Category: Neurology

The Latest Prognostication for Stroke

We have a fairly robust vascular neurology program at my institution, and – unsurprisingly – they’re rather pro-thrombolysis.  While our disagreements over the efficacy of thrombolysis for acute strokes are generally set aside in a truce stemming from academic and research interests, the main philosophical difference between our services remains this: the difference between eligible and indicated.

Vascular neurology tends to treat these terms as synonymous regarding thrombolysis and acute stroke, while it’s clear from the literature that not every patient benefits from thrombolysis.  The most recent issue of Neurology features another prognostic tool, the SPAN-100, which is the simplest by far: NIHSS + age.  If this score is >100, fewer patients will benefit from tPA than will be harmed.  There’s a quality-of-life discussion to be had regarding individualized treatment decisions in SPAN-positive patients, and this is derived from a very small cohort, but it’s consistent with the remaining literature.

The accompanying editorial is also pro-thrombolysis, but does recognize these scoring systems are important clinical tools in educating patients and families regarding the potential for benefits and harms. Most importantly, this table from the editorial summarizes the growing body of literature available to assist the decision-making process:


I look forward to seeing these develop such that clinicians have better tools with which to separate eligible from indicated.

“Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100″
www.ncbi.nlm.nih.gov/pubmed/23175723

Evidence Summary for Bell’s Palsy

Although the incidence of stroke in young people is rising, some of these “strokes” can still be clinically diagnosed with Bell’s Palsy.

However, once the diagnosis is made, the practice variation is extensive.  In light of this, the American Academy of Neurology has published an update to their evidence-based guidelines for the treatment of Bell’s Palsy.

Short answer:
 – Steroids are good, with a 12 to 15% increased chance of functional recovery.
 – Antivirals have no consistent evidence of benefit.

Long answer:
 – Only ~4% of Bell’s Palsy sufferers are left with severe residual deficits, with the remainder fully recovering or with slight/mild deficits.  Some folks would pose the question whether any of these treatments are necessary, considering the minimal absolute benefits, even if relative benefits are consistent.

Another risk/benefit decision to discuss with patients.

“Evidence-based guideline update: Steroids and antivirals for Bell palsy : Report of the Guideline Development Subcommittee of the American Academy of Neurology”

Predicting Immediate Improvement After tPA

tPA for stroke remains controversial, to say the least.  The reasons behind the Emergency Medicine/Neurology disconnect are complex and covered elsewhere.  Regardless, thrombolysis is here to stay – and probably helps some patients.  The hard part is finding those patients with the most favorable risk/benefit ratio.

This is a study that looked at diffusion-weighted imaging to try and predict which patients were most likely to rapidly improve with tPA.  These authors enrolled sixty-six patients with acute stroke eligible for tPA under the Japanese license and performed diffusion-weighted MRI on each of them.  Previous studies had suggested an ASPECTS score > 7 predicted response to tPA – and this study confirmed it.  Essentially, this translates as larger vascular territories showing greater improvement in NIHSS after tPA than smaller vascular territories.

There’s a bit of a bias in this study, since smaller vascular territories may have produced smaller initial NIHSS.  The population was quite old for a stroke study – median age 79.  And, truly, the more interesting data presented is the breakdown demonstrating the massively favorable impact of early (within 1 hour) recanalization after tPA administration.

But, mildly interesting paper, important as part of a slow, gradual trend of attempts to delineate which patients have the best potential to benefit from tPA.

“DWI-ASPECTS as a Predictor of Dramatic Recovery After Intravenous Recombinant Tissue Plasminogen Activator Administration in Patients With Middle Cerebral Artery Occlusion”
www.ncbi.nlm.nih.gov/pubmed/23212169

The Hazards of Love

“Sexual activity is mechanically dangerous, potentially infectious and stressful for the cardiovascular system.”

Indeed!

According to this retrospective review of 11 years of electronic health records from University Hospital Bern, Switzerland, they identified 445 patients seeking emergency care secondary to sexual intercourse.  The majority of emergency department visits were secondary to suspected infectious etiologies (62%), but neurologic complaints, trauma, and cardiovascular incidents comprised the remaining portion.  

The trauma portion probably speaks for itself without need for additional detail.  There was one myocardial infarction and one aortic dissection.  Among the “various complaints”, two patients were diagnosed with “eczema”.  However, among the neurologic emergencies, there were 12 cases of subarachnoid hemorrhage and 11 cases of – ah – “transient global amnesia”.

All things being equal, at least, sexual activity was only associated with 0.1% of emergency department visits – hardly the most dangerous of potential choices of recreation.

“Sexual activity-related emergency department admissions: eleven years of experience at a Swiss university hospital” 
http://www.ncbi.nlm.nih.gov/pubmed/23100321

What To Do With The “Dizzy” Patient?

As the authors in this retrospective review state, “Vertigo/dizziness is a common and challenging problem faced by the ER physician.”  And, this is obviously true.  Is it dysequilibrium?  Is it true vertigo?  Is it central or peripheral?  And, finally, “now what”?

This is a clearly pro-MRI and con-CT study which, unfortunately, leads to a massive disconnect with reality.  For most institutions, CT might be feasible, but MRI comes to town once a week for scheduled studies only.  But, in this review of 448 head CTs for dizziness, the CT picked up essentially 10 interesting findings – but 16% of the subset of follow-up MRIs performed changed the initial diagnosis.  Mostly, the missed diagnoses on CT were posterior circulation strokes and intracranial masses.  

So, essentially what they observed was more false negatives than true positives for CT.  This implies – at least in a retrospective fashion – that if your pretest probability is high enough for an intracranial process causing dizziness, the intention ought to be to conclude your investigations only with a negative MRI.  I think most folks – given infinite resources – would agree.  Otherwise, you’ll need to base imaging (if any) on clinical findings and risk factors for cerebrovascular disease in an attempt to develop an estimate for their true probability.

“Utility of head CT in the evaluation of vertigo/dizziness in the emergency department”
www.ncbi.nlm.nih.gov/pubmed/22940762

November Annals of EM Journal Club

Our EM Journal Club group down here at UT-Houston collaborated to write the Annals of Emergency Medicine monthly Journal Club installment, published in the November issue.

You get the questions now – at least, they’re available online starting today – but you’ll have to wait in suspense for months to hear our “answers”.

I don’t know if it was an editorial decision to put our thinly veiled IST-3 critique on page 666 of this year’s volume, but I can’t imagine it’s just a coincidence….

“rt-PA and Stroke: Does IST-3 Make It All Clear or Muddy the Waters?”
http://www.ncbi.nlm.nih.gov/pubmed/23089093

tPA of The Future

“The potential benefits associated with this approach are faster reperfusion, lower risk of hemorrhage, and earlier initiation of fibrinolytic therapy, possibly by first responders.”  

Sounds lovely, yes?  This is the pie-in-the-sky version of tPA, complete with flying cars and hoverbuses.  It’s a “Clinical Implications of Basic Research” article from NEJM covering a Science article about shear-activated nanoparticles.

Essentially, in a mouse model of acute arterial thrombosis and pulmonary embolism, researchers bound tPA to aggregated nanoparticles.  In normal vasculature, these aggregates remain unaffected.  However, in regions of turbulence and shear associated with stenosis, the aggregates break apart, exposing the biochemically active tPA in greater quantities.  The authors, taking cue from the current political season, promise potential 100-fold reductions in dosing of tPA associated with this serendipitously targeted approach rather than standard systemic therapy.

So, someday, instead of taking an aspirin and calling 911 – home thrombolytics?

“The Shear Stress of Busting Blood Clots”
www.ncbi.nlm.nih.gov/pubmed/23034026

“Say Anything”, Regardless of the Data

As we’ve learned from prior publications, the conclusions section of the abstract is the ideal location to “spin” your article to generate news releases.  This article, from JAMA Neurology, compares thrombolysis to endovascular intervention for acute carotid artery occlusions and states “Intravenous thrombolysis should be administered as first-line treatment in patients with early cervical ICA occlusion.”

That’s a pretty strong statement, without qualifiers.  And, it means it received press coverage from MedPage Today, the ACEP News network, etc.

And, they base that statement on retrospective review of a cohort of 21 patients, 13 of whom received thrombolysis and 8 of whom received endovascular intervention.  The tPA patients did better, done and done, OR for early neurologic recovery 77 (95% CI 3 to 500).  But, then, Table 2 is a mini-systematic review of prior studies – and it turns out the rate of neurologic recovery is more like 40-50% with endovascular treatment, not the 1 in 8 they found in their retrospective cohort.  Indeed, the authors go on to state in the article “These findings are in contrast to the results of previous studies”, and have an entirely reasonable, non-conclusive discussion of their findings in context of the other daa.

But, if you want news coverage, say something “interesting” in your abstract.

“Stroke From Acute Cervical Internal Carotid Artery Occlusion”
http://www.ncbi.nlm.nih.gov/pubmed/23007611

Intensive Blood Pressure Control in ICH

Not much works to treat ICH – and this retrospective analysis of INTERACT1 tries to coordinate a couple leaps to pull a different spin out of old data.  Unfortunately, it’s still a re-analysis of essentially a negative trial, and that limits its utility for the purists.

INTERACT1 randomized patients with ICH to either “intensive” blood pressure lowering or conventional treatment – most of whom received some BP control – and noted significant improvements in hematoma volume.  However, the 90-day safety/clinical outcomes data did not show any difference in mortality or dependency.  This publication reverses the strategy, taking a look at the associations between good clinical outcomes and hematoma volume – and finds that increases in hematoma volume at 24 hours clearly predict poor clinical outcomes.

So, if intensive BP control reduces hematoma expansion and reduced hematoma expansion improves clinical outcomes, then why was INTERACT1 negative?  I suspect we’ll find out more when INTERACT2 is published….

“Hematoma growth and outcomes in intracerebral hemorrhage: The INTERACT1 study”

Platelet Transfusion & Intracerebral Hemorrhage


This systematic review is published in Annals of Emergency Medicine under the section heading of “Best Available Evidence”, which somehow to me seems to pleasantly understate the unfortunate lack of data on this topic.


Intracererbral hemorrhage in the setting of antiplatelet use unfortunately is one of those clinical situations where outcomes are so dire that the philosophy seems to be to throw the kitchen sink of potentially beneficial interventions at patients.  Use of clopidogrel, and to a lesser extent aspirin, are associated with increased hematoma size and poorer outcomes.  Platelet transfusions, using measures of platelet aggregation activity, are demonstrated to improve and reverse inhibition in approximately two-thirds of patients.  Therefore, it follows that platelet transfusions would improve outcomes in intracranial hemorrhage.


Unfortunately, the “best” evidence – which is mostly retrospective data of small cohorts – fails to demonstrate any improvement in mortality or morbidity.  It is not possible to say from the data whether the platelets do not show efficacy at treating the extension of the ICH, or whether the poor outcomes result from parallel transfusion-related complications.  The article concludes that withholding platelet transfusion should be considered to be within the standard of care.  I tend to agree that resource-intensive treatments should be required to demonstrate benefit before widespread adoption, and therefore agree with these authors.


The authors additionally note a prospective, multicenter trial is underway.


“Does Platelet Transfusion Improve Outcomes in Patients With Spontaneous or Traumatic Intracerebral Hemorrhage?”

http://www.ncbi.nlm.nih.gov/pubmed/22841709