The organisation of the acute ischemic stroke management: key notes of the Italian Neurological Society and of the Italian Stroke Organization.

The main aim of acute ischemic stroke treatment is the as much possible prompt, safe and effective arterial recanalisation, in order to restore reperfusion into the ischemic brain area. The procedures obtaining this result are rapidly evolving and in the last years, we observed new evidences that affirmed the therapeutical benefit of the concomitant treatment using endovenous thrombolysis and mechanical thrombectomy in selected patients with ischemic stroke. However, all treatments are time-sensitive and the main limitation for their application is represented by the time. For this reason, the optimisation of the acute stroke management that includes a pre-hospital and an in-hospital phase is essential to reduce the avoidable delay, increasing the number of patients potentially treatable. The purpose of this document is to define the main elements and to suggest the principal key points constituting the optimal pathway of stroke management in Italian care settings, in line with the recommendations coming from the current national and international guidelines.

Declining incidence of intracerebral hemorrhage over two decades in a population-based study.

BACKGROUND AND PURPOSE: The incidence and case-fatality rate (CFR) of primary intracerebral hemorrhage (PICH) over two decades were assessed in a prospective population-based study. METHODS: Cases of incident first-ever PICH were recorded over a 2-year period (2011-2012) from multiple sources in the district of L'Aquila, central Italy. Included patients were followed up to 1 year after the event to ascertain CFRs. Current data were compared with those previously collected from 1994 through 1998. RESULTS: In all, 115 patients (52 men; 45.2%) with a first-ever PICH were included. Mean age ± SD was 77.4 ± 11.8 years. The hemorrhage was lobar in 43 (37.4%) patients, deep in 56 (48.7%), in the posterior fossa in 11 (9.6%) and intraventricular or multiple localized in five (4.3%). Crude annual incidence rate was 19.3 per 100 000 and 14.8 per 100 000 when standardized to the 2011 European population, indicating a 48% reduction comparing data of 2011-2012 to those of 1994-1998 (incidence rate ratio 0.52; 95% confidence interval 0.43-0.64; P < 0.001). In 2011-2012, the 7-day CFR was 27.8%, the 30-day CFR was 42.6% and the 1-year CFR was 52.2%; the 1-year standardized mortality ratio was 0.81 (95% confidence interval 0.63-1.04) compared with 1994-1998. CONCLUSIONS: The annual incidence rate of PICH was lower than that found two decades before and close to the rates recently found in other western countries. Data also indicated a non-significant trend towards a decrease in mortality, which nonetheless remained high, pointing to the need for more appropriate treatments in order to reduce PICH severity and mortality.

Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis.

Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan-Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

Migraine and risk of ischaemic heart disease: a systematic review and meta-analysis of observational studies.

BACKGROUND AND PURPOSE: Several studies have assessed the risk of ischaemic heart diseases in migraineurs, drawing different conclusions. To define and update the issue, a systematic review and meta-analysis of the available observational studies was performed. METHODS: PubMed and EMBASE were systematically searched up to April 2014 for observational studies dealing with the risk of any form of ischaemic heart disease in migraineurs. Studies assessing migraine as exposure and several types of ischaemic heart disease as outcomes were included in the analysis. A random effects model was used to pool the effect sizes. RESULTS: Out of 3348 records, 15 studies (one case-control, one cross-sectional and 13 cohort studies) were identified and were included in the meta-analysis. The pooled analysis indicated an increased risk of myocardial infarction (pooled adjusted effect estimate 1.33, 95% confidence interval 1.08-1.64; P = 0.007) and of angina (pooled adjusted effect estimate 1.29, 95% confidence interval 1.17-1.43; P < 0.0001) in migraineurs compared to non-migraineurs. CONCLUSIONS: Based on our data indicating an association of migraine with myocardial infarction and angina and on previous data showing an association of migraine, and particularly migraine with aura, with an increased risk for stroke, migraine can be appropriately considered an overall risk factor for cardiovascular diseases.

Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68%; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93%; the proportion of patients free from combined clinical activity was 65%; the proportion of patients free from MRI activity was 77%; and the proportion of patients free from any disease activity was 53%. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Insulin resistance in migraineurs: results from a case-control study.

OBJECTIVES: Several studies have suggested an association between migraine and insulin resistance (IR) without adequately addressing the issue according to migraine type. We assessed IR in subjects with migraine with aura (MwA) and migraine without aura (MwoA) to estimate the consistency of the possible association. METHODS: In a case-control study we included case subjects with MwA and MwoA, who were consecutively selected from those referred to our Regional Headache Center from September 2011 to February 2013, and age-matched control subjects selected using general practitioners' databases. IR was calculated by means of the homeostatic model assessment of IR (HOMA-IR), ß-cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) measuring glucose and insulin values in a blood sample collected in the morning after overnight fasting. Data regarding anthropometric measures, comorbidity risk factors, and migraine characteristics were also recorded. RESULTS: We recruited 50 case subjects with MwA (38 women) and 50 with MwoA (40 women) and 50 control subjects (40 women). Proportions of arterial hypertension, cigarette smoking, hypercholesterolemia, use of oral contraceptives, and mean values of the body mass index (BMI) were similar in the three groups. We found significantly different glucose values among and within groups considering case subjects with MwA and MwoA and control subjects (4.9 ± 0.6 vs 4.7 ± 0.5 vs 4.6 ± 0.5 mmol/l; P = 0.018) in the absence of any difference in insulin (53.1 ± 24.0 vs 56.7 ± 34.4 vs 53.8 ± 24.4 pmol/l; P = 0.811), HOMA-IR (1.6 ± 0.8 vs 1.7 ± 1.0 vs 1.6 ± 0.7; P = 0.765), HOMA-B (121.4 ± 71.1 vs 149.2 ± 93.8 vs 162.8 ± 109.7; P = 0.107), and QUICKI (0.36 ± 0.03 vs 0.37 ± 0.03 vs 0.37 ± 0.03; P = 0.877) values. The logistic regression model showed increased odds of MwA in subjects exposed to the highest tertile of glucose values. This association was confirmed in the adjusted model, in which case subjects with MwA were compared with those with MwoA but not with control subjects. CONCLUSIONS: In contrast to what has been shown by the majority of the available studies, the results of our study do not support the association of migraine with IR. As our study was not population-based and several patients had low disease activity, these findings need further confirmation.

Ascertainment bias in dementias: a secondary to tertiary centre analysis in Central Italy and conceptual review.

BACKGROUND AND AIMS: Ascertainment bias (AB) indicates a bias of an evaluation centre in estimating the prevalence/incidence of a disease due to the specific expertise of the centre. The aim of our study was to evaluate classification of different types of dementia in new cases appearing in secondary and tertiary centres, in order to evidence possible occurrence of AB in the various (secondary to tertiary) dementia centres. METHODS: To assess the mechanism of AB, the rates of new cases of the different forms of dementia reported by different centres were compared. The centres involved in the study were 11 hospital-based centres including a tertiary centre, located in the University Department of Clinical Neurology. The tertiary centre is endowed with state-of-the-art diagnostic facilities and its scientific production is prominently focused on dementia with Lewy bodies (DLB) thus suggesting the possible occurrence of a bias. Four main categories of dementia were identified: Alzheimer's disease (AD), DLB, fronto-temporal dementia (FTD), vascular dementia (VaD), with other forms in a category apart. The classification rate of new cases of dementia in the tertiary centre was compared with rates reported by secondary centres and rates of recoding were calculated during a follow-up of 2 years. RESULTS: The study classified 2,042 newly diagnosed cases of dementia in a population of 1,370,000 inhabitants of which 315,000 were older than 65. AD was categorized in 48-52 % of cases, DLB in 25-28 %, FTD in 2-4 % and VaD in 17-28 %. During the 2-year follow-up the diagnosis was re-classified in 40 patients (3 %). The rate of recoding was 5 % in the tertiary centre, 2-8 % in referrals from secondary to tertiary centre, 2-10 % in recodings performed in secondary centres and addressed to tertiary centre. Recoding or percentages of new cases of AD or DLB were not different in the comparison between secondary or between secondary and tertiary centres. FTD and VaD were instead significantly recoded. CONCLUSION: The results of the study suggest that in a homogeneous area, AB is not interfering with diagnosis of AD or DLB.

Effectiveness of intensive neurorehabilitation in patients with Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and behavioral impairments that differ in their presentation and progression across subjects. Studies validating the effectiveness of intensive neurorehabilitation such as a strategy to reducing functional impairments and to improving motor capacities in HD patients are limited and heterogeneous. AIM: To design and test an intensive multifunctional neurorehabilitative protocol in symptomatic patients with HD in the attempt to limit the progression of neurological deficits and to preserve and maintain independence in the activities of daily living. DESIGN: Case series. SETTING: Rehabilitation nursing home. POPULATION: Thirty-four patients (12 men and 22 women) with HD. METHODS: Three-week in-hospital intensive multifunctional neurorehabilitation. The evaluation of patients was performed before and at the end of the 3-week neurorehabilitative treatment by the Barthel Index (BI) and the Total Functional Capacity Scale (TFCS) assessing independence in the activities of daily living, by the Physical Performance Test (PPT) assessing motor performances on functional tasks, and by the Tinetti Scale (TS) assessing balance and gait. A telephone follow-up interview evaluating individual autonomy by the BI was scheduled 3 months after discharge in order to evaluate the short-term results. RESULTS: We found a significant increase (P<0.001) of the mean scores of BI, TS, PPT and TFCS in all patients at the end of the 3-week in-hospital intensive multifunctional neurorehabilitation with respect to the score values obtained before rehabilitative treatment. The differences of BI, TS, PPT and TFCS scores (Δ scores) observed in HD patients assuming tetrabenazine and in patients not assuming the drug, before and after rehabilitation, were not statistically different. The improvement in independence in the activities of daily living evaluated by BI vanished 3 months after discharge (P<0.05). CONCLUSION: Rehabilitative treatment in HD patients needs to be multifunctional and continuous to improve or maintain motor performances and functional independence. CLINICAL REHABILITATION IMPACT: Despite Huntington's disease is a progressive and incurable disease intensive neurorehabilitation lessens patients' disability and improves their quality of life ameliorating autonomy and delaying the progression of motor dysfunction.

Soluble CD30: a biomarker for evaluating the clinical risk versus benefit of IFNbeta1A treatment in multiple sclerosis patients.

Aberrant redox regulation occurs in immune and neurological pathologies, hence targeting the pathways involved in the regulation of the redox system could provide further insights into these diseases and open up new avenues for therapy. Soluble (s) CD30 is of key clinical importance in this respect, as its levels reflect the functionality of the CD30 receptor (CD30R), the specific lymphocyte receptor for thiol disulfide/oxidoreductase thioredoxin 1 (Trx1) which is known to regulate important immune and neurological processes. Increased levels of sCD30 appear to be a common element of oxidative stress, immunological alterations and neurological deficit, therefore these increases could be used as a clinical biomarker and target for therapy. We targeted sCD30 in our study of dendritic cell (DC) regulation of the T helper (Th) cell network in multiple sclerosis (MS) patients, as abnormalities in T regulatory (Treg)/Th1/Th17 pathways contribute to the pathogenesis of this immunological/neurological disease. DC profiles in Treg/Th1/Th2/Th17-types of cytokine production in culture supernatants were used as they determine the type of Th differentiation. Our results show that sCD30 levels increase significantly in MS patients, reflecting the disruption in the regulation of the Treg/Th1/Th17 cell network. A fall in the level of soluble CD30, induced by IFNbeta1a therapy, opposed the increase of neurological deficit through increasing IL10 and TGFbeta levels, thus re-establishing network homeostasis but only when this was accompanied by an increase in IL12p70 levels. Since IL12p70 cytokine production is regulated by Trx1, our results indicate that redox system alterations may be the cause of IFNbeta1a therapeutic inefficacy. We conclude that an increase in the level of IL10, TGFbeta and IL12p70 and a fall in the level of sCD30 represent a means of evaluating the clinical risk/benefit of IFNbeta1a treatment.

Gender and stroke: acute phase treatment and prevention.

Stroke is the third most common cause of death in women and a major cause of disability. Many aspects of stroke are similar in men and women, including clinical presentation, main risk factors, and distribution of the main subtypes. There are, however, some gender differences and specificities in stroke including some aspects related to treatment. Women are less likely to receive thrombolysis than men; however, in treated cases, the efficacy of intravenous thrombolysis is higher in women than in men. Hormone replacement therapy has been suggested as a possible strategy to reduce the occurrence of stroke in postmenopausal women but several clinical trials failed to show any benefit in stroke and cardiovascular disease prevention. Also in stroke prevention with antiplatelets there emerge some important gender differences: in primary prevention of stroke, aspirin was effective in women but not in men while in secondary prevention no gender differences were found with any of the available antiplatelet agents.

Relationship between biofeedback and oxidative stress in patients with chronic migraine.

Chronic migraine (1.5.1) is burdened with headache-related disability. During noxious stimulation, changes of cerebral blood flow enhance the release of oxygen free radicals that react with nitric oxide (NO). We investigated the role of biofeedback in limiting migraine disability by influencing oxidative stress. Peroxides, NO and superoxide dismutase (SOD) were analysed in 20 female subjects with chronic migraine and in 20 female healthy controls before and after biofeedback sessions. NO(x) levels (23.7 +/- 4.2 vs. 34.9 +/- 4.6 microm; P < 0.05) and SOD activity (6.5 +/- 1.0 vs. 8.0 +/- 0.7 U/ml; P < 0.05) were lower in migraine sufferers before treatment than in healthy controls, whereas peroxide levels (145.8 +/- 40.3 vs. 78.0 +/- 20.0 microm; P < 0.05) were higher in migraine sufferers before treatment than in healthy controls. In migraine sufferers NO(x) levels (23.7 +/- 4.2 vs. 31.3 +/- 7.1 microm; P < 0.05) and SOD activity (6.5 +/- 1.0 vs. 7.9 +/- 0.9 U/ml; P < 0.05) were lower before than after treatment, whereas peroxide levels (145.8 +/- 40.3 vs. 82.4 +/- 21.1 microm; P < 0.05) were higher before than after treatment. SOD serum activity correlated positively with NO(x) serum levels and negatively with peroxide serum levels in healthy controls and in chronic migraine sufferers before and after biofeedback. The mean Migraine Disability Assessment Score before biofeedback sessions was higher than after treatment (36.9 +/- 13.9 vs. 18.8 +/- 10.4; P < 0.001). The effectiveness of biofeedback in limiting chronic migraine may be related to muscular relaxation associated with decreased oxidative stress accompanied by psychological well-being.

The Stroke in Italy and Related Impact on Outcome (SIRIO) study: design and baseline data.

The SIRIO study collected detailed information on the stroke care of patients treated in neurological departments in Italy. This report refers to the baseline profile of patients. Each centre recorded the incident cases of ischaemic and haemorrhagic stroke, excluding SAH, for 1-4 months. Baseline data include demographics, risk factors, comorbidities, pre-event medications, social conditions, NIHSS and Rankin scale on entry, Barthel Index pre-event, diagnostic tests and treatments applied on entry. Overall, 3018 patients (56.7% men; mean age 72.1+/-12.2 years) with ischaemic (85.3%) or haemorrhagic stroke were hospitalised in 103 centres; 51% arrived by ambulance. Median time to hospital was 140 min (RIQ: 60-615). TOAST classification of the 2573 ischaemic strokes was: 29.4% large-artery atherosclerosis, 24.6% cardioembolic, 26.2% small vessels occlusion, 6.5% other determined causes and 13.3% undetermined. CT and/or MR were performed in all patients. Total Greenfield's comorbidity score was 5.4+/-3.5. Mean Barthel Index pre-event was 93+/-17; Rankin score on entry was 4-5 in 48% of the patients and 0-1 in 25%. Mean NIHSS on entry was 7.1+/-5.4; 52% of the patients had a NHISS <6 and 1% >22. SIRIO began giving the expected insights on the in-hospital management of stroke in Italy. Further information will be provided by the longitudinal phase of the study, which is in progress. Pre-event patient management and mode of reporting call for additional educational actions.

A population-based study of the incidence and prognosis of lacunar stroke.

OBJECTIVE: To evaluate incidence and prognosis of lacunar stroke in a prospective, population-based patient registry. METHODS: The authors included first-ever strokes occurring between 1994 and 1998. They assessed incidence, risk factors, mortality, and recurrence in patients with lacunar stroke. RESULTS: The authors identified 491 patients (15.3%) with lacunar stroke (252 men and 239 women) and 2,153 patients (67.3%) with nonlacunar stroke (998 men and 1,155 women). Crude annual incidence rate for a first-ever lacunar stroke was 33.0/100,000 (95% CI 30.2 to 36.0). At the univariate logistic regression analysis among patients with lacunar stroke there was a higher proportion of cigarette smoking and hypercholesterolemia and a lower proportion of chronic atrial fibrillation than in patients with nonlacunar stroke. For lacunar stroke, the 30-day case-fatality rate was 4.3% (95% CI 2.5 to 6.1) and the 1-year case-fatality rate was 13.0% (95% CI 10.0 to 16.0). During the first year of follow-up the average annual stroke recurrence rate was lower in patients with lacunar (2.83%; 95% CI 1.36 to 4.30) than in those with nonlacunar stroke (5.10%; 95% CI 4.17 to 6.03) while from the second year onward, rates were similar in both groups. CONCLUSION: In the short term, patients with nonlacunar stroke had more vascular events, but in the long term, the risk of death and of stroke recurrence was similar.

Word-stem completion task to investigate semantic network in patients with Alzheimer's disease.

Semantic impairment in patients with Alzheimer's disease (AD) is revealed by tasks of verbal naming, verbal fluency, and semantic knowledge. Causes of the deficit remain unclear in spite of many studies to investigate whether AD patients suffer from the inability to have voluntary access to an almost intact semantic store or from its break down. Word-stem completion (WSC) tasks have been utilized in healthy subjects in order to study semantic memory and network by exploiting the possibility of the involuntary access to them. Available conflicting data refer to the presence of semantic prime in AD patients. To explore the semantic network in AD, patients were requested to complete with the first word that sprang to their mind a stem submitted immediately after presentation of the word prime, as a WSC task. Stems consisted of the three beginning letters of words that were semantically related to primes. We compared data obtained with this task from patients with mild to moderate AD with those from normal controls (NC). AD patients completed less stems (P<0.001) with the expected words than NC, suggesting a break down of the semantic network rather than a deficit in the access to the semantic store.

Changes in the use of anti-asthmatic medication in an international cohort.

The aim of this study was to describe changes in pharmacotherapy for asthma since the early 1990s in an international cohort of young and middle-aged adults. A total of 28 centres from 14 countries participated in a longitudinal study. The study included 8,829 subjects with a mean follow-up time of 8.7 yrs. Change in the prevalence of use for medication was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. The use of anti-asthmatics was found to have increased by 3.1% (2.4-3.7%) and the prevalence of symptomatic asthma by 4.0% (3.5-4.5%). In the sample with asthma in both surveys (n=423), the use of inhaled corticosteroids increased by 12.2% (6.6-17.8%). Despite this, only 17.2% were using inhaled corticosteroids on a daily basis at follow-up. Females with continuous asthma were more likely, compared with males, and smokers with asthma, to have started using inhaled corticosteroids since the first survey. The use of anti-asthmatics has increased in a pattern consistent with current consensus on treatment. However, despite increased use of inhaled corticosteroids, a large majority of subjects with symptomatic asthma do not use this treatment on a daily basis, particularly males and smokers with asthma.