Silvia Di Legge

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 ≥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.

The reciprocal risks of stroke and cognitive impairment in an elderly population

Stroke, dementia, and cognitive impairment no dementia (CIND) pose major threats to the elderly but have rarely been studied together in the same population. We aimed to compare the relative frequencies of stroke, CIND, and dementia in an elderly population and to examine whether cognitive impairment poses a risk for stroke.

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.

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

Abstract.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.

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.

The Canadian Neurological Scale and the NIHSS: Development and Validation of a Simple Conversion Model

Background: The Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) are among the most reliable stroke severity assessment scales. The CNS requires less extensive neurological evaluation and is quicker and simpler to administer. Objective: Our aim was to develop and validate a simple conversion model from the CNS to the NIHSS. Methods: A conversion model was developed using data from a consecutive series of acute-stroke patients who were scored using both scales. The model was then validated in an external dataset in which all patients were prospectively assessed for stroke severity using both scales by different observers which consisted of neurology residents or stroke fellows. Results: In all, 168 patients were included in the model development, with a median age of 73 years (20–94). Men constituted 51.8%. The median NIHSS score was 6 (0–31). The median CNS score was 8.5 (1.5–11.5). The relationship between CNS and NIHSS could be expressed as the formula: NIHSS = 23 – 2 × CNS. A cohort of 350 acute-stroke patients with similar characteristics was used for model validation. There was a highly significant positive correlation between the observed and predicted NIHSS score (r = 0.87, p < 0.001). The predicted NIHSS score was on average 0.61 higher than the observed NIHSS score (95% CI = 0.31–0.91). Conclusions: The CNS can be reliably converted to the NIHSS using a simple conversion formula: NIHSS = 23 – 2 × CNS. This finding may have a practical impact by permitting reliable comparisons with NIHSS-based evaluations and simplifying the routine assessment of acute-stroke patients in more diverse settings.

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.

Intra-arterial Thrombectomy versus Standard Intravenous Thrombolysis in Patients with Anterior Circulation Stroke Caused by Intracranial Arterial Occlusions: A Single-center Experience

BACKGROUND Severely impaired patients with persisting intracranial occlusion despite standard treatment with intravenous (IV) administration of recombinant tissue plasminogen activator (rtPA) or presenting beyond the therapeutic window for IV rtPA may be candidates for interventional neurothrombectomy (NT). The safety and efficacy of NT by the Penumbra System (PS) were compared with standard IV rtPA treatment in patients with severe acute ischemic stroke (AIS) caused by large intracranial vessel occlusion in the anterior circulation. METHODS Consecutive AIS patients underwent a predefined treatment algorithm based on arrival time, stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS) score, and site of arterial occlusion on computed tomographic angiography (CTA). NT was performed either after a standard dose of IV rtPA (bridging therapy [BT]) or as single treatment (stand-alone NT [SAT]). Rates of recanalization, symptomatic intracranial bleeding (SIB), mortality, and functional outcome in NT patients were compared with a historical cohort of IV rtPA treated patients (i.e., controls). Three-month favourable outcome was defined as a modified Rankin Scale (mRS) score ≤2. RESULTS Forty-six AIS patients were treated with NT and 51 with IV rtPA. The 2 groups did not differ with regard to demographics, onset NIHSS score (18.5±4 v 17±5; P=.06), or site of intracranial occlusion. Onset-to-treatment time in the NT and IV rtPA groups was 230 minutes (±78) and 176.5 (±44) minutes, respectively (P=.001). NT patients had significantly higher percentages of major improvement (≥8 points NIHSS score change at 24 hours; 26% v 10%; P=.03) and partial/complete recanalization (93.5% v 45%; P<.0001) compared to controls. Treatment by either SAT or BT similarly improved the chance of early recanalization and early clinical improvement. No significant differences were observed in the rate of SIB (11% v 6%), 3-month mortality (24% v 25%), or favorable outcome (40% v 35%) between NT and IV rtPA patients. CONCLUSIONS Despite significantly delayed time of intervention, NT patients had higher rates of recanalization and early major improvement, with no differences in symptomatic intracranial hemorrhages. Early NIHSS score improvement did not translate into better 3-month mortality or outcome. NT seems a safe and effective adjuvant treatment strategy for selected patients with severe AIS secondary to large intracranial vessel occlusion in the anterior circulation.

Usefulness of Primitive Reflexes in Demented and Non-Demented Cerebrovascular Patients in Daily Clinical Practice

The aim of this study was to investigate the usefulness of primitive reflexes (PRs) as additional alert signs in a routine clinical setting of cognitive decline in an elderly population of chronic ischemic cerebrovascular patients. We considered the occurrence of grasp, palmomental, glabellar and snout reflexes in 75 demented (VaD) and 75 non-demented (VaND) patients, and in 75 healthy elderly controls. We never elicited more than two PRs in controls. The occurrence of three or four PRs provided the strongest correlation with dementia (p < 0.0001), with 93% specificity irrespective of low sensitivity. In conclusion, the occurrence of more than two PRs might serve as an additional warning sign of possible mild cognitive impairment in chronic ischemic cerebrovascular patients.

Stroke Prevention: Managing Modifiable Risk Factors

Prevention plays a crucial role in counteracting morbidity and mortality related to ischemic stroke. It has been estimated that 50% of stroke are preventable through control of modifiable risk factors and lifestyle changes. Antihypertensive treatment is recommended for both prevention of recurrent stroke and other vascular events. The use of antiplatelets and statins has been shown to reduce the risk of recurrent stroke and other vascular events. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are indicated in stroke prevention because they also promote vascular health. Effective secondary-prevention strategies for selected patients include carotid revascularization for high-grade carotid stenosis and vitamin K antagonist treatment for atrial fibrillation. The results of recent clinical trials investigating new anticoagulants (factor Xa inhibitors and direct thrombin inhibitors) clearly indicate alternative strategies in stroke prevention for patients with atrial fibrillation. This paper describes the current landscape and developments in stroke prevention with special reference to medical treatment in secondary prevention of ischemic stroke.