Dataset Information

Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.

ABSTRACT: Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM. Methods Eleven consecutive HIV-negative patients with CM who presented at one of three emergency hospitals in Japan from April 2001 to March 2018 were enrolled. For all patients, we retrospectively assessed the relationships between clinical and laboratory information and the presence of WMLs. Results At presentation, 6 patients had WMLs on magnetic resonance imaging (MRI). The cerebrospinal fluid immunoglobulin G (CSF IgG) index was significantly higher in the patients with WMLs than in those without WMLs (mean, 1.34 vs. 0.70, p=0.017). The time from the symptom onset to initial neuroimaging was also significantly longer in the patients with WMLs than in those without WMLs (median, 31.5 vs. 7.0 days; p=0.008). The clinical outcome was comparable among the patients with and without WMLs. Conclusion In HIV-negative patients with CM, a persistent, aberrant immune response to Cryptococcus, such as intrathecal IgG synthesis, may induce WML formation.

SUBMITTER: Ohyagi M

PROVIDER: S-EPMC6875458 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.

Ohyagi Masaki M Irioka Takashi T Ohkubo Takuya T Ishibashi Satoru S Takahashi Yuko K YK Amano Eiichiro E Machida Akira A Kuwahara Hiroya H Yokota Takanori T

Internal medicine (Tokyo, Japan) 20190627 21

Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM. Methods Eleven consecutive HIV-negative patients ...[more]

PMID: 31243232

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Project description:IntroductionIndividuals with persistent developmental stuttering display deficits in aligning motor actions to external cues (i.e., sensorimotor synchronization). Diffusion imaging studies point to stuttering-associated differences in dorsal, not ventral, white matter pathways, and in the cerebellar peduncles. Here, we studied microstructural white matter differences between adults who stutter (AWS) and fluent speakers using two complementary approaches to: (a) assess previously reported group differences in white matter diffusivity, and (b) evaluate the relationship between white matter diffusivity and sensorimotor synchronization in each group.MethodsParticipants completed a sensorimotor synchronization task and a diffusion MRI scan. We identified the cerebellar peduncles and major dorsal- and ventral-stream language pathways in each individual and assessed correlations between sensorimotor synchronization and diffusion measures along the tracts.ResultsThe results demonstrated group differences in dorsal, not ventral, language tracts, in alignment with prior reports. Specifically, AWS had significantly lower fractional anisotropy (FA) in the left arcuate fasciculus, and significantly higher mean diffusivity (MD) in the bilateral frontal aslant tract compared to fluent speakers, while no significant group difference was detected in the inferior fronto-occipital fasciculus. We also found significant group differences in both FA and MD of the left middle cerebellar peduncle. Comparing patterns of association with sensorimotor synchronization revealed a novel double dissociation: MD within the left inferior cerebellar peduncle was significantly correlated with mean asynchrony in AWS but not in fluent speakers, while FA within the left arcuate fasciculus was significantly correlated with mean asynchrony in fluent speakers, but not in AWS.ConclusionsOur results support the view that stuttering involves altered connectivity in dorsal tracts and that AWS may rely more heavily on cerebellar tracts to process timing information. Evaluating microstructural associations with sensitive behavioral measures provides a powerful tool for discovering additional functional differences in the underlying connectivity in AWS.

Project description:Background: White matter lesions (WML) have been proved to be significantly associated with many brain diseases. Precise evaluation of burden of WML at early stage could provide insights in the prognosis and assist in intervention. However, acute ischemic lesions (AIL) exhibit hyperintensities on FLAIR images either, and are detected by diffusion weighted imaging (DWI). It is challenging to identify and segment WML in the patients with WML and AIL. Convolutional neural network (CNN) based architecture has been validated as an efficient tool for automatic segmentation. This study aimed to evaluate the performance of U-net in evaluation of WML in the patients with WML and AIL. Methods: A total of 208 cases from Chinese Atherosclerosis Risk Evaluation (CARE II) study were recruited in the present study. All subjects underwent imaging of FLAIR and DWI on 3.0 Tesla scanners. The contours of WML delineated by the observer and its scores rated by the observer were considered as gold standard. Among all 208 cases, 108 were randomly selected as train set, and the remaining 100 cases were used as test set. The performance of lesion segmentation toolbox (LST) and three U-net models were evaluated on three levels: pixel, lesion, and subject levels. The performance of all methods in WML identification and segmentation was also evaluated among the cases with different lesion volumes and between the cases with and without AIL. Results: All U-net models outperformed LST on pixel, lesion, and subject levels, while no differences were found among three U-net models. All segmentation methods performed best in the cases with WML volume (WMLV) > 20 ml but worst in those with WMLV < 5 ml. In addition, all methods showed similar performance between the cases with and without AIL. The scores determined by U-net exhibited a strong correlation with the gold standard (all Spearman correlation coefficients >0.89, ICCs >0.88, p-values <0.001). Conclusion: U-net performs well on identification and segmentation of WML in the patients with WML and AIL. The performance of U-net is validated by a dataset of multicenter study. Our results indicate that U-net has an advantage in assessing the burden of WML in the patients suffered from both WML and AIL.

Project description:Although male predominance was documented in previous studies on cryptococcal meningoencephalitis (CM), there has been no statistical study about female CM patients despite recently noticeable increase in female prevalence. In the current study, we aimed to investigate the independent gender-specific contributing risk factors for onset of CM and factors related to survival time in female patients by chosen statistical tools.There have been 108 patients diagnosed with CM from July 1, 1998 to June 30, 2013 in Nanfang Hospital that were included in our study. This 15-year retrospective study compared demographic and clinical features of 31 female patients with 77 males. Multivariate analysis was performed for detection of the contributors to the onset of CM in female patients. The independent variables for multivariate analysis were selected according to statistical significance in univariate analysis. Furthermore, Cox regression model was used to evaluate the factors related to survival length.Use of corticosteroids or other immunosuppressants (32.3% versus 11.7%; p = 0.011) and history of systemic lupus erythematosus (SLE) and other autoimmune diseases (29% versus 3.9%; p < 0.001) were more common in females, but only the history of SLE or other autoimmune diseases was significant (OR 10.59, 95% CI 1.49-74.77, p = 0.02) by multivariate analysis. The ratio of cerebrospinal fluid (CSF) glucose-to-blood glucose was related to the survival time (p = 0.03, 95% CI 0-0.71).The results showed that the history of SLE or other autoimmune diseases rather than chronic use of corticosteroids and/or immunosuppressants was the independent gender-specific contributing risk factor in female CM patients. Therefore, more attention should be made to the prevention of infection from the genus Cryptococcus spp. in female patients with SLE or other autoimmune diseases. In addition, decreased ratio of CSF glucose-to-blood glucose before antifungal therapy predicted the worse prognosis.

Dataset Information

Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.

Publications

Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.

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