High Cerebrospinal Fluid Protein Concentration Research Articles

Prospective Cohort Study of Next-Generation Sequencing as a Diagnostic Modality for Unexplained Encephalitis in Children.

Encephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens. Hospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database. Twenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis. We describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.

Clinical and Laboratory Characteristics of Symptomatic and Asymptomatic Neurosyphilis in HIV-Negative Patients: A Retrospective Study of 264 Cases

A retrospective study was performed to compare the differences in clinical and laboratory features of asymptomatic neurosyphilis (ANS) and symptomatic neurosyphilis (SNS). A total of 264 HIV-negative inpatients with neurosyphilis were enrolled from Beijing Ditan Hospital and Beijing Tiantan Hospital between January 2014 and May 2018, including 110 SNS and 154 ANS. The SNS group had more patients in males, older median age and without antisyphilis treatment than ANS group (P<0.001, P<0.001, and P<0.001, respectively). The laboratory findings showed that the SNS group had higher pretreatment serum rapid plasma regain (RPR) titer, current serum RPR titer, cerebrospinal fluid (CSF) white blood cell (WBC) counts, CSF protein concentrations, and higher positive CSF RPR rate than those in the ANS group (P=0.011, P<0.001, P<0.001, P<0.001, and P<0.001, respectively). The multivariate logistic regression analysis revealed that male (OR=2.833, P=0.009), age≥45 years (OR=3.611, P=0.001), without antisyphilis treatment (OR=0.247, P<0.001), higher current serum RPR titer (OR=1.373, P=0.022), positive CSF RPR (OR=4.616, P<0.001), and higher CSF protein concentration (OR=1.017, P=0.026) were independent risk predictors for SNS. Therefore, clinical and laboratory features between SNS and ANS are quietly different. Male gender, age≥45 years, and lack of antisyphilis treatment are risk factors for SNS. The elevated level of serum RPR titer, CSF protein concentration, and CSF RPR titer may indicate the development of neurosyphilis and the aggravation of neurological symptoms.

Sequelae of tick-borne encephalitis in retrospective analysis of 1072 patients.

Tick-borne encephalitis (TBE) is an emerging vector-borne disease in Europe. The aim of the study was to evaluate sequelae and to analyse the potential risk factors predisposing to sequelae development. We performed a retrospective analysis of medical records of 1072 patients who received a 1-month follow-up appointment after hospital discharge. Medical data, such as patients' age, gender, place of living, subjective complaints, neurological and psychiatric sequelae were evaluated twice: at the moment of discharge and at follow-up visits 1 month after discharge. We observed that sequelae may affect 20.6% of TBE patients. Subjective sequelae were more frequent than subjective complaints during the hospitalisation (P < 0.001), while objective neurological symptoms during the hospitalisation were more pronounced than neurological sequelae (P < 0.001). Patients with meningoencephalomyelitis were predisposed to neurological complications, while subjective symptoms were more common in meningoencephalitis. Independent risk factors for sequelae development were: age and cerebrospinal fluid (CSF) protein concentration. The risk of late neurological complications persisting was increased in patients with higher CSF protein concentration. Based on the results of our study we concluded that, there is a need for a better vaccination program, which would prevent the development of sequelae.

Primary central nervous system lymphoma: a new prognostic model for patients with diffuse large B-cell histology.

BackgroundAge and performance status are important prognostic factors in primary central nervous system (CNS) lymphoma. Although several prognostic models have been proposed, there is no consensus on the optimal model for patients with diffuse large B-cell histology.MethodsSeventy-seven patients with primary CNS diffuse large B-cell lymphoma were retrospectively analyzed to determine factors affecting survival. Three Western models were applied to our eligible patients; we devised a novel model based on our findings.ResultsThe median patient age was 59 years (range, 29–77); the median event-free and overall survival (OS) durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and Memorial Sloan Kettering Cancer Center models were applicable to our cohorts. Multivariate analysis showed that advanced age, multifocal lesions, and high cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A novel model for predicting prognosis was then developed based on these variables. Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3 were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very high-risk groups (N=4), respectively. Sixty-one patients were eligible considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).ConclusionAdvanced age, multifocal lesions, and high CSF protein concentration were adversely related with prognosis. Our model can be helpful in pre-treatment risk stratification for patients with primary CNS lymphoma with diffuse large B-cell histology.

Clinical and imaging characteristics in neonatal refractory purulent meningitis

Objective To identify the clinical and imaging characteristics in neonatal refractory purulent meningitis. Methods Clinical data of 70 cases of neonatal purulent meningitis admitted to the neonatal intensive care unit at Children's Hospital of Fudan University from January, 2009 to December, 2014 were reviewed retrospectively. The patients were divided into refractory group (n=28) and non-refractory group (n=42) according to the course of antimicrobial therapy. The clinical and brain MRI characteristics of neonatal refractory purulent meningitis were analyzed. Parameters were compared between the two groups using Chi-square or Fisher's exact tests, and Wilcoxon tests where appropriate. Risk factors of neonatal refractory purulent meningitis were investigated by univariate and multivariate Logistic regression analysis. Results Among the 70 cases, 31(44.3%) were positive for cerebrospinal fluid (CSF)/blood culture. The positive rate was higher in the refractory group than in the non-refractory group [75.0% (21/28) vs 23.8% (10/42), χ2=17.843, P<0.01]. The most common pathogenic bacteria isolated in the refractory group were Escherichia coli [8 cases (38.1%)] and group B streptococci [5 cases (23.8%)]. Compared to the non-refractory group, patients in the refractory group were more likely to have seizure, higher CSF white blood cell count, higher CSF protein concentration and lower CSF glucose concentration [53.6%(15/28) vs 7.1% (3/42), 965.0 (463.0-2 200.0)×106/L vs 116.5 (61.0-327.5)×106/L, 3 221.1(2 354.3-4 633.5) mg/L vs 1 487.6(988.2-1 924.1) mg/L, and 0.2 (0.1-0.8) mmol/L vs 1.5 (1.2-1.8) mmol/L; all P<0.01]. Multivariate Logistic regression analysis showed that seizure, low CSF glucose concentration on admission, and a positive CSF/blood culture result neonatal refractory purulent meningitis (OR=9.6, 95%CI: 1.2-76.0; OR=15.0, 95%CI: 5.6-63.3; and OR=7.3, 95%CI: 1.5-36.0, respectively). Abnormal brain MRI findings, including intracranial extracerebral space abnormality, ventricular dilatation and periventricular white matter injury, were more common in the refractory group [100.0%(28/28) vs 61.9%(26/42), χ2=13.827 totally; 64.3%(18/28) vs 21.4%(9/42), χ2=13.023 for intracranial extracerebral space abnormality; 60.7%(17/28) vs 19.0%(8/42), χ2=12.704 for ventricular dilation and 28.6%(8/28) vs 2.4%(1/42) for periventricular white matter injury; all P <0.01]. Compared with the non-refractory group, the refractory group had a longer hospital stay [(48.0±17.4) d vs (26.0±10.2) d, t=6.016, P<0.01] and more adverse events [67.9%(19/28) vs 31.0%(13/42), χ2=9.220, P=0.002], including hearing impairment and requirement of neurosurgical intervention [14/18 ears vs 10/46 ears (21.7%), χ2=4.292, P=0.038]. There was no death in both groups during hospitalization. Conclusions Neonates with seizure, low CSF glucose concentration and positive CSF/blood culture results are more likely to have refractory purulent meningitis. Brain MRI abnormalities are more common in neonatal refractory purulent meningitis. Key words: Meningitis, bacterial; Magnetic resonance imaging

A systematic review of the risks factors associated with the onset and natural progression of hydrocephalus

The purpose of this study was to systematically assess and synthesize the world literature on risk factors for the onset and natural progression of hydrocephalus, thereby providing a basis for policy makers to identify appropriate risk management measures to mitigate the burden of disease in Canada. Evidence for risk factors was limited for both onset and progression. Two meta-analyses that examined a risk factor for onset met the inclusion criteria. One found a significant protective effect of prenatal vitamins among case control studies, but not cohort/randomized controlled trials (RCTs). The second found maternal obesity to be a significant risk factor for congenital hydrocephalus. Significant risk factors among 25 observational studies included: biological (multiple births, maternal parity, common cold with fever, maternal thyroid disease, family history, preterm birth, hypertension, ischemic heart disease, ischemic ECG changes, higher cerebrospinal fluid protein concentration following vestibular schwannoma); lifestyle (maternal obesity, high-density lipoprotein (HDL) cholesterol, maternal diabetes, maternal age), healthcare-related (caesarean section, interhospital transfer, drainage duration following subarachnoid hemorrhage, proximity to midline for craniectomy following traumatic brain injury); pharmaceutical (prenatal exposure to: tribenoside, metronidazole, anesthesia, opioids); and environmental (altitude, paternal occupation). Three studies reported on genetic risk factors: no significant associations were found. There are major gaps in the literature with respect to risk factors for the natural progression of hydrocephalus. Only two observational studies were included and three factors reported. Many risk factors for the onset of hydrocephalus have been studied; for most, evidence remains limited or inconclusive. More work is needed to confirm any causal associations and better inform policy.

Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein

Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1–4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis.

Factors influencing shunt malfunction in patients with tuberculous meningitis

Abstract Hydrocephalus secondary to tuberculous meningitis (TBM) is a challenging condition to treat. Though ventriculo-peritoneal (VP) shunt is an accepted modality of treatment for hydrocephalus in TBM, there is a high rate of complications associated with the same. The study was planned to evaluate various factors associated with shunt malfunction in patients undergoing VP shunt surgery for hydrocephalus due to TBM. A retrospective review of all the patients undergoing VP shunt and shunt revision for TBM between 2004 and 2008 was performed. 449 VP shunt surgeries were performed in 432 patients for hydrocephalus due to TBM. Among these 70 shunt revisions were performed in 53 patients. Shunt malfunction rate in our series was 16.2%. High cerebrospinal fluid (CSF) protein concentration (&gt;200 mg/dL) was associated with 5 times increased incidence of shunt malfunction. Patients with hyponatremia (Na+ &lt;130 mEq/dL) prior to surgery had a 3 times increased incidence of shunt malfunction (P &lt; 0.05). Other factors such as duration of symptoms, presence of neurological deficits, Evan’s index, third ventricular diameter, thickness of exudates, presence of infarcts, anemia, CSF cellularity and CSF glucose concentration were not associated with increased incidence of shunt malfunction. Analysis showed that shunt viability was longest in patients with normal serum sodium levels and CSF protein concentration less than 200 mg/dL and shortest in patients with low serum sodium and CSF protein concentration more than 200 mg/dL. Patients with pre-operative hyponatremia and high CSF protein concentration have a higher incidence of shunt malfunction and need to be followed-up closely.

Factors for poor prognosis of neonatal bacterial meningitis in a medical center in Northern Taiwan

Bacterial meningitis has long been a severe infectious disease in neonates, as well as a leading cause of adverse outcomes. We designed this study to know the factors for poor prognosis in neonatal bacterial meningitis. We enrolled children aged less than 1 month who were admitted to Mackay Memorial Hospital from 1984 to 2008 and had culture-proven bacterial meningitis. The laboratory data and children's clinical features were recorded. The patients' outcomes were divided into four groups: death, having sequelae, complete recovery, and loss to follow-up. Patients with the outcomes of death and having sequelae were regarded as having a poor prognosis. Those who were lost to follow-up were excluded from the analysis of outcome. Multivariate analyses were performed to find the risk factors for poor prognosis. One hundred fifty-six neonates fulfilled the inclusion criteria. Among these, 96 were boys (61.5%) and 102 (65.4%) had concomitant bacteremia. Group B streptococci (39.1%) and Escherichia coli (20.1%) were the two leading pathogens. Excluding those who were lost to follow-up (4.5%), 22 of 149 patients (14.8%) died, 36 (24.2%) had sequelae, and 91 (61.1%) recovered completely. Cerebrospinal fluid (CSF) protein more than 500 mg/dL at admission {odds ratio (OR): 171.18 [95% confidence interval (CI): 25.6-1000]}, predisposition to congenital heart disease [OR: 48.96 (95% CI: 6.06-395.64)], hearing impairment found during hospitalization [OR: 23.40 (95% CI: 3.62-151.25)], and seizure at admission or during hospitalization [OR: 10.10 (95% CI: 2.11-48.32)] were the factors predicting poor prognosis. In this 25-year study of newborns with bacterial meningitis, approximately one-seventh of the patients died, while two-fifths had sequelae. Nearly two-thirds of these had concomitant bacteremia. Group B streptococci and E. coli remained the two leading pathogens throughout the study period. Several factors for poor prognosis in newborns with culture-proven bacterial meningitis were found: high CSF protein concentration, congenital heart disease, hearing impairment, and seizure.

Reversible extensive leukoencephalopathy in Sweet disease: A case report

Sweet disease, also known as acute febrile neutrophilic dermatosis, is an idiopathic multisystem inflammatory disorder characterised by erythematous skin lesions and fever. “Neuro-Sweet disease” is a rare central nervous system involvement that coexists with the characteristic cutaneous lesions of Sweet disease. Here, we report a case of Sweet disease complicated with acute encephalopathy. This case showed extensive lesions in the cerebral white matter on magnetic resonance imaging (MRI) and high protein concentration in the cerebrospinal fluid (CSF) without pleocytosis. After steroid therapy, the patient's clinical syndrome recovered completely with no significant neurological deficits or abnormal findings on brain MRI, and normalization of the high CSF protein concentration. Both clinical and MRI findings suggested that the marked leukoencephalopathy in this case was mainly due to reversible oedema rather than destructive structural alterations in the cerebral parenchyma.

The relation of cerebrospinal fluid and plasma glycine levels in propionic acidaemia, a ‘ketotic hyperglycinaemia’

The characteristic elevation of plasma glycine concentrations observed in propionic acidaemia (PA) and other 'ketotic hyperglycinaemias' has been attributed to secondary inhibition of the hepatic glycine cleavage system (GCS) by accumulating CoA derivatives of branched-chain amino acid metabolites. In nonketotic hyperglycinaemia (NKH), cerebrospinal fluid (CSF) and plasma glycine levels and their ratio are increased due to primary deficiency of central nervous system (CNS) as well as hepatic GCS. Whether the GCS in the CNS is also inhibited in PA is unclear, as there are scant data available on CSF glycine levels in this disorder. We studied the relation of CSF and plasma glycine levels in 6 paired samples from 4 PA patients, including one PA patient with bacterial meningitis who underwent ventriculoperitoneal shunting and multiple CSF analyses (n = 26). In contrast to the CSF glycine levels which were generally elevated in all four PA patients, the CSF/plasma glycine concentration ratios in paired samples were normal (0.016-0.029), with the exception of a single sample (0.132) with extremely high CSF protein concentration (2010 mg/L) during the course of meningitis indicating a disturbed blood-brain barrier. This finding of normal CSF/plasma glycine ratio in PA suggests that the observed elevations of CSF glycine levels are a reflection of the concurrent hyperglycinaemia resulting from secondary inhibition of hepatic GCS, but that brain GCS is not affected, in contrast to the situation in NKH. The neurological sequelae in PA are therefore unlikely to be related to disturbed glycine metabolism.

ETIOPATHOLOGICAL FACTORS RELATED TO HYDROCEPHALUS ASSOCIATED WITH VESTIBULAR SCHWANNOMA

We retrospectively analyzed various clinical factors to determine whether or not these factors are etiopathologically related to the development of hydrocephalus in patients with vestibular schwannomas. There were 68 patients (29 men, 39 women) in this study who underwent resection of a vestibular schwannoma. The age at the time of surgery ranged from 19 to 76 years (mean age, 51.4 yr). The maximum diameter of the tumor in the cerebellopontine cistern ranged from 0 (localized within the internal auditory canal) to 56 mm (mean, 32.0 +/- 12.9 mm). Cerebrospinal fluid (CSF) protein concentration in the cerebellomedullary cistern was measured intraoperatively in all patients. Sixteen (23.5%) of the 68 patients exhibited radiographic evidence of hydrocephalus. Univariate analysis of various factors revealed that both tumor size and CSF protein concentration were positively related to development of hydrocephalus (P < 0.05 and P < 0.01, respectively). However, in multiple logistic regression analysis, only the CSF protein concentration was predictive for development of hydrocephalus (P = 0.022). There was a trend toward increased CSF protein concentration in patients with a large tumor (> or = 40 mm) compared with those with a small tumor (< 40 mm) (P = 0.06). A high CSF protein concentration in fluid from the cerebellomedullary cistern is one of the most important factors contributing to hydrocephalus associated with vestibular schwannoma. It is important to judge whether or not any further treatment is required for hydrocephalus, in addition to tumor resection, especially in patients with communicating hydrocephalus.

Agarose gel electrophoresis of cerebrospinal fluid proteins of dogs after sample concentration using a membrane microconcentrator technique

Cerebrospinal fluid (CSF) is produced in the cerebral ventricles through ultrafiltration of plasma and active transport mechanisms. Evaluation of proteins in CSF may provide important information about the production of immunoglobulins within the central nervous system as well as possible disturbances in the blood-brain barrier. The objective of this study was to measure the concentration and fractions of protein in CSF samples using a membrane microconcentrator technique followed by electrophoresis, and to compare the protein fractions obtained with those in serum. CSF samples from 3 healthy dogs and 3 dogs with canine distemper virus infection were concentrated using a membrane microconcentrator having a 0.5 to 30,000 d nominal molecular weight limit (Ultrafree, Millipore, Billerica, MA, USA). Protein concentration was determined before and after concentration. Agarose gel electrophoresis was done on concentrated CSF samples, serum, and serial dilutions of one of the CSF samples. Electrophoretic bands were clearly identified in densitometer tracings in CSF samples with protein concentrations as low as 1.3 g/dL. The higher CSF protein concentration in dogs with distemper was mainly the result of increased albumin concentration. The microconcentrating method used in this study enables characterization of the main protein fractions in CSF by routine electrophoresis and may be useful for interpreting the underlying cause of changes in CSF protein concentrations.

Clinical features, complications, and outcome in adults with pneumococcal meningitis: a prospective case series

Bacterial meningitis is a grave disease of high incidence, especially in less developed countries. Here, we describe its clinical presentation, spectrum of complications, prognostic factors, and outcome in adults with pneumococcal meningitis. From October, 1998, to April, 2002, we assessed 352 episodes of community-acquired pneumococcal meningitis, confirmed by culture of cerebrospinal fluid (CSF), which occurred in patients older than 16 years. Predictors for an unfavourable outcome (Glasgow outcome scale score 1-4) were identified by logistic regression with multiple imputation techniques. 245 (70%) episodes of pneumococcal meningitis were associated with an underlying disorder. Cranial CT was done for 85% of episodes and revealed underlying disorders in 17% (50/299) and meningitis-associated intracranial complications in 39% (117/299). Independent predictors for an unfavourable outcome were a low score on the Glasgow coma scale, cranial nerve palsies, a raised erythrocyte sedimentation rate, a CSF leucocyte count less than 1000 cells per mm(3), and a high CSF protein concentration on admission. Overall in-hospital mortality was 30%. Prevalence of neurological and systemic complications did not differ between patients aged younger than 60 years and those aged 60 years and older; however, systemic complications were the cause of death in 59% (32/54) of fatal episodes in patients aged 60 years and older, whereas neurological complications were the cause of death in 65% (20/31) of fatal episodes in younger patients. Pneumococcal meningitis is associated with high mortality and morbidity rates in adults. Whereas neurological complications are the leading cause of death in younger patients, elderly patients die predominantly from systemic complications.

Tick-borne encephalitis in north-eastern Poland in 1997-2001: a retrospective study.

The aim of this study was to characterize the epidemiology and clinical features of tick-borne encephalitis in north-eastern Poland. Clinical and epidemiological data were analysed of patients hospitalized with the diagnosis in the Department of the Infectious Diseases and Neuroinfections of the Medical University in Bialystok in 1997-2001. Tick-borne encephalitis was diagnosed in 152 patients: 51 (34%) presented with meningitis, 89 (59%) with meningoencephalitis and 12 (8%) with meningoencephalomyelitis. Headache (84%) and fever (81%) were the most common symptoms. Meningeal signs were present in 137 patients (90%). Most common neurological abnormalities were: Oppenheim and Babinski signs (74 patients, 49%), ataxia (37, 24%), impaired consciousness (37, 24%) and pareses (16, 10%). Of patients examined, 146 (96%) had raised pleiocytosis, frequently accompanied by high cerebrospinal fluid protein concentration (90%), raised erythrocyte sedimentation rate (65%), peripheral blood leucocytosis (26%) and increased aminotransferase activity (16%). There was only 1 forest worker among the patients. Tick-borne encephalitis remains common in north-eastern Poland but, possibly because of effective vaccination, it has virtually disappeared among forest employees. The diagnosis appears difficult in some cases, as meningeal signs may not be present and laboratory findings may not be suggestive of a viral infection.

The prognostic factors of adult tuberculous meningitis.

Our aim was to analyze the prognostic factors and therapeutic outcomes of adult tuberculous meningitis (TBM). Clinical data of 36 patients with adult TBM were retrospectively identified at our institution over a period of 5 years. 36 adult TBM patients, 23 males and 13 females, aged 16-83 years, were included in this study. The 36 patients were also divided into three groups (stages I, II and III) according to the severity of TBM on admission. Therapeutic outcomes at 3 months were determined using a modified Barthel Index (BI). For the purpose of statistical analysis, the patients were divided into two groups: good outcome (BI > or = 12) and poor outcome (BI < 12). Positive cerebrospinal fluid (CSF) culture was found in 47% (17/36) of patients and isoniazid-resistant strains were found in 18% (3/17) of culture-proven TBM. We statistically compared clinical manifestations, CSF features and therapeutic results of the two patient groups. Significant prognostic factors included severity of TBM at the time of admission, the presence of headache, fever, hydrocephalus, high CSF protein concentration and high CSF lactate concentration. In stepwise logistic regression analysis, only the presence of hydrocephalus and severity of TBM on admission were strongly associated with therapeutic failure even after adjusting for other potentially confounding factors. In Taiwan, TBM is an important public health issue and the emergence of resistant strains of this disease in recent years presents a therapeutic challenge. Because delay in diagnosis is directly related to poor outcome, early diagnosis and early treatment are essential for survival.