Lefties are Never Right: Is Atherosclerotic plaque in the Left carotid artery more vulnerable than on the Right?
Selwaness M, van den Bouwhuijsen Q, van Onkelen RS, Hofman A, Franco OH, van der Lugt A, et al. Atherosclerotic Plaque in the Left Carotid Artery Is More Vulnerable Than in the Right. Stroke. 2014
Left hemispheric strokes can be devastating, impacting the patient’s language center and leading to hemiparesis and hemiplegia. Large vessel atherosclerosis is an established stroke subtype and plaque located at the carotid bifurcation has been implicated in as high as 18% of all strokes. Selwaness et al open their paper by noting that a significantly higher proportion of ischemic events are diagnosed in the left hemisphere compared to the right. The team hypothesize that the higher incidence of events occurring in the lefthemisphere is related to either a higher prevalence, severity or vulnerability of atherosclerotic disease in the left carotid artery.
~ George Bernard Shaw
It’s tough to make predictions, especially about the future but DWI reversal after tPA for stroke helps
Stroke in Paradise: Implementing and Evaluating Prevention in a Afro-Caribbean Population in Martinique
Olindo S, Chausson N, Mejdoubi M, Jeannin S, Rosillette K, Saint-Vil M, et al. Trends in Incidence and Early Outcomes in a Black Afro-Caribbean Population From 1999 to 2012: Etude Réalisée en Martinique et Centrée sur l’Incidence des Accidents vasculaires cérébraux II Study. Stroke. 2014
The Afro-Caribbean (AC) population of Martinique, a French Caribbean island, was found to have a high prevalence of vascular risk factors in a stroke epidemiology study conducted in 1998-1999 (ERMANCIA I). This led to initiation of community-based prevention strategies and a follow-up study using the same methodology (ERMANCIA II) was completed 13 years later (2011-2012). This program involved a large number of local healthcare professionals, both specialists and general practitioners, focusing on patient education regarding health behaviors (diet, physical activity) and engaging patients in tracking their risk factors (blood pressure, blood glucose). A dedicated stroke unit was also formed in 2003 at the local University Hospital of Fort de France.
In this article, Olindo et al evaluated this implementation program. In both ERMANCIA I and II, a comprehensive approach to determination of every stroke by a thorough evaluation of all hospital records and community resources was completed. Patient demographics, vascular risk factors, stroke subtypes, and outcomes were tracked.
The population of Martinique was stable between the study periods (380,000-390,000 people), and the majority is AC. First-ever stroke was identified in 544 AC patients during the ERMANCIA II study period, compared to 580 in 1998-1999. The age-standardised rates significantly decreased by 31% overall between the two evaluations (26% in males, 34% in females). Though the stroke rate of older people declined, a significant increase in those in a 35-44 year age group was noted, with an incidence rate ratio [IRR] 2.25 (95% confidence interval of 1.07-3.70). Frequencies of pre-morbid dyslipidemia, smoking, and atrial fibrillation were significantly higher in the 2011-2012 period; hypertension, diabetes, alcoholism, and coronary disease frequencies remained unchanged. When looking at subtypes, only ischemic stroke was found to be (statistically) significantly reduced over time, and only in women. Overall, the 30-day case-fatality ratio did not change, but the proportion of patients with a good outcome at 1 month (modified Rankin score ≤2) was significantly higher in ERMANCIA II (47% vs. 37.6% in 1998-1999, p=0.03). Along with decreasing stroke incidence, a stable high prevalence of hypertension and diabetes as well as increased proportion with dyslipidemia and tobacco use was found over the two time periods.
There were clearly limitations and challenges – the authors pointed out a lower proportion of patients evaluated by phone or from next of kin reports in ERMANCIA II compared to I. A noted decrease in the proportion of lacunar infarction could partly be explained by change in principal neuroimaging modality, from CT to more extensive MRI use in 2011-2012. This report describes stroke incidence in two periods of time; we cannot get an extensive understanding of the temporal trends. Nevertheless, there is a lot that can be learned from this work, which should be improved and emulated more extensively. It demonstrated that, even within this particular ethnic cohort, an increased stroke incidence was found in males compared to females aged 55-74 years. Just as is occurring elsewhere, the disturbing trend of increased smoking and obesity is contributing to higher stroke rates in younger population groups in Martinique.
This manuscript is another demonstration of the fact that efforts targeting prevention and appropriate management of stroke patients (patient education, dedicated stroke unit care) can reduce its incidence and improve outcomes. Further reduction of stroke incidence in Martinique will need to include addressing tobacco use and medication noncompliance in more effective ways. Much more can still be done. As shown in this report, large-scale epidemiology studies that track a condition, with its risk factors (and facilitators/barriers to addressing them), over time can be very powerful. If we were able and willing to do this for stroke in a coordinated manner at various levels (in a given city/state/country, regionally and even internationally), we could accelerate progress in addressing the enormous burden of cerebrovascular disease. Much can be learned from not only tracking health metrics (including risk factors, care quality, costs, and outcomes) over time, but also by comparing regions/populations where progress is being made and where it is not.
Jones SA, Gottesman RF, Shahar E, Wruck L, Rosamond WD. Validity of Hospital Discharge Diagnosis Codes for Stroke: The Atherosclerosis Risk in Communities Study. Stroke. 2014
Epidemiological estimates regarding stroke prevalence and mortality are often based on ICD-9-CM codes from hospital discharge. The accuracy of such statements is dependent on the codes actually corresponding to the labelled diagnosis. The authors sought to investigate the sensitivity and positive predictive values of ICD-9-CM codes for stroke and intracranial hemorrhage using diagnoses from the Atherosclerosis Risk in Communities (ARIC) study as the gold standard.
The ARIC study is comprised of nearly 16,000 patients in four communities in the US, and the database was searched for hospitalizations for ischemic strokes and intracranial hemorrhage. Strokes were identified by use of a stroke/hemorrhage related ICD-9-CM code, keywords in the discharge summary, or cerebral radiographic findings and validated by both computer algorithm and physician reviewer. Using this group of validated stroke and hemorrhage diagnoses the ICD-9-CM codes were compared.
Looking at AHA/ASA code groupings for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage they found the positive predictive value to be 76% and sensitivity of 68%. An alternative grouping using more ICD codes increased sensitivity to 83%. These numbers are lower than previously published values and suggest stroke incidence may be underestimated based on ICD-9-CM codes.
Cho W, Kim JE, Kim CH, Ban SP, Kang H, Son Y, et al. Long-Term Outcomes After Combined Revascularization Surgery in AdultMoyamoya Disease. Stroke. 2014
De Maria R, Campolo J, Marina Frontali M, Taroni F, Federico A, Inzitari D, et al. Effects of Sapropterin on Endothelium-Dependent Vasodilation in Patients With CADASIL: A Randomized Controlled Trial. Stroke. 2014.
De Maria et al bravely go where no study has gone before, and they should be commended for their efforts. They evaluated the effects of tetrahydrobiopterin (BH4), an essential co-factor for nitric oxide synthesis in endothelial cells, in CADASIL patients. This was a multi-center randomized, double blinded, placebo-controlled trial. Sixty-one CADASIL patients ages 30-65 were randomized to receive placebo or sapropterin, 200-400 mg BID, depending on their weight to target 5 mg/kg. Primary outcome was peripheral arterial tonometry (RH-PAT) performed at 24 months. The thought was that an increase RH-PAT value was determined to be a favorable outcome; meaning that there was more vasodilation and flow. The ITT population included 61 patients. RH-PAT was increased after 24 months in 37% of patients on sapropterin and 28% in placebo. However, when controlling for age, sex and clinical characteristics, improvement was not associated with the treatment arm.
Peripheral arterial tonometry was chosen by De Maria et al as an indirect and surrogate marker for amelioration of endothelial dysfunction seen in CADASIL based on the following thoughts 1) Previous studies in CADASIL patient describe impaired vasoreactivity in both cerebral and peripheral circulation. 2) PAT is independently shown to be associated with incident cardiovascular events in high risk patients. De Maria et al should be applauded for attempting to quantify a method which may be predictive of deterioration in CADASIL patients. However, while it does seem that there is a relationship in CADASIL patients between peripheral arteries and CNS arteries; we still do not know what the extent of that relationship is. More-over, how does that translate to development of disease progression or clinical deterioration?
Ultimately, this study should be lauded for its unique niche and massive undertaking to perform a RTC in such a rare disease entity. The primary outcome was not reached. If the thought is that there may be some improved benefit still of the sapropterin, this could be due either to a sample size that is too small (albeit very large for such a rare disease), a dosing that is too low, an effect is not actually seen in in the 24 month window, or the parameter used to measure improved outcome in these patients may actually be flawed. This was a phase-two study designed to show safety, and that outcome was achieved. While there is the potential to pursue a large scale RCT to evaluate for treatment effect, feasibility of such a process would be called into question as this is a rare disease.
The continued search to better prognosticate patients receiving IV tPA External Validation of the BASIS and M1-BASIS in Thrombolysed Patients
Rajbeer Singh Sangha, MD
Yeo LLL, Paliwal PR, Wakerley B, Khoo CM, Teoh HL, Ahmad A, et al. External Validation of the Boston Acute Stroke Imaging Scale and M1-BASIS inThrombolyzed Patients. Stroke. 2014
A scoring system for AIS must be simple, rapid, reproducible and possible in a variety of clinical settings. Detailed clinical rating instruments are commonly used in the settings of a clinical trial, and while these settings help in determining the efficacy of the instrument, it is often difficult to transition them to everyday practice. As seen from the results of this study, M1-BASIS classification system correlates well with the clinical severity of stroke and can reliably prognosticate outcome in AIS patients treated with systemic thrombolysis. Further analysis and evaluation should be performed to develop this score to be included in a paradigm which can be applied in a rapid fashion during AIS. As technology and the ability of computers to exponentially combine information and perform calculations increases, the stroke community should continue to adapt and utilize these tools from the careful observations and analysis made from our studies.
Howard G, Voeks JH, Meschia JF, Howard VJ, and Brott TJ. Picking the Good Apples: Statistics Versus Good Judgment in Choosing Stent Operators for a Multicenter Clinical Trial. Stroke. 2014
When I performed a cursory search on how to quantify operator performance, I was surprised to learn that the data is very limited. An article in the NEJM last year found that technical skill of practicing bariatric surgeons in Michigan as assessed by peer rating of operative skill was associated with fewer postoperative complications. At the end of the day, it probably relates to the fact that procedural skills are as much of an art as science. And only experience and peer evaluations may have the best odds at correctly triaging operator skill and technical prowess!