Prediction of motor outcome using remaining corticospinal tract in patients with pontine infarct: Diffusion tensor imaging study

The aim of this study was to investigate the relationship between the remaining corticospinal tract (CST) as determined by diffusion tensor imaging (DTI) and 6-month motor outcome in patients with pontine infarct. Ratios of fractional anisotropy (FA), fiber number (FN), and CST area were calculated, and the FN ratio and CST area ratio showed significant correlation with all 6-month motor outcome. Thus, the remaining CST in the pons measured using DTI at early stage of stroke could predict motor outcome in patients with pontine infarct.     

Diffusion Tensor Imaging of the Auditory Neural Pathway for Clinical Outcome of Cochlear Implantation in Pediatric Congenital Sensorineural Hearing Loss Patients

Although conventional structural MRI provides vital information in the evaluation of congenital sensorineural hearing loss (SNHL), it is relatively insensitive to white matter microstructure. Our objective was to evaluate possible changes in microstructure of the auditory pathway in children with congenital sensorineural hearing loss (SNHL), and the possible distinction between good and poor outcome of cochlear implantation (CI) patients by using diffusion tensor imaging (DTI). Twenty-four patients with congenital SNHL and 20 healthy controls underwent conventional MRI and DTI examination using a 1.5T MR scanner. The DTI metrics of fractional anisotropy (FA) and mean diffusivity (MD) of six regions of interest (ROIs) positioned along the auditory pathway—the trapezoid body, superior olivary nucleus, inferior colliculus, medial geniculate body, auditory radiation and white matter of Heschl''s gyrus—was measured in all subjects. Among the 24 patients, 8 patients with a categorie of auditory performance (CAP) score over 6 were classified into the good outcome group, and 16 patients with a CAP score below 6 were classified into the poor outcome group. A significant decrease was observed in FA values while MD values remained unchanged at the six ROIs of SNHL patients compared with healthy controls. Compared to good outcome subjects, poor outcome subjects displayed decreased FA values at all of the ROIs. No changes were observed in MD values. Correlation analyses only revealed strong correlations between FA values and CAP scores, and strong correlations between CAP scores and age at implant were also found. No correlations of FA values with age at implant were observed. Our results show that preoperative DTI can be used to evaluate microstructural alterations in the auditory pathway that are not detectable by conventional MR imaging, and may play an important role in evaluating the outcome of CI. Early cochlear implantation might be more effectively to restore hearing in SNHL patients.     

Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity

Purpose

To investigate the potential of diffusion tensor imaging (DTI) parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology.

Methods

MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA) as well as axial, radial and mean diffusivity (AD, RD, and MD) was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) as markers of axon integrity, and distal motor latency (dml) and sensory nerve conduction velocity (sNCV) as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons.

Results

DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr.) but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr.) but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr.) and sNCV (r=0.68, p=0.001, Bonf. corr.) but not with markers of axon integrity.

Conclusion

AD reflects axon integrity, while RD (and FA) reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies.     

White Matter Changes in Patients with Amnestic Mild Cognitive Impairment Detected by Diffusion Tensor Imaging

Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer’s disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.     

Admission C – reactive protein after acute ischemic stroke is associated with stroke severity and mortality: The 'Bergen stroke study'

Background

There is growing evidence that inflammation plays an important role in atherogenesis. Previous studies show that C-reactive protein (CRP), an inflammatory marker, is associated with stroke outcomes and future vascular events. It is not clear whether this is due a direct dose-response effect or rather an epiphenomenon. We studied the effect of CRP measured within 24 hours after stroke onset on functional outcome, mortality and future vascular events.

Methods

We prospectively studied 498 patients with ischemic stroke who were admitted within 24 hours after the onset of symptoms. CRP and NIH stroke scale (NIHSS) were measured at the time of admission. Short-term functional outcome was measured by modified Rankin scale (mRS) and Barthel ADL index (BI) 7 days after admission. Patients were followed for up to 2.5 years for long-term mortality and future vascular events data.

Results

The median CRP at admission was 3 mg/L. High CRP was associated with high NIHSS (p = 0.01) and high long-term mortality (p < 0.0001). After adjusting for confounding variables, high CRP remained to be associated with high NIHSS (p = 0.02) and high long-term mortality (p = 0.002). High CRP was associated with poor short-term functional outcomes (mRS > 3; BI < 95) (p = 0.01; p = 0.03). However, the association was not significant after adjusting for confounding variables including stroke severity (p = 0.98; p = 0.88). High CRP was not associated with future vascular events (p = 0.98).

Conclusion

Admission CRP is associated with stroke severity and long-term mortality when measured at least 24 hours after onset. There is a crude association between high CRP and short-term functional outcome which is likely secondary to stroke severity. CRP is an independent predictor of long-term mortality after ischemic stroke.     

Identification of Neonatal White Matter on DTI: Influence of More Inclusive Thresholds for Atlas Segmentation

Purpose

Semi-automated diffusion tensor imaging (DTI) analysis of white matter (WM) microstructure offers a clinically feasible technique to assess neonatal brain development and provide early prognosis, but is limited by variable methods and insufficient evidence regarding optimal parameters. The purpose of this research was to investigate the influence of threshold values on semi-automated, atlas-based brain segmentation in very-low-birth-weight (VLBW) preterm infants at near-term age.

Materials and Methods

DTI scans were analyzed from 45 VLBW preterm neonates at near-term-age with no brain abnormalities evident on MRI. Brain regions were selected with a neonatal brain atlas and threshold values: trace <0.006 mm²/s, fractional anisotropy (FA)>0.15, FA>0.20, and FA>0.25. Relative regional volumes, FA, axial diffusivity (AD), and radial diffusivity (RD) were compared for twelve WM regions.

Results

Near-term brain regions demonstrated differential effects from segmentation with the three FA thresholds. Regional DTI values and volumes selected in the PLIC, CereP, and RLC varied the least with the application of different FA thresholds. Overall, application of higher FA thresholds significantly reduced brain region volume selected, increased variability, and resulted in higher FA and lower RD values. The lower threshold FA>0.15 selected 78±21% of original volumes segmented by the atlas, compared to 38±12% using threshold FA>0.25.

Conclusion

Results indicate substantial and differential effects of atlas-based DTI threshold parameters on regional volume and diffusion scalars. A lower, more inclusive FA threshold than typically applied for adults is suggested for consistent analysis of WM regions in neonates.     

Microstructure abnormalities in adolescents with internet addiction disorder

Background

Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction.

Methodology/Principal Findings

We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD.

Conclusions

Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.     

Population-Based Stroke Atlas for Outcome Prediction: Method and Preliminary Results for Ischemic Stroke from CT

Background and Purpose

Knowledge of outcome prediction is important in stroke management. We propose a lesion size and location-driven method for stroke outcome prediction using a Population-based Stroke Atlas (PSA) linking neurological parameters with neuroimaging in population. The PSA aggregates data from previously treated patients and applies them to currently treated patients. The PSA parameter distribution in the infarct region of a treated patient enables prediction. We introduce a method for PSA calculation, quantify its performance, and use it to illustrate ischemic stroke outcome prediction of modified Rankin Scale (mRS) and Barthel Index (BI).

Methods

The preliminary PSA was constructed from 128 ischemic stroke cases calculated for 8 variants (various data aggregation schemes) and 3 case selection variables (infarct volume, NIHSS at admission, and NIHSS at day 7), each in 4 ranges. Outcome prediction for 9 parameters (mRS at 7th, and mRS and BI at 30th, 90th, 180th, 360th day) was studied using a leave-one-out approach, requiring 589,824 PSA maps to be analyzed.

Results

Outcomes predicted for different PSA variants are statistically equivalent, so the simplest and most efficient variant aiming at parameter averaging is employed. This variant allows the PSA to be pre-calculated before prediction. The PSA constrained by infarct volume and NIHSS reduces the average prediction error (absolute difference between the predicted and actual values) by a fraction of 0.796; the use of 3 patient-specific variables further lowers it by 0.538. The PSA-based prediction error for mild and severe outcomes (mRS = [2]–[5]) is (0.5–0.7). Prediction takes about 8 seconds.

Conclusions

PSA-based prediction of individual and group mRS and BI scores over time is feasible, fast and simple, but its clinical usefulness requires further studies. The case selection operation improves PSA predictability. A multiplicity of PSAs can be computed independently for different datasets at various centers and easily merged, which enables building powerful PSAs over the community.     

Plasma Midregional Pro-Adrenomedullin Improves Prediction of Functional Outcome in Ischemic Stroke

Background

To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke.

Methods

In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied.

Results

Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3–6) compared to favourable (mRS 0–2) outcomes. MR-proADM levels were entered into a predictive model including the patients'' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI = 0.175; p = 0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles.

Conclusions

Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients'' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients'' functional outcome.     

Linear Associations between Clinically Assessed Upper Motor Neuron Disease and Diffusion Tensor Imaging Metrics in Amyotrophic Lateral Sclerosis

Objective

To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI).

Methods

This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates.

Results

For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003).

Conclusions

Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination.     

Asymmetry of Deep Medullary Veins on Susceptibility Weighted MRI in Patients with Acute MCA Stroke Is Associated with Poor Outcome

Background and Purpose

Due to its sensitivity to deoxyhemoglobin, susceptibility weighted imaging (SWI) enables the visualization of deep medullary veins (DMV) in patients with acute stroke, which are difficult to depict under physiological circumstances. This study assesses the asymmetric appearance of prominent DMV as an independent predictor for stroke severity and outcome.

Materials and Methods

SWI of 86 patients with acute middle cerebral artery (MCA) stroke were included. A scoring system from 0 (no visible DMV) to 3 (very prominent DMV) was applied for both hemispheres separately. A difference of scores between ipsi- and contralateral side was defined as asymmetric (AMV+). Occurrence of AMV+ was correlated with the National Institute of Health Stroke Scale (NIHSS) Score on admission and discharge, as well as the modified Rankin Scale (mRS) at discharge. Ordinal regression analysis was used to evaluate NIHSS and mRS as predictors of stroke severity, clinical course of disease and outcome.

Results

55 patients displayed AMV+ while 31 did not show an asymmetry (AMV–). Median NIHSS on admission was 17 (11–21) in the AMV+ group and 9 (5–15) in the AMV– group (p = 0.001). On discharge median NIHSS was 11 (5–20) for AMV+ and 5 (2–14) for AMV– (p = 0.005). The median mRS at discharge was 4 (3–5) in the AMV+ group and 3 (1–4) in AMV– (p = 0.001). Odds ratio was 3.19 (95% CI: 1.24–8.21) for AMV+ to achieve a higher mRS than AMV– (p = 0.016).

Conclusion

The asymmetric appearance of DMV on SWI is a fast and easily evaluable parameter for the prediction of stroke severity and can be used as an additional imaging parameter in patients with acute MCA stroke.     

Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke

Background

Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever.

Methods

We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3–6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months.

Results

Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41–36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months.

Conclusion

Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.     

Combining Diffusion Tensor Imaging and Gray Matter Volumetry to Investigate Motor Functioning in Chronic Stroke

Motor impairment after stroke is related to the integrity of the corticospinal tract (CST). However, considerable variability in motor impairment remains unexplained. To increase the accuracy in evaluating long-term motor function after ischemic stroke, we tested the hypothesis that combining diffusion tensor imaging (DTI) and gray matter (GM) volumetry can better characterize long-term motor deficit than either method alone in patients with chronic stroke. We recruited 31 patients whose Medical Research Council strength grade was ≤ 3/5 in the extensor muscles of the affected upper extremity in the acute phase. We used the Upper Extremity Fugl-Meyer (UE-FM) assessment to evaluate motor impairment, and as the primary outcome variable. We computed the fractional anisotropy ratio of the entire CST (CST_ratio) and the volume of interest ratio (VOI_ratio), between ipsilesional and contralesional hemispheres, to explain long-term motor impairment. The results showed that CST_ratio, VOI_ratio of motor-related brain regions, and VOI_ratio in the temporal lobe were correlated with UE-FM. A multiple regression model including CST_ratio and VOI_ratio of the caudate nucleus explained 40.7% of the variability in UE-FM. The adjusted R2 of the regression model with CST_ratio as an independent variable was 29.4%, and that of using VOI_ratio of the caudate nucleus as an independent variable was 23.1%. These results suggest that combining DTI and GM volumetry may achieve better explanation of long-term motor deficit in stroke patients, than using either measure individually. This finding may provide guidance in determining optimal neurorehabilitative interventions.     

Voxel-Based Analysis of Fractional Anisotropy in Post-Stroke Apathy

Objective

To explore the structural basis of post-stroke apathy by using voxel-based analysis (VBA) of fractional anisotropy (FA) maps.

Methods

We enrolled 54 consecutive patients with ischemic stroke during convalescence, and divided them into apathy (n = 31) and non-apathy (n = 23) groups. We obtained magnetic resonance images of their brains, including T1, T2 and DTI sequences. Age, sex, education level, Hamilton Depression Scale (HAMD) scores, Mini-Mental State Examination (MMSE) scores, National Institutes of Health Stroke Scale (NIHSS) scores, and infarct locations for the two groups were compared. Finally, to investigate the structural basis of post-stroke apathy, VBA of FA maps was performed in which we included the variables that a univariate analysis determined had P-values less than 0.20 as covariates.

Results

HAMD (P = 0.01) and MMSE (P<0.01) scores differed significantly between the apathy and non-apathy groups. After controlling for age, education level, HAMD scores, and MMSE scores, significant FA reduction was detected in four clusters with peak voxels at the genu of the corpus callosum (X = −16, Y = 30, Z = 8), left anterior corona radiata (−22, 30, 10), splenium of the corpus callosum (−24, −56, 18), and right inferior frontal gyrus white matter (52, 24, 18), after family-wise error correction for multiple comparisons.

Conclusions

Post-stroke apathy is related to depression and cognitive decline. Damage to the genu of the corpus callosum, left anterior corona radiata, splenium of the corpus callosum, and white matter in the right inferior frontal gyrus may lead to apathy after ischemic stroke.     

Regionally specific white matter disruptions of fornix and cingulum in schizophrenia

Limbic circuitry disruptions have been implicated in the psychopathology and cognitive deficits of schizophrenia, which may involve white matter disruptions of the major tracts of the limbic system, including the fornix and the cingulum. Our study aimed to investigate regionally specific abnormalities of the fornix and cingulum in schizophrenia using diffusion tensor imaging (DTI). We determined the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) profiles along the fornix and cingulum tracts using a fibertracking technique and a brain mapping algorithm, the large deformation diffeomorphic metric mapping (LDDMM), in the DTI scans of 33 patients with schizophrenia and 31 age-, gender-, and handedness-matched healthy controls. We found that patients with schizophrenia showed reduction in FA and increase in RD in bilateral fornix, and increase in RD in left anterior cingulum when compared to healthy controls. In addition, tract-based analysis revealed specific loci of these white matter differences in schizophrenia, that is, FA reductions and AD and RD increases occur in the region of the left fornix further from the hippocampus, FA reductions and RD increases occur in the rostral portion of the left anterior cingulum, and RD and AD increases occur in the anterior segment of the left middle cingulum. In patients with schizophrenia, decreased FA in the specific loci of the left fornix and increased AD in the right cingulum adjoining the hippocampus correlated with greater severity of psychotic symptoms. These findings support precise disruptions of limbic-cortical integrity in schizophrenia and disruption of these structural networks may contribute towards the neural basis underlying the syndrome of schizophrenia and clinical symptomatology.     

Vascular Risk Factors in Patients with Different Subtypes of Ischemic Stroke May Affect Their Outcome after Intravenous tPA

Intravenous (IV) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS). However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with IV tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scores (mRS), and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received IV tPA, 217 were in the large artery atherosclerosis (LAA) group, 146 in the small vessel occlusion(SVO) group, and 140 in the cardioaortic embolism(CE) group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with IV tPA may be related to different vascular risk factors associated with different subtypes of stroke.     

Microstructural abnormalities of uncinate fasciculus as a function of impaired cognition in schizophrenia: A DTI study

Neuropsychological studies have reported that attention, memory, language, motor and emotion processing are impaired in schizophrenia. It is known that schizophrenia involves structural alterations in the white matter of brain that contribute to the pathophysiology of the disorder. Uncinate fasciculus (UNC), a bundle of white matter fibres, plays an important role in the pathology of this disorder and involved in cognitive functions such as memory, language and emotion processing. Therefore, the present study aimed to investigate microstructural changes in UNC fibre in schizophrenia patients relative to controls and its correlation with neuropsychological scores.Diffusion tensor imaging (DTI) and Hindi version of Penn Computerised Neuropsychological Battery test was performed in 14 schizophrenia patients and 14 controls. DTI measures [fractional anisotropy (FA) and mean diffusivity (MD)] from UNC fibre were calculated and a comparison was made between patients and controls. Pearson’s correlation was performed between neuropsychological scores and DTI measures.Schizophrenia patients showed significantly reduced FA values in UNC fibre compared to controls. In schizophrenia patients, a positive correlation of attention, spatial memory, sensorimotor dexterity and emotion with FA was observed. These findings suggest that microstructural changes in UNC fibre may contribute to underlying dysfunction in the cognitive functions associated with schizophrenia.     

Risks and Benefits of Early Antithrombotic Therapy after Thrombolytic Treatment in Patients with Acute Stroke

Background

Current guidelines recommend withholding antithrombotic therapy (ATT) for at least 24 h in patients with acute ischemic stroke treated with thrombolytic therapy. Herein, we report a retrospective analysis of a single-centre experience on the safety and efficacy of antithrombotic therapy (ATT) started before or after 24 h of intravenous thrombolysis in a cohort of acute ischemic stroke patients.

Methods

A total of 139 patients (Rapid ATT group) received antithrombotic therapy before 24 h of thrombolysis, and 33 patients (Standard ATT group) after 24 h. The brain parenchyma and vessel status were assessed using simple CT scan on admission, multimodal CT scan at the end of thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using the modified Rankin Scale (mRS) at day 90.

Results

The two ATT groups had similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies, vessel-patency rates at the end of thrombolysis, and incidence of bleeding complications at follow up. At day 3, the Rapid ATT group had a non-significant improved vessel-patency rate than the Standard ATT group. At day 90, a greater proportion of patients in the rapid ATT group had shifted down the mRS, and had improved in the NIHSS score.

Conclusions

ATT initiated before 24 h of intravenous thrombolytic therapy in acute stroke patients disclosed no safety concerns compared with a conventional antithrombotic therapy delay of 24 h and showed better functional outcome at follow up. The value of early initiation of ATT after thrombolysis deserves further assessment in randomized controlled trials.     

Microstructural Changes in the Striatum and Their Impact on Motor and Neuropsychological Performance in Patients with Multiple Sclerosis

Grey matter (GM) damage is a clinically relevant feature of multiple sclerosis (MS) that has been previously assessed with diffusion tensor imaging (DTI). Fractional anisotropy (FA) of the basal ganglia and thalamus might be increased in MS patients, and correlates with disability scores. Despite the established role of the striatum and thalamus in motor control, mood and cognition, the impact of DTI changes within these structures on motor and neuropsychological performance has not yet been specifically addressed in MS. We investigated DTI metrics of deep GM nuclei and their potential association with mobility and neuropsychological function. DTI metrics from 3T MRI were assessed in the caudate, putamen, and thalamus of 30 MS patients and 10 controls. Sixteen of the patients underwent neuropsychological testing. FA of the caudate and putamen was higher in MS patients compared to controls. Caudate FA correlated with Expanded Disability Status Scale score, Ambulation Index, and severity of depressive symptomatology. Putamen and thalamus FA correlated with deficits in memory tests. In contrast, cerebral white matter (WM) lesion burden showed no significant correlation with any of the disability, mobility and psychometric parameters. Our findings support evidence of FA changes in the basal ganglia in MS patients, as well as deep GM involvement in disabling features of MS, including mobility and cognitive impairment. Deep GM FA appears to be a more sensitive correlate of disability than WM lesion burden.     

Relevance of Post-Stroke Circulating BDNF Levels as a Prognostic Biomarker of Stroke Outcome. Impact of rt-PA Treatment

The recombinant form of tissue plasminogen activator (rt-PA) is the only curative treatment for ischemic stroke. Recently, t-PA has been linked to the metabolism of brain-derived neurotrophic factor (BDNF), a major neurotrophin involved in post-stroke neuroplasticity. Thus, the objective of our study was to investigate the impact of rt-PA treatment on post-stroke circulating BDNF levels in humans and in animals. Serum BDNF levels and t-PA/plasmin activity were measured at hospital admission and at up to 90 days in stroke patients receiving (n = 24) or not (n = 14) rt-PA perfusion. We investigated the relationships between serum BDNF with concurrent t-PA/plasmin activity, neurological outcomes and cardiovascular scores at admission. In parallel, serum BDNF levels and t-PA/plasmin activity were assessed before and after (1, 4 and 24h) the induction of ischemic stroke in rats. Our study revealed higher serum BDNF levels and better neurological outcome in rt-PA-treated than non-treated patients. However, serum BDNF levels did not predict stroke outcome when the whole cohort of stroke patients was analyzed. By contrast, serum BDNF levels when measured at admission and at day 90 correlated with cardiovascular scores, and those at day 1 correlated with serum t-PA/plasmin activity in the whole cohort of patients whereas no association could be found in the rt-PA-treated group. In rats devoid of cardiovascular risk, no difference in post-stroke serum BDNF levels was detected between rt-PA- and vehicle-treated animals and no correlation was found between serum BDNF levels and t-PA/plasmin activity. Overall, the data suggest that serum BDNF levels may not be useful as a prognostic biomarker of stroke outcome and that endothelial dysfunction could be a confounding factor when serum BDNF levels after stroke are used to reflect of brain BDNF levels.