Efficacy of systemic thrombolysis within 4.5 h from stroke symptom onset: a single-centre clinical and diffusion-perfusion 3T MRI study.

PURPOSE: The efficacy of thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) within 3 h from stroke onset has been extensively supported by randomised placebo-controlled multicentre trials. In our single-centre study, we investigated the efficacy of intravenous (IV) administration of rt-PA within 4.5 h of stroke onset, in terms of clinical and radiological outcome, using a 3T magnetic resonance (MR) scanner in a cohort of patients similar to that of multicentre clinical trials. MATERIALS AND METHODS: Consecutive patients treated with IV rt-PA were compared with an historical cohort of untreated patients (controls). Inclusion criteria were: (1) infarction of the middle cerebral artery territory, (2) eligibility for IV rt-PA treatment, and (3) 3T perfusion- and diffusion-weighted MR imaging and MR angiography performed within 4.5 h and repeated after 5-7 days. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Growth of the DWI lesion, saved hypoperfused tissue, and clinical outcome was assessed and compared in treated patients and controls. RESULTS: Forty-three patients treated with rt-PA and 69 controls were eligible for the analysis. Treated patients showed higher percentages of saved hypoperfused tissue (75 vs. 40 %; p = 0.009), vessel recanalisation (65 vs. 27.5%; p = 0.003), and haemorrhagic transformation (21 vs. 7%; p = 0.004), without any clinically significant haemorrhages. Furthermore, treated patients had a significant improvement of NIHSS at 24 h (p < 0.001), at discharge (p ≤ 0.001), and at the 3-month clinical evaluation (p < 0.001), while similar rates of both treated patients and controls achieved a 3-month modified Rankin scale ≤ 2 (62 and 65%; p = 0.7). CONCLUSION: Treatment with IV rt-PA within 4.5 h of stroke onset preserves a significant amount of brain tissue from final infarction, and increases the possibility of early and late clinical improvement.

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.

Floating carotid thrombus treated by intravenous heparin and endarterectomy.

Among different subtypes of ischemic stroke, atherosclerotic stroke carries the greatest risk (30%) of worsening and recurrence during the acute phase of hospitalization with a 7.9% risk ≤ 30 days. Causes of this high risk include plaque rupture leading to thrombus formation, thrombus propagation with consequent vessel occlusion, and distal embolism. In this context, emergent endarterectomy or anticoagulation, followed by deferred endarterectomy, are both controversial. We report a patient with an ischemic stroke caused by thromboembolism from an ulcerated plaque with floating thrombus of the internal carotid artery (ICA). A controversial use of heparin is discussed.

Is stroke history reliably reported by elderly with cognitive impairment? A community-based study.

BACKGROUND/AIMS: Self-reported history of stroke has been questioned in the elderly due to the high prevalence of cognitive impairment. We tested the validity of response to a stroke questionnaire versus clinical diagnosis of stroke among elderly people with and without cognitive impairment. METHODS: Community-dwelling participants to the phase 1 Canadian Study of Health and Aging were screened for self-reported stroke. Physician-diagnosed stroke was set as the gold standard. The positive predictive value (PPV), sensitivity and specificity were determined. RESULTS: 1,536/ 1,659 (93%) participants aged 65 years and over had stroke information from both sources. Among stroke positive responders, the PPV was 81% overall: 76% for cognitively normal, 84% for cognitively impairment with no dementia (CIND), and 82% for demented. Among stroke diagnosed by physicians, history of stroke was reported by 38% cognitively normal, 54% CIND, and 55% demented. The specificity was over 97% in all cognitive categories. CONCLUSION: Among community-dwelling elderly people, any cognitive impairment did not imply inaccurate self-reported history of stroke. High prevalence of stroke and frequent contacts with health services among cognitively-impaired elderly may increase the awareness of stroke symptoms and signs. Stroke increases the risk of developing dementia in both cognitively normal and CIND, and efforts to accomplish stroke prevention are justified, especially in these categories.

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 x 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 x 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.

Ultrasound evaluation of early changes in arterial dissection.

We show magnetic resonance imaging, computed tomography-angiography, and ultrasound images of internal carotid artery dissection in a patient with acute ischemic stroke. Arterial changes occurring during the first few days were detected by serial ultrasound examinations. Neurologic and functional outcome are provided and therapeutic options discussed.

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.

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.

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

BACKGROUND: 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. METHODS: Prevalences of stroke, CIND, and dementia were estimated among participants in the first clinical examination of the Canadian Study of Health and Aging (CSHA-1, n = 2,914). Incidence rates were determined at the 5-year follow-up (CSHA-2) among those cognitively normal and stroke free at CSHA-1 (n = 828). The associations between cognitive impairment and stroke were assessed by Cox regression analyses. RESULTS: Among elderly Canadians, the age-standardized prevalence of stroke, CIND, and dementia were 8%, 17%, and 8%, respectively. Alone or combined, they affected one fourth of the elderly. Among stroke survivors, 64% had cognitive impairment compared with 21% among stroke-free persons. Among the cognitively impaired, 25% had a stroke compared with 4% among the cognitively normal. The incidence rates of stroke, CIND, and dementia were 3, 6, and 3 per 100 person-years, respectively. Compared with cognitively normal subjects, the adjusted risk for incident stroke was 1.3 (95% confidence interval [CI], 0.9 to1.9) in patients with CIND and 2.3 (95% CI, 1.7 to 3.2) in patients with dementia regardless of whether "questionable stroke" was included. CONCLUSIONS: Stroke and cognitive impairment pose risk for each other. CIND is highly prevalent, and some of its subtypes may represent treatable preludes to stroke and/or dementia.

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.

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.

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.

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.

Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

BACKGROUND AND PURPOSES: This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. METHODS: A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. RESULTS: At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). CONCLUSIONS: Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.