Thalamocortical dysconnectivity in paroxysmal kinesigenic dyskinesia: Combining functional magnetic resonance imaging and diffusion tensor imaging.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is associated with macrostructural and microstructural abnormalities in the thalamus. OBJECTIVES: To examine functional and structural connectivity of thalamocortical networks in paroxysmal kinesigenic dyskinesia and to further investigate the effect of mutation of the proline-rich transmembrane protein 2 on thalamocortical networks. METHODS: Patients with paroxysmal kinesigenic dyskinesia (n = 20), subdivided into proline-rich transmembrane protein 2-mutated (n = 8) and nonmutated patients (n = 12) and healthy controls (n = 20) underwent resting-state functional MRI and diffusion imaging scan. The functional properties of correlations in neural activity (functional connectivity) and the structural properties of white matter probabilistic tractography (structural connectivity) were analyzed to characterize thalamocortical networks. Furthermore, the effect of proline-rich transmembrane protein 2 mutation on functional and structural connectivity of thalamocortical networks were examined using one-way analysis of variance among three groups. RESULTS: Patients had increased functional and structural connectivity between ventral lateral/anterior thalamic nuclei and a lateral motor area, as compared to controls. This functional connectivity positively correlated with disease duration. Interestingly, proline-rich transmembrane protein 2-mutated patients showed decreased functional connectivity and preserved structural connectivity, between mediodorsal nucleus and prefrontal cortex, compared to nonmutated patients and controls. CONCLUSIONS: Thalamomotor/premotor hyperconnectivity suggests abnormal communication between thalamus and motor cortex in patients. Furthermore, thalamoprefrontal hypoconnectivity in proline-rich transmembrane protein 2-mutated patients might indicate that proline-rich transmembrane protein 2 mutations result in inefficient thalamoprefrontal integration. Our findings facilitate a deeper understanding of the crucial role of thalamocortical dysconnectivity in the pathophysiological mechanisms of paroxysmal kinesigenic dyskinesia. © 2017 International Parkinson and Movement Disorder Society.

The anti-depression effect of Xylaria nigripes in patients with epilepsy: A multicenter randomized double-blind study.

PURPOSE: The comorbidity of depression in patients with epilepsy is common and treatment is still controversial. This pilot study was aimed at evaluating the efficacy and safety of Xylaria nigripes for treating depressive symptoms in patients with epilepsy during 12 weeks of treatment. METHODS: A multicenter, double-blind, placebo-controlled, randomized superiority study was performed. A total of 104 patients with epilepsy who fulfilled the study criteria were randomized 1:1 to receive Xylaria nigripes (the Wu Ling group) or placebo (the placebo group) treatment in the 12-week period of study. The participants were visited on weeks 0, 2, 4, 8, and 12 of the treatment course. RESULTS: Eighty-one patients finished all of the visits. The primary efficacy endpoint in this study was the total effective rate for depression, which was significantly greater in the Wu Ling group (51.3%, n=39) than in the placebo group (35.7%, n=42, 0.51-0.36=0.15, 95% CI -0.06 to 0.37, U=2.83, P=0.002) after 12 weeks of treatment. No differences in seizure frequency or changes in severity were found between the Wu Ling and the placebo groups. In addition, the quality of life and seizure worry subscale scores in patients with epilepsy were also improved more notably in the Wu Ling group than in the placebo group (P<0.05). Most of the adverse effects (AEs) in this study were mild and had no differences between the Wu Ling and the placebo groups. CONCLUSION: Xylaria nigripes could alleviate depressive symptoms within 12 weeks treatment and was well tolerated in patients with epilepsy.

[A comparison study on cognitive function in patients with single subcortical lesion stroke of four different areas].

OBJECTIVE: Comparing the characteristics of cognitive impairment of patients with single subcortical lesion stroke of four different areas, we are to explore the cognitive function of the thalamus and basal ganglia and this is help for early identification of vascular cognitive impairment (VCI). METHODS: 63 patients with single subcortical lesion stroke (including 14 left thalamic stoke group, 17 left basal ganglia stroke group, 15 right thalamic stroke group, 17 right basal ganglia stroke group) and 34 healthy subjects participated in the current study, whose age, sex and education were matched. A comprehensive neuropsychological battery was used for evaluation. RESULTS: Compared to the normal control group, there was an overall decline of cognitive functions in patients with single subcortical lesion stroke in memory, attention/executive function, language, and visuospatial ability (P < 0.05). The scores of the left thalamic stroke group were worse than the other three stroke groups in language (BNT16.6 ± 2.6), auditory verbal learning test-immediate recall (12.8 ± 4.4), auditory verbal learning test-delayed recall (2.4 ± 2.3), listening recognition (19.1 ± 3.1), structure delayed recall (9.1 ± 4.7) and symbol digit modalities test-recall (0.9 ± 1.1) (P < 0.05). However, the left basal ganglia stroke group did better in tests manipulated by the right hand [including Trial making test (part A) score (75 ± 22), Trail making test (part B) score (204 ± 81), Clock drawing test (23.5 ± 4.6), Symbol digit modalities test (24 ± 9)] than other three stroke group, as good as the normal group (P < 0.05). CONCLUSIONS: Single subcortical stroke patients may have general, non-selective cognitive impairment. But, different stroke areas have their own characteristics. The scores of the left thalamic stroke group were worse than the other three stroke groups.

[Effect of hyperbaric oxygen treatment on mitochondrial free radicals after transient focal cerebral ischemia in rats].

OBJECTIVE: To investigate the effect of hyperbaric oxygen(HBO)therapy on mitochondrial free radicals after transient focal cerebral ischemia in rats. METHODS: The male SD rats were randomly assigned into two groups, control and HBO groups. All animals were subjected to 90 min intra-luminal middle cerebral artery occlusion (MCAO) with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. HBO treatment was performed in a pressure chamber with 100% O(2)(3 ATM 1 h) 3 h after ischemia. Twenty-four hours after ischemia, mitochondria in the ischemic core and penumbra were isolated and the contents of H(2)O(2), O(2)(*-), MDA, SOD, GSH-PX and GSH in mitochondria were measured respectively. RESULT: After cerebral ischemia-reperfusion, contents of mitochondrial H(2)O(2), O(2)(*-), MDA increased, while the SOD, GSH-PX and GSH in the mitochondria decreased significantly both in the ischemic core and the ischemic penumbra, compared with those in the normal controls(P<0.05). In the ischemic penumbra, HBO therapy increased significantly the content of O(2)(*-)(P<0.05), enhanced the activity of SOD, and decreased the level of MDA (P<0.05). However, HBO therapy did not change the level of MDA, though it also increased the content of O(2)(*-) and the activity of SOD in the ischemic core. HBO therapy had no significant effect on the contents of H(2)O(2), GSH-PX and GSH in the ischemic mitochondria. CONCLUSION: HBO therapy initiated early after acute transient cerebral ischemia in rats can increase the mitochondrial free radicals level, but also increase the activity of the anti-radical enzymes. HBO treatment inhibits the lipid peroxidation damage of mitochondria in the ischemic penumbra, but not in the ischemic core, which indicates that the mitochondrial function plays a role in the reaction of the free radical in the ischemic area after HBO therapy.

[Effects of puerarin with aspirin on the markers of damaged vascular endothelial cells in patients with acute cerebral infarction].

OBJECTIVE: To investigate the effects of puerarin with aspirin on the markers of damaged vascular endothelial cells, as von Willebrand factor (vWF), and thrombomodulin (TM) in patients with acute cerebral infarction (ACI). METHOD: Forty-five patients with ACI were included in this study and divided into basic treatment and puerarin groups, meanwhile 26 healthy persons selected as control group. The serum vWF and sTM concentrations were measured by enzyme-linked immunosorbant assay (ELISA) and national institute health stroke scale (NIHSS) score was evaluated at admission and 14 days later after treatment. RESULT: The level of serum vWF significantly increased in patients with ACI compared to control and major stroke had higher vWF level than minor stroke (P < 0.01), but the serum level of sTM had no obviously differences respectively. Correlation analysis showed that there is a positive correlation between the level of vWF and NIHSS score (P < 0.05, r = 0.368), while the significant correlations between the level of vWF and sTM, sTM and NIHSS score were not observed. After 14 days treatment, the level of serum vWF and NIHSS score were obviously decreased in patients treated with puerarin and aspirin, not in basic treated patients. The level of sTM was increased in patients after 14 d, while puerarin treated patient has lower sTM level than patients with basic treatment (P < 0.05). CONCLUSION: Patients with ACI cotreated with puerarin and aspirin improved the neurological function, decreased the levels of serum vWF and sTM, indicating puerarin with aspirin had the protective effects on the damaged vascular endothelial cells.

[Effects of puerarin on expression of nuclear factor kappaB after cerebral ischemia/reperfusion in rats].

OBJECTIVE: To investigate the activation of nuclear factor kappaB (NF-KB) and the influence of puerarin on it after cerebral ischemia-reperfusion in rats. METHOD: Cerebral ischemia-reperfusion injury was induced by 90 min of middle cerebral artery (MCA) occlusion and followed by 2, 6, 12, 24, 72 h reperfusion. Puerarin or saline was intra-peritoneally injected 1h before MCA occlusion and then the drugs were administered once every six hours. The infarct volume and brain edema were determined by TTC stain. Level of NF-kappaB P65 subunit was determined by immunohistochemistry and western blot. RESULT: Immunohistochemistry revealed the translocation of NF-kappaB. A time course of NF-kappaB induction in brain showed that NF-kappaB P65 subunit obviously increased at 6 h, peaked at 24 h and then decreased by 72 h post-reperfusion. Puerarin decreased the level of NF-kappaB at 24, 72 h after reperfusion. There was a decrease trend in brain infarct volume between puerarin and control. CONCLUSION: NF-kappaB is translocated and its level is increased after ischemia-reperfusion. Puerarin may attenuate the ischemia-reperfusion injury through inhibition of NF-kappaB activation.

[Effect of hyperbaric oxygenation treatment on the apoptotic cell death pathway after transient focal cerebral ischemia].

AIM: To evaluate the effects of administration of hyperbaric oxygenation(HBO) when initiated at different time after acute transient ischemia. Apoptosis in the ischemic penumbra was further investigated to search for the possible mechanism. METHODS: The male SD rats were randomly assigned to the following groups: control, HBO therapy initiated 3 h after ischemia, HBO therapy initiated 6 h after ischemia, HBO therapy initiated 12 h after ischemia. All animals were subjected to 90 min intraluminal middle cerebral artery occlusion (MCAO) with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. HBO treatment was performed in a pressure chamber with 100% O2, 3 arm for 1 h. Neurological deficits and infarct volumes were assessed at 24 hours after ischemia. The immunohistochemical changes of apoptosis in the penumbra were evaluated by detecting the expression of cleaved Caspase-3, cleaved Caspase-9, Bcl-2, Bax and TUNEL staining. RESULTS: HBO therapy initiated at 3 and 6 hours after ischemia significantly improved the neurological function and reduced infarct volume. Meanwhile, it increased the expression of Bcl-2 protein and decreased the expression of activated Caspase-3, activated Caspase-9 and TUNEL-positive cells. However, HBO therapy administrated 12 hours after ischemia aggravated the neurological deficits and enlarged infarct volume, while it showed no significant reduction of apoptotic change compared with control. CONCLUSION: There is a therapeutic window for the use of HBO in acute transient cerebral ischemia in rats. HBO-treatment is highly effective in reducing infarct volume when initiated up to 6h after the onset of ischemia. Inhibition of apoptotic cell death in the penumbra appears to be the underlying protective effect of early therapy.

[Clinical study on Zhuyu Tongfu serial recipe combined with acupuncture and massotherapy in treating hypertensive cerebral hemorrhage].

OBJECTIVE: To observe the clinical efficacy and mechanism of Zhuyu Tongfu (ZYTF) Serial Recipe combined with acupuncture and massotherapy in treating hypertensive cerebral hemorrhage (HCH). METHODS: One hundred and eighteen patients with hypertensive cerebral hemorrhage, on the basis of conventional Western medicine treatment, were randomly divided into ZYTF combined with acupuncture and massotherapy group (treated group) and simple Western medicine group (control group); the clinical efficacy, neurofunction deficit scoring (NDS) alterations and hematoma absorption rate of both groups were observed, and also the plasma superoxide dismutase (SOD) activity, plasma lipid peroxidase (LPO) content, erythrocyte glutathion peroxidase (GSH-Px) activity, hematocrit (Ht) and the whole blood viscosity (Va) change were also observed. RESULTS: In the treated group, the clinical efficacy, NDS improvement and hematoma absorption rate were superior to that of the control group; comparison between the two groups after treatment showed that plasma SOD activity and GSH-Px activity got more elevated and plasma LPO content, Ht and Va more lowered in the the treated group than those in the control group. CONCLUSION: ZYTF combined with acupuncture and massotherapy has better effect, its therapeutic mechanism was possibly correlated to the elevation of plasma SOD activity, GSH-Px activity and lowering of plasma LPO content, Ht and Va.