Use of rivaroxaban in patients with stroke.

Rivaroxaban, an inhibitor of Factor Xa, is a direct oral anti-coagulant that has been found to be non-inferior to warfarin in preventing cerebral ischemia in patients with non-valvular atrial fibrillation and in the subgroup of patients with a history of the previous stroke or transient ischemic attack. Vascular neurologists in daily clinical practice may encounter patients taking rivaroxaban or patients who may benefit from its use. In this paper, we review the current clinical indications, contraindications, and clinical management guidelines for rivaroxaban while providing a special focus on neurological aspects and expert opinions on rivaroxaban therapy management in various situations that a neurologist may encounter when treating patients with an ischemic stroke (including those requiring intravenous or intra-arterial reperfusion therapy) and patients with an intracerebral hemorrhage. Since data from clinical trials and real-life data are missing in some clinical situations, strong recommendations are not always available. Nevertheless, practical guidelines should be adopted to maximize benefits from this oral anti-coagulant.

Recommendations for the use of new oral anticoagulants (NOACs) after TIA or stroke caused by atrial fibrillation (AF), after a consensus conference among Italian neurologists (the Venice group).

Vascular neurologists of Veneto and Friuli Venezia Giulia, north-east regions of Italy, have sought an agreement on the two following questions: (A) what prophylactic treatment should we recommend to patients with a stroke ascribed to atrial fibrillation (AF), who were not previously on antithrombotic treatment, to prevent further strokes? (B) What should we do in the event of an ischemic or hemorrhagic stroke associated with AF in patients who were already on antithrombotic treatment? There was a unanimous consensus for preferring the new oral anticoagulants (NOACs) in patients not taking any antithrombotics and in cases treated with antithrombotic drugs (coumadin and/or antiplatelets), due to a lower incidence of intracranial bleeding complications and a noninferiority for recurrent stroke or TIA. Even after intracranial bleeding complications, when it is useful or necessary to continue anticoagulant treatment, the group of experts preferred the NOACs, suggesting, however, to be very cautious in cases with widespread leukoaraiosis or microbleeds, practice frequent monitoring of creatinine clearance (CrCl) and avoid using NOACs when CrCl is <30 mL/min.

The social and economic burden of stroke survivors in Italy: a prospective, incidence-based, multi-centre cost of illness study.

BACKGROUND: The aim of this study was to estimate the one-year societal costs due to a stroke event in Italy and to investigate variables associated with costs in different phases following hospital admission. METHODS: The patients were enrolled in 44 hospitals across the country and data on socio-demographic, clinical variables and resource consumption were prospectively surveyed for 411 stroke survivors at admission, discharge and 3, 6 and 12 months post the event. We adopted a micro-costing procedure to identify cost generating components and the attribution of appropriate unit costs for three cost categories: direct healthcare, direct non-healthcare (including informal care costs) and productivity losses. The relation between costs of stroke management and socio-demographic and clinical characteristics as well as disability levels was evaluated in a series of bivariate analyses using non parametric tests (Mann Whitney and Kruskal-Wallis). Multiple linear regression analyses were performed to determine predictors of costs incurred by stroke patients during the acute phase and follow-up of 1 year. RESULTS: On average, one-year healthcare and societal costs amounted to €11,747 and € 19,953 per stroke survivor, respectively. The major cost component of societal costs was informal care accounting for € 6,656 (33.4% of total), followed by the initial hospitalisation, (€ 5,573; 27.9% of total), rehabilitation during follow up (€ 4,112; 20.6 %), readmissions (€ 439) and specialist and general practioner visits (€ 326). Mean drug costs per patient over the follow-up period was about € 50 per month. Costs associated to the provision of paid and informal care followed different pattern and were persistent over time (ranging from € 639 to € 597 per month in the first and the second part of the year, respectively). Clinical variables (presence of diabetes mellitus and hemorrhagic stroke) were significant predictors of total healthcare costs while functional outcomes (Barthel Index and Modified Ranking Scale scores) were significantly associated with both healthcare and societal costs at one year. CONCLUSIONS: The significant role of informal care in stroke management and different distribution of costs over time suggest that appropriate planning should look at both incident and prevalent stroke cases to forecast health infrastructure needs and more importantly, to assure that stroke patients have adequate "social" support.

Acute stroke admission and diagnostic procedures according to the hour and day of onset: the SIRIO collaborative data.

BACKGROUND: Variations in stroke onset are related to stroke type and severity. We evaluated the impact of hourly and daily stroke onset variations on the pattern of patient hospital referral and on the time interval from stroke onset to hospital admission and brain neuroimaging investigations. METHODS: This multicenter observational study recorded all incident acute strokes within a 4-month period. RESULTS: One hundred and three participating centers collected data on 3,018 stroke cases. Stroke onset was more frequent on Mondays and between 08.00 and 10.59 h. Median time to admission after symptom onset was higher on Fridays (173.5 min) and between 20.00 and 22.59 h (207 min). Rescue by ambulance was associated with a greater stroke severity. Median time from hospital admission to brain neuroimaging investigations was higher on Saturdays (178.5 min) and between 23.00 and 10.59 h when the most severe strokes were hospitalized. CONCLUSIONS: The pattern of patient hospital referral and the time interval from stroke onset to hospital admission and brain neuroimaging investigations varied widely according to the hour and weekday of onset as well as to the reduced availability of hospital resources. An adequate distribution of the available resources should be planned in order to meet the demand.

Depression after first-ever ischemic stroke: the prognostic role of neuroanatomic subtypes in clinical practice.

BACKGROUND: The relationship between poststroke depression (PSD) and Oxford Community Stroke Project (OCSP) subtypes is uncertain. METHODS: 713 first-ever ischemic stroke patients recruited in a multicenter investigation to evaluate prevalence, onset time and severity of PSD. Stroke subtypes were considered as independent predictors of PSD occurrence by logistic regression. RESULTS: Results showed similar prevalence of PSD in stroke subtypes with the exception of TACI. Only patients with total anterior cerebral ischemia (TACI) showed a higher PSD occurrence (OR: 1.76, CI: 1.14-2.71). Multivariate analysis underlined the role of severe functional impairment, previous depressive disorders and female sex. Neither the OCSP subgroups, nor left and right involvement were predictive of PSD. TACI and left-sided strokes were related to higher depression severity scores. CONCLUSIONS: In clinical practice, the definition of neuroanatomic subtypes provides little contribution specifically to PSD prediction after a first-ever ischemic stroke.

Intravenous thrombolysis with rt-PA in acute ischemic stroke patients aged older than 80 years in Italy.

BACKGROUND: Intravenous (i.v.) thrombolysis with rt-PA within 3 h from symptom onset is the only approved treatment of pharmacological revascularization in acute ischemic stroke. However, little information exists on its use in elderly patients, in particular those aged >80 years, who at present are excluded from treatment. METHODS: In a multicenter Italian study on i.v. thrombolysis, patients aged >80 years (n = 41) were compared with those aged 80 years had a higher mortality (34.1%) as compared to those aged 80-year-old group. CONCLUSIONS: Acute ischemic stroke patients aged >80 years treated with i.v. rt-PA have a higher mortality than younger patients, but there are no differences for SICH nor for favorable outcome. Our data suggest that thrombolytic therapy should not be a priori denied for appropriately selected >80-year-old patients but randomized controlled clinical trials are necessary before definite recommendations can be given.

The Italian multicenter observational study on post-stroke depression (DESTRO).

Despite growing information, questions still surround various aspects of post-stroke depression (PSD). The Italian multicenter observational study Destro was designed to help clarify in a large sample the frequency and clinical impact of PSD. A total of 53 centers consecutively admitted 1064 patients with ischemic or hemorrhagic stroke, assessing them periodically in the first 9 months after the event. Patients with depression were followed for two years. Depression was diagnosed on clinical examination, verbal (Beck Depression Inventory) and non-verbal rating systems (Visual Analog Mood Scale), identifying the nosographic condition attributable to the mental state. The patient's clinical history, residual independence, and post-ictus quality of life were also taken into account. PSD was detected in 383 patients (36 %), most of whom had minor depression (80.17 %), with dysthymia, rather than major depression and adaptation disorder. About 80% developed depression within three months of the stroke. Cases with later onset tended to have less severe symptoms. Risk factors were a history of depression, severe disability, previous stroke and female sex, but not the type and site of the vascular lesion. PSD was not correlated with any increase in mortality or cerebrovascular recurrences, but these patients had lower autonomy and quality of life ratings. In conclusion, patients should be close observed in the first few weeks after a stroke in order to check for depression,which is more likely in those with clear risk factors and may spoil their quality of life.

Measuring accuracy of discharge diagnoses for a region-wide surveillance of hospitalized strokes.

BACKGROUND AND PURPOSE: Measuring the impact of stroke through population-based stroke registers is complex and costly. The aim of the present study is to assess the validity of hospital discharge diagnoses (all ages) and to estimate the total number of hospitalized stroke events in the Veneto region (Northeastern Italy, 4,500,000 inhabitants). METHODS: All discharges covering a 1-year period (1999) from Veneto hospitals with International Classification of Diseases, 9th Revision codes 342, 430 to 434, and 436 to 438 were identified. A stratified sample was extracted and submitted to retrospective clinical record review according to the World Health Organization MONItoring trends and determinants in CArdiovascular disease stroke project. Using the positive predictive value (PPV) for validated acute stroke of each code to adjust for inaccuracy of discharge diagnoses, an estimate of hospital strokes was obtained. RESULTS: 4015 admissions were reviewed. Codes 430, 431, 434, and 436 as primary diagnoses had the highest PPV, which sharply decreased in the other diagnostic levels. Code 342 also showed a high PPV. The probability of suspected events meeting the stroke definition increased with age and was highest for patients admitted to neurological wards and for fatal events. Overall 9400 strokes (first-ever and recurrent) were estimated to be hospitalized in 1999, with an attack rate of 208 per 100,000. CONCLUSIONS: Our data indicate that once validation studies are undertaken on a sample of all hospitalized events, hospital discharge records can provide a valuable source of information on the actual burden of strokes on hospital services.

Variability of the clinical phenotype in an Italian family with dementia associated with an intronic deletion in the GRN gene.

Mutations in the progranulin gene (GRN) were recently identified as an important cause of familial frontotemporal dementia (FTD). More than 60 pathogenic mutations have been reported up to now and prominent phenotypic variability within and among affected kindreds has been described. We have studied an Italian family with clinical evidence of dementia, and here we report detailed clinical records, imaging, sequential neurological examinations, cognitive assessments, and genetic analysis of three affected members of the same generation. Genetic analysis revealed the presence of the null mutation IVS6 + 5_8delGTGA in GRN, leading to haploinsufficiency, as documented by mRNA analysis. The mutation is associated with wide variation of the clinical phenotype, ranging from FTD to Alzheimer's disease and to a rapidly-progressive dementia. In summary, the patients of this kindred showed highly variable clinical features that do not have a close correspondence with the pattern of the cerebral atrophy. Our data extend the phenotypic spectrum and the complexity of neurodegenerative diseases linked to GRN mutations.

The neurologist in the emergency department. An Italian nationwide epidemiological survey.

A nationwide survey has been undertaken to evaluate the resources and the activities of Italian hospital neurology units (NU) in the emergency setting. NU are widely disseminated throughout the entire country and 220 (84%) are located in hospitals with an emergency room (ER). Complete data about hospital setting, structural and functional characteristics of each NU and clinical activities were obtained from 159 (72.3%). Each NU has, on average, 25 beds (7% bedside monitoring), 7 neurologists and 17 nurses. A neuroscience department is present in 25% of the hospitals. The ER is the source of 71% of the 148,040 annual admissions and of 57% of the 577,279 annual neurological consultations. Stroke is the most common cause of admission (29%), followed by epilepsy/headache and transient ischaemic attacks. Head trauma prevails in hospitals with no neurosurgical units. Cerebrovascular disorders are the main cause of neurological consultations (28%), followed by headache (22%), dizziness (13%), head trauma (13%), impairment of consciousness (12%) and epilepsy (9%). Only 36% of NU have a 24-h/day, 7 days/week on-duty neurologist and 28% have a stroke unit. The burden of neurological activities is unrelated to the geographical area and hospital's complexity (size, structural and functional context, ER organisation, presence of stroke units, neurosurgery units or 24/7 neurological service).

Plasma cytokine levels in migraineurs and controls.

BACKGROUND: The vasoactive peptide, calcitonin gene-related peptide (CGRP), is released from primary afferent neurons in the trigemino-vascular circulation during migraine headache. CGRP at physiological concentrations and possibly via stimulation of its selective receptors on T-cells, triggers the secretion of cytokines. Cytokines play an important role in several physiological and pathological settings such as immunology, inflammation, and pain. OBJECTIVE: To investigate plasma levels of pro- and anti-inflammatory cytokines in migraineurs and healthy controls. METHODS: We studied 25 migraine patients, during and outside attacks, and 18 healthy control subjects measuring plasma levels of IL-6, IL-10, tumor necrosis factor alpha (TNFalpha), IL-4, IL-1 beta, and IL-2 using ELISA. RESULTS: Circulating levels of IL-10, TNFalpha, and IL-1 beta during attacks were significantly higher in comparison to their levels outside attacks (P=.0003, P=.03, and P=.05, respectively). IL-10 and TNF serum levels were higher in patients studied soon after headache onset and lower over time (P=.004 and P=.05). CONCLUSION: Our results suggest that TNFalpha, IL-1 beta, and IL-10 may be involved in the pathogenesis of migraine attacks.

Endogenous task shift processes in relapsing-remitting multiple sclerosis.

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower to respond to an item of task A if it was preceded by an item of task B, than when it was preceded by an item of task A. Shifts between sets of cognitive operations can be internally or externally generated. Endogenous task shift refers to advance preparation for the new task. In the present study, we tested endogenous shift cost in relapsing-remitting multiple sclerosis patients. The results indicate a greater shift cost for patients than for non-brain damaged controls.