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Monthly Archives: December 2014

Spinning to an Answer: Use of Arterial Spin Labeling for Arterial Occlusion Localization

Vikas Pandey, MD

Yoo R, Yun TJ, Rhim JH, Yoon B, Kang KM, Choi SH, et al. Bright Vessel Appearance on Arterial Spin Labeling MRI for Localizing Arterial Occlusion in Acute Ischemic Stroke. Stroke. 2014

The role of imaging is critical to stroke care as it not only confirms the stroke neurologist’s assessment from the physical exam, but it also can pick up subtle strokes with no clinical correlate. Currently, there is a race to discover and develop the next big series or imaging sequence that will provide key information during stroke evaluations and the group from South Korea has brought us a comparative assessment of the use of arterial spin labeling (ASL) and how this compares to susceptibility weighted imaging when using MR angiography as the reference standard to detect arterial occlusions.

The group gathered radiological data on 117 consecutive patients with stroke symptoms who underwent ASL imaging, which is now part of the standard stroke protocol at their institution, as well as DWI, FLAIR, SWI and 3D TOF MR angiography. The best way to really see how a clot appears on ASL imaging is to read the article mentioned and look at the images, however the best way I can explain the appearance is a “lighting up” of the vessel in question, termed by the authors as a “bright vessel appearance”. This was compared to the presence of a susceptibility vessel sign (dark dot in the vessel on SWI imaging) using an MRA cutoff or stenosis as the standard. The group found that 35 of the 117 patients enrolled with stroke symptoms (30%) had arterial occlusion on MRA. ASL bright vessel appearance, susceptibility vessel sign and FLAIR vascular hyperintensity were all more common in the group with occlusion than in the group without (P<.001). Of the 35 patients with MRA arterial occlusions, 33 of 35 (94%) had bright vessel sign on ASL imaging while 23 of 35 (66%) had susceptibility vessel sign, a statistically significant difference between the groups (P= .002). In the MRA negative cases, ASL imaging demonstrated significantly more additional occlusions than the susceptibility vessel sign (21% vs 10%, respectively, P=.012) showing that ASL may be better for detecting these smaller, peripheral occlusions.

The ASL imaging however did occasionally miss stenoses proximal to occlusion sites as well as not showing a bright vessel sign in every area with stroke, only those with occlusion sites. The modality has very good interobserver agreement with kappa=0.86. There may also be applicable uses of the technique for detecting collateral flow (given the detection of an “arterial transit artifact) but this needs to be better studied. The application reflected by this paper however, shows a very reliable, rather easy to interpret, and very accurate modality that can possibly be another sequence that is routinely checked during imaging review during a stroke evaluation. The images yielded by the ASL technique can be interpreted with confidence and with better correlation to true occlusion and better detection of smaller, peripheral occlusions than SWI imaging.


What’s the best way to predict outcome after endovascular treatment for stroke?

Daniel Korya, MD

McTaggart RA, Jovin TG, Lansberg MG, Mlynash M, Jayaraman MV, Choudhri OA, et al. Alberta Stroke Program Early Computed Tomographic Scoring Performance in a Series of Patients Undergoing Computed Tomography and MRI: Reader Agreement, Modality Agreement, and Outcome Prediction. Stroke. 2014

In his writings, Hippocrates first described the phenomenon of sudden paralysis that is often associated with ischemia. The Greek term apoplexy, meaning “struck down with violence”, was used to describe this occurrence. The word “stroke” was derived from this original description and continues to be used to this day. 

In addition to providing accurate clinical descriptions of stroke, Hippocrates started to take things a step further in 400 B.C. He wrote, “When persons in good health are suddenly seized with pains in the head and straightaway are laid down speechless and breathe with stertor, they die in seven days.” Essentially, he provided the basis for a predictive model for patients with hemorrhagic stroke. He was able to generate a relatively accurate prognosis for patients who presented with these symptoms based on his clinical observations.

Today, we continue to look for ways to better prognosticate and predict outcome for our patients. This quest is usually driven by patients and their families and is echoed in the phrase most often heard by physicians: “Am I, or is he/she going to be alright?” Or, will this be the end?

For ischemic stroke, previous studies have validated the Alberta Stroke Program Early CT Scoring (ASPECTS) as a straightforward and quick way to use non-contrast CT scans to predict functional outcome and hemorrhage risk in patients eligible for IV tPA. The ASPECTS score was later adapted to the MRI since this modality was known to be more sensitive and specific for diagnosing stroke.

Even though the ASPECTS was originally designed to aid in decision making about which patients were more likely to benefit from IV tPA, it was also used to predict outcome and likelihood of reperfusion in the IMS III study.

So far, we had a score that used the non-contrast CT scan prior to treatment to help us predict outcome for patients about to receive IV tPA. But, the MRI was found to be a better modality for predicting outcome for IV tPA patients. More recently, the non-contrast CT version of this score was also validated for patients who not only received IV tPA, but also underwent endovascular therapy. The most logical next step was to try the MRI version of this score and see which one did a better job of predicting outcome: the non-contrast CT version of the ASPECTS score, or the diffusion-weighted MRI version. That’s what Dr. McTaggart and his colleagues did.

They prospectively evaluated 74 patients with acute ischemic stroke. All patients had a non-contrast CT and an MRI prior to undergoing endovascular treatment within 12-hours of symptom onset. Based on their imaging, these patients were then given an ASPECT score with both the diffusion-weighted MRI and the non-contrast CT. Each patient had two scores, one derived from each modality. Two expert clinicians determined these scores completely independently of each other (i.e. they were blinded to the other’s scoring). A third scorer then compared the scoring of the original two scorers, and chose the more accurate of the two for inclusion in the study. The scores were then compared with the modified Rankin Score (mRS) at 90-days.

To determine if different ASPECT scores correlated with outcome, the scale was evaluated in several different ways: The entire scale (ASPECTS 1-10), two groups (ASPECTS 0-7 and 8-10) and three groups (ASPECTS 0-4, 5-7 or 8-10), were compared with the 90-day mRS.

Although the sample size was not very large, the results were significant. Dr. McTaggart and colleagues found that the DWI-ASPECTS and CT-ASPECTS correlated well with the DWI volume. However, the DWI-ASPECTS correlated better with DWI volume. Furthermore, the area under the ROC curve (AUC) for predicting good outcome for DWI-ASPECTS was 0.705 (95% CI, 0.587-0.822), 0.581 (95% CI, 0.440-0.722) for time interval from stroke onset to procedure start, and 0.548 (95% CI, 0.411-0.685) for the CT-ASPECTS. The AUC difference for DWI-ASPECTS vs. CT-ASPECTS was significant (p=0.026) whereas the difference between DWI-ASPECTS and time interval from stroke onset to cath lab was not (p=0.20).

DWI-ASPECTS grouped into three (8-10, 5-7, and 0-4), correlated with good functional outcome (GFO) at rates of were 53%, 27%, and 10%, (p=0.004 for this trend), whereas CT-ASPECTS did not (corresponding GFO rates were 39%, 37%, and 20%, p=0.534).

While reading this paper, there were two major questions that came up and required answering. Fortunately, these questions were answered in the discussion the authors provided.

The primary question concerned the time difference between when the CT scan of the head was obtained and when the procedure was performed and when the MRI was performed in relation to the treatment and eventual outcome. Since this data was obtained from the DEFFUSE-2 trial, it was pointed out that the CT head was always obtained before the MRI was obtained. So, for evolving strokes, it only makes sense that the MRI would be more accurate since it is capturing the evolution at a later time than the CT scan. However, the authors attempt to dispel this notion by stating that the mean DWI- ASPECTS scores were not significantly lower than the CT scores (7.6 vs 7.0) and the difference between the scores did not increase in relation to the time difference between CT and MRI.

The second question was more of a surprised exclamation ending in a question: “How could time to reperfusion be less important that the DWI-ASPECTS?” The authors answered this question by suggesting that the finding of DWI-ASPECTS being a stronger predictor of outcome than time-to-reperfusion may reflect the variable growth rate of DWI lesions over time, and implies that the volume of irreversible tissue injury is a more potent predictor of clinical outcome than time to reperfusion. Essentially, to quote the movie The Fifth Element, the authors are saying “time not important, only life, important”, the life of viable brain cells, that is.

Life after Stroke? Changes in functional outcome over the first year post stroke

Michelle Christina Johansen, MD

Ullberg T, Zia E, Petersson J, and Norrving B. Changes in Functional Outcome Over the First Year After Stroke: An Observational Study From the Swedish Stroke Register. Stroke. 2014

Research looking at functional decline and patient centered quality of life outcome measures will only grow in the upcoming years. As doctors, it behooves us to work towards a better understanding of the patients’ view of their deficits. Have we as physicians historically ignored that which is of concern to the patient and focused more on that which is bothersome to the provider? This research looks at the other side of the equation and is critical in helping us answer caregiver questions about what to expect in the future. 

Stroke is a devastating disease. Life can be dramatically altered in its aftermath including taking away from the patient the ability to care for their basic needs or activities of daily living (ADLs). There has been literature looking at potential causes for worse outcomes after ischemic stroke such as presenting seizure, hemorrhagic transformation, age and NIHSS at time of presentation but there is a paucity of longitudinal studies investigating reasons for change in functional outcome post stroke.

Ullberg et al attempt to bridge that gap through an observational study looking at functional decline after 3 months post stroke, a common end point in acute stroke trials. The aim of the study was to analyze case fatality and disability levels at 3 and 12 months as well as changes in functional outcomes between 3 and 12 months and predictors of dependency in ADLs. The data was obtained from the Swedish Stroke Register from 2008-2010 using ICD 10 codes for cerebral infarction, intracerebral hemorrhage or unspecified cerebrovascular event. The patients had to be completely independent in all ADLs prior to their stroke for enrollment. Data on functional ability was collected using a questionnaire at 3 and 12 months and it was noted whether the patient or someone else provided the input. ADL independence was defined as independent dressing, toileting and mobility indoors.

Of a total study population of 64,746 subjects, 8,483 patients (13.1%) were deceased by 3 months and 11,799 (18.2%) at 12 months. Of the remaining patients, 14.6% of men and 18% of women were ADL dependent in some capacity at 3 months with 8.1% of the total reporting performed without any participation from the patient (assisting person completed follow up). At 12 months, the numbers stating dependency had grown to 22.6% of men and 34.9% of women with an assisting person completing follow up in 10% due to patient inability. In a comparison of those who deteriorated between 3 and 12 months to those whose were stably independent at 12 months, the majority were women over 75y. Factors found to significantly predict deterioration were smoking, diabetes, atrial fibrillation, previous stroke, hemorrhagic stroke and a decreased consciousness level at time of admission.

In consideration of the results of this study, it would have been helpful for the authors to specify the percent change of the three reported ADLs. For example, how many patients only reported a decline in one ADL versus all three? The study associated prior stroke with loss of independence, but did infarct location play a role? What about size of the infarct or presenting NIHSS? One could easily imagine that a patient suffering a large MCA stroke for example would continue to decline after 3 months. Another helpful consideration would have been a description of support in the home. A higher proportion of independent subjects at 12 months were living alone, but did they have caregivers geographically close? Did someone provide some degree of in-home care? What about the percentage of patients discharged to rehab or who received outpatient physical therapy? Does this help combat dependency?

As vascular neurologists, we understand the significance of the mantra “time is brain” and for that reason, we rush to treat acute stroke emergently. The study by Ullberg et al demonstrates clearly that functional decline continues for up to a year post stroke. Further research into protective strategies is needed to prevent this decline, thereby significantly improving our patients’ quality of life.

Follow up imaging is clinically and economically futile in patients with peri-mesencephalic subarachnoid hemorrhage

Prachi Mehndiratta, MD

Kalra VB, Wu X, Matouk CC, and Malhotra A. Use of Follow-Up Imaging in Isolated Perimesencephalic Subarachnoid Hemorrhage: Meta-Analysis. Stroke. 2014

Hemorrhage isolated to the peri-mesencephalic cistern is seen in about 5% of all patients with subarachnoid hemorrhage (SAH) and is thought to be of venous origin. CT angiogram is an extremely sensitive diagnostic tool and has been shown to reliably identify aneurysms in 10% of patients with peri-mesenchephalic SAH (pSAH). Studies till date have demonstrated that follow up imaging in patients with pSAH does not add clinically significant information, at the risk of increased cost to the patient. The authors performed a retrospective review of patients admitted to their center with pSAH and a meta-analysis of all studies of pSAH to determine the utility of follow up imaging in these patients. 

A retrospective review of imaging reports identified 214 patients with pSAH on initial non contrast CT head. Other inclusion criteria included performance of CTA/DSA within 24 hours of admission as well as follow up imaging. Those with history of trauma, diffuse SAH, presence of intraventricular blood were excluded. A total of 18 patients met inclusion criteria and their images, both acute and follow up, were reviewed by neuroradiology and were assessed for a positive diagnostic yield. Additionally a meta-analysis of 40 studies of patients with pSAH was performed, excluding those with less than 5 patients, lack of follow up imaging, increased loss to follow up and CSF xanthocromia without pSAH. Patients from these were classified based on the type of acute and follow up imaging (Conventional angiogram only, CTA only and both conventional angiogram and CTA). Demographic data was analyzed however neurologic deficits and outcomes were not evaluated. Two-way ANOVA analysis of aneurysm detection rate based on initial and follow-up protocols was used to evaluate the effects of each initial and follow-up imaging strategy. The risk of bias within individual studies and across studies was also assessed.

The institutional analysis of 18 patients and the overall meta-analysis of 1,440 patients across 40 studies did not elicit benefit of utilizing follow up imaging. Mean age was 51.9 years and 1,031 of 1440 patients had follow up imaging available. Two-way ANOVA test yielded a p-value of 0.353 for the three initial diagnostic strategies, 0.701 for the three follow-up strategies, and 0.916 for the interaction term of initial and follow-up strategies. There was no statistically significant benefit to performing DSA during the initial evaluation or of any follow-up angiographic studies. Only eight aneurysms in eight patients (0.78%) were detected on any of the follow-up imaging.

This study re-enforces prior observations in this field. Peri-mesencephalic SAH is associated with a low risk of recurrence, vasospasm and hydrocephalus and is often venous in origin. The utility of re-imaging during follow up is low as the negative predictive value of the initial test (CTA or DSA) is high (91-96%). There still remains a possibility of missing small <3mm aneurysms with either test however the low rate of detection with a second imaging study does not justify the cost and risk of subjecting a patient to repeated imaging. These results have clinical implications and like many studies before this one, their application to practice may be difficult as physicians are often compelled to find reasons and search for the etiology of SAH. Regardless, each case has to be handled differently and some may continue to warrant follow up imaging.

Statins just can’t catch a break…

Rajbeer Singh Sangha, MD

Wong GKC, Chan DYC, Siu DYW, Zee BCY, Poon WS, Chan MTV, et al. High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage: Multicenter Randomized Controlled Double-Blinded Clinical Trial. Stroke. 2014

The authors of this study delved into a subject that has been of much discussion as of late. Following aneurysmal SAH, 18–56% of patients demonstrate evidence of secondary ischemia with clinical deterioration, which is also known as delayed ischemic deficit (DID). Statins amongst its many functions has been known to improve endothelial vasomotor function, increase nitric oxide bioavailability, possess antioxidant properties, counter thrombus formation, induce angiogenesis, endogenous cell proliferation and neurogenesis, induce vascular stabilization and suppress cytokine responses during cerebral ischemia. All of these factors in theory work to stabilize the cerebrovascular system following injury. 

Two randomized, placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite a lower dose of simvastatin (40mg daily) did not improve clinical outcomes. The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). While no safety concerns were noted, it was concluded by the authors that statins should not be given during the acute period SAH. The objective of this study was to determine whether a high dose of simvastatin for the treatment of aneurysmal SAH is superior to a lower dose in terms of clinical outcomes and cost-effectiveness.

This study was an investigator-initiated, multicenter, randomized controlled trial with blinded outcome assessment performed at multiple centers in China. 255 patients were randomized to be in either the low dose simvastatin group or high dose simvastatin group. The results showed no difference was observed between the groups treated with the high dose or the lower dose of simvastatin in the incidence of DID (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7–2.0; p = 0.586). Furthermore, the two groups did not show difference in the rate of favorable outcomes (mRS 0–2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6–1.9; p=0.770).

While the power in this study is limited, it further confirms what was found in the STASH trial and protocols should be amended given the evidence that is gathering that statins are not beneficial in terms of treatment in sub-arachnoid hemorrhage.

By |December 24th, 2014|clinical|0 Comments

Strokes Take Us Off Tract: White Matter Ischemic Changes in Hyperacute Ischemic Stroke

Mark N. Rubin, MD

Nael K, Trouard TP, Lafleur SR, Krupinski EA, Salamon N, and Kidwell CS. White Matter Ischemic Changes in Hyperacute Ischemic Stroke: Voxel-Based Analysis Using Diffusion Tensor Imaging and MR Perfusion. Stroke. 2014

Multiparametric “physiologic” acute stroke imaging (e.g., CT or MR perfusion) is all the rage in academe and clinical practice alike. This is because these imaging modalities provide what is thought to be a representation of microstructural changes in the brain – as in what happens when membrane pumps stop doing their thing – and a way to differentiate how much of the brain can be salvaged as opposed to a sense that the proverbial horses have already left the barn, thus the door need not be slammed. These data, in turn, inform early management.

Some University of Arizona investigators sought to describe another physiologic imaging parameter in acute stroke: fractional anisotropy (FA) in affected white matter tracts. So, if our familiar diffusion-weighted MRI sequences for stroke (e.g., DWI) give us information on diffusion restriction (as a biomarker of neuronal injury) in a region of brain, testing FA in white matter tracts (e.g., DTI sequence) tells us about diffusion restriction along the scanned extent of the white matter tract. The authors of this manuscript hypothesized that changes in FA may be a useful surrogate for loss of structural and/or functional integrity in the hyperacute phase of ischemic stroke, and compared this to other more recognizable sequences such as ADC & Tmax with perfusion. An ADC threshold was set for infarct vs hypoperfusion.

This was a small, exploratory study which recruited 21 patients (14 male) within 6 hours of acute ischemic stroke and a demonstrable “penumbra” (e.g., diffusion-perfusion mismatch). The sequences of interest, namely DTI, ADC and perfusion-based Tmax, were co-registered and quantified (voxel-based, third-party software) and compared to the homologous region on the contralateral side as an “internal control.”

The findings based on the primary hypothesis were interesting, and have some overlap with more recognizable imaging variables that suggest potential clinical utility. As expected, there was a significant difference in FA between normal, hypoperfused and infarcted white matter. What was interesting was that the pathologic states varied in opposite directions; FA increased in the hypoperfused white matter and decreased in the infarcted white matter. These findings are consistent with previous studies suggesting that cytotoxic edemia in white matter may restrict diffusion but not greatly affect the cellular architecture, whereas decreasing FA with infarct suggests uniform restriction of diffusion in the region which would be expected with frank injury.

Multiparametric imaging, although clinically mainstream and deserving of the many research dollars invested, is yet imperfect. Studies like these, exploring other physiologic parameters that may serve as that elusive “should I or shouldn’t I?!” biomarker for acute stroke treatment outside of the typical clinical indications, are a way to improve upon diagnosis and management of our acute stroke patients.

MRI marker helps determine clot composition in acute stroke

Chirantan Banerjee, MD

Yamamoto N, Satomi J, Tada Y, Harada M, Izumi Y, Nagahiro S, and Kaji R. Two-Layered Susceptibility Vessel Sign on 3-Tesla T2*-Weighted Imaging Is a Predictive Biomarker of Stroke Subtype. Stroke. 2014

As opposed to myocardial infarction, stroke is a heterogenous entity. The burning question that a vascular neurologist seeks to answer when a patient presents with acute ischemic stroke is where is the acute intracranial or extra cranial occlusion. Where did the clot come from? Was it an in situ thrombus atop an underlying atherosclerotic plaque that ruptured, or did it come from a central embolic source, vis-a-vis the heart. Depending on where a thrombus is formed, it may be white, red or mixed. Traditionally, it has been thought that white thrombi develop on ruptured plaques and comprise of aggregated platelets, whereas red thrombi form in cardiac and venous systems, and are rich in fibrin and trapped erythrocytes. However, recent histopathological studies looking at clots retrieved by endovascular retriever devices failed to show an obvious association between clot composition and stroke mechanism.

Over the years, there have been several studies trying to identify radiologic biomarkers to identify clot composition accurately, thereby ultimately attempting to establish the mechanism. Animal studies also have shown that erythrocyte rich thrombi may be more amenable to thrombolysis by tPA as opposed to fibrin rich ones. Hyperdense vessel sign on CT is one such marker, and has been associated with erythrocyte rich clots.

The sequence of degradation from oxyhemoglobin to paramagnetic deoxyhemoglobin, methemoglobin, and hemosiderin within the hemoglobin components in trapped erythrocytes in a clot can be exploited by MRI T2*-weighted gradient echo imaging (GRE), whereby red thrombi in occlusive vessels may be seen as hypointense signals within vascular wall . This has been called susceptibility vessel sign. SVS has been associated with cardioembolic stroke mechanism and subsequent recanalization.

In the current study, Yamamoto et al. investigate if two-layered SVS on 3T T2*-weighted imaging (hypo intense core surrounded by hyper intense rim) also associated with cardioembolic etiology. 132 consecutive patients with ICA or MCA occlusion were included, with an mean age of 74 years. As opposed to prior studies, traditional SVS was not associated with cardioembolic mechanism, but two-layered-SVS was found to have high specificity and positive predictive value for cardioembolism. One of the major drawbacks of the study is that no histological analysis of the clots was done. Also, very few stroke centers have access to 3T MRIs in the acute setting. Thus, these findings have poor external validity to most clinical sites. Regardless, it builds up on the prior studies and makes a case for us to pay more attention to the vessels on GRE in patients with large vessel occlusions, especially when the source is elusive. MRI technology has brought stroke care a long way since its inception. And it may be our best noninvasive tool at showing us clot composition moving forward.

Postural Instability, Asymptomatic Cerebrovascular Disease, and Cognitive Decline

Rizwan Kalani, MD

Tabara Y, Okada Y, Ohara M, Uetani E, Kido T, Ochi N, et al. Association of Postural Instability With Asymptomatic Cerebrovascular Damage and Cognitive Decline: The Japan Shimanami Health Promoting Program Study. Stroke. 2014

Cerebral small vessel disease (cSVD) – lacunar infarcts (LI), periventricular hyperintensities (PVH), and microbleeds (MB) on brain magnetic resonance imaging (MRI) – has been associated with older age, hypertension and reduced physical activity. In this study, Tabara et al evaluated for a potential link between postural instability and asymptomatic cSVD in a middle-aged and older cohort.

Data originated from the Japan Shimanami Health Promoting Program (JSHIPP), a medical evaluation program that assessed age-related pathologies, at Ehime University Hospital over a 7 year period. 1387 healthy individuals with no history of symptomatic stroke or dementia that completed optional brain MRI were incorporated in this study. Postural instability was measured by one-leg standing time (OLST), time until raised leg was put down measured twice (with a maximum of 60 seconds), and posturography. Standard MRI definitions for LI and MB were used; PVH was classified into 5 grades (based on Japan Brain Dock Society guideline) with grade 2 or higher considered pathologic. Cognitive impairment was assessed using a computerized dementia assessment scale (DAS) (which tested immediate and short-term memory, temporal orientation, and visual-spatial perception). Carotid intima-media thickness (CIMT) (evaluated by ultrasonography) was used as a measure of arteriosclerosis.

As expected, subjects with cSVD were older, more often hypertensive, and had higher CIMT. The novel finding was that the frequency of short OLST (especially <20 sec) increased linearly with number of LI (p<0.001), number of MB (p=0.023), and PVH grade (p<0.001). After adjusting for covariates (age, sex, BMI, smoking, hypertension, diabetes, CIMT), the association with LI and MB remained significant. Short OLST was also independently associated with lower DAS (p<0.001).

This is the first report of an independent association of OLST with LI and MB as well as with impaired cognitive function. Interestingly, the association between short OLST and cognitive decline was independent of cSVD. Observational design, lack of functional measures, and brief cognitive testing are notable limitations to this study. Nevertheless, it does warrant further research on the clinical implications and prognostic significance of postural instability as well as better understanding of its relationship with asymptomatic cerebrovascular pathology and cognition.

Sum of Its Parts: NIHSS Item Profiles as a Predictor of Patient Outcome

Vikas Pandey, MD

Abdul-Rahum A, Fulton R, Sucharew H, Kleindorfer D, Khatri P, Broderick J, et al. National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Independent Trial Data. Stroke. 2014

The NIH stroke scale is something repeated to the point of unintentional memorization for neurologists across the country, but the logical response to hearing the total NIHSS value that a patient has obtained is “What did the patient get points for?”. As inherent with any scale, the points may be achieved by an extremely high number of combinations. An NIHSS of 18 may be achieved by a patient with hepatic encephalopathy with no focal weakness or a patient with a full right MCA syndrome. Also now evident is that patients with low NIHSS scores (i.e. 0-5) may still be left with significant disability, nullifying the fact that significant disability is only for those with high NIHSS scores. To investigate the predictive value of different NIHSS profiles on stroke outcome, the group from the United Kingdom and Cincinnati retrospectively analyzed patients from the VISTA registry of collaborated acute stroke trails and took the patients that received either placebo or receiving a study drug with no proven efficacy on stroke outcome, however did include those receiving IV tPA as standard of care. 

The patient cohort included 10,271 patients with acute ischemic stroke and separated them according to NIHSS item profiles A to F, in decreasing order of stroke severity (median NIHSS 19 for profile A and NIHSS 4 for profile F). The profiles consisted of phenotypes essentially translated with profile A being a dominant hemisphere large stroke, profile B being a non-dominant hemisphere large stroke, profile C being a dominant stroke with language deficit, profile D being a dominant stroke without language deficit, profile E being a mild non-dominant hemisphere stroke and profile F being a very mild stroke. The more severe profiles were more likely to receive IV thrombolysis treatment. They analyzed the 90 day outcome in terms of mRS and mortality rates and found that across the different profiles, the less severe profiles had increasing odds of better outcome in a step-wise manner, even with adjustments made for age and thrombolysis treatment. Interestingly, those in profile C and D had similar baseline NIHSS (10 and 9, respectively) however had a significant difference in risk of 90 day mortality (43% and 81%, respectively relative to Profile A risk). These results were validated with secondary independent latent class analysis using different distinct NIHSS item profiles.

Looking deeper in to the difference in the profiles, one can see that the main difference between the profiles C and D mentioned were that profile C includes language deficit whereas profile D did not, and profile C had significantly less stroke mortality reduction compared to profile D. This is not surprising given the concept that aphasia has significant effects on rehabilitation prospects, leading to greater disability. Missed in the profiles, however, is the concept of neglect in non-dominant hemisphere strokes which is also a poor predictor of rehabilitation benefit. The group sheds light on the concept that comes to every neurologists’ mind when assessing the true symptoms a patient possesses when making decisions for thrombolysis and further intervention which is that a point given for aphasia is different than a point given for sensory deficit (all points are not equal). Perhaps this may be an early step in an NIHSS overhaul such as giving more points for things such as aphasia or finding a way to present patients as fitting a certain NIHSS profile instead of simply reporting a number, as we can see that the profile provides more valuable information regarding stroke outcome.


Metaclopramide Preventing Aspiration Pneumonia in Stroke Patients with NG Tube Feeds

Duy Le, MD

Anushka Warusevitane A, Dumin Karunatilake D, Julius Sim J, Frank Lally F, and Christine Roffe C. Safety and Effect of Metoclopramide to Prevent Pneumonia in Patients With Stroke Fed via Nasogastric Tubes Trial. Stroke. 2014

Warusevitane et al evaluate whether metoclopramide, given to stroke patients with NG-tubes can decrease the rate of aspiration pneumonia. Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of NGT were recruited into this double blinded randomized placebo controlled trial in the UK. A total of 196 patients were evaluated and ultimately 60 patients were recruited to this study. Reasons for exclusions included chest infections and recruitment to another trial. 30 participants received 10 mg metoclopramide and 30 participants recieved placebo three times daily via NGT for 21 days or until NG feeds were discontinued. Pneumonia was diagnosed if patient had relevant clinical signs, inflammatory markers and new infiltrates on chest radiograph. Results showed that there was significant decrease in episodes of pneumonia in the metoclopramide group (rate ratio = 5.24; p <0.001; 26 from the control and 8 in the metoclopramide group experienced pneumonia). Baseline NIHSS for patient groups were high, averaging about 19 and 18 in the metoclopramide vs. placebo group. There was no significant difference in mortality between the groups. Almost all patients (98%) were fed via NGT for at least one week, 31 patients (51%) for two weeks and 19 patients (31%) for three weeks.

This is the first RCT to show that metoclopramide improves rate of pneumonia in stoke patients with NG tube feeds. The assumption is that the mechanism of pneumonia in these patients is due to an aspiration event. Through increasing gastric motility and decreasing stagnation of gastric contents, one can decrease the risk of aspiration. Additionally, what is impressive is that there were no untoward effects of dyskinesia or tardive dyskinesia. The results and mechanism are convincing on first impression, although a larger study is needed to confirm this finding.

By |December 16th, 2014|clinical|1 Comment