Surgery for Central Nervous System Tuberculosis in Children.

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

Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review.

Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology.

Cerebral tuberculosis in a patient with systemic lupus erythematosus following cyclophosphamide treatment: a case report.

Central nervous system (CNS) tuberculosis (TB) is a rare but catastrophic event in patients with systemic lupus erythematosus (SLE). Here we report a case of cerebral TB in a patient with lupus myocarditis and nephritis, following cyclophosphamide immunosuppression. To our knowledge this is the first reported case of cerebral TB in SLE in a non-endemic country. A 31-year-old female with SLE and a history of regular travel to Kenya presented to our centre with clinical features of acute heart failure. She was diagnosed with severe lupus myocarditis, and a renal biopsy also confirmed lupus nephritis. Prior to admission, she had also had a cough, fever and weight loss and was under investigation for suspected TB infection. She was treated with ivabradine, beta-blockers and diuretics together with methylprednisolone and cyclophosphamide immunosuppression. Subsequent sputum cultures confirmed TB and she was commenced on triple therapy. Despite this, she developed confusion, dizziness, blurred vision and fluctuating consciousness. Magnetic resonance imaging (MRI) and lumbar puncture revealed CNS TB infection resulting in meningitis. This was later complicated by obstructive hydrocephalus due to TB abscesses. A ventriculoperitoneal (VP) shunt was inserted and TB medications were given intravenously (IV) with dexamethasone. Following a prolonged hospital admission, the patient eventually recovered and rituximab treatment was used to control her SLE. TB infection has been associated with SLE flares. It is likely in this case that TB exacerbated a lupus flare and subsequent immunosuppression resulted in mycobacterial dissemination to the CNS. Systemic and CNS features of TB and SLE are difficult to distinguish and their contemporaneous management represents a diagnostic and therapeutic challenge.

Tuberculosis of the central nervous system in children.

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.

Neuro-otologic manifestations of tuberculosis. "The great imitator".

OBJECTIVE: To demonstrate the different neuro-otologic clinical presentations of tuberculosis. STUDY DESIGN: Retrospective clinical analysis. RESULT: 83.3% of the cases of ear or central nervous system TB were without concomitant lung disease. 2 cases had primary infection in the central nervous system. The neuro-otologic manifestation was as follows: 85.7% sensorineural hearing loss; 42% polyneuropathy. 71.4% had granulation tissue. 2 had normal otoscopy. In 6 patients the histopathology and Ziehl Neelsen were confirmatory. One case was confirmed by the positive response to treatment with antituberculosis drugs. CONCLUSIONS: Tuberculosis has a wide variety of neurotologic manifestations from chronic otitis media cadres to vestibular, audiological and neurological manifestations as well as a large variability in imaging studies.

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.

Guidelines versus ground lines: Tuberculosis of the central nervous system.

AIM: This questionnaire-based national survey is aimed at understanding the patterns of practice of various aspects of central nervous system (CNS) tuberculosis (TB) among neurologists. SETTINGS AND DESIGN: Neurology department of a tertiary medical college. MATERIALS AND METHODS: A questionnaire was sent through email to all practicing neurologists in India. The responses were analyzed. STATISTICAL ANALYSIS: Inferential statistics. RESULTS: In all, 144 responses were received (out of the 853 questionnaires sent). The major discrepancies were in the primary antitubercular drug regimen (HRZE + HR), duration for tubercular meningitis (TBM) [12 months] and tuberculoma (12-18 months) to develop, follow-up (varied), linezolid use (varied), proportion of drug-resistant cases (<25%), and not taking histological aids (91%). The cerebrospinal fluid (CSF) TB polymerase chain reaction (PCR) utility (75%), not using CSF adenosine deaminase [ADA] (58%), the strategy to stop antitubercular drugs, and the use of steroids (77%) were according to guidelines. CONCLUSION: The present survey, for the first time, provides ground-level evidence of various aspects of CNS TB as practiced by neurologists in India. The major diversity was observed in therapeutics such as the choice of antitubercular drugs, its duration, linezolid use beyond the recommended duration, and knowledge of drug resistance. The monitoring aspects of CNS TB also showed variations. The investigational aspects of CNS TB such as using TB PCR, not using CSF ADA, and regular neuroimaging revealed a good clinical practice. Other CSF parameters require uniformity. This survey thus helps to identify areas of future work in CNS TB in India.

Uncommon case of Mycobacterium bovis brain abscess complicated by suppurative fistula, and review of the literature. / Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa y revisión de la bibliografía.

INTRODUCTION: Mycobacterium bovis is an infrequent cause of central nervous system tuberculosis in Spain, with few cases described in the literature. Since compulsory pasteurization of milk and implementation of eradication programs on infected cattle, human sporadic illness with this organism has dramatically declined in developed countries. CASE REPORT: A 71-year-old immunocompromised male, who presented a calvarial lytic lesion. A craniotomy for the total resection of the lesion was performed and the microbiology results were positive for M. bovis, therefore antituberculous therapy was initiated. Despite of the correct treatment, the patient developed a tuberculous abscess that required an aggressive surgical management followed by a suppurative fistula. Based on the treatment of tuberculous lymphadenitis, we decided to perform a conservative management with antituberculous therapy (isoniazid + rifampicin + ethambutol + moxifloxacin + steroids during 12 months) and avoided new surgical cleanings of the surgical bed obtaining a good response and a good clinical evolution. CONCLUSIONS: As far as we know, this is the first case reported of a suppurative fistula after the resection of a cerebral abscess caused by M. bovis, therefore, there is no report in the literature about the treatment of this complication.

TITLE: Caso insólito de absceso cerebral por Mycobacterium bovis complicado con fístula supurativa y revisión de la bibliografía.Introducción. Mycobacterium bovis es una causa infrecuente de tuberculosis del sistema nervioso central en España, del cual existen pocos casos descritos en la bibliografía. Desde la pasteurización obligatoria de la leche y la implementación de programas de erradicación del ganado infectado, la enfermedad esporádica humana con este organismo ha disminuido drásticamente en los países desarrollados. Caso clínico. Varón inmunoafectado de 71 años, que presentaba una lesión lítica esporádica en la calota. Se realizó una craneotomía de la lesión y los resultados de microbiología fueron positivos para M. bovis, por lo que se inició tratamiento con terapia antituberculosa. A pesar del tratamiento correcto, el paciente desarrolló un absceso tuberculoso, que requirió un tratamiento quirúrgico agresivo, seguido de una complicación con una fístula supurativa. Sobre la base del tratamiento descrito para la linfadenitis tuberculosa, se decidió realizar un tratamiento conservador de la fístula supurativa, sin realizar nuevas limpiezas del lecho quirúrgico, y mantener de manera prolongada la terapia antituberculosa (isoniacida + rifampicina + etambutol + moxifloxacino + esteroides durante 12 meses), con lo que presentó una buena evolución clínica. Conclusiones. Hasta la fecha, éste es el primer caso descrito de una fístula supurativa después de la resección de un absceso cerebral causado por M. bovis, por lo que no existe en la bibliografía artículo alguno que describa el tratamiento adecuado de esta complicación.

Primary Pituitary Tubercular Abscess: A Case Report.

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.

Experimental animal models of central nervous system tuberculosis: A historical review.

Animal models are and will remain valuable tools in medical research because their use enables a deeper understanding of disease development, thus generating important knowledge for developing disease control strategies. Central nervous system tuberculosis (CNS TB) is the most devastating disease in humans. Moreover, as the variability of signs and symptoms delay a timely diagnosis, patients usually arrive at the hospital suffering from late stage disease. Therefore, it is impossible to obtain fresh human tissue for research before an autopsy. Because of these reasons, studies on human CNS TB are limited to case series, pharmacological response reports, and post mortem histopathological studies. Here, we review the contribution of the different animal models to understand the immunopathology of the disease and the host-parasitic relationship, as well as in the development of new strategies of vaccination and to test new drugs for the treatment of CNS TB.

Holistic care of complicated tuberculosis in healthcare settings with limited resources.

In recent years, most of the focus on improving the quality of paediatric care in low-income countries has been on improving primary care using the Integrated Management of Childhood Illness, and improving triage and emergency treatment in hospitals aimed at reducing deaths in the first 24 hours. There has been little attention paid to improving the quality of care for children with chronic or complex diseases. Children with complicated forms of tuberculosis (TB), including central nervous system and chronic pulmonary TB, provide examples of acute and chronic multisystem paediatric illnesses that commonly present to district-level and second-level referral hospitals in low-income countries. The care of these children requires a holistic clinical and continuous quality improvement approach. This includes timely decisions on the commencement of treatment often when diagnoses are not certain, identification and management of acute respiratory, neurological and nutritional complications, identification and treatment of comorbidities, supportive care, systematic monitoring of treatment and progress, rehabilitation, psychological support, ensuring adherence, and safe transition to community care. New diagnostics and imaging can assist this, but meticulous attention to clinical detail at the bedside and having a clear plan for all aspects of care that is communicated well to staff and families are essential for good outcomes. The care is multidimensional: biomedical, rehabilitative, social and economic, and multidisciplinary: medical, nursing and allied health. In the era of the Sustainable Development Goals, approaches to these dimensions of healthcare are needed within the reach of the poorest people who access district hospitals in low-income countries.

Intradural spinal tuberculosis in the absence of vertebral or meningeal tuberculosis: a case report.

We present a patient with spinal intradural tuberculosis in the absence of both vertebral and meningeal tuberculosis. Diagnosis was made based on intra-operative findings and was confirmed by histopathology. Early surgical decompression along with a combination of steroid and antitubercular therapy resulted in a good outcome. At 26-month follow-up, the patient regained bladder control and was able to walk with support. Clinical features, magnetic resonance imaging, and intra-operative findings are described. Pathology and the relevant literature are discussed.

Tuberculosis infection presenting as brain abscess in an immunocompromised host.

Despite advances in modern treatment, tuberculosis remains an ever-present problem. With the HIV epidemic, the prevalence of tuberculosis has risen. Contributing to this trend has been the development of multi-resistant tuberculosis strains, as well as rising immigration from nations where tuberculosis is endemic. Although tuberculosis most commonly manifests as a pulmonary process, milary tuberculosis is also on the rise. Neurotuberculosis, a rare but dangerous progression of pulmonary tuberculosis, remains a difficult diagnostic and treatment dilemma to practitioners both in the United States and abroad. We describe an unusual presentation of neurotuberculosis infection in a previously asymptomatic patient. Early recognition and treatment of intracranial tuberculosis is important if mortality is to be prevented.

Tuberculous otitis media with mastoiditis and central nervous system involvement.

Tuberculosis of the middle ear and mastoid is currently a rare disease in developed countries, but this disease still occurs and may cause serious consequences. We report a case of disseminated tuberculosis involving the middle ear, mastoid, lung and central nervous system. Tuberculosis should be considered in the differential diagnosis of chronic ear drainage, especially in young children.

Central nervous system (CNS) tuberculosis following allogeneic stem cell transplantation.

Tuberculosis is an uncommon infectious complication after stem cell transplantation. We report a patient who presented with a brain mass, 3 months after pulmonary tuberculosis had been diagnosed and while he was receiving triple antituberculous therapy. He had extensive chronic GVHD. The diagnosis was made after biopsy of the lesion. The cerebral mass was excised, antituberculous treatment was maintained and the patient made a complete neurologic recovery. Six months later, he died of gram-negative septic shock. Mycobacterial infections should be considered in allograft recipients with chronic GVHD and solid lesions in the brain. Bone Marrow Transplantation (2000) 25, 567-569.

Central nervous system tuberculosis.

Involvement of the central nervous system (CNS) by Mycobacterium tuberculosis, particularly meningitis, is the most severe form of tuberculous infection. Parenchymal CNS involvement can occur in the form of tuberculoma or, more rarely, abscess. Although surgery was initially advocated as the mainstay of therapy, more recent evidence suggests that parenchymal forms of CNS tuberculosis can be cured with medical treatment alone. Also, damage of the spinal cord, roots, and spine can occur in the form of spinal meningitis, radiculomyelitis, spondylitis, or spinal cord infarction.

Tuberculosis of the central nervous system in children.

Tuberculosis remains one of the most common and important infectious diseases in the world. Between 1% and 2% of children with untreated tuberculosis infection will develop tuberculous meningitis. In 1997, 186 cases of tuberculous meningitis were reported in the United States. The initial clinical manifestations of tuberculous meningitis are protean, making early disease difficult to recognize. The clinical and radiographic manifestations of tuberculous meningitis result from the combination of basilar meningitis, infarction, and vasculitis. Early diagnosis can be problematic as Mycobacterium tuberculosis is difficult to detect by rapid tests. Although the response to antituberculosis chemotherapy is generally favorable, complications commonly occur, particularly if the diagnosis is delayed. With appropriate public health management of known tuberculosis cases, cases of CNS tuberculosis in children can be prevented.

Intramedullary spinal tuberculoma: a case report.

STUDY DESIGN: A case report showing an intramedullary thoracic spinal tuberculoma secondary to pulmonary tuberculosis in a 16-year-old patient with findings of subacute spinal cord compression. OBJECTIVES: The significance and the use of magnetic resonance imaging in the diagnosis of intramedullary tuberculoma, and the treatment of the patient that involves surgically the excision of intramedullary lesion followed by appropriate antituberculous therapy. SUMMARY OF BACKGROUND DATA: Tuberculomas of spinal cord are rare entities. The possibility of intramedullary tuberculoma should be seriously considered when an intraspinal mass is found, provided that pulmonary tuberculosis is present in the history of the patient. METHOD: Th4-Th5 laminectomy was performed. Intramedullary tuberculoma was excised through a myelotomy. Antituberculous treatment was applied after the surgery. RESULTS: Excellent clinical outcome was obtained with a combination of both medical and surgical treatments. CONCLUSION: The intramedullary spinal tuberculoma, although a rare entity, must be considered in the differential diagnosis of the spinal cord compression in patients with a history of tuberculosis, human immunodeficiency virus, and those who have a bad socioeconomic condition and bad nutrition habit. When confronted with a progressing neurologic deficit, a combination of microsurgical resection and antituberculous chemotherapy with the avoidance of steroids should be the choice of treatment for intramedullary tuberculomas.