American Heart Association

Monthly Archives: May 2013

Non-relevant cerebral atherosclerosis

Vasileios-Arsenios Lioutas, MD

Kim J, Song T-J, Song D, Lee HS, Nam CM, Nam HS. Nonrelevant Cerebral Atherosclerosis is a Strong Prognostic Factor in Acute Cerebral Infarction. Stroke. 2013

In this interesting study, Drs. Heo et al address the clinical relevance of overall atherosclerotic burden of cervical and cerebral vessels in ischemic stroke outcome.

More specifically, after excluding patients with cardioembolic etiology they retrospectively studied the short-term clinical improvement measured by NIHSS, as well as 3-month functional outcome, using mRS as a metric. They focus on “non-relevant cerebral atherosclerosis”, that is >50% stenosis or occlusion of vessels not directly implicated in the arterial territory of the infarct. Despite baseline differences in age and some of the risk factors, multivariate adjusted analysis showed less early improvement and worse functional outcome in patients with non-relevant atherosclerosis (adjusted OR of 2.54) . Of interest, exclusively intracranial atherosclerosis showed the strongest association with worse outcome, as opposed to solely extracranial disease that was not a significant predictor.

It is important to note that data regarding recurrent strokes and the status of collateral flow are not available and that is a limitation of the study. Moreover it would be important to know post-stroke treatment choices (i.e. antiplatelet regimen, or if anticoagulation was used in some patients), LDL levels and lipid-lowering regimen choices, as aggressive statin therapy is a treatment of choice in patients with extensive intracranial atherosclerosis.

Despite its limitations, the study results lend support to what most clinicians would suspect intuitively; that “non-relevant” atherosclerosis is in reality quite relevant.

A New Generation of Flow Diverter

Diogo C. Haussen, MD

 De Vries J, Boogaarts J, Van Norden A, Wakhloo AK. New Generation of Flow Diverter (Surpass) for Unruptured Intracranial AneurysmsA Prospective Single-Center Study in 37 Patients. Stroke. 2013

Flow-diverting stents (FDS) became recently available as a treatment alternative for large and/or wide necked cerebral aneurysms. These devices have relative higher metal surface area coverage, reaching 30-35%. The low stent porosity bridges the aneurysm neck and deflects the flow that would typically fill the aneurysm back into the parent arterial lumen. This generates flow stagnation inside of the aneurysmal sac, and consequently promotes intraaneurysmal thrombosis. The stent struts endothelialize after a few weeks and “reconstruct” the vessel wall while side branches and penetrators remain remarkably patent. Currently, the only approved FDS in the US is the PipelineTM, and substantial literature has accrued over the past years regarding the use of this device. Although promising, not uncommon complications may occur (mostly thromboembolic and hemorrhagic – related to required double antiplatelet regimen). Some series report very low complication rates, however others describe that almost 1 in 10 patients experience significant morbidity or mortality.

De Vries et al. report their initial experience with a new FDS (SurpassTM) in 37 patients harboring unruptured aneurysms. A main theoretical advantage of this device resides on the fact that the implant maintains a uniform pore-density across the aneurysm neck unaffected by parent artery diameter – stents with larger width are built with more wires. Conversely, PipelineTM encompasses the same number of wires independent of the stent diameter. Weather this may result in better occlusion rates is unknown. The use of a mean 1.0 stent per patient is relatively low while their 6 months total obliteration rates are relatively similar compared to published PipelineTM series. Another attractive SurpassTM feature resides on the addition of platinum wires for improved visibility.

The effective and safe delivery of the PipelineTM stent demands sophisticated technique, which makes the reader wonder how easily manageable SurpassTM may be. Moreover, the Pipeline is not resheathable in case of an improper partial unsheathing (implant needs to be retracted and discarded); it is unclear whether the SurpassTM is resheathable as per this report. The community certainly welcomes the successful initial SurpassTM experience and enthusiastically awaits for further data.

Laacunar infarcts and white matter tract integrity

Jose Gutierrez, MD, MPH

Reijmer YD, Freeze WM, Leemans A, and Biessels GJ. The Effect of Lacunar Infarcts on White Matter Tract Integrity.Stroke. 2013

Among markers of small vessel disease, lacunar infarcts have long been associated with worse cognitive performance. Several hypotheses have been invoked to explain this association and in this Stroke article, Reijmer and his group from Netherlands add on information about these questions. In a small sample of 17 subjects without dementia but with evidence or history of stroke localized to one hemisphere. Subjects underwent 3T MRI to obtain Fractional Anisotropy and Mean Diffusivity in tracts related to the infarcts compared to homonymous tracts in the non-affected hemisphere. Measures of cognition were obtained from each participant as well as WMH load (visual rating) and tract volumes.

The authors found that the affected tracts in relationship to lacunar infracts showed decreased anisotropy and increased mean diffusivity suggestive of WM loss of integrity compared to the unaffected contralateral tracts. These measures were correlated with worse cognitive performance including verbal fluency, information processing speed and word recall test. The association remained significant for all except memory after controlling for WMH load and hemisphere side with the exception of memory. Repeating the analysis in tracts not containing the infarcts did not reproduce these associations.

These are exciting results, although caution is advised due to its limited sample size. Some questions arise that might be worth exploring. What are the effects of cognition in tracts that are not known to play a role in the cognition, for example, primary motor cortex? Would these lesions be related to worse cognition? Some potential etiologies of lacunar infarcts include microatheroma, embolism or branch occlusive disease, is the etiology of a lacunar infarct important in determining the extent to which white matter is disrupted in the affected tracts? Is wallerian degeneration the explanation for the decreased fractional anisotropy and increased mean diffusivity in the surroundings of an infarct or could there be a role for perilesional inflammation? These questions seem important because understanding the pathophysiology of this cascade might offer some potential target to intervene and blunt the increasing prevalence of vascular cognitive impairment. 

Storke belt in China

Jiaying (Jayne) Zhang, MD

Xu G, Ma M, Liu X, and Hankey GJ. Is there a “stroke belt” in China and why? Stroke. 2013

In the thought provoking paper by Xu et. al., the authors conducted a systematic review of studies looking at the incidences of stroke in China in order to establish if and where there is a “stroke belt” in China. Prevalence of stroke risk factors in these provinces was extrapolated from nationwide epidemiological surveys. The “stroke belt” is defined as provinces ranked in the top third for stroke incidence in the nation with at least one third of their prefectural regions ranked in the top two sevenths of prefectural regions for stroke incidence. Nine provinces met criteria for the “stroke belt”. The incidence of stroke within the belt was more than twice of other regions. It appears that there is a noticeable north-south gradient with provinces that met the criteria in northern and western China. Hypertension and BMI > 25 correlated with higher stroke incidences in those provinces.

It is interesting to note that most of the studies the authors included analyzing the incidences of stroke in China were from the 1980s. As the world knows, the staggering pace of Chinese economic growth is rapidly changing the population distribution in China. One challenge to future stroke epidemiological studies in China is its growing “flowing population”, as people move from the country side to the city, from underdeveloped economic areas to developed ones, and from central and western regions to coastal regions. It will be important for future studies to account for this dynamic variable as well as the increasing westernization of diet and living habits and deleterious environmental changes in the face of globalization.

Candesartan in acute stroke on cognitive function and quality of life

Nandakumar Nagaraja, MD

Hornslien and colleagues evaluated the data from Scandinavian Candesartan Acute Stroke Trial (SCAST) for the effect of high blood pressure treatment with candesartan in the acute phase of stroke on cognitive function and quality of life. 2029 patients with ischemic and hemorrhagic stroke with SBP ≥ 140mmHg were enrolled into the study within 30hours of onset and they were randomized to candesartan or placebo group for 7 days. Cognitive function was assessed by MMSE and quality of life by EuroQol(EQ) instrument at 6months.
There was no significant difference in the distribution of MMSE scores between the candesartan and placebo group. However, there were small differences with disfavor of candesartan for the five individual EQ-5D domains.
Though this study was not powered to evaluate these outcomes, it suggests that treatment of high blood pressure in the acute phase of stroke is not beneficial for cognitive function or quality of life and rather may be harmful.
Previous studies have shown that long term treatment with perindopril (PROGRESS study) and ramipril (HOPE study) reduce the risk of recurrent stroke. In addition, long term treatment with perindopril resulted in reduced risk of cognitive decline and dementia associated with recurrent stroke. However in the SCAST study, patients were treated with candesartan for short period of 7days in the acute phase of stroke and there was no reduction in recurrent stroke.

Transcranial Laser Therapy and Infarct Volume

Jose Gutierrez, MD, MPH

Containing the brain damage after an acute stroke has been an elusive goal and neuroprotective strategies have not been successful . In this article, Kasner et al. present results from a multicenter, international, randomized clinical trial of Transcranial Laser Therapy (TLT) for acute cortical stroke (NEST-2). The authors hypothesized that TLT would be associated with reduced cortical stroke volumes. They used predominantly brain CT to assess the infarct size, expressed in volume, and two other surrogates of infract size, ASPECTS and a modified ASPECT that reflects cortical involvement. 

The authors present data on 640 patients enrolled in whom TLT was provided 24 hrs after an acute stroke and neuroimaging was available at day 5 after the acute stroke. The authors did not find evidence that TLT was associated with smaller infarct size (in either volume or by the ASPECTS or modified ASPECTS scores). The primary analysis and the prespecified subgroup analyses (NIHSS > 10, syndromes localized to the anterior circulation were negative.

The lack of benefit of yet another therapy for acute stroke is distressing to the stroke community. Trials after trial have failed to improve the odds of recovery after stroke, with the exception of IV-TPA. So what is next? Is focusing in acute stroke treatment/recovery the best strategy to alleviate the societal burden that stroke represents? 

Decreased Corticospinal Tract Fractional Anisotropy

Waimei Tai, MD

Puig et. al recently published a paper suggesting to use the ratio of fractional anisotropy (rFA) in diffusion tensor imaging (DTI) to help predict long term prognosis after motor stroke.  It suggests how this technology can help assess patients and provide better prognostic information at a 30 day scan, to predict long term eventual motor outcome at 2 years.  The threshold values using area under the curve analysis suggest that rFA <0.982 for slight-moderate and rFA <0.689 for severe deficit are quite good suggesting that it may potentially have a good correlation with predicted outcome. The study was limited by a small number of patients who had limited or poor motor outcomes at 2 years.

I am not sure how I would use this information in current standard practice. I do think that providing prognostic information to patients earlier in the course is useful, as it may help guide decision making in adjustments and adaptations in lifestyle for various levels of disability, but I think this is quite limited and early data to suggest that it limit or offer more physical rehabilitation for patients who have either a very high rFA or low rFA value. I would still recommend further rehabilitation for all my patients who suffer from motor deficits, even at 30 days.

But perhaps this type of imaging information may be helpful in identifying patients who may benefit from neuro-recovery therapeutic trials, such as stem cell studies that are currently being proposed.
How do you think new forms of advancing imaging will play a role as we progress in our ability to further prognosticate in stroke care?

DWI-FLAIR mismatch on 3T MRI to identify acute patients

Tareq Kasshout, MD

Emeriau S, Serre I, Toubas O, Pomboureq F, Oppenheim C, Pierot L. Can DWI-FLAIR Mismatch at 3 Tesla Identify Stroke Patients at < 4.5 hours? Stroke. 2013

Because there is some uncertainty about the value of the DWI/FLAIR mismatch on 3T MRI to discriminate patients imaged within the standard thrombolytic time window and those who had symptom onset beyond such time period, Emeriau and colleagues conducted a study to determine whether DWI-FLAIR mismatch at 3T may idiscriminate between both groups of patients.
In their retrospective study of 194 patients, delayed MRI acquisition was the only predictive factor of FLAIR visibility. This means that the 3T FLAIR sequence may provide information that can be use to estimate the age of stroke. But DWI/FLAIR mismatch in this study had moderate specificity and sensitivity and a low negative productive value to identify patients presenting <4.5 hours after symptom onset because 45% of patients imaged within that time frame already had FLAIR signal changes.

In short, the link between FLAIR signal intensity and time of symptom onset is not yet fully understood. This study, however, suggests that the cutoff delay between symptom onset and MRI that best predicts FLAIR positivity is 170 minutes, which is less than the thrombolysis delay.

Foot Drop Stimulation vs Ankle Foot Orthosis

Shruti Sonni, MD

“Foot drop”, difficulty in dorsiflexing (DF) the foot, is a common result of corticospinal damage due to stroke (both ischemic and hemorrhagic). The Functional Ambulation: Standard Treatment vs. Electrical Stimulation Therapy (FASTEST) trial is a randomized trial comparing 30 weeks of traditional ankle foot orthosis (AFO) with a foot drop stimulator (FDS) for foot DF weakness among 197 patients who were >3 months post stroke. FDS is a type of functional electrical stimulation of the peroneal nerve to dorsiflex the foot in the swing phase of gait every time the foot is raised to take a step. Both interventions were found to benefit the gait speed in patients without a significant difference between the two groups.
Traditional AFOs have drawbacks including discomfort, limited ankle mobility, difficulty with standing from a chair and unfavorable aesthetics- all leading to poor compliance. Better user satisfaction was seen in the FDS group (though this group had greater number of patients with AEs from skin irritation). Also, the AFO group received transcutaneous electrical nerve stimulation (TENS) treatment as a “sham” procedure which may have had a beneficial or placebo effect similar to that of the FDS. The patients included in this study had a stroke of any etiology- ischemic or hemorrhagic. Is there enough evidence to show that these two conditions recover in the same way and time course?
Given the equivocal findings regarding these two treatments, the important question arises- what is the cost differential between these two devices, and subsequently how will insurance coverage change given findings of this study?  In addition, the authors mention other meaningful measures that can be compared in the future between the two groups including obstacle avoidance, ankle DF strength, cortical pathways used for muscle activation and use of a validated measure of user satisfaction. This study is the largest randomized trial to date that compares these two interventions in stroke patients. We look forward to further advances in this very important area of stroke rehab.

Atherosclerosis in a General Population: the Hisayama Study

Vasileios-Arsenios Lioutas, MD

White-coat hypertension (WCHT) is often considered a benign phenomenon, a temporary reaction of the patient’s sympathetic nervous system to the stress-provoking environment of a hospital or doctor’s office. The investigators in this cross-sectional population-based study in Japan sought to shed light in the association of WCHT and cardiovascular disease, using carotid artery metrics (intima-media thickness and stenosis by ECST criteria) as markers.

Despite methodological shortcomings and limitations due to design, the data presented imply that WCHT is not as innocent as commonly thought. In fact, patients with WCHT were found to be older and significantly more likely to have “traditional” cardiovascular risk factors, such as diabetes and hyperlipidemia, when compared to patients with normotension. More interestingly, there is a significant difference in the percentage of carotid stenosis and in absolute measurements of mean and maximum intima-media thickness between normotensive patients and those with WCHT, with the latter showing evidence of carotid atherosclerosis much more frequently- more precisely, the age- and sex-adjusted OR (95%CI) is 2.45.

By all means, the age, risk factor and carotid artery markers profile of patients with WCHT is very similar to those with masked and sustained hypertension and differs significantly from healthier adults with normal blood pressure. Although the cross-sectional design of the study doesn’t allow causative associations, this study’s findings seem to defy the notion that white coat hypertension is benign.