Effects of corticospinal tract integrity on upper limb motor function recovery in stroke patients treated with repetitive transcranial magnetic stimulation.

BACKGROUND: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. METHODS: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. RESULTS: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. CONCLUSIONS: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.

Comparison of conventional therapy, intensive therapy and modified constraint-induced movement therapy to improve upper extremity function after stroke.

OBJECTIVE: To compare the effects of 4 weeks of intervention using conventional rehabilitation, intensive conventional rehabilitation and modified constraint-induced movement therapy on the hemiplegic upper extremity in stroke patients. METHODS: Thirty stroke patients (mean age: 63.3, standard deviation 9.63 years; mean time since stroke: 11.33, standard deviation 8.29 weeks) were randomly divided into 3 groups: conventional rehabilitation, intensive conventional rehabilitation, and modified constraint-induced movement therapy (10 individuals in each). Motor function was assessed using the Wolf Motor Function Test before treatment, and 2 weeks and 4 weeks after treatment. RESULTS: The constraint-induced movement therapy and intensive conventional rehabilitation groups improved their function ability scores in the Wolf Motor Function Test significantly more than the conventional rehabilitation group after 2 weeks of treatment (p < 0.05), but all groups reached comparable levels at the end of 4 weeks of intervention. However, only the constraint-induced movement therapy intervention proved to have robust and systematic effects on the function ability scores, as revealed by the large, positive and significant correlation between the initial scores and the scores 2 and 4 weeks after the intervention. The median performance time of the Wolf Motor Function Test decreased significantly in all groups after 4 weeks of treatment (p < 0.05), but only the modified constraint-induced movement therapy group showed significant improvements both 2 and 4 weeks after the initiation of treatment. CONCLUSION: Compared with classical intervention, modified constraint-induced movement therapy showed an apparent advantage over both conventional intervention and intensive conventional rehabilitation for patients after stroke.

Lack of association between PCDH11X genetic variation and late-onset Alzheimer's disease in a Han Chinese population.

Protocadherin 11X (Pcdh11X) has been suspected to be associated with Alzheimer's disease through participating in the metabolism of PP1α and ß-catenin or by altering the synaptic functions. A recent genome-wide association study reported that a common single nucleotide polymorphism (SNP, rs5984894) in the gene encoding Pcdh11X was associated with susceptibility to late-onset Alzheimer's disease (LOAD) in Caucasians. In order to assess the involvement of the PCDH11X polymorphism in the risk of developing AD in Chinese, we analyzed the genotype and allele distributions of the PCDH11X rs5984894 polymorphism in a Han Chinese population (355 LOAD cases and 399 healthy controls). Our results failed to find any significant association between the tested SNP and LOAD, indicating that PCDH11X gene polymorphism does not play a major role in the genetic predisposition to LOAD in this Han Chinese population.

Implication of CLU gene polymorphisms in Chinese patients with Alzheimer's disease.

BACKGROUND: Clusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians. METHODS: The study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry. RESULTS: The minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR=1.39, 95% CI=1.13-1.72, P=0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR=1.66) and a protective haplotype (CCC)(OR=0.70). CONCLUSIONS: Our findings implicate CLU as a susceptibility gene for LOAD in Han Chinese.

Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease.

The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population.

New sesquiterpenes from Ligularia macrophylla.

From the roots of Ligularia macrophylla, a bisesquiterpene, ligumacrophyllal (1), and an eremophilane sesquiterpene, ligumacrophyllatin (2) were isolated. Their structures were elucidated by 2D-NMR herein. Additionally, seven known compounds (3-9) were afforded from the plant, and compound 3 was found as natural product for the first time.