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.

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.

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.

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.

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.

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.

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.

From head to toe: Sex and gender differences in the treatment of ischemic cerebral disease.

Stroke is a major cause of mortality and morbidity, particularly in the older ages. Women have a longer life expectancy and are more likely to experience stroke than men. Interestingly, the increased risk of ischemic stroke in women seems to be independent from age or classical cardiovascular risk factors. Notwithstanding the fact that stroke outcomes and survival are usually poorer in women, current evidence suggests that thrombolysis, antiplatelet and anticoagulant therapies are more beneficial in women than in men. A possible explanation of this paradox might be that females are often undertreated and they have fewer chances to be submitted to an effective and timely treatment for stroke than the male counterpart. The first step in the attempt to solve this obvious discrimination is surely to emphasize any reasons for differences in the therapeutic approach in relation to gender and then to denounce the lack of a sustainable motivation for them. In this article, we aimed to review the existing literature about gender-related differences on efficacy, administration and side effects of the most common drugs used for the treatment of ischemic stroke. The most striking result was the evidence that the therapeutic approach for stroke is often different according to patients' gender with a clear detrimental prognostic effect for women. A major effort is necessary to overcome this problem in order to ensure equal right to treatment without any sexual discrimination.

Raven coloured progressive matrices in migraine without aura patients.

Conflicting results emerged from studies investigating cognitive performances in migraine patients. Based on clinical and neuroradiological aspects, the possible involvement of executive functions has been especially taken into consideration. The aim of this study was to evaluate, in a population of subjects affected by migraine without aura (MwoA), frontal lobe cognitive functions. We enrolled all the consecutive patients affected by MwoA referred to our headache centre for a first evaluation. Each patient underwent a neuropsychological evaluation including Raven coloured progressive matrices (CPM). We collected variables as age, education, years of migraine, frequency of attacks and CPM scores. Relationship between continuous variables was explored with multiple regression lines, selecting the best-fitting trendline for each relationship. We obtained a final sample of 36 subjects (females: 62.5%; mean age: 42.25 ± 10.21 years). Patients had mean length of migraine history of 12.25 ± 11.00 years and a mean frequency of attacks of 8.06 ± 7.15 per month. Linear regression underlines a progressive decrease of CPM score with the increase of the migraine history's length (R 2 = 0.8871; p < 0.001), and the frequency of migraine attacks (R 2 = 0.3122; p < 0.05). Our findings suggest that pathological CPM scores can be associated with the severity of migraine. These data seem to confirm the hypothesis of an impairment of executive functions in MwoA. Different hypotheses to explain cognitive impairment in migraine have been postulated including the impact of the typical white matter lesions and a long history of drug abuse. The possible relevant clinical consequence of a full comprehension of this particular aspect related to migraine deserves further attention and consideration.

Charlson comorbidity index as a predictor of in-hospital death in acute ischemic stroke among very old patients: a single-cohort perspective study.

Chronic diseases are increasing worldwide. Association of two or more chronic conditions is related with poor health status and reduced life expectancy, particularly among elderly patients. Comorbidities represent a risk factor for adverse events in several critical illnesses. We aimed to evaluate if elderly patients are affected by multiple chronic pathologies, assessed by Charlson comorbidity index (CCI), showed a reduced in-hospital survival after ischemic stroke. In a 3-year period, we evaluated all the subjects admitted to our internal medicine department for ischemic stroke. Age, sex, NIHSS score and all the comorbidities were recorded. Days of hospitalization, hospital-related infections and in-hospital mortality were also assessed. For each patient, we evaluated CCI, obtaining four classes: group 1 (CCI: 2-3), group 2 (CCI: 4-5), group 3 (CCI: 6-7) and group 4 (CCI: ≥8). Survival was evaluated with Kaplan-Meier and Cox regression analyses. The complete model considered in-hospital death as the main outcome, days of hospitalization as the time variable and CCI as the main predictor, adjusting for NIHSS, sex and nosocomial infections. Patients in CCI group 3 and 4 had an increased risk of in-hospital mortality, independently of NIHSS, sex and nosocomial infections. Elderly patients with multiple comorbidities have higher risk of in-hospital death when affected by ischemic stroke.

Acute Occlusion of the Percheron Artery during Pregnancy: A Case Report and a Review of the Literature.

OBJECTIVES: The Percheron artery (PA) is a rare variant vessel. Its acute occlusion can cause a bilateral symmetrical thalamic stroke, clinically manifested as a sudden alteration of consciousness that could vary from sleepiness to coma. In this paper, we illustrate a case of acute PA occlusion in a young, pregnant woman and present a review of the literature, focusing on the possible causes of the acute occlusion. METHODS: A 35-year-old woman, at the fourth week of pregnancy, came to the emergency department of our hospital because of a sudden onset and persistent loss of consciousness. Brain magnetic resonance imaging (MRI) showed a symmetrical and bilateral thalamic infarction without evidence of other ischemic lesions, compatible with an acute PA occlusion. RESULTS: The patient, who showed full clinical recovery within a few hours of symptom onset, received a short-term anticoagulant treatment followed by aspirin for long-term prevention. CONCLUSIONS: We reviewed the literature about the possible causes of acute PA occlusion. This ischemic condition is usually associated with cardioembolic or small-vessel disease. However, in our patient, we did not find any element supportive for coagulative alteration or embolyzing conditions. PRACTICE: The presence of this type of thalamic stroke should be considered in the management of persistent loss of consciousness. PA occlusion is rare, but it needs a brain MRI examination for a correct diagnosis, a narrow evaluation of all the possible causes, and a long-term anticoagulant therapy. Pregnancy itself should constitute a rare but possible cause of a PA occlusion.

Metabolic syndrome and cerebrovascular impairment in Alzheimer's disease.

OBJECTIVE: Metabolic Syndrome (MeS) has inconstantly been associated with cognitive impairment. The aim of this study was to investigate the influence of MeS on cerebrovascular reactivity and the possible consequences on cognitive impairment in patients with Alzheimer's disease (AD). METHODS: A total of 162 AD patients were enrolled and grouped depending on the presence/absence of MeS. An ultrasound assessment of the neck vessels was performed to evaluate common carotid artery intima-media thickness (IMT). Cerebral hemodynamics was assessed by the transcranial Doppler-based breath-holding index (BHI) test. The relationship between BHI and MeS was explored first with a nested binary logistic model and then with a general linear model/adjusted model. Both models were corrected for sex, age, education, BMI, smoking attitude, and IMT treated as covariates. RESULTS: Pathologic BHI values were significantly more frequent among patients with MeS (risk ratio (RR):1.477; 95% CI: 1.177-1.848). MeS significantly improved the prediction of a pathologic BHI in the binary logistic model (odds ratio (OR):11.64; 95% CI: 1.001-135.304; p < 0.05). Moreover, AD patients affected by MeS had significantly lower mean Mini-Mental State Evaluation values than the unaffected ones (16.06; 95% CI: 14.96-17.15 vs 17.79; 95% CI: 17.05-18.53; p < 0.0001). CONCLUSIONS: Our data show an association between the presence of MeS and cerebral hemodynamics. The possibility that a cluster of potentially treatable vascular risk factors may influence AD patients' prognosis deserves consideration.

Cognitive deterioration in bilateral asymptomatic severe carotid stenosis.

BACKGROUND AND PURPOSE: This study aimed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. METHODS: One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile, and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler-based breath-holding index test. As a measure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. RESULTS: The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bilaterally abnormal breath-holding index (P<0.0001). Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change. CONCLUSIONS: Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments.

Visit-to-visit blood pressure variability in Alzheimer disease.

The aim of this study was to evaluate visit-to-visit blood pressure (BP) variability in a cohort of patients with Alzheimer disease (AD) and healthy controls. Patients with clinically diagnosed mild or moderate AD and cognitively normal controls matched for age and sex were recruited and followed up for 6 months. To characterize the BP status of each individual, mean, maximum and minimum values, SD, and coefficient of variation were obtained for both systolic BP (SBP) and diastolic BP (DBP). Seventy AD patients and 140 controls were enrolled. No meaningful differences were found in prevalence or treatments of various vascular risk factors. AD patients had higher maximum and lower minimum values and greater SD and coefficient of variation of both SBP and DBP. Group differences in mean values were significant only for SBP. In the multiple logistic regression analysis, adjusted for confounding variables, all the indices related to BP variability were significantly associated with AD. Our results show that AD patients have a greater variability of both SBP and DBP in comparison with age-matched cognitive normal controls, suggesting potential implication in the pathogenesis or progression of the disease.

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.

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.