Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms.

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

The Frequency and Associated Factors of Asymmetrical Prominent Veins: A Predictor of Unfavorable Outcomes in Patients with Acute Ischemic Stroke.

Objectives: The present study is aimed at investigating the frequency and associated factors of asymmetrical prominent veins (APV) in patients with acute ischemic stroke (AIS). Methods: Consecutive patients with AIS admitted to the Comprehensive Stroke Center of Shanghai Fourth People's Hospital between January 2013 and December 2017 were enrolled. MRI including diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and susceptibility-weighted imaging (SWI) was performed within 12 hours of symptom onset. The volume of asymmetrical prominent veins (APV) was evaluated using the Signal Processing In nuclear magnetic resonance software (SPIN, Detroit, Michigan, USA). Multivariate analysis was used to assess relationships between APV findings and medical history, clinical variables as well as cardio-metabolic indices. Results: Seventy-six patients met the inclusion criteria. The frequency of APV ≥ 10 mL was 46.05% (35/76). Multivariate analyses showed that proximal artery stenosis or occlusion (≥50%) (P < 0.001, adjusted odds ratio (OR) = 660.0, 95%CI = 57.28-7604.88) and history of atrial fibrillation (P < 0.001, adjusted OR = 10.48, 95%CI = 1.78-61.68) were independent factors associated with high APV (≥10 mL). Conclusion: Our findings suggest that the frequency of APV ≥ 10 mL is high in patients with AIS within 12 hours of symptom onset. History of atrial fibrillation and severe proximal artery stenosis or occlusion are strong predictors of high APV as calculated by SPIN on the SWI map.

Power of Hypoperfusion in Predicting Recurrent Transient Ischemic Attacks: Protocol of a Prospective Cohort Study.

Background: Transient ischemic attack (TIA) has a high incidence of recurrent vascular events. Hypoperfusion is one of the factors that are closely correlated with 7-day recurrence of TIA. This study aimed to evaluate the power of hypoperfusion shown on magnetic resonance (MR) perfusion imaging in predicting the incidence of 7-day recurrence of ischemic events after TIA. Methods/Design: REATTACK is a prospective multi-centered cohort study on the correlation between MR perfusion and TIA recurrence. Ninety patients aged ≥18 years with recent (<7 days after onset) clinical TIA will be continuously included. All the patients will undergo diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) assessments within 24 h after the onset of TIA. The subjects will then be divided into a PWI positive group and a PWI negative group according to the time-to-maximum of the residue function (T max ). PWI will be repeated after 7 days and in 3 months. The primary clinical outcome will be the recurrence of TIA within 7 days after the onset of TIA. Secondary outcomes will be the recurrence of TIA in 3 months and modified Rankin scale (mRS) score. A chi-square test will be performed to compare the difference in the incidence of recurrent TIA between the two groups, and rank sum test in the mRS score. Multivariate logistic regression will be simultaneously performed to analyze the risk factors for the recurrence of TIA. Discussion: The results of this study will confirm whether abnormal T max helps to identify the patients with TIA who have high risks of recurrent ischemic events. This would largely improve the prognosis of patients with TIA. Trial Registration: www.chictr.org.cn, registration number: ChiCTR2000031863, registered on 12 April 2020.

Risk Factors of Hypoperfusion on MRI of Ischemic Stroke Patients Within 7 Days of Onset.

Objective: Hypoperfusion is an important factor determining the prognosis of ischemic stroke patients. The present study aimed to investigate possible predictors of hypoperfusion on MRI of ischemic stroke patients within 7 days of stroke onset. Methods: Ischemic stroke patients, admitted to the comprehensive Stroke Center of Shanghai Fourth People's Hospital affiliated to Tongji University within 7 days of onset between January 2016 and June 2017, were recruited to the present study. Magnetic resonance imaging (MRI), including both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), was performed within 7 days of the symptom onset. Time to maximum of the residue function (T max ) maps were automatically evaluated using the RAPID software. The volume of hypoperfusion was measured outside the infarct area based on ADC < 620 × 10-6 mm2/s. The 90 d mRS score was assessed through either clinic visits or telephone calls. Multivariate step-wise analysis was used to assess the correlation between MR findings and clinical variables, including the demographic information, cardio-metabolic characteristics, and functional outcomes. Results: Among 635 patients admitted due to acute ischemic stroke within 7 days of onset, 241 met the inclusion criteria. Hypoperfusion volume of 38 ml was the best cut-off value for predicting poor prognosis of patients with cerebral infarction (90 d-mRS score ≥ 2). The incidences of MR perfusion T max > 4-6 s maps with a volume of 0-38 mL or >38 mL were 51.9% (125/241) and 48.1% (116/241), respectively. Prior stroke and vascular stenosis (≥70%) were associated with MR hypoperfusion. Multivariate step-wise analysis showed that prior stroke and vascular stenosis (≥70%) were risk factors of T max > 4-6 s maps, and the odds ratios (OR) were 3.418 (adjusted OR 95% CI: 1.537-7.600), and 2.265 (adjusted OR, 95% CI: 1.199-4.278), respectively. Conclusion: Our results suggest that prior stroke and vascular stenosis (≥70%) are strong predictors of hypoperfusion in patients with acute ischemic stroke within 7 days of stroke onset.

Quantitative susceptibility-weighted imaging may be an accurate method for determining stroke hypoperfusion and hypoxia of penumbra.

OBJECTIVES: To quantitatively evaluate the volume of the ischemic penumbra using susceptibility-weighted imaging and mapping (SWIM) of asymmetrical prominent cortical veins (APCVs) in patients with acute ischemic stroke. METHODS: Eighty-five eligible patients with acute ischemic stroke on admission within 12 h from symptom onset were studied. The APCVs on SWIM were quantitatively (SWI-volume) and semi-quantitatively (SWI-Alberta Stroke Program Early CT Score, SWI-ASPECTS) evaluated to calculate mismatch. To assess the diagnostic efficacy of APCVs on SWIM, comparative analyses were performed between SWIvolume-DWI mismatch and SWIASPECTS-DWI mismatch, using PWI-DWI mismatch as a reference. Correlations were calculated between the mismatches, as well as between SWI-volume and time-to-maximum (Tmax) > 6 s volume. Additionally, each of these mismatches was correlated with the National Institute of Health Stroke Scale (NIHSS). RESULTS: The sensitivity, negative predictive value, and accuracy of SWIvolume-DWI mismatch were demonstrably higher than SWIASPECTS-DWI mismatch (100% vs. 53.7%, 100% vs. 9.5%, 97.7% vs. 54.5%, respectively). A significant positive correlation was found between SWIvolume-DWI and PWI-DWI mismatch (r = 0.691, p < 0.01), as well as between SWI-volume and Tmax > 6 s volume (r = 0.786, p < 0.001). A significant negative correlation was found between SWIvolume-DWI mismatch and NIHSS (r = - 0.360, p = 0.022), as well as between SWIASPECTS-DWI mismatch and NIHSS (r = - 0.499, p = 0.001). CONCLUSIONS: SWIvolume-DWI mismatch had higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra and showed good consistency with PWI-DWI mismatch in acute ischemic stroke. Quantitation of APCVs using SWIM provided an accurate method for determining hypoperfusion and provided a reliable method to reflect the hypoxia of penumbra. KEY POINTS: • SWIvolume-DWI mismatch has higher diagnostic efficacy than SWIASPECTS-DWI mismatch in defining the ischemic penumbra. • SWIvolume-DWI mismatch shows good consistency with PWI-DWI mismatch in managing penumbra in acute ischemic stroke. • Quantitation of APCV volume using SWIM provided an accurate method for determining the hypoperfusion area and provided a reliable method to reflect the hypoxia of penumbra.

Human Adipose Tissue-Derived Mesenchymal Stem Cells in Parkinson's Disease: Inhibition of T Helper 17 Cell Differentiation and Regulation of Immune Balance Towards a Regulatory T Cell Phenotype.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder displaying a typical neuroinflammation pathology that may result from an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Human adipose tissue-derived mesenchymal stem cells (Ad-MSCs) exert immunomodulatory effects by inhibiting effector T cell responses and have been used to treat diverse immune disorders. We aimed to investigate the modulating effect of human Ad-MSCs on peripheral blood mononuclear cells (PBMCs) of patients with PD, focusing on differentiation into Th17 and Treg cells. METHODS: We isolated human peripheral blood CD4+T cells and co-cultured them with Ad-MSCs at a ratio of 4:1 under either Th17 or Treg cell polarizing conditions for 4 days to detect the proportions of IL-17-producing CD4+T (Th17) and CD4+CD25+Foxp3+regulatory T (Treg) cells by flow cytometry. We also determined the mRNA expression levels of the retinoid-related orphan nuclear receptor (RORγt) transcription factor and those of interleukin-6 receptor (IL-6R), interleukin-23 receptor (IL-23R), leukemia inhibitory factor (LIF), and LIF receptor (LIFR) by quantitative reverse transcription PCR. We detected levels of cytokines in the supernatant (including LIF, IL-6, IL-23, IL-10, and TGF-ß) using ELISA. RESULTS: Our results showed that Ad-MSCs specifically inhibited the differentiation of PBMCs of patients with PD into IL-17-producing CD4+T cells by decreasing expressions of IL-6R, IL-23R, and RORγt (the key transcription factor for Th17 cells). Moreover, Ad-MSCs induced a functional CD4+CD25+Foxp3+T regulatory cell phenotype as evidenced by the secretion of IL-10. The levels of IL-6, IL-23, and TGF-ß remained constant after co-culture under either the Th17 or the Treg cell polarizing condition. In addition, levels of LIF protein and its receptor mRNA were significantly increased under both polarizing conditions. CONCLUSION: The present in vitro study found that Ad-MSCs from healthy participants were able to correct the imbalance between Th17 and Treg found in PBMCs of PD patients, which were correlated with an increase in LIF secretion and a decrease in expression of IL-6R, IL-23R, and RORγt. These findings should be confirmed by in vivo experiments.

History of Hypertension Is Associated With MR Hypoperfusion in Chinese Inpatients With DWI-Negative TIA.

Objectives: The present study aimed to examine the prevalence of and risk factors for magnetic resonance (MR) perfusion abnormality in a Chinese population with transient ischemic attack (TIA) and normal diffusion-weighted imaging (DWI) findings. Methods: Patients with TIA admitted to our stroke center between January 2015 and October 2017 were recruited to the present study. MRI, including both DWI and perfusion-weighted imaging (PWI), was performed within 7 days of symptom onset. Time to maximum of the residue function (Tmax) maps were evaluated using the RAPID software (Ischemaview USA, Version 4.9) to determine hypoperfusion. Multivariate analysis was used to assess perfusion findings, clinical variables, medical history, cardio-metabolic, and the ABCD2 scores (age, blood pressure, clinical features, symptom duration, and diabetes). Results: Fifty-nine patients met the inclusion criteria. The prevalence of MR perfusion Tmax ≥ 4 s ≥ 0 ml and ≥ 10 mL were 72.9% (43/59) and 42.4% (25/59), respectively. Multivariate analyses revealed that history of hypertension is an independent factor associated with MR perfusion abnormality (Tmax ≥ 4 s ≥ 10 mL) for Chinese patients with TIA (P = 0.033, adjusted OR = 4.11, 95% CI = 1.12-15.11). Proximal artery stenosis (>50%) tended to lead to a larger PW lesion on MRI (p = 0.067, adjusted OR = 3.60, 95% CI = 0.91-14.20). Conclusion: Our results suggest that the prevalence of perfusion abnormality is high as assessed by RAPID using the parametric Tmax ≥ 4 s. History of hypertension is a strong predictor of focal perfusion abnormality as calculated by RAPID on Tmax map of TIA patients with negative DWI findings.

Risk factors of perfusion and diffusion abnormalities on MRI in hemispheric TIA: a case-control study.

BACKGROUND: To assess the prevalence and potential predictors of MR diffusion and perfusion abnormalities in a Chinese population with hemispheric transient ischemic attacks (TIA). METHODS: Patients with temporary (<24 hours) focal cerebral dysfunction of probable vascular origin were considered to be potential candidates for this study in the emergency room. Those who were admitted to the stroke center of Shanghai Fourth People's Hospital affiliated to Tongji University between January 2015 and December 2018 were recruited to the present study. MRI, including both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI), was performed within 7 days after the last symptom attack. Time to maximum of the residue function (Tmax) maps were auto-evaluated using the RAPID software to determine hypoperfusion. Multivariate analysis was used to assess the correlation of MR findings with clinical variables, medical history, cardio-metabolic characteristics, and the ABCD2 scores (age, blood pressure, clinical features, symptom duration and diabetes). RESULTS: Sixty-six out of 207 patients met the inclusion criteria. Baseline MRI showed DWI lesions in 20 patients (30.3%). The prevalence of MR perfusion Tmax >4 s >0 mL and ≥10 mL were 77.3% (51/66) and 50% (33/66), respectively. Male patients tended to develop DWI lesions after a TIA. Limb weakness was an independent factor associated with MR perfusion abnormalities (Tmax >4 s ≥10 mL) in this Chinese population (adjusted OR =7.41, 95% CI: 1.57-34.89, P=0.011). CONCLUSIONS: Our results suggest that limb weakness is a strong predictor of perfusion abnormalities calculated by RAPID on Tmax maps of hemispheric TIA patients without DWI positive findings. Male patients are more likely to develop cerebral infarction.

3D imaging of PSD-95 in the mouse brain using the advanced CUBIC method.

AIMS: Postsynaptic density - 95 kDa protein (PSD95) is an important molecule on the postsynaptic membrane. It interacts with many other proteins and plays a pivotal role in learning and memory formation. Its distribution in the brain has been studied previously using in situ hybridization as well as immunohistochemistry. However, these studies are based on 2 dimensional (2D) sections and results are presented with a few sections. The present study aims to show PSD-95 distribution in 3 dimensions (3D) without slicing the brain tissue of C57BL/6 mice into sections using the advanced CUBIC technique. METHODS: Immunofluorescent staining using a PSD-95 antibody was performed on a half of the mouse brain after clarifying it using the advanced CUBIC protocol. The brain tissue was imaged using a Zeiss Z1 light sheet microscope and 3D reconstruction was completed using the Arivis Vision 4 dimensional (4D) software. RESULTS: The majority of brain nuclei have similar distribution pattern to what has been reported from in situ hybridization and immunohistochemical studies in the mouse. The signal can be easily followed in the 3D and their spatial relationship with adjacent structures clearly demarcated. In the present study, some fiber bundles also showed strong PSD-95 signal, which is different from what was shown in previous studies and need to be confirmed in future studies.

Orthostatic Hypotension Predicts Cognitive Impairment in the Elderly: Findings from a Cohort Study.

BACKGROUND: Orthostatic hypotension (OH) is a known risk factor for cerebral ischemia, but its correlation with cognitive impairment (CI) is not well established. OBJECTIVE: The aim of this study is to explore the relationship between OH and CI in the elderly. METHODS: The study group consisted of 44 OH patients who presented with drowsiness, vertigo, and fatigue between January 2009 and December 2011 (OH group). Eighty-eight healthy elderly were paired with those in the OH group in a 1:2 based on their education levels (NOH group). Baseline sociodemographic information and cognition-related measures were collected for both groups. Cognitive function was assessed 4 years later using MMSE. RESULTS: The overall incidence of CI was 14.0% among the 114 subjects who completed the follow-up assessment. There was a significant difference in the incidence of CI between the OH group (23.7%) and the NOH group (9.2%) (χ2 = 4.399, P = 0.036). After excluding the influence of age (OR = 1.199, 95% CI: 1.072-1.340, P = 0.001) and education years (OR = 0.568, 95% CI: 0.371-0.869, P = 0.009), OH (OR = 4.047, 95% CI: 1.144-14.313, P = 0.030) became an independent risk factor for CI. CONCLUSION: OH can lead to CI. We suggest that future studies, with a larger sample size, use OH exposure time instead of OH exposure population to verify the conclusion of this study.

The Prognostic Value of a Four-Dimensional CT Angiography-Based Collateral Grading Scale for Reperfusion Therapy in Acute Ischemic Stroke Patients.

OBJECTIVE: Leptomeningeal collaterals, which affects tissue fate, are still challenging to assess. Four-dimensional CT angiography (4D CTA) originated from CT perfusion (CTP) provides the possibility of non-invasive and time-resolved assessment of leptomeningeal collateral flow. We sought to develop a comprehensive rating system to integrate the speed and extent of collateral flow on 4D CTA, and investigate its prognostic value for reperfusion therapy in acute ischemic stroke (AIS) patients. METHODS: We retrospectively studied 80 patients with M1 ± internal carotid artery (ICA) occlusion who had baseline CTP before intravenous thrombolysis. The velocity and extent of collaterals were evaluated by regional leptomeningeal collateral score on peak phase (rLMC-P) and temporally fused intensity projections (tMIP) (rLMC-M) on 4D CTA, respectively. The cutoffs of rLMC-P and rLMC-M score for predicting good outcome (mRS score ≤ 2) were integrated to develop the collateral grading scale (CGS) (rating from 0-2). RESULTS: The CGS score was correlated with 3-months mRS score (non-recanalizers: ρ = -0.495, p = 0.01; recanalizers: ρ = -0.671, p < 0.001). Patients with intermediate or good collaterals (CGS score of 1 and 2) who recanalized were more likely to have good outcome than those without recanalization (p = 0.038, p = 0.018), while there was no significant difference in outcome in patients with poor collaterals (CGS score of 0) stratified by recanalization (p = 0.227). CONCLUSIONS: Identification of collaterals based on CGS may help to select good responders to reperfusion therapy in patients with large artery occlusion.

The velocity of collateral filling predicts recanalization in acute ischemic stroke after intravenous thrombolysis.

The aim of this study was to evaluate the impact of pretreatment quality of collaterals, involving velocity and extent of collateral filling, on recanalization after intravenous thrombolysis (IVT). A retrospective analysis was performed of 66 patients with acute middle cerebral artery (MCA) M1 segment occlusion who underwent MR perfusion (MRP) imaging before IVT. The velocity of collateral filling was defined as arrival time delay (ATD) of contrast bolus to Sylvian fissure between the normal and the affected hemisphere. The extent of collateral filling was assessed according to the Alberta Stroke Program Early CT (ASPECT) score on temporally fused maximum intensity projections (tMIP). Arterial occlusive lesion (AOL) score was used to assess the degree of arterial recanalization. ATD (OR = 0.775, 95% CI = 0.626-0.960, p = 0.020), but not tMIP-ASPECT score (OR = 1.073, 95% CI = 0.820-1.405, p = 0.607), was independently associated with recanalization (AOL score of 2 and 3) at 24 hours after IVT. When recanalization was achieved, hemorrhagic transformation (HT) occurred more frequently in patients with slow collaterals (ATD ≥ 2.3 seconds) than those with rapid collaterals (ATD < 2.3 seconds) (88.9% vs 38.1%, p = 0.011). In conclusion, the velocity of collaterals related to recanalization, which may guide the decision-making of revascularization therapy in acute ischemic stroke.

Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion.

Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden's Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time ≥ 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF ≤ 30% within delay time ≥ 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time ≥ 3 s and rCBF ≤ 30% within delay time ≥ 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy.

The expression of SEIPIN in the mouse central nervous system.

Immunohistochemical staining was used to investigate the expression pattern of SEIPIN in the mouse central nervous system. SEIPIN was found to be present in a large number of areas, including the motor and somatosensory cortex, the thalamic nuclei, the hypothalamic nuclei, the mesencephalic nuclei, some cranial motor nuclei, the reticular formation of the brainstem, and the vestibular complex. Double labeling with NeuN antibody confirmed that SEIPIN-positive cells in some nuclei were neurons. Retrograde tracer injections into the spinal cord revealed that SEIPIN-positive neurons in the motor and somatosensory cortex and other movement related nuclei project to the mouse spinal cord. The present study found more nuclei positive for SEIPIN than shown using in situ hybridization and confirmed the presence of SEIPIN in neurons projecting to the spinal cord. The results of this study help to explain the clinical manifestations of patients with Berardinelli-Seip congenital lipodystrophy (Bscl2) gene mutations.

Emerging malnutrition during hospitalisation independently predicts poor 3-month outcomes after acute stroke: data from a Chinese cohort.

OBJECTIVE: Questions exist regarding the causal relationship between malnutrition and stroke outcomes. This study aimed to determine whether nutritional status changes or malnutrition during hospitalisation could predict 3-month outcomes in acute stroke patients. METHODS: During a 10-month period, patients who suffered their first stroke within 7 days after stroke onset were included in this prospective multi-centre study. The demographic parameters, stroke risk and severity factors, malnutrition risk factors and dysphagia were recorded. Nutritional status was assessed by 3 anthropometric and 3 biochemical indices. Changes in nutritional status were defined by comparing the admission values with the 2-week values. A Modified Rankin Scale score of 3-6 was defined as a poor outcome at the 3-month follow-up. Univariate and multiple logistic regression analyses were used to investigate the power of nutritional status changes in predicting poor patient outcomes. RESULTS: Data from 760 patients were analysed. Poor outcomes were observed in 264 (34.7%) patients. Malnutrition prevalence was 3.8% at admission and 7.5% after 2-weeks in hospital, which could not predict 3-month outcome. Emerging malnutrition was observed in 36 patients (4.7%) during the 2-week hospitalisation period and independently predicted poor 3-month outcomes after adjusting for confounding factors (odds ratio 1.37, 95% confidence interval 1.03-1.83). CONCLUSIONS: Emerging malnutrition during hospitalisation independently predicted poor 3-month outcomes in acute stroke patients in this study.

Distribution of raphespinal fibers in the mouse spinal cord.

BACKGROUND: Serotonergic raphespinal neurons and their fibers have been mapped in large mammals, but the non-serotonergic ones have not been studied, especially in the mouse. The present study aimed to investigate the termination pattern of fibers arising from the hindbrain raphe and reticular nuclei which also have serotonergic neurons by injecting the anterograde tracer BDA into them. RESULTS: We found that raphespinal fibers terminate in both the dorsal and ventral horns in addition to lamina 10. There is a shift of the fibers in the ventral horn towards the dorsal and lateral part of the gray matter. Considerable variation in the termination pattern also exists between raphe nuclei with raphe magnus having more fibers terminating in the dorsal horn. Fibers from the adjacent gigantocellular reticular nucleus show similar termination pattern as those from the raphe nuclei with slight difference. Immunofluorescence staining showed that raphespinal fibers were heterogeneous and serotoninergic fibers were present in all laminae but mainly in laminae 1, 2, medial lamina 8, laminae 9 and 10. Surprisingly, immunofluorescence staining on clarified spinal cord tissue revealed that serotoninergic fibers formed bundles regularly in a short distance along the rostrocaudal axis in the medial part of the ventral horn and they extended towards the lateral motor neuron column area. CONCLUSION: Serotonergic and non-serotonergic fibers arising from the hindbrain raphe and reticular nuclei had similar termination pattern in the mouse spinal cord with subtle difference. The present study provides anatomical foundation for the multiple roles raphe and adjacent reticular nuclei play.

Impact of early enteral nutrition on short term prognosis after acute stroke.

We hypothesized that early enteral nutritional support would improve the short term prognosis of acute stroke patients with dysphagia, demonstrated by lower malnutrition rates, lower complication rates, and lower National Institutes of Health Stroke Scale (NIHSS) scores at 90 days post stroke. Nutrition support is an essential element in the care of stroke patients and many studies have investigated the effect of specific nutritional elements on stroke patients. However, few studies have looked at the impact of complete enteral nutrition on Chinese patients with acute stroke. To investigate this, we conducted a randomized controlled trial of 146 patients with acute stroke and dysphagia, among whom 75 were supported with nasogastric nutrition and 71 received family managed nutrition after randomization. Nutritional status, nosocomial infection and mortality rates were recorded on day 21 of hospitalization. Neurological deficits were evaluated by the NIHSS activities of daily living Barthel index (ADLBI) and the modified Rankin scale (mRS) and compared between the two groups. We found that the nasogastric nutrition group had a better nutritional status and reduced nosocomial infection and mortality rates after 21 days compared with patients in the family managed nutrition group. In addition, the nasogastric nutrition group showed a lower score on the NIHSS than the control group. However, the differences in the scores of the ADLBI and the 90 day mRS between the groups were not significant. Taken together, the present study shows that early enteral nutrition support improves the short term prognosis of acute stroke patients with dysphagia.

Vascular imaging adds value in investigation of basal ganglia hemorrhage.

The risk of basal ganglia hemorrhage (BGH) increases in patients of older age and with hypertension. Current guidelines do not recommend routine vascular imaging. However, a proportion of patients with BGH have underlying vascular abnormalities, and these patients may require a different treatment approach. We aimed to assess the proportion of underlying vascular abnormalities in patients with BGH. In this retrospective study, we included all patients who presented with BGH between January 2007 and December 2009 at a single institution. The following data were collected: patient demographics, vascular risk factors, medications, volume of hematoma, CT scans, CT angiogram, magnetic resonance angiography and digital subtraction angiography. We determined the proportion of underlying vascular abnormalities and correlated these findings with risk factors for BGH. A total of 113 consecutive patients with BGH were identified, and vascular imaging was performed in 61. The median age was 62 years and 48 (78.7%) of these patients were male. Forty-two (68.9%) of 61 patients had hypertension. Positive vascular imaging findings were identified in eight of 61 patients (13.1%): three intracranial aneurysms, three cavernous malformations, one Moyamoya disease and one arteriovenous malformation. There were no significant associations between demographic features, vascular risk factors and the hematoma volume between patients with positive and negative vascular imaging. Specifically, an underlying vascular abnormality was not associated with age (≥ 60 years, 6/36 patients had an underlying vascular abnormality, compared with 2/25 patients< 60 years; p=not significant [n.s.]). There was no relationship with hypertension (5/42 hypertensive patients and 3/19 normotensive patients (n.s.) had an underlying vascular abnormality). We concluded that there is a significant proportion of relevant underlying vascular abnormalities in patients with BGH. This likelihood is not predicted by risk factors such as hypertension and age. These findings indicate the importance of vascular imaging in patients with BGH who are not neurologically devastated.