Objective To investigate relationships between cognitive domains and white matter changes in different regions in patients with cognitive deficits after traumatic brain injury (TBI). Methods Databases 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. Results Significant pooled FA-executive correlations (p<0.001) were found across various regions, including the corpus callosum (CC) (r=0.42, 95% CI 0.30 to 0.54), superior longitudinal fasciculus (r=0.50, 95% CI 0.41 to 0.59) and internal capsule (IC) (r=0.49, 95% CI 0.37 to 0.61). The fornix (r=0.62, 95% CI 0.45 to 0.78) and cingulum (r=0.57, 95% CI 0.34 to 0.81) particularly correlated with memory (p<0.001). The CC and IC also showed significant relationships with attention and processing speed (p<0.001). Demographic factors had no influence overall, except that studies with a greater proportion of males had stronger correlations between memory and white matter (p<0.05). Conclusions FA 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.
Objective Post-traumatic headache (PTH) is one of the most frequent and persistent physical symptoms following mild traumatic brain injury (mTBI) and develop in more than 50% of this population. This study aimed to investigate the periaqueductal grey (PAG)-seeded functional connectivity (FC) in patients with mTBI with acute post-traumatic headache (APTH) and further examine whether the FC can be used as a neural biomarker to identify patients developing chronic pain 3 months postinjury. Methods 70 patients with mTBI underwent neuropsychological measurements and MRI scans within 7 days postinjury and 56 (80%) of patients were followed up at 3 months. 46 healthy controls completed the same protocol on recruitment to the study. PAG-seeded resting-state FC analysis was measured in 54 patients with mTBI with APTH, in comparison with 46 healthy volunteers. Results The mTBI+APTH group presented significantly reduced PAG-seeded FC within the default mode network (DMN), compared with healthy volunteers group. The connectivity strength can also predict patients' complaints on the impact of headache on their lives. Crucially, the initial FC strength between the PAG-right precuneus as well as the PAG-right inferior parietal lobule became the important predictor to identify patients with mTBI developing persistent PTH 3 months postinjury. Conclusions Patients with mTBI+APTH exhibited significant PAG-related FC differences mainly within the DMN. These regions extended beyond traditional pain processing areas and may reflect the diminished top-down attention regulation of pain perception through antinociceptive descending modulation network. The disrupted PAG-DMN FC may be used as an early imaging biomarker to identify patients at risk of developing persistent PTH.
Background and objective Aetiology and pathogenesis of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the most common autoimmune encephalitis, is largely unknown. Since an association of the disease with the human leucocyte antigen (HLA) has not been shown so far, we here investigated whether anti-NMDAR encephalitis is associated with the HLA locus. Methods HLA loci of 61 patients with anti-NMDAR encephalitis and 571 healthy controls from the Chinese Han population were genotyped and analysed for this study. Results Our results show that the DRB1*16:02 allele is associated with anti-NMDAR encephalitis (OR 3.416, 95% CI 1.817 to 6.174, p=8.9x10(-5), p(adj)=0.021), with a higher allele frequency in patients (14.75%) than in controls (4.82%). This association was found to be independent of tumour formation. Besides disease susceptibility, DRB1*16:02 is also related to the clinical outcome of patients during treatment, where patients with DRB1*16:02 showed a lower therapeutic response to the treatment than patients with other HLA alleles (p=0.033). Bioinformatic analysis using HLA peptide-binding prediction algorithms and computational docking suggested a close relationship between the NR1 subunit of NMDAR and the DRB1*16:02. Conclusions This study for the first time demonstrates an association between specific HLA class II alleles and anti-NMDAR encephalitis, providing novel insights into the pathomechanism of the disease.
Objective To describe an expanded teased nerve fibre classification in disease association. Methods We reviewed four newly proposed teased nerve fibre types (Types J-M): Type J, rope-like fibres; K, fibril-like clumps of osmium positivity; L, cellular debris along and within nerve fibres; M, circular axonal inclusions surrounded by thin myelin. Different clinical pathological entities were studied for these fibre types including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP: N=20); amyloid polyneuropathy (N=20); intraneural B-cell lymphoma (N=20) or adult-onset polyglucosan body disease (APBD: N=6) in comparison with 112 disease controls. Student's t-test was used to test significance of association between the identified fibre types and the specific clinical diagnosis. Results Each fibre type significantly associated (p<0.001) with particular disease categories: Type J, 60% of CIDP cases; Type K, 75% of amyloid cases; Type L, 75% of intraneural lymphoma cases; Type M, 100% of APBD cases. Rarely were these fibres found in the other disease control cases <= 3% of cases. In three cases, the teased fibre findings were so striking additional paraffin nerve preparations were made to make the pathological diagnosis when initial paraffin sections were non-diagnostic. Conclusions Teased nerve fibre Types J-M associate with commonly seen pathological diagnosis and are helpful in the consideration of specific neuropathy diagnoses.
Background Information from well-established dementia risk models can guide targeted intervention to prevent dementia, in addition to the main purpose of quantifying the probability of developing dementia in the future. Methods We conducted a systematic review of published studies on existing dementia risk models. The models were assessed by sensitivity, specificity and area under the curve (AUC) from receiver operating characteristic analysis. Results Of 8462 studies reviewed, 61 articles describing dementia risk models were identified, with the majority of the articles modelling late life risk (n= 39), followed by those modelling prediction of mild cognitive impairment to Alzheimer's disease (n= 15), mid-life risk (n= 4) and patients with diabetes (n= 3). Age, sex, education, Mini Mental State Examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery, Alzheimer's Disease Assessment Scale-cognitive subscale, body mass index, alcohol intake and genetic variables are the most common predictors included in the models. Most risk models had moderate-to-high predictive ability (AUC>0.70). The highest AUC value (0.932) was produced from a risk model developed for patients with mild cognitive impairment. Conclusion The predictive ability of existing dementia risk models is acceptable. Population-specific dementia risk models are necessary for populations and subpopulations with different characteristics.
Objective Inflammation plays a crucial role in the pathogenesis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Our study aimed to analyse previous inconsistent results of inflammatory markers in AD and MCI quantitatively. Methods Studies reporting concentrations of peripheral or cerebrospinal fluid (CSF) markers were included, and eligible data on AD, MCI and control were extracted. Pooled Hedges's g was adopted to illustrate comparisons, and various confounding factors were used to explore sources of heterogeneity. Results A total of 170 studies were included in the meta-analysis and systematic review, which demonstrated increased peripheral levels of highsensitivity C reactive protein (Hedges's g 0.281, p< 0.05), interleukin-6 (IL-6) (0.429, p<0.005), soluble tumour necrosis factor receptor 1 (sTNFR1) (0.763, p<0.05), soluble tumour necrosis factor receptor 2 (sTNFR2) (0.354, p<0.005), alpha1-antichymotrypsin (alpha 1-ACT) (1.217, p<0.005), IL-1 beta (0.615, p<0.05) and soluble CD40 ligand (0.868, p<0.005), and CSF levels of IL-10 (0.434, p<0.05), monocyte chemoattractant protein-1 (MCP-1) (0.798, p<0.005), transforming growth factorbeta 1 (1.009, p<0.05), soluble triggering receptor expressed on myeloid cells2 (sTREM2) (0.587, p<0.001), YKL-40 (0.849, p<0.001), alpha 1-ACT (0.638, p<0.001), nerve growth factor (5.475, p<0.005) and visinin-like protein-1 (VILIP-1) (0.677, p<0.005), in AD compared with the control. Higher levels of sTNFR2 (0.265, p<0.05), IL-6 (0.129, p<0.05) and MCP-1 (0.779, p<0.05) and lower levels of IL-8 (-1.293, p<0.05) in the periphery, as well as elevated concentrations of YKL-40 (0.373, p<0.05), VILIP-1 (0.534, p<0.005) and sTREM2 (0.695, p<0.05) in CSF, were shown in MCI compared with the control. Additionally, increased peripheral sTNFR1 (0.582, p<0.05) and sTNFR2 (0.254, p<0.05) levels were observed in AD compared with MCI. Conclusion Significantly altered levels of inflammatory markers were verified in comparison between AD, MCI and control, supporting the notion that AD and MCI are accompanied by inflammatory responses in both the periphery and CSF.
Over two decades have passed since posterior reversible encephalopathy syndrome (PRES) was first described in 1996. It has becoming increasingly recognised because of improved and more readily available imaging modality. The exact pathophysiological mechanism is not completely understood and remains controversial at present. Precise diagnosis is essential to guide prompt, proper management. Our ability of differentiating it from other acute neurological disorders is likely to improve as we learnt more about the spectrum of this entity in the last 20 years. We emphasise the importance of recognising its diagnostic criteria and biomarker, which would be of great relevance to either outcome evaluation or study design. PRES has a favourable prognosis generally, but neurological sequelae and even fatalities can occur, especially in severe forms that might cause substantial morbidity and even mortality, particularly when the syndrome is complicated by intracranial haemorrhage or brain infarction. In this review, the pathophysiology, approach to diagnosis, some controversies as to the prognosis, as well as the future research direction of PRES are described.
Background Higher docosahexaenoic acid (DHA) intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. Objective Our study aimed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (A beta)-mediated autophagy in elderly subjects with MCI. Methods This was a randomised, double-blind, placebo-controlled trial in Tianjin, China. A total of 240 individuals with MCI were identified and randomly divided into intervention (DHA 2 g/day, n= 120) and control (corn oil as placebo, n= 120) groups. Cognitive function and blood A beta-related biomarkers were measured at baseline, 6, 12, 18 and 24 months. Data were analysed using generalised estimating equation. Results A total of 217 participants (DHA: 109, placebo: 108) completed the trial. During the follow-up, scores of full-scale IQ, verbal IQ and subdomains of information and digit span were significantly higher in the intervention group than the convention group (p<0.05). In the intervention group, blood A beta-42 level and expression of A beta protein precursor mRNA were decreased (p<0.05), while Beclin-1 and LC3-II levels and expression of LC3-II mRNA were increased (p<0.05). Conclusion Daily oral DHA supplementation (2 g/day) for 24 months may improve cognitive function and change blood biomarker-related A beta-mediated autophagy in people with MCI. Larger longer-term confirmatory studies are warranted.