Clinical phenotypes of embolic strokes of undetermined source.

BACKGROUND AND PURPOSE: The embolic stroke of undetermined source (ESUS) represents a heterogeneous clinical entity. The aim of this study was to investigate whether distinct clinical phenotypes may be identified in the ESUS population. METHODS: We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. Baseline characteristics and diagnostic workup findings were collected. Hierarchical cluster analysis was carried out to classify clinical features and identify different groups of ESUS patients. RESULTS: One hundred twenty-seven patients with a mean age of 68.6 (12.5) years were included. Three main clusters were identified. The first cluster associated young age, male sex, presence of patent foramen ovale, and posterior circulation infarct. The second phenotype linked hypertension, severe stroke, left atrial cardiopathy, diabetes mellitus, and involvement of multiple vascular territories. The third cluster gathered smoking, dyslipidemia, ipsilateral vulnerable sub-stenotic carotid plaque, and infarct of anterior vascular territory. CONCLUSIONS: Distinct clinical phenotypes have been identified within the ESUS population, which may supply clues to the underlying pathogenic mechanisms.

Sleep actigraphic patterns and cognitive status.

We performed an actigraphic assessment of sleep characteristics in healthy subjects and patients with cognitive impairment. Thirty subjects were included and classified into controls (10 subjects), mild cognitive impairment (10 patients) and mild-to-moderate Alzheimer's disease (10 patients). Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Participants had a 7-day actigraphic record. Sleep parameters collected were time in bed, total sleep time, sleep efficiency, sleep latency, wakefulness after sleep onset, number of awakenings, and mean motor activity. Significant differences between mild cognitive impairment and controls patients were found for sleep latency (p = 0.05); Alzheimer's disease patients had significantly worse scores for Pittsburgh Sleep Quality Index (p = 0.01), time in bed (p = 0.001), total sleep time (p = 0.04), sleep latency, sleep efficiency, motor activity (p = 0.0001) and wakefulness after sleep onset (p = 0.001) compared to controls. When comparing Alzheimer's disease and mild cognitive impairment, differences were significant for sleep latency (p = 0.01), wakefulness after sleep onset (p = 0.004), sleep efficiency, number of awakenings and motor activity (p = 0.0001). In addition to showing a high prevalence of sleep alterations in subjects with cognitive impairment, our data suggest that they are evident from the earliest stages of cognitive decline. Further studies are needed to assess whether early correction of sleep alterations can positively influence the evolution of cognitive impairment. The opportunity to provide clinically meaningful information with a simple assessment of sleep characteristics based on actigraphy suggests that wider use of the approach in patients with cognitive decline should be considered.

Prediction of Outcome in Embolic Strokes of Undetermined Source.

BACKGROUND AND AIM: Predicting outcome after stroke is a major goal and research field. The Embolic Stroke of Undetermined Source (ESUS) is a recently introduced clinical construct, and the prediction of outcome in this population has to be further explored. The aim of the study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in patients with ESUS. METHODS: Consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria were identified and the ASTRAL scores estimated. The study endpoint was the 3-month unfavorable outcome (modified Rankin Scale>2). Predictive performance was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Among 202 patients with ESUS, 67 (33.2%) had unfavourable 3-month outcome. The ASTRAL score was an independent predictor of poor outcome [adjOR = 1.44, 95% confidence interval (CI) 1.30-1.60, P < .001], showed good discriminatory power (area under the receiver operating characteristic curve .913, 95% CI .871-.956) and was well calibrated (Hosmer-Lemeshow test P = .496). CONCLUSIONS: The ASTRAL score was an independent predictor of 3-month functional outcome and showed high predictive accuracy in patients with ESUS.

Impact of sleep disorders on the risk of seizure recurrence in juvenile myoclonic epilepsy.

OBJECTIVE: The aim of this study was to investigate the presence of sleep disturbances in patients with juvenile myoclonic epilepsy (JME) using sleep questionnaires. Further, we tried to evaluate whether alterations in sleep quality may influence the clinical expression of JME. METHODS: Sixty-two patients with JME treated with levetiracetam were included. Demographic and clinical variables were collected. Moreover, all patients submitted the Pittsburgh Sleep Quality index (PSQI) and the Epworth Sleepiness Scale (ESS) in order to respectively assess sleep quality during the last month and daytime sleepiness. All patients were followed up for a 6-month period and divided in two groups: seizure-free (Group 1) and seizure recurrence (Group 2). The PSQI and ESS scores were synthesized as binary variables <5/≥5 and <10/≥10, respectively. A comprehensive analysis was performed to evaluate the independent effect of the sleep quality and daytime sleepiness on the risk of having seizures during the follow-up. RESULTS: Both reduced sleep quality during the last month and daytime sleepiness were associated with an increased risk of suffering from seizures during the follow-up period. In fact, a PSQI score<5 or an ESS score<10 resulted significantly associated with the absence of seizure recurrence (p<0.004 and p<0.001, respectively). Increasing age had a significantly protective effect in the risk of seizure relapse. CONCLUSIONS: Our findings show that reduced sleep quality and daytime sleepiness in patients with JME increase the risk of seizure occurrence in spite of an appropriate pharmacological treatment. This negative effect seems to be more relevant in younger patients. Sleep disorders and their specific correction should be taken into consideration for the management of patients with JME.

Lacunar stroke and heart rate variability during sleep.

OBJECTIVE: Autonomic instability during sleep can influence the risk of cerebrovascular diseases. In this study, we performed a polygraphy to evaluate, heart rate variability (HRV) in a group of patients with lacunar stroke that is a condition at high risk of recurrence. METHODS: Twenty-one lacunar stroke patients were enrolled one month after stroke occurrence. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The presence of common sleep disorders and autonomic changes during the night was investigated by a polygraphy monitoring. Results were compared with those obtained in a group of 21 healthy subjects. RESULTS: Patients and controls were similar for age, sex distribution and main cardiovascular risk factors with the exception of the body mass index. Significant differences were detected for all polysomnographic (PSG) parameters and for the PSQI score. By considering HRV values, patients with pathologic values (12 patients, HRV>2) showed significantly higher values in BMI (31 ± 2.9 vs. 26.6 ± 3.6, p = 0.006) and PSQI scores (7.9 ± 2.6 vs. 4.2 ± 1.9) with respect to patients with normal HRV values (nine patients, HRV≤2). CONCLUSIONS: The results of this study suggest that the prevalence of nocturnal autonomic dysfunction is high in lacunar stroke patients even in the absence of the commonest sleep-related disorders. An abnormal HRV may contribute to increase the risk of stroke recurrence. Based on our results, the indication to polygraphy in patients with lacunar stroke should be carefully considered.

Sleep in multiple sclerosis patients treated with interferon beta: an actigraphic study.

OBJECTIVE: Sleep disorders in multiple sclerosis (MS) patients are common and complex. Some evidences suggest that interferon beta (IFN-ß), a first line disease modifying therapy can be involved in the induction of sleep architecture changes. The aim of this study was to evaluate and characterize actigraphic patterns in MS patients treated with IFN-ß. METHODS: Ten relapsing remitting MS patients with low to mild disability (Expanded Disability Status Scale<2.5), aged 20-50y treated with IFN-ß for more than 6 months were enrolled. Actigraphy was used to study sleep pattern. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Ten sex-and age-matched healthy subjects served as controls. In patients, a comparison between drug free nights and nights following drug administration was made. RESULTS: Patients had significantly higher PSQI (p = 0.006), sleep onset latency (p = 0.029), sleep efficiency percentage (p = 0.001) and number of wake episodes (p = 0,0001) values, when compared with controls. When comparing the actigraphic results acquired in the nights after treatment with those acquired in the free-drug nights, the only significant difference (p = 0.038) was detected for time in bed that was higher after IFN-ß administration. CONCLUSIONS: Our results, besides confirming the presence of alterations in sleep patterns in MS patients, suggest that IFN-ß may contribute to promote alteration in sleep architecture. Actigraphy is a simple diagnostic tool, able to support an objective measure of sleep parameters. The relative simplicity of application and low costs may allow considering its use for an adequate screening of sleep disorders in MS patients.

Endovascular treatment and cognitive outcome after anterior circulation ischemic stroke.

The impact of reperfusion therapies on cognition has been poorly explored and little knowledge exists. We explored the influence of endovascular treatment (EVT) on cognitive outcome in patients with anterior circulation ischemic stroke. Patients presenting with ischemic stroke due to anterior large vessel occlusion who underwent intravenous thrombolysis (IVT) alone or EVT plus IVT were recruited. Cognitive abilities were evaluated at 6 months from stroke through a neuropsychological test battery. A total of 88 patients with a mean age of 66.3 ± 12.9 years were included, of which 38 treated with IVT alone and 50 with IVT plus EVT. Compared to patients treated with IVT alone, patients who received EVT plus IVT performed significantly better at the neuropsychological tests exploring executive functions, attention, abstract reasoning, visuospatial ability, visual and verbal and memory. At multivariable regression analysis, the EVT was independently associated with the 6-month cognitive performance after the adjustment for age, sex, admission National Institutes of Health Stroke Scale score, systolic blood pressure, glucose level, Alberta Stroke Program Early CT score, side of stroke, site of occlusion, and Back Depression Inventory score [Stroop Test Word Reading: adjß = 13.99, 95% confidence interval (CI) 8.47-19.50, p < 0.001; Stroop Test Colour Naming: adjß = 6.63, 95% CI 2.46-10.81, p = 0.002; Trail Making Test-A: adjß = - 92.98, 95% CI - 153.76 to - 32.20, p = 0.003; Trail Making Test-B: adjß = - 181.12, 95% CI - 266.09 to - 96.15; p < 0.001; Digit Span Test Forward: adjß = 1.44, 95% CI 0.77-2.10, p < 0.001; Digit Span Test Backward: adjß = 1.10, 95% CI 0.42-1.77, p = 0.002; Coloured Progressive Matrices: adjß = 5.82, 95% CI 2.71-8.93, p < 0.001; Rey Complex Figure Test-Copy: adjß = 6.02, 95% CI 2.74-9.30, p < 0.001; Rey Complex Figure Test-Immediate recall: adjß = 6.00, 95% CI 2.34-9.66, p = 0.002; Rey Complex Figure Test-Delayed recall: adjß = 5.73, 95% CI 1.95-9.51, p = 0.003; Rey Auditory Verbal Learning Test-Immediate recall: adjß = 12.60, 95% CI 6.69-18.52, p < 0.001; Rey Auditory Verbal Learning Test-Delayed recall: adjß = 1.85, 95% CI 0.24-3.45, p = 0.025]. Patients treated with EVT plus IVT had better cognitive performance than patients treated with IVT alone at 6 months from anterior circulation ischemic stroke.

The P-wave terminal force in embolic strokes of undetermined source.

BACKGROUND: The Embolic Stroke of Undetermined Source (ESUS) is a recently developed clinical construct which describes stroke patients for whom the embolic source remains undetermined despite recommended investigations. The aim of the study was to characterize the ESUS population according to the abnormality in the P-wave terminal force in lead V1 (PTFV1). METHODS: We retrospectively identified consecutive patients hospitalized for acute ischemic stroke who met the ESUS diagnostic criteria. The PTFV1 was obtained from the admission 12-lead ECG. Increased PTFV1 was defined a value >5000µV·ms. Baseline and diagnostic work-up findings were compared between the PTFV1 patient groups. RESULTS: Among 109 patients with ESUS, 31 (28.4%) had evidence of increased PTFV1. The patients with the ECG-defined left atrial abnormality had higher rates of hypertension (77.4% versus 55.1%; p=0.031), history of prior stroke or TIA (35.5% versus 16.7%; p=0.032), and moderate to severe left atrial enlargement (29.0% versus 7.7%; p=0.004) and ventricular hypertrophy (35.5% versus 16.7%; p=0.032), whereas they were less likely to have patent foramen ovale (9.7% versus 28.2%, p=0.038) and unstable sub-stenotic atherosclerosis of aortic arch and cranial arteries (12.9% versus 32.1%, p=0.041). CONCLUSIONS: The abnormally increased PTFV1 was observed in about one third of patients with ESUS and it was inversely associated with artery-to artery and paradoxical potential sources of stroke. Left atrial cardiopathy could be involved in the ESUS pathogenesis and the ECG-defined abnormality could point towards the risk of cardiac embolism.

Persistence to oral disease-modifying therapies in multiple sclerosis patients.

Dimethyl fumarate (DMF), fingolimod (FTY) and teriflunomide (TFN) are oral disease-modifying therapies (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS) whose efficacy and tolerability have been separately assessed in phase III trials. Conversely, little evidence exists about their head-to-head comparison. The aim of the study was to evaluate the 1-year persistence to DMF, FTY and TFN in patients with RRMS. Patients affected by RRMS who started treatment with DMF, FTY or TFN were identified. The study end-point was 12-month drug persistence as time to discontinuation and proportion of patients who discontinued medication within 1-year. A total of 307 patients were included (DMF = 114, FTY = 129, TFN = 64). The mean times to discontinuation were 144 (84), 189 (72) and 138 (120) days in the DMF, FTY and TFN cohorts (p = 0.036). At 12-month, the proportion of patients discontinuing medication was lower for subjects taking FTY (9.8%) compared with those starting DMF (21.9%) and TFN (23.6%) (p = 0.020). Compared to FTY cohort, DMF [adjOR = 3.26 (1.38-7.70); p = 0.007] and TFN [adjOR = 2.89 (1.10-7.63); p = 0.032] treated patients were more likely to have discontinued their drug at 1-year since initiation. In patients with RRMS, FTY was associated with a better persistence profile as compared to DMF and TFN.

Sleep Apnea, Cognitive Profile, and Vascular Changes: An Intriguing Relationship.

BACKGROUND: Sleep breathing disorders can affect cognitive performances through complex brain anatomical and functional changes. OBJECTIVE: Our aim was to evaluate the correlations between cognitive performances and obstructive sleep apnea syndrome (OSAS), as well as the possible influence of vascular factors. METHODS: Thirty-four non-demented OSAS patients and 34 controls were submitted to a neuropsychological evaluation and to a vascular screening including the study of cerebrovascular reactivity by means of the breath-holding index (BHI) calculation. After 6 months, polisomnographic, neuropsychologic, and hemodynamics assessment was repeated in patients. RESULTS: At baseline, some cognitive performances involved in executive and memory functions were significantly lower in patients with respect to controls. Significantly lower values in mean BHI were also detected in patients with respect to controls (p < 0.0001). At the 6-month evaluation, 18 patients had a reduction in OSAS severity (group 1) and 16 remained stable (group 2). Group 1 patients had a significant improvement in left and mean BHI (p < 0.001) and in short-term (p = 0.02) and long-term Rey Auditory Verbal Learning Test (p < 0.001). No change in cerebrovascular reactivity and cognitive profile was detected in group 2 patients. CONCLUSIONS: Patients with OSAS may experience a reduced cognitive efficiency. Improvement of OSAS was associated to favorable hemodynamic changes and increased level of performances in verbal memory tasks so suggesting an involvement of vascular underlying mechanisms in sustaining cognitive dysfunctions in OSAS. Our preliminary data suggest the need for further studies to deepen the knowledge about the relationships between OSAS, cerebral hemodynamic compromise, and cognitive impairment risk.