Robert Gan

Patent Foramen Ovale Size and Embolic Brain Imaging Findings Among Patients With Ischemic Stroke

BACKGROUND AND PURPOSE Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ischemic stroke patients. METHODS As part of the Northern Manhattan Stroke Study, 95 patients with first ischemic stroke over age 39 underwent transesophageal echocardiography (TEE) for evaluation of a cardiac source of embolism. The stroke subtype was determined by modified NINDS Stroke Data Bank criteria. Stroke subtype and MRI/CT imaging data were evaluated blind to the presence of a PFO. These findings were compared between two groups: patients with medium to large PFO (> or =2 mm) and small (<2 mm) or no PFO. RESULTS Of the 95 patients who underwent TEE, 31 (33%) had a PFO. The frequency of PFO was significantly greater among patients with cryptogenic infarcts (19 of 42; 45%) compared with patients with determined cause of stroke (12 of 53, 23%; P=0.02). Medium to large PFOs were found more often among cryptogenic strokes than among infarcts of determined cause (26% versus 6%; P=0.04). Superficial infarcts occurred more often in the group with larger PFOs than in the group with small or no PFOs (50% versus 21%; P=0.02). Patients with medium or large PFOs more frequently had occipital and infratentorial strokes (57% versus 27%; P=0.02). CONCLUSIONS Stroke patients with larger PFOs show more brain imaging features of embolic infarcts than those with small PFOs. Larger PFOs may be more likely to cause paradoxical embolization and may help explain the stroke mechanism among patients with no other definite cause.

Testing the validity of the lacunar hypothesis: The northern Manhattan stroke study experience

Backgrouncd/Objective Few studies have attempted to validate the “lacunar hypothesis.” The accuracy of identifying lacunar and other nonlacunar mechanisms of infarction will be increasingly important in evaluating potential stroke treatments. The aim of this study was to determine the value of lacunar syndromes in predicting radiologic lacunes and the value of clinicoradiologic lacunes in predicting “lacunar infarction” as final stroke mechanism. Methods From 1990 to 1994, 591 patients with cerebral infarction, who were from northern Manhattan and over the age of 39, were prospectively examined. Data were collected on the admitting clinical syndrome (lacunar or nonlacunar) and brain imaging findings. Lacunar syndromes were categorized as pure motor hemiparesis (PMH), pure sensory syndrome (PSS), sensorimotor syndrome (SMS), ataxic-hemiparesis (A-H), and other lacunar syndromes. Brain imaging findings were classified as radiologic lacune or nonlacune. Positive predictive values, sensitivities, and specificities of lacunar syndromes for identifying radiologic lacunes were calculated. The final mechanism of infarction was determined after review of all the diagnostic tests and compared among the lacunar groups. Results Lacunar syndromes occurred in 225 cases. PMH was the most common lacunar syndrome, accounting for 45%, SMS 20%, A-H 18%, and PSS 7%. Lacunar syndromes had an overall positive predictive value (PPV) of 87% for detecting radiologic lacune: PSS loo%, A-H 95%, SMS 87%, and PMH 79%. Among the 195 patients who presented with a lacunar syndrome and had this condition confirmed radiologically, 147 were classified as having a final diagnosis of lacunar mechanism of infarction (PPV = 75%). Atherosclerosis accounted for 17 (9%), cardioembolism 10 (5%), cryptogenic 17 (9%), and other unusual causes 4 (2%). Conclusion While lacunar syndromes, especially PSS and A-H, are highly predictive of lacune, in about one in four patients presenting with lacunar syndromes confirmed radiologically the condition is associated with nonlacunar mechanisms of infarction. Noninvasive neurovascular and cardiac evaluations are still warranted even among patients with lacunes.

Danqi Piantang Jiaonang (DJ), a Traditional Chinese Medicine, in Poststroke Recovery

Background and Purpose— Stroke is a leading cause of death and disability worldwide. Despite improvements in acute stroke treatment, many patients only make a partial or poor recovery. Therefore, there is a need for treatments that would further improve outcome. Danqi Piantang Jiaonang (DJ; NeuroAid), a traditional Chinese medicine widely used in China to improve recovery after stroke, has been compared with another traditional Chinese medicine in 2 unpublished randomized clinical trials. The results of these studies were pooled and reanalyzed to assess efficacy and safety. Methods— Six hundred five subjects were randomized in 2 randomized double-blinded, controlled trials to receive either DJ or Buchang Naoxintong Jiaonang. Subjects were treated for 1 month. Inclusion criteria were: (1) patients with recent (from 10 days to 6 months) ischemic stroke; (2) patients satisfying Western diagnostic standards for stroke and traditional Chinese medicine standards for diagnosis of apoplexy; and (3) Diagnostic Therapeutic Effects of Apoplexy score ≥10. Results— The functional outcome, measured by the Comprehensive Function Score component of the Diagnostic Therapeutic Effects of Apoplexy scale, showed a statistically significant superiority of DJ over the control treatment group (relative risk, 2.4; 95% CI, 1.28 to 4.51; P=0.007). Tolerance was excellent in both groups. Conclusions— The pooled analysis of 2 unpublished trials of DJ, a traditional Chinese medicine currently approved in China to improve neurological recovery after stroke, shows good tolerability and superiority of DJ over another traditional Chinese medicine also approved for stroke. A large double-blind randomized clinical trial is required to further assess the safety and efficacy of DJ.

Carotid bruit for detection of hemodynamically significant carotid stenosis: the Northern Manhattan Study

Abstract Objective: The prevalence of carotid bruits and the utility of auscultation for predicting carotid stenosis are not well known. We aimed to establish the prevalence of carotid bruits and the diagnostic accuracy of auscultation for detection of hemodynamically significant carotid stenosis, using carotid duplex as the gold standard. Methods: The Northern Manhattan Study (NOMAS) is a prospective multiethnic community-based cohort designed to examine the incidence of stroke and other vascular events and the association between various vascular risk factors and subclinical atherosclerosis. Of the stroke-free cohort (n=3298), 686 were examined for carotid bruits and underwent carotid duplex. Main outcome measures included prevalence of carotid bruits and sensitivity, specificity, positive predictive value, negative predictive value and accuracy of auscultation for prediction of ipsilateral carotid stenosis. Results: Among 686 subjects with a mean age of 68.2 ± 9.4 years, the prevalence of ≥60% carotid stenosis as detected by ultrasound was 2.2% and the prevalence of carotid bruits was 4.1%. For detection of carotid stenosis, sensitivity of auscultation was 56%, specificity was 98%, positive predictive value was 25%, negative predictive value was 99% and overall accuracy was 97.5%. Discussion: In this ethnically diverse cohort, the prevalence of carotid bruits and hemodynamically significant carotid stenosis was low. Sensitivity and positive predictive value were also low, and the 44% false-negative rate suggests that auscultation is not sufficient to exclude carotid stenosis. While the presence of a bruit may still warrant further evaluation with carotid duplex, ultrasonography may be considered in high-risk asymptomatic patients, irrespective of findings on auscultation.

Effects of Posture on Right-to-Left Shunt Detection by Contrast Transcranial Doppler

Background and Purpose— There is controversy about the optimal patient position for the detection of right-to-left shunt (RLS). The study was performed to investigate which patient position best detects RLS during contrast-enhanced transcranial Doppler. Methods— We prospectively evaluated consecutive patients with ischemic stroke or TIA referred to our Noninvasive Cerebrovascular Laboratory for suspected paradoxical embolism. The standard protocol for RLS detection recommended by the International Consensus Criteria was followed. Each patient was examined at rest and after Valsalva maneuver in 4 positions: supine, right lateral decubitus, right lateral leaning, and upright sitting, in random order. RLS was graded 0 (no microbubbles [mB] detected), 1 (1–10 mB), 2 (>10 mB but no curtain), and 3 (curtain, shower of mB). Blood pressure, heart rate, and neurological symptoms were monitored. Data were analyzed using SPSS version 17. Results— RLS was detected in at least 1 position in 89 of 240 patients (37.1%; 95% CI, 33.1%–43.3%). The detection of at least 1 mB with normal breathing was lowest in supine position and highest in right lateral decubitus. With Valsalva maneuver, this was highest in upright sitting (20.4% versus 8.3%; P<0.0002). If mB were undetected on upright sitting position, then they may still be detected in other positions. Changes in the position of the body and the injection of agitated saline were well-tolerated. Conclusions— RLS is best detected in the upright sitting position with Valsalva maneuver. If negative, then other positions may be used. Validation of our findings by other centers may be helpful.

The NeuroAiD Safe Treatment (NeST) Registry: a protocol

Introduction NeuroAiD (MLC601, MLC901), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries. The NeuroAiD Safe Treatment (NeST) Registry aims to assess its use and safety in the real-world setting. Methods and analysis The NeST Registry is designed as a product registry that would provide information on the use and safety of NeuroAiD in clinical practice. An online NeST Registry was set up to allow easy entry and retrieval of essential information including demographics, medical conditions, clinical assessments of neurological, functional and cognitive state, compliance, concomitant medications, and side effects, if any, among patients on NeuroAiD. Patients who are taking or have been prescribed NeuroAiD may be included. Participation is voluntary. Data collected are similar to information obtained during standard care and are prospectively entered by the participating physicians at baseline (before initialisation of NeuroAiD) and during subsequent visits. The primary outcome assessed is safety (ie, non-serious and serious adverse event), while compliance and neurological status over time are secondary outcomes. The in-person follow-up assessments are timed with clinical appointments. Anonymised data will be extracted and collectively analysed. Initial target sample size for the registry is 2000. Analysis will be performed after every 500 participants entered with completed follow-up information. Ethics and dissemination Doctors who prescribe NeuroAiD will be introduced to the registry by local partners. The central coordinator of the registry will discuss the protocol and requirements for implementation with doctors who show interest. Currently, the registry has been approved by the Ethics Committees of Universiti Kebangsaan Malaysia (Malaysia) and National Brain Center (Indonesia). In addition, for other countries, Ethics Committee approval will be obtained in accordance with local requirements. Trial registration number NCT02536079.

Using the full span of the SPAN-100 index to predict functional outcome in the CHIMES study.

The SPAN-[Stroke Prognostication using Age and National Institutes of Health Stroke Scale (NIHSS)]100 index is a prognostic tool for ischemic stroke calculated as age plus baseline NIHSS. In its original derivation, it was dichotomized at a threshold of 100. Patients who were SPAN-100-positive (≥100) had poorer outcome following intravenous thrombolysis compared with SPAN-100negative (<100) patients (1,2). One limitation of this dichotomy is the low proportion of patients with scores >100 (9·9% in National Institute of Neurological Disorders and Stroke, 10·5% in Virtual International Stroke Trials Archive). Patients less than 58 years old cannot achieve a SPAN-100-positive status even if they had maximum NIHSS score of 42. We aimed to study the relationship of SPAN-100 index as a continuous variable with functional outcomes measured by the modified Rankin score (mRS). The Chinese Medicine NeuroAid Efficacy on Stroke Recovery (CHIMES) trial is a randomized, placebo-controlled study that investigated the efficacy of NeuroAid in improving functional outcome (3,4). We applied the SPAN-100 index to the placebo group of the CHIMES trial to evaluate its ability to predict mRS scores at month-3. The last-observation-carriedforward-method was used for missing data. Of 1099 patients included in the CHIMES study, 1061 (97%) had mRS outcome at month-3 with mean age of 61·4 ± 11·3 years. A total of 531 out of 549 patients (97%) in the placebo group had month-3 data. Only one patient was SPAN-100-positive. There was a positive correlation between SPAN-100 index and month-3 mRS (Spearman correlation coefficient r = 0·316, P ≤ 0·001). Figure 1 shows the shift across the range of mRS as the SPAN-100 score increases. Our study shows that the SPAN-100 index can predict functional outcome following ischemic stroke across its spectrum. This finding implies a potential utility of the SPAN-100 index beyond dichotomization, particularly among patients with scores below 100, in predicting prognosis, benefits, and risks of treatment, including intravenous thrombolysis. These results need confirmation in larger cohorts.