Multiple tuberculomas in an immunocompetent patient and their diagnostic challenge in a high prevalence country: Case report and literature review.

CONTEXT: Intracranial tuberculomas are rare yet lethal forms of tuberculosis. Diagnosis is often difficult because of its nonspecific symptoms and radiological findings. AIM: This study aims to perform a literature review of multiple tuberculomas to improve disease recognition and management in immunocompetent patients along with presenting a case report on the topic. DATA SOURCES: Scopus, LILACS, Ovid MEDLINE and EMBASE. STUDY SELECTION: Case reports and case series up to December 2018 in English, Spanish, and Portuguese focusing on intracranial tuberculomas in adult and pediatric immunocompetent patients. Data on presentation, diagnostic workup, and treatment was analyzed. DATA EXTRACTION: Cochrane Collaboration/Cochrane Handbook and PRISMA guidelines. RESULTS: Twenty reports involving 21 patients were included. Most patients were male (57.14%). The average age at diagnosis was 26.9 ± 14.9 years. Headache was the most common presenting symptom (52.4%; 11/21), followed by motor weakness (47.6%; 10/21) and vomiting (23.8%; 5/21). MRI was the most used image technique (17/21). Most lesions occurring in the cerebral hemispheres (16/21); we found five or more lesions in 66.6% (14/21) of the patients. The majority treated with anti-tuberculous drugs resulted in a favorable outcome. CONCLUSIONS: Immunocompetent patients living in TB endemic areas whose clinical evaluation and neuroimaging findings are compatible with tuberculoma should undergo anti-tubercular treatment despite a lack of bacteriological confirmation.

Brainstem tuberculoma: A delayed IRIS.

We describe a twenty six years old lady with tuberculous meningitis who developed new onset left ptosis and binocular diplopia with features of left fascicular 3rd nerve palsy after 9 months of anti tubercular therapy (ATT) and imaging revealed new onset tuberculoma in the mid-brain. Tuberculoma responded to steroids while continuing ATT. Formation of new tuberculoma as a part of immune reconstitution inflammatory syndrome (IRIS) is possible even after prolonged therapy of 9 months, which responded well to only steroids without altering ATT.

Immune reconstitution inflammatory syndrome in non-HIV patients with tuberculosis. A case series.

Tuberculosis associated Immune reconstitution inflammatory syndrome (IRIS) in a HIV negative patient can present with a multitude of clinic-radiological presentations that are often confused with drug resistance/treatment failure. Being a diagnosis of exclusion, this clinical entity is often prone to under-diagnosis. We present a series of 5 patients who presented with varied but uncommon IRIS manifestations. High index of suspicion coupled with clinical reasoning and judicious use of phenotypic and genotypic culture methods helped in their timely detection and successful treatment.

Brain tuberculoma, an unusual cause of stroke in a child with trisomy 21: a case report.

BACKGROUND: Tuberculosis remains a public health problem in developing countries and is associated with lethal central nervous system complications. Intracranial tuberculomas occur in 13% of children with neurotuberculosis. Patients with trisomy 21 have an increased risk for stroke, which usually stems from cardiovascular defects. CASE PRESENTATION: We report a case of a 12-year-old Sudanese boy with trisomy 21 who was presented to our hospital with focal convulsions and right-sided weakness. The results of neuroimaging and histopathological examinations were consistent with cerebral tuberculoma. The patient had a good initial response to antituberculosis drugs and steroids. To the best of our knowledge, this is the first case report of multiple brain tuberculomas described in a child with trisomy 21. CONCLUSIONS: Patients with trisomy 21 have an increased risk for stroke. Our patient had an exceptional case of stroke caused by tuberculoma. The present case emphasizes the need to consider tuberculomas in the differential diagnosis of children with neurological symptoms living in areas of high tuberculosis incidence.

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.

Movement disorders identified in patients with intracranial tuberculomas.

INTRODUCTION: movement disorders have been associated with deep brain lesions. This study was performed to describe the frequency and characteristics of movement disorders in patients with intracranial tuberculomas. METHODS: patients admitted consecutively between 1989 and 2004 to the Neurology Service of Eugenio Espejo Hospital (Quito, Ecuador), with a diagnosis of intracranial tuberculomas. All patients were examined clinically, and laboratory tests and imaging studies performed. Follow-up continued up to one year after the tuberculosis treatment was completed. A nested case-control analysis was performed to compare clinical characteristics, number and location of tuberculomas, between cases with movement disorders and controls. RESULTS: forty-nine patients with tuberculomas (31.7±20.5 years; males 53.1%) were studied. We found 16 cases (32.6%; 95%CI=19.9% - 47.5%) of movement disorders: chorea (n=7; 43.8%), tremor (n=5; 31.3%), dystonia (n=3; 18.8%) and myoclonus (n=1; 6.3%). Most cases (87.6%) developed early (10.4±5.2 days of hospitalization). On admission, patients with movement disorders showed higher severity of the illness than controls (68.7 vs. 30.3%; p=.01), along with greater motor impairment (75.0 vs. 39.4%; p=.01) and sensitivity impairment (43.8 vs. 9.1%; p=.01). The cases showed higher frequency of multiple tuberculomas (68.7 vs. 36.4%), with deep brain deep (31.3 vs. 21.2%) and more severe motor impairment (25.0 vs. 12.1%). CONCLUSIONS: our results suggest a causal relationship between tuberculomas and movement disorders. Deep location and multiple tuberculomas may increase the risk of develop movement disorders.

Paroxysmal autonomic instability with dystonia in a child: rare manifestation of an interpeduncular tuberculoma.

The term 'paroxysmal autonomic instability with dystonia' was first given for a group of symptoms comprising diaphoresis, intermittent agitation, hypertension, hyperthermia, tachycardia, tachypnea, and extensor posturing. This usually occurs as a complication of severe brain injury and is infrequently reported in cases of cerebral infection. We report a 1-year-old child with intracranial tuberculoma with symptoms of paroxysmal autonomic instability with dystonia. Pertinent literature is reviewed emphasizing pathophysiology and available treatment options.

Ophthalmic manifestations of central nervous system tuberculosis--two case reports.

In this report, we present two unusual ocular manifestations due to CNS tuberculosis. One of the cases is a 7 years' old boy with brain stem tuberculoma who presented with horizontal gaze palsy. The other is a 14 years' old girl with temporal lobe tuberculoma who presented with unilateral sixth nerve paresis and papilledema. Both responded well to treatment with antitubercular drugs. It highlights the importance of gaze palsy as a rare manifestation of CNS tuberculosis.

Paradoxical vision loss associated with optochiasmatic tuberculoma in tuberculous meningitis: a report of 8 patients.

BACKGROUND: Paradoxical appearance of new or expansion of existing optochiasmatic tuberculoma, leading to severe vision loss, is a devastating complication in patient with tuberculous meningitis. METHODS: We report a series of 8 cases of tuberculous meningitis that developed paradoxical vision loss associated with optochiasmatic tuberculoma. Clinical assessment and magnetic resonance imaging (MRI) done at presentation, at the time of deterioration, and at 9 months were analyzed. RESULTS: All patients had good vision acuity and normal visual field at baseline. None of them had optochiasmatic tuberculoma on magnetic resonance imaging at baseline, though 3 patients had optochiasmatic arachnoiditis. The mean interval of onset of paradoxical optochiasmatic tuberculoma was 41 days after starting antituberculosis therapy. Paradoxical optochiasmatic tuberculoma was associated with vision deterioration in all patients, 6 of whom developed severe vision loss (vision acuity

Vision impairment in tuberculous meningitis: predictors and prognosis.

BACKGROUND: Vision impairment is a devastating complication of tuberculous meningitis. In the present study we evaluated the predictors and prognostic significance of vision impairment in tuberculous meningitis. METHODS: In this study, 101 adult patients with tuberculous meningitis were evaluated for vision status and physical disability and were followed up for 6 months. Contrast enhanced magnetic resonance imaging (MRI) was performed at baseline and 6 months. RESULT: Out of 101 patients, 74 patients had normal vision and 27 patients had low vision or blindness at enrollment. Thirteen patients died during the study period. Out of 88 patients who survived at 6 months, 68 patients had good vision, 11 patients had low vision and 9 patients had blindness. Predictors of vision deterioration were papilledema, cranial nerve palsies, raised cerebrospinal fluid protein (>1g/L), and presence of optochiasmatic arachnoiditis in MRI. Predictors of blindness, at 6 months, were found to be papilledema, vision acuity < or =6/18, cranial nerve palsies, tuberculous meningitis stage II or III, raised cerebrospinal fluid protein (>1g/L), optochiasmatic arachnoiditis, and optochiasmal tuberculoma. At 6 months, 27 patients had death or severe disability. Predictors of death or severe disability at 6 months were vision acuity < or =6/18, cranial nerve deficits, hemiparesis, clinical stage II or III, and presence of infarct in MRI. CONCLUSION: Vision impairment occurred in one-fourth of patients with tuberculous meningitis. Principal causes of vision loss were optochiasmatic arachnoiditis and optochiasmal tuberculoma. Impaired vision predicted death or severe disability.

Tumor de Pott / Pott´s Puffy tumor

Tumor de Pott (Pott‘s Puffy tumor) é uma comorbidade caracterizada por um ou mais abscessos sub-periosteais do osso frontal associados a osteomielite subjacente. As etiologias incluem trauma e sinusite, entre outras. Relatamos o caso de uma paciente de 17 anos que se apresentou com abaulameto doloroso, calor local e flutuação na região frontal à direita há um mês, bem como cefaléia holocraniana e hipertermia. O diagnóstico de Tumor de Pott como uma complicação de uma sinusite frontal foi estabelecido pela clínica e confirmado por tomografia computadorizada de crânio. Foi tratada com sucesso com esquema inicial de amoxicilina mais clavulanato, o qual foi substituído por ciprofloxacina, associados à craniotomia, com craniectomia do osso acometido. Esta é uma doença que por ser infreqüente muitas vezes não é diagnosticada. Deste modo enfatizamos o diagnóstico e tratamento precoces como forma de evitar seqüelas neurológicas.

Pott‘s Puffy Tumor is a comorbidity characterized by one or multiple subperiosteal abscesses of the frontal bone associated with underlying osteomyelitis. Etiologies include trauma and sinusitis among others. Here we report the case of a 17-year-old female patient with painful bulging, local heat, and fluctuation in the frontal region on the right for a month, as well as holocranial headache and hyperthermia. The diagnosis of Pott‘s Puffy Tumor as a complication of frontal sinusitis was clinically established and confirmed by computerized tomography of the skull. It was successfully initially treated with amoxicilin + clavunate, followed by ciprofloxacin, combined with craniotomy and craniectomy of the affected bone. Because of its rarity, this disorder often goes underdiagnosed. Thus we emphasize an early diagnosis and treatment so as to avoid neurological sequels.

Secretory phospholipase A2 plays an essential role in microglial inflammatory responses to Mycobacterium tuberculosis.

In previous studies, we have shown that reactive oxygen species (ROS)-mediated inflammatory signaling is essential for microglial proinflammatory responses to Mycobacterium tuberculosis (Mtb). To further investigate the molecular mechanisms governing these processes, we sought to describe the role of phospholipase A(2) (PLA(2)) in Mtb-induced ROS generation and inflammatory mediator release by microglia. Inhibition of secretory PLA(2) (sPLA(2)), but not cytosolic PLA(2) (cPLA(2)), profoundly abrogated Mtb-mediated ROS release, the generation of various inflammatory mediators (tumor necrosis factor, interleukin-6, cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-2 and -9), and the activation of nuclear factor (NF)-kappaB and MAPKs (ERK1/2, p38, and JNK/SAPK) by murine microglial BV-2 cells or primary mixed glial cells. Interruption of the Ras/Raf-1/MEK1/ERK1/2 pathway abolished Mtb-induced sPLA(2) activity, whereas the blockage of JNK/SAPK or p38 activity had no effect. Specific inhibition of sPLA(2), but not cPLA(2), suppressed the upregulation of ERK1/2 phosphorylation by Mtb stimulation, suggesting the existence of a mutual dependency between the ERK1/2 and sPLA(2) pathways. Moreover, examination of the protein kinase C (PKC) family revealed that classical PKCs are involved in Mtb-induced sPLA(2) activation by microglia. Taken together, our results demonstrate for the first time that sPLA(2), either through pathways comprising Ras/Raf-1/MEK1/ERK1/2 or the classical PKC family, plays an essential role in Mtb-mediated ROS generation and inflammatory mediator release by microglial cells.

[Intracranial tuberculoma: a case report and review of the literature]. / Tuberculoma intracraneal: caso clínico y revisión de la bibliografía.

INTRODUCTION: Cerebral tuberculoma constitutes an important neurotuberculosis clinical form with high morbimortality and important diagnoses difficulty. CASE REPORT: Only giant cerebral tuberculoma case in 3 years-old man who present dizziness and surgically treated by diagnostic suspicion of cerebral tumor. CONCLUSION: Cerebral tuberculomas can often be confused with cerebral tumors when they are not included in differential diagnosis.

Pontine tuberculoma presenting with horizontal gaze palsy.

A 38-year-old immunocompetent man presented with a horizontal supranuclear gaze palsy as the only neurologic manifestation of a pontine tuberculoma. Although a biopsy of the brain lesion was not performed, it was attributed to tuberculosis because of chest x-ray evidence. The patient was given empirical anti-tuberculous therapy. After one month, the gaze palsy had fully recovered and repeat MRI showed a decrease in the size of the lesion. This is the first reported case of supranuclear gaze palsy without diplopia as a manifestation of a tuberculous brain stem lesion.

Miliary tuberculosis associated with multiple intracranial tuberculomas.

In this study we have reported a 12-year old girl patient who visited out-patient clinic with the history of headache and convulsion. The patient was diagnosed as miliary tuberculosis and multiple brain tuberculomas. Miliary infiltration was observed in chest x-ray and high-resolution thorax computed tomography (CT), and multiple tuberculomas surrounded with wide edema was observed in Magnetic Resonance Imaging (MRI). Acid-fast bacilli were detected in inducted sputum and gastric fluid. Focal epileptiform activity was seen in electroencephalography (EEG). The patient was administered antitubercular, anti-edema and antiepileptic therapy. The patient had not experienced convulsion for the second time and EEG had been normal; therefore her treatment was completed within 12 months. Chest x-ray and high-resolution thorax CT findings turned to normal and brain MRI findings improved significantly. As a conclusion, tuberculosis disease has very different clinical pattern depending on the organs it involves. The significance of our case is due to the presence of both the miliary tuberculosis and intracranial tuberculomas. The patient was admitted to the hospital due to central nervous system symtoms rather than pulmonary symptoms.