White matter and cortical gray matter microstructural abnormalities in new daily persistent headache: a NODDI study.

BACKGROUND: New daily persistent headache (NDPH) is a rare primary headache with unclear pathogenesis. Neuroimaging studies of NDPH are limited, and controversy still exists. Diffusion tensor imaging (DTI) is commonly used to study the white matter. However, lacking specificity, the potential pathological mechanisms of white matter microstructural changes remain poorly understood. In addition, the intricacy of gray matter structures impedes the application of the DTI model. Here, we applied an advanced diffusion model of neurite orientation dispersion and density imaging (NODDI) to study the white matter and cortical gray matter microstructure in patients with NDPH. METHODS: This study assessed brain microstructure, including 27 patients with NDPH, and matched 28 healthy controls (HCs) by NODDI. The differences between the two groups were assessed by tract-based spatial statistics (TBSS) and surface-based analysis (SBA), focusing on the NODDI metrics (neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISOVF)). Furthermore, we performed Pearson's correlation analysis between the NODDI indicators and clinical characteristics. RESULTS: Compared to HCs, patients with NDPH had a reduction of density and complexity in several fiber tracts. For robust results, the fiber tracts were defined as comprising more than 100 voxels, including bilateral inferior fronto-occipital fasciculus (IFOF), left superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), as well as right corticospinal tract (CST). Moreover, the reduction of neurite density was uncovered in the left superior and middle frontal cortex, left precentral cortex, and right lateral orbitofrontal cortex and insula. There was no correlation between the NODDI metrics of these brain regions and clinical variables or scales of relevance after the Bonferroni correction. CONCLUSIONS: Our research indicated that neurite loss was detected in both white matter and cortical gray matter of patients with NDPH.

The gut microbial signatures of patients with lacunar cerebral infarction.

BACKGROUND: Emerging evidence revealed that gut microbial dysbiosis is involved in the pathogenesis of multiple neurological diseases, but there is little available data on the relationship between gut microbiota and lacunar cerebral infarction (LCI). METHODS: Fecal samples from acute LCI patients (n = 65) and matched healthy controls (n = 65) were collected. The compositions and potential functions of the gut microbiota were estimated. RESULTS: The results showed that there were significant gut microbial differences between LCI and control groups. Patients with LCI had higher abundances of genus Lactobacillus, Streptococcus, Veillonella, Acidaminococcus, Bacillus, Peptoclostridium, Intestinibacter, Alloscardovia and Cloacibacillus but lower proportions of genus Agathobacter and Lachnospiraceae_UCG-004. Investigating further these microbes such as Lactobacillus and Veillonella were correlated with clinical signs. Moreover, we found that 9 gene functions of gut microbiota were different between LCI patients and controls, which were associated with amino acid metabolism and inflammatory signal transduction. Notably, four optimal microbial markers were determined, and the combination of Streptococcus, Lactobacillus, Agathobacter, Lachnospiraceae_UCG-004 and the three risk factors achieved an area under the curve (AUC) value of 0.854 to distinguish LCI from controls. CONCLUSION: These findings revealed the characterizing of gut microbiota in LCI patients and provided potential microbial biomarkers for clinical diagnosis of LCI.

miR-219-5p inhibits tau phosphorylation by targeting TTBK1 and GSK-3ß in Alzheimer's disease.

As the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by memory, perception, and behavioral damage, which may ultimately lead to emotional fluctuation and even lethal delirium. Increasing studies indicate that microRNAs (miRNAs) are associated with pathological features of AD. However, the role of miR-219-5p in AD progression is still unclear. In this study, the functions of miR-219-5p were analyzed in vitro and in vivo. miR-219-5p was notably overexpressed in brain tissues of patients with AD. The overexpression of miR-219-5p activated the phosphorylation of Tau-Ser198, Tau-Ser199, Tau-Ser201, and Tau-Ser422. We further showed that miR-219-5p could mediate a decrease in the protein levels of tau-tubulin kinase 1 (TTBK1) and glycogen synthase kinase 3ß (GSK-3ß) by directly binding to their 3'-untranslated region, thereby promoting the phosphorylation of tau in SH-SY5Y Cells. Rescue experiments further revealed that the phosphorylation of tau-mediated by miR-219-5p was dependent on the inhibition of TTBK1 and GSK-3ß. Moreover, suppressing the expression of both TTBK1 and GSK-3ß using miR-219-5p remarkably rescued AD-like symptoms in amyloid precursor protein/presenilin 1 mice. Our findings indicate that the upregulation of TTBK1 and GSK-3ß mediated by the loss of miR-219-5p is a possible mechanism that contributes to tau phosphorylation and AD progression.

Myasthenia gravis and chronic inflammatory demyelinating polyneuropathy in the same patient - a case report.

PURPOSE: To investigate the clinical character, diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy accompanying myasthenia gravis so as to improve the understanding of such diseases. MATERIALS AND METHODS: A case of chronic inflammatory demyelinating polyneuropathy combined with myasthenia gravis were analyzed retrospectively with review of the literature. RESULTS: This man was presented with chronic progressive sensory symptoms, flaccid tetraparesis, areflexia and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study was indicative of demyelinating neuropathy. He was suspected as chronic inflammatory demyelinating polyneuropathy and treated with high-dose glucocorticoids. However, his condition worsened. Four months later, he was admitted and was diagnosed as combination of chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. Good clinical results were observed after he was treated with pyridostigmine bromide, prednisone and mycophenolate mofetil. CONCLUSIONS: This case warns clinicians to be aware of these two diseases presenting in the same patient, and the possible implications on treatment choices. A common immunological abnormality might exist in this rare association, but it still remains unknown.

The Influence of Patent Foramen Ovale on the Clinical Features of Migraine without Aura: A Cross-Sectional Study.

Objective: To investigate the influence of patent foramen ovale (PFO) on the clinical features of migraine without aura (MoA). Methods: We consecutively enrolled 390 MoA patients and compared the frequency of headache, episode duration, and the Visual Analogue Scale (VAS), Headache Impact Test 6 (HIT-6), and European Health Interview Survey-Quality of Life 8-item index (EUROHIS-QOL8) scores of patients with and without PFO, those with the mild right-to-left shunt (RLS) and moderate to large RLS, and those with permanent RLS and latent RLS using a nonparametric Mann-Whitney U-test. In addition, we analyzed the clinical features of migraine in 39 MoA patients before and after PFO closure treatment using the paired Wilcoxon test. Results: The prevalence of PFO in the 390 MoA patients was 44.4%. Patients with PFO had significantly higher frequency of headaches, VAS scores, HIT-6 scores, and incidence of white matter lesions than those without PFO (all p< 0.05). Patients with moderate to large RLS had significantly higher VAS scores than those with mild RLS (p = 0.002). Additionally, 39 MoA patients underwent PFO closure, which remarkably decreased their frequency of headache, episode duration, VAS scores, and HIT-6 scores, and increased their EUROHIS-QOL8 scores. Conclusion: The migraine features in MoA patients could be influenced by PFO, especially in patients with moderate to large shunt, in whom PFO closure improved the symptoms.

Predictive microbial feature analysis in patients with depression after acute ischemic stroke.

Introduction: Post-stroke depression (PSD) is the most common emotional problem following a stroke, which requires early diagnosis to improve the prognosis. Gut microbiota plays important role in the pathological mechanisms of acute ischemic stroke and influences the outcome of patients. However, the relationship between PSD and gut microbiota remains unknown. Here, we explored whether the microbial signatures of gut microbiota in the patients with stroke could be an appropriate predictor of PSD. Methods: Fecal samples were collected from 232 acute ischemic stroke patients and determined by 16s rRNA sequencing. All patients then received 17-Hamilton Depression Rating Scale (HAMD-17) assessment 3 months after discharge, and were further divided into PSD group and non-PSD group. We analyzed the differences of gut microbiota between these groups. To identify gut microbial biomarkers, we then established microbial biomarker model. Results: Our results showed that the composition of gut microbiota in the PSD patients differed significantly from that in non-PSD patients. The genus Streptococcus, Akkermansia, and Barnesiella were significantly increased in PSD patients compared to non-PSD, while the genus Escherichia-Shigella, Butyricicoccus, and Holdemanella were significantly decreased. Correlation analyses displayed that Akkermansia, Barnesiella, and Pyramidobacter were positively correlated with HAMD score, while Holdemanella was negatively correlated with HAMD score. The optimal microbial markers were determined, and the combination achieved an area under the curve (AUC) value of 0.705 to distinguish PSD from non-PSD. Conclusions: Our findings suggest that PSD patients had distinct gut microbiota compared to non-PSD patients, and explore the potential of microbial markers, which might provide clinical decision-making in PSD.

Low-dosage of rituximab in Chinese patients with neuromyelitis optica spectrum disorder.

Rituximab has been effectively used for treating neuromyelitis optica spectrum disorder (NMOSD) for several years. However those regimens exert a heavy burden on Chinese patients. The aim of our study was to investigate an effectiveness, economic alternatives of RTX. The enrolled patients received different immunosuppressant drugs. Annual relapse rate (ARR), neurological disability (Expanded Disability Status Scale, EDSS), time to the next relapse were evaluated after treatments. Fourteen patients treated with RTX and 37 relapse events from 23 patients treated with traditional immunosuppressant drugs (ISDs) were analyzed in our study. Patients with NMOSD treated with RTX showed a reduction in ARR (2.0 ±â€¯1.8 to 0.2 ±â€¯0.3, p = 0.002) and improve disability (EDSS: 3.7 ±â€¯2.1 to 2.3 ±â€¯2.3, p < 0.001) at last follow-up. Kaplan-Meier analysis indicated that patients treated with RTX had a longer time to next relapse compared with those who were treated with traditional ISDs. Our regimens of RTX treatment were effective in NMOSD patients, and exerted a lower risk of adverse events might be lower than did the high-dose RTX regimens. Moreover, our regimen provides an economic and convenient alternative for NMOSD patients.

Low serum levels of uric acid and albumin in patients with Guillain-Barre syndrome.

Free radical toxicity due to poorly maintained cellular redox levels is crucial events that have been associated with the pathogenesis of Guillain-Barre syndrome (GBS) patients. Uric acid (UA) and albumin correlate with oxidative stress in some degree. We aimed to evaluate the relationship between GBS and serum levels of UA and albumin in the present study.The serum levels of UA and albumin were determined in 203 individuals including 88 patients with GBS and 153 healthy controls (HC).We found that serum levels of UA and albumin in patients with GBS were significantly lower than those in HC group. Besides, similar phenomenon was observed when the male and female subgroups were estimated, respectively. Additionally, we found that there is no statistic difference among subgroups of GBS regarding UA and albumin. The univariate analysis revealed that both the high UA and high albumin were protective factors for patients with GBS (odds ratio [OR] 0.140; 95% confidence interval [CI]: 0.074-0.264; P < .001 and OR 0.016; 95% CI: 0.006-0.038; P < .001, respectively). It was further confirmed by the multivariable logistic regression analysis after adjusting for other potential confounding factors (OR 0.168; 95% CI: 0.055-0.514; P = .002 and OR 0.027; 95% CI: 0.011-0.071; P < .001, respectively).In conclusion, we found that patients with GBS had significantly low serum UA and albumin levels. Moreover, we demonstrated that both the high UA and high albumin were protective factors for patients with GBS.