72 Hour Stroke/ Bundle after Acute Stroke

(A) shows Kaplan Meier curves comparing survival of participants with mild stroke in the control and intervention groups.

 (B) shows Kaplan Meier curves comparing survival of participants with moderate stroke in the control and intervention groups. 

(C) shows Kaplan Meier curves comparing survival of participants with severe stroke in the control and intervention groups. 

(D) shows Kaplan Meier curves comparing survival of participants with very severe stroke in the control and intervention groups. The p values were obtained from the log rank tests. 

Mortality within 7 days was higher in the intervention group compared to controls (RR 13.1, 95% CI 3.3–52.9). There was no difference in 30-day mortality between the two groups (RR 1.2, 95% CI 0.5–2.6). There was better 30-day survival in patients with severe stroke in the intervention group compared to controls (P = 0.018). The median survival time was 30 days (IQR 29–30 days) in the control group and 30 days (IQR 7–30 days) in the intervention group. In the intervention group, 41patients (32.3%) died in hospital compared to 23 (18.1%) in controls (P < 0.001). The median length of hospital stay was 8 days (IQR 5–12 days) in the controls and 4 days (IQR 2–7 days) in the intervention group. There was no difference in functional outcomes between the groups (RR 0.9, 95% CI 0.4–2.2).

Cortical Complexity of Spinocerebellar Ataxia Type 3

Each voxel of gray matter in every T1-weighted image was anatomically assigned to the resulting 97 labeled brain regions, which were displayed in different colors in the lower right panel.   

Cortical and sub-cortical regions defined in Automated Anatomical Labeling template image in standard stereotaxic space (Each region is divide into left and right).

The cortical dysfunction of SCA3 patients in cerebellar cortex (SARA; left vertical axis) and in cerebral cortex (MMSE; reight vertical axis) were incoherent.

The result shows significantly increasing SARA scores throughout duration of disease (r = 0.5672; p = 0.0344), but nonsignificant correlation between MMSE scores and duration of disease (r = -0.2138; p = 0.4100). (SARA: Y = 0.72494x+7.6755; MMSE: Yp = -0.0182x+28.6531). 

Cerebral cortex of SCA3 patients.

(a) significant decrease in 3D-FD values in comparison with that of normal subjects. (b) A significant correlation was observed between decreased 3D-FD values and disease duration in cerebral cortex of SCA3 (r = -0.0330, p = 0.0287). 

Cerebellar cortex of SCA3 patients.

(a) significant decrease in 3D-FD values in comparison with that of normal subjects. (b) A significant correlation was observed between decreased 3D-FD values and disease duration in cerebellar cortex of SCA3 (r = -0.0318, p = 0.0354). 

 Widespread area in supratentorial regions show decreased 3D-FD value in SCA3 patients.

(a, b) Frontal and parietal lobe of SCA3 exhibit decreased 3D-FD values, respectively. c, d Green, aqua-blue, violet and blue regions exhibit decreased 3D-FD value in the occipital lobe, temporal lobe, subcortical regions and limbic system, respectively. 

The progression rates of cortical atrophy in the supratentorial regions were similar.

(a) Excluding the age effect, the 3D-FD values of 32 cerebral regions had significant negative correlations with disease duration. (b) No significant difference was observed among these individual regions using ANOVA with Bonferroni post-hoc analysis (Degrees of freedom for regions = 98 and F = 0.02)

Stereotactic Biopsies Using an Intraoperative MR-scanner for Brain Lesions

Location of biopsy targets.

Procedure duration stratified by imaging modality.

The duration of the procedures (time spent in the stereotactic frame) was significantly influenced by the imaging modality used to acquire the stereotactic dataset (One-way ANOVA, p < .000). Post-hoc testing (LSD-Bonferroni) showed significant differences between each individual imaging modality with exception of the CT/MRI pair. Procedures performed with intraoperative CT (iCT) required the least amount of time (median 110 min) followed by iMRI-based biopsies in second place (median 120 min). Imaging performed outside the OR (CT and MRI) considerably increased overall procedure time.

Postoperative imaging, hematoma and neurologic status in the control cohort.

Complication rates and diagnostic yield showed no significant differences between both groups. Mortality was 0.6%, 95% CI = [0.12%, 1.74%], in the iMRI and 0.0% [0.00%, 3.62%], in the control group with a morbidity of 5.4% [3.6%, 7.8%] and 6.0% [2.2%, 12.6%] and a diagnostic yield of 96.8% [94.9%, 98.2%] and 96.0% [90.1%, 98.9%]. Mean procedure duration was 124 [121, 127] minutes using iMRI and 112 [106, 118] minutes in the control group

Tau or neurofilament light— Biomarker for HD

Correlations between NFL and disease progression in HD

(A) Neurofilament light (NFL) and tau levels are significantly correlated. NFL correlates positively with (B) disease burden and (C) 5-year probability of disease onset but negatively with (D) total functional capacity. ○ Premanifest gene expansion carrier • Manifest Huntington’s disease.

Correlations between tau and disease progression in Huntington’s disease.

Tau does not correlate with (A) 5-year probalility of disease onset but correlations with (B) disease burden, (C) total functional capacity, and (D) total motor score were significant. ○ Premanifest gene expansion carrier • Manifest Huntington’s disease.

Comparing the correlations of neurofilament light and tau with cognitive test scores.

Neurofilament light (NFL) has stronger correlations with clinical scores like (A) stroop interferens, and (B) category fluency, compared with (C and D) tau. ○ Premanifest gene expansion carrier • Manifest Huntington’s disease.

External Validation of the A2DS2 Score to Predict Stroke-Associated Pneumonia in Population

Flowchart of study population.

The flowchart was used to illustrate how the study population was selected.   

SAP was 18.8%, which ranged from 9.0% in patients with lower A2DS2 scores (0–4) to 65.0% in those with higher scores of 5 to 10 (P for trend <0.001). The C statistic was 0.836 (95% confidence interval, 0.803–0.868) through the A2DS2 score, suggesting excellent discrimination in the HNSR. 

PRRT2 Mutations in Paroxysmal Kinesigenic Dyskinesia with Convulsions in Cohort

PRRT2 mutations in patients with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC).

Twenty-one different mutations have been identified in PRRT2 in familial and sporadic PKD/IC patients, with the majority resulting in a truncation of the PRRT2 protein. p.R217Efs*12 is particularly common and accounts for 75.5% (71/94) of the patients with PRRT2 mutations. The mutations identified in this study are labeled in red and the novel ones with “#”, and those found in previous studies are labeled in black . Numbers within parentheses denote the number of the patients with the specific mutations.  

The PRRT2 mutations identified in patients with paroxysmal kinesigenic dyskinesia with infantile convulsionin this study.

The PRRT2 heterozygous mutations, (A) c.272delC (p.P91Qfs*24), (B) c.595G>T (p.E199X), (C) c.604_607delTCAC (p.S202Hfs*16), (D) c.649_650insC (p.R217Pfs*8), (E) c.649del (p.R217Efs*12), (F) c.718C>T (p.R240X), and (G) c.922C>G (p.R308C) are shown by sequencing both the mutant and normal strands of the TA-subcloned PCR fragments. 

Haplotype analyses of the patients carrying PRRT2 p.R217Pfs*8 mutation.

Five unrelated PKD/IC pedigrees carry the PRRT2 p.R217Pfs*8. Patients 4 (A), 5 (B), 6 (C), 7 (D), and 8 (E) are indicated with arrows. Asterisks (*) depict the individuals who were haplotyped. The squares and circles denote males and females, and the close and open symbols represent affected and unaffected members, respectively. The grey symbols denote undetermined disease status. The PRRT2 genotype is labeled below the symbols. The alleles with an unknown phase are labeled and separated with a slash. The haplotypes linked to the PRRT2 p.R217Pfs*8 in the seven unrelated index patients are showed in (F). Five patients shared a common haplotype at loci rs9922666, rs7205278, rs4788186, rs7204252, and rs889695 linked to the PRRT2 p.R217Pfs*8 (G-T-p.R217Pfs*8-A-T-T).

Single & Multiple Injections of Human Umbilical Tissue-Derived Cells Stroke

Neurological outcome and lesion volume measurements after stroke.

Panels A–C show mNSS (A) foot-fault (B) and adhesive-removal (C) tests after stroke in the 4 experimental groups: 1. Combined Control (Co-Con.). 2. 3×106 hUTC administered at 1 day after MCAo (3M/1d). 3. 3×106 hUTC administered at 1 and 3 days after MCAo (3M/1&3d). 4. 3×106 hUTC administered at 1 and 7 days after MCAo (3M/1&7d). Panel D shows the lesion volume in the 4 experimental groups. SE = standard error. *p<0.05 vs Co-control.

hUTC treatment effect on vascular density, perimeter and synaptophysin expression.

Panel A shows significant increase in Synaptophysin expression in the IBZ in all hUTC treatment groups compared to the co-control group. Panels B–C show significant increase in vascular density and perimeter in the IBZ in all hUTC treatment groups compared to the co-control group. *p<0.05 vs Co-control. SE = standard error. Scale bar in A,B and C = 100µm. 

Spatial Reorganization of Putaminal Dopamine D2-Like Receptors in Cranial

Matched coronal sections from the MP-RAGE (top) and late image (bottom) for one subject.

The lines in each image cross at the location of peak putaminal [18F]spiperone binding in this subject.  

Coronal view of peak [18F]spiperone binding in striatum in cranial and hand dystonia.

The location of peak [18F]spiperone binding in striatum is plotted for each dystonic subject by atlas |x| and z coordinates according to which part of the body is affected by dystonia. On average, the peak was 2.1 mm more superior in the hand cramp group (red triangles) than in the group with dystonia affecting the face (blue circles). The mean location for each dystonia group is indicated by a plus sign; note that the mean (and median) cranial dystonia peak lies inferior to every hand cramp peak. The three left-handed subjects are indicated by dashed symbols. The large black lines intersect at the mean peak location for the control group.   

Peak putaminal [18F]spiperone binding does not vary significantly with age.

The location of peak [18F]spiperone binding in striatum (atlas z coordinate) is graphed versus age, for a group of normal volunteers. There is no meaningful correlation of this measure with age, and the line that best fits the data has a nearly flat slope

Increased BBB Hyperpermeability with Mast Cell Activation and Cuprizone

BBB impairment seen with Cuprizone administration.

(A) Fluorescent images of vessels stained with Evans blue showing increased extravasation of the dye during  cuprizone treatment. 200x mag, Scale bar = 200 μm. (B) Intensity measures showed highest levels in vessel permeability at 3 days with significant differences measured at all time points (mean ± s.e.m.). n = 6, Asterisk denotes significance (p = < 0.05) (C) Western Blot analysis of corpus callosum. Occludin at 3 days of cuprizone administration. Representative blots of Occludin and GAPDH in mice after 3 days of cuprizone administration. (D) Densitometry of western blot shows significant decrease in Occludin levels compared to controls. Data are expressed as a percentage of control with the highest control set at 100. n = 3. Asterisk denotes significance (p = < 0.05).

Myelin signal measures through time period of cuprizone treatment.

(A) T2-RARE MR imaging of cuprizone induced demyelination in the corpus callosum. No visible changes in myelin signal in the corpus callosum was detected after 2 weeks of treatment and these did not differ between rostral and caudal regions as has been previously reported.[41,42] (B) Quantification of corpus callosum signal intensity shows no increases in T2 signal between groups or across time (mean± s.e.m.). Acquisition parameters: TR = 85 ms, TE = 2800.218 ms. White arrows indicate corpus callosum position. (n = 6, p < 0.05) (C) Fluoromyelin fluorescent staining of cortical and corpus callosum tissue in 3 days to 6 weeks of cuprizone treated tissue. (D-E) Quantification of cortex and corpus callosum showed no significant decrease in fluorescent signal through 2 weeks of treatment with cuprizone (mean± s.e.m.). Scale bar = 500 μm, n = 6. Asterisk denotes significance (p = < 0.05). 

A) 4x images show changes across cortical and corpus callosum. Cell counts were taken from 20x Cortex and 20x Corpus Callosum regions of each slice. (B-C) Quantification of GFAP+ astrocytes within both regions (mean ± s.e.m.). Reactive gliosis was significantly increased by 2 weeks in cortical tissue but not in the corpus callosum over the control tissue. 4x Scale bar = 500 μm, 20x Scale bar = 200 μm, n = 6. Asterisk denotes significance (p = < 0.05).    

(A) Fluorescent images of IBA-1 stained microglia in both cortical and corpus callosum regions. (B-C) Total counts of microglia increased significantly in both cortex and corpus callosum after 1 week of cuprizone administration. Within the total counts, there was significant increases at 1 week for both inactive and active morphologies of microglia in both regions (mean ± s.e.m.). 20x Scale bar = 200 μm, n = 6. Asterisk denotes significance (p = < 0.05).

Posteromedial Cortex Deactivation MCI/AD

Postero-medical cortex (PMC), denoted in red and overlaid on a canonical T1-weighted brain template image in three orthogonal views,

 was used as an apriori functional region of interest.

In this region parameter estimates for activation magnitude showed a lesser-to-greater activation from Control, to MCI, to AD subjects.Comparable values in AD higher percentage.

Bar graph demonstrates the proportion of activators and deactivators among the four diagnostic groups.

The proportion of deactivators was significantly different (p<0.05) across diagnostic groups after adjusting for age, education and baseline MMSE score, with significantly fewer deactivators with increasing cognitive impairment grouping

Bar graph demonstrates activation magnitude parameter estimate in the PMC region (Fig 1), demonstrating a continuum from control, to MCI-Nonconverter, to MCI-Converter, to AD.

There were statistically significant (p<0.05) differences between all groups with the exception of the control and MCI-Nonconverter group, and the AD and MCI-Converter group. Note the overall pattern of negative activation magnitude in the Control and MCI-Nonconverter groups, and positive activation magnitude in the AD and MCI-Converter groups. Activation in AD more clearly defined and clear active in all regions.

ID Multi-Genomic Biomarkers AD

The selection of SNPs in upstream 5K boundary for each gene.

Top 7 connected components with biomarkers identified using M-Lasso mapped to prior network.

Absence of EEG correlates Processing Depth in ALS

Healthy individuals, and B. ALS patients. Inset plot shows for every frequency band the modulation of the mean log-band powers in the self-referential conditions relative to the control (“count”) condition. The mean log-band power is averaged over subjects and trials for every frequency band. γ1 indicates low γ and γ2 indicates high γ. Note that modulations relative to the control condition were used only for visualisation 

Color shows voxels with p < 0.05.   

Decreased levels of serotonin and reduced activations of the DMN observed 

in amyotrophic lateral sclerosis (ALS) 

Dysfunctional processing of the medial prefrontal cortex.

Serotonin-innervated neurons outside of the motor cortices are involved in 

high cognitive processing

Cerebral Metabolic Differences Associated with Cognitive Impairment in PD

Glucose metabolism associated with different cognitive states in Parkinson’s disease (PD).

PD-MCI patients exhibited limited areas of hypometabolism in the frontal, temporal and para-hippocampal gyrus compared with the PD-NC pat-Hients (p < 0.01). PDD patients had bilateral areas of hypometabolism in the frontal and posterior parietal-occipital lobes compared with PD-MCI patients (p < 0.01), and exhibited greater metabolic reductions in comparison with PD-NC patients (p < 0.01). Hypometabolism was much higher in the PDD patients than in PD-MCI patients.

Group comparison of regional metabolic changes between PD groups utilizing voxel-based 

statistical parametric mapping analysis.

Metabolic increases are displayed using a red–yellow scale and declines are displayed using a blue–purple scale. Both displays were superimposed on a single-subject MRI brain template and thresh holded at p = 0.01 (uncorrected). (A) PD-MCI VS. PD-NC, (B) PDD VS. PD-MCI, (C) PDD VS. PD-NC.

The cognitive domains affected in PD-MCI patients were as follows: 1 patient (5%) had only the attention domain affected; 7 patients (35%) had two domains affected; 7 patients (35%) had three domains affected; 4 patients (20%) had four domains affected; and 1 patient (5%) had five domains affected.

PDD group had FDG uptake reduction in the right superior frontal gyrus, left precentral gyrus, left parietal lobule, right angular gyrus, left supra-marginal gyrus, left precuneus and cuneus, associated with increased metabolism in the left cingulate gyrus compared with PD-MCI group (p < 0.01). 

PDD patients exhibited more widespread hypometabolism, mainly located in the posterior parietal-occipital regions, compared with PD-MCI patients, and exhibited greater metabolic reductions in comparison with cognitively unimpaired PD patients.

Hypometabolism has been detected in the posterior cingulate, parietal, and temporal association regions, with a lesser involvement of the frontal cortex, when compared with nondemented PD patients. The PDD subjects in this study also had significantly hypometabolism involving the frontal lobes compared with PD-MCI patients. A recent study found that hypometabolism exceeds atrophy in some brain regions in PD patients with cognitive impairment.

Detected the hypometabolism predominantly in the frontal and temporal cortices in PD-MCI patients compared with PD-NC patients.

Tau or Neurofilament light HD

Correlations between NFL and disease progression in Huntington’s disease.

(A) Neurofilament light (NFL) and tau levels are significantly correlated. NFL correlates positively with (B) disease burden and (C) 5-year probability of disease onset but negatively with (D) total functional capacity.  Premanifest gene expansion carrier • Manifest Huntington’s disease.

Correlations between tau and disease progression in Huntington’s disease.

Tau does not correlate with (A) 5-year probability of disease onset but correlations with (B) disease burden, (C) total functional capacity, and (D) total motor score were significant. ○ Premanifest gene expansion carrier • Manifest Huntington’s disease.

Neurofilament light (NFL) has stronger correlations with clinical scores like (A) stroop interferens, and (B) category fluency, compared with (C and D) tau. ○ Premanifest gene expansion carrier • Manifest Huntington’s disease.

Long-Term Post-Stroke Changes Include Myelin Loss, Specific Deficits in Sensory & Motor Behaviors

Regional brain Amyloid-β Accumulation Domain-specific Cognitive Performance in PD

Six individual cortical ROIs and a cerebellum ROI were analyzed for regional 18F-florbetapir binding and to calculate a composite ROI. Representative trans-axial images from a Aβ negative (left) and positive (right) study demonstrate each ROI: (A) parietal cortex and precuneus; (B) frontal cortex; (C) anterior and posterior cingulate gyrus; (D) temporal cortex; and (E) cerebellum. Darker regions indicate higher 18F-florbetapir retention. 

Cognitive and motor characteristics of the study population.

A. Total DRS-2 score was significantly lower in PD-MCI participants (134.3, 131.7 to 136.9) as compared to PD-NC (139.3, 138.1 to 140.6) (t(57) = 4.12, p < 0.001). B. Total DRS-2 score was not significantly different among H&Y stages (F(5,53) = 0.54, p = 0.75). C. UPDRS part 3 score was significantly higher in PD-MCI (24.5, 19.9 to 29.2) as compared to PD-NC (17.1, 14.5 to 19.7) (t(59) = 3.07, p = 0.003). D. UPDRS part 3 score was significantly higher with advanced H&Y stage (1.0: 13.5, 0.2 to 26.8; 1.5: 14.8, 12.4 to 17.1; 2.0: 18.2, 15.5 to 20.9; 2.5: 17.3, 11.8 to 22.9; 3.0: 28.1, 22.3 to 33.9; 4.0: 48) (F(5,55) = 6.57, p < 0.001). There was no association between motor phenotype (TD vs. PIGD) and H&Y stage (data not shown). Data depicted are mean ± 95% C.I. Significance identified by one-way ANOVA post-hoc test. *** p < 0.005, **** p < 0.001. 

No correlation between composite 18F-florbetapir ROI SUVr and global cognition or memory performance

(A) Total DRS-2 score did not significantly correlate with composite ROI SUVr values, either analyzed in aggregate (F(1,57) = 2.39, p = 0.13) or by cognitive diagnosis (for PD-NC, F(1,39) = 0.02, p = 0.90; for PD-MCI, F(1,16) = 2.15, p = 0.16). (B) DRS-2 memory sub-score did not significantly correlate with composite ROI SUVr values, either analyzed in aggregate (F(1,57) = 3.80, p = 0.06) or by cognitive diagnosis (for PD-NC, F(1,39) = 0.00, p = 0.97; for PD-MCI, F(1,16) = 3.03, p = 0.10).

AD: Analyzing

11 AD markers in 10 loci.

 phenotypic variance, by chromosome, explained by all SNPs

Real and hypothetical variants are graphed by effect size (y-axis) and population frequency (x-axis). Known AD and SNPs are blue circles and hypothetical SNPs are red circles