Intravenous thrombolysis in young stroke patients: results from the SITS-ISTR.

OBJECTIVE: To assess safety and efficacy of thrombolysis in 18- to 50-year-old patients compared to those aged 51 to 80 years recorded in the Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR). METHODS: A total of 27,671 patients aged 18-80 years treated with IV alteplase within 4.5 hours of symptom onset were enrolled in SITS-ISTR between 2002 and 2010. Main outcome measures were symptomatic intracerebral hemorrhage (SICH; deterioration of ≥4 points on the NIH Stroke Scale [NIHSS] within 24 hours and type 2 parenchymal hematoma), mortality, and functional independence (modified Rankin Scale [mRS] 0-2) at 3 months. RESULTS: In the 3,246 (11.7%) patients aged 18-50, SICH occurred in 0.6% vs 1.9% in those aged 51-80 (adjusted odds ratio [aOR] 0.53; 95% confidence interval [CI] 0.31-0.90, p = 0.02). Three-month mortality was 4.9% and 14.4%, respectively (aOR 0.49; 95% CI 0.40-0.60, p < 0.001) and functional independence was 72.1% vs 54.5%, respectively (aOR 1.61; 95% CI 1.43-1.80, p < 0.0001). In multivariable analysis in young patients, baseline systolic blood pressure (SBP) was the only independent factor associated with SICH (p = 0.04). Baseline NIHSS, baseline glucose, and signs of infarction in baseline imaging scan were associated with higher mortality and poorer functional outcome. Male gender, mRS before stroke, and atrial fibrillation (AF) were associated with higher mortality, and age, SBP, and previous stroke were associated with mRS. CONCLUSIONS: Treatment with IV alteplase is safe in young ischemic stroke patients and they benefit more compared to older patients. We found several factors associated with SICH, mortality, and functional outcome. These can be used to help in the selection of young ischemic stroke patients for thrombolysis. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that younger patients (18-50 years) with ischemic stroke symptoms treated with IV alteplase have lower morbidity and mortality compared to older patients (51-80 years).

Chlamydia pneumoniae infection in young stroke patients: a case--control study.

Retrospective and cross-sectional studies have suggested that both bacterial and viral infections may be risk factors for atherosclerosis, ischemic stroke and acute coronary events. The correlation between Chlamydia pneumoniae and atherosclerosis remains a source of controversy. Our case-control study is aimed at evaluating the frequency of C. pneumoniae infection in a cohort of young adults with recent cerebrovascular disease and in particular etiologic stroke subtypes. Chlamydia pneumoniae IgG, IgM and IgA antibodies were evaluated by microimmunofluorescence method and antibody titers to both recombinant antigens chlamydial outer protein 2 and 60-kDa chlamydial heat shock protein (HSP60) by ELISA. The two groups differed with regard to the prevalence of C. pneumoniae IgA (P < 0.001) and IgG (P < 0.0001), as well as the titer of anti-R-HSP60 IgG (P < 0.001). We found an increase in IgA titers, suggestive of persistent, chronic active infection, in 16 patients in whom the etiology of the cerebral ischemic event was large-vessel atherothrombosis. Persistent, active C. pneumoniae infection may be an additional risk factor for ischemic stroke mainly of atherotrombotic origin in young subjects. However, a large-scale prospective confirmation of our findings is required.

Morphological and functional characteristics of patent foramen ovale and their embolic implications.

BACKGROUND AND PURPOSE: Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this patency are still a matter of debate. METHODS: We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits. RESULTS: Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P:<0. 05). Patients with these characteristics were considered to be at high risk. During a median follow-up period of 31 months (range, 4 to 58 months), 8 PFO and 18 cryptogenic stroke patients experienced recurrent cerebrovascular events. The cumulative estimate of risk of cerebrovascular event recurrence at 3 years was 4.3% (95% confidence interval [CI], 0% to 10.2%) for "low-risk" PFO patients, 12.5% (95% CI, 0% to 26.1%) for "high-risk" PFO patients, and 16.3% (95% CI, 7. 2% to 25.4%) for cryptogenic stroke patients (high-risk PFO versus low-risk PFO, P:=0.05). CONCLUSIONS: The association of right-to-left shunting at rest and high membrane mobility, as detected by contrast TEE, seems to identify PFO patients with cerebrovascular ischemic events who are at higher risk for recurrent brain embolism.

Central nervous system vasculitis.

Vasculitis is inflammation of blood vessel walls, which produces dysfunction in both the peripheral and central nervous system (CNS). Cerebral ischemia is the major cause for neurological manifestations of CNS vasculitis. Unfortunately, a universally accepted classification of vasculitis has not emerged. Vasculitis affecting the CNS alone is referred to as primary angiitis of the CNS; secondary vasculitis occurs in association with a variety of conditions, including infections, drug abuse, lymphoproliferative disease and connective tissue diseases. The pathogenesis of vasculitis includes different immunological mechanisms. Recently, anti-neutrophil cytoplasmatic antibody (ANCA) has been demonstrated to play an active role in the immunopathogenesis of the vasculitis. Diagnosis of vasculitis depends on a combination of clinical, radiographic and pathologic features. A wide spectrum of clinical features may occur. The most typical clinical picture of CNS vasculitis is troke, encephalopathy or seizures. Assays for ANCA, serum cytokines, antibodies to endothelial cell antigens have been reported to be useful in diagnosing or monitoring the disease activity. The gold standard in diagnosis is confirmation of vasculitis in a biopsy specimen. Angiography may suggest the diagnosis but no abnormalities are pathognomonic. Ideally, the therapy of each vasculitis would focus on the specific immunologic mechanism causing the disease. Such specific interventions are not yet available. In general the most important approaches induce global immunosuppression. The goal of therapy, however, is to prevent recurrence of disease.

Long-term prognosis after a minor stroke: 10-year mortality and major stroke recurrence rates in a hospital-based cohort.

BACKGROUND AND PURPOSE: Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in a cohort of minor ischemic strokes. METHODS: A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with P<.1 at the log-rank test were evaluated by multivariate Cox analysis. RESULTS: The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension. CONCLUSIONS: In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.

Functional basis of memory impairment in multiple sclerosis: a[18F]FDG PET study.

Structural neuroimaging has been used to correlate lesional patterns with the cognitive profile of patients with multiple sclerosis (MS), especially for "frontal" dysfunction. However, a clear-cut anatomical explanation has yet to be found for the long-term memory deficit which is a hallmark of MS cognitive impairment. We have used PET to measure regional cerebral glucose metabolism (rCMRglc) in a group of 15 MS patients with involvement of verbal and/or spatial long-term memory. These patients were compared with 10 normal controls and 13 MS patients unimpaired on all neuropsychological tests. Relative to the controls, MS patients with memory deficits showed a significant bilateral reduction of rCMRglc in the hippocampus, cingulate gyrus, thalamus, associative occipital cortex, and cerebellum. Direct comparisons between patients with memory deficits and the group of unimpaired MS patients showed a metabolic reduction in the left thalamus and in both hippocampi. Seven of the memory-impaired patients also had neuropsychological signs of frontal dysfunction. These patients were compared with patients who had isolated memory deficit. Here we observed a further metabolic reduction in a number of brain regions including bilateral prefrontal cortex, inferior parietal cortex, and basal ganglia. Our findings indicate that hypometabolism of thalamic and deep cortical gray structures of the temporal lobe is associated with episodic memory dysfunction in MS. On the other hand, pathological performance on tests designed to assess frontal functions was associated with widespread reduction of glucose metabolism.

[Stroke in the young: a diagnostic protocol]. / Ictus giovanile: protocollo diagnostico.

This study attempts to propose guidelines for diagnostic procedures in young adults with focal cerebral ischemia. Our data indicate that the most common etiologies are atherothrombosis (primarily in 40-47-year-old subjects), and cardioembolism (more prevalent in subjects under 30 years old). Autoimmune conditions were observed in 12.6%, and arterial dissections in 11% of our patients. Despite extensive diagnostic studies, we were unable to determine the etiology of the cerebral ischemic event in 10% of our patients.

A controlled study of potential risk factors preceding exacerbation in multiple sclerosis.

A wide variety of potential risk factors for acute exacerbations in multiple sclerosis were evaluated in a one year case-control study. Eighty nine consecutive patients with clinically definite multiple sclerosis and relapsing remitting course presenting with a relapse between January and December 1992 were compared with patients matched for age, sex, and degree of disability, who did not experience clinical exacerbations during the same period. Only potential risk factors occurring in the three months preceding the interview were considered patients. Relapsing patients reported no significant increase in the frequency of any risk factor in the three month period before exacerbation compared with the control group. These results suggest that most relapses are not preceded by the conditions commonly considered as risk factors.

[Transesophageal echocardiography in patients with ischemic stroke with and without clinical evidence of heart disease]. / L'ecocardiografia transesofagea nei pazienti con ictus ischemico con e senza evidenza clinica di cardiopatia.

Transesophageal echocardiography (TEE) is useful in the assessment of potential cardiac sources of emboli in patients with ischemic stroke and clinical history of heart disease. Aim of our study was to assess the utility of TEE in stroke patients with and without clinical evidence of cardiac disease. In addition, we evaluated if multiplane TEE, versus mono and biplane TEE, provides additional information about potential cardiac sources of emboli. A total of 89 ischemic stroke patients were studied: 30 patients with a history and clinical evidence of cardiac disease (Group A) and 59 patients without evidence of cardiac disease (Group B). All patients had a documented ischemic lesion of the brain. Patients who had an extracardiac potential source of emboli were excluded from the study. In all patients, transthoracic (TTE) and biplane TEE were performed, whereas omniplane TEE was performed in 40 patients only. In Group A, sources of emboli were disclosed by TTE in 33% of the patients. When TEE was performed the percentage of positive cases raised to 83% (p < 0.001). In Group B, TTE was positive in only 10% of the patients as opposed to 43% with TEE (p < 0.001). Omniplane TEE revealed a potential source of emboli in 23 out of 40 (57%) patients versus 16/40 (40%) and 20/40 (50%) with monoplane and biplane, respectively. TEE is useful in patients with cardiovascular disease in whom clinical evaluation and TTE are negative for sources of emboli. TEE is of great value in stroke patients without clinical evidence of cardiovascular disease in whom an extracardiac potential source of emboli has been excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomical and functional correlates of cognitive deficit in multiple sclerosis.

This brief article reviews the present state of knowledge concerning the relationship between structural and functional cerebral abnormalities and the cognitive deficits associated with multiple sclerosis. Currently available neuroimaging techniques have substantially contributed to a better understanding of the latter, suggesting that cortical-subcortical disconnection is the most likely cause of the cognitive disturbance. Longitudinal studies are needed to determine the natural history of the cognitive deficit and its relationship to the cerebral changes detected by neuroimaging techniques.

Cognitive and brain imaging measures of multiple sclerosis.

In this review we will describe the cognitive deficiency in Multiple Sclerosis (MS) and analyze the relationship between the performance on neuropsychological tests and the anatomofunctional findings assessed by neuroimaging techniques. Memory, abstract reasoning, and visuospatial abilities impairments are correlated with lesion extension and with corpus callosum atrophy, quantified on MRI. On the other hand, in MS patients with cognitive disturbance, PET and SPET studies show metabolic alterations and perfusion deficits at the cortical level, particularly in the left hemisphere and in the frontal and temporal lobes.

Structural brain correlates of neurologic abnormalities in multiple sclerosis.

We examined the relationship between cerebral magnetic resonance imaging (MRI) findings and urinary dysfunction in 70 consecutive patients with definite multiple sclerosis. MRI-weighted lesion scores for seven different brain regions were recorded according to the number and size of cerebral lesions. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Subjects with urinary symptoms exhibited greater overall functional disability and a higher midbrain MRI-weighted lesion score than asymptomatic patients. No statistically significant group differences were found for the other brain regions.

Relationship between bladder dysfunction and brain MRI in multiple sclerosis.

We studied 70 consecutive patients with definite multiple sclerosis (MS) to examine the relationship between magnetic resonance imaging (MRI) cerebral findings and urinary disturbances. Thirty-two subjects (46%) had urinary symptoms and 38 (54%) were asymptomatic. Patients with urinary symptoms exhibited greater overall functional disability. A significant correlation between the presence of midbrain lesions and urinary dysfunctions was found which may indicate an important role of the mesencephalic formation to preserve continence.