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.

Neurotuberculosis: A mystery seeking it's answers in pulmonary tuberculosis.

Neurotuberculosis remains a mystery and presents a formidable challenge in diagnosis and management. While pulmonary tuberculosis has a well understood pathophysiology and well researched management strategies, CNS tuberculosis still has plenty of unanswered questions. The purpose of this review is to highlight the debatable issues in the current understanding of the clinical, diagnostic, and therapeutic aspects of Neurotuberculosis.

Distinguishing clinical characteristics of central nervous system tuberculosis in immunodeficient and non-immunodeficient individuals: a 12-year retrospective study.

BACKGROUND: Central nervous system tuberculosis (CNS TB) is a severe Mycobacterium tuberculosis (MTB) infection. It is unclear whether a patient's immune status alters the clinical manifestations and treatment outcomes of CNS TB. METHODS: Between January 2007-December 2018, chart reviews of CNS TB, including tuberculous meningitis (TBM), tuberculoma/abscess, and TB myelitis, were made. Subjects were categorized as immunodeficient (ID) and non-immunodeficient (NID). RESULTS: Of 310 subjects, 160 (51.6%) were in the ID group-132 (42.6%) had HIV and 28 (9.0%) had another ID, and 150 (48.4%) were in the NID group. The mean age was 43.64 ± 16.76 years, and 188 (60.6%) were male. There were 285 (91.9%) TBM, 16 (5.2%) tuberculoma/abscess, and 9 (2.9%) myelitis cases. The TBM characteristics in the ID group were younger age (p = 0.003), deep subcortical location of tuberculoma (p = 0.030), lower hemoglobin level (p < 0.001), and lower peripheral white blood cell count (p < 0.001). Only HIV individuals with TBM had an infection by multidrug-resistant MTB (p = 0.013). TBM mortality was varied by immune status -HIV 22.8%, other ID 29.6%, and NID 14.8% (p < 0.001). Factors significantly associated with unfavorable outcomes in TBM also differed between the HIV and NID groups. CONCLUSIONS: TBM is the most significant proportion of CNS TB. Some of the clinical characteristics of TBM, such as age, radiographic findings, hematological derangement, and mortality, including factors associated with unfavorable outcomes, differed between ID and non-ID patients.

Diagnostic Dilemma of Central Nervous System Tuberculosis with Neurocysticercosis and Neurosarcoidosis: A Case Report.

Multiple ring-enhancing lesions are commonly encountered abnormalities in neuroimaging. There are many differentials for such lesions as infections, neoplasms, vascular lesions, inflammatory and demyelinating conditions, and granulomatous diseases. In developing countries, tuberculoma and neurocysticercosis are the two important etiologies to be considered. This case report illustrates how multiple ring-enhancing lesions can lead to our management in one direction while the true diagnosis remains elusive. A 53-year-old male who presented with a headache was initially diagnosed and treated as neurocysticercosis, then neurosarcoidosis ultimately turned out to be a case of Central Nervous System Tuberculosis on further evaluation. Consideration of only clinical scenarios and neurological imaging can lead to diagnostic inaccuracy, mismanagement and poor outcome, therefore, other supporting lab investigations should be considered for making a correct diagnosis. Keywords: brain; case reports; neurocysticercosis; sarcoidosis; tuberculoma.

Seizures and epilepsy associated with central nervous system tuberculosis.

Central nervous system (CNS) tuberculosis is a life-threatening condition that usually presents with seizures, particularly in children and HIV-infected patients. Tuberculous meningitis (TBM) and tuberculomas are the two forms of CNS tuberculosis that can present with seizures. Seizures usually resolve after successful treatment of the underlying infection. However, the success of the treatment is usually based on an early diagnosis. Delay in the treatment of CNS tuberculosis increases the risk of its associated complications, such as stroke. This would lead to the development of epilepsy. Early seizures may be related to meningeal irritation and cerebral edema, whereas late seizures are often associated with structural brain lesions that generally require more advanced and prolonged treatment. Risk factors associated with the development of epilepsy include young age, refractory seizures, tuberculoma, cortical involvement, epileptiform discharges, and residual lesions. Treatment of CNS tuberculosis is based on early initiation of appropriate anti-tuberculous drugs, antiseizure medications, and correction of associated predisposing factors. Finally, further research into the mechanisms of seizures and the development of epilepsy in CNS tuberculosis could help improve management of these conditions.

Pelvic and central nervous system tuberculosis complicated by a paradoxical response manifesting as a spinal tuberculoma: a case report.

BACKGROUND: The post-partum period is a risk factor for tuberculosis (TB), possibly including the period after miscarriage as illustrated here. This case demonstrates how non-specific symptoms can hide widely disseminated TB. CASE PRESENTATION: A healthy 26-year-old female with a history of recent miscarriage presented to the emergency department with non-specific symptoms of headache, abdominal pain, and sub-acute fevers. She had immigrated to the United States from the Marshall Islands 9 years prior. Two months prior to presentation she had a miscarriage at 18 weeks of pregnancy. On admission, transvaginal ultrasound revealed retained products of conception and abdominal computed tomography revealed findings consistent with tubo-ovarian abscesses and peritonitis. The obstetrics and gynecology service performed dilation and curettage (D&C) to remove retained products of conception. Acid-fast bacilli cultures from cerebrospinal fluid as well as specimens from D&C and intra-abdominal abscesses subsequently all grew TB. She was diagnosed with TB meningitis, peritonitis, endometritis, and tubo-ovarian abscesses. Her treatment course was complicated by a paradoxical response resulting in a spinal tuberculoma causing lower extremity weakness. The tuberculoma was treated with surgical decompression as well as continuation of treatment with anti-tubercular chemotherapy and steroids. CONCLUSION: Disseminated and extrapulmonary TB can present with non-specific symptoms. Recognition of risk factors for TB is critical for prompt diagnostic evaluation and treatment of this deadly disease. A paradoxical reaction needs to be taken into consideration when any new neurological symptoms occur during TB treatment.

Predictors of outcomes in children with Central Nervous System tuberculosis.

BACKGROUND: Central Nervous system tuberculosis (CNS-Tb) is the most lethal form of extra-pulmonary tuberculosis in children. The lack of markers of outcome provides little information on the efficacy of the current treatment protocols for CNS-Tb and thus results in a higher mortality rate than other extrapulmonary manifestations of tuberculosis. This study aims to identify significant factors that will reliably predict the outcomes at discharge in children admitted with CNS-Tb. METHODS AND MATERIAL: This is a prospective observational study in children with neurotuberculosis admitted at a tertiary care hospital. Clinical presentations at the time of admission were studied. Outcomes at the end of in-patient care (completely cured, survival with some/severe disability or death) were correlated with clinical, laboratory, microbiological, and radiological parameters. Univariate and multivariate analyses were applied to study the parameters and a p-value ≤ 0.05 with a confidence interval (CI) of 95% was considered as statistically significant. FINDINGS: The study included 100 children between 4 months and 12 years of age with a mean of 5.84 (±3.5) years. At discharge, 55% of children recovered completely, 20% had some or severe disability and 25% died. On multivariate analysis, high CSF protein (p = 0.050) and drug resistance (p = 0.034) were highly associated with fatality. Meningeal enhancements with basal exudates (p = 0.021) and CSF lymphocyte count >90% were highly associated with survival with disability. Stage I disease at presentation (p < 0.0001) was the only variable associated with complete recovery. INTERPRETATION: Reliable prognostic markers for CNS-Tb can aid in predicting the efficacy of the current treatment and the anticipated outcome in the children with this disease. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Drug Resistance in Children with Central Nervous System Tuberculosis from a Tertiary Care Center in Mumbai.

INTRODUCTION: Central Nervous System tuberculosis (CNS-TB) is the most lethal form of extra-pulmonary TB, especially in children. In this study, we have discussed patterns of drug resistance in pediatric CNS-TB. MATERIALS AND METHODS: Prospective observational study conducted on 100 children at a tertiary care center. Diagnosed cases of CNS-TB were enrolled. GeneXpert MTB/RIF was used upfront for diagnosis, and in cases where TB MGIT culture was positive, a phenotypic Drug Susceptibility Test (DST) was done. Patients were divided into resistant to at least one drug (DR) and drug-susceptible (DS). Various parameters were compared between these groups. RESULTS: Mean age of participants was 5.84 ± 3.5 years, with a male-to-female ratio of 1.08 : 1; 14% of children had drug-resistant CNS TB (DR-CNS-TB). A higher proportion of children previously treated for TB were associated with drug resistance (p = 0.009), and those with disseminated TB also had a higher drug resistance (p = 0.002). Apart from this, the DR and DS groups had no statistically significant differences in demographic, clinical or epidemiological parameters. CONCLUSIONS: Previous history of being treated for TB and disseminated TB was an independent risk factor for DR-CNS-TB. Ensuring proper adherence and compliance to anti-tubercular treatment could help in preventing the emergence of DR TB.

Tuberculoma in the Fourth Ventricle: An Unusual Location.

To present a young immunocompetent patient with a fourth ventricle tuberculoma without pulmonary tuberculosis. A previously healthy young male patient presented with a history of headache, nausea, and blurred vision. Neuroimaging revealed a mass present in the fourth ventricle. The lesion was successfully resected. Histological and microbiological findings suggested the presence of a tuberculoma. Tuberculomas can be found in the posterior fossa in adults. This infectious pathology should not be forsaken when considering the differential diagnosis for infratentorial masses.

Case reports of chronic myeloid leukemia and tuberculosis: Is imatinib the link between the two?

Current standard of care for treatment of CML is based on tyrosine kinase inhibitors (TKI's). Imatinib is most frequently used first line tyrosine kinase inhibitor. Various side effects of TKI's are known, but some may still be unknown. We are reporting three cases of CML who developed tuberculosis while on treatment with imatinib or dasatinib. Two cases developed CNS tuberculosis and other one was tubercular pleural effusion. These cases indicate that imatinib and other TKI's probably interfere with immunological functions and predispose patients for tuberculosis.

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.

Cerebrospinal Fluid Analysis.

Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.

Central nervous system tuberculosis.

PURPOSE OF REVIEW: Central nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis. RECENT FINDINGS: Insight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival. SUMMARY: Recent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.

Cognitive impairment in patients with central nervous system tuberculosis.

INTRODUCTION: Tuberculosis (TB) in Mexico remains an important cause of morbidity and mortality; in the past 4 years, 110,681 cases of pulmonary tuberculosis and 1571 cases of tuberculous meningitis were reported. OBJECTIVE: To determine the neurocognitive sequelae, clinical presentation and neuroimaging alterations in patients with central nervous system tuberculosis. METHODS: A retrospective, analytical, and cross-sectional study was carried out from 2010 to 2019. Patients with central nervous system tuberculosis, with and without HIV/AIDS coinfection, were included. RESULTS: During the study period, 104 cases with a definitive or probable central nervous system tuberculosis diagnosis were included; 38% had HIV/AIDS coinfection, and 55%, various comorbidities (p = 0.0001); 49% had cognitive alterations, and 14% died. CONCLUSIONS: Although HIV/AIDS infection can contribute to cognitive decline in patients with tuberculous meningitis, no differences were observed between patients with and without HIV/AIDS. Cognitive sequelae showed improvement during follow-up with adequate management and therapeutic control of the patients.

INTRODUCCIÓN: La tuberculosis en México sigue siendo causa importante de morbimortalidad; en los últimos cuatro años, se reportaron 110 681 casos de tuberculosis pulmonar y 1571 casos de tuberculosis meníngea. OBJETIVO: Determinar las secuelas neurocognoscitivas, presentación clínica y alteraciones en los estudios de neuroimagen en pacientes con tuberculosis del sistema nervioso central. MÉTODOS: Se realizó un estudio retrospectivo, analítico y transversal de 2010 a 2019. Se incluyeron pacientes con tuberculosis del sistema nervioso central, con y sin coinfección por VIH/sida. RESULTADOS: Durante el periodo de estudio se incluyeron 104 casos con diagnóstico definitivo y probable de tuberculosis del sistema nervioso central; de acuerdo con los criterios de Marais, 38 % presentó coinfección por VIH/sida y 55 %, diversas comorbilidades (p = 0.0001); 49 % presentó alteraciones cognoscitivas y 14 % falleció. CONCLUSIONES: Aunque la infección por VIH/sida puede contribuir al deterioro cognitivo del paciente con tuberculosis meníngea, no se observaron diferencias entre pacientes con y sin VIH/sida. Las secuelas cognoscitivas mostraron mejoría en el seguimiento con el adecuado manejo y control terapéutico de los pacientes.

The immunological architecture of granulomatous inflammation in central nervous system tuberculosis.

Of all tuberculosis (TB) cases, 1% affects the central nervous system (CNS), with a mortality rate of up to 60%. Our aim is to fill the 'key gap' in TBM research by analyzing brain specimens in a unique historical cohort of 84 patients, focusing on granuloma formation. We describe three different types: non-necrotizing, necrotizing gummatous, and necrotizing abscess type granuloma. Our hypothesis is that these different types of granuloma are developmental stages of the same pathological process. All types were present in each patient and were mainly localized in the leptomeninges. Intra-parenchymal granulomas were less abundant than the leptomeningeal ones and mainly located close to the cerebrospinal fluid (subpial and subependymal). We found that most of the intraparenchymal granulomas are an extension of leptomeningeal lesions which is the opposite of the classical Rich focus theory. We present a 3D-model to facilitate further understanding of the topographic relation of granulomas with leptomeninges, brain parenchyma and blood vessels. We describe innate and adaptive immune responses during granuloma formation including the cytokine profiles. We emphasize the presence of leptomeningeal B-cell aggregates as tertiary lymphoid structures. Our study forms a basis for further research in neuroinflammation and infectious diseases of the CNS, especially TB.

Fatal central nervous system co-infection with SARS-CoV-2 and tuberculosis in a healthy child.

BACKGROUND: Central and peripheral nervous system symptoms and complications are being increasingly recognized among individuals with pandemic SARS-CoV-2 infections, but actual detection of the virus or its RNA in the central nervous system has rarely been sought or demonstrated. Severe or fatal illnesses are attributed to SARS-CoV-2, generally without attempting to evaluate for alternative causes or co-pathogens. CASE PRESENTATION: A five-year-old girl with fever and headache was diagnosed with acute SARS-CoV-2-associated meningoencephalitis based on the detection of its RNA on a nasopharyngeal swab, cerebrospinal fluid analysis, and magnetic resonance imaging findings. Serial serologic tests for SARS-CoV-2 IgG and IgA showed seroconversion, consistent with an acute infection. Mental status and brain imaging findings gradually worsened despite antiviral therapy and intravenous dexamethasone. Decompressive suboccipital craniectomy for brain herniation with cerebellar biopsy on day 30 of illness, shortly before death, revealed SARS-CoV-2 RNA in cerebellar tissue using the Centers for Disease Control and Prevention 2019-nCoV Real-Time Reverse Transcriptase-PCR Diagnostic Panel. On histopathology, necrotizing granulomas with numerous acid-fast bacilli were visualized, and Mycobacterium tuberculosis complex DNA was detected by PCR. Ventricular cerebrospinal fluid that day was negative for mycobacterial DNA. Tracheal aspirate samples for mycobacterial DNA and culture from days 22 and 27 of illness were negative by PCR but grew Mycobacterium tuberculosis after 8 weeks, long after the child's passing. She had no known exposures to tuberculosis and no chest radiographic findings to suggest it. All 6 family members had normal chest radiographs and negative interferon-γ release assay results. The source of her tuberculous infection was not identified, and further investigations by the local health department were not possible because of the State of Michigan-mandated lockdown for control of SARS-CoV-2 spread. CONCLUSION: The detection of SARS-CoV-2 RNA in cerebellar tissue and the demonstration of seroconversion in IgG and IgA assays was consistent with acute SARS-CoV-2 infection of the central nervous infection. However, the cause of death was brain herniation from her rapidly progressive central nervous system tuberculosis. SARS-CoV-2 may mask or worsen occult tuberculous infection with severe or fatal consequences.

"There is more than what meets the eye" - Extensive spinal tuberculosis presenting as ocular tuberculosis.

Ocular tuberculosis (OTB) is a rare form of extrapulmonary Tuberculosis (EPTB) and a rare presenting feature of tuberculosis (TB) in children. We report such a case in a 3-year-old boy who presented with a painless swelling over left upper eyelid. Mycobacterium tuberculosis bacilli were isolated from the swelling by a Fine Needle Aspiration Cytology (FNAC) which confirmed the diagnosis. Investigating him for the extent of disease, we found him to have intracranial extension to involve the ethmoid sinus on contrast enhance Computed Tomography and Pott's disease causing a compression fracture of L3 with bilateral paravertebral collection, epidural extension and a left psoas abscess on Magnetic Resonance Imaging. After starting antitubercular therapy, the child is doing well and on regular follow up. We are presenting this case to highlight the fact that extensive spinal tuberculosis can present without any neurological deficit and may even present only as a benign looking orbital swelling.