American Heart Association

Monthly Archives: September 2014

High-Dose Atorvastatin and Renal Function After Stroke

Rizwan Kalani, MD

Amarenco P, Callahan A, Campese III VM, Goldstein LB, Hennerici MG, Messig M, et al. Effect of High-Dose Atorvastatin on Renal Function in Subjects With Stroke or Transient Ischemic Attack in the SPARCL Trial. Stroke. 2014

Chronic kidney disease (CKD) shares many risk factors with cerebrovascular disease – principally hypertension, diabetes, and dyslipidemia. Lowering low-density lipoprotein (LDL) cholesterol in patients with dyslipidemia and coronary artery disease or diabetes has been shown to be renoprotective in addition to reducing cardiovascular events. CKD has several implications for patients with cerebrovascular disease including conferring an increased risk for stroke and being an independent predictor of mortality and outcomes after stroke. Thus, CKD, which is also a global public health problem, should also be of interest to neurologists.

In this study, Amarenco et al conducted a post-hoc analysis of data from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. The effect of atorvastatin 80mg per day (vs. placebo) on change in renal function, measured by estimated glomerular filtration rate (GFR), in patients with and without baseline CKD was assessed. Those with GFR<60 ml/min/1.73m2 were defined as having CKD. Secondary analysis by baseline glycemic/metabolic status (presence or absence of type 2 diabetes and metabolic syndrome) was also conducted given its effects on renal function.
Of the 4731 SPARCL patients, 4393 had available serial renal function data (66% had GFR>60 at baseline, and 34% had CKD – majority of which had stage 3 CKD [GFR of 30-59]). Baseline GFR was similar between the statin and placebo groups. There was significant improvement in GFR in the atorvastatin-treated group (vs placebo) after 1, 2, 3, 4, and 5 years of treatment. The GFR increase (from baseline) at 5 years in the statin group averaged 3.46 vs 1.42 in the placebo group (p<0.001). This improvement was independent of initial renal function – in those with CKD, the atorvastatin-treated patients had a mean 4.24 rise in GFR at 5 years whereas those without CKD had an average 3.27 increase. This was seen in the setting of a 40% reduction in LDL in patients with CKD and a 37% reduction in those without CKD. In those with a history of diabetes at baseline, an average GFR increase of 1.12 was seen in the statin group vs a decrease of 1.69 in the placebo group (at 5 years) (p=0.016).

This study is consistent with prior reports suggestive of the idea that statin treatment is nephroprotective in high-risk patients with vascular disease. In the SPARCL patient population, an effect was seen within a year and is maintained for the 5 years of follow-up. Its important to note that the study cohort also had adequate blood pressure control and appropriate management of other vascular risk factors. Also, a small number of patients in this study had stage 4 or 5 CKD, so it is difficult to assess if 80mg atorvastatin treatment could benefit those with more severe renal dysfunction. Though the degree of improvement in GFR may seem modest, this is just another reason to use high intensity statin (atorvastatin) after non-cardioembolic stroke/TIA.

By |September 15th, 2014|treatment|1 Comment

What’s In a Number? Looking at eGFR and its relation to Stroke Outcome

Vikas Pandey, MD

Luo Y, Wang X, Matsushita K, Wang C, Zhao X, Hu B, et al. Associations Between Estimated Glomerular Filtration Rate and Stroke Outcomes in Diabetic Versus Nondiabetic Patients. Stroke. 2014.

In the United States, a commonly recited phrase among neurologists in regards to stroke epidemiology is that stroke is the fourth leading cause of death in the U.S. and the leading cause of disability. In China however (1.3 billion, most populous country in the world), stroke is the leading cause of both death and disability. For this reason, the authors were motivated to identify stroke-related risk factors in their home country, in this case the link between kidney function (based on estimated glomerular filtration rate [eGFR]) and stroke risk in diabetic and non-diabetic patients. Estimated GFR has been linked previously with poor clinical outcomes in stroke patients but whether this link could be modified by accounting for particular disease (in this case, diabetes) is still unclear.

The group used a prospective cohort of 17280 patients of which 26.8% were diabetic from 2 large national databases and followed them after one year for all-cause mortality, stroke recurrence, and stroke disability. They did not differentiate between the types of stroke (ischemic, subarachnoid hemorrhage, or hemorrhagic infarct) in regards to the primary outcomes. Diabetes was defined as fasting glucose > 126 mg/dl, non-fasting glucose > 200 mg/dl, previous symptoms of hyperglycemic crisis, use of glucose lowering drugs or self-reported history of diabetes. EGFR was calculated using CKD-EPI equation with an adjusted coefficient of 1.1 for the Asian population. The eGFR was split into categories of <45, 45-59, 60-89, 90-119 and >120 ml/min/1.73m^2. The 90-119 group served as the reference group for analysis due to the idea that hyperfiltration (>120 group) may have been due to muscle loss related to malnutrition or diabetes-related kidney hyperfiltration or other confounders. All of the endpoints were found to have significantly increased Odds ratio (OR) in those with a reduced eGFR (<45) in non-diabetics however in the diabetic group with eGFR <45, the stroke disability measure reached non-significance with the other two measures of all-cause mortality and stroke recurrence being significant. On the higher end (eGFR >120), the group found that non-diabetic patients had only increased risk of all-cause mortality, but not with stroke recurrence or stroke disability. Among diabetic patients with eGFR >120, all of the endpoints were significantly increased.

Diabetes is an undeniable risk factor for both kidney dysfunction and stroke and thus the question asked by the authors of whether there is truly a link between eGFR and poor stroke outcome is a valid one. The data reaffirms that a low eGFR (<45) is an indicator of poor stroke outcome, regardless of if the patient is diabetic or not. A topic that is more obsolete and with more conflicting previous data, however, is the idea that an increased eGFR also has a potential role in predicting poor stroke outcome.  The group found that the risk gradient for increased eGFR predicting mortality, stroke recurrence and stroke disability is steeper in the diabetic group versus the non-diabetic group. The group admits that the conditions that lead to increased eGFR such as lower muscle mass, inflammation, differences in body composition and undiagnosed malignancy may confound some of the results as these lead to increased mortality however aside from these causes is the idea of kidney hyperperfusion in diabetics which may be a result of diabetic pathophysiology and may signify hyperperfusion elsewhere (i.e. intracerebral). Thus dividing ischemic and hemorrhagic stroke subtypes and looking at the same endpoint and testing whether ischemic stroke may do better with higher eGFR and hemorrhagic strokes better with low eGFR may be a future area of study for the group. The study has many limitations including lack of generalizability (one ethnicity studied), selection bias (eGFR largely based off initial values) and the confounders previously mentioned but the study does perform the function of having clinicians worldwide pay closer attention to kidney dysfunction and its role in stroke.

Adherence to ECASS III 3-4.5 Hour Exclusions and Association with Outcome

Rajbeer Singh Sangha, MD

Cronin CA, Sheth KN, Zhao X, Messé SR, Olson DM, Hernandez AF, et al. Adherence to Third European Cooperative Acute Stroke Study 3- to 4.5-Hour Exclusions and Association With Outcome: Data From Get With The Guidelines-Stroke. Stroke. 2014

The Third European Cooperative Acute Stroke Study (ECASS III) showed a benefit to IV tPA treatment 3-4.5 hours from symptom onset.  Under instructions from European regulatory authorities, ECASS III excluded 4 patient groups in addition to the standard exclusions in use for 0-3 hours in the United States: (1) age >80, (2) history of stroke and diabetes, (3) any oral anticoagulant treatment regardless of coagulation test results, and (4) NIHSS>25. The authors of this study analyzed data from the national Get With The Guidelines–Stroke (GWTG) database to determine the degree of adherence to additional exclusion criteria for patients treated >3-4.5 hours from symptom onset in the USA.

The results of the study showed that the patients treated in the later time window were younger (mean age 67.1 vs.69.7) and presented with less severe symptoms (NIHSS median 9 vs. 11). Medical comorbidities were similar, except that patients treated in the later time window had a lower rate of atrial fibrillation and coronary artery disease, and a higher rate of smoking. Both these results were interesting as perhaps it reflects overall patient attitude towards their symptoms. Due to the fact that their symptoms were less severe, or the mechanisms involved did not cause significant disability initially, could it be that these patients were waiting for the symptoms to resolve thus leading them to present at a later time.

Interesting results from the analysis showed Age >80 was generally associated with worse outcomes, but without significant differences between time windows except that age >80 was associated with less risk of being non-ambulatory in the >3-4.5hr window compared with the 0-3hr window. Similarly, the combination of prior stroke and diabetes was associated with less risk of being non-ambulatory in the >3-4.5hr window vs. the 0-3hr window.
From the data, the authors determine that strict adherence to clinical trial exclusion criteria is not supported and and thus we should consider patients above the age of 80, NIHSS>25 and warfarin use with INR ≤1.7 amongst others for the time window of 3-4.5 hrs in the administration of tPA. It is my hope that we take the results of this study and apply it to our day to day practice in the hopes that we have positive outcomes that can further be reported. As a greater proportion of the population begins to exceed the age of 80, we must continue to push the limits and boundaries of treatment therapy in a safe and controlled manner. Randomized controlled trials should continue to be conducted to confirm and support the results of this analysis.
By |September 11th, 2014|treatment|0 Comments

Contrast Enhanced Ultrasound: The Wave of the Future for evaluation of Carotid Arteries?

Michelle Christina Johansen, MD

Saito K, Nagatsuka K, Ishibashi-Ueda H, Watanabe A, Kannki H, and Iihara K. Contrast-Enhanced Ultrasound for the Evaluation of Neovascularization in Atherosclerotic Carotid Artery Plaques. Stroke. 2014

In 1948, Dr. George Ludwig, a Navy physician first used ultrasound technology to diagnose gallstones in the United States. Six years previously, Dr. Karl Dussik, Neurologist and Psychiatrist at the University of Vienna, described the use of ultrasound in diagnosis of brain tumors. In the ensuing decades, the use of ultrasound for medical diagnosis dramatically escalated, and this modality that relies upon high frequency sound waves to produce dynamic images of internal structures, is still heavily relied upon in some specialties. The advent of CT and MRI however directed the neurologist away from ultrasound, particularly in regard to blood vessel imaging. 

Saito et al. postulate that the use of contrast-enhanced ultrasound (CEUS) in patients with known carotid stenosis to quantitatively evaluate neo-vessels would aid in the identification of vulnerable plaques. The foundation for the study centers on the idea that proliferation of blood vessels in plaque predicts vulnerability for rupture. It is known that plaque disruption tends to occur at points where the plaque surface is weakest and most vulnerable. This coincides with points where stresses (biomechanical or hemodynamic) acting on plaques are concentrated. The authors therefore utilized CEUS on the plaque shoulder. Fifty consecutive patients who underwent carotid endarterectomy (CEA) were enrolled. Carotid ultrasound was performed and the plaques were classified as echolucent or echogenic.  CEUS was then performed and the investigators calculated enhanced intensity (EI) in the core, plaque shoulder and vessel lumen. Plaque specimens from these patients status post CEA were obtained and the histopathology was reviewed. 

The authors found that the contrast (EI) of plaque shoulders was greater than that of plaque cores. This correlated with histopathology that revealed fewer neo-vessels in the cores. The authors also found EIs associated with density of neo-vessels in the plaque shoulders.  EIs were significantly higher in ruptured plaques as well as in symptomatic plaques. The conclusion of the investigators is that CEUS can predict and stratify plaque vulnerability thereby enhancing evaluation and treatment of atherosclerotic disease.

In the era of increasing medical costs, the study makes an appealing argument. Ultrasound is less invasive, easily transportable and takes relatively less time than the average diagnostic brain MRI. So should all accredited stroke centers invest in more ultrasound machines? There are many questions that the practicing vascular neurologist should contemplate before relying upon this tool for clinical decision making. While ultrasound is a dynamic imaging modality, it is also highly dependent on the operator and thus the reproducibility of results is an important issue to consider. This study also revolves around contrastenhanced ultrasound which over the preceding years, has been an object of contention for the FDA. In 2007, they issued a black box warningand mandated a 30-minute monitoring period after use in all patients. This has since been removed but the administration of contrast still remains a consideration. CEUS also remains relatively inaccessible. This study was also conducted in an Asian population which represents an isolated cohort. Literature has demonstrated that the risk factors and pathophysiology of strokes in this demographic is different than those with other ethnic backgrounds. How accurate then are these results when applied to other patient populations?

While catching the wave of contrast enhanced ultrasound is a thrilling prospect, more research is certainly needed before this modality is ready for primetime.      

A Day Late and a Dollar Short: Cerebral Metabolism of Oxygen in Moyamoya Disease.

Mark N Rubin, MD

A Japanese roommate of mine back in medical school told me that moyamoya translates better to “miasma” than “puff of smoke,” the latter of which is most typically associated with the characteristic angiographic findings in the setting of proximal cerebral arterial occlusion(s). I suppose that is a more apt phrase physiologically, given the well-documented miasma-like “bad air” issues of moyamoya, including altered oxygen extraction fraction and metabolic consumption of oxygen (CMRO2). A group of Japanese investigators sought to better clarify the effect surgical revascularization with extracranial-to-intracranial (EC-IC) bypass surgery.

The study included 12 children and 30 relatively young (30s to 50s) adults. The underwent sophisticated functional neuroimaging with positron emission tomography (PET) scans that allowed the investigators to assess numerous hemodynamic and physiologic parameters including cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral blood volume (CBF), and CMRO2. This study was performed pre- and 3-to-4-months post-EC-IC bypass to assess for any difference the intervention may have made. The main pre-operative finding was that most patients had diminished CBF and CMRO2 with elevated CBV and OEF: a hemodynamic pattern that makes sense in the setting of myriad, structurally unsound, tiny collaterals trying to take the place of major arterial “highways.” In brief, the main post-operative finding was that most of these radiographically-determined hemodynamic parameters were corrected toward normalcy with one major caveat: CMRO2 only improved in the kiddos. This finding led the investigators to speculate that perhaps only a young brain without obvious clinical stroke or silent cerebral ischemia can fully recover metabolic activity (as inferred by CMRO2) toward a normal state after revascularization because it can “hibernate.”

To be sure, CMRO2 is only a single functional parameter and is not a direct surrogate of outcome of any sort, so one should not take from this that adults with moyamoya are “a day late and a dollar short.” In fact, the reported outcome over 10 years of follow-up seems favorable (although lacking in details). The idea that a younger, incompletely developed brain maintains some ischemic resilience and plasticity is interesting and plausible, and needs to be investigated further. 

By |September 9th, 2014|treatment|0 Comments

Reduction in day to day SBP variability after TIA or stroke: Replicating clinic findings at home

Prachi Mehndiratta, MD

Webb AJS, Wilson M, Lovett N, Paul N, Fischer U, and Rothwell PM. Response of Day-to-Day Home Blood Pressure Variability by Antihypertensive Drug Class After Transient Ischemic Attack or Nondisabling Stroke. Stroke. 2014

Prior studies have established that Calcium channel blockers and Thiazide diuretics have maximum impact on the Systolic Blood Pressure (SBP) and the variability in blood pressure thereby decreasing primary and recurrent stroke risk. The authors of this study investigated the impact of several antihypertensive class medications on home blood pressure variability and if the effect was greater at a certain time of the day. Five hundred and thirty six patients were recruited from the Oxford Vascular Study’s TIA and Stroke clinic. At the first ascertainment visit, one month after the index event, patients underwent BP monitoring in the clinic. BP was measured in the non-dominant arm in a sitting position 5 minutes after rest and two separate readings 5 minutes apart were recorded.  The patients were instructed to monitor their BP at home at the first opportunity after discharge which could be before or at the one month visit.

Three sets of home measurements were taken utilizing a pre specified equipment type upon waking, at mid-morning and before bed. These measurements recorded by a Bluetooth-enabled, regularly-calibrated, telemetric BP monitor were then transmitted by a Bluetooth radio to a mobile phone, for secure transmission to a server hosting a password-protected website for review and download of readings. Goal mean BP was 130/80 mm Hg and medications to achieve this goal were started either in clinic or after one week of home monitoring. A standardized protocol utilizing a combination of thiazide diuretics (TI) , calcium channel blockers (CCB)  and renin angiotensin inhibitors (RASi) was most commonly used, however medications could be altered based on adverse reactions and physician discretion.  Mean, minimum and maximum SBP and DBP were assessed and compared between two periods- 3-10 days prior to intervention and 8-15 days after. Diurnal variability in SBP was measured as the coefficient of variation of the cluster averages for each day and Day-to-day variability in SBP and DBP was measured as the residual CV about a moving average over 5 days. Multivariate linear regression and Chi-square tests were used for analysis of data.

The authors report a significant reduction in home SBP variability following treatment with CCBs or Tis as compared with RASis. Differences in change in SBP variability persisted after adjustment for age, gender and cardiovascular risk factors and baseline mean and variability in SBP (CCB/diuretic vs combination vs RASi p=0.005). The reduction in day to day SBP variability was greatest for early morning readings and there was no significant impact observed on DBP variability or on mean SBP.

How can we translate these results to general practice? And what does this mean for our patients? The lack of outcome data, rate of recurrent ischemia etc. makes it difficult to apply these findings in clinical practice. Although the SBP variability was decreased on home BP monitoring by Calcium channel blockers and thiazide diuretics, did these patients benefit from this reduction in variability? Additionally only a few medications from each class were used and some like Indapamide are not widely prescribed in the US. BP was recorded only three times a day which may be too few to measure an actual effect on variability, another alternative would be to use ambulatory BP monitors. Well, in my mind this study is useful in understanding that CCB’s and TI’s reduced SBP variability in TIA and stroke measurements even when BP is recorded in the home setting, BUT I am left asking for more clinically significant outcome data. 

By |September 8th, 2014|treatment|0 Comments

A Banana a Day May Also Send the Doctor Away

Daniel Korya, MD

Seth A, Mossavar-Rahmani Y, Kamensky V, Silver B, Lakshminarayan K, Prentice R, et al. Potassium Intake and Risk of Stroke in Women With Hypertension and Nonhypertension in the Women’s Health Initiative. Stroke. 2014

The old saying of “an apple a day sends the doctor away” is said to have started in the 1860’s in the region of Pembrokeshire in Wales. The original phrase was actually “eat an apple on going to bed, and you’ll keep the doctor from earning his bread.” The phrase eventually evolved from its origins to “an apple a day, no doctor to pay”; and finally, the familiar “an apple a day sends the doctor away.” 

Apples are low in calories, low in sodium and high in vitamin C. A meta-analysis published in Stroke (2013) showed an inverse relationship between vitamin C intake and stroke risk.  Recently, potassium has been investigated for its ability to ward off stroke. Everyone seems to associate bananas with potassium since they are believed to have high levels of potassium (the average banana has 118 g of potassium, other foods with high potassium are mentioned below). So, perhaps another saying should be “a banana a day sends the doctor away”.  Or, should it?
The study published by Arjun Seth and his colleagues presented statistical analysis of a subgroup of the Women’s Health Initiative Observational Study (WHI-OS) cohort. The population was women aged 50-79 from 40 states who were prospectively followed for a mean of 11.1 years. Outliers based on caloric intake were removed and the data of quantity of daily potassium intake was derived from the food frequency questionnaires (FFQs). There were 90,137 patients remaining who were evaluated for the development of ischemic stroke during the follow-up period. The study controlled for age, ethnicity, BMI, history of smoking, alcohol intake, hypertension, aspirin use, hormone therapy, diabetes, history of MI, dyslipidemia and activity level.
After identifying this sub-cohort, the authors described their statistical methods and analysis. In summary, the group was broken down into quartiles based on mean daily potassium intake and an analysis of variance or a chi squared was performed to compare the quartiles with the covariates. Then, hazard ratios were estimated from the Cox proportional hazards model comparing the highest quartile with the lowest quartile of potassium intake. 
With regard to the analysis of hypertensive versus non-hypertensive patients, the researchers used a history of hypertension as opposed to hypertension during the follow-up period.  The argument for this distinction was the belief that potassium intake may be related to blood pressure and the possibility of hypertension being a mediator between potassium intake and stroke.  Essentially, the idea is that potassium may be mitigating the development of stroke through its blood pressure lowering effects. 
The results of the study are interesting. It was found that blacks, current smokers, and non-drinkers had lower dietary potassium intake.  Patients who were more active actually had more potassium intake. The highest quartile of potassium intake had a 27% lower incidence of stroke than the lowest quartile. This effect was 30% in a subgroup of patients with normal BMIs. There was a lower rate of small vessel strokes in non-hypertensive patients as compared with hypertensives.
To conclude, the authors remind us that this is the largest U.S. cohort of post-menopausal women and they reiterate the results. But, more importantly, a summary of the information this study provided is as follows: the amount of daily potassium post-menopausal women consumed was calculated based on the foods they reportedly ate. Foods that are high in potassium are salmon, green leafy vegetables, avocados, beans, baked potatoes, yogurt and bananas. Patients who ate those foods also tended to be non-smokers, non-blacks, who were drinkers with higher activity levels. Also, these patients were less likely to have small vessel ischemic strokes if they were not hypertensive. 

Looking for markers to predict cerebral amyloid angiopathy and cerebral superficial siderosis

Duy Le, MD

Charidimou A, Jäger H, Peeters A, Vandermeeren Y, Laloux P, Baron JC, and Werring D. White Matter Perivascular Spaces Are Related to Cortical SuperficialSiderosis in Cerebral Amyloid Angiopathy. Stroke. 2014

Sporadic cerebral amyloid angiopathy (CAA) is a common entity that we see manifested as intracerebral hemorrhages in elderly patients. This article attempts to identify imaging markers which may be associated with patients who may develop CAA or cerebral superifical siderosis (CSS). The feeling is that MRI-visible centrum semiovale perivascular spaces (CSO-PVS) is such a potential biomarker for these two entities.

To achieve this, the Charidimou et al retrospectively evaluated 138 CAA patients based on possible/probably CAA according to the Boston Criteria. This was a multicenter study. Raters were blinded and patients were deemed to have degree of CSO-PVS (0=no PVS, 1=<10 PVS, 2=11-20 PVS, 3=21-40 PVS and 4=>40 PVS) based on 1.5T MRIs. This was evaluated for both the centrum semi ovale and the basal ganglia. The results show that High CSO-PVS degree was present in 61.2% of CAA cases. There was no correlation or increase with basal ganglia PVS. The prevalence of any CSS or disseminated CSS (involving > 3 sulci), was higher in patients with high CSO-PVS degree as compared to the low CSO-PVS degree. Using multivariable logistic regression analysis, CSS presence (OR 4.78; p 0.004) was an independent predictor of high CSO-PVS degree.

Ultimately, this study shows that a high degree of MRI-visible CSO-PVS are prevalent in patients with CAA. Although only correlation can be drawn from this study, and not causation, this supports the potential idea that patients with CAA may have underlying fluid drainage impairment within the perivascular spaces. Because of this, beta amyloid is trapped and deposited in the walls of small arteries. Although the results of this study cannot change current clinical practice, it opens up the opportunity for a prospective study which may be able to establish causation. And from there, if we can predict the chances of someone developing CAA, we can decide who to be wary of anti-coagulating.

Add Some Color To Your Life: using color-coded FLAIR to detect signal change more reliably

Vikas Pandey, MD

Kim BJ, Kim Y, Kim Y, Ahn S, Lee DH, Kwon S, et al. Color-Coded Fluid-Attenuated Inversion Recovery Images Improve Inter-Rater Reliability of Fluid-Attenuated Inversion Recovery Signal Changes Within Acute Diffusion-Weighted Image Lesions. Stroke. 2014

Stroke imaging is a very sophisticated area that has been constantly evolving leaving the burden on neurologists to be able to maintain the ability for proper interpretation of different imaging modalities and sequences. Series such as DWI and FLAIR are cornerstones to stroke diagnosis and ischemic lesion aging, but whether a lesion that is seen on DWI is also present on FLAIR is a matter that, many times, is up for debate between treating team members.  To help solve the argument, the authors utilized a method similar to what was done to televisions back in the 1950s, they added color! They used color-coded FLAIR imaging with the idea that this would improve inter-rater agreement on determination if lesions were present on FLAIR or not for improved ischemic lesion aging.

The authors used retrospective case design to view the records of 113 ischemic stroke patients who were admitted to Asan Medical Center in Korea within 24 hours of clear onset of symptoms. The patients received a 1.5 Tesla MRI scan and the DWI slice with the largest lesion and the slice of corresponding FLAIR image were prepared (both the conventional FLAIR, as well as 256-color coded voxel imaging using auto-contrast to assign color intensity). These three slices were prepared and administered to two groups, well-trained stroke neurologists and neurologists is residency training. To avoid learning effect, they presented the images with DWI with the color-coded image first, then one week later with the conventional FLAIR image. These were categorized into obvious, subtle and negative (which would be positive for DWI-FLAIR mismatch). The results showed that the average NIHSS was 4, and the patients received the imaging approximately 7 hours on-average from symptom-onset. 13.3% had received IV tPA before and during MRI. The inter-rater agreement of DWI-FLAIR mismatch was kappa= 0.538 with conventional images and kappa=0.754 with color and the p-value for difference in percent agreement was p=0.004. The categorization of subtle change was higher in conventional than with color-coded images (38.1% vs 25.7%, p=0.01). 34 patients out of the 113 had discrepant ratings with conventional images however this discrepancy was resolved in 28/34 patients (82.4%) with the color-coded. These 28 patients had a higher amount of cardioembolic strokes and cortical lesion strokes. The positive predictive value of DWI-FLAIR mismatch predicting lesion within 4.5 hours was 85.3% and 71.9% with conventional FLAIR images, and 95.7% and 82.1% with color-coded FLAIR images for the experienced and resident groups, respectively.

The data appears to be most applicable for cardioembolic and cortical stroke lesions as it is these that seem to be not detected in conventional flair imaging (less inter-rater agreement) which improved with color-coded imaging. The idea that occasionally some of these lesions may be missed on conventional FLAIR is frightening given the concept that these usually signify older lesions that may increase hemorrhagic risk if thrombolysis is given. The data also showed that those lesions rated “subtle” decreased with color-coded imaging because the color contrast made the lesions more obvious given that the heterogenous nature of infarcted tissue comes out more with color coding. The improved positive predictive value of being within 4.5 hours of time of onset has therapeutic implications as this modality can be used in those with unknown time of onset as well as the wake-up stroke population. The use of color and resolution has improved quality of things such as high definition televisions and video gaming systems and no doubt stroke imaging modalities will improve in much the same manner with similar improvements in color, resolution and imaging strength. In thirty years, perhaps clinicians will look back at how primitive we were with things such as DWI and FLAIR and be shocked with how we hadn’t come up with things like 30 Tesla HD 1080p No-Radiation 4-D Super Simultaneous Thrombolysis/CT/MRI/Perfusion/Angiogram/Facebook-Uploading Scanners that they may be using at that time.