BACKGROUND: Tuberculous meningitis (TBM) is associated with high mortality and morbidity despite administering anti-tuberculous chemotherapy to the patients. Differential diagnosis between TBM and viral meningitis (VM) is difficult in some clinical situations. METHODS: We reviewed and analyzed records of adult patients who were admitted and diagnosed with TBM or VM at a tertiary hospital in Korea, between January 2006 and December 2015. Diagnostic criteria for TBM were categorized into three groups: definite, probable, and possible TBM. The VM group included patients with no evidence of other meningitis who achieved complete recovery with only conservative treatments. Clinical, laboratory and radiological findings, as well as outcomes, were compared between the TBM and VM groups. RESULTS: Ninety-eight patients were enrolled. Among the study patients, 47 had TBM and 51 had VM. Based on univariate analysis and multivariate logistic regression, sodium < 135 mmol/L in serum (hyponatremia), lactate dehydrogenase > 70 (U/L) in cerebrospinal fluid (CSF), protein > 160 (mg/dL) in CSF, voiding difficulty, and symptoms of cranial nerve palsy were significant predictive factors for TBM in the final model. We constructed a weighted scoring system with predictive factors from multiple regression analyses. Receiver operating characteristic curve analyses and decision tree analyses were plotted to reveal an optimum cutoff point as 4 with this scoring system (range: 0–13). CONCLUSION: For differential diagnosis between TBM and VM, we created a new weighted scoring system. This scoring system and decision tree analysis are simple and easy to apply in clinical practice to differentiate TBM from VM.
Adult ; Cerebrospinal Fluid ; Cranial Nerve Diseases ; Decision Trees ; Diagnosis, Differential* ; Drug Therapy ; Humans ; Korea ; L-Lactate Dehydrogenase ; Logistic Models ; Meningitis ; Meningitis, Viral* ; Mortality ; ROC Curve ; Sodium ; Tertiary Care Centers ; Tuberculosis, Meningeal*

OBJECTIVETo introduce co-word analysis into the analysis of the current research status of childhood tuberculous meningitis, to compare the similarities and differences in research topics of the field in China and abroad over the past decade, and to discover the advantages and weak links in the study field in China.

METHODSPubMed, CNKI, VIP, and Wanfang Data were searched for the articles which met the inclusion criteria. Ucinet 6.0 and Netdraw were used for co-occurrence analysis, and the co-article relationship between high-frequency key words was visualized.

RESULTSA total of 226 articles abroad and 186 Chinese articles on childhood tuberculous meningitis were obtained. The figures for co-occurrence analysis of high-frequency key words in research articles on childhood tuberculous meningitis in China and abroad were successfully plotted. Compared with the studies in China, the studies abroad were more sophisticated and well-developed, with more studies on drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis. The key words listed in the studies abroad were more standard. The studies in China on childhood tuberculous meningitis concentrated on vaccination and nursing.

CONCLUSIONSIn general, the studies on childhood tuberculous meningitis in China and abroad have the same directions. The studies abroad have a complicated network and use more standard key words. The studies on childhood tuberculous meningitis are well conducted in China. However, more studies are needed for drug-resistant tuberculosis, the relationship between tuberculosis and AIDS, and the epidemiology of tuberculosis in future.

BACKGROUND/AIMS: The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal fluid-mononuclear cells (CSF-MCs) and peripheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis (TBM) over the course of anti-TB therapy. METHODS: Adult patients (> or = 16 years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were prospectively enrolled between April 2008 and April 2011. Serial blood or CSF samples were collected over the course of the anti-TB therapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT) assay. RESULTS: Serial ELISPOT assays were performed on PBMCs from 17 patients (seven definite, four probable, and six possible TBM) and CSF-MC from nine patients (all definite TBM). The median number of interferon-gamma (IFN-gamma)-producing T-cells steadily increased during the first 6 months after commencement of anti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune responses during the first 6 weeks of anti-TB therapy, though early increases in CSF-MC ELISPOT results were associated with treatment failure or paradoxical response. CONCLUSIONS: Serial analysis of PBMCs by ELISPOT during the course of treatment was ineffective for predicting clinical response. However, increases in TB-specific IFN-gamma-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.
Adult ; Antitubercular Agents/therapeutic use ; Biological Markers/blood/cerebrospinal fluid ; *Enzyme-Linked Immunospot Assay ; Female ; Humans ; Interferon-gamma/blood/cerebrospinal fluid ; *Interferon-gamma Release Tests ; Kinetics ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Republic of Korea ; T-Lymphocytes/drug effects/*immunology/metabolism/microbiology ; Treatment Outcome ; Tuberculosis, Meningeal/blood/cerebrospinal fluid/*diagnosis/drug therapy/immunology/microbiology

We report a rare case of oculomotor nerve palsy and choroidal tuberculous granuloma associated with tuberculous meningoencephalitis. A 15-year-old male visited our hospital for an acute drop of the left eyelid and diplopia. He has been on anti-tuberculous drugs (isoniazid, rifampin) for 1 year for his tuberculous encephalitis. A neurological examination revealed a conscious clear patient with isolated left oculomotor nerve palsy, which manifested as ptosis, and a fundus examination revealed choroidal tuberculoma. Other anti-tuberculous drugs (pyrazinamide, ethambutol) and a steroid (dexamethasone) were added. After 3 months on this medication, ptosis of the left upper eyelid improved and the choroidal tuberculoma decreasedin size, but a right homonymous visual field defect remained. When a patient with tuberculous meningitis presents with abrupt onset oculomotor nerve palsy, rapid re-diagnosis should be undertaken and proper treatment initiated, because the prognosis is critically dependent on the timing of adequate treatment.
Adolescent ; Antitubercular Agents/therapeutic use ; Blepharoptosis/diagnosis/drug therapy/microbiology ; Choroid Diseases/diagnosis/drug therapy/*microbiology ; Dexamethasone/therapeutic use ; Drug Therapy, Combination ; Ethambutol/therapeutic use ; Glucocorticoids/therapeutic use ; Humans ; Magnetic Resonance Imaging ; Male ; Meningoencephalitis/diagnosis/drug therapy/*microbiology ; Mycobacterium tuberculosis/*isolation & purification ; Oculomotor Nerve Diseases/diagnosis/drug therapy/*microbiology ; Perimetry ; Pyrazinamide/therapeutic use ; Radiography, Thoracic ; Tuberculoma/diagnosis/drug therapy/*microbiology ; Tuberculosis, Meningeal/diagnosis/drug therapy/*microbiology ; Tuberculosis, Ocular/diagnosis/drug therapy/microbiology ; Visual Fields

A 23-month-old girl visited with chronic cough and her chest radiograph showed miliary tuberculosis. There was no neurological abnormality. But CSF findings showed WBC 22/mm3(lymphocyte 20%, neutrophil 80%) and positive result of polymease chain reaction(PCR) for M. tuberculosis. MR imaging showed multiple ring enhanced nodules and ovoid nonenhancing bright signal lesion on the cerebrum, cerebellar parenchyme, and left basal ganglia. Antituberculous chemotherapy was done and follow-up MR imaging was done after six months. One month after treatment, the number and size of nodules had decreased. Six months after treatment, the multiple enhanced nodules and leptomeningeal enhancement were not observed, and high signal intensity of genu portion of left internal capsule and posterior portion of putamen were decreased.
Basal Ganglia ; Brain* ; Cerebrum ; Cough ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Infant ; Internal Capsule ; Magnetic Resonance Imaging* ; Neutrophils ; Putamen ; Radiography, Thoracic ; Tuberculosis* ; Tuberculosis, Meningeal ; Tuberculosis, Miliary*

Central nervous system(CNS) involvement by tuberculosis is uncommon in comparison to the involvement of other systems. Untreated tuberculous meningitis is characterized by progressive stupor and a fatal outcome within 4 to 8 weeks of the onset of symptoms. So rapid detection of Mycobacterium tuberculosis is of vital importance for these patients. In almost all patients with tuberculous meningitis, acid-fast bacteria are undetectable in the CSF. Culture techniques that permit the identification of the isolated mycobacterial species require several weeks. We report a case of tuberculous meningitis with intracranial tuberculoma in 8-year old male who experienced pleural effusion, repeatedly. CSF findings did not reveal diagnosis tuberculous meningitis. In MRI study, multiple intracranial tuberculomas were located at the cerebellum. Prolonged treatment with anti- tuberculous chemotherapy and high-dose corticosteroids led to complete recovery.
Adrenal Cortex Hormones ; Bacteria ; Cerebellum ; Child ; Culture Techniques ; Diagnosis ; Drug Therapy ; Fatal Outcome ; Humans ; Magnetic Resonance Imaging ; Male ; Mycobacterium tuberculosis ; Pleural Effusion* ; Stupor ; Tuberculoma* ; Tuberculoma, Intracranial ; Tuberculosis ; Tuberculosis, Meningeal

PURPOSE: Tuberculosis may cause a serious complication in children with cancer who are receiving the chemotherapy. But its diagnosis is not easy if we do not suspect the disease in patients with uncontrolled persistent fever. We studied retrospectively the importances of prevention and early diagnosis of tuberculosis in cancer patients. METHPDS: Twelve patients were diagnosed as having tuberculosis during cancer chemotherapy in Kyungpook National University Hospital from May, 1981 to May, 1998. We reviewed their clinical features, diagnostic methods, treatment and prevention. RESULTS: The median age of the patients was 14 (2~18) years. The underlying diseases were seven acute lymphoblastic leukemia (ALL), two acute undifferentiated leukemia (AUL), one acute nonlymphoblastic leukemia (ANLL), one mixed-lineage leukemia, and one Burkitt's lymphoma. The disease categories of tuberculosis were seven pulmonary tuberculosis, two tuberculous pleurisy, one miliary tuberculosis, one bone and endotracheal tuberculosis and one tuberculous meningitis. The family history of tuberculosis is positive in one case. The clues of the suspicion of tuberculosis infections were 9 cases of persistent fever despite broad spectrum of antibiotics and/or antifungal agent therapy, 2 chronic cough and 1 chest pain. We could diagnose four by AFB culture, three cases by AFB smear, two by polymerase chain reaction (PCR), one by pleural biopsy, one by transbronchial lung biopsy and one by chest X-ray and CSF study. We treated pulmonary tuberculosis and tuberculous pleurisy by triple therapy (isoniazid, rifampin, pyrazinamide) and miliary, bone, endotracheal tuberculosis and tuberculous meningitis by quadriple therapy (isoniazid, rifampin, pyrazinamide, streptomycin or kanamycin). The mean duration of defervescence after treatment was 15.4 days. One died of fulminant hepatitis probably by hepatitis B after completion of cancer chemotherapy, one died of adult respiratory distress syndrome, two died of DIC, three died of relapse of underlying disease, but no one died of tuberculosis infection itself. CONCLUSION: The early diagnosis of tuberculosis is an important factor for decreasing the mortality rates of cancer patients, so we should have a suspicion of this disease in patients with persistent fever in spite of appropriate antibiotic and antifungal agents. Isoniazid prophylaxis may be needed in childhood cancer patients with chemotherapy in Korea.
Anti-Bacterial Agents ; Antifungal Agents ; Biopsy ; Burkitt Lymphoma ; Chest Pain ; Child ; Cough ; Dacarbazine ; Diagnosis ; Drug Therapy* ; Early Diagnosis ; Fever ; Gyeongsangbuk-do ; Hepatitis ; Hepatitis B ; Humans ; Isoniazid ; Korea ; Leukemia ; Leukemia, Myeloid, Acute ; Lung ; Mortality ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Pyrazinamide ; Recurrence ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Rifampin ; Streptomycin ; Thorax ; Tuberculosis* ; Tuberculosis, Meningeal ; Tuberculosis, Miliary ; Tuberculosis, Pleural ; Tuberculosis, Pulmonary

Intradural extramedullary (IDEM) tuberculoma of the spinal cord is uncommon entity and moreover, few reports have been documented on concurrent IDEM and intracranial tuberculomas. Authors report a case of IDEM spinal tuberculoma having intracranial lesion simultaneously. A 49-year-old woman suffered from paraparesis and urinary incontinence while being given medical treatment for tuberculous meningitis. Magnetic resonance imaging (MRI) revealed an IDEM mass lesion between the T1 and T2 spinal levels, and multiple intracranial tuberculous granulomas. Surgical resection of the IDEM tuberculoma followed by anti-tuberculous medication resulted in good outcome.
Brain/radiography ; Case Report ; Female ; Follow-Up Studies ; Human ; Magnetic Resonance Imaging ; Middle Age ; Mycobacterium tuberculosis/isolation & purification ; Spinal Cord Diseases/radiography* ; Tuberculoma/surgery ; Tuberculoma/radiography ; Tuberculoma/drug therapy ; Tuberculoma/complications* ; Tuberculosis, Meningeal/surgery ; Tuberculosis, Meningeal/radiography ; Tuberculosis, Meningeal/drug therapy ; Tuberculosis, Meningeal/complications*

Syringomyelia can occur as a complication of tuberculous meningitis despite of appropriate chemotherapy and almost it is founded with motor and sensory disturbances. We have experienced a case of an extensive syringomyelia & syringobulbia in tuberculous meningitis who complained only mild numbness & diplopia without specific motor disturbance. So we think that we should not overlook even mild symptoms and have to evaluate the syringomyelia timely by radiographic study.
Diplopia ; Drug Therapy ; Humans ; Hypesthesia ; Paraplegia* ; Syringomyelia* ; Tuberculosis, Meningeal*

Ommaya reservoir implantation has been used for sterile assessment into ventricular CSF or direct chemotherapy of chronic meningitis and meningeal involvement of malignancy since 1963. We experienced two cases with chronic meningitis, one was tuberculous meningitis with obstructive hydrocephalus which was not improved by repetitive shunt and the other was cryptococcal meningitis which was not improved by traditional chemotherapy of intravenous amphotericin B and oral flucytosine. Ommaya reservoir was implanted for daily CSF drainage of intractable hydrocephalus in the first patient and for direct injection of amphotericin B into ventricle in the second patient. Both of two cases were successfully managed by the reservoir. Therefore, Ommaya reservoir could be useful in patients with chronic meningitis which are not improved by traditional management.
Amphotericin B ; Drainage ; Drug Therapy ; Flucytosine ; Humans ; Hydrocephalus ; Meningitis ; Meningitis, Cryptococcal ; Tuberculosis, Meningeal