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

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

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

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

Neuroimaging of central nervous system tuberculosis.

A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.

Tuberculosis revisted: classic imaging findings in childhood.

Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.

Pediatric Neurotuberculosis: A cases series and review of the literature.

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.

Central Nervous System Mycobacterium Infection: Tuberculosis and Beyond.

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.

Absence of posterior pituitary bright spot in adults with CNS tuberculosis: A case-control study.

INTRODUCTION: Current diagnostic methods used in Central Nervous System Tuberculosis (CNS TB) are limited by the paucibacillary nature of this form of tuberculosis. Posterior pituitary bright spot (PPBS) refers to an area of T1 hyperintensity in the posterior pituitary in MR imaging of the brain. It is found in 80-90% of healthy children and adults. In children with CNS TB, nearly half have absence of PPBS. This finding has not been described in adults. Our study looked for absence of PPBS in MR imaging and its association with CNS tuberculosis. OBJECTIVE: To study prevalence of the absence of PPBS in patients with CNS tuberculosis when compared to a control group of normal patients. METHODS: This was a retrospective case-control study of 100 patients with CNS tuberculosis and 200 controls (matched in 1:2 ratio) of patients with normal MRI brain. The MRI images were presented to a blinded radiologist in a randomised sequence to report for absence of PPBS. The data was subsequently analysed to look for association of absence of PPBS with CNS tuberculosis. RESULTS: Absence of PPBS (cases (47%), controls (8.5%)) was significantly associated with CNS tuberculosis in (Odds ratio-7.90, 95%CI 4.04-15.44, P-value<0.0001). The specificity, sensitivity, positive predictive value and positive likelihood ratio are 91.5%, 47%, 73.4% and 5.53 respectively. Adding of absence of PPBS as an additional radiological feature in diagnosis of CNS TB increased the sensitivity from 77% to 84%. CONCLUSION: Absence of PPBS is significantly associated with CNS tuberculosis and could be a relatively simple diagnostic aid in the diagnosis of CNS tuberculosis.

Pulse corticosteroids for the management of extensive CNS tuberculosis presenting with acute-onset quadriparesis.

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy.

Tuberculous Encephalitis May Be Undetectable on Magnetic Resonance Imaging but Detectable on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Neurotuberculosis (NT) continues to be a global health problem with severe morbidity and mortality. The manifestations of NT are well-known and encompass forms such as meningitis, tuberculomas, military tuberculosis, ventriculitis, and brain abscess. Data of all patients with central nervous system tuberculosis who underwent magnetic resonance imaging (MRI) and/or 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) were analyzed. Over a 7-year period (2014-2021), we encountered three patients who had dense neurological deficits and 18F-FDG PET-CT results suggesting focal cortical encephalitis. 18F-FDG PET-CT demonstrated focal hypermetabolism involving focal-regional areas of the left hemisphere that corresponded to clinical deficits in two of the three patients. Follow-up 18F-FDG PET-CT showed improvement in cortical hypermetabolism in all three patients that corresponded with clinical improvement. MRI of the brain with contrast showed subtle leptomeningeal enhancement in these areas, along with other features of NT, but it could not detect cortical involvement. A literature review also revealed some previous descriptions that seemed to be consistent with tuberculous encephalitis (TbE). TbE seems to be a distinct subset of NT and may coexist with other features of NT or disseminated tuberculosis. It may be detected by 18F-FDG PET-CT even when brain MRI does not show any evident abnormality to explain a focal neurological deficit. 18F-FDG PET-CT can be considered during the evaluation and monitoring of NT to detect TbE. The presence of TbE may affect the prognosis and treatment duration of NT.

The ring in the neck-managing paraparesis in cervical intramedullary tuberculoma: Inputs from a neurorehabilitation desk.

Central nervous system (CNS) tuberculosis is a less common entity even in endemic countries like India. Involvement of spine is much less frequent than brain, but concurrent involvement of brain and spine by tuberculoma is rare. A 23-year-old female with paraparesis was diagnosed as having cervical ring enhancing lesion in MRI suggesting intramedullary tuberculoma along with long segment cervicodorsal edema. On brain screening she had multiple intracerebral tuberculomas without any evidence of tuberculosis elsewhere in the body. She was treated with a multidisciplinary approach including neurological management and neurorehabilitation, with remarkable clinical recovery. In presence of acute neurological deficit, early start of rehabilitation along with medical management can give outstanding results in terms of neuro-recovery and improvement of residual neurodeficits. Surgical intervention can be avoided in many cases.

Neurological issues during severe COVID-19 in a tertiary level hospital in Western India.

BACKGROUND: India has the second largest COVID-19 epidemic in the world as per current estimates. Central and peripheral nervous system involvement in COVID-19 (Neuro COVID-19) has been increasingly identified and reported. This letter is the first report of the spectrum of neurological disorders observed in patients with severe COVID-19 from a resource limited setting like India. Till October 30th 2020, Noble hospital and research center, Pune, India has admitted 2631 patients of COVID-19. Out of these, 423 patients had severe COVID-19. NEUROLOGIC COMPLICATIONS IN SEVERE COVID-19 IN PUNE, INDIA: Of the 423 patients with severe COVID-19, 20 (4.7%) had pre-existing neurologic co-morbidities, with cerebrovascular disease (8 patients) being the most common. Poliomyelitis (4 patients) was also an important co-morbidity associated with severe COVID-19. Bodyache or myalgia (207/423, 49 %) and headache (59/423, 13.9 %) were the most common neurologic symptoms observed in patients. Encephalopathy (22/423, 5.2 %) and new onset large vessel ischemic stroke secondary to cerebral artery thrombosis (5/423, 1.1%) were the most common secondary neurologic complications noted in our cohort. Two cases of COVID-19/central nervous system tuberculosis co-infection were also identified. CHALLENGES IN MANAGEMENT OF NEURO COVID-19 IN INDIA: Various challenges like an overwhelmed health care system, inadequate workforce, lack of exhaustive reporting of symptoms and poor availability of neuroimaging in ventilated COVID-19 patients leads to underestimation of Neuro COVID-19 in resource limited settings like India.

A woman with disseminated tuberculosis experienced preterm delivery, fallopian tube pregnancy, and delivered successfully following in vitro fertilization: a case report.

BACKGROUND: Disseminated tuberculosis (TB) is a fatal disease resulting from hematogenous dissemination of Mycobacterium tuberculosis. Spontaneous pregnancy rate of women with TB is low; furthermore, live birth, spontaneous abortion or ectopic pregnancy may be the outcomes even if pregnancy occurs. CASE PRESENTATION: We report a case of a woman with disseminated TB who had a series of complications including preterm delivery with congenital TB and infant death of pulmonary TB, fallopian tube pregnancy. She was treated by in vitro fertilization-embryo transfer (IVF-ET), and gave birth to a healthy baby. CONCLUSION: Disseminated TB has a significant impact on female fertility. We should take more active efforts to diagnose and treat this disease in a timely fashion. Moreover, IVF treatment is a feasible approach for an infertile woman after TB.

Central nervous system tuberculosis.

The purpose of this article is to review the many facets of central nervous system tuberculosis (CNS-TB). The entities described are tuberculous meningitis (TBM) and its complications, spinal cord disorders, tuberculomas and co-infection with the human immune-deficiency virus (HIV). The latter has become a common problem worldwide becoming a more fulminant disease. The accuracy of the conventional and the modern molecular techniques for the diagnosis of TBM have a high specificity but a low to moderate sensitivity. Computerised tomographic scans and magnetic resonance imaging have many characteristic features which have vastly improved the diagnostic accuracy of CNS-TB. The recommended therapeutic regimens are an extrapolation of the regimen used for pulmonary TB, hence the optimal composition, dosage and duration of the therapy are not yet established. Multidrug resistant TB is emerging as a global threat and the delay in recognition of drug resistance combined with the lack of data on appropriate drug regimen adds to its high mortality.

[Central nervous system tuberculosis : don't miss the diagnosis !] / Errance diagnostique dans un cas de tuberculose du système nerveux central Nebie A (1), Ali D (1), Bosquee L (2), Gorur Y (3), Cardos B (4).

We are presented a 35-year-old patient with no previous relevant medical history who was admitted to the emergency department for fever, altered mental status and diffuse abdominal pain. Initial evaluation failed to the demonstrated the presence of thoracic or abdominal deep infection. The clinical course was marked by a deterioration of the neurological condition. The cerebral MRI showed diffuse and extensive involvement of the brainstem and cerebellar hemispheres associated with hydrocephalus consistent with tuberculous meningoencephalitis. Antituberculous therapy was started with some delay but no clinical improvement was achieved and the patient died.

Une patiente âgée de 35 ans, sans antécédents médicaux particuliers, est admise au service des urgences pour fièvre accompagnée d'un syndrome confusionnel et de douleurs abdominales diffuses. La prise en charge initiale ne permet pas de mettre en évidence une infection profonde au niveau thoracique et abdominal. L'évolution clinique est marquée par une détérioration de son état neurocognitif. L'IRM cérébrale montre une atteinte diffuse et étendue des hémisphères cérébraux, du tronc cérébral et du cervelet, associée à une hydrocéphalie, liée à une probable méningo-encéphalite tuberculeuse. Un traitement antituberculeux est instauré avec un certain délai, mais aucune amélioration clinique n'est observée et la patiente finit par décéder.

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

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

Intradural extramedullary tuberculoma of the spinal cord in patient of tubercular meningitis - an uncommon scenario.

Intradural extramedullary tuberculoma of the spinal cord (IETSC) is a rare and unanticipated manifestation of CNS tuberculosis. A 28 years old female diagnosed case of tubercular meningitis (TBM), already on antitubercular therapy (ATT) for last nine months, developed sensory and motor weakness in lower limbs along with saddle anaesthesia. Magnetic resonance imaging (MRI) with contrast of the spine revealed the presence of multiple space occupying lesions in dorsal spinal cord. She received oral steroid therapy for six weeks with escalation of ATT after which neurological functions improved remarkably.