American Heart Association

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A History of the TOAST Classification

Vikas Pandey, MD

Adams, HP Jr, Bendixenb BH, Kappelle LJ, Biller J, Love BB, Gordon DL, and Marsh EE, 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 2015

The TOAST Classification system was developed to be able to better classify ischemic strokes that patients had suffered on the basis of etiology as this had an impact on the patient’s prognosis and risk of stroke recurrence. Additionally, the TOAST classification system has been used by different research trials to be able to report the stroke subtype population that their study encountered and by using the same system across different studies, the populations could be better compared with one another.


The article by Drs. Adams and Biller emphasizes the history of the TOAST (or the obviously more convenient name Trial of Org 10172 in Acute Stroke Treatment) classification system, specifically how and why it was developed, and the idea behind which stroke etiologies should be included in the five broad categories (Large artery, small artery, cardioembolic, other, undetermined). An example is how it was intended for large artery strokes to specifically mean strokes related to large artery atherosclerotic disease, and that these patients should usually have evidence of symptomatic atherosclerotic disease elsewhere i.e. coronary or peripheral arteries. They clearly defined that the “other” category included patients that had an established cause of stroke but could not be categorized in the large artery, small artery, or cardioembolic categories, such as non-atherosclerotic vasculopathies, dissections, hypercoagulable states, etc. The reason for inclusion in the “undetermined” group was three-fold as this category included patients for which no etiology was found due to complete but negative workup, incomplete workup, or multifactorial etiologies possible for stroke.

The TOAST scale is easy to use and has good inter-rater agreement and intra-rater reproducibility. The authors recognize the limitations and criticisms of the TOAST scale including how it cannot be applied to pediatric stroke, the plea for dissection-related strokes to be a separate category, and the varying prognosis of different cardioembolic disorders. They also mention how a full workup is always needed for patients to not be put in the undetermined category, so the application of the scale may not be omnipresent. The scale has undergone numerous modifications but the idea has endured the test of time and it is the basis for which new scales are being developed. The TOAST Scale original paper has been cited >4800 times making it one of the most commonly cited contributions to the Stroke journal. The TOAST scale has helped define the thought process that stroke neurologists around the world use when working up a stroke patient and its contribution to our field is invaluable.

@DrVikasNeuro

The Obese Prince and the Smoking Pauper: the interaction between smoking, hypertension and socioeconomic status on stroke risk

Vikas Pandey, MD


“Rich people diseases” have stereotypically been defined as obesity, diabetes, hypertension, and gout, while “poor people diseases” have classically been diseases such as dysentery, malaria, and typhoid. This class struggle has always been a point of philosophical intrigue given the irony that poor people can avoid diseases of the poor by obtaining wealth, only to suffer from a different subset of medical illnesses that affect the wealthy. Education, another measure of socioeconomic status, has previously been linked to increased incidence of both ischemic and hemorrhagic strokes given the increased exposure to risk factors and inability to address these risk factors.  Knowing which groups are most at risk for stroke is important from the public health standpoint given that specified intervention in these subgroups can potentially prevent the most cases.



The authors were testing the hypothesis that while there is a clear link to smoking and stroke risk, as well as hypertension and stroke risk, there is limited data on the interplay between socioeconomic position, smoking and hypertension and their combined effect on ischemic and hemorrhagic stroke incidence. The authors used a pooled cohort study with 68,643 participants from Denmark aged 30-70 and included information on socioeconomic position based on their highest attained education level. Qualitative smoking data and categorized hypertension data was also obtained. The authors analyzed this data using an additive hazards model that is used for assessing additive interactions in survival analyses. They found that smoking was clearly more frequent in those with low education and level of blood pressure was only slightly higher in the low education group. Out of 100,000 person years, low education was deemed to cause 181 extra cases of ischemic stroke in men and 93 extra cases in women. This difference was less marked in hemorrhagic stroke. The combined effect of exposure to all three risk factors was associated with 566 extra cases among men and 438 extra cases among women compared to no exposure. This result was more than what would be expected as a sum of their separate effects demonstrating a synergistic effect of the risk factors with one another.

The article demonstrated an additive effect between the three risk factors specifically studied as well as numerous synergistic links between subgroups of the risk factors.  While some of the data may contain flaws such as underreporting (i.e. incorrect smoking reporting due to low education level) and confounding variables that are difficult to control for, the end message is still convincing in showing that legislation and public health campaigns may be more beneficial if aimed toward the lower socioeconomic classes as the same reductions in risk factors in both groups would reduce a larger number of cases in the lower socioeconomic class. Though the intention of this conclusion is well-guided, I feel that it is equally plausible that such a campaign toward the lower socioeconomic classes would have less of an impact. From personal experience in Miami-Dade county (approximately 20% living below the poverty line), stroke prevention measures do not seem to spur a change in health decisions for those of lower socioeconomic status as they do for aware and educated patients in a higher socioeconomic class. This aspect may be a little lost in the cohort studied from Denmark given the adjusted poverty rate is approximately 6% in the country, one of the lowest for any developed nation. For this reason, I feel future studies in evaluating the reception and comprehension of different stroke prevention policies as well as cultural differences in viewpoints toward personal health may further allow us to pinpoint more accurately the subgroup of patients for which our public health measures may be of the most benefit.

@DrVikasNeuro

INTRAVENTRICULAR FIBRINOLYSIS: Removing the clog and restoring drainage

Prachi Mehndiratta, MD

Khan NR, Tsivgoulis G, Lee SL, Jones GM, Green CS, Katsanos AH, et al. Fibrinolysis for Intraventricular Hemorrhage: An Updated Meta-Analysis and Systematic Review of the Literature. Stroke. 2014


Intraventricular hemorrhage (IVH) results when parenchymal blood dissects or breaks the lining of the fluid filled cavities within the brain. IVH is associated with Intracerebral hemorrhage (ICH) in about 40% of cases and results in a varying but high mortality rate of 40-80%. When present, it requires placement of external ventricular drains to avoid complications such as hydrocephalus. The placement of such a drain for prolonged periods of time carries its own risks of infections such as ventricultis. Recently several studies such as the CLEAR IVH trial have been randomizing patients to receive intraventricular tissue plasminogen activator to decrease clot burden. The authors of this Meta analyses describe the pooled results of studies till date that have explored the use of intraventricular fibrinolysis (IVF).  


A total of 24 retrospective cohort, prospective cohort and randomized controlled studies that met the inclusion criteria of patients’ age >18years, non-traumatic IVH treated with IVF and provided control data were studied. Total sample size, number of patients in each arm, dosage and method of fibrinolysis, IVF complications and outcomes were carefully evaluated. The primary outcome was all cause mortality until one year after treatment whereas secondary outcome was defined as a good functional outcome (modified Rankin score 0-3), as well as lower rates of rehemorrhage, ventriculitis and shunt placement.

The pooled results were starkly in favor of IVF. There was a significantly decreased likelihood of mortality (RR= 0.55, 95%CI: 0.42-0.71; p<0.00001) with IVF and significantly increased likelihood of good functional outcome in the pooled analyses ((RR: 1.66, 95%CI: 1.27-2.19; p=0.0003). These results were primarily driven by the prospective and retrospective studies and only a trend towards significance was noted amongst randomized trials. There was no increase in the rates of ventriculitis, rehemorrhage or shunt requirement associated with IVF use.

These are promising results but should be understood with caution. The decreased relative risk for mortality and increased relative rate of good outcome were not observed in randomized studies. Additionally this Meta analyses represented a widely heterogeneous population with studies utilizing different fibrinolytics in varied doses. A well conducted randomized controlled trial would certainly provide some answers. Let us hope that our doubts about IVF are soon CLEARed.

A Smashing Success? Another look at the etiologic classification of intracerebral hemorrhage

Michelle Christina Johansen, MD

Yeh SJ, Tang SC, Tsai LK, and Jeng JS. Pathogenetical Subtypes of Recurrent Intracerebral Hemorrhage: Designations by SMASH-U Classification System. Stroke. 2014

Intracerebral hemorrhage (ICH) composes a high percentage of admissions to neurointensive care units and they remain a major cause of mortality. Not all hemorrhages are created equal and Dr. Yeh et.al investigate the data surrounding different bleed subtypes in an effort to offer insight into functional outcomes and mortality. Their study employed the SMASH-U classification method which separates ICH etiologies into Structural, Medication related, Amyloid Angiopathy, Systemic Disease, Hypertension and Undetermined. They focused much discussion on the two most common etiologies, Hypertension and Amyloid. They state that the approaches to these distinct patient populations differs and that other classification systems, such as those that use location of bleed are not sufficient to distinguish between these two groups.



The researchers took advantage of their access to the National Taiwan University Hospital Stroke Registry which documents all patients who had a stroke (based on head CT and ICD codes) within two weeks of admission. They obtained data from 4,578 acute ICH patients, classified the patients into the six SMASH-U types and then analyzed the outcomes of first ever ICH cases versus recurrent ICH cases similarly stratified. They excluded trauma or tumor related, subdural/epidural/subarachnoid hemorrhage and stroke hemorrhagic transformation resulting in thorough examination of 3,785 cases. Two raters independently assigned classifications and if after discussion no consensus was reached, they were labeled Undetermined. The bleed was designated Structural if there were vascular lesions in the area of ICH; Medication related if INR≥2, new oral anticoagulant within three days or use of heparin/thrombolytic agent; Amyloid related if the ICH met Boston Criteria; Systemic disease related if there were evidence of thrombocytopenia, liver cirrhosis or non-medication induced coagulopathy and Hypertension induced according to guidelines laid out by the original SMASH-U paper. Notably the investigators added renal failure in consideration of systemic disease. 

The most common etiologies were hypertension and amyloid followed by systemic disease, undetermined, structural and medication related. Of the 185 cases of recurrent ICH classified, the etiology was different in 34. Among the 44 amyloid cases, 31 recurred with the same etiology but 10 were classified as hypertension related. Seventy eight of the 93 recurrent hypertension classified ICH were the same etiology but 7 were re-classified as amyloid related. The main reason for reclassification appears to be the location of the bleed (lobar versus deep structures). The authors appropriately point out that location alone is not sufficient to determine etiology and that amyloid angiopathy can occur in younger patients calling into question the Boston classification scheme. 

The importance of accurate classification is not only deciding treatment but also reflects patient survival.  In evaluation of results, those with Systemic Disease related (51-62%) or Medication induced (49-60%) had worse survival while those with Structural etiology (5-6%) had the best survival.  Interestingly, this article suggests that those with amyloid related hemorrhages (17-27%) fared worse than those with hypertension induced ICH (12-18%) as contrasted to the similar survival curve demonstrated in the SMASH-U study by Meretoja et al. 

While confounders such as the addition of renal failure to systemic disease must be acknowledged, there are many considerations raised for the treating neurologist when assessing this data. Our first year of training is usually dedicated to learning general medicine and it is all too easy to forget this realm with increasing specialization. The importance of appropriate recognition and treatment of comorbid illness such as ITP or cirrhosis is only confirmed by this data. The worse survival curve in patients with amyloid is also something to ponder. How does one decide the appropriate treatment for a patient with Afib and suspected amyloid angiopathy? In the era of rapid expansion and development of oral anticoagulants, many with unestablished methods of reversal, does this preclude the above patients from these medications? While ICH unfortunately remains a staple admission to neurologic intensive units, perhaps consideration of etiology will lead to appropriate and more accurate therapy and assessment of risk.

Flow Diversion Versus Conventional Treatment for Carotid Cavernous Aneurysms

Rajbeer Singh Sangha, MD

Zanaty M, Chalouhi N, Starke R, Guiherme B, Saigh M, Schwartz E, et al. Flow Diversion Versus Conventional Treatment for Carotid Cavernous Aneurysms. Stroke. 2014


With continuing advances in technology and healthcare, several endovascular options have emerged for the treatment of cavernous carotid aneurysms (CCA). These strategies include balloon-assisted coiling (BAC), stent-assisted coiling (SAC), carotid vessel destruction (CVD) and flow diversion. The reported recurrence rate and incomplete angiographic occlusion after treatment with conventional endovascular technique remains high, discouraging their use in complex aneurysms. Recently, Flow-diversion has been emerging as a novel treatment, however there is currently not enough data to establish its superiority over the conventional modalities.  The authors of this study compared the above treatment modalities looking at morbidity, mortality, evolution of mass symptoms and aneurysm occlusion/rate of retreatment. 



Analysis of 157 patients showed no difference in age, gender, and mean aneurysm size between those treated with PED and those treated with conventional endovascular procedures. The patients treated with PED had a significantly lower proportion of small size aneurysms (<10mm), significantly higher rate of improvement (92.16%) and a shorter follow-up duration. The rate of complete occlusion was 81.36% (48/59) for PED, 42.25% (39/71) for SAC, 27.27% (6/22) for coiling and 73.33% (11/15) for CVD.  The rate of major complications was 6.6% (11/167). Patients that were treated with PED or SAC had 3.84 lower odds to develop complications (OR= 0.26 p<0.05).

The authors make a compelling case through this study for the use of flow diversion (PED) technique for treatment of symptomatic CCA. The results of this study certainly do provide merit to the argument and given the low rate of complications, it is difficult to see why such a technique should not be aggressively studied further. Given the retrospective nature of the study and the possible biases which are acknowledged by the authors, a large multicenter trial would provide the power and validity required to show that PED is likely superior versus traditional endovascular methods that have been employed. It is refreshing to see an endovascular procedure which has lower rates of complication and less requirements for retreatment given the discouraging news that has been surrounding the field with recent studies the past few years.


Atrial Fibrillation, Subclinical Infarcts, and Cognitive Decline

Rizwan Kalani, MD

Chen LY, Lopez FL, Gottesman RF, Huxley RR, Agarwal SK, Loehr L, et al. Atrial Fibrillation and Cognitive Decline−The Role of Subclinical Cerebral Infarcts: The Atherosclerosis Risk in Communities Study. Stroke. 2014

Atrial Fibrillation (AF) is the most common cardiac arrhythmia, with increasing prevalence, incidence, and associated mortality worldwide. The increased risk of stroke is well known to all of us, but more recent studies have demonstrated an association of AF with cognitive impairment or dementia. Large epidemiologic series have shown that patients with AF have both an increased risk of dementia and faster cognitive decline, even without a clinical history of symptomatic stroke. We all probably have seen patients with a history of AF with clinically silent infarcts (SI) on neuroimaging; the authors of this study hypothesized that these lesions are associated with greater cognitive impairment in AF patients.

Chen et al evaluated data from the Atherosclerosis Risk in Communities (ARIC) biracial, multicenter, population-based study. The 935 patient cohort analyzed completed study visits that included three serial cognitive assessments (between 1993-1995, 1996-1998, and 2004-2006) and brain MRI at two points in time (between 1993-1995 and 2004-2006). AF diagnosis was obtained from ECG’s at study visits and hospital records, with cardiologist confirmation; patients were also clinically monitored for incident clinical stroke. Attention, executive function, and recent memory were assessed using the digit symbol substitution (DSS), word fluency (WF), and delayed word recall (DWR) tests, respectively. SI were defined as asymptomatic T2/PD hyperintense, T1 hypodense, focal, >3mm non-mass lesions on MRI.
The main novel findings were that patients who developed AF had significantly greater annual average rate of decline in DSS (-0.77) and WF (-0.80) in a linear model compared to those who did not develop AF, after adjusting for demographics/education/vascular risk factors. In subgroup analysis, patients who had more prevalent SI’s on baseline imaging who developed AF had greater decline in WF (-2.65) than those who didn’t develop AF during follow-up. In those that were found to have new SI’s on serial imaging during the study period, the ones that developed AF had greater decline in DSS (-1.51) than those who did not develop AF. Furthermore, in patients with incident AF, the proportion that developed SI’s was nearly twice that of those without new AF. In individuals without SI’s, incident AF was not associated with cognitive testing scores.
This study suggests that the association between incident AF and cognitive decline is mediated by SI’s. Most of these lesions turned out to be in the deep grey nuclei or deep supratentorial white matter; though not classic AF-related ischemia, up to 15% of patients with lacunar infarction have demonstrated an embolic source in prior reports. It is important to note that the role of shared vascular risk factors (HTN, DM, APO-e4 genotype, etc) contributing to cognitive decline cannot be excluded in this study.

The implications and questions raised by the results are important given the global epidemics of stroke, dementia, and AF. Future studies will need to evaluate risk of SI in those with low CHA2DS2-VASc scores and if anticoagulation reduces risk of cognitive decline in AF patients. Other questions raised are if we should be looking for occult AF in patients with SI’s or should we treat them with anticoagulants without documented AF?

Lagoons vs. Lacunes – Understanding the depth of the matter.

Prachi Mehndiratta, MD

Elnan Kvistad CE, Oygarden H, Logallo N, Moen G, Thomassen L, Waje-Andreassen U, and Naess H. A Dark Side of Subcortical Diffusion-Weighted Lesions? Characteristics, Cause, and Outcome in Large Subcortical Infarction: The Bergen Norwegian Stroke Cooperation Study. Stroke. 2014

While we have all read plenty about small vessel disease infarcts or lacunar infarcts, less has been said about large subcortical infarcts (LSI) that can be colloquially referred to as lagoons. In this study the authors aimed to identify the differences in clinical characteristics, etiologic factors and outcome amongst patients with LSI when compared with lacunar infarcts (LI), cortical infarcts (CI) or infarcts elsewhere (no LSI).



All patients admitted to the Stroke unit between Feb 2006 and July 2013 were screened. In total, MRI scanning was performed on 1979 patients and 1886 with positive diffusion weighted lesions were included in the analysis. Infarcts were classified as subcortical >15mm and <15mm in size. LSI were found in 6.8% of the patients with the remainder being LI (16.8%), CI (28.8%) and no LSI (47.6). LSI infarcts were further classified as belonging to the following territories- lenticulostriate, anterior choroidal, thalamic and white matter. Clinically, patients with LSI had more severe strokes than those with LI, CI or no LSI. There was a significantly greater proportion of patients with atrial fibrillation (p=0.003) and fewer number of smokers in the LSI group (p=0.014).

Vascular imaging demonstrated that complete or partial occlusion of the proximal MCA segment was more frequent in the LSI group as compared to those with LI (39.1% vs. 1.6%, p<0.001), CI (15 [7.9%], p<0.001) and no-LSI (39.1% vs. 17.1%, p<0.001). Large artery disease and cardio-embolism was more common in patients with LSI as compared to those with LI. Cryptogenic stroke mechanism was found in 60.9% of LSI patients which was significantly higher than the number of cryptogenic strokes in all other groups. Intuitively, due the larger stroke size and higher likelihood of a proximal vessel occlusion, patients with LSI were more likely to have progressive symptoms and had a worse overall short term outcome (graded on the modified Rankin scale) and these results were statistically significant. Those with anterior choroidal artery infarcts did worse than others.

This study highlights how a large subcortical infarct may initially “look like a duck” but “not quack like one”. Clinically a LSI may appear to mimic a lacunar syndrome; however there is a higher likelihood for progression of symptoms and presence of a large vessel occlusion. These characteristics underscore the importance for early treatment with IV tpa and need for diffusion weighted imaging. Although a large proportion of these patients had unclear mechanism of stroke, I would have liked to know more about the extent of stroke workup that these patients were subjected to. Also, were the raters of clinical symptoms and MRI findings independent?  If not, there definitely could have been introduction of bias.  As one would have expected with a larger stroke size, these patients had worse short term outcome. But, how about long term outcome? I hope to see more literature in the near to help answer some of these questions.   


Predicting the addition of an insult to an injury: spontaneous intracerebral hemorrhage and pneumonia.

Mark N. Rubin, MD

Ji R, Haipeng H, Pan Y, Du W, Wang P, Liu G, Wang Y, et al. Risk Score to Predict Hospital-Acquired Pneumonia After SpontaneousIntracerebral Hemorrhage. Stroke. 2014


Unequivocally, our patients with intracerebral hemorrhage are quite ill. Clinical experience with this highly morbid and potentially fatal disease demonstrates that patients with this condition are at multisystem risk, including worsening hemorrhage, thromboembolism, cardiac complications, and infections including pneumonia. While it comes as no surprise that patients with intracerebral hemorrhage, who are often neurologically disabled if not comatose, experience hospital-acquired pneumonia on an all-too-frequent basis, it seems to happen in spite of our best multidisciplinary efforts to screen for dysphagia and adhere to infection precautions. This is a particularly important issue for hemorrhagic stroke patients because the development of pneumonia is a predictor of worse outcome overall and increased mortality. This is also of major health economic concern, as the development of hospital-acquired pneumonia is a heavily scrutinized aspect of hospital performance in the United States and tied to reimbursement for services. A group of Chinese investigators – who already brought us a pneumonia prediction score for acute ischemic stroke quite recently – have collaborated again with an eye toward pneumonia prediction in patients with spontaneous intracerebral hemorrhage.



The investigators put together a cohort of nearly 5000 patients with spontaneous intracerebral hemorrhage across many institutions in China, collectively referred to as the China National Stroke Registry. This cohort was split for derivation and validation of clinical features that might predict the development of pneumonia based on previously published risk factors. In brief, they derived a 20+ point risk score that reasonably predicted the development of pneumonia after intracerebral hemorrhage, irrespective of hematoma volume, particularly in patients admitted for greater than 48 hours. They found that older age, current smoking, chronic obstructive pulmonary disease, pre-stroke dependence, low admission Glasgow Coma Score, high National Institute of Health Stroke Scale score, and dysphagia were independently and significantly associated with the development of hospital-acquired pneumonia after intracranial hemorrhage.

The natural goal after the development of such scores is to predict so that we may prevent. This score requires  external validation, but the hope is that the score can inform clinical trials aimed at the prevention of pneumonia in these very ill patients, thus averting the addition of the proverbial insult to an already grave injury.

Comparison of stroke risk factor profiles in ischemic stroke v/s hemorrhagic stroke patients with type 1 diabetes as a guide to understanding pathophysiology

Chirantan Banerjee, MD

Hägg S, Thorn LM, Forsblom CM, Gordin D, Saraheimo M, Tolonen N, et al. Different Risk Factor Profiles for Ischemic and Hemorrhagic Stroke in Type 1 Diabetes Mellitus. Stroke. 2014

Risk factor epidemiology is the crux of cerebrovascular prevention. It guides us towards appropriate targets to ameliorate future strokes. Prospective cohort studies, albeit expensive, are one of the most effective ways to learn the most about stroke epidemiology in a population, as they give us the ability to ask varied questions within the same study framework. The Finnish Diabetic Nephropathy Study (FinnDiane) was founded to uncover the risk factors and mechanisms of diabetic micro and macro-vascular complications, with a focus on type 1 diabetes, and has previously reported associations between diabetic nephropathy as well as severe diabetic retinopathy and stroke.




In this issue of Stroke, Hagg et al attempt to identify and compare risk factors for stroke and its subtypes in the FinnDiane multicenter observational cohort. 4083 stroke free participants with type 1 diabetes were enrolled at baseline, and data on clinical as well as laboratory variables was collected. Outcome was ascertained by questionnaires, death certificates, and the Finnish National Hospital Discharge Register, and confirmed by medical records, neuroimaging. There were 149 incident strokes, with more than usual proportion of hemorrhage (30%) and lacunar (55% of ischemic) strokes. Diabetic nephropathy and higher systolic blood pressure were associated with both ischemic and hemorrhagic strokes. Although longer duration of diabetes, higher HbA1c, insulin resistance and history of smoking were associated with ischemic stroke, they were not associated with hemorrhagic stroke. Lower BMI was independently associated with hemorrhagic strokes. Sex, waist circumference, metabolic syndrome, triglycerides, LDL and HDL cholesterol were not associated with either stroke.

Several thoughts come to mind with these novel findings. The fact that higher systolic blood pressure is associated with stroke despite adjusting for nephropathy, hints that not all of the effect of high SBP on stroke risk is mediated by nephropathy in these patients. Also, the fact that metabolic syndrome, sex, triglycerides, as well as LDL and HDL cholesterol were not associated with any stroke suggest that the pathophysiology of stroke in Type 1 diabetics may be distinct from those in Type 2 diabetes patients. 

Although an association between glycemic control and microvascular complications has been demonstrated previously, there had been conflicting evidence with regard to macrovascular complications. This study found HbA1C levels to be independently associated with ischemic stroke in Type 1 diabetes patients. With regards to lower BMI being associated with hemorrhagic stroke, some of the effect may be driven by the fact that most of the hemorrhagic stroke patients had diabetic nephropathy, which has been associated with cachexia and platelet dysfunction. 

The study has several weaknesses. The findings cannot be generalized to Type 2 diabetes patients or the general stroke at risk population. Outcome assessment was based on questionnaires and the national register, where silent strokes would be missed, thus biasing towards null. Also, including subarachnoid hemorrhages in the composite hemorrhagic stroke outcome may be a confounder as the etiology of SAH is disparate from intraparenchymal hemorrhage.

Despite having a restricted cohort with a specific phenotype, this study generates several pathophysiological hypotheses, and stresses on the need for further inquiry into modifiable risk factors in diabetic patients. As stroke clinicians, we should tailor our preventative efforts to each patient!”

Lacunar Strokes in Diabetics

Rizwan Kalani, MD


Palacio S, McClure LA, Benavente OR, Bazan III C, Pergola P, and Hart RG. Lacunar Strokes in Patients With Diabetes Mellitus: Risk Factors, Infarct Location, and Prognosis: The Secondary Prevention of Small Subcortical Strokes Study. Stroke. 2014


Diabetes mellitus (DM) is a well established and an increasingly more prevalent risk factor for ischemic stroke. It confers a two-fold increased risk of cerebrovascular ischemia. Prior studies have demonstrated increased risk of initial lacunar stroke among diabetics as well as an increased prevalence of lacunes compared to other ischemic stroke subtypes in this patient population.


Palacio et al looked at 3020 patients from the SPS3 (Secondary Prevention of Small Subcortical Strokes) trial to compare baseline demographics, vascular risk factors, and neuroimaging findings in diabetics compared to non-diabetics. Data on vascular events (including recurrent ischemic stroke and their subtypes) over a mean 3.6 year follow-up period was also analyzed between the two groups.

Diabetes was independently associated with Hispanic ethnicity (36% vs 28%), ischemic heart disease (11% vs 6%), and peripheral vascular disease (5% vs 2%) compared to non-diabetics. Patients with DM also had significantly more posterior circulation territory lacunar strokes and more frequent intracranial arterial stenosis of 50% on baseline neuroimaging (23% vs 14% in non-DM patients). After adjusting for other predictors – the rate of recurrent ischemic stroke of any subtype (11.4% in diabetics and 5.9% in non-diabetics), disabling/fatal recurrent stroke, MI, all-cause mortality, and death from vascular (& uncertain) etiology were approximately two-fold higher in DM patients during follow-up.

This report adds to the literature that demonstrates worse clinical outcomes in patients with stroke and diabetes. A notable limitation of this study is that DM control during follow-up was not available. Regardless, this manuscript does raise some important and interesting questions that should be evaluated in future studies. What factors contribute to worse outcomes in diabetics with lacunar strokes? How can we effectively monitor and improve our secondary (and even primary) stroke prevention strategies in patients with DM? At this point, it is well worth considering more frequent and longer outpatient stroke neurology follow-up in this high-risk patient population and ensure aggressive risk factor control.