Category: Stroke

Missed a Stroke? You’re Not Alone

It’s easy to fall prey to the quality assurance shaming associated with your hospital’s stroke team.  It’s nearly impossible to find the right balance between over-triage of any remotely neurologic complaint, and getting the inevitable nastygram follow-ups resulting from unexpected downstream stroke diagnoses.

Take heart: it’s not just you.

This retrospective review of evaluated patients discharged with a diagnosis of acute stroke at two hospitals – one an academic teaching institution, and one a non-teaching community hospital.  All patients discharged with such a diagnosis were reviewed manually by a neurologist, and charts were analyzed specifically to quantify the frequency with which an Emergency Physician did not initially document acute stroke as a possible diagnosis, or a consultant neurologist did not make a timely diagnosis of stroke when asked.

Out of 465 patients included in their one-year review period, 103 of strokes were missed – 22% of those at the academic institution and 26% of those at the community hospital.  And, again, take heart – 20 of 55 patients missed at the academic institution were neurology consults for acute stroke, but were initially misdiagnosed by our neurology consultants, as well.  Posterior strokes were twice as likely to be missed as anterior strokes, and symptoms such as dizziness and nausea and vomiting were more frequent in missed presentations.  Focal weakness, neglect, gaze preference, and vision changes were less frequently missed.

Entertainingly, these authors are mostly verklempt over the fact half of missed stroke diagnoses presented within time windows for tPA or endovascular intervention – although, no other accounting of potential eligibility is presented other than timeliness.

“Missed Ischemic Stroke Diagnosis in the Emergency Department by Emergency Medicine and Neurology Services”
http://www.ncbi.nlm.nih.gov/pubmed/26846858

Give More tPA, Pretty Please?

There’s been another scientific update from Genentech-by-proxy, this time lamenting the low utilization for tPA in ischemic stroke patients.  This guideline panel from the AHA notes administering tPA in a safe and timely fashion to stroke patients is a non-trivial organizational exercise, but, what really gets their goat are the various exclusion criteria.  These criteria – minor symptoms, elevated blood pressure, acute trauma, etc. – are aimed at reducing the overall harms of tPA use, but to “help” as many patients as possible, the stroke neurologists believe it is necessary to break all the eggs.

This document, most prominently, is an entertaining exercise in linguistic calisthenics.  Clearly, these authors would like to treat as many patients as possible with tPA.  In their pursuit of these justifications, absent evidence, they torture the English language into providing he most diverse possible assortment of non-committal positivity.  To wit:

  • “There should be no exclusion …”
  • “Intravenous alteplase treatment is reasonable …”
  • “Intravenous alteplase administration for ischemic stroke may be considered …”
  • “…  it is reasonable that urgent intravenous alteplase treatment not be delayed …”
  • “Intravenous alteplase may be considered on a case-by-case basis.”
  • “Intravenous alteplase may be reasonable …”
  • “Use of intravenous alteplase in carefully selected patients … may be considered …”
  • “In acute ischemic stroke patients … intravenous alteplase may be carefully considered …”
  • “… administration of intravenous alteplase is reasonable and probably recommended …
  • “Intravenous alteplase treatment is probably recommended …”
  • “Patients … may benefit from intravenous alteplase …”
  • “… intravenous alteplase treatment appears safe and may be beneficial …”
  • “… intravenous alteplase may be as effective … and may be a reasonable option …”
  • “Intravenous alteplase is probably indicated …”

I.e., this scientific update may be a reasonably probably carefully considered option.  Or, as I’ve heard Jerry Hoffman say, each instance of the word “may” should be paired with its logical partner – “may not” – for the appropriately even-handed reading.

Other gems:

The risk of symptomatic intracranial hemorrhage in the SM population is quite low; thus, starting intravenous alteplase is probably recommended in pref- erence over delaying treatment to pursue additional diagnostic studies (Class IIa; Level of Evidence B).

The authors devote half a page to overstating the safety margin of tPA in stroke mimics by focusing on a single 100-patient cohort.  The clinical anecdotes of the two patient suffering sICH, and being lucky enough to survive, in this cohort are provided as apparently definitive reassurance.

And:

For patients with mild but disabling stroke symptoms, intravenous alteplase is indicated within 3 hours from symptom onset of ischemic stroke. There should be no exclusion for patients with mild but nonetheless disabling stroke symptoms in the opinion of the treating physician from treatment with intravenous alteplase because there is proven clinical benefit for those patients (Class I; Level of Evidence A).

The pursuit of treating mild, but nonetheless disability symptoms is not new – and not specifically offensive.  However, they give this recommendation “Class I, Level of Evidence A”, which is the strongest level of support, based on, apparently, multiple randomized clinical trials or meta-analyses.  Except, however, their justification in the text for this recommendation is merely:

Alteplase may be beneficial for milder stroke cases judged as potentially disabling despite low NIHSS scores. The NINDS trialists explored 5 different definitions of minor stroke in a post hoc analysis and found benefit for alteplase across all definitions. However, data are not available on the effect of alteplase for milder stroke cases judged as not potentially disabling at presentation. Because nearly 3000 such cases of ischemic stroke were excluded from the 2 NINDS trials for mild symptoms, any analysis of mild symptoms within the 2 NINDS trials is difficult to interpret.

Why let the true level of evidence affect the final recommendation categorization?

If left to my own devices, this post could meander onward for an eternity.  I will, then, now step aside to allow the motivated reader to move along to source document itself.

“Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke”
http://stroke.ahajournals.org/content/early/2015/12/22/STR.0000000000000086.abstract

Hunting for Strokes in Vertigo

The vast majority of presentations for “dizziness” in the Emergency Department are benign diagnoses – various dysequilibrium syndromes, vestibulitis, neuritis, and other disorders of the otologic canalicular system.  But, then, some are strokes – and it’s quite challenging to balance diagnostic accuracy and MRI utilization.

This is an observational study performed at the University of Michigan evaluating patients presenting with complaint and exam findings consistent with acute dizziness – requiring either nystagmus or demonstrated gait instability.  Of these patients, all underwent a standardized neurologic examination, including HINTS examination, and subsequent MRI.  A stroke was the presumed diagnosis if an MRI was performed within 14 days and diagnostic of hemorrhage or acute infarction.

There were 320 patients enrolled, and 272 completed the clinical evaluation and an MRI.  Overall, 29 (10.7%) of patients had positive imaging – and, unfortunately, little was strongly predictive.  The few predictive features that shook out of their logistic regression model were the ABCD2 score, a positive HINTS exam, a central pattern to nystagmus, or the presence of other neurologic deficits.  Those individuals hitting all the risk factors ended up with ~20% risk of stroke, while those with none were <5%.  The remaining patients were simply in the intermediate risk group, reflecting the overall baseline level, and approximately one-third of the cohort fell into each category.

I do like their objective criteria for enrollment, based on a minimum of nystagmus or gait abnormality.  I tend to feel many patients receive MRI for similar complaints absent any of these features.  There is, unfortunately, no accounting of any general background rate of diagnosis of posterior circulation stroke at their institution, so there’s no way to estimate the miss rate or added value of their inclusion criteria.  I think their general observations are fair starting points for shared decision-making, although there’s still not quite enough information here to dramatically improve imaging yield.

“Stroke risk stratification in acute dizziness presentations: A prospective imaging-based study”
http://www.ncbi.nlm.nih.gov/pubmed/26511453

It’s Not Time, It’s Brain

The evidence continues to mount that, simply, we’re doing it wrong.

Part of this is an acceptable confusion: we didn’t have the computational power or acquisition resolution capable of evaluating the intracranial circulation or perfusion when treating stroke.  However, as the evidence continues to mount from advanced imaging, it seems clear the “time” aspect is not the best determinant of outcome in stroke.

This is a small review of patients from DUST and MR CLEAN with MCA stroke and CT perfusion imaging available.  CTA is frequently performed to evaluate intracranial vasculature and estimate collateral circulation, but CT perfusion provides a dynamic look at contrast flow throughout the brain.

Based on this small 70 patient cohort, the reliability of the observations is hardly bulletproof, with wide 95% confidence intervals.  However, there is a reasonable, linear decrease in good outcomes as poor perfusion characteristics proliferate.  The best perfused collateral circulation led to 15 of 26 patients recovering to mRS 0-2.  While the flow rate and quality of the collaterals degraded, those with good recovery dropped to 12 of 26, then 1 of 12, and finally to 0 of 6.

The horizon is not far now where, hopefully, we’ll look back at the “time is brain” mantra as the infantile scramblings of the dark ages of acute stroke treatment.  Better imaging technology continues to demonstrate some brain is unrecoverable, regardless of timeframe, while others are likely excellent candidates for preservation of some function.  We ought to have much better options for tailoring treatment to the individual in the near future – and as this technology spreads.

“Impact of Collateral Status Evaluated by Dynamic Computed Tomographic Angiography on Clinical Outcome in Patients With Ischemic Stroke”
http://www.ncbi.nlm.nih.gov/pubmed/26542691

When Peripheral Vertigo Isn’t

But, such misdiagnosis is rather rare.

These authors conduct a retrospective, administrative database study of patients discharged from an Ontario, Canada, Emergency Department between 2006 and 2011 with a diagnosis of peripheral vertigo.  They identify 41,794 patients with appropriate data and an explicit diagnosis of peripheral vertigo, and follow them for adverse outcomes.  Most importantly for this paper, looking at subsequent stroke diagnoses, they find 57 (0.14%) received a diagnosis of stroke within 7 days.  To these authors, this number represents a miss rate for actual cerebrovascular causes of vertigo on initial presentation.

It’s a little hard to put great confidence in this precise number, however, because there were actually 270,865 visits discharged with diagnoses of dizziness & vertigo.  The largest cohort of these, 71% of them, were discarded from analysis because their diagnosis was “Dizziness, giddiness, lightheadedness, vertigo NOS”, which was not specific enough for these authors’ purposes.  It would have been enlightening to have included this less-specific cohort in this analysis, at least as a parallel comparison group, for additional insight.

However, the authors do something I quite like in this paper, and something I think would improve the robustness of many other studies:  a propensity-matched analysis attempting to establish a baseline level of risk.  For these authors, they choose renal colic – a generally benign, yet frequent, condition, that ought confer no special additional risk of stroke.  These authors have no difficulty finding 34,872 of patients to pool into a cohort relatively well-matched on important risk factors.  These renal colic patients have very similar rates of falls and fractures in the short-term after discharge – but they have many fewer strokes.  Most of the difference between cohorts arises in the first 7 days, with 50 occurring in the vertigo cohort versus zero in renal colic.  Between day 7 and and 365, however, the rate difference narrows, with 74 strokes in the vertigo cohort and 49 in renal colic.

Despite the massive limitations of retrospective review and relying on diagnosis codes, I think the authors’ general observation is correct.  Dizziness can be a quite challenging diagnosis to evaluate in the Emergency Department, and clearly some patients are being erroneously given diagnoses of peripheral etiologies.  However, the rate of misdiagnosis in this cohort is likely somewhere better than 1 in 700, which I find generally clinically acceptable considering the impossibility of utilizing advanced imaging in such a vast population.

We can certainly endeavor to do better, but we have a lot of work cut out for ourselves in improving the specificity of our clinical evaluation first.

“Outcomes among patients discharged from the emergency department with a diagnosis of peripheral vertigo”

Tissue, Not Time, for Stroke

The new AHA guidelines for the use of endovascular therapy in acute ischemic stroke broadly include any patient within six hours of symptom onset.  These criteria are based, mostly, on MR-CLEAN – in spite of the follow-up EXTEND-IA, ESCAPE, and SWIFT-PRIME showing the highest yield patients are clearly those with salvageable tissue.  Treatment beyond six hours, however, is still considered reasonable – and this cohort from DEFUSE-2 seems to indicate as such.

Based on 78 patients with target mismatch volume on MRI prior to endovascular therapy, they found: time doesn’t matter, only reperfusion.  The reperfusion outcomes for intervention under six hours are, grossly, no different than the outcomes for those greater than six hours.  And, this makes sense – salvageable tissue is salvageable:

Frankly, this is probably the paradigm for which we should ultimately be moving for all stroke treatment.  Time should not be a limiting factor – and, vice versa, should not be the sole indicating factor.  Dead brain simply can’t benefit from revascularization – no matter how quickly it is provided, regardless of time window.  The traditional “non-contrast head CT” is no longer adequate to provide optimal stroke care – CT angiography with perfusion calculations, or a rapid MRI protocol, should probably form the basis of modern stroke care moving forward.

“Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue”
http://www.ncbi.nlm.nih.gov/pubmed/26224727

It’s Time to Fix NIHSS

The purpose of the National Institute of Health Stroke Scale is to describe stroke severity.  Every point represents a deficit on exam, so, higher is worse – except it’s not that simple.

Every point on the scale is, unfortunately, clearly unequal.  Partial paralysis of the face is 2 points.  Profound hemi-inattention is also 2 points.  One of those patients – unless they’re Derek Zoolander – is not disabled.

This is a study, along with others in a similar vein, that translates that common sense directly into an indictment of the NIHSS as currently used.  These authors retrospectively evaluate six “profiles” of patients with discrete clinical manifestations of stroke, by basing their analysis on specific NIHSS item.  They use the NIHSS data from 6,843 patients in the SITS-MOST data, and, essentially, they find very different survival curves for patients with similar NIHSS when specifically categorized by clinical syndromes.

This leads to two main points:

  • We shouldn’t be using the NIHSS the way we’re used to using it.
  • The clinical variability of patients with similar NIHSS can vastly affect stroke trials with low sample sizes.

Time to fix the NIHSS!

“National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome”

Endovascular Sans tPA in Bern

The first hints of a rollback in tPA use are starting to emerge – not unexpectedly, from those working to improve the outcomes of their endovascular programs.

This is a retrospective evaluation of patients from Bern, Switzerland, all treated with endovascular therapy.  Their registry includes 372 patients since 2004, all treated for MCA or ICA occlusions and with DWI measurements pre-treatment.  As with any data dredge, any findings are just hypotheticals – but, there’s a couple interesting tidbits:

  • Smaller lesions did much, much better – 54.5% achieved mRS 0-2 if lesion volume was <70mL, compared with 21.2% with lesion volume >70mL.
  • If you failed to reperfuse a lesion volume >70mL, mRS 0-2 outcomes sank to 8.6%.
  • Symptomatic intracranial hemorrhage jumped to 19.7% for lesion volume >70mL.
  • There were only 66 patients over >70mL lesion volume, but the best outcomes?  The 19 with mechanical therapy only – balancing 21.1% mRS 0-2 with only 5.3% SICH.

The authors ultimately conclude endovascular therapy for large lesion volumes might be best without any thrombolytic involved.

Wasn’t it lovely how fashionable tPA was – until endovascular therapy finally reached a tipping point in terms of efficacy?

“Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment”
http://stroke.ahajournals.org/content/early/2015/08/06/STROKEAHA.115.010250.short

Better Less than More for tPA

Ah, but this is not one of those rants about the inefficacy of tPA.  This is just an amuse-bouche of a mention of an article from Stroke, regarding a line of investigation in Asian countries.

In these countries, particularly Korea and Japan, there is some substantial thought given to “low dose” tPA being just as effective, with a lower risk of intracranial hemorrhage.  Interestingly, approximately 40% of acute stroke patients in Asian countries is at this lower dose, 0.6 mg/kg compared with the typical 0.9 mg/kg.  This study is a retrospective evaluation of registry data from 13 academic stroke centers, comparing 3-month outcomes on the modified Rankin Scale.

There were, essentially, two entertaining bits from this article:

  • The rate of symptomatic ICH in centers contributing at least 100 patients during the study period ranges from 3.7% on the low side up to 13.0% on the high.
  • Given the constraints of the study, they were unable to demonstrate any reliable difference between the two doses.  In fact, as you can see from the figure below, retrospective data can be adjusted, propensity matched, or essentially tortured to show whatever advantage preferred:

Should we be using low-dose?  And why stop at 0.6 mg/kg – why not 0.3 mg/kg?  And, further down the rabbit hole, back to the ideal dose of … none.  Ah, but I kid, I kid ….

“Low-Versus Standard-Dose Alteplase for Ischemic Strokes Within 4.5 Hours: A Comparative Effectiveness and Safety Study”
http://www.ncbi.nlm.nih.gov/pubmed/26243232

Retinal Photography to Diagnose TIAs?

Our diagnostic approach to suspected cerebrovascular disease is quite simple.  Concerning neurologic findings or history?  Magnetic resonance imaging.

However, this approach is grossly inefficient – and, thus, the rise of various clinical scores such as the ABCD2 variants.  And, now, ocular fundus photography.  It generally makes sense – the retinal vessels travel through the optic nerve sheath.  They are, then, a unique window into the cerebrovascular circulation – and, accordingly, the degenerative diseases within.

It sort of works.

Looking at patients presenting to the ED with a report of focal neurologic deficits, the multivariate regression OR for cerebrovascular disease in patients with arterial narrowing in 2 segments is reported as 8.1 for stroke and 5.1 for TIA.  However, this finding was only present in 4 of 22 (18%) stroke patients and 6 of 59 (10%) TIA patients – compared with 5 of 176 (3%) patients who did not receive a diagnosis of cerebrovascular disease.

So, yes – it is probably true, as the authors claim, that finding arterial focal narrowing in the retinal vessels increases the likelihood of cerebrovascular disease (stroke and TIA).  But, clearly, the positive predictive value is still quite low, and the number of patients for whom this ocular photography adds substantially to the diagnosis is quite small.  At ~$25,000 a pop for the camera system, and the need for a specialist to screen the images for abnormalities, I do not share these authors’ enthusiasm for its eventual adoption into clinical practice.

“Ocular fundus photography of patients with focal neurologic deficits in an emergency department”
http://www.ncbi.nlm.nih.gov/pubmed/26109710