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Tuberculosis is a contagious infectious disease caused by Mycobacterium tuberculosis, and is the leading cause of death from a single infectious agent worldwide. Imaging plays an important role in the early diagnosis of central nervous system tuberculosis and may prevent unnecessary morbidity and mortality. This article presents an extensive review of pathogenesis, clinical symptoms, typical and atypical imaging appearances of intracranial and spinal tuberculosis, and advanced imaging of intracranial tuberculosis. Furthermore, we explore central nervous system infection of nontuberculous mycobacteria and leprosy and their imaging findings., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB., Methods: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2 -/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains., Results: Intra-cerebroventricular infection of Nos2 -/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2 -/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice., Conclusions: Intra-cerebroventricular infection of Nos2 -/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB., (© 2022. The Author(s).)

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

In vitro culture models of the blood-brain barrier (BBB) provide a useful platform to test the mechanisms of cellular infiltration and pathogen dissemination into the central nervous system (CNS). We present an in vitro mouse model of the BBB to test Mycobacterium tuberculosis (Mtb) dissemination across brain endothelial cells. One-third of the global population is infected with Mtb, and in 1%-2% of cases bacteria invade the CNS through a largely unknown process. The "Trojan horse" theory supports the role of a cellular carrier that engulfs bacteria and carries them to the brain without being recognized. We present for the first time a protocol for an in vitro BBB-granuloma model that supports the Trojan horse mechanism of Mtb dissemination into the CNS. Handling of bacterial cultures, in vivo and in vitro infections, isolation of primary astroglial and endothelial cells, and assembly of the in vitro BBB model is presented. These techniques can be used to analyze the interaction of adaptive and innate immune system cells with brain endothelial cells, cellular transmigration, BBB morphological and functional changes, and methods of bacterial dissemination. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolation of primary mouse brain astrocytes and endothelial cells Basic Protocol 2: Isolation of primary mouse bone marrow-derived dendritic cells Support Protocol 1: Validation of dendritic cell purity by flow cytometry Basic Protocol 3: Isolation of primary mouse peripheral blood mononuclear cells Support Protocol 2: Isolation of primary mouse spleen cells Support Protocol 3: Purification and validation of CD4+ T cells from PBMCs and spleen cells Basic Protocol 4: Isolation of liver granuloma supernatant and determination of organ load Support Protocol 4: In vivo and in vitro infection with mycobacteria Basic Protocol 5: Assembly of the BBB co-culture model Basic Protocol 6: Assembly of the combined in vitro granuloma and BBB model., (© 2020 Wiley Periodicals LLC.)

Infections of the central nervous system cause significant morbidity and mortality in immunocompetent and immunocompromised individuals. A wide variety of microorganisms can cause infections, including bacteria, mycobacteria, fungi, viruses, and parasites. Although less invasive testing is preferred, surgical biopsy may be necessary to collect diagnostic tissue. Histologic findings, including special stains and immunohistochemistry, can provide a morphologic diagnosis in many cases, which can be further classified by molecular testing. Correlation of molecular, culture, and other laboratory results with histologic findings is essential for an accurate diagnosis, and to minimize false positives from microbial contamination., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Central nervous system (CNS) tuberculomas are a challenging manifestation of extrapulmonary tuberculosis often leading to neurological complications and post-treatment sequelae. The role of adjunctive corticosteroid treatment is not fully understood. Most guidelines on management of tuberculosis do not distinguish between tuberculous meningitis and CNS tuberculomas in terms of corticosteroid therapy., Methods: We describe five patients with CNS tuberculomas who required intensified dexamethasone treatment for several months, in two cases up to 18 months., Results: These patients were initially treated with the standard four-drug tuberculosis regimen and adjuvant dexamethasone. Neurological symptoms improved rapidly. However, multiple attempts to reduce or discontinue corticosteroids according to guideline recommendations led to clinical deterioration with generalized seizures or new CNS lesions. Thus, duration of adjunctive corticosteroid therapy was extended eventually leading to clinical cure and resolution of lesions., Conclusion: In contrast to tuberculous meningitis, the treatment for CNS tuberculomas appears to require a prolonged administration of corticosteroids. These findings need to be verified in controlled clinical studies.

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., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Primary pituitary tubercular abscess is a very rare disease. It may present clinically with visual loss, headache, seizure, hormonal abnormalities or with cranial nerve palsies. MRI is the diagnostic modality and shows a cystic-solid mass in the sellar and suprasellar region, isointense on T1 and T2W images with heterogeneous areas and ring enhancement on contrast. Surgery remains the initial treatment and it is approached through the trans-sphenoidal/trans-nasal or transcranial route followed by anti-tubercular therapy. We report a case of primary pituitary tubercular abscess managed successfully with a brief review of its pathology. Keywords: abscess; pituitary gland; pyogenic; sella; tuberculosis.

Background: Central nervous system tuberculosis (CNS TB) in children is still a socioeconomic problem in developing countries. It has varied manifestations, symptoms are nonspecific, diagnosis can be challenging, and treatment may be difficult. It is often missed or overlooked. Among the various pathological entities, tuberculous meningitis is the most common and devastating manifestation. The resultant vasculitis, infarction, and hydrocephalus can be life-threatening. It can have grave cognitive, intellectual, and endocrine sequelae if not treated in time resulting in handicap, especially in resource constraint countries. Early diagnosis and treatment of tuberculous meningitis is the single most important factor determining outcome. Tuberculous hydrocephalus needs to be recognized early, and cerebrospinal fluid diversion procedure needs to be performed in adequate time to prevent morbidity or mortality in some cases. Tuberculous pachymeningitis and arachnoiditis are rare in children. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Drug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted., Aim: The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized., Conclusion: Heightened clinical suspicion, early diagnosis, appropriate antituberculous treatment, and surgery in relevant situation are essential for a gratifying outcome and preventing complications.

The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (p = 0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (p < 0.001), which indicated more apoptosis in neurons. Thus, neuronal death and survival of infected astrocytes together with high expression of VEGF might be associated with formation of brain tuberculosis. In conclusion, neurons could be more vulnerable than astrocytes in human tuberculosis brain with high expression of VEGF., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pregabalin, widely used in the treatment of several pain disorders, is usually well tolerated. Uncommonly, the drug may induce cardiac side effects, rarely prolongation of the PR interval. The latter has never been described in patients with healthy heart or normal renal function. We characterize a unique case of a young man with extrapulmonary tuberculosis and no detectable or known cardiac or kidney diseases, treated with pregabalin to control the severe pain due to the involvement of the spinal cord by the tuberculosis, showing an atrioventricular (AV) block due to pregabalin administration. The reported case emphasizes the need of monitoring PR interval during treatment with pregabalin, even in patients without background of cardiac or renal diseases.

Background: Central nervous system tuberculosis (CNS-TB) may be fatal even with treatment. Neutrophils are the key mediators of TB immunopathology, and raised CSF matrix metalloproteinase-9 (MMP-9) which correlates to neutrophil count in CNS-TB is associated with neurological deficit and death. The mechanisms by which neutrophils drive TB-associated CNS matrix destruction are not clearly defined., Methods: Human brain biopsies with histologically proven CNS-TB were stained for neutrophils, neutrophil elastase, and MMP-9. Neutrophil MMP-9 secretion and gene expression were analyzed using Luminex and real-time PCR. Type IV collagen degradation was evaluated using confocal microscopy and quantitative fluorescent assays. Intracellular signaling pathways were investigated by immunoblotting and chemical inhibitors., Results: MMP-9-expressing neutrophils were present in tuberculous granulomas in CNS-TB and neutrophil-derived MMP-9 secretion was upregulated by Mycobacterium tuberculosis (M.tb). Concurrent direct stimulation by M.tb and activation via monocyte-dependent networks had an additive effect on neutrophil MMP-9 secretion. Destruction of type IV collagen, a key component of the blood-brain barrier, was inhibited by neutralizing neutrophil MMP-9. Monocyte-neutrophil networks driving MMP-9 secretion in TB were regulated by MAP-kinase and Akt-PI 3 kinase pathways and the transcription factor NF-kB. TNFα neutralization suppressed MMP-9 secretion to baseline while dexamethasone did not., Conclusions: Multiple signaling paths regulate neutrophil-derived MMP-9 secretion, which is increased in CNS-TB. These paths may be better targets for host-directed therapies than steroids currently used in CNS-TB.

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

Background/purpose: Childhood tuberculosis (TB) continues to be a major public health problem in Taiwan. Taiwan remains a highly endemic area despite neonatal Bacillus Calmette-Guérin (BCG) vaccination and the availability of anti-TB therapy. The presentation is highly variable and it is often difficult to make an accurate diagnosis. This study was designed to evaluate the demographic, clinical, and laboratory findings and outcomes of TB in children with emphasis on central nervous system (CNS) complications., Methods: The medical records of 80 children diagnosed with TB at a medical center in southern Taiwan over the past 24 years (1988-2012) were reviewed., Results: Among them, 48.8% (39/80) had pulmonary TB, 27.5% (22/80) had isolated extrapulmonary TB, and 23.7% (19/80) had disseminated TB. Most infected cases were aged either < 4 years or > 12 years. TB contact history was found in 42.5% (34/80) cases. Fourteen (17.5%) of the cases had CNS involvement. The most common presentations were fever (85.7%), signs of increased intracranial pressure (71.4%), drowsiness (64.3%), and focal neurological signs (57.1%). The major radiological findings were tuberculoma (50%), basilar enhancement (41.6%), infarction (41.6%), hydrocephalus (16.6%), and transverse myelitis (16.6%). The case fatality of CNS TB was 14.3% and 21.4% had neurologic sequelae., Conclusion: Findings suggest that positive exposure history and suspicious clinical presentations are important clues for further confirmatory laboratory and image studies in childhood TB. CNS TB usually presented as part of disseminated TB in children. Early diagnosis and treatment may lead to favorable outcomes in CNS TB., (Copyright © 2013. Published by Elsevier B.V.)

Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent years and accounts for 8 million deaths annually in the world. Central nervous system involvement is one of the most serious forms of this infection, acting as a prominent cause of morbidity and mortality in developing countries. The rising number of cases in developed countries is mostly attributed to factors such as the pandemic of acquired immunodeficiency syndrome and increased migration in a globalized world. Mycobacterium TB is responsible for almost all cases of tubercular infection in the central nervous system. It can manifest in a variety of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal infection may result in spondylitis, arachnoiditis, and/or focal intramedullary tuberculomas. Timely diagnosis of central nervous system TB is paramount for the early institution of appropriate therapy, because delayed treatment is associated with severe morbidity and mortality. It is therefore important that physicians and radiologists understand the characteristic patterns, distribution, and imaging manifestations of TB in the central nervous system. Magnetic resonance imaging is considered the imaging modality of choice for the study of patients with suspected TB. Advanced imaging techniques including magnetic resonance perfusion and diffusion tensor imaging may be of value in the objective assessment of therapy and to guide the physician in the modulation of therapy in these patients.

Extrapulmonary tuberculosis (EPTB) accounts for a significant proportion of tuberculosis cases worldwide. Nevertheless, the diagnosis is often delayed or even missed due to insidious clinical presentation and poor performance of diagnostic tests. Culture, the classical gold standard for tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. In this review the authors outline current diagnostic options for the main forms of EPTB. The authors also discuss the opportunities and challenges linked in particular to microbiological diagnostics and to the attempts to find a new gold standard test for EPTB. Finally, new biomarkers and tests currently under evaluation are hopefully on the way to introduce significant improvements in EPTB diagnosis, for which clinical suspicion will nevertheless be essential.

Central nervous system tuberculosis (CNS-TB) is a devastating manifestation of tuberculosis (TB) caused by the hematogenous spread of Mycobacterium tuberculosis. Here, I present a retrospective analysis of 20 CNS-TB cases in Israel, a country with a low incidence of TB over an 11-year period (2000-2010). Most of the cases were those of African migrants, with an increased prevalence in adult females and in those with HIV coinfections. Clinical manifestations were usually non-specific, and miliary infiltrates were rare. Lymphocytic meningitis was frequent with bacteriological confirmation in 50% of the cases. The yields of cerebrospinal fluid smear examinations were low (20%). Brain computed tomography revealed tuberculomas (45%) and hydrocephalus (15%). All patients received individual treatment on the basis of drug susceptibility patterns and adjunctive steroid therapy. However, 35% of the patients died within the first year and the mortality rate was strongly correlated to disease severity (90%), HIV coinfection (85%), and hydrocephalus (66%). Progress in new diagnostic tests and early treatment may improve the current high mortality and morbidity rates.

Tuberculosis remains a serious health problem worldwide, particularly affecting the poorest in both high-income and developing countries. It was declared a global emergency by the World Health Organization in 1993. Central nervous system (CNS) tuberculosis is caused by mycobacteria belonging to the Mycobacterium tuberculosis complex, and is acquired through inhalation of aerosolized droplet nuclei. Meningitis represents the most frequent and severe form of CNS tuberculosis. Parenchymal CNS involvement can occur in the form of tuberculoma or, more rarely, abscess. Also, damage of the spinal cord, roots, and spine can occur in the form of spinal meningitis, radiculomyelitis, spondylitis, or spinal cord infarction. Diagnosis remains a challenge due to the slow growth of the organisms and the low yield of cerebrospinal fluid cultures, as well as the frequent absence of evidence of infection elsewhere. This results in frequent empirical therapy, based on a combination of four drugs (isoniazid, rifampicin, pyrazinamide and ethambutol) for 2 months, followed by 10 additional months with two drugs (isoniazid and rifampicin) to a total duration of 12 months. Shorter regimens have also been successful, but there have been few controlled trials in patients with extrapulmonary disease. Corticoid therapy seems to be associated with a reduced risk of death, and is usually indicated. Evidence of multidrug resistance requires variable combinations of first- and second-line drugs; fortunately, resistance does not seem to represent a serious threat for CNS tuberculosis at present, but still requires the utmost vigilance., (© 2014 Elsevier B.V. All rights reserved.)

A 13-year-old immunocompromised girl developed neurotuberculosis. Arterial spin labeling technique indicated areas of hypoperfusion in the vascular territories of the left posterior cerebral artery and superior cerebellar artery without restricted diffusion, suggesting early tuberculous arteritis. MR angiography confirmed vascular involvement, so adjunctive anticoagulant therapy was initiated. Complete resolution of arterial spin labeling findings was observed 1 month later. This documents early tuberculous vasculopathy revealed by arterial spin labeling in a child with neurotuberculosis. Since there may be a paucity of clinical symptoms in the evolution of arteritis in neurotuberculosis, arterial spin labeling may help indicate early hypoperfusion and alert for modification of treatment before irreversible vascular damage occurs.

Granulomatous myelitis due to infection with Mycobacterium avium was diagnosed in a 4-year-old male neutered European mink (Mustela lutreola). The causative agent was detected by an acid-fast stain and further characterized by polymerase chain reaction and DNA sequencing of the PCR product. A thorough histological evaluation of the remaining organs revealed no granulomatous lesions or detectable acid-fast organisms. Although minks are generally highly susceptible for mycobacteria, localised infections, especially of the central nervous system, are unusual and may represent an atypical chronic form of the disease.

Tubercular abscess of the brain is a rare form of central nervous system tuberculosis. These lesions usually occur in the supratentorial compartment. They are associated with a state of immune deficiency. We report two immunocompetent individuals with tubercular abscess of the cerebellum and discuss the management of these lesions.

Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB, characterized morphologically by brain granulomas and tuberculous meningitis (TBM). Experimental strategies for the study of the host-pathogen interaction through the analysis of granulomas and its intrinsic molecular mechanisms could provide new insights into the neuropathology of TB. To verify whether cerebellar mycobacterial infection induces the main features of the disease in human CNS and better understand the physiological mechanisms underlying the disease, we injected bacillus Calmette-Guerin (BCG) into the mouse cerebellum. BCG-induced CNS-TB is characterized by the formation of granulomas and TBM, a build up of bacterial loads in these lesions, and microglial recruitment into the lesion sites. In addition, there is an enhanced expression of signaling molecules such as nuclear factor-κB (NF-κB) and there is a presence of inducible nitric oxide synthase (iNOS) in the lesions and surrounding areas. This murine model of cerebellar CNS-TB was characterized by cellular and biochemical immune responses typically found in the human disease. This model could expand our knowledge about granulomas in TB infection of the cerebellum, and help characterize the physiological mechanisms involved with the progression of this serious illness that is responsible for killing millions people every year., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously., Results: We screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum., Conclusions: Our findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children.

An estimated one-third of the world's population (2 billion people) is infected with the tubercle bacilli (TB), which is estimated to cause 6% of all deaths worldwide. Despite there being a decline in the incidence of tuberculosis seen in Europe, there are still some countries in the rest of the world where the estimated number of new cases is very high. When a person presents with persistent fever with or without neurological symptoms, the diagnosis of TB cannot be excluded. We present a case report of a 26-year-old male patient, who died of CNS tuberculosis. Such case studies will help keep neuroscience nurses alert to potential medical issues in multiethnic patient populations.

Background: Studies of the apoptosis mechanisms involved in the pathogenesis of tuberculosis have suggested that Mycobacterium tuberculosis can actively interfere with the apoptosis of infected cells. In vivo studies have been performed in adult populations but have not focused on this process in children. In the present study, we analyzed spontaneous T lymphocyte (PBT) apoptosis in the peripheral blood of children with central nervous system tuberculosis (CNS TB), before and after chemotherapy, and compared the results with healthy controls., Methods: A case-control study was conducted from January 2002 to June 2009. It included 18 children with CNS TB and 17 healthy controls. Spontaneous apoptosis of PBTs, including CD4+, CD8+ and CD8+/CD28+ T cells, was evaluated after 24 and 72 h of culture in complete medium, using the Annexin V detection test. Analysis was conducted before and after chemotherapy, and expression of the apoptotic markers CD95 (Fas) and Fas ligand (FasL) was evaluated., Results: Higher percentages of apoptotic T cells and CD4 lymphocytes were isolated from children with acute phase CNS TB than from children in the control group (p < 0.05). This difference significantly decreased after 60 days of specific treatment. In children with CNS TB, high levels of Fas ligand expression were detected in lymphocyte populations, associated with a high percentage of Fas positive cells, before and after treatment. In contrast to the CD4+ apoptosis profile, we did not find any significant difference in total CD8+ cell apoptosis between children with acute phase disease and the control group. However, the percentage of apoptotic CD8+/CD28+ T cells was significantly higher in the children with acute phase disease than in the healthy controls., Conclusions: Our findings indicate that CNS TB in pediatric patients increases the sensitivity of CD4 and CD8+/CD28+ T cells to apoptosis, suggesting a hypoergic status of this infection. This could play a key role in the immunopathogenesis of this complicated form of TB. Interestingly, specific chemotherapy is able to normalize both apoptosis sensitivity and T-cell activation.

Objective: To study the clinicalpathologic features of intracranial multiple lesions., Methods: The clinical, radiologic and pathologic features of intracranial multiple lesions in 62 cases during the period from 2005 to 2009 in Xuanwu Hospital were retrospectively reviewed., Results: There were 32 males and 30 females in 62 cases. The mean age of seize onset and duration of disease were 37.4-year-old and 11.6 months, respectively. The lesions could affect cerebral hemisphere, basal ganglia, brain stem, cerebellum and other parts, most lesions were located above the tentorium. Pathological diagnosis as follows: 13 patients with glioma; metastatic tumors in 13 cases; 12 cases of central nervous system infection; immune-mediated inflammatory demyelinating disease in 8 cases; 5 cases of primary lymphoma of central nervous system; primary angiitis of the central nervous system 3 cases; mitochondrial encephalopathy 2 cases; vein thrombosis in 2 cases; Rosai-Dorfman disease in 2 cases; 2 case of radiation encephalopathy. Among them, mitochondrial encephalopathy and vein thrombosis lesions located in the cortex; metastatic tumor and blood-borne infection mainly involving junction of grey and white matter; glioma, radiation encephalopathy and demyelinating disease include white matter lesions; vascular inflammation showed cortical and subcortical white matter lesions., Conclusions: A variety of tumor and non-neoplastic diseases can be expressed in intracranial multiple lesions, which gliomas, metastatic tumor and central nervous system infections are more common. In order to improve the diagnosis of intracranial multiple lesions, active work in the brian biopsy, study the clinical, imaging and pathological findings must be closely.

Chronic granulomatous CNS infections may be caused by tuberculosis, fungi and rarely by free-living amoeba, especially in immunocompromised individuals. We report a rare, fatal case of granulomatous amoebic encephalitis in an immunocompetent patient mimicking CNS tuberculosis, and review the imageological features and diagnostic tests., (© 2010 Japanese Society of Neuropathology.)

Tuberculous encephalopathy (TBE) is an established disease entity of diffuse cerebral damage occurring with tuberculosis and an underlying immune pathogenesis. However, the presence of this disease entity remains controversial. We report a 15-year-old boy with seizures and a progressive decline of cognitive function. Brain MRI showed diffuse, hyperintense lesions in the white matter on a T2-weighted image, with gadolinium enhancement on a T1-weighted image. Brain biopsy revealed demyelination and granuloma in the white matter. Ziehl-Neelsen staining showed acid-fast bacilli in the granulomas. Antituberculous medication with concomitant steroid treatment resulted in radiological resolution in addition to clinical improvement. Clinicopathological evidence in this case provides additional convincing evidence of TBE as a disease entity distinct from tuberculous meningitis., (Copyright © 2011 S. Karger AG, Basel.)

Tuberculous cerebellar abscess is a rare manifestation of central nervous system tuberculosis. An 8-year-old boy is described who presented with acute hydrocephalus and right hemiparesis owing to a cerebellar abscess.

Objectives: The purpose of this study is to amplify the knowledge base of the epidemiology, symptoms, and signs of extrapulmonary tuberculosis (EPTB) in Afghanistan., Methods: This is a retrospective review of EPTB diagnosed at CURE International Hospital and CURE Family Health Center (FHC) in Kabul, Afghanistan during a recent 20-month period., Results: One hundred eighteen cases were identified from patients presenting to the hospital and FHC. This group represents the spectrum of EPTB seen at a single referral center in Kabul. The ratio of females to males was 2.03:1. Lymph node tuberculosis comprised the greatest number of EPTB cases (37.3%, n=44). The central nervous system was the next most frequent site of EPTB involvement (20.3%, n=24), followed in descending order by skeletal, pleural, abdominal, cutaneous, genitourinary, pericardial, miliary, and breast tuberculosis., Conclusions: The 2:1 ratio of female to male EPTB cases coincides with the unusual epidemiologic pattern seen in smear-positive pulmonary TB in Afghanistan. As the first epidemiological report of EPTB from Afghanistan, this study illustrates the varied presentations of EPTB that should be known by healthcare workers throughout the country., (Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Tubeculosis commonly involves the nervous system, but involvement of spinal cord in the form of intramedullary tuberculoma is rare and concurrent occurrence of cranial and intramedullary tuberculomas is extremely rare. We report a case of concurrent occurrence of intramedullary tuberculoma with multiple intracranial tuberculomas in a young girl from Islamabad, who presented with one month history of paraplegia and with a sensory level at T6. MRI spine showed a well circumscribed lesion opposite T6, which was diagnosed as intramedullary tuberculoma. On cranial imaging, she was found to have multiple round contrast enhancing lesions which were diagnosed as intracranial tuberculomas based on their typical MRI findings. She had complete recovery with conventional treatment of ATT and steroids, without any surgical intervention. The follow-up MRI of patient showed disappearance and complete resolution of most of the lesions.

The lack of specific symptoms and signs in patients with tuberculous meningitis makes early diagnosis difficult. In this report, we reviewed the clinical features and laboratory findings of 6 infants with central system nervous tuberculosis during a 10-year period. One of the patients had multifocal tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact source was identified in only 2 patients. All 6 patients had abnormal cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic predominance. Computerized tomography (CT) and/or magnetic resonance imaging (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient developed pontocerebellar and pituitary tuberculomas, which were responsible for compression and diabetes insipidus, 1 year after antituberculous treatment. These localizations are very rare. On the follow-up, 3 patients had hypoacousia and only 1 had severe sequelae, despite a diagnostic delay.

Pathologic processes within the cerebellopontine angle (CPA) may present because of mass effect on local structures or on the pons or cerebellum. MR imaging is superior to CT for evaluation of the complete extent of a CPA mass and for characterization of its likely nature. MR is also superior to CT for the detection of leptomeningeal processes. Arriving at a short list of differential diagnoses requires a methodical approach, keeping in mind the location, signal, diffusion, and enhancement characteristics of the lesions. Advanced MR imaging techniques, such as magnetic resonance spectroscopy, are not usually needed routinely but may aid in the differential diagnosis when presented with atypical masses.

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

Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesis of CNS tuberculosis are based on necropsy studies done in 1933, which suggest that tuberculous meningitis develops subsequent to the rupture into the cerebrospinal fluid of tuberculomas that form around M. tuberculosis deposited in the brain parenchyma and meninges during the initial hematogenous dissemination. Foreign antigens including pathogens deposited in the brain parenchyma are not detected efficiently by the immune system in the CNS. These experimental data may explain the clinical observation of delayed "paradoxical" enlargement or development of intracranial tuberculomas, observed several weeks to months in patients receiving anti-tuberculous therapy. Since severe sequelae are observed even when CNS tuberculosis is treated effectively, it is important to develop preventive strategies for this disease. Recent data utilizing animal models suggests that, in addition to host factors, M. tuberculosis genes and their encoded proteins may contribute specifically to bacterial invasion and survival in the CNS. Understanding how these microbial factors affect CNS disease would be essential to developing such preventive strategies.

Infection with human immunodeficiency virus (HIV) clade C is the most common HIV infection worldwide, yet its impact on the nervous system remains largely unknown. Autopsy studies from regions affected by this virus are scarce, and HIV dementia has only rarely been reported from these countries. Most patients who develop neurologic complications die of opportunistic infections. We thus conducted a neuropathologic study from a single institution in India to characterize the HIV-infected cells in the inflammatory infiltrates in a total of 15 cases (5 patients each who died of either CNS toxoplasmosis, tuberculosis, or cryptococcal meningitis). Nearly, all patients had HIV-infected cells in the brain, although these cells were most abundant in patients with toxoplasma encephalitis. Interestingly, none of the patients had any multinucleated giant cells. HIV-infected cells were found in the parenchyma, perivascular regions, and choroid plexus and found infiltrating the parenchyma from the meninges, suggesting multiple portals of entry into the brain. These findings suggest the possibility that patients, even if successfully treated for an opportunistic inflection, may be at high risk of developing HIV encephalitis and subsequent dementia.