Impact of cerebral large-artery disease and blood flow in the posterior cerebral artery territory on cognitive function.

OBJECTIVES: The purpose of this study was to elucidate the association of cerebral large artery disease (CLAD) with cerebral blood flow (CBF) in the posterior cerebral artery (PCA) territory and cognitive performance. METHOD: We prospectively registered patients with CLAD who had internal carotid or middle cerebral artery (MCA) with the degree of stenosis ≥50%. Automated brain segmentation was used to quantify CBF in the thalamus, hippocampus, and PCA and MCA territories. We measured cognitive function of patients using the Wechsler Memory Scale Revised (WMS-R), the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment. Patients were divided into 3 groups according to CBF of the cortical and subcortical PCA territory. RESULTS: There were 60 patients included in this study. The degree of stenosis was significantly correlated with CBF in the PCA territory (Γ = 0.35, P = .006) and hippocampus (Γ = 0.34, P = .008). Verbal memory, general memory, and reproduction on WMS-R and MMSE were significantly reduced areas with low CBF in the PCA territory compared with areas with middle and high CBF. CONCLUSIONS: CBF of the PCA territory was significantly inversely correlated with the degree of stenosis in CLAD patients. Low CBF of the PCA territory was significantly associated with reduced cognitive and memory functions.

Design, Application and Infield Validation of a Pre-Hospital Emergent Large Vessel Occlusion Screening Tool: Ventura Emergent Large Vessel Occlusion Score.

BACKGROUND: The outcome of endovascular treatment for emergent large vessel occlusion (ELVO) is dependent on timely recanalization. To identify ELVO in the field, we present a simplified score, which has been applied and validated in the field by emergency medical services (EMS). Methods and Analysis: Ventura ELVO Scale (VES) comprise of 4 components: Eye Deviation, Aphasia, Neglect, and Obtundation with score range 0-4. The score of greater than or equal to 1 will be considered as ELVO positive. A positive VES along with positive Cincinnati scale prompts ELVO activation. EMS then notify to neurointervention protocol at the receiving stroke center. The performance of VES was evaluated retrospectively. For statistical analysis, SAS version 9.4 was used and Fisher's modelling was used for the comparative analysis. RESULTS: Total 184 patients were included in the final analysis, 62 (33.7%) patients were called VES positive from the field. Out of 62, 36 (58%) patients had ELVO. The mean NIHSS on arrival was 16 in VES positive and 5 in VES negative patients. VES was 94.7% sensitive and 82.4% specific while the PPV and NPV of VES were 58.1% and 98.4%, respectively. It showed 84.9% accuracy. CONCLUSIONS: VES is an effective and simplified prehospital screening tool for detection of ELVO in the field. Its implementation can beat the target door to groin time to improve outcomes and in future it can be used for rerouting of ELVO patients to comprehensive stroke center.

Validation of the National Institutes of Health Stroke Scale-8 to Detect Large Vessel Occlusion in Ischemic Stroke.

BACKGROUND: Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. AIMS: We aimed to assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 [NIHSS-8]) for identification of patients with acute stroke with LVO. METHODS: We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. RESULTS: Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve .82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of .81, specificity of .75, and Youden index of .56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (κ = .69). CONCLUSIONS: Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.

Cerebrovascular Reactivity and Intellectual Outcome in Childhood Stroke With Transient Cerebral Arteriopathy.

BACKGROUND: Hypercapnic-challenge blood oxygen level-dependent magnetic resonance imaging cerebrovascular reactivity (CVR), measures the regional perfusion response to altered carbon dioxide. CVR correlates with the tissue-level microvascular dysfunction and ischemic risk. Among children with arterial ischemic stroke, transient cerebral arteriopathy (TCA) is a frequent, nonprogressive unilateral intracranial arteriopathy, which typically results in basal ganglia infarction and chronic cerebral artery stenosis. Therefore TCA provides a model for studying the consequences of chronic nonprogressive stenosis using CVR and intellectual outcome. We hypothesized that children with TCA and chronic nonprogressive intracranial artery stenosis have impaired CVR distal to the stenosis and associated cognitive impairment. METHODS: We studied children with a prior diagnosis of TCA as defined by infarction limited to the basal ganglia, internal capsule, or both; and significant (greater than 50% diameter) residual stenosis of the supraclinoid internal carotid artery, its proximal branches or both. All children had CVR, intellectual function, and infarct volumes quantified. RESULTS: We performed CVR studies in five children at mean 8.96 years (3.33 to 14.58 years) poststroke. Impaired CVR was limited to the infarct zone and adjacent white matter in most children. Intellectual function was broadly average in all but one subject. CONCLUSIONS: In children with typical TCA, ipsilateral cortical CVR and intellectual function seem to be preserved despite persistent arterial stenosis in the majority. These findings suggest that chronic revascularization strategies in these children may not be indicated and require further exploration in a larger cohort of children.

Cognitive impairment and neurovascular function in patients with severe steno-occlusive disease of a main cerebral artery.

OBJECTIVE: Patients with severe steno-occlusive disease of a main cerebral artery may demonstrate cognitive impairment without identification of causative lesions on magnetic resonance imaging. We investigated whether cognitive impairment in these patients is associated with regional cerebral blood flow (rCBF), leukoaraiosis, risk factors of atherosclerosis and cerebrovascular reserve (CVR), which shows so-called clinical neurovascular function. METHODS: In 65 patients with severe steno-occlusive disease of an internal carotid artery or a middle cerebral artery (MCA) and no cerebral infarction (CI), we examined cognitive function with COGNISTAT, grades of leukoaraiosis, and CBF and CVR as calculated by iodine-123-N-isopropyl-p-iodoamphetamine single photon emission computed tomography and blood data. We compared such values of the left and right sided diseases. rCBF and CVR on the affected side were compared to other side. RESULTS: Logistic regression analysis revealed that CVR correlated with cognitive impairment. There was no significant difference in rCBF, CVR, or COGNISTAT score when comparing the left and right sided diseases. There were good correlations between CBF or CVR of the ipsilateral MCA area and ipsilateral and contralateral other areas. CONCLUSION: Cognitive impairment is associated with CVR in the whole brain. Nonselective widespread neurovascular mild dysfunction can be a reason for cognitive impairment in patients with severe steno-occlusive disease of a main cerebral artery and no CI.

Urinary kallidinogenase for the treatment of cerebral arterial stenosis.

AIM: Urinary kallidinogenase (UK) has shown promise in improving cerebral perfusion. This study aimed to examine how UK affects cognitive status and serum levels of amyloid betas (Aßs) 1-40 and 1-42 in patients with cerebral arterial stenosis. METHODS: Ninety patients with cerebral arterial stenosis were enrolled, of whom 45 patients received UK + conventional treatment (UK group), and 45 patients received conventional treatment alone as control group. Cognitive status and Aß1-40 and Aß1-42 serum levels were determined before treatment and at 4 weeks and 8 weeks after treatment. RESULTS: At 4 weeks after treatment, cognitive status in patients treated with UK clearly improved accompanied by Aß1-40 serum levels decreasing while there was no change of Aß1-42. Cognitive status in patients receiving UK continued to improve, Aß1-40 serum levels declined further as well as Aß1-42 serum levels began to decrease dramatically at 8 weeks after treatment. CONCLUSION: UK could improve cognitive status and decrease both Aß1-40 and Aß1-42 serum levels to prevent ischemic cerebral injury, which represents a good option for patients with cerebral arterial stenosis.

Long-term outcome after arterial ischemic stroke in children and young adults.

OBJECTIVE: To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) from 2 large registries. METHODS: Prospective cohort study comparing functional and psychosocial long-term outcome (≥2 years after AIS) in patients who had AIS during childhood (1 month-16 years) or young adulthood (16.1-45 years) between January 2000 and December 2008, who consented to follow-up. Data of children were collected prospectively in the Swiss Neuropediatric Stroke Registry, young adults in the Bernese stroke database. RESULTS: Follow-up information was available in 95/116 children and 154/187 young adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4) and did not differ between the groups (p = 0.122). Long-term functional outcome was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14% (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not differ (p = 0.759). Overall psychosocial impairment and quality of life did not differ, except for more behavioral problems among children (13% vs 5%, p = 0.040) and more frequent reports of an impact of AIS on everyday life among adults (27% vs 64%, p < 0.001). In a multivariate regression analysis, low Pediatric NIH Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable outcome (p < 0.001). CONCLUSION: There were no major differences in long-term outcome after AIS in children and young adults for mortality, disability, quality of life, psychological, or social variables.

Intracranial stenosis, cerebrovascular diseases, and cognitive impairment in chinese.

Extracranial carotid artery disease has been shown to be related to cognitive deficits. However, limited data are available on intracranial stenosis (ICS) and cognitive impairment. We investigate the association between ICS and cognitive impairment in Chinese. Subjects (n=278), recruited from the Epidemiology of Dementia in Singapore Study, underwent comprehensive clinical evaluation, neuropsychological testing, and brain magnetic resonance imaging (MRI), including 3-dimensional-time-of-flight magnetic resonance angiography (MRA). Cognitive function was expressed as composite and domain-specific Z-scores. Cognitive impairment no dementia and dementia were diagnosed according to internationally accepted diagnostic criteria. Linear and logistic regression models were adjusted for age, sex, education, vascular risk factors, and other MRI markers. A total of 29 (10.4%) persons had ICS on MRA, which was significantly associated with both composite cognitive Z-scores [mean difference in Z-score, presence vs. absence of ICS: -0.37 (95% confidence interval: -0.63, -0.12)] and specific domains including executive function, language, visuomotor speed, verbal memory, and visual memory. ICS was also related to significant cognitive impairment (odds ratio: 5.10 [1.24 to 21.02]). With respect to other MRI markers, adjusted for the presence of lacunar infarcts, the associations of ICS with both composite and domain-specific Z-scores, and significant cognitive impairment became nonsignificant; however, adjustment for other MRI markers did not alter these associations. In this Chinese population, presence of ICS was associated with cognitive impairment independent of vascular risk factors. These associations may be mediated through the presence of infarcts.

Selective neuronal damage and Wisconsin Card Sorting Test performance in atherosclerotic occlusive disease of the major cerebral artery.

BACKGROUND: In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA) disease, selective neuronal damage can be detected as a decrease in central benzodiazepine receptors (BZRs) in the normal-appearing cerebral cortex. This study aimed to determine whether a decrease in the BZRs in the non-infarcted cerebral cortex is associated with poor performance on the Wisconsin Card Sorting Test (WCST), which assesses executive functions. METHODS: The authors measured the BZRs using positron emission tomography and (11)C-flumazenil in 60 non-disabled patients with unilateral atherosclerotic ICA or MCA disease and no cortical infarction. Using three-dimensional stereotactic surface projections, the abnormally decreased BZR index (extent (%) of pixels with Z score >2 compared with controls × average Z score in those pixels) in the cerebral cortex of the anterior cerebral artery (ACA) or MCA territory was calculated and found to be correlated with the patient's score on the WCST. RESULTS: On the basis of the WCST results, 39 patients were considered abnormal (low categories achieved) for their age. The BZR index of the ACA territory in the hemisphere affected by arterial disease was significantly higher in abnormal patients than in normal patients. The BZR index of the MCA territory differed significantly between the two groups when patients with left arterial disease (n=28) were analysed separately. CONCLUSIONS: In atherosclerotic ICA or MCA disease, selective neuronal damage that is manifested as a decrease in BZRs in the non-infarcted cerebral cortex may contribute to the development of executive dysfunction.

Combined effect of cerebral hypoperfusion and white matter lesions on executive functioning - The SMART-MR study.

BACKGROUND/AIMS: It has been hypothesized that cerebral hypoperfusion may contribute to cognitive deterioration. Patients with white matter lesions (WML) may be more vulnerable to a decrease in cerebral blood flow (CBF) due to an impaired autoregulation. We investigated the association between CBF and cognitive performance and whether WML modified this relation. METHODS: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 472 patients (mean age 57 +/- 10 years, 77% male). Total CBF was measured with magnetic resonance angiography in the internal carotid arteries and basilar artery, and was expressed per 100 ml brain volume. Neuropsychological tests assessing executive functioning and memory were performed and composite scores were calculated. We used linear regression analyses, adjusted for age, sex, education and intelligence, to investigate the association between CBF and cognitive performance. RESULTS: We found that WML modified the association between CBF and executive functioning (p for interaction <0.001); the association between lower CBF and worse performance on executive functioning became stronger and significant with increasing volumes of WML. Lower CBF was not associated with worse memory. CONCLUSION: Our results suggest that a combination of lower CBF and WML may impair executive functioning but not memory.

Long-term functional end points following middle cerebral artery occlusion in the rat.

The purpose of the present study was to assess the magnitude and stability of a number of functional deficits in rats subjected to occlusion of the middle cerebral artery (MCAO). Three groups of rats, treated with 90-min, 120-min, or sham occlusion were used in functional studies for 22 weeks following surgery. The following tests were used: methamphetamine-induced rotation, the staircase test, acquisition of operant responding, running-wheel behavior, and performance of operant differential reinforcement of a low-rate responding (DRL) schedule of reinforcement. Histology performed at 23 weeks following infarct showed on average modest damage of a 19% reduction in hemispheric volume. Of the behavioral tests conducted, rotation, the staircase test, and the operant DRL were sensitive to ischemic damage, and were under some circumstances related to lesion size. These data show that long-term functional deficits following MCAO are demonstrable, and hence, assessment of long-term neuroprotection is feasible.

White matter dementia in CADASIL.

Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia.

Quantitative MRI in CADASIL: correlation with disability and cognitive performance.

OBJECTIVE: To study correlations between total lesion load on brain MRI and clinical features, and to evaluate the influence of demographic variables on quantitative MRI variables in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: CADASIL is a hereditary form of small-vessel disease caused by mutations within the Notch3 gene. MRI abnormalities have been found both in asymptomatic and symptomatic CADASIL individuals. METHODS: Quantitative measurements on cerebral MRI were performed in 64 CADASIL individuals. MRI lesions were quantified using a semi-automated segmentation technique based on local thresholds. RESULTS: MRI total lesion volume correlated significantly with disability (Rankin Scale) on both T1- and proton density (PD)-weighted images. There was a significant inverse correlation between total lesion volume and overall cognitive performance as determined by the Mini-Mental State Examination. Age but not sex was correlated with lesion load both on T1- and PD-weighted images. There was no detectable influence of the Notch3 genotype on quantitative MRI variables. CONCLUSIONS: This study demonstrates correlations between MRI lesion volume and clinical characteristics in CADASIL. Longitudinal studies are now warranted to investigate whether quantitative MRI could be used as an adjunct outcome measure in future therapeutic trials in CADASIL.

Effects of thyrotropin-releasing hormone on behavioral disturbances in middle cerebral artery-occluded rats.

The effects of thyrotropin releasing hormone (TRH) on behavioral and histological changes were studied in rats subjected to left middle cerebral artery occlusion. The drug was given i.p. once or several times a day from 1 week after occlusion for 2 weeks. A single administration of TRH (1 and 10 mg/kg) did not affect the neurological deficits, but recovery of the deficits was accelerated by multiple administration (7 times a day) of TRH and single administration (once a day) of YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), a new TRH analogue with a longer half-life. Both YM-14673 and single (1 and 10 mg/kg) and multiple administration of TRH ameliorated the disturbance of passive avoidance learning. Neuronal degeneration in the cerebral cortex and striatum was not influenced by the administration of TRH. Thus, we found that neurological deficits and disturbance of passive avoidance learning behavior in middle cerebral artery-occluded rats could be ameliorated by administration of TRH.

["My hand" sign associated with tactile extinction in two patients with callosal lesion].

Two patients with "my hand" sign in association with tactile extinction from callosal lesion, one due to left anterior cerebral artery occlusion, the other due to right anterior cerebral artery aneurysm rupture, were reported. The examination of "my hand" sign was performed with the methods proposed by Brion et al. Our patients correctly responded when they grasped their own or the examiner's thumb with their left hand. But they replied "my finger"when they grasped not only their own but also the examiner's thumb with their right hand. Left tactile extinction was observed after a routine extinction test in one patient, and it was observed in the other after the following method: both patient's index fingers were disposed in his midline position. In these methods of extinction test, they made errors in saying "right" when both fingers were touched simultaneously. However, they said "both" when their right index finger alone was touched (synchiria) during an extinction test using the following method: both index fingers of patients were approached by examiner to touch each other or for one of them to touch the examiner's finger. When they were asked whose finger they touched in this method (whose finger test), they made the same errors as seen in "my hand" sign test. These test results suggest that there is a common underlying mechanism in the "my hand" sign and extinction, because the sense of double stimulations felt when only one stimulation is given (synchiria), is a possible explanation for the "my hand" sign and the pathogenesis of synchiria appears to be related to extinction.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of word comprehension in a case of pure word deafness.

A case of pure word deafness due to a left temporal infarct is reported. The results of dichotic tests suggest that auditory verbal material may be processed in the right hemisphere. The inability to repeat nonsense words, the frequent semantic paraphasias in real-word repetition tasks, and the capacity to give a partial account of the meaning of a word that the patient cannot repeat show that despite the impairment of the phonological analysis, lexical semantic processing is possible. An attempt is made to demonstrate that the patient resorts to this semantic processing and that this reflects the linguistic competence of the right hemisphere.