Topological alterations in white matter anatomical networks in cervical dystonia.

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

Abnormal supplementary motor areas are associated with idiopathic and acquired blepharospasm.

Blepharospasm is a common form of focal dystonia characterized by excessive and involuntary spasms of the orbicularis oculi. In addition to idiopathic blepharospasm, lesions in various brain regions can also cause acquired blepharospasm. Whether these two types of blepharospasm share a common brain network remains largely unknown. Herein, we performed lesion coactivation network mapping, based on meta-analytic connectivity modeling, to test whether lesions causing blepharospasm could be mapped to a common coactivation brain network. We then tested the abnormality of the network in patients with idiopathic blepharospasm (n = 42) compared with healthy controls (n = 44). We identified 21 cases of lesion-induced blepharospasms through a systematic literature search. Although these lesions were heterogeneous, they were part of a co-activated brain network that mainly included the bilateral supplementary motor areas. Coactivation of these regions defines a single brain network that encompasses or is adjacent to most heterogeneous lesions causing blepharospasm. Moreover, the bilateral supplementary motor area is primarily associated with action execution, visual motion, and imagination, and participates in finger tapping and saccades. They also reported decreased functional connectivity with the left posterior cingulate cortex in patients with idiopathic blepharospasm. These results demonstrate a common convergent abnormality of the supplementary motor area across idiopathic and acquired blepharospasms, providing additional evidence that the supplementary motor area is an important brain region that is pathologically impaired in patients with blepharospasm.

Neural Correlates of Facial Emotion Recognition Impairment in Blepharospasm: A Functional Magnetic Resonance Imaging Study.

Selective impairment in recognizing facial expressions of disgust was reported in patients with focal dystonia several years ago, but the basic neural mechanisms remain largely unexplored. Therefore, we investigated whether dysfunction of the brain network involved in disgust recognition processing was related to this selective impairment in blepharospasm. Facial emotion recognition evaluations and resting-state functional magnetic resonance imaging were performed in 33 blepharospasm patients and 33 healthy controls (HCs). The disgust processing network was constructed, and modularity analyses were performed to identify sub-networks. Regional functional indexes and intra- and inter-functional connections were calculated and compared between the groups. Compared to HCs, blepharospasm patients demonstrated a worse performance in disgust recognition. In addition, functional connections within the sub-network involved in perception processing rather than recognition processing of disgust were significantly decreased in blepharospasm patients compared to HCs. Specifically, decreased functional connections were noted between the left fusiform gyrus (FG) and right middle occipital gyrus (MOG), the left FG and right FG, and the right FG and left MOG. We identified decreased functional activity in these regions, as indicated by a lower amplitude of low-frequency fluctuation in the left MOG, fractional amplitude of low-frequency fluctuation in the right FG, and regional homogeneity in the right FG and left MOG in blepharospasm patients versus HCs. Our results suggest that dysfunctions of the disgust processing network exist in blepharospasm. A deficit in disgust emotion recognition may be attributed to disturbances in the early perception of visual disgust stimuli in blepharospasm patients.

Cortico-basal ganglia networks dysfunction associated with disease severity in patients with idiopathic blepharospasm.

Background: Structural changes occur in brain regions involved in cortico-basal ganglia networks in idiopathic blepharospasm (iBSP); whether these changes influence the function connectivity patterns of cortico-basal ganglia networks remains largely unknown. Therefore, we aimed to investigate the global integrative state and organization of functional connections of cortico-basal ganglia networks in patients with iBSP. Methods: Resting-state functional magnetic resonance imaging data and clinical measurements were acquired from 62 patients with iBSP, 62 patients with hemifacial spasm (HFS), and 62 healthy controls (HCs). Topological parameters and functional connections of cortico-basal ganglia networks were evaluated and compared among the three groups. Correlation analyses were performed to explore the relationship between topological parameters and clinical measurements in patients with iBSP. Results: We found significantly increased global efficiency and decreased shortest path length and clustering coefficient of cortico-basal ganglia networks in patients with iBSP compared with HCs, however, such differences were not observed between patients with HFS and HCs. Further correlation analyses revealed that these parameters were significantly correlated with the severity of iBSP. At the regional level, the functional connectivity between the left orbitofrontal area and left primary somatosensory cortex and between the right anterior part of pallidum and right anterior part of dorsal anterior cingulate cortex was significantly decreased in patients with iBSP and HFS compared with HCs. Conclusion: Dysfunction of the cortico-basal ganglia networks occurs in patients with iBSP. The altered network metrics of cortico-basal ganglia networks might be served as quantitative markers for evaluation of the severity of iBSP.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Mental health and quality of life in patients with craniofacial movement disorders: A cross-sectional study.

Background: Facial appearance and expressions influence social interaction. Hemifacial spasm (HFS), blepharospasm (BPS), and blepharospasm-oromandibular dystonia (BOD) are common forms of craniofacial movement disorders. Few studies have focused on the mental burden and quality of life (QoL) in patients with craniofacial movement disorders. Therefore, this study investigated mental health and QoL in these patients. Methods: This cross-sectional study included 90 patients with craniofacial movement disorders (HFS, BPS, and BOD; 30 patients per group) and 30 healthy individuals without craniofacial movement disorders (control group) recruited from October 2019 to November 2020. All participants underwent QoL and mental health evaluations for depression, anxiety, and stigma using the 36-item Short Form Health Survey (SF-36), Hamilton Anxiety Rating Scale (HAMA), Hamilton Rating Scale for Depression-24 (HAMD-24) and a questionnaire related to stigma. Results: Depression was diagnosed in 37 (41.11%) patients, whereas 30 patients (33.33%) had anxiety. HAMA scores were significantly higher in the BPS and BOD groups than in the control group. Nineteen patients (21.11%) experienced stigma and SF-36 scores were lower in various dimensions in the movement disorders groups compared to healthy controls. The role-physical and social function scores were significantly lower in the movement disorders groups than in the control group all p < 0.05. The vitality scores of the BPS group and mental health scores of the BPS and BOD groups were significantly lower than those of the control group. Correlation analysis showed that the eight dimensions of SF-36 correlated with education level, disease duration, HAMD score, and HAMA score (all p < 0.05). Regression analysis demonstrated that the HAMD score correlated with general health, vitality, social function, role-emotional, and mental health (all p < 0.05). The HAMA score correlated with body pain after adjusting for education level and disease duration. Conclusion: This study highlights the significant frequency of mental symptoms, including depression, anxiety, and stigma, which lower QoL in patients with craniofacial movement disorders.

Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke in Asian countries. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme defect prevalent in Asian countries, has been associated with atherosclerotic cardiovascular disease and worse poststroke outcomes. However, the impact of G6PD deficiency on ICAS remains unclear. We aimed to compare the risk of ICAS in stroke patients with and without G6PD deficiency in a Chinese cohort. METHODS: We prospectively and consecutively recruited stroke patients from four centers in China. All patients received intracranial artery assessment by magnetic resonance/computed tomography angiography or digital subtraction angiography, as well as G6PD enzyme evaluation. The prevalence, burden, and characteristics of ICAS were compared between patients with and without G6PD deficiency using multivariate regression analysis. RESULTS: Among 1593 patients, 116 (63.7%) of 182 patients with G6PD deficiency and 714 (50.6%) of 1411 patients with normal G6PD levels were identified as ICAS. Age, hypertension, diabetes, and G6PD deficiency were independent predictors of ICAS. Among patients with ICAS, G6PD-deficient individuals were more likely to have multiple (≥2 segments) intracranial stenosis (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.25-2.81, p = 0.002). G6PD deficiency increased the risk of ICAS in patients who were male (OR = 1.82, 95% CI = 1.24-2.66, p = 0.002), aged ≥70 years (OR = 2.40, 95% CI = 1.33-4.31, p = 0.004), or hypertensive (OR = 1.88, 95% CI = 1.28-2.77, p = 0.001). CONCLUSIONS: Stroke patients with G6PD deficiency have a higher prevalence and ICAS burden than those with normal G6PD, particularly those who are male, older, and hypertensive.

Association between aspirin-induced hemoglobin decline and outcome after acute ischemic stroke in G6PD-deficient patients.

AIMS: The risk of hemoglobin decline induced by low-dose aspirin in glucose-6-phosphate dehydrogenase (G6PD) deficiency remains unknown, and its influence on stroke outcome remains to be investigated. This study aimed to evaluate the effect of G6PD deficiency on hemoglobin level during aspirin treatment and its association with outcome after acute ischemic stroke. METHODS: In total, 279 patients (40 G6PD-deficient and 239 G6PD-normal) with acute ischemic stroke treated with aspirin 100 mg/day from a cohort study were examined. The primary safety endpoint was a hemoglobin decline ≥25 g/L or 25% from baseline within 14 days after aspirin treatment. Poor outcomes were defined as a modified Rankin Scale score ≥2 at 3 months. The χ2 test was used to compare stroke outcomes, and multivariate logistic regression analyses were performed to analyze the association between hemoglobin level and outcomes. RESULTS: The G6PD-deficient group had lower baseline hemoglobin and tended to develop comorbid pulmonary infection more frequently (p < 0.05). The proportion of patients with hemoglobin decline ≥25 g/L or 25% from baseline (15.0% vs. 3.3%; p = 0.006) and anemia (30.0% vs. 14.6%; p = 0.016) after aspirin treatment was higher in the G6PD-deficient group, which was accompanied by a more significant bilirubin increase. The rate of poor functional outcomes at 3 months after acute ischemic stroke was higher in the G6PD-deficient group (Risk ratio = 1.31 [95% confidence interval (CI) = 1.10-1.56]; p = 0.017). Confounder-adjusted analysis showed that lower hemoglobin levels (odds ratio = 0.98 [95% CI = 0.96-0.99]; adjusted p = 0.009) increased the risk of poor functional outcomes. CONCLUSION: Hemoglobin decrease with bilirubin increase after aspirin treatment in patients with G6PD deficiency suggests hemolysis, which may influence stroke prognosis. The risk of hemoglobin decline should be carefully monitored in G6PD-deficient patients with ischemic stroke taking aspirin.

Topological Alterations in White Matter Structural Networks in Blepharospasm.

BACKGROUND: Accumulating evidence indicates regional structural changes in the white matter (WM) of brains in patients with blepharospasm (BSP); however, whether large-scale WM structural networks undergo widespread reorganization in these patients remains unclear. OBJECTIVE: We investigated topology changes and global and local features of large-scale WM structural networks in BSP patients compared with hemifacial spasm (HFS) patients or healthy controls (HCs). METHODS: This cross-sectional study applied graph theoretical analysis to assess deterministic diffusion tensor tractography findings in 41 BSP patients, 41 HFS patients, and 41 HCs. WM structural connectivity in 246 cortical and subcortical regions was assessed, and topological parameters of the resulting graphs were calculated. Networks were compared among BSP, HFS, and HCs groups. RESULTS: Compared to HCs, both BSP and HFS patients showed alterations in network integration and segregation characterized by increased global efficiency and modularity and reduced shortest path length. Moreover, increased nodal efficiency in multiple cortical and subcortical regions was found in BSP and HFS patients compared with HCs. However, these differences were not found between BSP and HFS patients. Whereas all participants showed highly similar hub distribution patterns, BSP patients had additional hub regions not present in either HFS patients or HCs, which were located in the primary head and face motor cortex and basal ganglia. CONCLUSIONS: Our findings suggest that the large-scale WM structural network undergoes an extensive reorganization in BSP, probably due to both dystonia-specific abnormalities and facial hyperkinetic movements. © 2021 International Parkinson and Movement Disorder Society.

Machine Learning for Predicting Individual Severity of Blepharospasm Using Diffusion Tensor Imaging.

Accumulating diffusion tensor imaging (DTI) evidence suggests that white matter abnormalities evaluated by local diffusion homogeneity (LDH) or fractional anisotropy (FA) occur in patients with blepharospasm (BSP), both of which are significantly correlated with disease severity. However, whether the individual severity of BSP can be identified using these DTI metrics remains unknown. We aimed to investigate whether a combination of machine learning techniques and LDH or FA can accurately identify the individual severity of BSP. Forty-one patients with BSP were assessed using the Jankovic Rating Scale and DTI. The patients were assigned to non-functionally and functionally limited groups according to their Jankovic Rating Scale scores. A machine learning scheme consisting of beam search and support vector machines was designed to identify non-functionally versus functionally limited outcomes, with the input features being LDH or FA in 68 white matter regions. The proposed machine learning scheme with LDH or FA yielded an overall accuracy of 88.67 versus 85.19% in identifying non-functionally limited versus functionally limited outcomes. The scheme also identified a sensitivity of 91.40 versus 85.87% in correctly identifying functionally limited outcomes, a specificity of 83.33 versus 83.67% in accurately identifying non-functionally limited outcomes, and an area under the curve of 93.7 versus 91.3%. These findings suggest that a combination of LDH or FA measurements and a sophisticated machine learning scheme can accurately and reliably identify the individual disease severity in patients with BSP.

Aspirin Therapy in Cardiovascular Disease with Glucose-6-Phosphate Dehydrogenase Deficiency, Safe or Not?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, which may present as acute hemolysis, neonatal jaundice, or chronic hemolysis. Ingestion of fava beans, as well as infection and certain drugs, are the most typical causes of acute hemolysis in people with G6PD deficiency. Aspirin, the cornerstone in current therapies for the prevention of cardiovascular disease (CVD), is occasionally reported to induce acute hemolysis in G6PD-deficient individuals. G6PD deficiency is typically asymptomatic and many CVD patients with this enzyme defect start to take long-term aspirin therapy without G6PD activity examination; however, no consensus on the safety of aspirin in this population has been reached. A few studies have reported on this issue and produced contradictory results. In this review, we discuss the possible mechanisms of aspirin-induced hemolysis, and summarize clinical evidence regarding the safety of aspirin in subjects with G6PD deficiency.

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

BACKGROUND AND PURPOSE: Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency. METHODS: Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis. RESULTS: Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients (p = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% (p = 0.045), and the percentages of all-cause death were 6.2% and 1.4% (p = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%; p = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust p = 0.048) and all-cause death during aspirin use (adjust p = 0.008). CONCLUSIONS: Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.

Structural Brain Changes in Blepharospasm: A Cortical Thickness and Diffusion Tensor Imaging Study.

White matter abnormalities in blepharospasm (BSP) have been evaluated using conventional intra-voxel metrics, and changes in patterns of cortical thickness in BSP remain controversial. We aimed to determine whether local diffusion homogeneity, an inter-voxel diffusivity metric, could be valuable in detecting white matter abnormalities for BSP; whether these changes are related to disease features; and whether cortical thickness changes occur in BSP patients. Diffusion tensor and structural magnetic resonance imaging were collected for 29 patients with BSP and 30 healthy controls. Intergroup diffusion differences were compared using tract-based spatial statistics analysis and measures of cortical thickness were obtained. The relationship among cortical thickness, diffusion metric in significantly different regions, and behavioral measures were further assessed. There were no significant differences in cortical thickness and fractional anisotropy between the groups. Local diffusion homogeneity was higher in BSP patients than controls, primarily in the left superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, and left posterior thalamic radiata (P < 0.05, family-wise error corrected). The local diffusion homogeneity values in these regions were positively correlated with the Jankovic rating scale (r s = 0.416, P = 0.031) and BSP disability index (r s = 0.453, P = 0.018) in BSP patients. These results suggest that intra- and inter-voxel diffusive parameters are differentially sensitive to detecting BSP-related white matter abnormalities and that local diffusion homogeneity might be useful in assessing disability in BSP patients.

Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes.

OBJECTIVE: To assess the risk of glucose-6-phosphate dehydrogenase (G6PD) on stroke prognosis, we compared outcomes between patients with stroke with and without G6PD deficiency. METHODS: The study recruited 1,251 patients with acute ischemic stroke. Patients were individually categorized into G6PD-deficiency and non-G6PD-deficiency groups according to G6PD activity upon admission. The primary endpoint was poor outcome at 3 months defined by a modified Rankin Scale (mRS) score ≥2 (including disability and death). Secondary outcomes included the overall mRS score at 3 months and in-hospital death and all death within 3 months. Logistic regression and Cox models, adjusted for potential confounders, were fitted to estimate the association of G6PD deficiency with the outcomes. RESULTS: Among 1,251 patients, 150 (12.0%) were G6PD-deficient. Patients with G6PD deficiency had higher proportions of large-artery atherosclerosis (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09-2.17) and stroke history (OR 1.93, 95% CI 1.26-2.90) compared to the non-G6PD-deficient group. The 2 groups differed significantly in the overall mRS score distribution (adjusted common OR 1.57, 95% CI 1.14-2.17). Patients with G6PD deficiency had higher rates of poor outcome at 3 months (adjusted OR 1.73, 95% CI 1.08-2.76; adjusted absolute risk increase 13.0%, 95% CI 2.4%-23.6%). The hazard ratio of in-hospital death for patients with G6PD-deficiency was 1.46 (95% CI 1.37-1.84). CONCLUSIONS: G6PD deficiency is associated with the risk of poor outcome at 3 months after ischemic stroke and may increase the risk of in-hospital death. These findings suggest the rationality of G6PD screening in patients with stroke.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Association between angiotensinogen T174M polymorphism and ischemic stroke: A meta-analysis.

BACKGROUND: Numerous studies have evaluated the association between the angiotensinogen (AGT) T174M polymorphism and ischemic stroke(IS) risk. However, the specific association is still controversial. MATERIALS AND METHODS: In order to explore this association more deeply, we performed a meta-analysis. All of the relevant studies were identified from PubMed, Embase, and Chinese National Knowledge Infrastructure database up to October 2014. Statistical analyses were conducted with STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. RESULTS: Six studies with 1290 cases and 1125 controls were included. No significant variation in IS risk was detected in any of the genetic models in the overall (MM vs. TT: OR = 1.64, 95% CI = 0.51-5.28; MT vs. TT: OR = 0.93, 95% CI = 0.66-1.31; dominant model: OR = 1.08, 95% CI = 0.69-1.72; recessive model: OR = 0.61,95% CI = 0.20-1.91). Taking into account the effect of ethnicity, further stratified analyses were performed. The results showed that AGT gene T174M polymorphism might be associated with IS risk in Asians (MM vs. TT: OR = 3.28, 95% CI = 1.79-6.02; recessive model: OR = 0.31, 95% CI = 0.17-0.57). CONCLUSION: In conclusion, the AGT T174M polymorphism may be a susceptible predictor of the risk of IS in Asians. Further, large and well-designed studies are needed to confirm this conclusion.

The clinical characteristics and risk factors of cerebral venous sinus thrombosis complicated by cerebral hemorrhage / 中国神经精神疾病杂志

Objective To analyze the characteristics of clinical manifestations, risk factors, therapies and acute outcomes in patients with cerebral venous sinus thrombosis complicated by cerebral hemorrhage. Methods Seventy-five patients with cerebral venous sinus thrombosis were included in the study. According to the radiological findings on the brain image, patients were divided into two subgroups:cerebral hemorrhage group and non-hemorrhage group. The demo?graphic data, potential risk factors, clinical manifestations, radiological features, therapeutic strategies and acute out?comes were compared between two subgroups, and high risk factors were also analyzed. Results There were seventy-five patients with cerebral venous sinus thrombosis in the present study. Twenty-eight patients of them (37.2%) had cerebral hemorrhage whereas the remaining forty-seven patients (62.7%) did not have cerebral hemorrhage. Pregnancy/puerperi?um were significantly higher in patients with cerebral hemorrhage (with vs without;28.6%vs. 6.4%, P=0.015), while in?fection was markedly higher in patients without cerebral hemorrhage (with vs without;7.1% vs. 29.8%, P=0.021). Head?ache (92.9% vs. 70.2%, P=0.021), unconsciousness (25.0% vs. 6.4%,P=0.034), seizures (53.6% vs. 19.1%, P=0.002) and motor deficits (35.7% vs. 12.8%, P=0.019) were more common in patients with cerebral hemorrhage. Moreover, mul?tiple sinus involvement (1.4% vs. 44.7%, P=0.024) was significantly higher and the acute outcomes(mRS≥3: 46.4%vs.17.0%, P=0.006)were poorer in patients with cerebral hemorrhage. Binary Logistic analysis showed that pregnancy/pu?erperium (P=0.004) and multiple sinus involvement were positively, whereas infection was negatively correlated with cere?bral venous sinus thrombosis and hemorrhage ( P=0.007;P=0.03). Conclusions Pregnancy/puerperium, headache, uncon?sciousness, seizures, motor deficits and multiple sinus involvement are more frequently in patients with cerebral venous sinus thrombosis and hemorrhage, and the acute outcomes are poorer in patients with cerebral venous sinus thrombosis complicated by cerebral hemorrhage.

Secondary damage in left-sided frontal white matter detected by diffusion tensor imaging is correlated with executive dysfunction in patients with acute infarction at the ipsilateral posterior corona radiata.

BACKGROUND: Executive dysfunction has been observed in patients with left-sided anterior corona radiata infarction. However, whether left-sided posterior corona radiata infarction could cause executive dysfunction is unclear. Also, whether secondary damage in the left frontal white matter following ipsilateral posterior corona radiata infarct is causal or not and contributes to the occurrence and development of executive dysfunction, is still uncertain. METHODS: Twelve patients with posterior corona radiata infarction underwent diffusion tensor imaging (DTI) and an executive functional assessment at week 1 (W1), week 4 (W4), and week 12 (W12) after onset. Color duplex sonography and Transcranial Duplex Scanning (TCD) were performed at W1 and W12. Twelve healthy volunteers of similar ages and educational histories were examined as controls and assessed once. RESULTS: In the patients, we observed an increased mean diffusivity (MD) and a decreased fractional anisotropy (FA) in the left frontal white matter from W1 to W12. There were no significant changes in cerebral blood flow in patients between W1 and W12 according to the result of Color duplex sonography and TCD. Patients showed progressively impaired executive function during 12 weeks. Significant correlations were found between increased MD and decreased FA in the left frontal white matter with impaired degree of executive function. CONCLUSIONS: This study demonstrates that DTI detected secondary damage in left-sided frontal white matter in patients with acute infarction at the ipsilateral posterior corona radiata. This change may be correlated with executive functional changes in these patients.