Stroke after implantation of continuous flow left ventricular assist devices.

OBJECTIVE: Stroke remains a frequent and devastating complication after left ventricular assist device (LVAD) implantation, despite recent advances in device technology. The aim of this study was to analyze risk factors and outcomes of stroke following implantation of 200 continuous-flow LVADs at our institution. METHODS: We retrospectively analyzed patients who underwent LVAD implantation from 2011-2016. Data were available for a total of 200 patients. RESULTS: Post-LVAD stroke occurred in 13% of patients (26 of 200). Ischemic stroke occurred in 50% of patients (13 of 26), and hemorrhagic stroke in 50% (13 of 26). The median duration of LVAD support at the time of stroke was 257.4 days. Baseline characteristics did not differ significantly between the stroke and stroke-free cohorts. The mean international normalized ratio (INR) at the time of embolic stroke was 1.86 (range, 1.23-3.25) and 4.62 (range, 1.4-21.4) in patients with hemorrhagic stroke (P = .014). Mortality within 30 days of stroke was 31% (8 of 26). Mortality for hemorrhagic stroke was 63% (5 of 8) and 37% (3 of 8) for ischemic stroke ( P = .03). Among the 18 patients that survived stroke, 28% (5 of 18) received a heart transplant, 39% (7 of 18) are receiving ongoing LVAD support, and 33% (6 of 18) have died from unrelated causes. Multivariate analysis showed that INR level, aortic cross-clamping, a history of previous stroke, and postoperative infection were significant predictors for post-LVAD stroke. CONCLUSION: The occurrence of stroke significantly increases morbidity and mortality after LVAD implantation. Despite an adverse impact on survival and quality of life, several patients who suffered stroke still received a heart transplant. Furthermore, none of our patients had recurrence of a neurological event. Strict implementation of anticoagulation protocols is likely the mainstay of preventing this devastating complication.

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.

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.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Clopidogrel load for emboli reduction in patients with symptomatic carotid stenosis undergoing urgent carotid endarterectomy.

BACKGROUND AND PURPOSE: Microembolic signals (MES) on transcranial Doppler are an independent risk factor for recurrent stroke in patients with extracranial symptomatic/asymptomatic carotid artery stenosis (CARAS). Clopidogrel load (300 mg) combined with dual antiplatelet therapy has been shown to reduce MES in patients with symptomatic CARAS. We sought to determine feasibility of clopidogrel load in decreasing asymptomatic embolization in patients with symptomatic CARAS undergoing urgent carotid endarterectomy within the first 2 weeks from the index event. Subjects and METHODS: Consecutive patients with symptomatic CARAS (70%-99%) and presence of MES on 1-hour baseline (<24 hours from the index event) transcranial Doppler monitoring of ipsilateral middle cerebral artery were treated with clopidogrel load followed by clopidogrel (75 mg)±aspirin (100 mg) during the elapsed time period between hospital admission and urgent carotid endarterectomy at 3 tertiary-care stroke centers. Repeat 1-hour transcranial Doppler monitoring was performed the day before surgery. Bleeding complications during surgery and recurrent strokes or transient ischemic attacks during the first month of ictus were prospectively recorded. RESULTS: A total of 11 symptomatic CARAS patients (mean age, 66±7 years; 73% men; 64% acute ischemic strokes) were treated with clopidogrel load followed by dual (67%) or single (33%) antiplatelet therapy. MES count was significantly reduced between baseline (median count, 8 MES/h; interquartile range, 6-19) and repeat transcranial Doppler monitoring (0 MES/h; interquartile range, 0-3; P=0.003). No bleeding complications, recurrent strokes, or transient ischemic attacks were documented. CONCLUSIONS: Our pilot observational study provides preliminary nonrandomized data regarding the potential efficacy of clopidogrel load to reduce asymptomatic embolization in patients with symptomatic CARAS before urgent carotid endarterectomy.

Cognitive, Functional, and Emotional Changes During the COVID-19 Pandemic in Greek Patients with Neurocognitive Disorders.

BACKGROUND: Prolonged periods of social deprivation, such as COVID-19-related lockdowns, are associated with deleterious effects on cognitive functions. OBJECTIVE: The aim of this study was to gauge the effect of prolonged social isolation on the cognitive function of older adults with neurocognitive disorders. METHODS: We recruited 125 older adults with minor or major neurocognitive disorders divided into two groups. The control group was tested at the first period of the study (October 2018-May 2019), whereas the experimental group was evaluated at the second chronological period of the study (October 2020-May 2021) during the second wave of COVID-19. Neuropsychological tests were performed at baseline and six months after baseline. RESULTS: In the control group, significant changes in the scores from the Montreal Cognitive Assessment (MoCA; p = 0.049) and the Functional Rating Scale for Symptoms of Dementia (FRSSD; p = 0.005) were found between baseline and follow-up assessments, whereas no changes were identified in Mini-Mental State Examination (MMSE; p = 0.229) and Geriatric Depression Scale (GDS; p = 0.619) scores. In the experimental group, the scores from all neuropsychological tests (MoCA, MMSE, GDS, and FRSSD; p < 0.001 for all) were significantly different at follow-up when compared with those at baseline measurements. Moreover, significant deterioration of specific functions assessed in MMSE and FRSSD was detected, especially in the experimental group. CONCLUSION: This study highlights cognitive functions directly affected by social deprivation of individuals with neurocognitive disorders. The findings can be used in the rehabilitation from confinement and its negative consequences.

Safety of transcranial Doppler 'bubble study' for identification of right to left shunts: an international multicentre study.

BACKGROUND AND PURPOSE: A recent retrospective study using an online list service established by the American Academy of Neurology has suggested that ischaemic cerebrovascular events may occur in patients who undergo 'bubble studies' (BS) with either transcranial Doppler (TCD) or transoesophageal echocardiography (TOE). The safety of TCD-BS for right to left shunt (RLS) identification was evaluated prospectively in an international multicentre study. METHODS: Consecutive patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attack (TIA)) were screened for potential ischaemic cerebrovascular events following injection of microbubbles during TCD-BS for identification of RLS at three tertiary care stroke centres. TCD-BS was performed according to the standardised International Consensus Protocol. TOE-BS was performed in selected cases for confirmation of TCD-BS. RESULTS: 508 patients hospitalised with acute cerebral ischaemia (mean age 46±12 years, 59% men; 63% ischaemic stroke, 37% TIA) were investigated with TCD-BS within 1 week of ictus. RLS was identified in 151 cases (30%). TOE-BS was performed in 101 out of 151 patients with RLS identified on TCD-BS (67%). It was positive in 99 patients (98%). The rate of ischaemic cerebrovascular complications during or after TCD-BS was 0% (95% CI by the adjusted Wald METHOD: 0-0.6%). Structural cardiac abnormalities were identified in 38 patients, including atrial septal aneurysm (n=23), tetralogy of Fallot (n=1), intracardiac thrombus (n=2), ventricular septal defect (n=3) and atrial myxoma (n=1). CONCLUSION: TCD-BS is a safe screening test for identification of RLS, independent of the presence of cardiac structural abnormalities.

Signaling through the S1P-S1PR Axis in the Gut, the Immune and the Central Nervous System in Multiple Sclerosis: Implication for Pathogenesis and Treatment.

Sphingosine 1-phosphate (S1P) is a signaling molecule with complex biological functions that are exerted through the activation of sphingosine 1-phosphate receptors 1-5 (S1PR1-5). S1PR expression is necessary for cell proliferation, angiogenesis, neurogenesis and, importantly, for the egress of lymphocytes from secondary lymphoid organs. Since the inflammatory process is a key element of immune-mediated diseases, including multiple sclerosis (MS), S1PR modulators are currently used to ameliorate systemic immune responses. The ubiquitous expression of S1PRs by immune, intestinal and neural cells has significant implications for the regulation of the gut-brain axis. The dysfunction of this bidirectional communication system may be a significant factor contributing to MS pathogenesis, since an impaired intestinal barrier could lead to interaction between immune cells and microbiota with a potential to initiate abnormal local and systemic immune responses towards the central nervous system (CNS). It appears that the secondary mechanisms of S1PR modulators affecting the gut immune system, the intestinal barrier and directly the CNS, are coordinated to promote therapeutic effects. The scope of this review is to focus on S1P-S1PR functions in the cells of the CNS, the gut and the immune system with particular emphasis on the immunologic effects of S1PR modulation and its implication in MS.

Influence of Social and Demographic Factors on the Montreal Cognitive Assessment (MoCA) Test in Rural Population of North-Eastern Greece.

The current study aims to investigate the influence of socio-demographic factors on the Montreal Cognitive Assessment (MoCA) test results in a Greek-speaking population consisting of a sample of healthy older adults, individuals with mild cognitive impairment (MCI), and dementia patients in rural areas. In addition, the current research focuses on determining optimal cut-off scores for the clinical diagnoses of MCI and dementia. The data originated from 283 participants in an ongoing registry of the Neurology Department of Alexandroupolis University Hospital, recruited in different rural districts of north-eastern Greece, across a broad range of educational and occupational categories. Total and sub-domain scores for the MoCA varied significantly, according to sex, age, and education, among the three study groups. The optimal cut-off points of 25/26 for the MoCA total score was determined to classify healthy subjects from individuals with MCI, 24 to discriminate healthy participants from demented, and 21/22 to discriminate subjects with MCI from dementia. Overall, the clinical use of the MoCA test can be supported by demographically adjusted standard scores in a Greek-speaking rural population. These findings serve to improve the diagnostic accuracy and utility of the MoCA test.

Real-time hemodynamic assessment of downstream effects of intracranial stenoses in patients with orthostatic hypoperfusion syndrome.

BACKGROUND: Arterial flow velocity changes on transcranial Doppler can reflect changes in cerebral flow during position-induced ischemia if obtained during short-term monitoring of positional changes. SUBJECTS AND METHODS: Our multicenter group monitored symptomatic and asymptomatic arteries in patients with recurrent neurological deficits during positional changes and documented intracranial arterial stenosis. Bilateral posterior cerebral and middle cerebral arteries were monitored dependent on clinical symptom localization. The symptomatic artery was monitored distal to the intracranial stenosis, and mean flow velocities (MFV) were recorded at different body positions. The symptomatic artery relative MFV ratio was defined as the ratio of symptomatic artery MFV in the asymptomatic position--MFV in the symptomatic position/MFV in the asymptomatic position. RESULTS: Sixteen patients underwent transcranial Doppler monitoring: mean age 62 +/- 19 years, 11 (69%) men, 6 (40%) with transient ischemic attacks. Ten patients (63%) had posterior and 6 anterior circulation symptoms. Patients developed neurological symptoms while standing up (63%) and/or sitting (44%), walking (13%) or during neck extension (6%). Symptomatic artery MFV dropped by > or =25% from the resting to the symptomatic position in all patients except for one. The mean symptomatic artery MFV relative ratio was higher compared with the mean asymptomatic artery MFV relative ratio: 0.5 +/- 0.28 versus -0.02 +/- 0.1 (p = 0.001, Wilcoxon test). The symptomatic artery relative ratio of >0.25 had a 94% sensitivity and 100% specificity for predicting neurological symptom development during testing (kappa = 0.9, p < 0.001). CONCLUSIONS: A significant reduction in intracranial flow velocity distal to an intracranial stenosis can identify patients whose symptoms can worsen with positional changes. These patients may prove a target for interventional revascularization techniques.

Factors defining occurrence of ischemic and hemorrhagic strokes during continuous flow left ventricular assist device support.

OBJECTIVE: LVAD-related strokes occur at a much higher rate compared to traditional open heart surgery. The pathophysiology of ischemic and hemorrhagic strokes after LVAD implantation is not well defined. The aim of this study was to better describe the etiopathogenesis of strokes during continuous flow LVAD support based on our institutional experience. METHODS: We performed a retrospective analysis of 200 patients, with and without stroke that underwent implantation of a continuous flow LVAD from 2011 to 2016. RESULTS: The incidences of stroke in our patient population were 13% (26/200), of which 50% (13/26) were ischemic and 50% hemorrhagic (13/26). Only 8% of strokes occurred within the first 48 h from LVAD implantation, all of which were ischemic. The median duration of support was 148 days for ischemic and 351 days (p = 0.012) for hemorrhagic strokes. The average mean arterial pressure measurements at the time of hospital discharge were 89 mmHg for patients who subsequently developed stroke and 72 mmHg (p = 0.03) for stroke-free patients. The average outpatient pressure measurements were 96 mmHg and 76 mmHg (p = 0.02) for the stroke and stroke-free patients, respectively. The mean velocity index showed the potential impairment of cerebral autoregulation. Multivariate analysis demonstrated that INR, COPD, aortic cross clamping, previous stroke, and device infections were statistically significant risk factors for stroke occurrence after LVAD implantation. CONCLUSIONS: In addition to LVAD-related thrombogenicity, the subsequent need for anticoagulation, and an acquired von Willebrand syndrome, several clinical factors, such as deviation from the anticoagulation regimen, hypertension, COPD, device infections, and aortic cross clamping, appear to have an influence on the extremely high rate of postoperative ischemic and hemorrhagic strokes.

Vessel Density around Foveal Avascular Zone as a Potential Imaging Biomarker for Detecting Preclinical Diabetic Retinopathy: An Optical Coherence Tomography Angiography Study.

Purpose: The purpose of this study was to investigate the changes of optical coherence tomography angiography (OCTA) parameters in diabetic retinopathy (DR) using an updated software with 3D projection artifact removal. Methods: In this cross-sectional observational study, 192 eyes of 111 patients with diabetes mellitus (DM) and 55 eyes of 34 age-matched healthy subjects were included. Diabetic patients were divided into three subgroups: without DR, with mild non-proliferative DR, and with moderate-to-severe non-proliferative DR. All eyes underwent dilated fundoscopy along with 3x3mm and 6x6mm OCTA image acquisition. Vessel density (VD), retinal thickness and foveal avascular zone (FAZ) parameters were analyzed. Correlation analyses between OCTA parameters and DR severity were also performed. Results: There was a statistically significant difference in all OCTA parameters among groups, except for superficial foveal VD in 6x6mm scan and whole image retinal thickness in both 3x3mm and 6x6mm scans, while 3x3mm scan parameters were found to be diagnostically superior to the corresponding ones of 6x6mm scan. As the DR stage progressed, the mean VD values decreased. FD-300, which is the VD of a 300-µm width annulus surrounding FAZ, demonstrated the strongest inverse correlation with DR severity (r = -0.590/rs = -0.562, p < .001) and showed the highest area under the ROC curve (AUROC = 0.833 ± 0.030, p < .001) in scan 3 × 3. Conclusion: OCTA shows progressive decrease of VD parameters with increasing DR severity. Foveal VD, FAZ area, and perimeter are not very useful indexes due to the high interindividual variability of FAZ size. OCTA and specifically FD-300 may serve as a promising DR screening tool for detecting preclinical microvascular alterations.

Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. METHODS: We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. RESULTS: We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). CONCLUSIONS: Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time. RESULTS: in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Prevalence and risk factors associated with reversed Robin Hood syndrome in acute ischemic stroke.

BACKGROUND AND PURPOSE: Early deterioration can occur after acute stroke for a variety of reasons. We describe a hemodynamic steal and associated neurological deterioration, the reversed Robin Hood syndrome (RRHS). We aimed to investigate the frequency and factors associated with RRHS. METHODS: Consecutive patients with acute cerebral ischemia underwent serial National Institutes of Health Stroke Scale and bilateral transcranial Doppler monitoring with breathholding. Steal magnitude (%) was calculated from transient mean flow velocity reduction in the affected arteries at the time of velocity increase in normal vessels. Excessive sleepiness and likelihood of sleep apnea were evaluated by the Epworth Sleepiness Scale and Berlin Questionnaire. RESULTS: Among 153 patients (age, 61+/-14 years; 48% women; 21% transient ischemic attack) admitted within 48 hours from symptom onset, 21 (14%) had steal phenomenon (median steal magnitude, 20%; interquartile range, 11%; range, 6% to 45%), and 11 (7%) had RRHS. RRHS was most frequent in patients with proximal arterial occlusions (17% versus 1%; P<0.001). The following factors were independently (P<0.05) associated with RRHS (multivariate logistic regression model): male gender, younger age, persisting arterial occlusions, and excessive sleepiness (P<0.001). A 1-point increase in the Epworth Sleepiness Scale was independently related to an increased likelihood of RRHS of 36% (95% CI, 7% to 73%). CONCLUSIONS: RRHS and hemodynamic steal can be found in 7% and 14%, respectively, of consecutive patients with stroke without other known causes for deterioration. Patients with persisting arterial occlusions and excessive sleepiness can be particularly vulnerable to the steal.

Paraneoplastic autoimmunity and small-cell lung cancer: Neurological and serological accompaniments.

Paraneoplastic neurological autoimmunity is often associated with small-cell lung cancer (SCLC), a highly malignant neuroendocrine tumor. Paraneoplastic autoimmunity often correlates with longer survival. We describe the paraneoplastic neurological manifestations of patients with SCLC with and without SCLC-predictive autoantibodies and the correlation between autoimmunity and survival. We reviewed the records of 116 patients (51% male) from the Mayo Clinic with histopathologically confirmed SCLC for whom stored serum was available for neural autoantibody testing. Cancer was limited stage in 41%; the median age at diagnosis was 64 years. Paraneoplastic neurological manifestations were recorded in 61% (decreasing frequency: peripheral neuropathy, dysautonomia, cognitive decline, cerebellar ataxia, neuromuscular junction disorder, seizures, cranial neuropathy, movement disorder, brainstem disorder, or myelopathy). Neural autoantibodies, some with pathogenic potential, were detected in the sera of SCLC patients with and without neurological autoimmunity. The most frequent among patients with neurological manifestations were: anti-neuronal nuclear antibody-type 1, voltage-gated calcium channel (VGCC)-N-type, VGCC-P/Q-type, glutamic acid decarboxylase 65 (GAD65), SOX1, and muscle acetylcholine receptor (AChR); while the most common in patients without neurological manifestations were: GAD65, muscle-AChR, and VGCC-P/Q-type. Neither cancer stage at diagnosis nor survival correlated with neurological manifestations or autoantibody-positivity, except for shorter survival in patients with myelopathy. The only predictor of longer survival was limited-stage disease at diagnosis.

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.

Influence of sleep disturbance on quality of life of patients with epilepsy.

The frequency of sleep disturbances in patients with epilepsy and their impact on quality of life (QoL) have been documented in a few reports, and the results are conflicting. We identified 124 consecutive epilepsy out-patients who visited the epilepsy out-patient clinics at the University Hospital of Alexandroupolis, the AHEPA Hospital in Thessaloniki and the Aeginitio Hospital in Athens. We measured excessive daytime sleepiness (EDS) with the Epworth Sleepiness Scale (ESS), obstructive sleep apnea (OSA) with the Sleep Apnea scale of the Sleep Disorders Questionnaire (SA-SDQ), and insomnia with the Athens Insomnia Scale (AIS). We evaluated quality of life by the Quality of Life in Epilepsy Inventory (QOLIE-31). EDS was found in 16.9% (21/124) of epileptic patients, OSA in 28.2% (35/124), and insomnia in 24.6% (30/122). In multivariate analysis, we found that insomnia was an independent negative factor for Total score (p<0.001), Overall QoL (p=0.002), Emotional well-being (p<0.001), Energy/fatigue (p<0.001), Cognitive functioning (p=0.04) and Social functioning (p=0.03), and OSA only for Cognitive functioning (p=0.01). According to our findings, EDS, OSA, and insomnia are frequent in epileptic patients. Epileptic patients with sleep disturbance, mainly insomnia, have significant QoL impairment.