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Background and Purpose: Neuronal intranuclear inclusion disease (NIID) is associated with CGG repeat expansion in the NOTCH2NLC gene. Although pure or dominant peripheral neuropathy has been described as a subtype of NIID in a few patients, most NIID patients predominantly show involvements of the central nervous system (CNS). It is necessary to further explore whether these patients have subclinical peripheral neuropathy., Methods: Twenty-eight NIID patients, clinically characterized by CNS-dominant involvements, were recruited from two tertiary hospitals. Standard nerve conduction studies were performed in all patients. Skin and sural nerve biopsies were performed in 28 and 15 patients, respectively. Repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to screen the CGG repeat expansion in NOTCH2NLC., Results: All 28 patients can be diagnosed with NIID based on skin pathological and genetic changes. All patients predominantly showed CNS symptoms mainly characterized by episodic encephalopathy and cognitive impairments, but no clinical symptoms of peripheral neuropathy could be observed initially. Electrophysiological abnormalities were found in 96.4% (27/28) of these patients, indicating that subclinical peripheral neuropathy is common in NIID patients with CNS-dominant type. Electrophysiological and neuropathological studies revealed that demyelinating degeneration was the main pathological pattern in these patients, although mild axonal degeneration was also observed in some patients. No significant association between CGG repeat size and the change of nerve conduction velocity was found in these patients., Conclusions: This study demonstrated that most patients with CNS-dominant NIID had subclinical peripheral neuropathy. Electrophysiological examination should be the routinely diagnostic workflow for every NIID patient., (© 2022 European Academy of Neurology.)

Methods: From April 2017 to December 2020, we retrospectively recruited 477 patients with acute ischemic stroke (within 48 hours after onset). Progressive infarction was defined as an increase of ≥1 point in motor power or ≥2 points on the total National Institutes of Health Stroke Scale (NIHSS) within 7 days after admission and extension of the original infarction were further confirmed by diffusion-weighted imaging. Demographic characteristics, clinical information, and neuroimaging characteristics were evaluated after admission. All blood draws and initial imaging were completed within 24 hours of admission., Results: PI occurred in 147 (30.8%) patients. Univariate analysis comparing the two groups revealed that hypertension, initial NIHSS score, discharge NIHSS score, modified Rankin scale score at 90 days, monocyte level, creatinine level, fasting glucose level, LMR, monocyte-to-high-density lipoprotein ratio (MHR), and lesion location were significantly different ( P < 0.05). Multivariate logistic regression analysis showed that the odds ratio of PI increased as the quartile of LMR increased, with the lowest quartile as the reference value. Subgroup analyses showed that a high LMR was an independent predictor of PI only in large artery atherosclerosis (LAA) patients. The receiver operating characteristic (ROC) curve was drawn to estimate the predictive value of LMR for PI. For all cases, the area under the curve was 0.583 (95% CI 0.526-0.641), and the best predictive cutoff value was 3.506, with a sensitivity of 53.1% and a specificity of 63.9%. In patients with LAA, the area under the curve was 0.585 (95% CI 0.505-0.665), and the best predictive cutoff value was 3.944, with a sensitivity of 48.7% and a specificity of 72.8%., Conclusions: LMR was an independent predictor for progressive infarction in patients with acute ischemic stroke, especially in LAA cerebral infarction patients., Competing Interests: The authors declares that they have no conflicts of interest., (Copyright © 2022 Xiaocheng Mao et al.)

Parkinson's disease (PD) is a common degenerative disease of the central nervous system. Although some drugs can alleviate the progress of PD, their long-term use will lead to complications, so it is still necessary to find new drugs to delay or cure PD effectively. In view of the difficulty in developing new drugs, it is imperative to discover new functions of existing compounds that could be used to treat PD. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD symptoms in a mouse model. Subsequently, these mice were treated with the antibiotic ceftriaxone. Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP, downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively, and reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF- κ B)/NF- κ B in the brain of PD mice. In addition, ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus and increased the abundance of probiotic Akkermansia . Finally, ceftriaxone treatment increased the expression of the tight junction proteins zona occludens-1(ZO-1) and occludin in the colon, decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF- κ B in the colon, and decreased the serum concentration of the proinflammatory cytokines interleukin-1 β (IL-1 β ), IL-6, and tumour necrosis factor- α (TNF- α ). These results indicate that ceftriaxone had a neuroprotective effect on MPTP-induced PD mice, and its neuroprotective effect could be through regulating inflammation and intestinal microbiota. While we showed that ceftriaxone exerts a neuroprotective effect in an MPTP-induced PD mouse model, our findings are limited to the short-term effects of ceftriaxone. Additional work using transgenic mice is required to determine the long-term effects of ceftriaxone. In addition, the dose and frequency of ceftriaxone use should be evaluated., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Xiaoting Zhou et al.)