Clinical and Neuroimaging Characteristics in Embolic Stroke of Undetermined versus Cardioembolic Origin: A Population-Based Study.

BACKGROUND AND PURPOSE: Evidence suggests that cardioembolism represents the underlying mechanism in the minority of embolic strokes of undetermined source (ESUS). In this population-based study, we sought to compare the clinical and imaging characteristics as well as outcomes in patients with ESUS and cardioembolic stroke (CE). METHODS: We included consecutive patients with first-ever ischemic stroke (IS) from the previously published population-based Evros-Stroke-Registry identified as ESUS or CE according to standardized criteria. Baseline characteristics, admission NIHSS scores, cerebral edema, hemorrhagic transformation, stroke recurrence, functional outcomes (determined by modified Rankin Scale [mRS] scores), and mortality rates were recorded during the 1-year follow-up period. RESULTS: We identified 21 ESUS (3.7% of IS) and 211 CE (37.1% of IS) cases. Patients with ESUS were younger (median age: 68 years [interquartile range [IQR]: 61-75] vs 80 years [IQR: 75-84]; P < .001), had lower median admission NIHSS scores (4 points [IQR: 2-8] vs 10 points [IQR: 5-17]; P < .001), and lower prevalence of cerebral edema on neuroimaging studies (0 vs. 33.3%, P = .002). Functional outcomes were more favorable in ESUS at 28 (median mRS score: 2 [IQR: 1-3] vs 4 [IQR: 4-5]; P < .001), 90 (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 3-5]; P < .001), and 365 days (median mRS score: 1 [IQR: 0-2] vs 4 [IQR: 2-4]; P < 0.001). At 1-year, the mortality rate was lower in ESUS (0% [95% confidence interval [CI]: 0-13.5%] vs 34.6% [95% CI: 28.2-41.0%]; P < .001); the 1-year recurrent rate was also lower numerically (0% [95% CI: 0-13.5%] vs 9.5% [95% CI: 5.5-13.4%]; P = .140) but this difference failed to reach statistical significance due to the small study population. CONCLUSIONS: The clinical and neuroimaging profiles as well as clinical outcomes vary substantially between ESUS and CE indicating different underlying mechanisms.

Incidence, characteristics and outcomes in patients with embolic stroke of undetermined source: A population-based study.

Embolic stroke of undetermined source (ESUS) represents a subgroup of cryptogenic ischemic stroke (CS) distinguished by high probability of an underlying embolic mechanism. There are scarce population-based data regarding the incidence, characteristics and outcomes of ESUS. Consecutive patients included with first-ever ischemic stroke of undetermined cause in the previously published population-based Evros Stroke Registry were further subdivided into ESUS and non-ESUS CS. Crude and adjusted [according to the European Standard Population (ESP), WHO and Segi population] incidence rates (IR) for ESUS and non-ESUS CS were calculated. Baseline characteristics, admission stroke severity (assessed using NIHSS-score), stroke recurrence and functional outcomes [determined by modified Rankin Scale (mRS) scores], were recorded during the 1-year follow-up period. We identified 21 and 242 cases with ESUS (8% of CS) and non-ESUS CS. The crude and ESP-adjusted IR for ESUS were 17.5 (95%CI: 10-25) and 16.6 (95%CI: 10-24) per 100,000 person-years. Patients with ESUS were younger (p < .001) and had lower median admission NIHSS-scores (p < .001). Functional outcomes were more favorable in ESUS at 28, 90 and 365 days. ESUS was independently (p = .033) associated with lower admission NIHSS-scores (unstandardized linear regression coefficient: -13.34;95%CI: -23.34, -3.35) on multiple linear regression models. ESUS was not related to 1-year stroke recurrence, mortality and functional improvement on multivariable analyses. In conclusion we found that ESUS cases represented 8% of CS patients in this population-based study. Despite the fact that ESUS was independently related to lower admission stroke severity, there was no association of ESUS with long-term outcomes.

Stroke recurrence and mortality in northeastern Greece: the Evros Stroke Registry.

Up to date there is no population-based study from Greece providing long-term data on incidence of both all-cause mortality and stroke recurrence for patients with first ever stroke (FES). Adult patients with FES were registered during a 24-month period (2010-2012) and followed-up for 12 months. We calculated cumulative incidences of stroke mortality and recurrence. Univariable and multivariable Cox proportional hazards regression analyses were used to identify independent determinants of 1-year mortality and 1-year stroke recurrence. We prospectively documented 703 first ever stroke cases (mean age 75 ± 12 years; 52.8% males; ischemic stroke 80.8%, intracerebral hemorrhage 11.8%, subarachnoid hemorrhage 4.4%, undefined 3.0%) with a total follow-up time of 119,805 person-years. The cumulative incidence rates of mortality of all FES patients at 28 days, 3 months and 1 year were 21.3% (95% CI 18.5-24.5%), 26% (95% CI 22.9-29.4%) and 34.7% (95% CI 31.3-38.3%), respectively. The risk of 1-year mortality was independently (p < 0.05) associated with advancing age, history of hypertension, increased stroke severity on admission, and hemorrhagic FES type. Cumulative 1-year stroke mortality differed according to both index FES type (ischemic vs. hemorrhage; p < 0.001), but also across different ischemic stroke subtypes (p = 0.025). The cumulative incidence rates of recurrent stroke at 28 days, 3 months and 1 year were 2.0% (95% CI 1.2-3.6%), 4.2% (2.8-6.2%) and 6.7% (5.1-8.8%), respectively. Comparable to other population-based surveys, our study reports 1-year mortality and stroke recurrence rates in patients with FES. These findings highlight the need for effective secondary prevention strategies in a border region of southeastern Europe, which exhibits very high FES incidence rates.

Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.

BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. METHODS: Adult patients with first-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.

Association of SCN1A gene polymorphism with antiepileptic drug responsiveness in the population of Thrace, Greece.

INTRODUCTION: The aim was to examine the influence of the SCN1A gene polymorphism IVS5-91 rs3812718 G>A on the response to antiepileptic drugs (AEDs) in monotherapy or polytherapy. MATERIAL AND METHODS: Two hundred epilepsy patients and 200 healthy subjects were genotyped for SCN1A IVS5-91 rs3812718 G>A polymorphism using TaqMan assay. Patients were divided into drug-responsive and drug-resistant patients. The drug-responsive group was further studied, comparing monotherapy in maximum and minimum doses and monotherapy-responsive and -resistant groups. RESULTS: There were no statistically significant differences in the allelic frequencies and genotype distributions between patients and controls (p = 0.178). The distribution of SCN1A IVS5-91 rs3812718 G>A genotypes was similar between drug-responsive and drug-resistant patients (p = 0.463). The differences in genotype distributions (A/A or A/G vs. G/G) between monotherapy-responsive and -resistant groups were statistically significant (p = 0.021). Within the monotherapy-responsive group, patients with the A/A or A/G genotype needed higher dose AEDs than patients with the G/G genotype (p = 0.032). The relative risk for generalized epilepsy due to A-containing genotypes was of marginal statistical significance when compared with the G/G genotype (p = 0.05). CONCLUSIONS: Overall, our findings demonstrate an association of SCN1A IVS5-91 rs3812718 G>A polymorphism with AED responsiveness in monotherapy without evidence of an effect on drug-resistant epilepsy.

Autophagy and lysosomal related protein expression patterns in human glioblastoma.

Glioblastoma cells are resistant to apoptotic stimuli with autophagic death prevailing under cytotoxic stress. Autophagy interfering agents may represent a new strategy to test in combination with chemo-radiation. We investigated the patterns of expression of autophagy related proteins (LC3A, LC3B, p62, Beclin 1, ULK1 and ULK2) in a series of patients treated with post-operative radiotherapy. Experiments with glioblastoma cell lines (T98 and U87) were also performed to assess autophagic response under conditions simulating the adverse intratumoral environment. Glioblastomas showed cytoplasmic overexpression of autophagic proteins in a varying extent, so that cases could be grouped into low and high expression groups. 10/23, 5/23, 13/23, 5/23, 8/23 and 9/23 cases examined showed extensive expression of LC3A, LC3B, Beclin 1, Ulk 1, Ulk 2 and p62, respectively. Lysosomal markers Cathepsin D and LAMP2a, as well as the lyososomal biogenesis transcription factor TFEB were frequently overexpressed in glioblastomas (10/23, 11/23, and 10/23 cases, respectively). TFEB was directly linked with PTEN, Cathepsin D, HIF1α, LC3B, Beclin 1 and p62 expression. PTEN was also significantly related with LC3B but not LC3A expression, in both immunohistochemistry and gene expression analysis. Confocal microscopy in T98 and U87 cell lines showed distinct identity of LC3A and LC3B autophagosomes. The previously reported stone-like structure (SLS) pattern of LC3 expression was related with prognosis. SLS were inducible in glioblastoma cell lines under exposure to acidic conditions and 2DG mediated glucose antagonism. The present study provides the basis for autophagic characterization of human glioblastoma for further translational studies and targeted therapy trials.

Dabigatran etexilate for secondary stroke prevention: the first year experience from a multicenter short-term registry.

BACKGROUND: There are growing concerns for the side effects of dabigatran etexilate (dabigatran), including higher incidence of dyspepsia and gastrointestinal bleeding. We conducted a multicenter early implementation study to prospectively evaluate the safety, efficacy and adherence to dabigatran for secondary stroke prevention. METHODS: Consecutive atrial fibrillation (AF) patients with ischemic stroke (IS) or transient ischemic attack (TIA) received dabigatran for secondary stroke prevention during their hospital stay according to American Heart Association recommendations at five tertiary care stroke centers. The study population was prospectively followed and outcomes were documented. The primary and secondary safety outcomes were major hemorrhage and all other bleeding events respectively defined according to RE-LY trial methodology. RESULTS: A total of 78 AF patients (mean age 71 ± 9years; 54% men; 81% IS, 19% TIA; median CHADS2 (Congestive heart failure, Hypertension, diabetes mellitus, age >75 years, prior stroke or TIA); range 2-5) score 4 were treated with dabigatran [(110mg bid (74%); 150mg bid (26%)]. During a mean follow-up period of 7 ± 5 months (range 1-18) we documented no cases of IS, TIA, intracranial hemorrhage, systemic embolism or myocardial infarction in AF patients treated with dabigatran. There were two (2.6%) major bleeding events (lower gastrointestinal bleeding) and two (2.6%) minor bleedings [hematuria (n = 1) and rectal bleeding (n = 1)]. Dabigatran was discontinued in 26% of the study population with high cost being the most common reason for discontinuation (50%). DISCUSSION: Our pilot data indicate that dabigatran appears to be safe for secondary stroke prevention during the first year of implementation of this therapy. However, high cost may limit the long-term treatment of AF patients with dabigatran, leading to early discontinuation.

Caregiver burden in epilepsy: determinants and impact.

Aim. Caregiver burden (CB) in epilepsy constitutes an understudied area. Here we attempt to identify the magnitude of this burden, the factors associated with it, and its impact to caregiver quality of life (QOL). Methods. 48 persons with epilepsy (PWE) underwent video-EEG monitoring and their caregivers completed questionnaires providing demographic, disease-related, psychiatric, cognitive, sleep, QOL, and burden information. Results. On regression analysis, higher number of antiepileptic drugs, poorer patient neuropsychological performance, lower patient QOL score, and lower caregiver education level were associated with higher CB. Time allocated to patient care approximated but did not attain statistical significance. A moderate inverse correlation between CB and caregiver QOL physical component summary score and a stronger inverse correlation between CB and caregiver QOL mental component summary score were seen. Conclusion. In a selected cohort of PWE undergoing video-EEG monitoring, we identified modest degree of CB, comparable to that reported in the literature for other chronic neurological conditions. It is associated with specific patient and caregiver characteristics and has a negative effect on caregiver QOL.

Racial disparities in early mortality in 1,134 young patients with acute stroke.

We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.

Prevalence of symptomatic intracranial atherosclerosis in Caucasians: a prospective, multicenter, transcranial Doppler study.

BACKGROUND: There are limited data available regarding symptomatic intracranial atherosclerosis (SIA) prevalence in Caucasians. We sought to investigate SIA prevalence among Caucasian patients hospitalized with acute cerebral ischemia (ACI) in a prospective, multicenter Transcranial Doppler sonography (TCD) study. METHODS: Consecutive patients with ACI were prospectively evaluated with TCD over a 24-month-period. The previously validated criteria of SONIA trial were used for detection of >50% intracranial stenosis with TCD. Brain angiography was performed to confirm the diagnosis in cases with abnormal TCD findings. SIA was diagnosed when there was evidence of a cerebral infarction in the territory of the stenotic artery (identified by TCD and confirmed by Magnetic resonance angiography [MRA]/Computed tomography angiography [CTA]). RESULTS: A total of 467 consecutive patients with ACI (60.4% men, mean age 58 ± 14 years) were evaluated. SIA was documented in 43 patients (9.2%; 95%CI: 6.9%-12.2%). The most common SIA location was M1MCA (34.9%) followed by TICA (18.8%). Diabetes mellitus (OR: 4.25, 95%CI: 2.18-8.26; P < .001) and hypertension (OR: 2.41, 95%CI: 1.02-5.67; P = .045) were independently associated with SIA on multivariate models adjusting for potential confounders. CONCLUSIONS: SIA was identified in almost 10% of patients admitted with symptoms of ACI. These preliminary findings support further collaborative initiatives among stroke physicians to increase the yield of SIA detection in Caucasian patients with ACI.

Patient and caregiver quality of life in psychogenic non-epileptic seizures compared to epileptic seizures.

PURPOSE: Little is known about the effect of psychogenic non epileptic seizures (PNES) to caregiver quality of life (QOL), particularly as it compares to epileptic seizures (ES). We sought to characterize this effect and identify its determinants. METHODS: The study population comprised of 126 ES and 33 PNES patients who underwent video EEG monitoring along with 48 and 18 caregivers respectively who accompanied them to their investigations. Patients completed questionnaires providing demographic, disease-related, cognitive, psychiatric, sleep and QOL information on admission, prior to their diagnosis being clarified. Their caregivers completed questionnaires providing demographic, disease burden and generic QOL information. Paraclinical data were also gathered. Regression analysis was used to identify patient and caregiver related determinants of patient and caregiver QOL. RESULTS: QOL scores were significantly worse for PNES than ES patients and were mainly linked to depression levels. PNES and ES caregivers had comparable demographic characteristics and QOL scores. ES caregiver QOL was better in employed caregivers with lower burden scores for the physical component summary (PCS) and worse in female caregivers of depressed patients with higher burden scores for the mental component summary (MCS). Caregiver burden score was the strongest correlate of PNES caregiver MCS QOL score. CONCLUSION: Caregiver QOL in PNES does not differ from caregiver QOL in ES, while patient QOL is worse in PNES. Caregiver burden emerges as a consistent correlate of caregiver QOL both in ES and PNES. These findings advocate for consideration of caregiver burden and QOL in PNES in clinical practice and for future research paradigms.

Intravenous thrombolysis for acute ischemic stroke occurring during hospitalization for transient ischemic attack.

BACKGROUND: There are limited data regarding the use of intravenous thrombolysis in patients who experienced acute ischemic symptoms during their hospitalization for prior transient ischemic attack. AIM: We sought to prospectively evaluate the safety and efficacy of intravenous thrombolysis for the treatment of acute ischemic stroke occurring during hospitalization for transient ischemic attack in an international, multicenter study. METHODS: Consecutive patients with acute ischemic stroke that occurred during hospitalization for prior transient ischemic attack were treated with intravenous thrombolysis in five tertiary-care stroke centers. Early arterial recanalization was determined by transcranial Doppler at the end of recombinant tissue plasminogen activator infusion using previously validated criteria. Symptomatic intracranial hemorrhage complicating intravenous thrombolysis was evaluated using the National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study definition. Functional independence at three-months was defined as Modified Rankin Scale score of 0-2. RESULTS: Systemic recombinant tissue plasminogen activator infusion (median onset-to-treatment time 70 mins, interquartile range 50-150) was given in 25 consecutive patients (mean age 66 ± 10 years) who developed acute ischemic stroke symptoms (median National Institutes of Health Stroke Scale score 10 points; interquartile range 8-14) during hospitalization for prior transient ischemic attack (median ABCD(2) score 5 points; median time-to-symptom recurrence 24 h, interquartile range 24-48). No symptomatic intracranial hemorrhage (0%; 95% confidence interval 0-12%) was documented. Early complete recanalization occurred in 64% of patients (95% confidence interval 44-80%), and 84% (95% confidence interval 65-94%) achieved three-month functional independence. The rate of three-month functional independence was higher in patients treated with intravenous tissue plasminogen activator within 90 mins from symptom onset compared with those with onset-to-treatment time>90 mins (81% vs. 33%; P = 0.031). CONCLUSIONS: Intravenous thrombolysis for symptoms of acute ischemic stroke occurring after hospitalization for transient ischemic attack appears to be safe. These pilot data support resetting the clock if new symptoms recur shortly after transient ischemic attack.

The effect of epilepsy surgery on caregiver quality of life.

PURPOSE: Epilepsy surgery has been shown to improve patient quality of life (QOL). Little is known about its effect on caregiver QOL. METHODS: The study population comprised of 26 persons with epilepsy (PWE) who underwent long term video EEG monitoring at Massachusetts General Hospital for presurgical evaluation along with 16 caregivers. The PWE completed epilepsy directed QOL (QOLIE-31) and psychological (Beck depression-BDI and anxiety inventory-BAI) questionnaires before and after surgery. Their participating caregivers completed generic health related QOL (SF36v2) and disease burden (Zarit caregiver burden inventory-ZCBI) questionnaires before and after surgery. Demographic data for all participants and disease/surgery related data for the PWE were collected. Statistical analysis was performed to compare PWE and caregiver QOL before and after surgery. RESULTS: Mean patient age was 37 years. Most (77%) suffered from symptomatic partial epilepsy for approximately 18 years prior to surgery, averaging 4 seizures per month and 2.2 antiepileptic drugs (AEDs). 78% of them underwent an anterior temporal lobectomy and the rest extra-temporal resections. On follow up at approximately 9 months, 69% had a surgical outcome of Engel class I, 23% of class II and 8% class IV. Postoperatively, the PWE remained on average on 1.9 AEDs. There was a statistically significant improvement for both the aggregate QOLIE-31 score and all its subscales (except for medication effects) as well as the BAI scores. 96% of the PWE felt that the decision to go through surgery was worthwhile. Mean caregivers age was 47 years. Half of them were spouses to the PWE and the majority of the rest their parents. 50% of them stated that their overall time devoted to patient's care decreased after surgery and 50% that it remained unchanged. The mental component scale (SF36v2, MCS) of caregiver QOL showed statistically significant improvement. ZCBI score and the physical component scale of their QOL (SF36v2, PCS) did not significantly vary before and after surgery. 75% of caregivers deemed their QOL better post surgery vs 19% similar. 94% of the caregivers felt that the decision to go through surgery was worthwhile. CONCLUSIONS: Successful epilepsy surgery has a positive impact not only to patient QOL but also to their caregiver. To the best of our knowledge, this is the first pilot study to systematically address the impact of epilepsy surgery on caregivers providing additional support to epilepsy surgery as the optimal treatment modality in carefully selected patients. These findings call for further investigation on the caregiver quality of life in epilepsy and for its inclusion in the treatment plan and quality indicators for epilepsy surgery.

Bilateral claw hand: an uncommon presentation of regional Guillain-Barré syndrome.

We present an uncommon case of a 38-year-old man presented with bilateral subacute weakness of intrinsic hand muscles, manifesting as bilateral claw-hand, without sensory deficits and absent tendon reflexes in upper arms. Nerve conduction studies showed findings consistent with demyelinating GBS. During the fourth day of hospitalization the patient presented symmetrical distal leg weakness and was treated with intravenous immunoglobulin.

Mild cognitive impairment: effect of education on the verbal and nonverbal tasks performance decline.

We sought to longitudinally evaluate the potential association of educational level with performance on verbal and nonverbal tasks in individuals with mild cognitive impairment (MCI). We evaluated patients with MCI, age >50 years, no medication intake, absent vascular risk factors, and no lesions on brain magnetic resonance imaging (MRI). Each patient underwent a clinical assessment packet and a series of neuropsychological tests of the language and constructional praxis subtests of Cambridge Cognitive Examination (CAMGOG) and the Boston naming test (BNT), at baseline, 6 months, and 12 months. Educational levels were defined taking into account the total years of education, the school level, and diplomas. MCI patients with low education level showed a stepwise reduction in scores of naming objects (NO; P = 0.009), definition (DF; P = 0.012), language (LT; P = 0.021), constructional praxis (CD; P = 0.022), confrontation naming skills (BXB; P = 0.033), phonemic help (BFB; P = 0.041), and BNT (P = 0.002). Analysis of covariance, controlling for baseline scores, showed that education was associated with NO score (P = 0.002), DF score (P = 0.005), LT (P = 0.008), CD score (P = 0.008), BXB score (44.36 ± 1.84, P = 0.0001), BFB (P = 0.022), and BNT (P = 0.004). Our findings indicate that education appeared to affect verbal and nonverbal task performance in MCI patients. Despite the fact that higher educated patients are more acquainted with the tasks, slower deterioration in consecutive follow-up examinations could be explained by the cognitive reserve theory. The potential association of this protective effect with delayed onset of symptoms deserves further investigation.

Association of ultrasonographic parameters with subclinical white-matter hyperintensities in hypertensive patients.

Background and Purpose. Cerebral white matter hyperintensities (WMHs) are regarded as typical MRI expressions of small-vessel disease (SVD) and are common in hypertensive patients. Hypertension induces pathologic changes in macrocirculation and in microcirculation. Changes in microcirculation may lead to SVD of brain and consequently to hypertensive end-organ damage. This damage is regarded the result of interactions between the macrovascular and microvascular levels. We sought to investigate the association of cerebral WMHs with ultrasonographic parameters of cerebral macrocirculation evaluated by carotid duplex ultrasound (CDU) and transcranial doppler (TCD). Subjects and Methods. The study was prospective, cross-sectional and consecutive and included hypertensive patients with brain MRI with WMHs. Patients underwent CDU and TCD. The clinical variables recorded were demographic characteristics (age, gender, race) and vascular risk factors (hypertension, diabetic mellitus, hypercholesterolemia, current smoking, and body mass index). Excluded from the study were patients with history of clinical stroke (including lacunar stroke and hemorrhagic) or transient ischemic attack (either hemispheric or ocular), hemodynamically significant (>50%) extra- or intracranial stenosis, potential sources of cardioembolism, and absent transtemporal windows. WMHs were quantified with the use of a semiquantitative visual rating method. Ultrasound parameters investigated were (1) common carotid artery (CCA) diameter and intima-media thickness, (2) blood flow velocity in the CCA and internal carotid artery (ICA), and (3) blood flow velocity and pulsatility index of middle cerebral artery (MCA). Results. A total of 52 patients fulfilled the study inclusion criteria (mean age 71.4 ± 4.5 years, 54% men, median WMH-score: 20). The only two ultrasound parameters that were independently associated with WMH score in multivariate linear regression models adjusting for demographic characteristics and vascular risk factors were increased mean common carotid artery (CCA) diameter (beta = 0.784, SE = 0.272, P = 0.006, R(2) = 23.9%) and increased middle cerebral artery pulsatility index (MCA-PI; beta = 0.262, SE = 0.110, P = 0.025, R(2) = 9.0%). Among all ultrasound parameters the highest AUC (areas under the receiver operating characteristic curve) were documented for MCA-PI (AUC = 0.82, 95% CI = 0.68-0.95, P < 0.001) and mean CCA diameter (AUC = 0.80, 95% CI = 0.67-0.92, P < 0.001). Conclusions. Our study showed that in hypertensive individuals with brain SVD the extent of structural changes in cerebral microcirculation as reflected by WMHs burden is associated with the following ultrasound parameters of cerebral macrocirculation: CCA diameter and MCA-PI.