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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Neurologic diseases in HIV-infected patients.

Since the introduction of highly active antiretroviral therapy there has been an improvement in the quality of life for people with HIV infection. Despite the progress made, about 70% of HIV patients develop neurologic complications. These originate either in the central or the peripheral nervous system (Sacktor, 2002). These neurologic disorders are divided into primary and secondary disorders. The primary disorders result from the direct effects of the virus and include HIV-associated neurocognitive disorder (HAND), HIV-associated vacuolar myelopathy (VM), and distal symmetric polyneuropathy (DSP). Secondary disorders result from marked immunosuppression and include opportunistic infections and primary central nervous system lymphoma (PCNSL). A differential diagnosis which can be accomplished by detailed history, neurologic examination, and by having a good understanding of the role of HIV in various neurologic disorders will help physicians in approaching these problems. The focus of this chapter is to discuss neuropathogenesis of HIV, the various opportunistic infections, primary CNS lymphoma, neurosyphilis, CNS tuberculosis, HIV-associated peripheral neuropathies, HIV-associated neurocognitive disorder (HAND), and vacuolar myelopathy (VM). It also relies on the treatment recommendations and guidelines for the above mentioned neurologic disorders proposed by the US Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America.

Tuberculosis.

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.

Tuberculous cerebellar abscess in immunocompetent individuals.

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 tuberculoma.

The aim of this study was to outline the clinicoradiological features of central nervous system (CNS) tuberculoma, and highlight the importance of early treatment. We conducted a retrospective analysis between 1999 and 2008. Clinicoradiological, pathological and follow-up data of 23 patients were reviewed and analysed. The mean age at presentation was 30.3 years (range=17-43 years), and the average disease duration at presentation was six months (range=1-19 months). The tuberculoma location in the cohort was: thoracic region (10 patients); cervical region (six), cervicothoracic region (three); thoracolumbar region (one); and intracranial (six); three patients (13%) had multiple lesions. Nineteen (82.6%) and 15 (65.2%) patients had sensory-motor and bowel/bladder involvement, respectively. Two patients presented with headache and consciousness disturbance, and two patients had a history of pulmonary Koch's disease. Five patients had a history of tuberculous meningoencephalitis, and one patient had a history of enlarged cervical lymph nodes. Twenty-one patients underwent surgery, and two received conservative treatment; all patients received anti-tuberculosis therapy for 18 months. Seventeen of the 21 surgical patients and both conservatively managed patients achieved improved neurological function (with Karnofsky Performance Scale scores of 90-100). Patients presenting at an advanced disease stage had a poorer outcome. CNS tuberculoma is a benign condition with a good prognosis and effective therapy options. Enhanced brain and spine MRI should be performed to ensure the diagnosis is not missed. Early surgical decompression is recommended for intramedullary tuberculoma. Craniotomy is indicated for patients with intracranial hypertension, while more conservative therapy is appropriate for patients who have intracranial tuberculomas without intracranial hypertension.