. Controls were TB patients without CNS-TB, also reported in the FDOH TB registry during the same timeframe. We employed conditional logistic regression models to investigate the factors contributing to mortality in cases compared with controls. Results We analyzed data from 116 cases and 232 matched controls. Patients with CNS-TB had a 5.69-fold higher risk of death than those without CNS-TB (adjusted odds ratio [aOR], 5.69 [95% confidence interval {CI}, 2.91–11.6]). Increased risk of death was associated with human immunodeficiency virus (HIV) coinfection (aOR, 1.93 [95% CI,.82–4.37]) and diabetes (aOR, 3.13 [95% CI, 1.28–7.47]). Miliary TB and non-HIV immunosuppression were significantly associated with being a case, while cavitary TB was less likely to be associated with being a case. Conclusions Clinical management should prioritize screening and close monitoring of patients with HIV coinfection and diabetes to improve patient outcomes. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Abstract Recent advances in Nanotechnology have revolutionized the production of materials for biomedical applications. Nowadays, there is a plethora of nanomaterials with potential for use towards improvement of human health. On the other hand, very little is known about how these materials interact with biological systems, especially at the nanoscale level, mainly because of the lack of specific methods to probe these interactions. In this review, we will analytically describe the journey of nanoparticles (NPs) through the brain, starting from the very first moment upon injection. We will preliminarily provide a brief overlook of the physicochemical properties of NPs. Then, we will discuss how these NPs interact with the body compartments and biological barriers, before reaching the blood–brain barrier (BBB), the last gate guarding the brain. Particular attention will be paid to the interaction with the biomolecular, the bio‐mesoscopic, the (blood) cellular, and the tissue barriers, with a focus on the BBB. This will be framed in the context of brain infections, especially considering central nervous system tuberculosis (CNS‐TB), which is one of the most devastating forms of human mycobacterial infections. The final aim of this review is not a collection, nor a list, of current literature data, as it provides the readers with the analytical tools and guidelines for the design of effective and rational NPs for delivery in the infected brain.

Han Li,1,* Yinan Ding,2,* Jiayan Huang,1 Yanyan Zhao,1 Wei Chen,3 Qiusha Tang,2 Yanli An,4 Rong Chen,5 Chunmei Hu1 1Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Medical School of Southeast University, Nanjing, People’s Republic of China; 3Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, People’s Republic of China; 5Department of Oncology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunmei Hu, Department of tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210009, People’s Republic of China, Email njyy003@njucm.edu.cnBackground: Central nervous system tuberculosis (CNS-TB) is the most devastating form of extrapulmonary tuberculosis. Rifampin (RIF) is a first-line antimicrobial agent with potent bactericidal action. Nonetheless, the blood-brain barrier (BBB) limits the therapeutic effects on CNS-TB. Exosomes, however, can facilitate drug movements across the BBB. In addition, exosomes show high biocompatibility and drug-loading capacity. They can also be modified to increase drug delivery efficacy. In this study, we loaded RIF into exosomes and modified the exosomes with a brain-targeting peptide to improve BBB permeability of RIF; we named these exosomes ANG-Exo-RIF.Methods: Exosomes were isolated from the culture medium of BMSCs by differential ultracentrifugation and loaded RIF by electroporation and modified ANG by chemical reaction. To characterize ANG-Exo-RIF, Western blot (WB), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were performed. Bend.3 cells were incubated with DiI labeled ANG-Exo-RIF and then fluorescent microscopy and flow cytometry were used to evaluate the targeting ability of ANG-Exo-RIF in vitro. Fluorescence imaging and frozen section were used to evaluate the targeting ability of ANG-Exo-RIF in vivo. MIC and MBC were determined through microplate alamar blue assay (MABA).Results: A novel exosome-based nanoparticle was developed. Compared with untargeted exosomes, the targeted exosomes exhibited high targeting capacity and permeability in vitro and in vivo. The MIC and MBC of ANG-Exo-RIF were 0.25 μg/mL, which were sufficient to meet the clinical needs.Conclusion: In summary, excellent targeting ability, high antitubercular activity and biocompatibility endow ANG-Exo-RIF with potential for use in future translation-aimed research and provide hope for an effective CNS-TB treatment.Graphical Abstract: Keywords: exosome, central nervous system tuberculosis, blood-brain barrier, rifampin

Central nervous system tuberculosis (CNS) is a rare but extremely dangerous condition that has been reported in 5%-10% of extrapulmonary tuberculosis cases and accounts for approximately 1% of all tuberculosis cases. We present 2 cases of isolated central system tuberculosis in immunocompetent patients: a 57-year-old female and a 22-year-old young man, both of whom had MRI findings consistent with meningitis and tuberculomas and were complicated by cerebral ischemic infarction in the second case. Despite delaying therapy, both patients who had positive TB tests (PCR and QuantiFERON-TB Gold) nevertheless demonstrated clinical improvement. Although central nervous system tuberculosis has a high mortality rate and a high level of neurological morbidity, diagnosing it remains difficult because clinical symptoms and radiological findings can mimic other conditions such as pyogenic abscess, toxoplasmosis, sarcoidosis, and malignancy.

Introduction: The finding of multiple tuberculomas in the central nervous system (CNS) in pediatric patients is rare. Case of report: We present the case of a pediatric patient admitted with a 6-month history of behavioral change, weight loss, headache, and left hemiparesis. Imaging studies showed multiple CNS tuberculomas, pulmonary milia, and hepatic granulomas. The cerebrospinal fluid study showed elevated protein. BK studies and the tuberculin skin test were negative. The interferon gamma test (IGRA) was positive. The patient received treatment with the anti-TB regimen I, with a good response. Follow-up brain MRIs showed a decrease in the number and size of the lesions. Conclusions: The presentation of multiple CNS tuberculomas is uncommon, with a broad differential diagnosis and a varied clinical presentation. In endemic countries such as Peru, it should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Tuberculosis-immune reconstitution inflammatory syndrome is commonly seen among patients with acquired immunodeficiency syndrome either as a paradoxical worsening of an already diagnosed disease or as an uncovering of a dormant infection. There is evidence of paradoxical worsening of central nervous system tuberculosis (CNS-TB) once the treatment is instituted even among immunocompetent patients leading to significant morbidity. We report a case of a previously well young woman with paradoxical worsening of CNS-TB after commencement of treatment. This case highlights an important possible clinical sequelae of CNS-TB, a practicing physician should be aware of.

A 53-year-old lady with no known comorbidity had undergone cisternography for persistent rhinorrhea. Rhinorrhea resolved, and the report was normal. However, a week later, she complained of low back pain, followed by progressive quadriparesis and sphincter dysfunction. A detailed imaging revealed evidence of leptomeningitis around the brain stem, intradural cervical and dorsal collection with nodular enhancement, and clumping of cauda equina roots. Cerebrospinal fluid (CSF) showed pleocytosis with increased protein and hypoglycorrhachia. CSF cell count was 6000 (all lymphocytes), CSF proteins were 1138 mg%, and CSF glucose was 30 mg% (corresponding blood glucose level of 110 mg%). We did not get any systemic clue about the illness except progressive weight loss. Our team concluded either it is directly a deadly sequel of the dye-related complication of cisternography or activation of a chronic infection in the spine. We treated her with antitubercular drugs and steroids along with physiotherapy. We kept in mind the chronicity of the illness and endemicity of tuberculosis. She responded well and was mobilizable with minimal support. Hence, we continued the same regimen, keeping in mind the responsiveness of the patient to the same. We report this case to realize the possibility of this type of complication even with advanced dye and modern techniques of cisternography. Our case also underscores the requirement of prior imaging (magnetic resonance imaging of the spine) before undertaking such a procedure (cisternography). Last but not the least, sometimes we also need to make decisions based on our clinical knowledge as neurological investigations may be inconclusive in many circumstances.

Neurotuberculosis or central nervous system tuberculosis is a form of tuberculous infection that affects any part of the nervous system. Although it is more frequent in adults, pediatric cases have been reported in endemic countries and it is potentially a deadly affection. Therefore, any unusual neurological manifestation in a formerly healthy child, independently of their vaccination status, must bring suspicion of CNS tuberculosis among other diagnoses. We report four cases of pediatric neurotuberculosis with various clinical presentations and outcome and a brief review of the litterature. We conclude that clinical manifestations of pediatric neurotuberculosis are extremely variable and could be misleading. Extra-neurological sites are a key element for diagnosis especially in the pediatric population. A diagnosis and clinical outcome score, especially designed for children might help personalize the therapeutic approach and outcome measures. • Neurotuberculosis is a rare condition both in the adult and pediatric population. • We present four varied case studies of neurotuberculosis in children with different clinical manifestations and outcome. • We have described the diagnostic approach in our clinical cases and emphasized the importance of extra-neurological manifestations in the diagnostic orientation since biological confirmation is not always possible. • This article includes a review of neurotuberculosis in children includingclinical manifestations, imaging, confirmation methods, management and outcome. [ABSTRACT FROM AUTHOR]

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.

Tuberculosis (TB) affecting the central nervous system (CNS) is rare, often mimicking other intracranial pathologies such as meningiomas, especially when located in the anterior skull base. Despite a global reduction in TB incidence, CNS TB continues to present diagnostic challenges due to its nonspecific imaging characteristics. We report a case of a 39-year-old male with symptoms including persistent headache, vertigo, and visual disturbances. Initial imaging suggested meningioma; however, histopathology revealed a tuberculoma. The patient responded well to antitubercular therapy following surgery. This case emphasizes the necessity of considering TB in differential diagnoses of intracranial lesions, especially in endemic regions, to prevent misdiagnosis and ensure timely treatment. CNS TB, though rare, should be a differential consideration in intracranial lesions to avoid delays in diagnosis and improve clinical outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Badran et al.)

Paradoxical deterioration in patients with tuberculous meningitis is a significant diagnostic and treatment challenge. We present the case of a 55-year-old previously healthy male, human immunodeficiency virus (HIV)-negative, presenting with headache, fever, agitation and slurred speech, who was ultimately diagnosed with tuberculous meningoencephalitis confirmed by cerebrospinal fluid polymerase chain reaction positive for Mycobacterium tuberculosis complex. After initiation of a standard antitubercular therapy combined with glucocorticoids, the patient experienced an initial neurological improvement. However, after 3 months of therapy, he had a major stroke with neurological deterioration, clinically and radiologically attributable to a paradoxical deterioration or an immune reconstruction syndrome as described in HIV-positive patients. Due to the persistence of inflammatory symptoms and radiological evidence of worsening tuberculomas despite ongoing antituberculosis therapy, off-label use of the tumour necrosis factor (TNF) inhibitor infliximab was initiated. The patient received three doses of infliximab at 5 mg/kg at monthly intervals, which led to marked clinical and radiological improvement. Follow-up magnetic resonance imaging showed regression of lesions, and the patient was eventually discharged with a significant recovery of motor and speech functions. This case underscores the potential of TNF inhibitors in managing severe cases of paradoxical deterioration in patients with tuberculous meningitis, challenging existing treatment paradigms and suggesting a need for further research into the pathophysiology and treatment of this condition., Learning Points: Patients with tuberculous meningitis may experience a paradoxical deterioration in spite of correct antituberculosis treatment.The paradoxical deterioration may have a severe clinical presentation, requiring high vigilance and consideration of treatment escalation.Here we report that off-label administration of tumour necrosis factor-alpha blocker infliximab induced a significant clinical and radiological improvement in a severe case of paradoxical deterioration in a patient with tuberculous meningitis, suggesting its potential as a treatment when standard therapies fail., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Brain abscesses caused by Mycobacterium tuberculosis are rarely reported and are typically found in immunocompromised patients. The challenges in identifying the pathogen and the frequent delays in initiating appropriate therapy often result in a poor prognosis for patients. We herein report a rare case of a brain abscess caused by M. tuberculosis in a 63-year-old patient with a history of hypertension but no history of pulmonary tuberculosis. The patient was hospitalized twice because of worsening right upper limb weakness and speech difficulties. Both a pus culture and cerebrospinal fluid culture were negative. Ultimately, the diagnosis of M. tuberculosis infection was confirmed through next-generation sequencing and the tuberculosis-specific T-cell test (T-SPOT). The patient's symptoms improved following anti-tuberculosis treatment. This case highlights the importance of considering M. tuberculosis as a potential cause of brain abscesses, even in immunocompetent individuals, and underscores the need for early diagnosis for effective treatment., Competing Interests: Declaration of conflicting interestsThe authors declare that they have no conflicts of interest.

Wenbin Qiao,1,* Jiahui Fan,1,* Xiaoqian Shang,1,* Liang Wang,2 Bahetibieke Tuohetaerbaike,2 Ying Li,2 Li Zhang,2 YiShan Huo,1 Jing Wang,3 Xiumin Ma1,2 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3Respiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiumin MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Road, Urumqi, 830011, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaTel +86-13369649029Email maxiumin1210@sohu.comJing WangRespiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of ChinaTel +86-13629925886Email tlfwj@163.comObjective: Central nervous system tuberculosis is the most serious form of extrapulmonary tuberculosis. We aim to discover potential biomarkers involved in the development of the disease.Methods: Through gene difference analysis, construction of a protein interaction network and tissue specific analysis and other bioinformatics analysis methods, we found out the relatively high expression of important substances in the central nervous system, interferon induced protein with tetratricopeptide repeats 1. Subsequently, the lesion tissue and the resection margin tissue away from the lesion were collected from the 6 cases of central nervous system tuberculosis patients diagnosed from 2019 to 2020, and the pathological manifestations were observed by Hematoxylin and Eosin (H&E) staining, and the expression of IFIT1 was verified by immunohistochemistry.Results: A total of 101 differential genes were analyzed between extrapulmonary tuberculosis patients and normal people, and they were mainly enriched in the interferon pathway. The protein interaction network unearthed 34 key genes. Through tissue specific analysis, it was found that IFIT1 is relatively high in the central nervous system. H&E staining showed the expression of multinucleated macrophages, and immunohistochemistry showed that IFIT1 was significantly positively expressed in the lesion tissue.Conclusion: IFIT1 is an important substance involved in central nervous system tuberculosis.Keywords: central nervous system tuberculosis, biomarkers, interferon induced protein with tetratricopeptide repeats 1, hematoxylin and eosin staining, immunohistochemistry staining

Tubercular meningitis is the most devastating form of tuberculosis. Neuro-ophthalmic involvement can manifest as cranial nerve palsies, pupil abnormalities, disc changes, like papillitis, papilloedema, or optic atrophy and choroidal tubercles. The rate and extent of recovery are strongly. Related to early diagnosis and treatment. Herein, we describe a constellation of three cases of central nervous system tuberculosis with aberrant regeneration of oculomotor nerve, optochiasmatic arachnoiditis presenting as bilateral primary optic atrophy and the last case of parietal lobe tuberculoma presenting as homonymous hemianopia, each one with its own characteristic ocular findings.

• Tuberculous optochiasmatic arachnoiditis (TOA) is a very rare complication of tuberculous meningitis. • An exaggerated host response against tuberculous proteins is believed to play an important role in the development of TOA. • This case is special because many different affected brain areas were also identified including hydrocephalus, exudates in the pineal region, basal arachnoiditis, and ventriculitis of the fourth ventricle. [ABSTRACT FROM AUTHOR]

Immune reconstitution inflammatory syndrome to tuberculosis (TB-IRIS) is an inflammatory response to M. tuberculosis infection that arises following restoration of the immune system and is increasingly recognized as a risk in patients treated with tumor necrosis factor α inhibitors who develop active tuberculosis infection. We present the case of a 19-year-old man treated with adalimumab for Crohn's disease who presented with disseminated miliary tuberculosis. His treatment course was complicated by central nervous system TB-IRIS following cessation of his immunosuppression. We review the presentation and differential diagnosis of TB-IRIS, as well as risk factors for developing IRIS and the treatment of IRIS in this population. [ABSTRACT FROM AUTHOR]

Tubercular meningitis is prevalent in India as various clinical subtypes. Our case illustrates an unusual presentation of tuberculosis (TB) meningitis with cerebral venous sinus thrombosis. Our patient had presented with fever and headache for about 1 week, followed by acute onset left hemiparesis. His evaluation revealed features of cerebral venous sinus thrombosis (CVT) on neuroimaging along with cerebrospinal fluid picture of the central nervous system (CNS) TB. He was managed with antitubercular therapy with steroids and anticoagulation following which the patient recovered. The coexistence of CVT with CNS TB is very rare. It is pertinent to diagnose the same early to prevent life-threatening complications.

Background: Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. Methods: Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. Results: We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19–49 years old), developed a paradoxical manifestation within 4–14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. Conclusions: This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed. [ABSTRACT FROM AUTHOR]

Managing tuberculous meningitis (TBM) is challenging because of its poor prognosis and the difficulty in making an early diagnosis due to the low sensitivity of cerebrospinal fluid (CSF) polymerase chain reaction (PCR) evaluations. A 75-year-old woman presented with fatigue and multiple enlarged lymph nodes and was initially suspected of having metastatic cancer of unknown primary origin. Differential diagnoses included carcinomatous meningitis, neurosarcoidosis, and TBM, as suggested by the presence of multiple enhancing cerebral nodules. Despite 11 negative PCR evaluations, including nested PCR of CSF and biopsied lymph nodes within the first 3 days of empirical anti-tubercular treatment, TBM was eventually confirmed by CSF cultures 32 days later. This case highlights the need for repeated sampling.

Tuberculosis (TB) remains one of the leading infectious killers in the world, infecting approximately a quarter of the world’s population with the causative organism Mycobacterium tuberculosis (M. tb). Central nervous system tuberculosis (CNS-TB) is the most severe form of TB, with high mortality and residual neurological sequelae even with effective TB treatment. In CNS-TB, recruited neutrophils infiltrate into the brain to carry out its antimicrobial functions of degranulation, phagocytosis and NETosis. However, neutrophils also mediate inflammation, tissue destruction and immunopathology in the CNS. Neutrophils release key mediators including matrix metalloproteinase (MMPs) which degrade brain extracellular matrix (ECM), tumor necrosis factor (TNF)-α which may drive inflammation, reactive oxygen species (ROS) that drive cellular necrosis and neutrophil extracellular traps (NETs), interacting with platelets to form thrombi that may lead to ischemic stroke. Host-directed therapies (HDTs) targeting these key mediators are potentially exciting, but currently remain of unproven effectiveness. This article reviews the key role of neutrophils and neutrophil-derived mediators in driving CNS-TB immunopathology.

Objective To summarize the effective diagnosis and therapies of paradoxical reactions during anti-tuberculosis treatment for intracranial tuberculosis in adults. Methods We analyzed the time of occurrence, clinical manifestations, cerebrospinal fluid (CSF) test results, imaging features, and therapies of 11 patients with paradoxical reactions, retrospectively. Results Eleven cases of 56 patients had paradoxical reactions. Paradoxical reactions most often occurred 1 to 2 months after antituberculosis treatment, and the rest occurred 2 to 9 months. Five patients（45%) suffered from fever and headache, 3 patients（27%) had cognitive impairments, 1 patient had hemiparesis（9%), and 1 patient got dizziness, speech disorder, and blurred version（9%). The paradoxical reaction during the CSF examination was observed in 7 patients（64%), 6 patients had increased CSF protein, 4 patients（36%) had reduced levels of CSF chloride, and 3 patients had increased levels of CSF leukocytes and reduced levels of CSF glucose. Ten patients（91%) had neuroimaging paradoxical reaction in brain：5 patients had new tuberculomas and enlargement of tuberculoma, 4 patients（36%) had new cerebral infarction, 1 patient had new hydrocephalus, and 1 patient had no change. Ten patients with paradoxical re‐ actions received adequate treatment with first-line antituberculous medications (isoniazid, rifampicin, pyrazinamide and ethambutol), prednisone（60 mg/d), levofloxacin（0. 5 g/d) and linezolid（0. 6-1. 2g/d), 1 patient had combined treatment of intrathecal injection, 4 patients with new infarction had combined treatment of aspirin（100 mg/d), 1 patients with middle cerebral artery stenosis had the combined treatment of prednisone, and 1 patient with cerebral venous sinus thrombosis had the combined treatment of low molecular heparin calcium（4 000 IU, twice a day) and dabigatran etexilate (110 mg, twice a day) . Among them, 9 patients improved in areas of clinical manifestation and neuroimaging, 1 patient who had worsening hydrocephalus finally improved by ventriculo-peritoneal (V-P) shunt, and 1 patient died of heart failure. Conclusions Paradoxical reactions usually occur in one or two months after anti-tuberculosis treatment for patients with intracranial tuberculosis when they suffer from fever or headache, increased levels of CSF protein, neuroimaging changes of new tuberculomas and enlargement of tuberculomas. It is necessary to offer adequate anti-tuberculosis medications and effective intrathecal intervention; when necessary, lateral ventriculo-peritoneal drainage can significantly improve the prognosis of hydrocephalus. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains one of the leading infectious killers in the world, infecting approximately a quarter of the world's population with the causative organism Mycobacterium tuberculosis (M. tb). Central nervous system tuberculosis (CNS-TB) is the most severe form of TB, with high mortality and residual neurological sequelae even with effective TB treatment. In CNS-TB, recruited neutrophils infiltrate into the brain to carry out its antimicrobial functions of degranulation, phagocytosis and NETosis. However, neutrophils also mediate inflammation, tissue destruction and immunopathology in the CNS. Neutrophils release key mediators including matrix metalloproteinase (MMPs) which degrade brain extracellular matrix (ECM), tumor necrosis factor (TNF)-α which may drive inflammation, reactive oxygen species (ROS) that drive cellular necrosis and neutrophil extracellular traps (NETs), interacting with platelets to form thrombi that may lead to ischemic stroke. Host-directed therapies (HDTs) targeting these key mediators are potentially exciting, but currently remain of unproven effectiveness. This article reviews the key role of neutrophils and neutrophil-derived mediators in driving CNS-TB immunopathology. [ABSTRACT FROM AUTHOR]

Tuberculous meningitis is a highly lethal, often underrecognized disease with characteristic clinical and imaging features which can be cured if the diagnosis and subsequent treatment are begun at early stages. Frequently, there is a delayed diagnosis of this condition due to unfamiliarity of clinicians in non-endemic areas about its presentation and diagnostic workup. This article presents a case of rapid decline and fatality due to tuberculous meningitis in an 11-month-old child from a non-TB-endemic area and describes the characteristic clinical presentation, imaging findings, and diagnostic pitfalls associated with this condition. [ABSTRACT FROM AUTHOR]

Background: A tuberculous brain abscess is an unusual form of central nervous system tuberculosis, whereas Foster Kennedy syndrome is a rare condition characterized by ipsilateral optic atrophy, contralateral papilloedema, and ipsilateral anosmia. Foster Kennedy Syndrome and tuberculous brain abscess both are rare conditions with limited study. We report the first case of Foster Kennedy syndrome associated with tuberculous brain abscess. Case presentation: A 32 years old male presented with severe headache, memory impairment, speech difficulty, a slight right-side weakness, and vision impairment for eight weeks. The symptoms began with a low-grade fever, a dry cough, and a loss of appetite, which intensified over time. The patient was generally wasted and drowsy. Physical examination showed right-sided hemiparesis. An enhanced lesion in the left frontal lobe was seen on a plain computed tomography scan accompanied by perifocal edema. An open craniectomy was performed, and antituberculous therapy was begun immediately. The disability had significantly improved in a month. Conclusion: In patients with Foster Kennedy syndrome, a tuberculous brain abscess should be considered. Patients who have been diagnosed must undergo surgical surgery as well as antituberculous therapy to recover fully.

Background: To study the clinical outcome of tuberculous meningitis with hydrocephalus (TBMH) and the factors contributing to its poor clinical outcome. Methods: Clinical data of 143 adult patients diagnosed with TBM over a 6-year period in two tertiary hospitals in Malaysia were retrospectively reviewed. Relevant clinical and radiological data were studied. Patients with TBMH were further analysed based on their clinical grade and rendered treatment to identify associated factors and outcome of this subgroup of patients. The functional outcome of patients was assessed at 12 months from treatment. Results: The mean age of patients was 35.6 (12.4) years old, with a male gender predominance of 67.1%. Forty-four percent had TBMH, of which 42.9% had surgical intervention. In the good modified Vellore grade, 76.5% was managed medically with concurrent antituberculosis treatment (ATT), steroids and osmotic agents. Four patients had surgery early in the disease as they did not respond to medical therapy and reported a good outcome subsequently. Poor outcome (65.2%) was seen in the poor modified Vellore grade despite medical and surgical intervention. Multivariate model multiple Cox regression showed significant results for seizure (adjusted hazard ratio [aHR]: 15.05; 95% CI: 3.73, 60.78), Glasgow coma scale (GCS) (aHR: 0.79; 95% CI: 0.70, 0.89) and cerebrospinal fluid (CSF) cell count (aHR: 1.11; 95% CI: 1.05, 1.17). Conclusion: Hydrocephalus was seen in 44% of patients in this study. GCS score, seizure and high CSF cell count were factors associated with a poor prognosis in TBM. Patients with TBMH treated medically (TBMHM) had better survival function compared to TBMH patients undergoing surgical intervention (TBMHS) (P-value < 0.001). This retrospective study emphasises that TBMH is still a serious illness as 47.6% of the patients had poor outcome despite adequate treatment. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) continues to be a significant global health concern, with India contributing substantially to the global burden. The management of TB is further complicated by HIV-associated immunodeficiency and the emergence of drug-resistant TB strains. Early diagnosis and treatment are critical, particularly for tubercular meningitis (TBM), which is among the most severe forms of extrapulmonary TB. We present the case of a 55-year-old male who arrived at our emergency department with a one-week history of fever, headache, incoherent speech, and slurred speech. The patient had no relevant medical history or known contact with TB patients. Neurological examination revealed ptosis of the right eye and a left extensor plantar response. Laboratory investigations revealed a miliary pattern on chest radiography, and cerebrospinal fluid analysis showed an adenosine deaminase (ADA) level of 14.4 U/L, a total cell count of 110/mm³, glucose of 6 mg/dL, and protein of 228.4 mg/dL, supporting the diagnosis of TBM. Magnetic resonance imaging (MRI) indicated brain lesions consistent with TBM. TBM represents the most devastating form of extrapulmonary TB if left untreated. Therefore, prompt initiation of antitubercular therapy and continued vigilance in endemic regions are essential for addressing this complex global health issue., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharma et al.)

Tuberculosis (TB) is still one of the most challenging infectious diseases worldwide. Coinfection with HIV increases the likelihood of extrapulmonary involvement, including the tuberculosis of the central nervous system (CNS-TB). CNS-TB often presents as tuberculomas or tuberculous meningitis. Although tuberculomas can be single or multiple, asymptomatic carriage of numerous tuberculomas is seldom reported. We present a case of a 55-year-old man who carried at least 34 tuberculomas of different sizes asymptomatically before developing and succumbing to tuberculous meningitis. Furthermore, we highlight several possible public health challenges that might have complicated his clinical course, suggesting that future studies also focus on these variables alongside more traditional clinical issues., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alavidze et al.)

This data article presents datasets associated with the research article entitled “The immunological architecture of granulomatous inflammation in central nervous system tuberculosis’’ (Zaharie et al., 2020). The morphology of tuberculosis related granulomas within the central nervous system of human patients was visualized in six different three-dimensional (3D) models. Post-mortem, formalin fixed and paraffin embedded specimens from deceased tuberculous meningitis patients were immunohistochemically stained and 800 serial histologically stained sections were acquired. Images from all sections were obtained with an Olympus BX43 light microscope and structures were identified, labeled and made three-dimensional. The interactive 3D-models allows the user to directly visualize the morphology of the granulomas and to understand the localization of the granulomas. The 3D-models can be used for multiple purposes and provide both an educational source as a gold standard for further animal studies, human research and the development of in silico models on the topic of central nervous system tuberculosis.

Introduction: Tubercular meningitis (TBM) is a common cause of chronic meningitis in India; however, there is a paucity of literature on optimum duration and choice of drug therapy. Materials and Methods: This was an ambispective cohort study. Results: Two hundred and forty-four patients of central nervous system tuberculosis (CNS TB) who were seronegative for HIV were studied of whom 198 had TBM and 46 patients had tuberculoma without meningitis. Before completion of treatment, 84% of TBM patients underwent imaging. There was no difference in disability or mortality in patients, who were treated with various drug regimens in terms of duration of therapy or number of drugs at initiation of treatment. However when patients developed new complications, adding more drugs improved survival. Prolonging corticosteroid administration in patients with nonsatisfactory improvement at 8 weeks was not associated with prevention of disability. Conclusions: CNS TB is treated by neurologists and physicians in India, as per their experience due to different recommendations in various guidelines. There is a tendency to decide when to stop treatment based on neuroimaging given the fear of poor outcomes associated with recurrence of the disease. The duration of treatment or choice of drugs at the start of treatment did not affect disability.

Tuberculosis is a worldwide pandemic. Estimated that about 25% humans are colonized by Mycobacterium tuberculosis and about 1% are believed to develop the infection in the central nervous system (CNS-TB). Given the importance of this disease and its high levels of morbidity and mortality, it is imperative that every radiologist must be reminded of the most common findings of CNS-TB as there are several related differential diagnoses for this disease. The most common form CNS-TB is tuberculous meningitis (TBM), characterized mostly by basal meningitis, but infarction, hydrocephalus and tuberculomas could be present. Intracerebral tuberculosis is characterized by tuberculomas that can have different imaging features according to their stage. Vascular and spinal complications of tuberculosis are also reported. This review compiles the classic and unusual findings regarding CNS-TB together with new diagnostic scores in which neuroimaging have an important role. • Tuberculosis in the Central Nervous System (CNS-TB) involves different clinical, laboratorial and neuroimaging features. • Tuberculous basal meningitis is the most common form of Tuberculosis in the Central nervous system. • Peripherally enhancement lesions without diffusion restriction, infarction and hydrocephalus could be related to CNS-TB [ABSTRACT FROM AUTHOR]

Background Our goal was to describe the characteristics and posttreatment outcomes of pediatric patients with central nervous system (CNS) tuberculosis (TB) and to identify factors associated with poor outcome. Methods We included children aged 0 to 18 years with CNS TB reported to the California TB registry between 1993 and 2011. Demographics, clinical characteristics, severity of disease at presentation (Modified Medical Research Council stage I, II, or III [III is most severe]), treatment, and outcomes during the year after treatment completion were abstracted systematically from the medical and public health records. Patient outcomes were categorized as good or poor on the basis of disability in hearing, vision, language, ambulation, and development and other neurologic deficits. Results Among 151 pediatric CNS TB cases reported between 1993 and 2011 in California for which records were available, 92 (61%) cases included sufficient information to determine outcome. Overall, 55 (60%) children had a poor outcome. After we adjusted for age (0 to 4 years), children with stage III severity (vs I or II; prevalence rate ratio [PRR], 1.4 [95% confidence interval (CI), 1.1–1.9]), a protein concentration of >100 mg/dL on initial lumbar puncture (PRR, 1.2 [95% CI, 1.03–1.4]), or infarct on neuroimaging (PRR, 1.2 [95% CI, 1.04–1.3]) were at increased risk for a poor outcome. In multivariate analysis, an age of 0 to 4 years (vs >4 years; PRR, 1.4 [95% CI, 1.2–1.7]) and a stage II or III Modified Medical Research Council score (vs stage I; PRR, 1.2 [95% CI, 1.03–1.5]) remained significantly associated with poor outcome. Conclusions Pediatric patients with CNS TB in California are left with high rates of disabling clinical sequelae after treatment. The identification of modifiable factors is critical for improving outcomes. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is a paucity of literature related to the neuroimaging of CNS tuberculosis (TB) and largely covers pediatric CNS TB. The objective of this study was to determine the frequency of different forms of CNS TB and its associated complications and to study longitudinal disease course using computed tomography (CT) and MRI.Methods: Retrospective chart and imaging review of patients diagnosed with CNS TB in a tertiary care hospital in Pakistan over a 10-year period. A total of 452 initial brain MRI and 209 CT scans were reviewed by an expert radiologist specialized in neuroimaging. This was followed by review of 53 MRI/52 CT and 7 MRI/14 CT first and second follow-up scans, respectively.Results: Note that 559 patients, 296 males and 263 females were included in the study. On the initial CT scans, tuberculomas were found in 25 (12%), infarction in 54 (25%), basal meningeal enhancement in 29 (14%), and hydrocephalus in 84 (40%). On initial MRI, tuberculomas were found in 182 (40%), infarction in 120 (27%), basal meningeal enhancement in 184 (41%), and hydrocephalus in 116 (26%). On review of follow-up CT scans, 13 (25%) showed new or worsening hydrocephalus, 8 (15%) showed new infarcts, 1 exhibited new tuberculoma, and 5 showed worsening cerebral edema. On review of follow-up MRI scans, new or worsening hydrocephalus was seen in 3 (6%), new infarcts in 3 (6%), new tuberculoma in 10 (19%), worsening cerebral edema in 7 (13%), and TB myelitis in 4 (8%) patients.Conclusions: Tuberculoma, hydrocephalus, and cerebral infarcts are the most prominent findings in CNS tuberculosis. Our study showed development of new lesions on subsequent neuroimaging suggesting a dynamic and progressive nature of the disease process in some individuals. [ABSTRACT FROM AUTHOR]

Although tuberculosis of the central nervous system (CNS) is rarely seen, it may cause neurological sequelae and mortality if treatment is delayed. A nine-year-old girl was admitted to our clinic with the complaint of convulsion. Since her convulsions were persistent, steroid treatment had been administered for acute disseminated encephalomyelitis based on the cranial magnetic resonance imaging (MRI). In the examination of the patient, who was brought to our clinic due to recurrent convulsions, no pathological finding was detected except for bilateral papilledema. The tuberculin skin test revealed an induration of 19 mm. The positive tuberculin skin test, history of contact with an individual with tuberculosis, and findings indicating tuberculosis in the thorax and cranial imaging were assessed together with the symptoms and examination findings of the patient, and intracranial tuberculoma diagnosis was made. Antituberculosis treatment and dexamethasone treatment were initiated. No complications were observed in the two-year follow-up of the patient. Intracranial tuberculoma is a rare form of CNS tuberculosis with high rates of morbidity and mortality. Because clinical, laboratory, and imaging findings are nonspecific, it should be considered in the differential diagnosis of CNS disorders. Early diagnosis and treatment are crucial for a better prognosis.

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.