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While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA - comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA - language correlations, while sex had a moderating effect on the FA - comprehension correlation of the arcuate fasciculus, and age influenced the FA - naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.

In recent years, non-invasive brain stimulation (NIBS) interventions for post-stroke aphasia have received increasing attention, but their effects across different language domains and the influence of targeted locations and moderators remain unclear. Randomized controlled trials (RCTs) on NIBS in patients with post-stroke aphasia were searched. Standardized mean differences (SMDs) for pre-post language changes were pooled in Bayesian network meta-analyses. Moderators were examined using meta-regression. Of the 2105 records identified, 69 RCTs involving 1670 patients were included. Low-frequency (LF)-transcranial magnetic stimulation (rTMS) (SMD 0.84 [0.65,1.03]) was superior to anodal-transcranial direct-current stimulation (a-tDCS) (SMD 0.38 [0.05,0.71]) for global severity. Dual-tDCS was the leading option for naming and repetition. For spontaneous speech, both a-tDCS and dual-tDCS resulted in greater effects than LF-rTMS. As stimulation targets, the right inferior frontal gyrus ranked higher in global severity and spontaneous speech, while the temporoparietal region ranked higher in comprehension. Meta-regression demonstrated that therapeutic effects in the naming domain were moderated by the mean period of each therapy condition and the first language, while significant associations with age, therapy period, and number of sessions were observed for spontaneous speech. Overall, LF-rTMS is the most prioritized NIBS mode to alleviate global severity. Dual and anodal tDCS outperform rTMS for naming and repetition. The optimal stimulation region varies across different domains.

Background: Frozen shoulder is a common shoulder disorder characterized by pain and restriction. Various nonsurgical treatments have been reported, but there is no consensus about their comparative efficacy and the effects of moderators. Purpose: To compare the efficacy of different nonsurgical interventions and identify potential patient-specific moderating factors for frozen shoulder. Study Design: Systematic review and network meta-analysis. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception to February 18, 2019. The search was supplemented by manual review of relevant reference lists. Randomized controlled trials of participants with frozen shoulder that compared nonsurgical interventions were selected. Measured outcomes included pain, shoulder function in daily activities, and range of motion. Results: Of 3136 records identified, 92 trials were eligible, evaluating 32 nonsurgical interventions in 5946 patients. Intra-articular injection improved pain (pooled standardized mean difference [95% CI]: steroid injection, 1.68 [1.03-2.34]; capsular distension, 2.68 [1.32-4.05]) and shoulder function (steroid injection, 2.16 [1.52-2.81]; distension, 2.89 [1.71-4.06]) to a greater extent than placebo. Capsular distension and extracorporeal shockwave therapy showed the highest ranking for pain relief and functional improvement, respectively. Laser therapy also showed benefits for pain relief (3.02 [1.84-4.20]) and functional improvement (3.66 [1.65-5.67]). Subgroup analyses by disease stages revealed that steroid injection combined with physical therapy provided more benefits during the freezing phase, whereas joint manipulation provided more benefits in the adhesive phase. Adjunctive therapies, female sex, and diabetes were also identified as moderators of effectiveness. Conclusion: Capsular distension is a highly recommended choice for treatment of frozen shoulder, contributing greatly to pain relief and functional improvement; steroid injection is also a prevailing effective intervention. Among new options, extracorporeal shockwave therapy and laser therapy show potential benefits for multiple outcomes. Individualized optimal intervention should be considered, given that treatment effect is moderated by factors including the disease stage, time of assessment, adjunctive therapies, female sex, and diabetes.

Background: Frozen shoulder is a common musculoskeletal disorder, characterised by pain and movement restriction. Non-surgical approaches are the mainstay therapy for frozen shoulder. Our aim was to compare the effect of different non-surgical interventions, and to identify potential moderating variables of treatment effect. Methods: The following databases were searched, from their inception to October 18, 2018: PubMed, EMBASE, Cochrane Library, and Web of Science. The search was supplemented by manual review of relevant reference lists. Randomised controlled trials (RCTs) of non-surgical interventions, with a clear comparison group and measured outcomes, were selected. All records were screened by two independent reviewers, and the quality of studies assessed. Study characteristics and outcome data were extracted for pairwise and network meta-analyses. Measured outcomes included pain, shoulder function in activities of daily living, and range of motion (ROM). The mean change in value from baseline was the primary outcome measure, with the pooled standardised mean difference (SMD), and its 95% credible interval (CrI), used to compare outcomes between two groups. Findings: Of 2953 records identified, 92 RCTs were eligible, evaluating 32 non-surgical interventions, in 5946 patients. Of these, intraarticular injection improved pain (steroid injection, SMD 1·68 [95% CrI, 1·03-2·34]; capsular distension, SMD 2·68 [1·32-4·05]), and shoulder function (steroid injection: SMD 2·16 [1·52-2·81]; distension: SMD 2·89 [1·71-4·06]) to a greater extent than either a placebo or conventional physical therapy. Subgroup analyses revealed steroid injection combined with conventional physical therapy yielding improvement during the painful freezing phase, with joint manipulation yielding more benefits in the adhesive phase. Disease stage, female sex, and diabetes were identified as moderating factors of treatment outcome. Interpretation: Intra-articular injection is the prevailing non-surgical treatment for frozen shoulder. Factors (disease stage, sex, and diabetes) should be considered for individualised optimal options. Funding Statement: This work was funded by the grants from National Natural Science Foundation of China (No.81902278), and Zhejiang Provincial Natural Science Foundation (No. LY15H170002) Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This systematic review was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension statement, incorporating network meta-analyses. The study protocol has been submitted to PROSPERO (registration number CRD42018112971).

Spinal cord injury (SCI) is an independent risk factor for type 2 diabetes, and may induce insulin resistance that leads to this disease. Studies have shown that greater phosphoinositide 3-kinase (PI3K) activation in the hypothalamus leads to activation of the anti-inflammatory pathway, and the anti-inflammatory reflex may protect against insulin resistance and type 2 diabetes. However, the importance of this phenomenon in type 2 diabetes pathogenesis after SCI remains elusive. In the present study, the expression of c-Fos in the hypothalamus of rats with SCI was elevated, and the hypothalamus injury was observer following SCI. Then we showed that SCI could induce increased levels of blood glucose and glucose tolerance in rats. Also, we found that SCI could damage the liver, adipocyte and pancreas, and led to lipid position in liver. Western blots were used to detect the level of PI3K and p-Akt in the hypothalamus, and the results showed a significant downregulation of PI3K and p-Akt after SCI. Furthermore, to verify the activity of the PI3K signaling pathway, immunofluorescence was used to examine the expression of neurons positive for p-S6 (a marker of PI3K activation) after SCI. The results showed that the expression of p-S6-positive neurons decreased after SCI. In addition, the effect of SCI on peripheral inflammation was also investigated. Following SCI, the serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 increased. Collectively, our results suggest abnormality in glucose metabolism after SCI, and demonstrate that SCI may impair activation of the PI3K signaling pathway in the hypothalamus. The reduced activity of the PI3K signaling pathway in the hypothalamus may lead to peripheral inflammation, which might be the mechanism underlying the development of insulin resistance and type 2 diabetes following SCI.

ObjectiveTo investigate relationships between cognitive domains and white matter changes in different regions in patients with cognitive deficits after traumatic brain injury (TBI).MethodsDatabases including PubMed, Embase, Web of Science and CENTRAL were searched for studies published before 5 August 2017. Correlation coefficients between cognition and white matter integrity, measured by diffusion metrics, including fractional anisotropy (FA), were pooled from 49 studies including 1405 patients. The influence of demographic factors was assessed by meta-regression analysis.ResultsSignificant pooled FA–executive correlations (pConclusionsFA is the most sensitive metric for detecting post-TBI cognitive decline across various domains. Representative white matter regions, such as the CC and IC, perform better than whole-brain white matter for reflecting a wide range of cognitive domains, including memory, attention and executive functions. Moreover, the fornix and cingulum particularly reflect memory function. They yield insights into particular imaging indicators that have neuropsychological value.

Progressive motor deficits are relatively common in acute pontine infarction and frequently associated with increased functional disability. However, the factors that affect the progression of clinical motor weakness are largely unknown. Previous studies have suggested that pontine infarctions are caused mainly by basilar artery stenosis and penetrating artery disease. Recently, lower pons lesions in patients with acute pontine infarctions have been reported to be related to progressive motor deficits, and ensuing that damage to the corticospinal tracts may be responsible for the worsening of neurological symptoms. Here, we review studies on motor weakness progression in pontine infarction and discuss the mechanisms that may underlie the neurologic worsening.