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Silvia Di Legge

Publications and source records attributed to Silvia Di Legge.

16 recordsLinked to original sources

Neglecting the difference: does right or left matter in stroke outcome after thrombolysis?

BACKGROUND AND PURPOSE: Patients with right hemispheric strokes (RHSs) present later to an emergency department, have a lower chance to receive intravenous recombinant tissue plasminogen activator (IV rt-PA), and have worse clinical outcomes than do patients with left hemispheric strokes (LHSs). We analyzed outcomes after IV rt-PA with respect to the side of the affected hemisphere. METHODS: A prospective cohort of acute stroke patients was treated with IV rt-PA at the London Health Sciences Centre (December 1998 to March 2003). Differences between patients with RHS and LHS were identified by univariate analysis. Logistic-regression analysis was used to determine a subset of variables independently associated with major neurological improvement at 24 hours and good outcome at 3 months after treatment. RESULTS: Of 219 stroke patients who received IV rt-PA, 165 had hemispheric strokes (68 RHSs and 97 LHSs). Patients with RHSs were less hypertensive (P=0.001) and had lower pretreatment National Institutes of Health Stroke Scale (NIHSS) scores (P=0.005). LHS (odds ratio [OR], 2.29; 95% CI, 1.14 to 4.59; P=0.019), age (OR, 0.96; 95% CI, 0.93 to 0.99; P=0.012), and pretreatment NIHSS (OR, 0.83; 95% CI, 0.78 to 0.89; P<0.0001) were independent predictors of 3-month outcome. Female sex (OR, 3; 95% CI, 1.53 to 5.90; P=0.001) and LHS (OR, 2.07; 95% CI, 1.05 to 4.08; P=0.03) were independent predictors of major neurological improvement at 24 hours after IV rt-PA. CONCLUSIONS: Despite higher pretreatment NIHSS, patients with LHSs have a 2-fold increased chance of a good outcome 3 months after rt-PA treatment compared with patients with RHSs. This gain can be clinically detected at 24 hours after treatment. These results need to be coupled with neuroimaging and hemodynamic characteristics known to influence stroke outcome.

Aged↗

Predictors of major neurologic improvement after thrombolysis in acute stroke.

BACKGROUND: Major neurologic improvement at 24 hours after administration of recombinant tissue plasminogen activator (rt-PA) in acute stroke may predict good outcome at 3 months. OBJECTIVE: To identify predictors of major neurologic improvement at 24 hours after IV rt-PA administration and its relationship with outcome at 3 months. METHODS: The authors analyzed patients with acute stroke treated with IV rt-PA from two academic centers in London, Ontario, and 33 affiliated hospitals between 1999 and 2003. Major neurologic improvement was defined by a > or = 8-point improvement in NIH Stroke Scale (NIHSS) score or an NIHSS score of 0 or 1 at 24 hours. Good outcome was defined as a 3-month modified Rankin Scale of 0 to 1. RESULTS: Of 219 patients with acute stroke treated with rt-PA, 61 (28%) had major neurologic improvement at 24 hours. Glucose levels < 8 mmol/L (OR 4.98, 95% CI 1.6 to 15.2), lack of cortical involvement on 24 hour CT scan (OR 3.97, 95% CI 1.87 to 8.43), and female sex (OR 2.4, 95% CI 1.12 to 5.13) were associated with major neurologic improvement after adjusting for covariates. Patients with major neurologic improvement had a shorter hospital stay (6.7 vs 14.3 days; p = 0.001). Major neurologic improvement was an independent predictor of good outcome at 3 months (OR 12.8, 95% CI 4.72 to 34.6). CONCLUSIONS: Major neurologic improvement after rt-PA was observed in 28% of patients and independently predicted good outcome at 3 months. Female sex, glucose levels < 8 mmol/L, and absence of cortical involvement at 24 hours CT scan were associated with major neurologic improvement.

Aged↗

The impact of lesion side on acute stroke treatment.

BACKGROUND: Only a small percentage of patients with acute stroke are treated with recombinant tissue plasminogen activator (rt-PA). OBJECTIVE: To investigate why patients with right-hemisphere strokes seem at high risk of not receiving rt-PA. METHODS: This study includes two phases. Phase 1: the authors compared demographic, clinical, and outcome measures between patients with right- and left-hemisphere strokes in the rt-PA Registry of Southwestern Ontario (RSWO); Phase 2: the authors tested the hypotheses generated in Phase 1 using the Registry of the Canadian Stroke Network (RCSN). A multiple logistic analysis was applied to detect independent predictors of rt-PA administration. RESULTS: Phase 1: of 179 rt-PA-treated patients, 39% had right-hemisphere syndrome. Patients with right-hemisphere strokes had a longer hospital stay (15 vs 9 days; p = 0.03). Phase 2: of 990 stroke patients in the RCSN, 505 (51%) had a right- and 485 (49%) a left-hemisphere syndrome. Of 110 rt-PA-treated patients, 37 (34%) had a right-hemisphere syndrome (p = 0.0001). Negative independent predictors of rt-PA administration were right-hemisphere stroke (OR, 0.55; CI: 0.31 to 0.96; p = 0.037), onset-to-emergency department time (OR, 0.99; CI 0.98 to 0.99; p = 0.04), and CNS score (OR, 0.78; CI 0.71 to 0.86; p < 0.0001). Neglect predicted rt-PA administration (OR, 2.32; CI 1.29 to 4.16; p = 0.004). CONCLUSIONS: Patients with right-hemisphere strokes are 45% less likely to be treated with recombinant tissue plasminogen activator (rt-PA) compared to patients with left-hemisphere strokes. The presence of neglect confers a twofold increased likelihood of rt-PA administration. Prehospital delay and lack of standardized scores for the neglect syndrome may limit accessibility of patients with right-hemisphere stroke to thrombolysis.

Acute Disease↗

A longitudinal fMRI study on motor activity in patients with multiple sclerosis.

Using functional MRI (fMRI), patients with multiple sclerosis showed a greater extent of motor activation than controls. Although functional changes are often interpreted as adaptive and as a contributing factor in limiting the clinical deficit, no longitudinal studies have yet been performed for multiple sclerosis. Sixteen patients with multiple sclerosis, two patients with possible multiple sclerosis and nine age-matched controls underwent two fMRI studies with a time interval of 15-26 months. The motor task consisted of a self-paced sequential finger opposition movement with the right hand. Patients with multiple sclerosis exhibited greater bilateral activation than controls in both fMRI studies. At follow-up, patients showed a reduction in functional activity in the ipsilateral sensorimotor cortex and in the contralateral cerebellum. No significant differences between the two fMRI studies were observed in controls. Activation changes in ipsilateral motor areas correlated inversely with age, extent and progression of T1 lesion load, and occurrence of a new relapse. This study may help the understanding of the evolution of brain plastic changes in multiple sclerosis indicating that, in younger patients with a less structural brain damage and benign clinical course, the brain reorganizes its functional activity towards a more lateralized pattern of brain activation. The tendency towards a normalization of brain functional activity is hampered in older patients and in those developing relapses or new irreversible brain damage.

Adult↗

Lack of improvement in patients with acute stroke after treatment with thrombolytic therapy: predictors and association with outcome.

CONTEXT: The focus of thrombolytic therapy in acute stroke has been on favorable outcome at 3 months. Few studies have analyzed outcome at 24 hours. An early and reliable prediction of poor outcome has implications for clinical management and discharge planning. OBJECTIVE: To evaluate predictors of lack of improvement at 24 hours after receiving alteplase and their relationship with poor outcome at 3 months. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of consecutive patients with acute stroke who received alteplase and were admitted to a university hospital from January 1999 to March 2003. Participants were recruited from 2 academic centers in a major city in Ontario and 33 affiliated hospitals from 7 counties. MAIN OUTCOME MEASURES: Lack of improvement defined as a difference between the National Institutes of Health Stroke Scale score at baseline and at 24 hours of 3 points or less. Poor outcome at 3 months defined by a modified Rankin Scale score of 3 to 5 or death. RESULTS: Among 216 patients with acute stroke who were treated with alteplase, 111 (51.4%) had a lack of improvement at 24 hours. After adjusting for age, sex, and stroke severity, baseline glucose level on admission (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.40-5.99 for a glucose level >144 mg/dL [>8 mmol/L]), cortical involvement (OR, 2.66; 95% CI, 1.36-5.20), and time to treatment (OR, 1.01; 95% CI, 1.0-1.02 for each 1 minute increase in time to treatment) were independent predictors of lack of improvement. At 3 months, 43 patients (20.2%) had died; of the 170 survivors, 75 patients (44%) had poor outcomes. After adjusting for age, sex, and stroke severity, lack of improvement at 24 hours was an independent predictor of poor outcome (OR, 12.9; 95%CI, 5.7-29.6) and death (OR, 7.5; 95% CI, 2.9-19.6). Patients with a lack of improvement had longer lengths of hospitalization (14.5 vs 9.6 days; P = .02). CONCLUSIONS: Among patients with acute stroke treated with thrombolytic therapy, lack of improvement at 24 hours is associated with poor outcome and death at 3 months. Elevated glucose level, time to thrombolytic therapy, and cortical involvement were predictors of lack of improvement.

Aged↗

The relationship between inflammation and atrophy in clinically isolated syndromes suggestive of multiple sclerosis: a monthly MRI study after triple-dose gadolinium-DTPA.

OBJECTIVE: To examine the relationship between inflammation and brain atrophy in patients with a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). METHODS: Monthly triple-dose gadolinium (Gd/DTPA)-enhanced MRI scans over 6 months were obtained in 62 consecutive CIS patients with an abnormal baseline MRI scan. Subsequently MRI was performed at months 12 and 18. Patients who developed a clinically definite MS (i. e., a second clinical episode) ended the study at the time of the relapse. For each scan, the number and volume of newly active lesions (Gd-enhancement/new or newly enlarging T2 lesion that did not enhance), and the number and volume of T2 hyperintense lesions (T2-LL) and T1-black holes (T1-LL) were calculated. The percentage of brain volume changes (PBVC) was assessed using a fully automated technique (SIENA; Structural Image Evaluation using Normalization of Atrophy). RESULTS: Twenty-four (39%) developed clinically definite MS by month 18. Thirty-eight (61%) were relapsefree and completed the MRI follow-up. Relapse-free patients showed a progressive median increase between baseline and month 18 in T1-LL (25%, p<0.001), but not in T2-LL (8.5%, p=ns). PBVC decreased by 1.1% (p<0.001) in a time-dependent pattern (Kendall coefficient of concordance=0.85). Exploratory subgroup analyses showed a trend towards progressive decreases in brain volume in active patients (i. e., those with at least one newly active lesion during monthly MRI scanning; Spearman's R=-0.61; p<0.001), but not among inactive patients (Spearman's R=-0.10; p=0.53). Significant differences in median brain volume changes between the active and inactive patient groups were found at months 12 and 18; the difference detected at month 6 was not significant. The cumulative number and volume of new Gd-enhancing lesions developed during the 6 months of frequent MRI scanning were highly correlated with PBVC over the 18-month period (Spearman R values were 0.73 and 0.85, respectively). The strongest predictor of PBVC at 18 months was the cumulative volume of newly active lesions during frequent MRI scanning [ss=-0. 83, standard error (SE)=0.07, p<0.001]. CONCLUSIONS: This study shows that visible inflammation as detected by monthly, triple-dose Gd-enhanced MRI is an important factor in the pathogenesis of brain tissue loss in CIS patients. However, inflammation and brain atrophy do not proceed in parallel: atrophy appeared only after a delay of months following acute inflammation. Frequent MRI scanning allows for the detection of CIS patients who will develop brain atrophy in the short-term.

Adolescent↗

Prospects for prevention and treatment of vascular cognitive impairment.

With the aging population and rising prevalence of vascular disease in developed and developing countries, increasing numbers of individuals are at risk of cognitive impairment. Despite the potential of the therapeutics that are currently under investigation, none have yet fulfilled their promise for the prevention and treatment of dementia. The term vascular cognitive impairment (VCI) describes individuals with significant cognitive impairment arising from vascular disease. Risk factors predisposing to stroke correlate with brain changes, cognitive loss and Alzheimer's disease pathology. The volume of the infarcts and white matter changes, silent lacunar infarcts, and global and regional brain atrophy may be imaged non-invasively, targeted as surrogates of the dementia processes and considered parameters to be targeted for interventional strategies. As the greatest chance to prevent cognitive impairment and its progression is by intervening in the early stages or prior to any change, the development of preventative therapeutics is an important strategy. Non-invasive magnetic resonance imaging techniques may help to identify a subgroup of patients in whom infarct prevention, via risk factor control, may be of paramount importance. As the pathophysiology of dementia becomes more fully understood by coupling neuropsychological with neuroimaging, genetic and pathological features, there is the potential for the establishment of diagnostic criteria of the early phase of VCI and the testing of novel interventional strategies.

Aging↗

Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis.

The objectives of this study were to assess whether cortical motor reorganization in the early phase of multiple sclerosis (MS) is correlated with the clinical presentation and with specific damage to the corticospinal tract. Twenty patients with clinically isolated syndrome (CIS) and serial MR findings indicative of MS were selected. In 10 patients the CIS was hemiparesis (group H), and in 10 patients the CIS was optic neuritis (group ON). There were no significant differences in age, disease duration, total T2 lesion load (LL), and total T1 LL between group H and group ON. Ten age-matched healthy subjects served as controls (group C). All subjects were submitted to fMRI during a sequential finger-to-thumb opposition task of the right hand. Group H showed a significantly higher EDSS score and T1 LL calculated along the corticospinal tract than group ON. Three-group comparison by ANOVA showed significantly higher activation in group H than in the other two groups (P < 0.001). Significant foci were located in the sensory-motor cortex (BA 1-4), the parietal cortex (BA 40), the insula of the ipsilateral hemisphere, and the contralateral motor cortex (BA 4/6). Group ON showed, although at a lower level of significance (P < 0.01), higher activation of the contralateral motor-related areas than group C. Multiple regression analysis showed that T2 and T1 LL along the corticospinal tract and time since clinical onset positively correlated with activation in motor areas in both cerebral hemispheres (P < 0.005). Total T2 LL positively correlated with activation in motor areas in the contralateral hemisphere (P < 0.005). Total T1 LL and EDSS did not show any significant correlation. More severe specific damage to the motor pathway in patients with previous hemiparesis may explain the significantly higher involvement of ipsilateral motor areas observed in group H than in group ON. Furthermore, the significant correlation between the time since clinical onset and activation in motor areas suggests that cortical reorganization develops gradually in concomitance with the subclinical accumulation of tissue damage.

Adult↗

A longitudinal study of MR diffusion changes in normal appearing white matter of patients with early multiple sclerosis.

BACKGROUND AND PURPOSE: The stage at which normal appearing white matter (NAWM) abnormalities first appear in multiple sclerosis (MS) is not clear. The aim of our study was to monitor water diffusion changes over time in NAWM of patients with early MS. METHODS: Out of a consecutive series of patients enrolled in a MR study on clinically isolated syndrome (CIS), we selected 19 subjects who had completed a one year follow-up. The MR scans obtained at baseline and at 12 months were reviewed according to the new criteria on the diagnosis of MS. Lesion load on T2 and T1 weighted images and the trace of the apparent diffusion coefficient in NAWM were measured both at baseline and at 12 months in patients and in 12 healthy controls. RESULTS: In three patients the diagnosis of MS was done at baseline based on MR. Thirteen patients developed MS during the study and in three patients the diagnosis remained "possible MS." TADC in NAWM in patients was significantly higher than in controls at the 12 months' follow-up but not at baseline (controls mean tADC +/- sd = 0.745 +/- 0.02 mm(2)/sec x 10(-3); patients mean tADC(12) +/- sd = 0.767 +/- 0.02 mm(2)/sec x 10(-3); p < 0.02). TADC and T2 lesion load at 12 months were significantly correlated (p < 0.01). Patients exhibiting tADC(12) above a confidence interval had a significantly greater EDSS score at the same time period (EDSS(12) +/- sd = 1.9 +/- 0.5 and = 1.1 +/- 0.4 respectively; p < 0.01). CONCLUSIONS: This study suggests that diffusion MR cannot detect alterations in NAWM of patients with a CIS suggestive of MS. After one year, when most patients develop MS, diffusion MR abnormalities in NAWM become apparent. These abnormalities are correlated with T2 lesion load and may contribute to neurological impairment.

Adult↗

Cortical motor reorganization after a single clinical attack of multiple sclerosis.

In order to evaluate whether cortical motor reorganization occurs in the earliest phase of multiple sclerosis, we studied patients after a first clinical attack of hemiparesis. From a consecutive series of 70 patients enrolled in a study of patients with clinically isolated syndrome and serial MRI findings indicative of multiple sclerosis, we retrospectively selected 10 patients with hemiparesis as the onset symptom and no further clinical episode [mean age 32 +/- 9 years, disease duration 24 +/- 14 months, median Expanded Disability Status Score (EDSS) 1.25]. Ten age-matched, healthy subjects served as controls. Each subject was submitted to two functional MRI trials (one per hand) using a 1.5 T magnet during a sequential finger-to-thumb opposition task. Image analysis was performed using SPM99 software. Movements of both the 'affected' and the 'unaffected' hand activated significantly larger areas in patients than in controls in both the contralateral and ipsilateral cortical motor areas. Patients activated a greater number of foci than controls during both the right-hand and the left-hand movement. Most of these foci were located in cortical areas which were less or not at all activated in controls, such as the lateral premotor cortex [Brodmann area (BA) 6], the insula and the inferior parietal lobule (BA 40). Between-group analysis of patients versus controls showed significant (P < 0.001) foci in these areas, principally located in the ipsilateral hemisphere during right-hand movement and in both the cerebral hemispheres during left-hand movement. Time since clinical onset showed a significant positive correlation with the extent of activation in the ipsilateral motor areas (P = 0.006) during the right-hand movement and with the extent of activation in both the ipsilateral (P = 0.02) and contralateral (P = 0.006) motor areas during the left-hand movement. The T(1) lesion load along the motor pathway showed a significant positive correlation (P = 0.007) with the extent of activation in the contralateral motor areas during right-hand movement. Our study shows functional adaptive changes that involve both the symptomatic and asymptomatic hemisphere during a simple motor task in patients who had suffered a single clinical attack of hemiparesis. The extent of these changes increased with the time elapsed since disease onset and the severity of brain damage.

Acute Disease↗

Ischaemic penumbra: highlights.

The ischaemic penumbra was described for the first time in the late 1970s as a ring of hypoperfused zone surrounding the region of complete infarction. The penumbral zone is a functionally silent tissue which is able to regain its function if promptly reperfused. This implies that the ischaemic penumbra is not a static but a "dynamic" and "time-dependent" concept. In this paper we describe the role of neuroimmaging tecniques such as single photon emission tomography (SPET), positron emission tomography (PET), and diffusion-weighted and perfusion-weighted magnetic resonance imaging (DWI and PWI) in the study of ischaemic penumbra. These functional imaging techniques have the advantage of giving "in vivo" quantitative estimate of cerebral blood flow (CBF) as well as information on how the ischaemic tissue metabolic changes develop. It follows that, as therapeutic options for treating acute stroke evolve, neuroimaging strategies are assuming an increasingly important role in the initial evaluation and management of the acute ischaemic patient. In this regard, a wide range of therapeutic approaches have been investigated for either ameliorating the perfusion, or interfering with the pathobiochemical cascade leading to ischaemic neuronal damage, or improving endogenous neuroprotection pathways. The "time windows" required for these treatments to be effective varies being rather short for reperfusion and longer for neuroprotection. Salvaging more penumbra would enhance recovery and thereby allow the most appropriate candidate for therapeutic trials to be selected.

Blood Flow Velocity↗