Clinical and Radiological End Points to Stop Anti-Tubercular Treatment in Central Nervous System Tuberculoma and Predictors of Poor Outcome: A Retrospective Study.

The clinical and radiological end points to stop anti-tubercular treatment in central nervous system (CNS) tuberculoma are not known. This retrospective study was done to determine end points to stop anti-tubercular treatment and find the predictors of poor outcome in patients with CNS tuberculoma. Patients who were admitted with a diagnosis of brain/spine tuberculoma between January 2015 and December 2019 and who completed a minimum of 1-year follow-up were enrolled. Clinical and radiological end points to stop anti-tubercular treatment and predictors of death and poor outcome (modified Rankin scale > 2) were analyzed. One hundred and eight patients (male-to-female ratio, 47 [43.5%]:61 [56.5%]; brain tuberculoma, 102; spinal cord tuberculoma, 14; brain and spinal cord tuberculoma, 8) were included in the study. Median duration of anti-tubercular treatment was 24 months. Radiological resolution of tuberculoma (resolution of gadolinium-enhancing lesion, gliosis, calcification, cord atrophy, or syrinx formation) and radiological halt (no increase in size/number of tuberculoma on magnetic resonance imaging scans done 6 months apart) were used as end points to stop anti-tubercular treatment in 69 and 7 patients, respectively. Seven patients stopped their treatment by themselves, and 25 patients died. Altered sensorium, motor weakness, infarcts, hydrocephalus, and constitutional symptoms of tuberculous meningitis were predictors of poor outcome or death in CNS tuberculoma patients. Radiological resolution or radiological halt of brain/spinal cord tuberculoma was a reasonable end point to stop anti-tubercular treatment. However, this may require 24 months or more of anti-tubercular treatment. Associated tuberculous meningitis and its complications portend a poor prognosis.

Automated pupillometry and optic nerve sheath diameter ultrasound to define tuberculous meningitis disease severity and prognosis.

BACKGROUND: Tuberculous meningitis (TBM) causes high mortality and morbidity, in part due to raised intracranial pressure (ICP). Automated pupillometry (NPi) and optic nerve sheath diameter (ONSD) are both low-cost, easy-to-use and non-invasive techniques that correlate with ICP and neurological status. However, it is uncertain how to apply these techniques in the management of TBM. METHODS: We conducted a pilot study enrolling 20 adults with TBM in the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Our objective was to investigate the relationships between baseline and serial measurements of NPi and ONSD and disease severity and outcome. Serial NPi and ONSD were performed for 30 days, at discharge, and at 3-months, with measurements correlated with clinical progression and outcomes. RESULTS: ONSD and NPi measurements had an inverse relationship. Higher ONSD and lower NPi values were associated with lower Glasgow coma score. Baseline NPi was a strong predictor 3-month outcome (median NPi 4.55, interquartile range 4.35-4.65 for good outcomes versus 2.60, IQR 0.65-3.95 for poor outcomes, p = 0.002). Pupil inequality (NPi ≥0.7) was also strongly associated with poor 3-month outcomes (p = 0.006). Individual participants' serial NPi and ONSD were variable during initial treatment and correlated with clinical condition and outcome. CONCLUSION: Pupillometry and ONSD may be used to predict clinical deterioration and outcome from TBM. Future, larger studies are need explore the optimal timing of measurements and to define how they might be used to optimise treatments and improve outcomes from TBM.

Cerebral venous thrombosis (CVT) complicating tubercular meningitis.

BACKGROUND: Tuberculous meningitis (TBM), complicated with cerebral venous thrombosis (CVT), has been sparsely reported and needs to be investigated further. METHODS: Among those with tuberculous meningitis in Haihe Hospital, Tianjin University, 3 patients with venous sinus thrombosis were identified retrospectively. "Tuberculous meningitis" and "cerebral venous thrombosis" were used as keywords, and the retrieved literature was summarized and analyzed. Our data were combined with previously reported case data to describe this new condition. RESULTS: Among 28 patients with a median onset age of 31 years for TBM, 17 were females. The manifestations were fever, headache, and seizure. Magnetic resonance imaging (MRI) venography showed that the most common site of venous sinus thrombosis involved superior sagittal sinus, left transverse sinus, left sigmoid sinus, cavernous sinus, and straight sinus. The abnormalities found on MRI include hydrocephalus, exudates, hemorrhage, meningeal enhancement, infarction, and tuberculoma. In the acute phase, all patients received standard anti-TB treatment, and 14/28 patients received anticoagulant treatment. The mortality rate of these patients was 17.9%, and 21/28 (75%) became functionally independent. CONCLUSIONS: CVT is one of the rare complications of TMB and must be considered a differential diagnosis in patients with TBM who show poor clinical features and/or develop new neurological signs.

Neuroimaging of central nervous system tuberculosis.

A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.

Transcranial Doppler ultrasonography in tuberculous meningitis: A systematic review.

BACKGROUND AND PURPOSE: Tuberculous (TB) meningitis is a common type of central nervous system infection, and may cause multifocal cerebral infarctions due to the involvement of cerebral vasculature. This systematic review aims to review and synthesize the utility of transcranial Doppler (TCD) in TB meningitis. METHODS: This is a systematic review of observational studies on the use of TCD in patients diagnosed to have TB meningitis. Study outcomes included changes in TCD parameters during stages of TB meningitis, frequency of neurologic complications (such as hydrocephalus, vasculopathy, and cerebral infarction), correlation of TCD findings with neuroimaging, and functional outcomes. RESULTS: Five studies were included with a total of 141 participants, with ages from 4 months to 75 years. The most common neurologic complication was hydrocephalus (87.1%), cerebral infarction (29.2%), and arterial stenosis (26.3%). There was increased mean flow velocity (MFV) most commonly in the middle cerebral artery in the early stage of TB meningitis, and decreased MFV in the advanced disease stage. TCD findings of stenosis were well correlated with CT or MR angiogram. Among patients with hydrocephalus, pulsatility indices were significantly decreased after ventriculoperitoneal shunting. CONCLUSIONS: A considerable proportion of patients with TB meningitis develop cerebral hemodynamic disturbances which lead to cerebral ischemia and affect clinical outcomes. TCD is a reliable tool for the diagnosis of vasculopathy and increased intracranial pressure and can thus help monitor disease progression and treatment response. Future studies with larger populations and longer follow-ups are recommended to determine the association of TCD findings with functional outcomes.

Risk factors of poor developmental outcome in children with tuberculous meningitis.

BACKGROUND: Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. METHODS: We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. RESULTS: A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87-6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. CONCLUSION: Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness.

Blood-CSF-barrier permeability in tuberculous meningitis and its association with clinical, MRI and inflammatory cytokines.

Blood -cerebrospinal fluid-barrier (BCB) disruption in tuberculous meningitis (TBM) may be mediated by inflammatory cytokines, and may determine clinico-radiological severity and outcome. We report BCB permeability in TBM and its relationship with inflammatory cytokines (TNF-α, IL-1ß and IL-6), clinical severity, MRI changes and outcome. 55 TBM patients with a median age of 26 years were included. Their clinical, cerebrospinal fluid (CSF) and MRI findings were noted. The severity of meningitis was graded into stages I to III. Cranial MRI was done, and the presence of exudates, granuloma, hydrocephalus and infarctions was noted. BCB permeability was assessed by a ratio of CSF albumin to serum albumin (Qalb). The concentration of TNF-α, IL-1ß and IL-6 in CSF were measured by cytokine bead array. The Qalb in the patients was more than the mean + 2.5 SD of controls. In TBM, Qalb correlated with TNF- α (r = 0.47; p = 0.01), CSF cells (r = 0.29; p = 0.02) and exudate on MRI (0.18 ± 0.009 Vs 0.13 ± 0.008; p = 0.04). There was however no association of Qalb with demographic variables, stage, tuberculoma, infarction and hydrocephalus. At 6 months, 11(20%) died, 10(18.2%) had poor and 34(61.8%) had a good recovery. BCB permeability in TBM correlated with TNF-α, CSF pleocytosis and exudates but not with severity of meningitis and outcome.

Cerebrospinal Fluid Flow Analysis in Tuberculous Meningitis Using Phase Contrast Technique on 3 Tesla MRI: A New Paradigm and Our Initial Experience.

Background: Phase-contrast magnetic resonance imaging (PC-MRI) has been used for studying cerebrospinal fluid (CSF) dynamics in various CSF related disorders at aqueduct of Sylvius. Objective: To analyze the CSF flow dynamics qualitatively and quantitatively using PC-MRI across the aqueduct of Sylvius in diagnosed patients of tuberculous meningitis. Methods: Thirty patients, clinically diagnosed with tuberculous meningitis and mean age of 24 years (range: 12-60 years) were taken up to study the changes in CSF flow dynamics using PC-MRI with retrospective cardiac gating. Thirty age and sex matched healthy volunteers were also included for comparison and reference values. Flow quantification was done by through-plane scans acquired in the axial plane perpendicular to the aqueduct. For qualitative examination, in-plane phase contrast scans were acquired in the mid-sagittal plane. Encoding velocity was kept in craniocaudal direction. Calculated parameters were peak velocity (cm/s), average velocity (cm/s), average flow (mL/s), net forward volume (mL), and stroke volume (µL). Results: Qualitatively, loss of normal sinusoidal waveform of CSF flow was noted in two cases of hydrocephalus with exaggerated flows. Quantitatively, CSF flow parameters showed marked numerical difference in tuberculous meningitis patients with hydrocephalus on comparison with healthy volunteers and with cases without hydrocephalus. Conclusion: PC-MRI is a sensitive technique to analyze altered CSF flow dynamics in tuberculous meningitis patients. This is a useful adjunct in imaging these patients to extract both the qualitative and quantitative information about CSF flow for comprehensive evaluation.

MRI-based radiomics signature for identification of invisible basal cisterns changes in tuberculous meningitis: a preliminary multicenter study.

OBJECTIVE: To develop and evaluate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for identification of invisible basal cisterns changes in tuberculous meningitis (TBM) patients. METHODS: Our retrospective study enrolled 184 TBM patients and 187 non-TBM controls from 3 Chinese hospitals (training dataset, 158 TBM patients and 159 non-TBM controls; testing dataset, 26 TBM patients and 28 non-TBM controls). nnU-Net was used to segment basal cisterns in fluid-attenuated inversion recovery (FLAIR) images. Subsequently, radiomics features were extracted from segmented basal cisterns in FLAIR and T2-weighted (T2W) images. Feature selection was carried out in three steps. Support vector machine (SVM) and logistic regression (LR) classifiers were applied to construct the radiomics signature to directly identify basal cisterns changes in TBM patients. Finally, the diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA). RESULTS: The segmentation model achieved the mean Dice coefficients of 0.920 and 0.727 in the training and testing datasets, respectively. The SVM model with 7 T2WI-based radiomics features achieved best discrimination capability for basal cisterns changes with an AUC of 0.796 (95% CI, 0.744-0.847) in the training dataset, and an AUC of 0.751 (95% CI, 0.617-0.886) with good calibration in the testing dataset. DCA confirmed its clinical usefulness. CONCLUSION: The T2WI-based radiomics signature combined with deep learning segmentation could provide a fully automatic, non-invasive tool to identify invisible changes of basal cisterns, which has the potential to assist in the diagnosis of TBM. KEY POINTS: • The T2WI-based radiomics signature was useful for identifying invisible basal cistern changes in TBM. • The nnU-Net model achieved acceptable results for the auto-segmentation of basal cisterns. • Combining radiomics and deep learning segmentation provided an automatic, non-invasive approach to assist in the diagnosis of TBM.

Tuberculous myelitis: a prospective follow-up study.

BACKGROUND: Prospective studies regarding tuberculous myelitis are lacking. We aimed to prospectively evaluate patients with tuberculous myelitis to identify the features that distinguish tuberculous myelitis from other myelitis. METHODS: This was a prospective study. Patients presenting with paraparesis/quadriparesis, and MRI showing myelitis were included. All patients were subjected to clinical, neuroimaging, and laboratory evaluation. Diagnosis of definite tuberculous myelitis was made if GeneXpert test in CSF was positive. Probable tuberculous myelitis was diagnosed if there was evidence of tuberculosis elsewhere in the body. Patients were treated with methylprednisolone and antituberculosis treatment. Patients were followed for 6 months. We compared the clinical, laboratory, and neuroimaging parameters and response to treatment of tuberculous myelitis with other myelitis. P values were adjusted using the Benjamini-Hochberg (BH) procedure to control false discovery rate. RESULTS: We enrolled 52 patients. Eighteen (34.6%) patients had tuberculous myelitis. Headache (P = 0.018) was significantly more common in tuberculous myelitis. The CSF protein (P < 0.001), and CSF cell count (P < 0.001) were significantly higher in tuberculous myelitis. On neuroimaging, a LETM was common in tuberculous myelitis. Spinal meningeal enhancement (14; 77.8%), extra-axial collection, and CSF loculation (6; 33.4%), arachnoiditis (3;16.7%), and concomitant spinal tuberculoma (2;11.1%) were other common imaging features of tuberculous myelitis. Tuberculous myelitis patients showed a better response (P = 0.025) to treatment. CONCLUSION: Tuberculous myelitis was seen in approximately 35% of all myelitis cases, in a high tuberculosis endemic zone. Headache, markedly elevated CSF protein and spinal meningeal enhancement were distinguishing features. Tuberculous myelitis patients responded well to corticosteroids.

NMR based CSF metabolomics in tuberculous meningitis: correlation with clinical and MRI findings.

We report the potential role of 1H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with clinical-radiological parameters. Forty-three patients with TBM were included, and their severity of meningitis was graded as stages I to III, and patients with positive Mycobacterium tuberculosis or its nucleic acid was considered as definite TBM. 1H NMR-based metabolomic study was performed on (CSF) samples, and the significant metabolites compared to healthy controls were identified. Outcome at three months was defined as death, poor and good based on the modified Rankin Scale. These metabolites were compared between definite and probable groups of TBM, and also correlated with MRI findings. About 11 metabolites were found to be significant for distinguishing TBM from the controls. In TBM, lactate, glutamate, alanine, arginine, 2-hydroxyisobutyrate, formate, and cis-aconitate were upregulated, and glucose, fructose, glutamine, and myo-inositol were downregulated compared to the controls. For differentiating TBM from the controls, the AUC of the ROC curve generated using these significant metabolites was 0.99, with a 95% confidence interval from 0.96 to 1, demonstrating that these metabolites were able to classify cases with good sensitivity and specificity. Lactate concentration in CSF correlated with hemoglobin, CSF glucose, and infarction. The outcome did not correlate with metabolomics parameters. NMR-based CSF metabolomics have a potential role in differentiating TBM from the controls.

Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study.

BACKGROUND: Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). METHODS: Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-α gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-α concentration in CSF by cytokine bead array both in the patients and 14 matched controls. RESULTS: All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p < 0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60) days of treatment. Twelve (21.8%) patients only became afebrile within 10 days. The expression of TNF-α gene correlated with CSF concentration of TNF-α (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p = 0.01). CONCLUSION: In the patients with TBM, defervescence takes longer time, and TNF-α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-α-modifying drugs in TBM.

Concurrent central nervous system involvement in immunocompetent adults with pulmonary miliary TB: a prospective analysis.

BACKGROUND: Wallgren's tuberculosis (TB) timetable demonstrated co-occurrence of miliary TB and tuberculous meningitis in children. To verify the same in immunocompetent adults, we prospectively evaluated the prevalence and spectrum of central nervous system (CNS) involvement in patients with pulmonary miliary TB. MATERIALS AND METHODS: This was a tertiary care, University hospital-based, prospective evaluation performed from December 2018 to June 2020. Newly diagnosed patients with pulmonary miliary TB were subjected to a detailed clinical, laboratory and MRI-based evaluation. All patients received treatment as per WHO guidelines. RESULTS: Out of 342 patients with pulmonary TB, 53 patients met the eligibility criteria. The median age at presentation was 32 y and approximately two-thirds of patients were female. Clinically, only two-fifths of patients had features of CNS involvement. Cerebrospinal fluid (CSF) and imaging abnormalities were noted in 46 patients each. Twelve (23.5%) patients were diagnosed with definite-category tuberculous meningitis. Presence of an infarct significantly correlated with neurological features. Mantoux positivity correlated significantly with the presence of choroid tubercles, CSF changes and brain tuberculomas. CONCLUSION: This is the first study to endorse Wallgren's observations in immunocompetent adults. A high index of suspicion, even in asymptomatic patients, may uncover tuberculous lesions involving the CNS and guide optimal monitoring of patients.

Cerebrospinal fluid analysis is associated with enhancement on MRI in bacterial and tuberculous meningitis: A retrospective observational study.

OBJECTIVE: Along with cerebrospinal fluid (CSF) analysis, enhancement on contrast-enhanced MRI is useful to diagnose meningitis. However, the conditions for its appearance have not been clarified. This study aimed to investigate the association between CSF parameters and enhancement on contrast-enhanced head or spinal MRI in patients with bacterial meningitis (BM) or tuberculous meningitis (TM). METHODS: A total of 12 patients with BM and 23 patients with TM who underwent both CSF analysis and contrast-enhanced MRI were included. The correlation between CSF analysis and MRI findings has been examined using receiver operating characteristic (ROC) analysis. RESULTS: Contrast enhancement was found in 7 and 10 patients with BM and TM, respectively. Both CSF analysis and MRI were useful to distinct between BM and TM, and the enhancement implied the severity of them. In patients with BM, higher CSF protein and lower CSF glucose were associated with enhancement on MRI, while not only CSF protein and glucose but also leukocyte and lymphocyte counts were associated with it in TM. CSF adenosine deaminase (ADA) did not show discriminant ability of the MRI findings. CONCLUSIONS: CSF analysis is associated with enhancement on contrast-enhanced MRI both in BM and TM. Our findings indicate the importance of CSF analysis in assessing the need to perform contrast-enhanced MRI, which may be useful in diagnosis, distinction, and estimation of prognosis in those patients.

Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique.

Background: Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy. Methods: Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit). Results: Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease. Conclusion: Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention.

Efficacy of Xpert MTB/RIF Ultra in diagnosing tuberculosis meningitis: A systematic review and meta-analysis.

BACKGROUND: This study aimed to assess whether Xpert MTB/RIF Ultra (Xpert Ultra) can effectively diagnose tuberculosis meningitis (TBM) and to simultaneously compare its effectiveness with Xpert in diagnosing TBM in the same population. METHODS: On August 12, 2020, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed were searched for studies evaluating the diagnostic accuracy of Xpert Ultra for TBM. Then, we assessed the efficacy of Xpert Ultra against a composite reference standard and culture. If applicable, we also examined the diagnostic efficacy of Xpert in the same population. Heterogeneity was then explored by meta-regression, subgroup, and sensitivity analyses. RESULTS: Six studies containing 601 specimens reported the diagnostic efficacy of Xpert Ultra for TBM, with a composite reference standard. No study had compared the efficacy between Xpert Ultra and culture. The pooled sensitivity of Xpert Ultra was 64% (95% confidence interval [CI]: 45-80), and the I2 value was 86% (95% CI: 76-96); its specificity for TBM was consistently 100%. In the same population, 5 studies compared the diagnostic efficacy between Xpert Ultra and Xpert for TBM. The pooled sensitivity of Xpert Ultra and Xpert was 68% (95% CI: 46-84; I2 = 87%) and 37% (95% CI: 25-50; I2 = 72%), respectively. The studies were significantly heterogeneous in terms of sensitivity but not heterogeneous in specificity. CONCLUSIONS: Xpert Ultra was more sensitive than Xpert, but both were specific (100%). Therefore, Xpert Ultra had an excellent diagnostic efficacy for TBM, and it could be the preferred initial test for TBM.

Autoimmune GFAP astrocytopathy presenting with remarkable CNS hyperexcitability and oculogyric crises.

The autoimmune GFAP astrocytopathy has been associated with meningoencephalomyelitis that usually responds to glucocorticoids. We report a 20-year-old man that developed an acute and severe meningoencephalomyelitis with remarkable CNS hyperexcitability and oculogyric crises. CSF analysis showed hypoglycorrhachia, pleocytosis, elevated ADA, and CSF-immunofluorescence characteristic of autoimmune GFAP astrocytopathy. MRI showed lesions at thalamus, corpus-callosum, dorsal pons and dentate nucleus with associated myelitis. Immunotherapy led to a full recovery, although MRI activity was observed at follow-up. CNS hyperexcitability, typically seen in other immune-mediated syndromes, represents a novel presenting form to be included as part of the clinical spectrum of this entity.