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.

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.

Thalidomide Use for Complicated Central Nervous System Tuberculosis in Children: Insights From an Observational Cohort.

BACKGROUND: Much of the neurological sequelae of central nervous system (CNS) tuberculosis (TB) is due to an excessive cytokine-driven host-inflammatory response. Adjunctive corticosteroids, which reduce cytokine production and thus dampen the inflammation, improve overall survival but do not prevent morbidity. This has prompted investigation of more targeted immunomodulatory agents, including thalidomide. METHODS: We describe a retrospective cohort of 38 children consecutively treated with adjunctive thalidomide for CNS TB-related complications over a 10-year period. RESULTS: The most common presenting symptom was focal motor deficit (n = 16), followed by cranial nerve palsies and cerebellar dysfunction. Three of the 38 children presented with large dural-based lesions, manifesting as epilepsia partialis continua (EPC), 4 presented with blindness secondary to optochiasmatic arachnoiditis, and 2 children developed paraplegia due to spinal cord TB mass lesions. Duration of adjunctive thalidomide therapy (3-5 mg/kg/day) varied according to complication type. In children compromised by TB mass lesions, the median treatment duration was 3.9 months (interquartile range [IQR], 2.0-5.0 months), whereas in children with optic neuritis it was 2.0 months (IQR, 1.3-7.3 months) and in EPC it was 1.0 months (IQR, 1-2.5 months). Satisfactory clinical and radiological response was observed in 37 of the children. None of the children experienced rashes, hepatitis, or hematologic derangements or complained of leg cramps. CONCLUSIONS: This study is the largest cohort of adult or pediatric patients treated with adjunctive thalidomide for CNS TB-related complications. The drug has proved to be safe and well tolerated and appears to be clinically efficacious. The potential role of thalidomide or analogues in the treatment of other tuberculous meningitis-related complications requires further exploration.

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.

Case report: an area postrema syndrome revealing a neuromyelitis optica spectrum disorder associated with central nervous system tuberculosis in a young Togolese (black African) woman.

BACKGROUND: Area postrema syndrome (APS) is considered to be one of the most specific clinical presentations of neuromyelitis optica spectrum disorders (NMOSDs). In sub-Saharan Africa, NMOSDs and even more so those revealed by an APS, are rarely reported. However, studies among mixed populations have shown that NMOSDs disproportionately affect black people with relatively more frequent encephalic involvement. We report a case of APS revealing an NMOSD associated with central nervous system (CNS) tuberculosis in a young Togolese woman residing in Togo (West Africa). CASE PRESENTATION: A 28-year-old Togolese woman was admitted for left hemibody sensory problems with ataxia. These problems were observed while the patient was hospitalized for a few days in the hepato-gastroenterology department for persistent vomiting, abdominal pain and hiccups lasting for about a month. The examination confirmed left hemibody ataxia with nystagmus when looking to the left, pronounced left osteotendinous reflexes, and left hemibody hypoesthesia up to the base of the neck. Encephalic magnetic resonance imaging (MRI) showed a hypersignal lesion in the bulbar more lateralized on the left in the fluid-attenuated inversion recovery sequence, not enhanced after a gadolinium injection. Biological assessment showed the presence of Mycobacterium tuberculosis deoxyribonucleic acid in the cerebrospinal fluid and a sedimentation rate of 120 mm in the 1st hour. The result of the anti-AQP4 antibody test was positive. Two months from the onset of digestive problems with Lhermitte's sign and hand and foot contracture access without vesico-sphincter problems were established. Cervical medullary MRI showed an additional intramedullary hypersignal lesion in the T2 sequence at the C2 level, not enhanced after a gadolinium injection. A second course of intravenous corticosteroids was administered, and anti-tuberculosis treatment was continued. The outcome was favorable. After 8 months of anti-tuberculosis treatment, the patient started immunosuppressive therapy (azathioprine 50 mg twice daily) to limit the risk of recurrence of NMOSD. CONCLUSION: The recognition of an APS is an additional challenge for the diagnosis of NMOSDs, especially in countries with limited resources. CNS tuberculosis must be tested when faced with an NMOSD because it seems to be a major cause.

Endovascular treatment of HIV-associated spontaneous common carotid artery pseudoaneurysm in a case of miliary and CNS tuberculosis.

HIV and tuberculosis infections are known to be associated with vasculopathy including occlusive disease and aneurysm formation. We report a case of 43-year-old male with miliary and central nervous system (CNS) tuberculosis; recently, diagnosed as HIV seropositive, on antiretroviral and antitubercular treatment presenting with painful neck swelling. He was found to have common carotid artery (CCA) pseudoaneurysm that was managed by endovascular stent grafting. HIV vasculopathy-related CCA pseudoaneurysm is a potentially life-threatening rare entity. Treatment of an immunocompromised patient by endovascular approach minimizes hospital stay and avoids wound-related complications. To the best of our knowledge, there has been no case report describing endovascular treatment of CCA pseudoaneurysm in an HIV-positive patient with low CD4 count and coexistent disseminated tuberculosis.

Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis.

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

REVIEW OF THE CLINICAL, COMPUTERIZED TOMOGRAPHY SCAN AND/OR MAGNETIC RESONANCE IMAGING FINDINGS OF INTRACRANIAL TUBERCULOMA IN AN ETHIOPIAN TEACHING HOSPITAL.

ackground: Ethiopia is one of the countries that has high burden of all forms of tuberculosis and there is no published report on computerized tomography scan and/or magnetic resonance imaging of intracranial tuberculomas. Objective : to review the clinical, computerized tomography and/or magnetic resonance imaging features of intracranial tuberculoma. Methods: retrospective review of patient's medical records of patients operated for intracranial mass that had computerized tomography and/or magnetic resonance imaging brain scans and had histopathological diagnoses, at Tikur Anbessa Specialized Hospital between January 2009 and June 2013. Results: Of 222 operated cases of intracranial mass subjected to histopathological test 29 (14.6%) were found to have tuberculomas, 28 (14.1%) had caseous necrosis and one was a tuberculous abscess, in 25 cases imaging was available for review and were included in the study . There were 15 males and 10 females with age range being 2 to 65 years and with the Median age being 13 years. Twenty patients had computerized tomography and five patients had magnetic resonance imaging. Seizure 15/25 (60%) and headache 11/25 (44%) were the commonest presentation. Solitary or confluent large lesions were seen in 12/25 (48%) of patients. 14/25 (56%) of the lesions had their size between 2 cm and 5 cm. Majority of the lesions 15/25 (60%) were in the frontal and parietal lobes. The lesions were isodense on CT in 18/25 (72%) of the pre-contrast studies and 21/25 (84%) showed ring or rim enhancement after intravenous administration of the contrast medium. Conclusion: Tuberculoma, more frequently, presented with non-specific clinical findings and chronic seizure disorder and comonly occurred in young patients and often seen infratentorialy. It is often complicated with hydrocephalus in the pediatric age group. Computerized tomography scan and/or magnetic resonance imaging features are not different from reports from other 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.

Patient taking chemotherapy for a small cell lung cancer: not every cerebral nodule is a metastasis: the tree that hides the forest.

We report the case of a 53- year-old man in whom the diagnosis of small cell lung cancer (SCLC) was made by the biopsy of a mass of the right trapezius muscle. A tumor was revealed on flexible bronchoscopy which pathological study showed tuberculosis (TB). Chest computed tomography (CT) scan revealed findings related to the SCLC associated to micronodules and nodules compatible with pulmonary TB. Cerebral CT scan revealed a nodule of 4.5 mm in diameter presenting enhancement after contrast material injection thought to be a metastasis. The patient was administered antitubercular treatment. Fiveteen days later, the patient started chemoptherapy with etoposid and carboplatin. A control cerebral CT scan realized after the end of the chemotherapy (2 months and a half of antitubercular treatment) revealed numerous cortical and subcortical infracentimetric nodules with contrast enhancement with a tentorial and subtentorial location considered to be in relation with cerebral miliary TB. The nodule discovered on the first cerebral scan was therefore a posteriori considered to have been of tubercular origin. The PS of the patient rapidly worsened. He presented mental confusion and died in some days.

Cerebral infarction and tuberculoma in central nervous system tuberculosis: frequency and prognostic implications.

BACKGROUND: Tuberculoma and cerebral infarctions are serious complications of central nervous system (CNS) tuberculosis. However, there are no studies comparing prognostic value of tuberculoma and infarcts alone and in patients diagnosed with CNS tuberculosis. OBJECTIVE: The objective of this study was to identify frequency and prognostic value of tuberculoma and cerebral infarcts in a large sample of CNS tuberculosis patients. METHODS: Retrospective chart review of patients diagnosed with CNS tuberculosis in a tertiary care hospital in Pakistan over 10-year period was carried out. RESULTS: There were 404 patients included in this study (mean age of 43 years). There were 209 (52%) men and 195 (48%) women. Tuberculoma were present in 202 subjects (50%) while infarcts were present in 25% patients. 147 (36%) had tuberculous meningitis (TBM) without tuberculoma or infarction on CT or MRI, 158 (39%) had TBM with intracranial tuberculomas, 60 (15%) had TBM with cerebral infarction while 39 (10%) had TBM with both tuberculoma and infarction. At discharge, 249 patients (62%) were either normal (Modified Rankin Score (MRS)=0) or mild to moderately disabled (MRS=1-3) while 82 patients (20%) had severe disability (MRS=4-5). 73 (18%) patients died (MRS=6) during hospitalisation. Using logistic regression analysis, significant predictors of poor outcome included old age, high TBM grading, presence of infarction and presence of hydrocephalus. CONCLUSIONS: Tuberculomas were present in 50% of patients, while infarcts were present in 25%. Old age, TBM grading, presence of infarction and hydrocephalus were all predictors of poor outcome.

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.

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.

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.

Infectious causes of seizures and epilepsy in the developing world.

Central nervous system (CNS) infections are the main cause of seizures and acquired epilepsy in the developing world. Geographical variations determine the common causes in a particular region. Acute seizures are common in severe meningitis, viral encephalitis, malaria, and neurocysticercosis, and in most cases are associated with increased mortality and morbidity, including subsequent epilepsy. Neuronal excitability secondary to proinflammatory signals induced by CNS infections are an important common mechanism for the generation of seizures, in addition to various other specific mechanisms. Newer insights into the neurobiology of these infections and the associated epilepsy could help in developing neuroprotective interventions. Management issues include prompt treatment of acute seizures and the underlying CNS infection, correction of associated predisposing factors, and decisions regarding the appropriate choice and duration of antiepileptic therapy. Strategies for the prevention of epilepsy in CNS infections such as early anti-infective and anti-inflammatory therapy need scientific exploration. Prevention of CNS infections is the only definitive way forward to reduce the burden of epilepsy in developing countries.

Tuberculous encephalopathy without meningitis: pathology and brain MRI findings.

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

Primary tuberculous cerebellar abscess: case report.

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

[Central nervous system tuberculosis in adult patients]. / Felnottek központi idegrendszeri tuberkulózisa.

UNLABELLED: Central nervous system tuberculosis is the fifth most frequent and at the same time most severe form of extrapulmonary tuberculosis diseases. It presents with no typical signs, thus early diagnosis and treatment is of high importance concerning the outcome. Authors present the characteristics, diagnostic and therapeutic alternatives of central nervous system tuberculosis through a case report and a retrospective study of 15 patients. PATIENTS AND METHODS: Authors performed a retrospective analysis of medical records of patients with central nervous system tuberculosis in an academic teaching hospital (Department of Neurology and Infectious Diseases, United Szent István-Szent László Hospital, Budapest, Hungary). RESULTS: Median age of patients was 54.5 years, and 6 (40%) were females. Cerebrospinal fluid findings at admission showed elevated protein (1.54 g/l; 95% confidence interval (CI): 1.01-2.05), cell count (mean: 337/µl; CI: 171.9-502.5), and decreased glucose index (0.32; CI: 0.15-0.52). 14 patients (93.3%) had hyponatremia. Average duration of symptoms were 16.3 days (1-40). On physical examination meningeal irritation was absent in 9 patients (60%). On admission headache and altered consciousness was present in 53%, while headache, fever, nuchal rigidity was present in only 33.3%. Diagnosis was culture and/or PCR confirmed in 46.7% of the cases. Two third of patients were followed-up at least for one year, and nine patients presented neurological sequel. Authors found that patients with central nervous system tuberculosis present with unspecific symptoms, but later progressive disorientation, cranial nerve palsies and convulsions may develop. Headache and altered consciousness proved to be the leading symptoms among these patients. Even today, diagnostic gold standard procedure is cultivating M. tuberculosis on solid and liquid medium. The polymerase chain reaction, which is known to have sensitivity between 27% and 86%, was positive in two of eight samples. Revealing predisposing factors (immunodeficiency, HIV infection, previous tuberculosis exposure) promotes setting up early diagnosis. Co-administration of four antituberculotic drugs for 12 months cured all patients, but authors note that even in cases with early diagnosis and optimal treatment various neurological impairment and seldom death can occur. CONCLUSIONS: Central nervous system tuberculosis is a rare but regularly emerging disease with unspecific signs and symptoms. The diagnosis may be difficult. It should be considered as a differential diagnostic issue in patients with uncharacteristic subacute conditions with headache, disorientation, elevated protein and low glucose in cerebrospinal fluid.