Impact of Dimethylfumarate on Sleep in Multiple Sclerosis Patients: An Actigraphic Study.

BACKGROUND: Sleep disorders in multiple sclerosis (MS) patients are common. Dimethylfumarate is an oral disease-modifying drug (DMT), whose impact on sleep is unknown. OBJECTIVE: The aim of this study was to characterize actigraphic patterns in MS patients treated with dimethylfumarate. METHODS: Twenty relapsing-remitting MS patients with low to a mild disability, aged 20-50y, treated with dimethylfumarate for more than 6 months, were enrolled. All subjects had no history of sleep disorders. Actigraphy was used to study sleep patterns during a seven-day period. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Twenty healthy subjects served as controls. RESULTS: Our results showed statistically significant differences between some actigraphic patterns in MS patients treated with dimethylfumarate and healthy subjects, but the values for patients were still within normal limits. PSQI score was higher in MS patients compared to controls. CONCLUSION: Our findings suggest that dimethylfumarate, an oral DMT with a favourable benefit-risk profile, does not strongly alter sleep patterns in MS patients with low to mild disability and with no history of sleep disorders. Actigraphy is a simple diagnostic tool, able to support an objective measure of sleep parameters. The simplicity of application may allow considering its use for a screening of sleep disorders in MS patients.

Efficacy of Onabotulinum Toxin A on Obsessive-Compulsive Traits in a Population of Chronic Migraine Patients.

BACKGROUND: Drug addiction may play an important role in chronic migraine (CM) with medication-overuse headache (MOH). Psychiatric diseases are associated with CM, but data regarding obsessive-compulsive disorder (OCD) are lacking. We aimed to establish the prevalence of OCD traits in CM patients with MOH and the impact on onabotulinum toxin A (OBT-A) treatment. METHODS: A total of 75 patients with CM and MOH undergoing treatment with OBT-A in our Headache Centre were evaluated. At baseline and after four injection sessions, we assessed the migraine burden and the presence of OCD traits with the Obsessive-Compulsive Inventory-Revised (OCI-R) test. RESULTS: At baseline, 28% of patients had OCI-R scores compatible with borderline OCD aspects, while 22.7% were pathological. An improvement in headache was significantly associated with an increase in the number of subjects with a normal OCI-R score at T0 and T1, whereas patients with a pathological OCI-R score at T0 showed a significantly higher prevalence of CM at T1. CONCLUSIONS: Our data showed a significant rate of OCD traits at baseline, which could strengthen the hypothesis of an addictive disorder underlying CM with MOH. OCD traits seem to influence the OBT-A response. An OCD assessment could be useful in improving patients' selections before starting treatments.

Gender differences in obsessive-compulsive disorder traits among chronic migraine patients.

BACKGROUND: Psychiatric illnesses are often associated with severe forms of headache as chronic migraine (CM) with medication overuse headaches (MOH). Few data are available about obsessive-compulsive disorders (OCD) in migraineurs. This study aimed to investigate OCD traits in CM with MOH patients of both sexes and the impact on migraine treatment. METHODS: We enrolled all consecutive patients with CM and MOH treated with onabotulinumtoxin-A (OBT-A) in our Headache Center. Each subject was submitted to the Obsessive-Compulsive Inventory-Revised (OCI-R) test at the start (T0) and after four OBT-A sessions (T1). Statistical analysis compared OCI-R results at T0 and T1 according to sex with the chi-square test. RESULTS: We analyzed a sample of 60 subjects (40 females, 66.7%). At T0, 25% of males and 37.5% of females had a normal profile while 60% of males and 22.5% of females presented pathologic OCD traits. At T1, 30% of males and 60% of females were normal, while 40% of males and 15% of females resulted frankly pathologic. The difference in the OCI-R distribution was significant at T0 (p = 0.024) and at T1 (p = 0.047). Both males and females underwent a significant increase in normalization rates at T1 (p < 0.05). CONCLUSION: We observed a significant OCD traits rate at baseline, moreover among men. Females showed a more significant improvement in OCD traits at T1. OBT-A confirmed its high efficacy on CM, with a migraine severity improvement in both genders and all the OCI-R classes. Psychological attitude in the management of migraine should be better investigated in future studies.

Efficacy and safety of reperfusion treatments in middle-old and oldest-old stroke patients.

INTRODUCTION: Intravenous thrombolysis (IT) and mechanical thrombectomy (MT) have significantly changed the clinical outcome of acute ischaemic stroke (AIS). Concerns about possible complications often reduce the use of these treatment options for older patients, preferentially managed with antiplatelet therapy (AT). Aim of this study was to evaluate, in a population of middle-old (75-84 years) and oldest-old (≥ 85 years) subjects, the efficacy and safety of different treatments for AIS (IT, IT + MT, MT or AT), mortality and incidence of serious complications. PATIENTS AND METHODS: All patients aged over 75 years admitted for AIS in two Stroke Units were enrolled. The physician in each case considered all treatment options and chose the best approach. NIHSS and modified Rankin Scale (mRS) were obtained and differences between admission and discharge scores, defined as delta(NIHSS) and delta(mRS), were calculated. The relationship between delta(NIHSS), delta(mRS) and type of procedure was analysed with a GLM/Multivariate model. Differences in mortality and incidence of serious complications were analysed with the chi-square test. RESULTS: A total of 273 patients, mean age 84.07 (± 5.47) years, were included. The Delta(NIHSS) was significantly lower in patients treated with AT than in those treated with IT and MT (p < 0.009 and p < 0.005, respectively). Haemorrhagic infarction occurrence was significantly lower (p < 0.0001) among patients treated with AT (10.6%) or IT (16.7%) compared to MT (34.9%) or MT + IT (37.0%). No significant difference was observed for in-hospital mortality. Age did not influence the outcome. CONCLUSIONS: Our results suggest that IT and AT are effective and relatively safe approaches in middle-aged and older patients.

Inflammation markers in moderate and severe obstructive sleep apnea: the influence of sex.

PURPOSE: Obstructive sleep apnea (OSA) is the most prevalent sleep-related breathing disorder, with a negative impact on cardiovascular health. Different OSA symptoms and treatment response in males and females have been reported. The aim of this study was to investigate inflammatory markers in patients with OSA and the relationship of those markers to disease severity in male and female subjects. METHODS: We considered consecutive subjects referred to the outpatient Sleep Disorder Service of the Respiratory Medicine Department, San Marino Hospital. We included patients with a diagnosis of moderate or severe OSAS and an age range of 45-80 years. Concomitant inflammatory conditions were an exclusion criterion. A polygraphic study and a blood draw for inflammatory markers were performed for each subject. RESULTS: Of 110 subjects, 59 were males. Severe OSA affected 72 subjects. We analyzed data through a 4-level categorical variable according to sex and OSA severity (moderate OSA, males; severe OSA, males; moderate OSA, females; severe OSA, females), which showed significant differences for interleukin-6 (IL-6) and C-reactive protein (CRP) levels. A significant difference in IL-6 levels with a significant ascending trend (p = 0.045) from females with moderate OSAS to males with severe OSAS emerged in our pairwise comparison for estimated marginal means. Also, a significant trend (p = 0.0001) for CRP levels from males with moderate OSAS to females with severe OSAS was shown. CONCLUSIONS: OSA and inflammation are interconnected, and both are associated with vascular diseases. Sex-related differences in OSA phenotypes may help the clinicians aim for a more personalized approach.

Ischemic stroke as a presenting manifestation of polycythemia vera: a narrative review.

Polycythemia vera (PV) is a myeloproliferative disorder associated with an increased risk of cerebrovascular diseases. In this narrative review, we aimed to analyze the relationships between acute ischemic stroke and PV. We conducted a PubMed/Medline and Web of Sciences Database search using MeSH major terms. We found 75 articles and finally considered 12 case reports and 11 cohort studies. The ischemic stroke resulted as the first manifestation of PV in up to 16.2% of cases; the cumulative rate of cerebrovascular events was up to 5.5 per 100 persons per year and stroke accounted for 8.8% of all PV-related deaths; age, mutations, and a previous history of thrombosis were the main risk factors. The best approach to reduce stroke recurrence risk is unclear, even if some evidence suggests a potential role of lowering hematocrit below 45%. Ischemic stroke represents one of the most common PV manifestations but, despite their relationship, patients with both diseases have a very heterogeneous clinical course and management. PV-related strokes often remain underdiagnosed, especially for the low prevalence of PV. An early diagnosis could lead to prompt treatment with phlebotomy, cytoreduction, and low-dose aspirin to decrease the risk of recurrences. Clinicians should be aware of PV as a risk factor for stroke when approaching the differential diagnosis of cryptogenic strokes. An early diagnosis could positively influence patients' management and clinical outcomes. Further studies are required to evaluate the role of PV treatments in the prevention of cerebrovascular disease.

Sex-Related Differences in Polygraphic Parameters in a Population of Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Sex-related differences in the prevalence and clinical presentation of Obstructive Sleep Apnea Syndrome (OSAS) have been widely documented. The aim of this study was to investigate the influence of patients' sex on polygraphic parameters with particular attention to sleep autonomic changes in a population of OSAS patients. METHODS: Sixty OSAS patients aged 55-65 years (30 men, 30 women) were enrolled. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and daytime sleepiness with the Epworth Sleepiness Scale (ESS). The presence of respiratory events and autonomic changes during the night was investigated by polygraphy. RESULTS: Similar main cardiovascular risk factors prevalence was observed in both men and women. We observed a significant difference in PSQI (higher in women, p=0.0001) and ESS (higher in men, p=0.004) scores. Snoring (p=0.033), supine AHI (p=0.004), T90 (p=0.021), LO2 (p=0.0001), LF/HF ratio and LF (p=0.0001) were significantly higher in men. Sex differences in PSQI mean score and LF/HF ratio variability were preserved in all the subgroups of OSA severity. CONCLUSION: The influence of sex in modulating cardiovascular risk is a widely discussed topic. In our study, men showed more severe polygraphic parameters and an increase in LF/HF ratio compared to women. The results of our investigation suggest the relevance of delivering information about the different expressions of OSAS in men and women in order to improve diagnostic skills and in-depth prevention approaches.

Headache changes after kidney transplant.

Headache is considered as a possible complication of dialytic treatment in chronic kidney disease (CKD). The aim of this study was to evaluate possible change in headache characteristics after kidney transplantation in patients with CKD. During a 1-year period, we enrolled 110 subjects submitted to a kidney transplant in the previous 5 years. Headache characteristics before and after the transplant were investigated by a specific questionnaire. Possible effects of pharmacological therapies were also evaluated. 65.5% of patients complained of headache before the transplant (38.2% migraine and 14.5% dialysis headache). After transplant, 53.6% of patients reported changes in headache characteristics. In particular, 27.3% of the patients had a complete resolution, 19.1% presented a headache improvement and 7.2% showed a worsening. In both migraine and dialysis headache subgroups, steroids, beta-blockers and calcium channel blockers were associated with a significant improvement of headache. Kidney transplantation seems to impact significantly headache frequency and severity in patients with CKD. A careful evaluation and use of targeted treatments could improve both patients' compliance to therapies and quality of life.

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.

Carotid occlusion: Impact of cerebral hemodynamic impairment on cognitive performances.

OBJECTIVES: The aim of this study was to investigate whether the presence of carotid artery occlusion (CO) may be associated with different cognitive performances in relation to the side of the occlusion and its hemodynamic consequences. METHODS: During a 12-month period, 61 asymptomatic patients, 32 with right and 29 with left CO, were enrolled. Each patient underwent an assessment of cerebrovascular reactivity (CVR) to hypercapnia with transcranial Doppler (TCD) ultrasonography using the breath-holding index (BHI). Neuropsychological assessment evaluating performances of the hemisphere ipsilateral to CO were administered at entry (T0 ) and then repeated after 2 years (T1 ). RESULTS: Scores obtained at colored progressive matrices (CPM) and Rey Complex Figure Copy Test were significantly lower at T0 in patients with reduced BHI values ipsilateral to CO. Multivariate models showed that reduced BHI values were also associated to a significant decrease from T0 to T1 in scores obtained for CPM and Categorical Verbal Fluency tests, respectively, in patients with right (P = 0.002) or left CO (P = 0.004). CONCLUSIONS: These findings suggest that hemodynamic alterations could be involved in the reduction in cognitive function regulated by the hemisphere ipsilateral to CO. The assessment of CVR with TCD ultrasonography may be a reliable approach for the individuation of asymptomatic patients with CO at increased risk of cognitive deterioration.

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.

Atrial Fibrillation on Patients with Vascular Dementia: A Fundamental Target for Correct Management.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for cerebrovascular diseases and vascular dementia (VAD). The aim of this study was to evaluate the effect of the adherence to anticoagulant therapy guidelines in patients with dementia and AF on the risk of stroke/TIA or major bleeding (MB). METHODS: In a cohort of 1705 hospitalized patients with pre-existent AF, we observed 193 patients with vascular dementia (VAD). Non-demented AF patients were included as controls. For each subject, we calculated CHA2DS2-VASc, CHADS2, and HAS-BLED scores, and collected information regarding anticoagulant therapy, in-hospital therapeutic failure (TF) occurrence, stroke/TIA, and MB. RESULTS: According to CHA2DS2-VASc and CHADS2 scores, 99.5% of VAD patients had the indication to anticoagulant treatment, but only 69.9% were correctly treated. During hospitalization, MB occurred in 4.66% of VAD and 8.9% of non-demented patients (p = 0.048). In-hospital stroke/TIA were observed in 24.3% of VAD and 0.8% of non-demented patients (p = 0.0001). A similar proportion of TF among patients with VAD and with normal cognition (12.9% vs. 11.2%) was observed. CONCLUSION: In our cohort, we observed that VAD patients with pre-existent AF were undertreated despite a higher risk of stroke/TIA with respect to non-demented patients.

Sex influence in ischemic stroke severity and outcome among metabolically unhealthy overweight patients.

INTRODUCTION: The role of metabolically unhealthy (MU) overweight in influencing stroke prognosis has not been fully assessed and conclusive data about the impact of sex are lacking. Aim of this study was to evaluate the possible correlations among MU overweight, sex and ischemic stroke severity and outcome. METHODS: All consecutive patients with acute non-lacunar ischemic stroke observed over a one-year period were considered. MU subjects were selected and classified according to the body mass index (BMI) values. The relationships among sex, BMI and National Institutes of Health Stroke Scale (NIHSS) score at admission and modified Rankin scale (mRS) score at discharge were analysed with multivariate models. RESULTS: 180 patients were included. A significantly increasing trend in the NIHSS (p = .030) and in the mRS (p = .001) scores along with the increase of the BMI category was detected in women. Men showed a significantly decreasing trend in the NIHSS (p = .040) and a non-significant decreasing trend in the mRS (p = .290) scores with increasing BMI category. CONCLUSIONS: Our findings show that sex can influence stroke severity and outcome among MU patients. The worse outcome observed in women suggest the need of considering differential sex-based clinical approaches in stroke overweight patients.

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.

Predictors of cognitive functioning after carotid revascularization.

PURPOSE: High-grade carotid stenosis can affect cognition, but the relationship between stenosis correction and cognitive outcome is not fully understood, yet. The aim of this study was to evaluate the predictors of post-operative neurocognitive functioning in patients with symptomatic severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). MATERIALS AND METHODS: Patients with history of transient ischemic attack within the past 6 months and ipsilateral high-grade stenosis of ICA undergoing CEA were prospectively enrolled. Cerebral hemodynamics was assessed by means of the cerebral vasomotor reactivity (CVR) to hypercapnia measured through transcranial Doppler ultrasonography. Coloured Progressive Matrices plus Complex Figure Copy Test, and phonemic plus categorical (ca) Verbal Fluency tests were performed to assess right and left hemisphere cognitive functions, respectively. Cerebral hemodynamics and cognitive functions were assessed before and 6 months after CEA. RESULTS: One hundred and eighty-one patients were included. The mean age was 73.2 (6.9) years and 121 (66.9%) were males. At 6 months from CEA, the scores obtained in the cognitive tests exploring the re-vascularized hemisphere's functions and ipsilateral cerebral hemodynamics were improved. At multivariate linear regression analysis, the 6-month change in cognitive performance was inversely associated with age [ß = -0.17, 95% confidence interval (CI) -0.22 to -0.12; p < .001] and CVR value obtained before CEA on the side of ICA stenosis (ß = -6.25, 95% CI -7.40 to -5.10; p < .001). CONCLUSIONS: In patients with symptomatic high-grade ICA stenosis, age and cerebral hemodynamic status before CEA predicted the neurocognitive performance changes after surgical stenosis correction.

Influence of chronotype on migraine characteristics.

BACKGROUND: The aim of this study was to investigate chronotype in migraine patients and possible influences on the clinical expression of the disease. METHODS: During a one-year period, all consecutive patients admitted to two third-level headache centres with a new diagnosis of migraine were enrolled in a cross-sectional study. All subjects were submitted to the Morningness-Eveningness Questionnaire (MEQ-SA) and then classified in five different categories, from late to early-rising chronotype. Differences and trends among MEQ-SA categories and years from migraine onset, attacks' intensity and frequency were analysed first with analysis of variance, then with a multivariate/generalized linear model. RESULTS: One hundred seventy one migraine patients were included. Early-rising patients showed a lower migraine attacks frequency and longer disease duration with respect to late-rising patients. The categorical variable containing the five circadian types was able to identify a significantly different trend both for the monthly attacks frequency and for the disease duration (p < 0.0001 and p < 0.0001, respectively, analysis of variance). The results were also confirmed after correction for main influencing variables (multivariate/generalized linear model). The intensity of migraine attacks was not influenced by chronotype. CONCLUSIONS: According to the results of the present study, chronotype seems to influence number and duration of migraine attacks. Although sleep-wake cycle is a well-recognized factor able to influence thalamic-cortical synchronization, it usually does not receive appropriate consideration during migraine patients' assessment.