Gut microbiota and metabolome in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Gut dysbiosis and the resulting changes in the metabolites have been associated with neurological diseases. However, the relationship between the gut microbiota and sporadic Creutzfeldt-Jakob disease (sCJD) need to be clarified. The aim of this study was to evaluate the changes in the composition of gut microbiota and metabolome accompanying sCJD, and determine their correlation with disease severity. METHODS: Fecal samples were collected from 25 sCJD patients and 23 healthy controls. The composition of the fecal microbiota and metabolites was respectively analyzed by 16S ribosomal RNA sequencing and untargeted metabolomics. The correlation of gut microbiota and metabolites with MMSE, MoCA and MRC scores was analyzed. RESULTS: The sCJD patients showed significant differences in the composition of gut microbiota and metabolites relative to the healthy controls. Several bacteria taxa in sCJD patients were increased at genus level, such as Turicibacter, norank_f_Christensenellaceae, Eisenbergiella, Bilophila and Holdemania. A total of 547 differential metabolites were identified between these two groups (VIP > 1, FDR p < 0.05). As per KEGG analysis, the metabolites related to the biosynthesis of phenylpropanoids, especially biochanin A, showed the most obvious decrease in the sCJD group. In addition, most metabolites involved in the pathways related to linoleic acid metabolism and steroid hormone biosynthesis were associated with MRC scale. CONCLUSION: Our findings provide new insights into the relationship between gut microbiota and metabolites and sCJD. Some compounds, especially those related to the biosynthesis of phenylpropanoids were significantly altered in patients with sCJD, and those related to linoleic acid metabolism and steroid hormone biosynthesis might be biomarkers of evaluating disease severity.

Clinical characteristics and prognosis of anti-γ-aminobutyric acid-B receptor encephalitis: A single-center, longitudinal study in China.

Objective: Anti-γ-aminobutyric acid-B receptor (GABABR) encephalitis is a rare type of autoimmune encephalitis. There are only a few, small, published studies regarding prognosis, so prediction of prognosis is of limited accuracy. We identified 37 cases of anti-GABABR encephalitis in China. Here, we present these patients' clinical characteristics and long-term outcomes. Methods: We collected and retrospectively analyzed the clinical data of 37 patients with anti-GABABR encephalitis from Beijing Fengtai You'anmen Hospital. Results: The study cohort comprised 37 patients of anti-GABABR encephalitis of median age 61 years (range: 11-77), 28 of whom were male. The main clinical manifestations were epilepsy (91.9%, 34/37), psychiatric disorders (94.6%, 35/37) and cognitive impairment (97.3%, 36/37). Tumors were identified in 18 (48.6%) patients. First-line immunotherapy was administered to 34 patients, 31 of whom (90.6%) responded favorably. During a median follow-up of 18 months (range: 1-72 months), 21 patients had good outcomes [Modified Ranking Scale (mRS ≤2)], 16 (43.2%) died (mRS 6), and 7 (18.9%) relapsed. Age (P = 0.005), disturbance of consciousness (P = 0.018), admission to the Neurology Intensive Care Unit (P = 0.003), mechanical ventilation (P = 0.009), more numerous clinical manifestations (P = 0.008), comorbid malignancy (P = 0.008), multiple anti-neuronal antibodies (P = 0.029), and hyponatremia (P = 0.023) differed significantly between patients with good outcomes (mRS 0-2) and those with poor outcomes (mRS 3-6). Conclusion: Men aged 50-70 years accounted for most of the patients with anti-GABABR encephalitis in our case series. The main clinical manifestations were epilepsy and neuropsychiatric dysfunction. The participants often had concomitant lung cancer, particularly small-cell lung cancer. Patients with lung tumors and/or serious manifestations usually had a poor prognosis with high mortality. Early identification and treatment of tumors improved the poor prognosis to some extent.

Defective autophagy is associated with neuronal injury in a mouse model of multiple sclerosis.

Neurodegeneration, along with inflammatory demyelination, is an important component of multiple sclerosis (MS) pathogenesis. Autophagy is known to play a pivotal role in neuronal homeostasis and is implicated in several neurodegenerative disorders. However, whether autophagy is involved in the mechanisms of neuronal damage during MS remains to be investigated. Experimental autoimmune encephalomyelitis (EAE), an in vivo model of MS, was induced in female C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein p35-55. After that, autophagic flux in the spinal cord of mice was evaluated by detection of LC3-II and Beclin1 protein expressions. EAE mice were then administered with rapamycin and 3-methyladenine (3-MA) for 10 days. Afterward, the changes in LC3-II, Beclin1, and p62 expression, number of infiltrated inflammatory cells, demyelinated lesion area, and neuronal damage, as well as clinical scores, were assessed. Further, apoptotic cell rate and apoptosis-related protein expressions were monitored. We observed an impaired autophagic flux and increased neuronal damage in the spinal cords of EAE mice. We also found that rapamycin, an autophagy inducer, mitigated EAE-induced autophagy decrease, inflammation, demyelination and neuronal injury, as well as the abnormal clinical score. In addition, rapamycin suppressed cell apoptosis, and decreased Bax/Bcl-2 ratio and cleaved caspase-3 expression. Conversely, the effect of autophagy inhibitor 3-MA on EAE mice resulted in completely opposite results. These results indicated that autophagy deficiency, at least in part, contributed to EAE-induced neuronal injury and that pharmacological modulation of autophagy might be a therapeutic strategy for MS.

Staining with two observational methods for the diagnosis of tuberculous meningitis.

Ziehl-Neelsen (Z-N) staining of cerebrospinal fluid (CSF) for acid-fast bacilli (AFB) is the cornerstone of the laboratory diagnosis of tuberculous meningitis (TBM). However, the sensitivity of conventional Z-N staining for the detection of AFB in CSF specimens is suboptimal. The present study aimed to compare the practicality of modified Z-N staining with light microscopy and fluorescence microscopy in the same smear without auramine O. A total of 155 patients with 223 CSF specimens were enrolled and grouped according to the uniform case definition. The smears of each CSF specimen were subjected to modified Z-N staining and then observed using a light microscope under transmitted light and under fluorescence with a green-excitation wavelength in the same microscopic field. The results for different groups, inspection times, and prior to and following treatment were compared. Results indicated that the fuchsin-stained AFB were visible as bright orange-red fluorescing rods under fluorescence, or as red, lightly curved rods under transmitted light. The sensitivity of fluorescence microscopy was 96.2% while that of light microscopy was 84.6%. The positive rate of fluorescence microscopy was 79.2% prior to treatment compared with 61.7% post-treatment. In the same microscopic field, a greater number of AFB were observed using fluorescence compared with transmitted light, and AFB that were not visible under transmitted light were clearly observed under fluorescence. Furthermore, transmitted light and fluorescence could be interchanged directly when equivocal smears were encountered. The combination of modified Z-N staining and fluorescence microscopy without auramine O is sensitive and convenient for the diagnosis of TBM.

Suppression of murine experimental autoimmune encephalomyelitis development by 1,25-dihydroxyvitamin D3 with autophagy modulation.

Multiple sclerosis (MS) has been associated with a history of sub-optimal exposure to ultraviolet light, implicating vitamin D3 as a possible protective agent. We evaluated whether 1,25(OH)2D3 attenuates the progression of experimental autoimmune encephalomyelitis (EAE), and explored its potential mechanisms. EAE was induced in C57BL/6 mice via immunization with MOG35-55, and some mice received 1,25(OH)2D3. 1,25(OH)2D3 inhibited EAE progression. Additionally, 1,25(OH)2D3 reduced inflammation, demyelination, and neuron loss in the spinal cord. The protective effect of 1,25(OH)2D3 was associated with significantly elevated expression of Beclin1, increased Bcl-2/Bax ratio, and decreased LC3-II accumulation. Thus, 1,25(OH)2D3 may represent a promising new MS treatment.