Hock Luen Teoh

The Montreal Cognitive Assessment (MoCA) is superior to the Mini-Mental State Examination (MMSE) for the detection of vascular cognitive impairment after acute stroke

BACKGROUND The majority of patient with post-stroke Vascular Cognitive Impairment (VCI) have Vascular Cognitive Impairment No Dementia (VCIND). The Mini-Mental State Examination (MMSE) has been criticized as a poor screening test for VCIND due to insensitivity to visuospatial and executive function impairments. The Montreal Cognitive Assessment (MoCA) was designed to be more sensitive to such deficits and may therefore be a superior screening instrument for VCIND. METHODS Stable patients within 14days of their index stroke without significant physical disability, aphasia, dysarthria, active psychiatric illness or pre-existing dementia were eligible. Cognitive and neurological measures were administered after informed consent. RESULTS 100 patients were recruited. Of the 57 patients with unimpaired MMSE scores, 18 (32%) patients had an impaired MoCA score. By comparison, only 2 out of the 41 (4.9%) patients with unimpaired MoCA scores had impaired MMSE scores. Moreover, MMSE domain subtest scores could not differentiate between groups of differing screening test results, whilst MoCA domain subtest scores (Visuospatial/Executive Function, Attention and Recall) could. CONCLUSION The MoCA is more sensitive than the MMSE in screening for cognitive impairment after acute stroke. Longitudinal studies are required to establish the prognostic value of MoCA and MMSE evaluation in the acute post-stroke period for cognitive impairment as defined by the standard method of formal neuropsychological evaluation 3-6 months after stroke.

Velocity Criteria for Intracranial Stenosis Revisited An International Multicenter Study of Transcranial Doppler and Digital Subtraction Angiography

Background and Purpose— Intracranial atherosclerotic disease is associated with a high risk of stroke recurrence. We aimed to determine accuracy of transcranial Doppler screening at laboratories that share the same standardized scanning protocol. Methods— Patients with symptoms of cerebral ischemia were prospectively studied. Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) criteria were used for identification of ≥50% stenosis. We determined velocity cutoffs for ≥70% stenosis on digital subtraction angiography by Warfarin–Aspirin Symptomatic Intracranial Disease criteria and evaluated novel stenotic/prestenotic ratio and low-velocity criteria. Results— A total of 102 patients with intracranial atherosclerotic disease (age 57±13 years; 72% men; median National Institutes of Health Stroke Scale 3, interquartile range 6) provided 690 transcranial Doppler/digital subtraction angiography vessel pairs. On digital subtraction angiography, ≥50% stenosis was found in 97 and ≥70% stenosis in 62 arteries. Predictive values for transcranial Doppler SONIA criteria were similar (P>0.9) between middle cerebral artery (sensitivity 78%, specificity 93%, positive predictive value 73%, negative predictive value 94%, and overall accuracy 90%) and vertebral artery/basilar artery (69%, 98%, 88%, 93%, and 92%). As a single velocity criterion, most sensitive mean flow velocity thresholds for ≥70% stenosis were: middle cerebral artery >120 cm/s (71%) and vertebral artery/basilar artery >110 cm/s (55%). Optimal combined criteria for ≥70% stenosis were: middle cerebral artery >120 cm/s, or stenotic/prestenotic ratio ≥3, or low velocity (sensitivity 91%, specificity 80%, receiver operating characteristic 0.858), and vertebral artery/basilar artery >110 cm/s or stenotic/prestenotic ratio ≥3 (60%, 95%, 0.769, respectively). Conclusions— At laboratories with a standardized scanning protocol, SONIA mean flow velocity criteria remain reliably predictive of ≥50% stenosis. Novel velocity/ratio criteria for ≥70% stenosis increased sensitivity and showed good agreement with invasive angiography.

Multicenter external validation of the ABCD2 score in triaging TIA patients

Objectives: A simple clinical score (ABCD2 score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD2 score. We aimed to prospectively validate the former score in a multicenter case series study. Methods: We prospectively calculated the ABCD2 score (age [≥60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10–59 minutes: 1, ≥60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). Results: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%–12%) and 16% (95% CI 10%–22%). The ABCD2 score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57–0.88) and 90-day (c statistic 0.75, 95% CI 0.65–0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD2 score >3 points (28%, 95% CI 18%–38%) than in patients with an ABCD2 score ≤3 points (4%, 95% CI 0%–9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD2 score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04–20.84, p = 0.045). Conclusion: Our findings externally validate the usefulness of the ABCD2 score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD2 score >2.

Feasibility and Safety of Intravenous Thrombolysis in Multiethnic Asian Stroke Patients in Singapore

Treatment rates with intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (IS) remain low in Asian populations. Various logistic obstacles and higher anticipated bleeding risk in Asians are major concerns. We report on the feasibility and safety of IV-tPA therapy at our tertiary care center. Consecutive acute IS patients eligible for thrombolysis were treated with low-dose (maximum 50 mg) IV-tPA between January 2000 and September 2006 and with standard-dose (maximum 90 mg) IV-tPA between October 2006 and May 2008. The efficacy of IV-tPA was assessed by the modified Rankin Scale (mRS) score at 3 months and by absolute changes in the National Institute of Health Stroke Scale (NIHSS) score at hospital discharge and 3 months. The safety of IV-tPA was assessed by the rate of symptomatic intracranial hemorrhage (SICH). A total of 130 patients were included (mean age, 60±13 years; 60% males; median NIHSS score, 14). A total of 48 patients received low-dose IV-tPA, and 82 patients received standard-dose IV-tPA. The median onset to treatment time was 160 minutes. Some 59% of the patients achieved functional independence (mRS score 0-1) at 3 months with standard-dose tPA, compared with 35% in the low-dose group (P=.011). SICH occurred more frequently with the low dose (14.5%) than with the standard dose (1.2%; P=.004). In a multivariate logistic regression model, lower admission NIHSS score (odds ratio [OR]=0.78 per 1-point increase; 95% confidence interval [CI]=0.70-0.88), lower pretreatment blood glucose level (OR=0.76 per 1 mmol/L increase; 95% CI=0.60-0.95), shorter time from symptom onset to IV-tPA bolus (OR=0.97 per 1-minute increase; 95% CI=0.94-1.0), and standard-dose IV-tPA (OR=12.49; 95% CI=2.9-53.89) were associated with a higher likelihood for functional independence at 3 months. Our data indicate that standard-dose IV-tPA (0.9 mg/kg) was feasible and safe for treating acute IS in our multiethnic Asian population in Singapore.

Current status of intravenous thrombolysis for acute ischemic stroke in Asia

Background Data regarding thrombolysis for acute ischemic stroke in Asia are scarce and only a small percentage of patients are thrombolysed. The dose of intravenous tissue plasminogen activator (IV-tPA) in Asia remains controversial. Case-controlled observation studies in Asia included only Japanese patients and suggested the clinical efficacy and safety of low-dose IV-tPA (0·6 mg/kg body weight; max 60 mg) comparable to standard dose (0·9 mg/kg body weight; max. 90 mg). Reduced treatment cost, lower symptomatic intracerebral hemorrhage risk and comparable efficacy encouraged many Asian centers to adopt low-dose or even variable-dose IV-tPA regimens. We evaluated various Asian thrombolysis studies and compared with SITS-MOST registry and NINDS trial. Methods We included the published studies on acute ischemic stroke thrombolysis in Asia. Unadjusted relative risks and 95% Confidence intervals were calculated for each study. Pooled estimates from random effects models were used because the tests for heterogeneity were significant. Results We found only 18 publications regarding acute ischemic stroke thrombolysis in Asia that included total of 9300 patients. Owing to ethnic differences, stroke severity, small number of cases in individual reports, outcome measures and tPA dose regimes, it is difficult to compare these studies. Functional outcomes were almost similar (to Japanese studies) when lower-dose IV-tPA was used in non-Japanese populations across Asia. Interestingly, with standard dose IV-tPA, considerably better functional outcomes were observed, without increasing symptomatic intracerebral hemorrhage rates. Conclusions Variable dose regimens of IV-tPA are used across Asia without any reliable or established evidence. Establishing a uniform IV-tPA regimen is essential since the rapid improvements in health-care facilities and public awareness are expected to increase the rates of thrombolysis in Asia.

Penumbral mismatch is underestimated using standard volumetric methods and this is exacerbated with time.

Background and aim: The mismatch between perfusion weighted images (PWI) and diffusion weighted images (DWI) using MR is increasingly being applied in patient selection for therapeutic trials. Two approaches to the calculation of the mismatch volume exist—the commonly used volumetric and the more precise co-registration method, the latter of which considers lesion topography. That there are differences in the mismatch volume analysed by each method and that these are time dependent was hypothesised. Methods: Patients within 48 h of ischaemic stroke onset had baseline MR PWI/DWI mismatch and T2 outcome volumes at 3 months. Volumetric mismatch volume was defined as PWI minus DWI lesion. Co-registration mismatch volume was defined as the PWI defect lesion not overlapped by the co-registered DWI lesion. Results: 72 patients of median age 74.0 years were studied. Median baseline MR was at 5.9 h (IQR 3.0, 20.4 h) after stroke onset. Consistent underestimation of the mismatch volume occurred using the volumetric method (volumetric median 9.3 ml, IQR 0, 63 ml; co-registration median 20.1 ml, IQR 3.2, 69.8 ml; p<0.0001). This difference increased with time from stroke onset (p = 0.006). Conclusions: Volumetric analysis consistently underestimates the PWI/DWI mismatch volume compared with the more precise co-registration method. This effect increases with time.

Stroke Risk Factors and Outcomes Among Various Asian Ethnic Groups in Singapore

Data on interethnic differences in the Asian stroke population are limited. We evaluated the relationships among various cardiovascular risk factors, stroke subtypes, and outcomes in a multiethnic Singaporean population comprising consecutive ischemic stroke patients presenting to our tertiary center over a 1-year period. Strokes were classified based on criteria used in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Functional independence at hospital discharge was defined as a modified Rankin Scale (mRS) score of 0-2. The ethnic distribution of the study population (n = 481; mean age, 64.1 ± 11.9 years) was 74% Chinese, 17% Malay, and 9% Indian. The prevalence of risk factors was similar in the 3 ethnic groups except for diabetes (Chinese, 39.8%; Malay, 67.5%; Indian, 52.3%; P < .001). Hypertension and hypercholesterolemia were the most common cardiovascular risk factors. Lacunar stroke was the most frequent stroke subtype (47.9%). Large-artery atherosclerotic infarctions were more prevalent in Indians (25.0%), whereas lacunar infarctions occured more frequently in Chinese (51.8%; P < .01). No differences in in-hospital mortality and functional independence at discharge were seen among the 3 ethnic groups. Despite the differences in risk factors and in stroke subtypes classified by location or underlying etiology, short-term outcome measures were similar in the 3 different Asian ethnicities in Singapore.

Persistence of hyperdense middle cerebral artery sign on follow-up CT scan after intravenous thrombolysis is associated with poor outcome.

Background: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months. Methods: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0–1) and poor (mRS score 2–6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows. Results: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19–92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4–32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151–1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666–0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991–11.333, p = 0.039) were associated with poor outcome at 3 months. Conclusion: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome.

Safety of transcranial Doppler ‘bubble study’ for identification of right to left shunts: an international multicentre study

Background and purpose A recent retrospective study using an online list service established by the American Academy of Neurology has suggested that ischaemic cerebrovascular events may occur in patients who undergo ‘bubble studies’ (BS) with either transcranial Doppler (TCD) or transoesophageal echocardiography (TOE). The safety of TCD-BS for right to left shunt (RLS) identification was evaluated prospectively in an international multicentre study. Methods Consecutive patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attack (TIA)) were screened for potential ischaemic cerebrovascular events following injection of microbubbles during TCD-BS for identification of RLS at three tertiary care stroke centres. TCD-BS was performed according to the standardised International Consensus Protocol. TOE-BS was performed in selected cases for confirmation of TCD-BS. Results 508 patients hospitalised with acute cerebral ischaemia (mean age 46±12 years, 59% men; 63% ischaemic stroke, 37% TIA) were investigated with TCD-BS within 1 week of ictus. RLS was identified in 151 cases (30%). TOE-BS was performed in 101 out of 151 patients with RLS identified on TCD-BS (67%). It was positive in 99 patients (98%). The rate of ischaemic cerebrovascular complications during or after TCD-BS was 0% (95% CI by the adjusted Wald method: 0–0.6%). Structural cardiac abnormalities were identified in 38 patients, including atrial septal aneurysm (n=23), tetralogy of Fallot (n=1), intracardiac thrombus (n=2), ventricular septal defect (n=3) and atrial myxoma (n=1). Conclusion TCD-BS is a safe screening test for identification of RLS, independent of the presence of cardiac structural abnormalities.

Patent foramen ovale and prothrombotic markers in young stroke patients.

Patent foramen ovale (PFO) is more frequent in cryptogenic stroke patients than in the general population. The aim of this study was to determine prothrombotic markers regarding PFO in young cryptogenic stroke patients. We prospectively included consecutive cryptogenic stroke patients younger than 55 years. PFO was diagnosed with simultaneous transcranial Doppler and transesophageal echocardiography. We analyzed the following prothrombotic markers: antiphospholipid antibodies (APS), protein C and protein S deficiencies, factor V Leiden FVG1691A, prothrombin gene mutation PTG20210A and coagulation factor XII mutation FXIIC46T. From June 2005 to July 2006 we studied 39 patients, mean age 44.7 ± 8.6 years, 48.7% men. PFO was detected in 17 patients (43.6%). We found no differences between PFO and non-PFO patients regarding prothrombotic markers: APS (P = 0.851), protein S deficiency (P = 0.851), protein C deficiency (P = 0.249), FVG1691A (P = 0.202), PTG20210A (P = 0.401) or FXIIC46T (P = 0.966). Female gender was the only variable related to prothrombotic markers, independent of PFO (P = 0.001). The only prothrombotic marker related to PFO size (large PFO) was APS (P = 0.043). Large PFO were also related to deep venous thrombosis (P = 0.040) and atrial septal aneurysm (P = 0.010). PFO patients do not present more prothrombotic markers than non-PFO patients, but APS are more frequent in large PFO.