Do patients' and referral centers' characteristics influence multiple sclerosis phenotypes? Results from the Italian multiple sclerosis and related disorders register.

BACKGROUND: Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. METHODS: This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000-2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing-remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers' characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. RESULTS: In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. DISCUSSION: Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers' characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

[Recommendations on telestroke in Europe]. / Evropeiskie rekomendatsii po telemeditsine insul'ta.

INTRODUCTION: This paper is an adapted translation of recommendations on telestroke provided by the European Stroke Organization. Lack of stroke specialists determines that many European rural areas remain underserved. Use of telemedicine in stroke care has shown to be safe, increase use of evidence-based therapy and enable coverage of large areas of low population density. An aim of the study is to summarise the following recommendations of the Telestroke Committee of the European Stroke Organization on the setup of telestroke networks in Europe: Hospitals participating in telestroke networks should be chosen according to criteria that include population density, transportation distance, geographic specifics and in-hospital infrastructure and professional resources. Three hospital categories are identified to be part of a hub-and-spoke network: (1) the Telemedicine Stroke Centre (an European Stroke Organization stroke centre or equivalent with specific infrastructure and setup for network and telemedicine support), (2) the telemedicine-assisted stroke Unit (equivalent to an European Stroke Organization stroke unit but without 24 h onsite stroke expertise) and (3) the telemedicine-assisted stroke ready hospital (only covering hyperacute treatment in the emergency department and transferring all patients for further treatment).

Silent infarcts in stroke patients: patient characteristics and effect on 2-year outcome.

Although silent infarcts (SIs) are frequent in stroke patients, their clinical significance remains controversial, and their effect on stroke outcome remains unclear. This study evaluated the prevalence of SI on computed tomography, associated factors, and the effect on outcome in stroke patients. We studied 202 consecutive patients admitted for acute ischaemic or haemorrhagic stroke with clinical deficits lasting more than 24 h. Survivors were followed up for 24 months; no patient was lost to follow-up. Patients with Rankin scores of 2 or lower were considered separately. New vascular events were also recorded. Computed tomography showed that one-fourth of patients (52/202) had at least one SI; these were located in deep hemispheric areas in 46 patients, superficial hemispheric areas in 5, and the posterior fossa in 7. Logistic regression analysis showed the factors independently associated with SI to be severe leukoaraiosis (OR 1.71, 95% CI 1.26-2.31) and small-vessel occlusion as presumed cause of the index stroke (OR 2.66, 95% CI 1.22-5.79). SI did not affect vital or functional outcome or the occurrence of new vascular events within 2 years after stroke. Whether they affect cognitive outcome remains under evaluation over a longer follow-up period.

Rehabilitation of acquired brain injuries: a multicentric prospective survey.

BACKGROUND: The rehabilitation of the persons with Severe Acquired Brain Injury (ABI) is an important concern to be approached with a comprehensive program aimed to improve the recovery of patients.The efficacy of an early and intensive rehabilitation program has been shown in large number of studies. Few studies focused on the prevalence of TBI and the data are often extrapolated in indirect ways. AIM: An analysis of the demographic characteristics of the population included in the GISCAR (Gruppo Italiano per lo Studio delle Gravi Cerebrolesioni Acquisite e Riabilitazione- Italian Group for the Study of the severe ABI) database, type and conditions associated to the index event; the treatment administered during hospitalization; and the prognosis according to outcome measures. DESIGN: The study was an observational prospective survey looking at management of ABI (both traumatic and non-traumatic). SETTING: In hospital rehabilitation. POPULATION: Patients consecutively admitted in each of the 52 GISCAR centres. METHODS: Every centre included a consecutive cohort and recorded demographic data and index event characteristics. RESULTS: In the study population were included 2626 subjects suffering of a severe ABI. The difference of length of stay (LOS) was significantly different with 67.5 days for traumatic patients compared to the 80 days of non traumatic ones. In the study population the probability of discharge at home is significantly greater for the traumatic condition (odds ratio 0,4587; CI 0.3671-0.5731). The overall benefit of the rehabilitative treatment was encountered in a net gain in all disability scores taken into account: LCF classes; DRS as well as GOS scores. At discharge the main destination for severe ABI patients was home (67.2%). CONCLUSIONS: A large number of patients admitted in Italian rehabilitative facilities for a severe ABI suffered from a TBI, more often these subjects were young male victims of road accident. The majority of subjects during the rehabilitative hospitalization demonstrated a significant recovery. CLINICAL REHABILITATION IMPACT: Considering the evidence of an early treatment benefit the delay ofthe rehabilitation program start is far from being satisfactory. The high frequency of the home discharge indicate a good compliance of national family network.

Clinical pharmacology and vascular risk.

Pharmacological treatment and several drugs of abuse have been associated with ischemic heart disease (IHD) and cerebrovascular diseases (CVD). However, there is a paucity of data on the independent risk of vascular disease (VD) associated with pharmacological treatment and no controlled trials demonstrating a reduction in risk with abstinence. Information about IHD and CVD-related drug abuse is mainly limited to epidemiological studies focused on urban populations. The potential link between some pharmacological treatments (estrogen, some oncologic drugs and some atypical antipsychotics) and cerebrovascular adverse events was analyzed, but disagreement about an association persists. Drugs of abuse, including cocaine, amphetamines and heroin, have been associated with an increased vascular risk. These drugs can cause abrupt changes in blood pressure, vasculitic-type changes, lead to embolization caused by infective endocarditis, and hemostatic and hematologic abnormalities that can result in increased blood viscosity and platelet aggregation. Long-term treatment strategies based on medication, psychological support, and outreach programs play an important role in treatment of drug dependency. In these last years public interest in risk factors for VD has been constantly increasing and the successful identification and management of pharmacological treatment and drug abuse can be challenging. One of the major public health issues for the future will be to focus more on new vascular risk factor recognition and management. The objective of this chapter is to review the relevance of IHD and CVD associated with various pharmacological treatments and drug abuse with focusing on ischemic disease. This chapter reports the clinical evidence of this association and analyzes the experimental role of new drugs as a growing risk factor of VD with the hypothetical new association. In conclusion, in this chapter great attention is paid to evaluating the scientific and real evidence of cerebrovascular effect and drug use and abuse so as to identify a new groups of "modifiable" risk factors.

Cervical artery dissection: emerging risk factors.

Cervical artery dissection (CAD) represents an increasingly recognized cause of stroke and the most common cause of ischemic stroke in young adults. Many factors have been identified in association with CAD such as primary disease of arterial wall (fibrodysplasia) and other non-specific diseases related to CAD like Ehlers Danlos-syndrome IV, Marfan's syndrome, vessel tortuosity. Moreover, an underlying arteriopathy which could be in part genetically determined, has been suspected. The rule of emerging risk factors for CAD such as recent respiratory tract infection, migraine and hyperhomocysteinemia are still a matter of research. Other known risks factors for CAD are major head/neck trauma like chiropractic maneuver, coughing or hyperextension injury associated to car. We examined emerging risks factors for CAD detected in the last years, as CAD pathogenesis is still not completely understood and needs further investigations.

Type the Characteristics of Pacemaker (PM) Patients Admitted in Stroke Unit: The Stroke Pacemaker Study (SPACES).

Aims: According to recent surveys, despite health care authority’s budget reductions, the total amount of PM implants increased worldwide. Even if the diffusion of these devices is large no data are available concerning the characteristics of PM patients hospitalized for stroke. Study Design: The SPACES study is a retrospective observational study conducted in 3 hospital centres including paced patients consecutively admitted for acute stroke. The objective is to determine the characteristics of patients with PM admitted in the stroke units. Place and Duration of Study: In 3 Italian general hospital (Perugia, Milano, Mantova), from January 2005 to September 2008. Method: At admission all patients underwent non-contrast computed tomography (CT), routine biological tests, 12-lead ECG. The ECG was categorized in following subgroups: a) sinus rhythm; b) AF rhythm; c) PM-induced activity (when was not possible to state the underlying rhythm). Results: In the study population were recorded 73 ischemic strokes, 10 hemorrhagic events and 19 TIA. At the basal ECG a “pacemaker-induced” rhythm was diagnosed in 37 cases, sinus rhythm in 28, AF in 32 subjects. At the univariate analysis patients with an ECG-detected AF rhythm at admission were more often those with positive AF medical history (p<.001) and treated with aspirin prior to the index event (p=.023). Patients with an ECG-detected AF at admission more often suffered a Total Anterior Cerebral Infarction (TACI) subtype of stroke (p=.038) having cardioembolism as cause (p<.001). Conclusions: Our survey suggests that paced patients suffer more often, than unselected case-series, of ischemic strokes due to cardioembolic events. Moreover AF is the leading risk factor in PM subjects. Probably PM-induced electric activity may further confound the detection of the baseline ECG, with an underestimation of AF.

Secondary prevention of cardioembolic stroke: oldest and newest promises.

Atrial fibrillation (AF) is the most common cause of cardioembolism. An update on secondary prevention strategies used to protect from the risk of stroke AF patients is presented. The main line of actions of stroke prevention in AF are antithrombotics (anticoagulant or antiplatelet), antiarrhythmics (for rate control and sinus rhythm restore), mechanical means (for occlusion of the left atrial appendage or protection of the internal carotid artery from emboli). Classic pharmacological prevention with K vitamin Kantagonists such as warfarin may be overcome by direct thrombin inhibitors like ximelagatran and melagatran. New ablation technologies promise to cure, at least a part of Nonvalvolae AF in the community, restoring sinus rhythm. Recent achievements on endovascular procedures deploying carotid artery implants provide an opportunity to divert emboli to nonhazardous locations, whereas cardiac devices can seal left atrial appendages and avoid risk of clot migration in the blood stream. In the next decade, the challenge will be to understand competitiveness between old and new drugs with endovascular implants.

Early admission to stroke unit influences clinical outcome.

An improvement in patient arrival time to stroke unit (SU) is recommended, since earlier stroke management seems to improve 'per se' functional outcome. The objective of this study was to determine if early admission influences the outcome, reduces disability and mortality at discharge and three months later independent of tlirombolytic treatment. Consecutive acute stroke patients admitted to SU between January 1st 2000 and December 31st 2003 were studied in order to analyze the actual role of acute management independent specific pharmacological treatment, we excluded subjects who underwent rt-PA. 35.8% of 2,041 consecutive stroke patients arrived within 3 hours; 62.4% within 6 hours; 37.6% arrived later. Approximately 80% of the <6 hour patients presented a National Institutes of Health Stroke Scale (NIHSS) >4 and modified Rankin Scale (mRS) score >2 in comparison with 60% of the >6 hour patients. In hospital (8.7%) and three-month (7.3%) mortality in <3 hour patients were not significantly different from what observed in >3 hour patients (6.8% and 6.1% respectively) while functional outcome after three months was better in <3 hour patients (NIHSS: 34.6 vs 15.2; mRS: 32.9% vs 16.8%). Old age, history of TIA, cardioembolic etiology, severity of neurological deficit and hemorrhagic stroke type all led to earlier arrival time. Admission within 3 hours 'per se' improves outcome and reduced disability at three months.

Educational approach on stroke training in Europe.

According to the European Stroke Initiative (EUSI), stroke care is best delivered within a stroke unit by a specialized multidisciplinary stroke team led by stroke specialists. At present, there is no guideline or consensus regarding training requirements or clinical standards that stroke specialists should achieve. It is envisaged that stroke specialists in training would need to acquire adequate knowledge and competency across three major areas of stroke care: acute stroke, stroke rehabilitation, and stroke prevention. With an EUSI document, the European Association of Young Neurologists and Trainees Stroke Subspeciality Group aims to promote discussion on the many aspects of stroke training and the requirements to be a stroke specialist in the European community. The ultimate purpose is to agree on common standards to promote good clinical care and effective stroke prevention across Europe. In the future, this may be translated into better patient outcome and a reduction in the global burden of this condition.

Neurovascular territory involved in different etiological subtypes of ischemic stroke in the Perugia Stroke Registry.

UNLABELLED: We studied the correlation between the potential causes of stroke (TOAST etiological groups) and the involvement of different vascular territories seen on computed tomography (CT) scans in patients with ischemic stroke. Information from consecutive patients with a first-ever stroke have been prospectively coded and entered into a computerized data bank (Perugia Stroke Registry). A population of 1,719 patients were evaluated: 1,284 patients (74.7%) had ischemic stroke. Large artery disease was the main cause of entire middle cerebral artery (MCA) territory infarcts (40.9%), superficial MCA territory infarcts (35.7%), and watershed infarcts (68.2%). The highest presence of emboligenic heart disease was found in the entire MCA territory infarcts (28.8%) or superficial (29.4%) supratentorial infarcts and in cerebellar infarcts (36.8%). Small artery disease was the most common presumed cause of deep MCA infarcts (75.0%) and posterior cerebral artery (PCA) territory infarcts (52.1%). IN CONCLUSION: stroke location could depend on its etiology. Lacunar infarcts are the most prevalent (36.7%), being mostly localized in the deep MCA territory; large artery disease includes more than two-thirds of watershed infarcts; the most prevalent territories involved in cardioembolic stroke are the entire MCA and posterior fossa.

Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke.

The role of hyperhomocysteinemia as independent risk factor for stroke needs to be confirmed. The aims of our study were to assess (i) the association between risk of stroke and increasing values of plasma homocysteine and (ii) the interaction between mild hyperhomocysteinemia and conventional vascular risk factors. We studied 161 consecutive patients with first-ever ischemic stroke classified using TOAST criteria and 152 neurologically healthy controls. Homocysteine was measured using high performance liquid chromatography (HPLC). Homocysteinemia was elevated in all stroke subtypes: 13.0+/-2.5 micromol/l in patients with cardioembolic disease, 13.9+/-5.4 micromol/l in those with small vessel diseases, 15.5+/-6.8 micromol/l in cases of undetermined stroke, and 17.8+/-13.5 micromol/l in patients with large vessel disease. Mean homocysteinemia was 8.10 micromol/l (SD=2.5) in controls. The logistic regression analysis showed that important independent risk factors for ischemic stroke were hypertension (p<0.0001; OR= 3.205; 95% CI, 1.788-5.742), hyperhomocysteinemia (p<0.0001; OR=1.425; 95% CI, 1.300-1562) and hyperlipidemia (p=0.018; OR=2.243; 95% CI, 1.147-4.385). Hyperhomocyst(e)inemia is an independent risk factor for all stroke subtypes and should be routinely measured and treated in stroke patients.

Stroke and atrial fibrillation: is stroke prevention treatment appropriate beforehand? SAFE I Study Investigators.

OBJECTIVE: To undertake a pilot study before conducting a large European multicentre prospective study, to determine the proportion of patients with atrial fibrillation who were not receiving antithrombotic treatment before stroke onset, and their characteristics. DESIGN AND PATIENTS: The stroke in atrial fibrillation ensemble (SAFE) I study was an observational study conducted in 213 patients with atrial fibrillation consecutively admitted in 1997 to three European centres for an acute stroke or transient ischaemic attack (TIA). It was determined whether they were receiving prior antithrombotic treatment. RESULTS: Atrial fibrillation was known before stroke in 148 patients (69.5%). Of 213 patients, 34 (16.0%) were receiving anticoagulation treatment before stroke, but only six had an international normalised ratio between 2. 0 and 3.5; 65 (30.5%) were receiving antiplatelet treatment; and three (1.4%) were receiving both anticoagulation and antiplatelet treatment. Of 137 patients eligible for oral anticoagulation, 108 (78.8%) did not receive treatment. Of 142 patients eligible for any antithrombotic treatment, 62 (43.7%) were not treated. The logistic regression analysis, assuming anticoagulation treatment as a dependent variable, found digoxin treatment, absence of arterial hypertension, mitral stenosis, and cardioversion as independent factors. Assuming any antithrombotic treatment as a dependent variable, previously known atrial fibrillation, lower age, being a non-smoker, and absence of arterial hypertension were found to be independent factors. CONCLUSION: More than half of the patients with atrial fibrillation admitted for acute stroke or TIA were not receiving any antithrombotic treatment beforehand. New onset atrial fibrillation and contraindications account for a minority of non-prescriptions; thus, other reasons should be identified to improve stroke prevention in the community.