bluuebunny/crossref_metadata_2025 huggingface dataset:
A Canadian CADASIL Kindred: How sensitive is a skin biopsy?
Authors: Demaerschalk Bart , MacLeod Patrick M , Lee Donald H , Hammond Robert R , Ainsworth Peter J , Musyj Sherry K , Hachinski Vladimir
Published: July 2021

87

Background:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited arterial disease of mid-adulthood resulting from mutations of the Notch3 gene on chromosome 19. The presence of granular and osmiophilic material surrounding smooth muscle cells visualized under electron microscopy in a skin biopsy allows confirmation of the intra vitam diagnosis. The literature suggests that skin biopsy can establish the diagnosis with high certainty and that it be considered the diagnostic method of first choice. Until the sensitivity and specificity have rigorously been assessed, results from such tests should be interpreted with caution. Objective: To raise some concerns about the possible lack of sensitivity of skin biopsy in the early diagnosis of CADASIL by describing the second large Canadian kindred with this condition.
Methods:
All siblings of this family in which there was a clinical suspicion of CADASIL underwent neurological evaluation, magnetic resonance imaging (MRI), skin biopsy, and genetic testing. Findings: Nine siblings ranged in age from 40 to 63 years. Two (aged 60 and 62) presented with dementia, strokes, and depression, two (aged 58 and 63) presented with stroke and migraine with aura, three (aged 40, 48, and 51) presented with only migraine with aura, and two (aged 53 and 57) were asymptomatic. Eight consented to diagnostic evaluation. All eight siblings’ DNA-sequence analysis of the Notch3 gene revealed an Arg207Cys mutation in exon 4. All have MRI scans consistent with a diagnosis of CADASIL. Full thickness skin biopsies from all eight were submitted for histopathological and ultrastructural examination. Granular electron dense osmiophilic material was not found in any of the material submitted.
Conclusions:
In addition to providing an illustrative clinical example of the broad phenotypic variation of CADASIL in a Canadian kindred, this family demonstrates how insensitive the skin biopsy might be. The sensitivity and specificity of various non-genetic diagnostic tests such as skin and muscle biopsy must be rigorously assessed before claiming them as standards for screening or diagnosing CADASIL.
Neurotrophins promote bone marrow stromal cells (MSCs) to express neural proteins in vitro
Authors: Wang Lei , Li Yi , Lu Dunye , Chen Jieli , Chopp Michael
Published: July 2021

103

We tested the hypothesis that MSCs cultured in an environment containing neurotrophins promotes the expression of neural proteins. The effect of neurotrophins (brain-derived neurotrophic factor, BDNF; nerve growth factor, NGF) and the detection of corresponding receptors (TrkA-NGF, TrkB-BDNF) on the MSCs were investigated. MSCs were cultured in regular medium, i.e. Iscove s Modified Dulbecco s medium (IMDM) supplemented with 10% fetal bovine serum (FBS), and then isolated by their adherence to the plastic dishes from non-adherent hematopoietic cells at 72 h of incubation. Subsequently, the cells were cultured for 2 weeks under the following conditions: (A) regular medium, (B) regular medium + BDNF (100ng/ml), (C) regular medium + BDNF (100ng/ml) + NGF (100ng/ml ), or (D) regular medium + BDNF (100ng/ml ) + NFG (100ng/ml) + bFGF (10ng/ml). Using immunoflurescence staining, MSCs widely expressed TrkA and TrkB (the receptors of NGF and BDNF) in the medium (A). Medium (B) and (C) induced an increase of total number of cells (116%) derived from MSCs at 12 days, however, this did not reach statistical significance (P>0.05). Medium (D) significantly promoted the proliferation of MSCs (P<0.05), compared with controls (148%). Approximately 1% and 0.5% of MSCs expressed GFAP (an astroglial marker) and NeuN (a neuronal marker), respectively, in the medium (A). GFAP positive cells increased to 4%∼6% and NeuN positive cells increased to 1% in culture maintained in the medium (B) and (C). However, medium (D) exerted a dramatic effect on GFAP positive cells that reached 8% and NeuN positive cells reached 2%. Our data provide evidence that neurotrophins enhance the proliferation and differentiation of MSCs into the neural-like cells that express neural proteins in vitro.
Motor recovery after striato-capsular stroke (SCS) depends on normal laterality of brain activation: a longitudinal PET study
Authors: Calautti Cinzia , Leroy Francois , Guincestre Jean Yves , Marie Rose Marie , Viader Fausto , Baron Jean Claude
Published: July 2021

101

Introduction:
Although bilateral motor network overactivations during finger motion are documented after stroke, their relation with actual recovery is unknown. One longitudinal study reported a shift of activations from the affected to the unaffected hemisphere with elapsing time (Marshall et al,
Stroke
, 2000;31:656), but whether this shift was related to recovery was not assessed. Subjects and
Methods:
In this prospective, longitudinal study of 5 R-handed pts (59±13 yrs) with R-sided hemiparesis due to first-ever left SCS, we obtained two 3D-PET H
2
O
15
studies(ECAT HR+), the 1
st
at 1–4 and the 2
nd
at ∼8 months after onset (PET1 and PET2, respectively), replicating 4 times 2 conditions: i) rest with eyes closed, metronome on; ii) metronome-cued right thumb-to-index tapping (TIT) at fixed-rate (1.26 Hz). Data were assessed individually with SPM96 and p< 0.05, corrected; controls were 7 healthy age-matched R-handed subjects. We computed correlations between R hand motor performance (max number of TITs in 15 s) and Laterality Index

(LI = the

affected-to-unaffected-hemisphere ratio of activated voxels, Cramer et al,
Stroke
, 1997;28:2518). Results and comments: motor scores significantly improved from PET1 to PET2 (18±4 and 29±5, respectively, p<0.05, paired t-test); 2 pts exhibited mirror movement at PET1 and 1 at PET2. Significant overactivations at PET1 affected the whole motor network bilaterally, but were considerably less extensive at PET2, with a significant LI shift (.69±.11 and .08±.54, respectively, p<0.05). Shift magnitude was negatively correlated (Spearman rho= -.975, p<0.05) with clinical recovery (expressed as motor score changes), that is, the more the laterality shifted (i.e., deviated from normality), the lesser the recovery.
Conclusion:
The shift towards the unaffected hemisphere confirms earlier report, though performance was fixed here. This study is the first to document a correlation between recovery and brain activation patterns after stroke, such that the greater the shift, the worse the recovery.
CT Angiography Reveals Anatomic Features that Account for the Distribution of Emboli in the Anterior Cerebral Circulation
Authors: Liebeskind David S , Babikian Viken L , Llanes Jennifer N , Lim Silvester R , Villablanca J. Pablo , Wijman Christine A C , Saver Jeffrey L
Published: July 2021

108

Background:
Correlative analysis of vascular anatomy on CT angiography (CTA) with transcranial Doppler ultrasonography (TCD) patterns of embolism may elucidate dynamic embolic particle behavior in humans.
Methods:
CTA was performed in 81 consecutive patients (median age 62 years, range 8–90; 54% female), employing Vitrea™ software to obtain 2D multiplanar-reformatted and 3D volume-rendered images. Two independent observers measured angulation and luminal diameters of the supraclinoid carotid (ICA), and proximal anterior (ACA) and middle (MCA) cerebral arteries. Based on previously described TCD methods, ipsilateral ACA and MCA were monitored for emboli in 10 patients with extracranial ICA stenosis (mostly solid emboli) and 8 with prosthetic cardiac valves (mostly gaseous emboli).
Results:
Pathologic CTA findings at the terminal ICA bifurcation were noted in 12% (20/162), with hypoplastic A1 segments observed in 11% (16/142) of normal bifurcations. Diameter of the A1 segment was significantly smaller than the M1, mean 2.55 mm (95%CI ±.05) vs 3.19 mm (±.07), p<.0001. A1 diameter contralateral to a diseased A1 was significantly larger, 2.70 mm (p=.05). ACA-ICA angulation was more acute than MCA-ICA, 81.13° (±1.50) vs 134.87° (±1.10), p<.0001. Angle relative to gravity was greater for ACA than MCA in natural head posture (63.73° (±3.50) vs 30.59° (±14.00), p<.0001) and supine TCD position (26.27° (±3.50) vs -59.41° (±14.00), p<.0001). ICA emboli exhibited a greater tendency to enter the MCA than those from cardiac valves: ACA/MCA emboli ratio of .32 (44/138) vs .54 (241/449), p<.0001.
Conclusions:
Vascular anatomy and embolic particle composition interact to determine embolus destination at the terminal ICA bifurcation. Larger, heavier than plasma, solid emboli are proportionately more likely to enter the MCA due to its wider diameter, downward gravitational position, and lesser path angularity; smaller, lighter than plasma, gaseous emboli are more likely to enter the ACA due to its upward gravitational position, and their lesser susceptibility to momentum and vessel diameter influences.
Reduced Cerebrovascular CO
2
Reactivity in CADASIL
Authors: Pfefferkorn Thomas , von Sebastian Stuckrad-Barre , Herzog Juergen , Gasser Thomas , Hamann Gerhard F , Dichgans Martin
Published: July 2021

P1

Background and Purpose:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in
Notch3
. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells (VSMC). To study cerebrovascular function in CADASIL we performed measurements on cerebral hemodynamics using transcranial Doppler sonography (TCD).
Methods:
Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO
2
reactivity, and the resistance index (RI) were measured by bilateral TCD in 29 CADASIL individuals (mean age 49.0±2.4 years) and an equal number of age- and sex-matched controls.
Results:
Compared to controls, CO
2
reactivity was reduced in CADASIL (33.4±2.7% vs. 45.3±3.0%; p<0.01). This difference remained significant when non-disabled CADASIL individuals (Rankin=0) were compared to matched controls (36.8±3.4% vs. 48.6±3.9%; p<0.05). CO
2
reactivity was significantly lower in disabled than in non-disabled CADASIL individuals (24.5±2.7 vs. 36.8+3.4%; p<0.05). MCA MFV was reduced in CADASIL (45.6±2.2 vs. 54.2±2.4 cm/s; p<0.05) and correlated negatively with age both in affected individuals (r=-0.314; p<0.05) and controls (r=-0.339; p<0.05). RI was not significantly altered (59.0±1.0 vs. 57.7±1.2; p=0.42).
Conclusions:
In CADASIL there is a reduction of both CO
2
reactivity and basal MCA MFV, whereas vascular resistance appears to be normal. The reduced CO
2
reactivity suggests functional impairment of cerebral vasoreactivity probably related to VSMC dysfunction. The reduction of CO
2
reactivity in non-disabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.
QT Dispersion: A Predictor of Outcome Following Acute Neurologic Events
Authors: Wirkowski Elzbieta J , Moonjely Joseph , Cohen Todd J , Manzella Stephanie M , Smith Richard H , Lazar Jason M
Published: July 2021

P26

BACKGROUND:
QT dispersion (QTD) reflects heterogeneity of myocardial repolarization, which is modulated by the central nervous system. Pervious studies have shown increased QTD to be a predictor of adverse outcome in various cardiac disease states. However, the central nervous system effects on QTD and its relation to functional outcomes have not been previously studied in patients with acute neurological events (NE). The objective of this study was to determine whether increased QTD is related to functional outcome in patients with cerebrovascular accidents (CVA) and transient ischemic attacks (TIA).
METHODS:
We studied 140 consecutive pts. aged 72±10 yrs. (48% male) admitted to our institution with NE from 1/98 to 4/98. QTD was calculated from admission EKG as the difference between maximum and minimum QT intervals. 120 pts. had interpretable EKGs with measurable QT intervals in at least 11 of 12 leads. Three separate functional scales (NIHSS, Barthel, and Rankin) were obtained on admission and discharge were recorded.
RESULTS:
QTD was higher in pts. with intracerebral hemorrhage as compared to CVA and TIA (70±15 vs. 53±27 vs. 48±31 msecs. p=0.03). Increased QTD was associated with lower functional outcome on all 3 scales (all p<0.05) and with higher mortality (p=0.02). QTD was higher in pts. with congestive heart failure (80±43 vs. 47±24 msecs. p=0.006) and carotid disease (59±32 vs. 46±27 msecs. p=0.045) as compared to those without. QTD was not associated with atrial fibrillation or coronary disease. All patients with TIA survived. On multivariate analysis, other independent predictors of poorer outcome were QTD (OR 1.35, 95% CI 1.08–1.68) and a trend towards age (OR 1.07, 95% CI 0.99–1.16). On age-adjusted logistic regression, mortality increased by an OR 1.28, 95% (CI 1.02–1.61) for every 10 msec increase in QTD.
CONCLUSION:
QTD is an independent predictor of functional outcome and mortality following acute neurological events. In this setting, QTD reflects acute neurological injury as well as underlying heart disease. The mechanism of these findings merits further study.
Quantitative CT perfusion measurement: normal values and reproducibility in man
Authors: Lee Ting-Yim , Nabavi Darius G , Lee Donald H , Gulka Irene , Craen Rosemary A , Gelb Adrian W
Published: July 2021

P32

Purpose
To establish normal values of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) as measured by dynamic contrast enhanced computed tomography (CT Perfusion) and to determine their short-term variabilities in healthy volunteers.
Method and Materials
The studies involved ten healthy volunteers, 6 females and 4 males, between 39 and 49 years old. For each subject two single-slice contrast enhanced dynamic CT studies separated by an interval of 30 min were performed at the level of the basal ganglia. Arterial oxygen saturation (SaO
2
), end-tidal CO
2
tension (ETCO
2
), and blood pressure(BP) were continuously monitored to ensure the same basal conditions were maintained throughout the studies and the waiting period between them. Each study began with intravenous injection of 40 ml of contrast at 4 ml/s and at 5 s into the injection, 60 1 s CT scans were acquired continuously. Functional images of absolute CBF, CBV, and MTT were calculated by deconvolution of an intracranial artery’s contrast enhancement curve with tissue curves. Normal CBF, CBV and MTT values of the entire slice as well as those of frontal and insular grey matter, basal ganglia, frontal white matter, and the cerebellum were analyzed. Short-term variability was calculated using a standardized set of 24 regions of interest (ROI). The size of each ROI was about 4% of the entire brain slice.
Results
There were no significant differences in SaO
2
, ETCO
2
and BP between the two studies for each subject. CBF was the highest in insular grey matter (67.8 ml/100g/min), intermediate in frontal grey matter, basal ganglia, and cerebellum (42–48 ml/100g/min), and the lowest in frontal white matter (14.5 ml/100g/min). The values of CBV followed the same trend as CBF. Short-term variability was 13.3%, 12.4% and 8.8% for CBF, CBV and MTT respectively without significant differences among the parameters.
Conclusion
CT imaging of absolute CBF, CBV, and MTT in healthy volunteers provides results similar to those known from the literature. The short-term variabilities of these quantitative functional images are acceptable for clinical applications.
Headache in Cerebral Venous Thrombosis
Authors: S de Camargo Erica C , Massaro Ayrton R , Bacheschi Luiz A , Calderaro Marcelo , Caboclo Luis O S P , Yamamoto Fabio , Scaff Milberto
Published: July 2021

P37

Objectives:
Although headache is the most frequent and often the earliest symptom of cerebral venous thrombosis (CVT), few studies have attempted to define its clinical features. Our aim is to describe the main characteristics of headache in CVT patients.
Methods:
From March 1996 to June 2000 we prospectively evaluated 39 patients. After clinical examination, diagnostic confirmation was obtained by magnetic resonance imaging and/or angiography. Information about headache was recorded on a standardized form, including location, severity, duration, quality, worsening and associated features.
Results:
The group included 69% females (mean age 35 years; range 8–81). Headache occurred in 35 patients (89.7%), and was the initial symptom in 84.6%. In 28.6% an isolated intracranial hypertension syndrome occurred. Among 66 % with severe headaches, 70% had multiple sinus thrombosis and 43.4% had intraparenchymal lesions. Four patients (11.4%) had a thunderclap-like headache. Headache onset was acute (< 48 hours) in 9 patients (26%), subacute (48 hours to 30 days) in 7 (20%) and chronic (> 30 days) in the remaining 54%. Headache was mostly focal (63%) and pulsatile in 48.6% patients. Pain worsened with head movements in 31.4% of patients, physical activity in 23% and coughing or sneezing in 20%. The most striking feature was the presence of focal signs (aphasia, motor and sensory deficits and visual field defects) in 74% of patients. In 11 of the 23 patients with severe headache, mean initial CSF pressure was 37.6 cmH2O and in those with thunderclap headache it was 51.7 cmH2O. Prior history of headache was present in 17 of CVT patients (48.6%).
Conclusions:
Headache was a frequent symptom, usually severe and focal at onset in our CVT patients. The severity of headache seems to be associated with initial CSF pressures, however, a clear relationship with intraparenchymal lesions was not observed. A striking feature was the association of headache and other neurological abnormalities. Thunderclap headache is seldom considered in patients with CVT. Prior headache was frequent and may contribute to diagnostic delays. The recognition of headache characteristics may help earlier identification of CVT patients in the emergency room.
Predictors of Progression in Lacunar Stroke
Authors: Audebert Heinrich J , Pellkofer Tina S , Haberl Roman L
Published: July 2021

P47

Objective:
To identify predictors of deterioration in patients with lacunar syndromes.
Methods:
We prospectively evaluated 46 consecutive patients (12 women, 34 men; age 64.5 ± 13.7 yrs. [ mean ± SD ] ) with acute lacunar stroke by daily clinical neurological examination including NIHSS and follow-up using the Barthel Index after 3 months. In addition, we determined parameters of inflammation ( C-reactive protein, leukocytes, body temperature), coagulation (d-dimers, fibrinogen, PTT, vWF ), glutamate, as well as blood glucose and blood pressure. Progressive neurological deficit was defined as worsening of the NIHSS by 1 point in one singular item.
Results:
Eleven patients (23.9 % ) showed a clinical progression of stroke symptoms, 35 patients remained stable or improved. The NIHSS on admission was similar in both groups (4.2 ±2.7 vs. 3.8 ±2.2), but significantly higher in progressive patients on day 2 (5.4 ±3.5 vs. 2.6 ±2.0; p=0.02) and at discharge (3.7 ±3.3 vs. 1.6 ±1.7; p=0.046). Nine of the 11 progressive patients showed deterioration in the first 24 hours after admission. Barthel Index after 90 days was significantly lower in the progressive patients (87 ±18 vs. 95 ±19; p=0.005). Clinical progression was significantly associated with elevated body temperature (p=0.031 ), fibrinogen ( p=0.048 ) and a higher leucocyte count ( p=0.017 ) on admission. Mean blood glucose and blood pressure were also higher in progressive patients, but this difference did not reach the level of significance. There was no significant correlation for the other coagulation parameters, glutamate level on admission, risk factors, age and gender.
Conclusions:
In lacunar stroke there is a high rate (= 23.9 % ) of neurological worsening, and the long-term prognosis of progressive patients is worse compared to non-progressive patients. Progression usually occurs within 24 hours and may be related to an acute-phase response.
Patterns of core and penumbra in acute MI occlusion and their clinical correlates
Authors: Jovin Tudor G , Goldstein Steven , James Gebel M , Lawrence Wechsler R , Ott Margareth-Beth , Yonas Howard
Published: July 2021

P51

Background and Purpose:
The ischemic penumbra is composed of neurons that are functionally impaired but structurally intact, and thus potentially salvageable. Identifying the penumbra and its relationship with the ischemic core may lead to a more physiologic selection of patients who might benefit from recanalization therapy. We sought to explore the core/penumbra relationship by quantitatively measuring cerebral blood flow (CBF) in patients with acute M1 occlusion.
Methods:
19 patients with M1 occlusion proven by CT angiography or conventional cerebral angiography underwent a Xe-CT/CBF study within 6 hours of symptoms onset. Mean CBF values were measured in the ipsilateral cortical MCA territory. The core was defined as areas with CBF< 8 ml/100g/min and the penumbra was defined as areas with CBF 9–20 ml/100g/min. Findings were correlated with the admission NIH stroke scale (NIHSS).
Results:
In 6/19 patients (31.5%)(group 1), the size of the penumbra was greater than twice the size of the core. In 8/19 patients (42.1%) (group 2), the size of the penumbra was approximately equal the size of the core. In 5/19 patients (26.8%)(group 3) the size of the penumbra was less than half the size of the core. The median core volumes for each of the three groups, expressed as percentage of core relative to ipsilateral cortical MCA territory, increased from group 1 to group 3. While there was a trend towards a correlation between the admission NIHSS and the combined core and penumbral volumes, no such correlation could be established between admission NIHSS and core or penumbral volumes alone.
Conclusions:
In the first 6 hours after M1 occlusion, penumbral volumes that are larger than or equal to core volumes are present in 14 out of 19 patients. A smaller core volume is associated with an increased penumbra to core ratio. The admission NIHSS in patients with M1 occlusion correlates with the combined volumes of core and penumbra.
Does Leukoaraiosis Have Any Significance in TPA Treated Patients?
Authors: Al-Senani Fahmi M , Piriyawat Paisith , Malkoff Marc
Published: July 2021

P56

Background:
Leukoaraiosis (LA) has been associated with increased risk of hemorrhage in patients treated with anticoagulants in the SPIRIT, and has been associated with a higher incidence of deep intracerebral hemorrhages (ICH). Individuals with LA have a higher risk of death, and dependency 3 months after cerebral ischemia, recurrent strokes, MI, vascular deaths, and post-stroke dementia. Given the frequency of LA on CT, and its association with increased risk for hemorrhage with anticoagulants, this could represent a predictable risk for stroke patients about to receive TPA. We examined the correlation of LA with stroke severity, risk of hemorrhage, short-term outcome after TPA and associated stroke risk factors.
Methods:
We evaluated pre-treatment, non-contrast CT scans in patients with Middle Cerebral Artery (MCA) strokes, for the presence and extent of LA using the van Swieten rating system. The NIHSS scores were obtained at baseline and 24 hours. Lesion volumes were determined on a follow-up scan using the (A*B*C)/2 method. Admission systolic BP and glucose were also obtained.
Results:
A total of 54 TPA-treated patients were studied, aged (mean ±SD) 68 years ±14.9, and baseline NIHSS 16.5 ±6.1 (n=45). Leukoaraiosis was found in 37%(20/54) of all patients on pre-treatment CT scans. No relationship was found between LA presence on pre-treatment CT scans and hemorrhagic transformation, NIHSS scores at baseline and 24 hrs, age, gender, serum glucose, and ASPECT scores. There was, however, a negative correlation between LA scores and ASPECT scores (r=-0.32 p=0.05). Systolic blood pressure correlated significantly (r=0.38, p=0.01) with LA score. There was a non-significant trend towards higher LA scores and increasing age.
INITIAL ADC PREDICTS THE OCCURRENCE AND SEVERITY OF HEMORRHAGIC TRANSFORMATION IN EXPERIMENTAL STROKE
Authors: Adami Alessandro , Thijs Vincent N , Tong David C , Beaulieu Christian , Moseley Michael E , Yenary Midori A
Published: July 2021

P64

BACKGROUND:
We recently reported that early lower ADC values are associated with an increased hemorrhagic transformation (HT) risk in ischemic stroke patients. The ability to predict the individual HT risk could be of considerable importance, particularly among patients candidates for thrombolysis. In this study we analyzed the relationship between initial ADC value and secondary HT in an experimental embolic model. We hypothesized that 1) initial lower ADC values would be found in lesions destined to HT and 2) the degree of the initial ADC decrease could predict the severity of HT.
METHODS:
Embolic strokes were created in 14 rabbits by injection of heterologous thrombi. Thrombolysis was initiated 1 hour later. DWI was performed at 0.5 h after embolization and repeated at 1.75, 3 and 5 h. We applied ADC histogram analysis to the entire ischemic hemisphere. The severity of ADC reduction was expressed as cumulative percentage of pixels below the cut-off value of 550 X 10
-6
mm
2
/sec. The brains were then histologically examined for HT 6h after embolization.
RESULTS:
HT was present in 10/14 brains (4 confluent, 6 petechial). As early as 30 min after embolization ADC values were lower in HT destined lesions. There was a significant correlation between ADC reduction and subsequent HT type (r
2
= 0.734, p<0.001). The percentage of pixels under the cut-off ADC value was 10 ± 6% in hemispheres without HT, 17. ± 4% in those with petechial HT and 32 ± 6% in those with confluent HT. The number of pixels with severely reduced ADCs progressively increased over time in the confluent HT destined animals, but increased only slightly in the other groups. Further, the confluent HT destined group experienced a rapid ADC increase at 4 h, immediately before hemorrhage.
CONCLUSION:
We show that initial lower ADC values are associated with an increased risk of secondary HT. Moreover, the degree of ADC reduction correlated with the severity of HT. These findings are evident as early as 30 min after stroke onset. These results suggest that DWI may be helpful in predicting both HT occurrence and severity. This could have substantial implications for the use of MRI in acute stroke management.
NEUROPROTECTIVE EFFECTS OF KAPPA OPIOID RECEPTOR AGONIST IN TRANSIENT FOCAL ISCHEMIA
Authors: Bhardwaj Anish , Toung Thomas Jk , Kirsch Jeffrey R , Koehler Raymond C , Hurn Patricia D , Traystman Richard J
Published: July 2021

P91

Kappa (
K
) opioid receptors have been implicated in neuroprotection from ischemic neuronal injury. We tested the effects of a selective and specific
K
-opioid receptor agonist,
BRL 52537
and antagonist,
norBNI
on infarction volume following transient focal ischemia in the rat. Under controlled conditions of normoxia, normocarbia and normothermia, halothane (1–2%)-anesthetized male Wistar rats (250–300 g) were subjected to 2 hr of middle cerebral artery occlusion (MCAO) by the intraluminal occlusion-technique using laser Doppler perfusion to assess intensity of ischemia. In a blinded randomized fashion, rats were treated with either vehicle (saline) or 1 mg/Kg/hr
BRL 52537
with continuous iv infusion starting 15 min prior to MCAO. In a second set of experiments, rats were treated with vehicle (saline), 1 mg/Kg/hr
BRL 52537
, 1 or 5 mg/Kg/hr
norBNI
starting at onset of reperfusion. All infusions were at a rate of 0.5 ml/hr and continued until the end of the experiment. Infarction volume was assessed by triphenyltetrazolium chloride (TTC) staining at 22 hr of reperfusion in all rats. TTC-determined infarction volume of ipsilateral caudoputamen (CP) complex in rats pretreated with
BRL 52537
(N=7; 29±11 mm
3
; p<0.05) (mean±SEM) and cortex (61±32 mm
3
; p<0.05) was smaller than in rats treated with saline (N=7;72±4 mm3 and 174 ±24 mm
3
, respectively). Similarly, rats treated with
BRL 52537
at the onset of reperfusion had smaller infarction volume in CP complex (N=10;35±9 mm
3
) and cortex (73±32 mm
3
) compared to saline (N=10;64±5 mm
3
and 148±23 mm
3
, respectively). Rats treated with
norBNI
(N=10) at the onset of reperfusion had similar infraction volumes in the CP complex and the cortex as compared to saline controls. These data demonstrate that
K
-opioid receptor agonist provides significant neuroprotection when given as a pretreatment as well as following 2 hr of transient focal ischemia.
Delayed treatment with interleukin-1 receptor antagonist protects cortical neurons from injury after transient MCA occlusion
Authors: Liu Kai-Feng , Garcia Julio H , Fenstermacher Joseph D
Published: July 2021

P92

Background and Purpose:
Inhibiting interleukin-1 action with its receptor antagonist (IL-1ra) following
permanent
middle cerebral artery occlusion (MCA-O) reduces the volume of brain infarction and improves neurological function in Wistar rats. We varied the times of IL-1ra administration and tested if IL-1ra treatment reduces the lesion produced by
transient
MCA-O (tMCA-O).
Methods:
One MCA was transiently occluded for 1hr in 49 adult male Wistar rats. These animals were grouped according to time of starting IL-1ra treatment (100 mg/Kg, 3 times/day): A) before MCA occlusion; B) at time of reperfusion); C) after 1hr of reperfusion; and D) controls, i.e., placebo given at time of reperfusion. Neurological function and body weight were measured on the day of tMCA-O and daily thereafter. After 7 days of reperfusion, fixed brain sections were obtained and either stained with H&E or immunostained for NeuN, GFAP, and ED-I (neuronal, astroglial, and microglial proteins, respectively). Cellular damage was assessed using quantitative image analysis.
Results:
Body weight and neurological function were not significantly different among groups A-D. Most rats of groups A-D had small, focal areas of pannecrosis in the striatum at 7 days, but selective neuronal necrosis was the predominant change in the cortex. In the striatum, the area of focal infarction was less in IL-1ra treated groups than in placebo group, but the difference was not statistically significant because of the variability (i.e., large SD). The frequency (mean number/mm
2
) of surviving neurons in the cortex (showing strong positive nuclear staining with NeuN) was significantly greater (p < 0.001) in the treated groups (A = 532 ± 32; B = 556 ± 33; and C = 588 ± 31) than the untreated group (D = 276 ± 14).
Conclusion:
The neuroprotective effects derived from reopening the artery after 1 hr of MCA-O were enhanced by administering IL-1ra even when treatment was started 1hr after beginning reperfusion. The protection induced by treatment with IL-1ra seems to be more effective in cortex than striatum.
Human Intracerebral Hemorrhage and Brain Edema: Dose-Response Effect? A Diffusion-weighted Magnetic Resonance Imaging Study
Authors: Carhuapoma Juan R , Barker Peter B , Hanley Daniel F , Beauchamp Norman J
Published: July 2021

P99

Introduction:
Although laboratory research in brain edema pathogenesis after intracerebral hemorrhage (ICH) continues to provide more insight into mechanisms of secondary neuronal injury, perhaps triggered by blood and its by-products, our knowledge of the nature and progression of brain edema after human ICH remains limited. Recently, Diffusion-Weighted Imaging (DWI) has demonstrated consistent apparent diffusion coefficient (Dav) elevation in perihematoma brain tissue, suggesting vasogenic edema.
Objective:
To study the relationship between ICH volume and the degree of Dav elevation as surrogate marker of intensity of brain edema in 6 consecutive ICH patients. Design and
Methods:
Patients with acute supratentorial ICH were prospectively evaluated using DWI. Dav elevation in perihematoma brain tissue and its relation to the original hematoma volume, obtained using validated computerized MRI volumetric techniques, were analyzed.
Results:
Six patients, mean age of 64.5 (range 44 to 87) years, were enrolled. Mean time from symptom-onset to initial MRI was 3.2 (range 2 to 6) days; mean hematoma volume was 29.9 (range 4.6–64.9) cc. Dav

in perihematoma regions was 179.4 (range 120.1 to 302.5) x 10
-5
mm
2
/sec and 88.5 (range 76.5 to 102.1) x 10
-5
mm
2
/sec in contralateral corresponding regions of interest (p=0.01). Significant correlation between hematoma volume and Dav in perihematoma edema was found using Spearman’s correlation analysis (correlation coefficient rho = 0.9; p = 0.01). Dav in contralateral, homologous regions did not correlate with hematoma volume (rho = 0.6; p = 0.2)
Conclusions:
We report significant direct correlation between ICH volume and the degree of Dav elevation in perihematoma brain edema regions. These results suggest a dose-effect relationship between volume/concentration of blood products and intensity of surrounding vasogenic edema. Larger, prospective studies are needed to confirm this biologically meaningful correlation in ICH patients. If reproduced, this knowledge has the potential to further guide therapeutic trials in ICH research.
Dysplastic Vessels after Surgery for Brain Arteriovenous Malformations
Authors: Stapf C , Connolly E S , Pile-Spellman J , Siacca R R , Mast H , Mohr J P
Published: July 2021

P107

Background and Purpose:
To determine frequency and predictors of residual dysplastic vessels on cerebral angiography after surgery for brain arteriovenous malformation (AVM).
Methods:
The 240 prospectively enrolled surgical patients from the New York AVM Databank underwent 269 AVM-related surgical procedures between July-01, 1989 and June-30, 2000. Reported postoperative brain angiographic findings were classified post hoc as (1) normal, (2) persistent dysplastic vessels, (3) residual AVM, (4) focal hyperemia in the surgical bed, or (5) other changes. Univariate and multivariate models were applied to determine associations with dysplastic vessels on postoperative angiography. The factors evaluated were patient age, gender, preoperative AVM size, anatomic AVM location, number of embolization procedures prior to surgery, and the time interval between AVM surgery and the postoperative angiogram.
Results:
Of the 224 documented angiograms, 73 (34%) were performed immediately and 147 (65%) one or more days after surgery. In 100 (45%) of them, no abnormal changes were seen, while 78 (35%) showed dysplastic vessels, 24 (11%) had evidence for a residual AVM, 16 (7%) showed focal hyperemia, and 6 (2%) yielded other findings. The frequency of dysplastic vessels was significantly correlated with increasing initial size of the removed AVM (p=0.0001); the mean diameter of AVMs in patients showing dysplastic vessels after surgery was significantly larger (41mm, SD ±14) than in those without residual dysplastic vessels (27mm, SD±13; p<0.0001). No statistically significant association was found between residual dysplastic vessels and the occurrence of symptomatic perioperative intracerebral hemorrhage.
Conclusions:
The findings suggest that angiographic abnormalities may be found in as many as half of cases studied after AVM surgery, the most common abnormality being persistent dysplastic vessels. Preoperative AVM size was found to be an independent correlate with the occurrence of dysplastic vessels after surgery.
Time Course of Changes in Nitric Oxide Synthases Following Subarachnoid Hemorrhage in Primates
Authors: Macdonald Robert L , Yamini Bak , Weir Bryce K , Ono Shigeki
Published: July 2021

P114

Nitric oxide (NO) may be important in vasospasm following subarachnoid hemorrhage (SAH). We evaluated the time course of changes in 3 isoforms of NO synthase (NOS) after SAH in monkeys. Right SAH was created and vasospasm was assessed on angiograms obtained at baseline and after 3, 7 and 14 days. Animals were euthanized at these times (n = 4 - 6 per time) and the right and left (control) middle cerebral arteries were removed. Levels of nNOS, eNOS and iNOS messenger ribonucleic acid (mRNA) and protein were measured by reverse transcriptase polymerase chain reaction and Western blotting. Angiography showed a 45 ± 13% (mean ± s.d., p < 0.05) decrease in middle cerebral artery diameter 3 days, a 41 ± 23% (p< 0.05) decrease 7 days and an insignificant 6 ± 14% decrease 14 days after SAH. The RNA for eNOS was significantly reduced (1.7 ± 0.5-fold) 7 days after SAH. There was a significant, 1.7 ± 0.2-fold reduction in eNOS protein on days 3 and 7 after SAH that returned to normal by day 14. There were no significant changes in nNOS mRNA or protein at any time after SAH. There were no significant changes in iNOS mRNA whereas iNOS protein increased on days 3 and 7 (7 ± 9 and 2.7 ± 2.8-fold, respectively, p > 0.05) and significantly decreased (2.7 ± 1.1-fold, p < 0.05) on day 14. Immunohistochemistry localized eNOS to endothelium, nNOS to brain and perivascular adventitia of the middle cerebral arteries and iNOS to inflammatory cells in the subarachnoid space. These results show a correlation between decreased eNOS and increased iNOS during vasospasm, suggesting a complex role for changes in NO in vasospasm.
Recent Infection And Risk of Spontaneous Cervical Artery Dissection: A Case-Control Study
Authors: Guillon Benoit , Tzourio Christophe , Berthet Karine , Benslamia Lamia , Lucas Christian , Bousser Marie-Germaine
Published: July 2021

P124

Background and Purpose:
Spontaneous cervical artery dissection (SCAD) is a major cause of stroke in young adults, for which an underlying arteriopathy related to a generalized extracellular matrix defect could often be a predisposing condition. As triggering factors such as minor trauma/strenuous exercise or infection may be implicated in the occurrence of SCAD, we conducted a case-control study to assess the relationship between recent infection and risk of SCAD.
Methods:
Forty-eight patients with SCAD and 52 patients with ischemic stroke from other causes (controls) were recruited prospectively and consecutively from two centers during an 18-month period. Controls were included if they were roughly comparable to cases for sex and age. To analyze the history of recent infection (within one month before SCAD or ischemia), a face-to-face interview, with a structured questionnaire focused on symptoms typical of infection, was performed as soon as possible after admission.
Results:
Patients and controls were comparable for age (44.6 (7.5) vs 45.2 (9.1), P=0.72) and sex distribution (46% of women vs 43%, P=0.81). Recent infection was found in 31.3% (15/48) of patients with SCAD and 13.5% (7/52) of controls, yielding a crude odds ratio of 2.92 (95% CI, 1.07 to 8.74; P=0.032). In a logistic model adjusted for age, sex, center, educational level and migraine, the odds ratio for recent infection in cases was 3.05 (95% CI, 1.06 to 8.74; P=0.038).
Conclusion:
This prospective case-control study showed a significant association between recent infection and SCAD, consistent with the triggering role of an infectious process in the occurrence of SCAD.
Job Characteristics Influence Return to Work after Ischemic Stroke
Authors: Wozniak Marcella A , McCarthy Melissa , Langenberg Patricia , Price Thomas R , Kittner Steven J
Published: July 2021

P129

Background.
Prior work has shown that few factors other than stroke severity predict return to work after ischemic stroke. Although job characteristics have been studied as determinants of return to work after myocardial infarction, there are few data on the relationship between these characteristics and return to work after stroke.
Methods.
A prospective study of return to work was conducted in patients with first ischemic stroke, ages 24–64, employed full-time outside of the home immediately prior to the stroke, and discharged to home or acute rehabilitation. At 6 weeks after stroke, the patients completed standardized questionnaires describing job characteristics, including the Job Content Questionnaire. At 6 and 12 months after stroke, time to return to work was determined by telephone interview. Statistical methods were univariate lifetables and a multivariate forward stepwise Cox regression model with Barthel Index, age, and the job characteristics as independent variables.
Results.
Of 150 stroke patients, 64% were male and 48% were African-American, with a mean age of 51. Patients employed at 12 months had significantly less demanding jobs (both physically and psychologically) and less job insecurity (all p < 0.05) and more decision authority, more job-related social support, more job satisfaction, and fewer job hazards (nonsignificant trends). The independent predictors from the Cox model, in order of entry, were psychological job demands, Barthel Index, job physical exertion, and job insecurity.
Conclusion.
Job characteristics were strong predictors of return to work after ischemic stroke in patients with mild to moderately severe stroke. Implications. Interventions in the work environment may have potential to promote reemployment after stroke.
Isolated Systolic Hypertension and the Long-Term Risk of Stroke: A 20-Year follow-up of the National Health and Nutrition Survey.
Authors: Mohammad Yousef M , Qureshi Adnan , Suri M Fareed K , Ali Zulfiqar , Guterman Lee R , Hopkins Nelson L
Published: July 2021

P133

Background and Purpose:
Isolated systolic hypertension (ISH) is frequently observed in elderly persons. The effect of ISH on the long-term risk for stroke and stroke subtypes is unclear. We performed this study to evaluate the long-term risk of stroke in persons with ISH.
METHODS:
We evaluated the incidence of stroke and stroke subtypes(ischemic and hemorrhagic) in a nationally representative cohort of 14,047 adults who participated in the First National Health and Nutrition Examination Survey during the 20-year follow-up. ISH was defined as a systolic blood pressure(BP)>160mmHg and diastolic BP<90mmHg.
RESULTS:
A total of 376 persons with ISH, 8985 persons with normotension, and 4686 persons with classic hypertension were followed. During the follow-up period, the annual incidences of ischemic stroke and intracerebral hemorrhage for patients with ISH were 1.7% and .05% respectively. After adjusting for differences in age, race,and gender, the risk for ischemic stroke was increased in persons with ISH compared to persons with normotension (odds ratio [OR]=1.6, 95% confidence interval [CI]=1.1 to 2.2). The increased risk was similar to persons with classic hypertension (OR=1.3, 95% CI=1.03 to 1.6). The risk of intracerebral hemorrhage was increased in persons with classic hypertension (OR=3.0, 95% CI=1.5 to 7.1) but not in persons with ISH (OR=0.7, 95% CI=0.1 to 2.3).
CONCLUSION:
Persons with ISH are at increased risk for ischemic stroke, similar to those with classic hypertension.
Subarachnoid Hemorrhage is a Preventable Disease with a Heritable Component
Authors: Kissela Brett M , Sauerbeck Laura , Woo Daniel , Khoury Jane C , Shukla Rakesh , Moomaw Charlie , Graus Jessica A , Carrozzella Janice , Jauch Edward C , Pancioli Arthur M , Broderick Joseph P
Published: July 2021

P141

Background:
Subarachnoid hemorrhage (SAH) affects ≥ 16,000 Americans annually and ≥ 40% die within the first 30 days. Prevention of SAH is therefore of paramount importance. We present a preliminary analysis of risk factors for SAH from our case-control, population-based study.
Methods:
Cases were prospectively collected and matched to 2 age-, race-, and gender-matched controls. Risk factor history, family history, neuroimaging data, and genetic samples were obtained. Multivariable analysis was performed using logistic regression.
Results:
Between 6/97 and 2/00, 107 cases and 197 controls were enrolled in this study. By univariate analysis: hypertension, family history of SAH or intracranial aneurysm (IA), smoking (current or ever), alcohol use, low education level, low body mass index (BMI), and low estrogen state were risk factors for SAH (p < 0.05). Results of the multivariable analysis are presented below.
Conclusion:
Our data confirms previous reports that SAH is a heritable condition. Further work must be done to identify the genetic basis of SAH, so that families can be screened in an efficient and cost effective way. Risk for SAH may be reduced by treating hypertension, smoking cessation, and reduced alcohol intake. The importance of low BMI as a risk factor has been previously reported but is biologically puzzling and requires further study.
Relations between coagulation profiles, lipid profiles, and other risk factors with risk of first-ever ischemic stroke: a novel case-control study
Authors: Bai Chyi-Huey , Chen Jiunn-Rong , Hsiao C. Kate , Chiu Hou-Chang , Pan Wen-Harn
Published: July 2021

P156

Background and objectives:
Several hemostatic factors and lipid parameters are associated with risk of coronary heart disease. Few studies have investigated the relations between these factors and risk of ischemic stroke. The major aim of this study was to estimate the risks of hypercoagulability, hyperlipidemia, hypertension, and hyperglycemia in acquiring first-ever ischemic stroke. An ancillary aim was to observe changes including biochemical and coagulation profiles in first-ever ischemic stroke inpatients from admission to 3 months later.
Methods:
One hundred and forty-four first-ever ischemic stroke inpatients and two types of controls (including 142 stable ischemic stroke outpatients and 181 non-stroke outpatients) were recruited from 1996 to 1999. Uric acid and glucose levels, status of hypertension, diabetes, left ventricular hypertrophy (LVH), and atrial fibrillation (AF), and coagulation (clotting times, fibrinogen, factor VIIc, and factor VIIIc) and lipid (cholesterol, triglyceride, HDL-C and LDL-C) profiles were obtained.
Results:
The proportions of cases with elevated fibrinogen and factor VIIIc from admission to 3 months later were significantly higher than those of non-stroke controls, either with or without anticoagulants. The proportions of cases with decreased HDL-C and hyperglycemia were also significantly higher than those of non-stroke controls. After adjusting for multiple cardiovascular risk factors, elevated fibrinogen (OR=3.21; p=0.0071), hyperglycemia (OR=2.65; p=0.0076), hypertension (OR=1.97; p=0.0424), history of LVH (OR=3.15; p=0.0010), and carotid plaque states (OR=2.27; p=0.0185) were significantly associated with risk of first-ever ischemic stroke. Elevated factor VIIIc was at borderline significance level (OR=2.12; p=0.0722).
Conclusion:
Hypertension, hyperglycemia, LVH and positive carotid plaque were associated with risk of first-ever ischemic stroke. Elevated fibrinogen and factor VIIIc were also associated with first-ever ischemic stroke, indicating a role of coagulation profiles in the pathogenesis of ischemic stroke.