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*

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid (CSF) T-SPOT.TB test for the diagnosis of TB meningitis (TBM). A retrospective analysis of 96 patients with manifested meningitis was conducted; T-SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A receiver operating characteristic (ROC) curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T-SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients (54.2%) of the 96 enrolled patients. The area under the curve (AUC) was 0.910, and the sensitivities of CSF T-SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T-SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM.
China ; epidemiology ; Humans ; Sensitivity and Specificity ; Tuberculosis, Meningeal ; cerebrospinal fluid ; diagnosis ; epidemiology

Syringomyelia associated with tuberculous meningitis is an extremely rare condition. Only a few studies have reported clinical experience with syringomyelia as a late complication of tuberculous meningitis. Twenty-six years after a tuberculous meningitis episode, a 44-year-old man presented with progressively worsening spastic paresis of the lower limbs and impaired urinary function for 2 years. Radiological examination revealed syringomyelia extending from the level of C2 to T9 and arachnoiditis with atrophy of the spinal cord between C2 and T3. We performed laminectomy from C7 to T1, dissected the arachnoid adhesion and placed a syringo-pleural shunt via keyhole myelotomy. One year after the operation, his neurological condition improved. The postoperative control magnetic resonance imaging revealed the correctly located shunt and significantly diminished syringomyelia cavities. We aim to discuss the mechanism of syrinx formation following tuberculous meningitis and to share our surgical therapeutic experience with this rare disease entity.
Adhesives* ; Adult ; Arachnoid* ; Arachnoiditis* ; Atrophy ; Cerebrospinal Fluid Shunts ; Humans ; Laminectomy ; Lower Extremity ; Magnetic Resonance Imaging ; Muscle Spasticity ; Paresis ; Rare Diseases ; Spinal Cord ; Syringomyelia* ; Tuberculosis, Meningeal*

BACKGROUND: Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. MATERIALS AND METHODS: All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. RESULTS: Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. CONCLUSION: About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed.
Adenosine Deaminase ; Adult ; Cerebrospinal Fluid ; Diagnosis, Differential ; Diagnostic Tests, Routine ; Glucose ; Herpesvirus 3, Human ; Humans ; Intensive Care Units ; Korea ; Meningitis* ; Meningitis, Aseptic ; Seoul ; Tertiary Care Centers ; Tuberculosis, Meningeal

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

Pseudomembranous colitis (PMC) is known to be associated with the long-term administration of antibiotics, which alter normal gastrointestinal flora and allow overgrowth of Clostridium difficile. However, antituberculosis agents are rarely reported as a cause of this disease. Besides, most cases of antituberculosis agent-induced PMC have been observed in patients with pulmonary tuberculosis but not with tuberculous meningitis. This report presents a case of PMC associated with antituberculosis therapy in a patient with tuberculous meningitis. A 29-year-old female patient was admitted due to headaches and diplopia that had lasted for 2 weeks. She had not recently received antimicrobial therapy. She was diagnosed with tuberculous meningitis by cerebrospinal fluid findings and neurologic examination, including brain imaging study. She was treated with standard antituberculosis agents (HERZ regimen: isoniazid, ethambutol, rifampicin, and pyrazinamide). After 11 days of HERZ, she developed a fever, sudden widespread skin eruption, and elevation of liver enzymes. Considering adverse drug reactions, antituberculosis agents were stopped. One week later, her symptoms were relieved. Thus, antituberculosis agents were reintroduced one at a time after liver function returned to normal. However, she presented with frequent mucoid, jelly-like diarrhea, and lower abdominal pain. Sigmoidscopy revealed multiple yellowish plaques with edematous mucosa, which were compatible with PMC. She was treated with oral vancomycin considering drug interactions. Symptoms were relieved and did not recur when all antituberculosis agents except pyrazinamide were started again. Therefore, when a patient complains of abdominal pain or diarrhea after initiation of antituberculosis therapy, the physician should consider the possibility of antituberculosis agent-associated PMC.
Abdominal Pain ; Adult ; Anti-Bacterial Agents ; Cerebrospinal Fluid ; Clostridium difficile ; Diarrhea ; Diplopia ; Drug Interactions ; Drug-Related Side Effects and Adverse Reactions ; Enterocolitis, Pseudomembranous* ; Ethambutol ; Female ; Fever ; Headache ; Humans ; Isoniazid ; Liver ; Mucous Membrane ; Neuroimaging ; Neurologic Examination ; Pyrazinamide ; Rifampin ; Skin ; Tuberculosis, Meningeal* ; Tuberculosis, Pulmonary ; Vancomycin

Cerebral tuberculosis is the most severe type of extrapulmonary disease that is in developing countries highly predominant in children. Meningeal tuberculosis is the most common form and usually begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. In comparison with the lung, Mycobacterium tuberculosis induces a very different immune response when infect the central nervous system. Herein, we review several aspects of the pathogenesis and immune response in pulmonary and cerebral tuberculosis in humans and experimental models and discuss the implications of this response in the cerebral infection outcome.
Tuberculosis ; Tuberculosis, Meningeal ; Cerebrospinal Fluid

PURPOSE: Late diagnosis and treatment lead to high mortality and poor prognosis in tuberculous meningitis (TbM). A rapid and accurate diagnosis is necessary for a good prognosis. Neuron-specific enolase (NSE) has been investigated as a biochemical marker of nervous tissue damage. In the present study, the usefulness of NSE was evaluated, and a cut-off value for the differential diagnosis of TbM was proposed. MATERIALS AND METHODS: Patient charts were reviewed for levels of serum and cerebrospinal fluid (CSF) NSE, obtained from a diagnostic CSF study of samples in age- and gender-matched TbM (n=15), aseptic meningitis (n=28) and control (n=37) patients. RESULTS: CSF/serum NSE ratio was higher in the TbM group than those of the control and aseptic groups (p=0.001). In binary logistic regression, CSF white blood cell count and CSF/serum NSE ratio were significant factors for diagnosis of TbM. When the cut-off value of the CSF/serum NSE ratio was 1.21, the sensitivity was 86.7% and the specificity was 75.4%. CONCLUSION: The CSF/serum NSE ratio could be a useful parameter for the early diagnosis of TbM. In addition, the authors of the present study suggest a cut-off value of 1.21 for CSF/serum NSE ratio.
Adult ; Case-Control Studies ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Phosphopyruvate Hydratase/*blood/*cerebrospinal fluid ; Tuberculosis, Meningeal/blood/*diagnosis/metabolism

OBJECTIVETo improve the differential diagnosis of tuberculous meningitis (TBM) and reduced potential misdiagnosis of TBM.

METHODSThe clinical data of 47 misdiagnosed cases of TBM between January, 1994 and June, 2009 were investigated retrospectively. The clinical presentations and causes for the misdiagnoses were analyzed.

RESULTSThe 47 patients with misdiagnosed TBM included 28 male and 19 female patients with a mean age of 36.84∓16.41 years. Eight patients had an acute onset, 10 had a subacute onset, and 29 had chronic disease. The initial symptoms, in the descending order of their frequencies, included fever and headache (87.2%), anergia and dyskinesia (27.7%), cerebral nerve damage (23.4%), decreased level of consciousness (14.9%), and urinary and fecal incontinence (2%). Meningeal irritation was present in 25 cases and positive Babinksi sign was found in 19 cases. Elevated intracranial pressure occurred in 51.1% of the cases, and 16 cases showed papilloedema. Non-purulent CSF with elevated protein was found in 86.7%, decreased glucose in 50%, and decreased chlorinate in 53.3% of the cases. Eight out of 23 cases showed a positive result of PPD test. MRI identified abnormitis with meningeal enhancement in 15 cases, hydrocephalus in 7 cases and infarction in 14 cases. Tuberculoma was found in 2 cases, and spinal cord lesions were found 4 cases. All the patients received anti-tuberculosis therapy, which resulted in symptomatic improvement in 39 cases, fluctuated condition in 2 cases; 5 patients discontinued the treatment and 1 died.

CONCLUSIONEarly TBM often presents with atypical features and its differential diagnosis can be difficult. CSF monitoring and careful inspection of the radiographic data can be helpful in the diagnosis of suspected cases, for which early anti-TB treatment is an important means to reduce misdiagnosis.

Adult ; Diagnosis, Differential ; Diagnostic Errors ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tuberculosis, Meningeal ; cerebrospinal fluid ; diagnosis ; Young Adult

OBJECTIVETo investigate the significance of soluble DLL1 (Delta-like-1) levels of cerebrospinal fluid (CSF) and serum in the diagnosis of intracranial infection in children.

METHODSFifty children with intracranial infection, including 20 cases of tuberculous meningitis (TM), 20 cases of viral meningitis (VM) and 10 cases of purulent meningitis (PM), and 20 children without intracranial infection (control group) were enrolled. The levels of soluble DLL1 in CSF and serum were measured using ELISA.

RESULTSThe level of CSF soluble DLL1 in the TM group was significantly higher than that in the VM, PM and control groups (2.89 ± 1.72 ng/mL vs 0.14 ± 0.14 ng/mL, 0.27 ± 0.21 ng/mL, 0.13 ± 0.12 ng/mL; P<0.01). The level of serum soluble DLL1 in the TM group was also significantly higher than that in the VM, PM and control groups (12.61 ± 6.45 ng/mL vs 2.28 ± 2.27 ng/mL, 2.38 ± 1.79 ng/mL, 2.26 ± 2.10 ng/mL; P<0.01). The levels of soluble DLL1 in the CSF and serum in the VM and PM groups were not significantly different from those in the control group.

CONCLUSIONSSoluble DLL1 as a novel indicator might have potentially important value in the diagnosis of TM.

Adolescent ; Child ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; blood ; cerebrospinal fluid ; Male ; Membrane Proteins ; analysis ; blood ; cerebrospinal fluid ; Meningitis, Bacterial ; diagnosis ; Meningitis, Viral ; diagnosis ; Suppuration ; diagnosis ; Tuberculosis, Meningeal ; diagnosis