Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities.

BACKGROUND AND PURPOSE: Polymorphic paraoxonase (PON1) variants can variably prevent low- and high-density lipoprotein oxidation, but their role in provoking atherosclerosis remained unclear. We addressed this issue by profiling PON1 polymorphisms and enzymatic activities, and assessing atherosclerosis and cerebral arteriosclerosis severity in post-stroke patients. METHODS: Carotid artery intima-media-thickness (IMT), cerebral white matter lesions (WML), serum PON1 -108C/T, Q192R and L55M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients. RESULTS: Genetic variation at the PON1 locus showed a strong influence on PON1 activity in ischaemic stroke patients, but lacked direct influence on IMT. Stroke patients with PON1 QQ192 or MM55 genotypes demonstrated lower PON and arylesterase activities at both Day 1 and 12 months post-stroke than patients with either RQ/RR192 or LM/LL55 genotypes (P < 0.001). Furthermore, patients with carotid atherosclerosis and/or cerebral arteriosclerosis expressed as IMT, carotid plaques and WML had lower 12 months PON1 activity than patients without (P = 0.02, P = 0.027 and P = 0.001, respectively), and PON and AChE hydrolysis rates were more tightly correlated in patients carrying the PON1 192R compared with the 192QQ allele, in a gene dose-dependent manner (P < 0.001). CONCLUSION: Our findings show inverse PON1 activity-carotid atherosclerosis and -cerebral arteriosclerosis association in stroke patients: the lower the PON1 activity the more progressed is the atherosclerotic process and the weaker is the association with AChE activity. Extending previous PON1 genetic studies in stroke populations, our study emphasizes the PON1 activity as a potential anti-atherogenic element and proposes involvement of cholinesterase activities in its effects.

Cognitive assessment in proximity to acute ischemic stroke/transient ischemic attack: comparison of the montreal cognitive assessment test and mindstreams computerized cognitive assessment battery.

BACKGROUND/AIMS: Even mild stroke survivors may sometimes experience residual cognitive damage. No consensus has emerged about which cognitive test is most appropriate for the diagnosis of poststroke cognitive impairment. We aim to compare a computerized battery of neuropsychological tests for memory, attention and executive functions (MindStreams®) with the Montreal Cognitive Assessment (MoCA) to detect mild-to-moderate cognitive impairments in poststroke patients. METHODS: Subjects enrolled to the TABASCO (Tel Aviv Brain Acute Stroke Cohort) study, a prospective study which includes consecutive first-ever mild-to-moderate stroke patients, were included. All participants underwent neurological and cognitive evaluations. RESULTS: A total of 454 patients with transient ischemic attack (TIA) or stroke are reported. Their mean MoCA and MindStreams scores were lower than normal; however, the TIA group presented significantly better scores using either method. The correlation between the MoCA and the computerized global score was 0.6 (p < 0.001). A significant correlation was found between the subcategory scores (executive function, memory and attention). However, the MoCA identified many more subjects with low scores (<26) compared to the MindStreams (70.6 vs. 15.7%). CONCLUSION: Our results demonstrate that either of the modalities alone is sensitive enough for identifying subtle cognitive impairment and none picks up substantially more cognitive losses than the other in patients with cerebrovascular disease.

Stroke in the very elderly: characteristics and outcome in patients aged ≥85 years with a first-ever ischemic stroke.

BACKGROUND: Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged ≥85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry. METHODS: The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged ≥85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score. RESULTS: The proportion of very elderly (≥85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged ≥85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the ≥85-year-old patients had an NIHSS score ≥11 compared with 22.0% in the younger age group (p < 0.05). CONCLUSIONS: There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population.

Vasomotor reactivity as a predictor for syncope in patients with orthostatism.

OBJECTIVES: Syncope in patients with orthostatic hypotension (OH) may be the result of impaired cerebral autoregulation. Cerebral autoregulation status can be determined by assessing cerebral vasomotor reactivity (VMR). We assessed and compared VMR in patients with OH with and without syncope. MATERIAL AND METHODS: Twenty-nine patients with OH underwent transcranial Doppler (TCD) and the Diamox test (1 g acetazolamide IV) for assessing VMR during elaboration of their OH syndrome. The percent difference between cerebral blood flow velocities (BFV) in the middle cerebral (MCA) and vertebral (VA) arteries before and after acetazolamide was defined as VMR%. We considered increases of BFV of ≥ 40% as being indicative of good VMR and classified our study patients as having good or impaired VMRs accordingly. RESULTS: Mean VMR% values of the MCA and VA in patients with OH with syncope (n = 12) were significantly lower as compared with patients with OH without syncope (n = 17): 25.2 ± 20.5% and 42.5 ± 18.6%; 20.9 ± 15.5% and 40.8 ± 28.5%, respectively (P < 0.05). CONCLUSIONS: Among patients with OH, we found an association between the presence of syncope and impaired VMR. Assessment of VMR among patients with OH may predict those who are at higher risk to faint and fall and to support more aggressive intervention.

Triggered C-reactive protein (CRP) concentrations and the CRP gene -717A>G polymorphism in acute stroke or transient ischemic attack.

C-reactive protein (CRP) increases following an acute stroke/transient ischemic attack (TIA), but the increment level varies among patients. We analyzed CRP concentrations during an acute stroke/TIA in relation to the CRP gene -717A>G polymorphism. Six months following an acute ischemic stroke/TIA, basal concentrations of CRP were measured in 507 controls and 219 patients and were found to be unassociated with the CRP -717A>G polymorphism. However, during the acute phase of stroke/TIA, individuals with the AG/GG genotype had significantly elevated CRP concentrations as opposed to those with the AA genotype (2.02 +/- 1.59 vs. 1.73 +/- 1.69 mg/l, P = 0.027). In addition, significant 3.22-fold increments in CRP concentrations was noted in individuals carrying the -717G allele when comparing the acute phase with the basal state of each patient and averaging the results. CRP -717A>G polymorphism is associated with triggered CRP concentrations during acute stroke/TIA. These findings might shed more light on the mechanisms of CRP elevation in acute ischemic stroke/TIA.

High hair cortisol concentrations predict worse cognitive outcome after stroke: Results from the TABASCO prospective cohort study.

BACKGROUND AND PURPOSE: The role of stress-related endocrine dysregulation in the development of cognitive changes following a stroke needs further elucidation. We explored this issue in a longitudinal study on stroke survivors using hair cortisol concentrations (HCC), a measure of integrated long-term cortisol levels. METHODS: Participants were consecutive cognitively intact first-ever mild-moderate ischemic stroke/transient ischemic attack (TIA) survivors from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study. They underwent 3T magnetic resonance imaging (MRI) scanning and were cognitively assessed at admission, and at 6, 12 and 24 months post-stroke. Scalp hair samples were obtained during the initial hospitalization. RESULTS: Full data on baseline HCC, MRI scans and 2 years neuropsychological assessments were available for 65 patients. Higher HCC were significantly associated with a larger lesion volume and with worse cognitive results 6, 12 and 24 months post-stroke on most of the neurocognitive tests. 15.4% of the participants went on to develop clinically significant cognitive decline in the follow-up period, and higher HCC at baseline were found to be a significant risk factor for this decline, after adjustment for age, gender, body mass index and APOE e4 carrier status (HR=6.553, p=0.038). CONCLUSIONS: Our findings suggest that individuals with higher HCC, which probably reflect higher long-term cortisol release, are prone to develop cognitive decline following an acute stroke or TIA.

Characteristics of first ever ischemic stroke in the very elderly: profile of vascular risk factors and clinical outcome.

PURPOSE: Age is the most significant non-modifiable risk factor for ischemic stroke (IS). With increasing expectancy of life, the majority of IS patients will be elderly subjects. We studied the epidemiological, clinical and rehabilitation features of patients aged ≥85 years with first-ever IS. METHODS: Demographic data, prevalence of risk factors, etiology of stroke, severity of neurological deficit, major complications and mortality rates were collected from a hospital-based stroke registry and compared between patients at the age of 65-84 and ≥85. Clinical assessment was performed by means of the National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS). RESULTS: Among 216 patients aged ≥85 years there was significantly higher proportion of a history of atrial fibrillation than in 128 patients at the age of 65-84 years and lower prevalence of hypertension, diabetes mellitus, hyperlipidemia and smoking. Large artery atherosclerosis was more frequently identified in the older patients (49% vs. 32%, p=0.002). Although NIHSS scores on admission were lower in the older patients they were more disabled at discharge. CONCLUSIONS: With respect to the patients aged <85 years very old IS patients showed different vascular risk factors profile, clinical and rehabilitation course. These findings suggest specializing stroke care in the very elderly.

Interleukin-6 as an early predictor for one-year survival following an ischaemic stroke/transient ischaemic attack.

BACKGROUND: Early biomarkers for survival in an acute ischaemic stroke/transient ischaemic attack might serve as a useful tool for the clinician. Several studies have highlighted the role of inflammatory biomarkers as an early signal for acute ischaemic stroke prognosis. AIMS: This study examines the potential advantage of using high-sensitivity interleukin-6 as a possible biomarker at the early stages of acute stroke for identifying patients at a high risk for 12-month mortality. METHODS: Inflammatory biomarkers and neurological scores were determined in 250 patients following mild to moderate acute ischaemic stroke within 24 h of hospital admission. Outcome data on mortality were collected after 12 months. The signal detection methodology was used to identify subgroups that were at a high risk for 12-month mortality. RESULTS: Twelve months following the event, 234 of the 250 stroke patients survived. Signal detection identified predictors that distinguished individuals likely to die from those with a better recovery prediction. Plasma interleukin-6 concentration emerged as the optimal predictor, with a cut point of 6.47 pg/ml, chi(2) (l, N=250)=20.5, P<0.001. Interleukin-6 above 6.47 pg/ml during the acute phase predicted subsequent non-survival (P=0.006, odds ratio 8.0). CONCLUSIONS: This study demonstrates the clinical potential of using high-sensitivity interleukin-6 as an early signal for acute ischaemic stroke survival and suggests a clear cut point for patients at a high risk who might benefit from closer clinical surveillance and/or administration of therapeutic interventions.

Transcranial Doppler for evaluation of idiopathic intracranial hypertension.

OBJECTIVES: The value of transcranial Doppler (TCD) ultrasonography in assessing patients with Idiopathic Intracranial Hypertension (IIH) is uncertain. We sought to determine the contribution of TCD to their evaluation. MATERIALS AND METHODS: Twenty-three patients with suspected IIH underwent TCD. Mean blood flow (BFV), peak systolic (PSV) and end-diastolic (EDV) velocities, and pulsatility (PI) and resistance (RI) indexes were obtained in the middle cerebral (MCA) and vertebral (VA) arteries and compared (Student's t-test) between patients with confirmed IIH and controls. IIH patients and controls were comparable in terms of age, gender and weight. RESULTS: The mean +/- SD BFV(MCA), PSV(MCA), EDV(MCA) and PI(VA) in the 13 IIH patients were higher than in the ten controls (59 +/- 6.8, 94 +/- 28.5, 43 +/- 12.4, 0.86 +/- 0.16 and 50 +/- 8.6, 72 +/- 25.8, 32 +/- 11.5, 0.58 +/- 0.45 respectively, P < 0.05) but still within normal values. The mean +/- SD PI(MCA), RI(MCA) and RI(VA) values in the IIH patients and controls were similar. CONCLUSIONS: TCD parameters had no useful unique features for monitoring IIH patients.