Neurology – Page 11 – Emergency Medicine Literature of Note

Nonsensical Opiate Overuse in Adolescent Headache

The title says it all.

This is an observational cohort analysis of linked medical and pharmacy records for commercially insured patients across 14 health plans. Patients were identified by age 13-17 with, allegedly, new-onset atraumatic headache from claims database abstraction – limited, of course, by the nature of querying such a database. 8,373 patients were identified from their two year study period as meeting these criteria.

And 46% were prescribed opiates.

52% of those received more than one prescription for opiates, including 11% who received 5 or more prescriptions for opiates during the study period.

This study came about because the insurer contacted the American Academy of Pediatrics with a query regarding the appropriate frequency of use of opiates for headache. The answer ought to be a tiny fraction, as third-line or rescue therapy.

Considering all the problems this country has with prescription opiate abuse, it is maddening to see physicians inoculating such a vulnerable population with medication whose harms almost certainly outweigh the benefits.

“Opioid Use Among Adolescent Patients Treated for Headache”
http://www.jahonline.org/article/S1054-139X(13)00834-3/abstract

ABCD3 – Better, But Good Enough?

The ABCD2 score for the prediction of stroke after TIA was initially touted as a possible risk-stratification tool geared towards determining which patients could undergo delayed evaluation for modifiable risk factors. Unfortunately, the “low risk” cohort generated by the ABCD2 score still has an unacceptably high risk of stroke at 7 days, with poor predictive and discriminative power.

These authors try to take it to the next level – the ABCD3 score and the ABCD3-I score. Derived retrospectively from the Kyoto Stroke Registry, the third element of D3 is “Dual TIA” – which is having had another TIA within the prior 7 days. Then, the “I” is dependent upon having a positive MRI DWI lesion associated with concurrent ipsilateral carotid artery stenosis.

In their retrospective application of ABCD2, ABCD3, and ABCD3-I, as expected, the ABCD2 score showed minimal utility for the outcome of interest for the Emergency Department – the 7 day risk of stroke in the low-risk cohort was ~6%. The low-risk ABCD3 and ABCD3-I cohort, however, had a ~1 to 2% risk at 7 days. If verified prospectively, this begins to approach reliable utility for discharge decision-making in the ED. Given the ABCD2 score’s checkered past, I would certainly wait for the next bit of evidence.

“ABCD3 and ABCD3-I Scores Are Superior to ABCD2 Score in the Prediction of Short- and Long-Term Risks of Stroke After Transient Ischemic Attack”
http://stroke.ahajournals.org/content/45/2/418.full

Warning: Jolt At Your Own Risk…

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Jolt accentuation is a means of perturbing the meninges of a patient presenting with a headache, in the hopes of delineating those who have meningitis from those with a more benign cause. Similar to the “rock the gurney” test in appendicitis or the Dix-Hallpike in BPPV, we are exacerbating the patient’s symptoms in the hopes of better understanding their illness. It has been claimed that the jolt accentuation test is the most sensitive physical exam finding available to rule out meningitis. A recent article published in American Journal of Emergency Medicine suggests otherwise.

This elegantly constructed prospectively gathered cohort was performed at two inner city hospitals over a 4-year period. Authors enrolled all neurologically intact patients older than 18 years old presenting with symptoms suspicious for meningitis. Physicians were asked to answer a questionnaire of physical examination findings before receiving CSF results. Cunningly the authors surreptitiously placed the LP trays at the research staff’s station to ensure capture of eligible candidates.

47 patients (20%) out of 230 total enrolled were found to have CSF pleocytosis (defined as > 5 WBC ). The jolt accentuation test performed poorly at identifying these patients, with a sensitivity of 21% and a specificity of 82%. Kerning sign, Brudzinski sign, and nuchal rigidity performed no better with sensitivities and specificities of 2%, 2%, 13% and 97%, 98%, 80% respectively. Dishearteningly, the Emergency Physicians overall gestalt performed just as poorly with a sensitivity of 44% and a specificity of 40%.

Unfortunately the authors do not tell us how the jolt accentuation test performed in patients diagnosed with bacterial or fungal meningitis. In this cohort only 3 of the 230 patients had culture positive meningitis, with only 2 from bacterial or fungal sources (one Cryptococcal and one Meningococcal ). The Emergency Physician identified both of these cases as high-risk upon initial evaluation. The authors failed to mention whether the jolt accentuation was positive in either of these patients. To truly examine jolt accentuation’s diagnostic performance, further studies using culture positive bacterial meningitis rather than pleocytosis as our diagnostic criteria are needed. This would require a much larger cohort, including a significantly larger quantity of cases of bacterial meningitis. But until then perturb with caution…

“Jolt accentuation of headache and other clinical signs: poor predictors of meningitis in adults” www.ncbi.nlm.nih.gov/pubmed/24139448

The Eloquence of Stroke Neurologists

Entertainingly enough, as tPA proponents continue their push for longer time windows and less-stringent inclusion criteria, Stroke recently published a sort of head-to-head debate regarding tPA within the 3 – 4.5h window.

Despite the breathless madness typically exhibited by stroke neurologists and the current Level B recommendations from the AHA, Lawrence Wechsler from the University of Pittsburgh writes a very reasonable critique of ECASS III, incorporating data from ATLANTIS and IST-3. His general point, overall, is the theoretical effect size, if any, is small beyond 3 hours. Therefore, he proposes patients should be carefully selected – perhaps by penumbral perfusion imaging.

His opponents, from Germany, in their response, offer a critique featuring this well-written, professional, academic segment:

Is advanced imaging necessary to make this decision? Why, No?! Would a lacunar versus nonlacunar syndrome make a difference here? No!! It would not make a difference within 3 hours, would it? And what about an MRI without perfusion imaging/diffusion weighted imaging mismatch or with proof of a lacunar stroke, would this make a difference? Hell, no!!! There is no evidence at all for this conclusion. And is there any reason to believe that rt-PA does not work in the 3- to 4.5-hour time window or that it does work only in “a carefully selected set of patients”? What the h…, No, No No!!!!

In keeping with Patrick Lyden’s lovely ad hominem attacks on Anand Swaminathan (“young”, “naive”), it is yet again abundantly clear some proponents of tPA have no response in reasonable, scientific debate other than nonsensical, authoritative bluster.

“The 4.5-Hour Time Window for Intravenous Thrombolysis With Intravenous Tissue-Type Plasminogen Activator Is Not Firmly Established”
http://www.ncbi.nlm.nih.gov/pubmed/24526061

“4.5-Hour Time Window for Intravenous Thrombolysis With Recombinant Tissue-Type Plasminogen Activator Is Established Firmly”
http://www.ncbi.nlm.nih.gov/pubmed/24526060

Again on Giving tPA to TIAs

When I suggested to Jeff Saver in JAMA his analysis of the Get With the Guidelines Registry may have become unbalanced due to the presence of TIAs within the tPA cohort, he went back to the NINDS data and identified seven patients from the placebo arm with TIAs. Because 3 were in the 58 to 90 minute cohort and 4 were in the 91 to 180 minute cohort, he concludes there is an equal distribution of TIAs – and thus confounders – across all time periods. This, of course, is nonsense – he is generalizing a handful of patients from the placebo arm from NINDS, a carefully controlled trial run by stroke neurologists, to the GTWG-Stroke registry, a cohort of community hospitals rushing to hit time-based stroke quality measures. The contemporary evidence, such as this observational series from Japan, is that most TIAs present early in their symptom course – and earlier, if symptoms are more severe.

These authors retrospectively identified 464 patients admitted to 13 stroke centers in Japan with ultimate diagnosis of TIA based on complete clinical resolution of symptoms. 233 of them (55%) presented within the first three hours and the next 65 (15%) within six hours. The common elements for the TIAs presenting earliest were the greatest severity of symptoms, primarily motor and speech disturbances. A full 42% of their cohort had persistent symptoms upon arrival.

In the brave new world of tPA, hospitals are falling over themselves to treat these patients with thrombolytics – patients that ultimately would experience full clinical resolution of symptoms without intervention, and receive only the risks associated with tPA administration. These patients ultimately make their way into the GWTG-Stroke registry, and come out the back end analysis looking like tPA miracles, “proving” time-to-treatment matters with tPA. As “code stroke” protocols become more widespread, we will see even further such collateral damage.

“Factors Associated With Onset-to-Door Time in Patients With Transient Ischemic Attack Admitted to Stroke Centers”
http://www.ncbi.nlm.nih.gov/pubmed/24262324

Why Observational Data for tPA is Flawed

Much is made of retrospective comparisons derived from registry data in acute ischemic stroke. The most egregious of these attempt to match a subgroup of tPA-treated folks with a control group not receiving tPA.

This publication, from an Austrian stroke registry, pulls 890 patients from 54,917 with mild (NIHSS <5) symptoms to perform a comparison matched on many clinical features. In their matched comparison, 41% of tPA-treated patients were better off, 30% were identical on mRS, and 29% favored non-treatment. Therefore, these authors declare there is an overall shift towards favorable outcome with tPA.

What is wrong with drawing anything but hypothesis-generating conclusions from this data (or, any retrospective, observational data)? While the authors control for a few factors, there are many pre-existing comorbid conditions influencing treatment or non-treatment with tPA. For example, a patient with advanced metastatic cancer will almost certainly be excluded from treatment with tPA – and certainly have poor 3-month functional outcomes – but that comorbid state cannot not be captured by this registry. Then, just as we saw in IST-3, patients who are treated with tPA frequently receive more vigilant initial stroke care. Adherence to clinical pathways as well as the control of hyperglycemia, fever, and swallowing dysfunction have profound effects on subsequent death and disability far exceeding the effect size supposed for tPA. This registry, taking place over the course of a decade of evolving stroke care, cannot control for follow-up treatment and therapy.

This is, essentially, why all retrospective, observational comparisons are almost guaranteed to favor the tPA cohort.

Just as an added note – for anyone considering responding directly to the authors in the pages of Stroke – you will be charged $35 for typesetting for an electronic-only publication which then resides behind a paywall. Traditional scientific journals are for profit, not for science – that’s where FOAMed comes in!

“Thrombolysis in Patients With Mild Stroke: Results From the Austrian Stroke Unit Registry”
http://stroke.ahajournals.org/content/early/2014/01/30/STROKEAHA.113.003827.abstract

Maddening Lack of Perspective in Endovascular Stroke Therapy

Despite three negative trials in the New England Journal of Medicine last year, accompanied by an editorial calling for a moratorium on reimbursement for endovascular therapy for acute stroke, proponents of this therapy forge ahead. The negative trials, at the very least, have encouraged researchers to recognize – where tPA advocates fail to see – that patient selection is key, and not all candidates eligible for endovascular therapy are likely to benefit.

However, these authors, despite their well-intentioned effort to better target endovascular interventions, completely miss the mark. This is a retrospective review of patients undergoing endovascular therapy between 2008 and 2012, stratified by selection protocols. In 2010, the institution switched from an “all-comers” strategy to an MRI diffusion-weighted imaging-guided protocol. The hypothesis: patients selected for endovascular therapy on the basis MRI-guided infarct characteristics would display better outcomes than the “all-comers” selection cohort.

And, their registry provides them the necessary substrate. Between 2008 and 2010, 85 patients with median NIHSS 17 underwent endovascular therapy with dismal outcomes: 9.5% mRS 0-2 at 30 days and 47.6% mortality. After implementation of the imaging-based protocol, only half of eligible patients qualified – and of the 92 patients with median NIHSS 15.5 who eventually underwent endovascular therapy under the new protocol, 23.9% had mRS 0-2 and mortality dropped to 19.7%. Victory! So say these authors.

However, there’s another cohort visible only by its absence in their tabular data – the post-protocol group that did not undergo endovascular therapy. These 87 patients, with a median NIHSS ~16.5, had imaging characteristics thought by these authors to not qualify for endovascular therapy. For this group, 23.1% had mRS 0-2 and 30% mortality. These outcomes are not statistically different from the endovascular group.

The authors do not in any manner address this inconsistency in their data set – and the seemingly favorable intervention of lack-of-intervention. Rather than the authors’ conclusion imaging could guide therapy – the better conclusion is that endovascular therapy was frighteningly harmful to many in the pre-protocol phase, and simply reducing the number of patients undergoing unnecessary intervention improved global outcomes. And, for just added perspective: the placebo group in NINDS, with median NIHSS 15, had 26% mRS 0-1 and 21% mortality at 3 months – and this is before the modern post-stroke care that does more to improve outcomes than tPA could ever claim.

The madness continues.

“Addition of Hyperacute MRI Aids in Patient Selection, Decreasing the Use of Endovascular Stroke Therapy”
http://stroke.ahajournals.org/content/early/2014/01/09/STROKEAHA.113.003880.short

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

Since the publication of IMS-3, SYNTHESIS and MR RESCUE in the NEJM earlier this year, proponents of endovascular interventions for acute ischemic stroke have hypothesized why these trials were universally negative. Among the various explanations, one of the most prominent was that the trial designs selected the wrong patients. In order to fully highlight the benefits of endovascular therapy it must be performed on large vessel occlusions with ischemic but viable brain tissue down stream. The authors of a recently published study in STROKE have suggested a solution for this very problem. With the publication of their derivation and validation cohorts of the second generation of the HIAT score, HIAT-2 score, they postulate this decision rule will help predict which patients will benefit from endovascular interventions. The second revision of the HIAT score incorporates the original 3 factors, age, NIHSS and blood glucose at presentation in addition to the ASPECT score of the initial non-contrast CT. As opposed to the initial iteration of HIAT (1 point allotted for each of the 3 factors), HIAT-2 is a 10-point scale (10 being most severe) with age, ASPECT score, NIHSS and blood glucose level relatively weighted in descending order of influence.

The score was retrospectively derived and validated from two prospectively gathered databases of patients who underwent endovascular treatment for acute ischemic stroke. Older patients, with increased NIHSS and more ischemic changes on their initial CT fared far worse than their younger less critically presenting counterparts. In patients with a HIAT-2 scores of 5 or greater, 80% had a mRS of >4 at 90 days. A HIAT-2 score of >7 resulted in 100% of patients having a mRS of >4 at 90 days. The authors conclude that since patients with a high HIAT-2 score had poor 90-day outcomes, endovascular interventions should be limited to patients with a HIAT-2 score of 5 or less.

Never mind that the HIAT-2 score is only moderately capable of identifying those with a poor outcome after endovascular intervention (AOC is only 0.73), the more egregious logical fallacy committed by these authors was to conclude that the HIAT-2 score will differentiate those who will benefit from an endovascular intervention from those who will not. HIAT-2 does nothing of the sort. It is merely a predictor of prognosis at 90 days. Older patients, with more severe strokes at presentation (both clinically and radiologically) will have a worse prognosis no matter what interventions are performed. Interestingly, if the HIAT-2 score is utilized as proposed by its authors, it would exclude the patients who were originally hypothesized to benefit from these endovascular interventions. Patients with symptoms severe enough (usually NIHSS 10 or greater) to be large vessel occlusions are the types of strokes, which lend themselves to endovascular interventions. These are the types of infarcts the HIAT-2 score would exclude from endovascular treatment options.

Finally, in the IMS-3 trial though the HIAT-2 score was not specifically measured, age, NIHSS and the ASPECT score were all recorded. 31% of the cohort was younger than 65, over half the cohort was ASPECT 8,9, or 10 and greater than 80% had a NIHSS at presentation of 19 or less. No benefit of endovascular treatment over tPA was seen in any of the subgroups that are the most heavily weighted components of the HIAT-2 score.

The HIAT-2 score would require prospective validation before it can be used clinically, but I argue that in its current form, HIAT-2 is unable to answer the question for which it was conceived. At present the best evidence we have demonstrates endovascular interventions are no better than tPA (and some would argue tPA is no better than placebo). More high quality trials are needed to identify if there is a subgroup of patients who may benefit from endovascular interventions but pseudoscience and logical fallacies do nothing to augment the knowledge we have gained so far.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

HIAT-2 for Prognosticating Outcomes After Endovascular Interventions in Stroke: Proving Once Again Sick People are Sick

A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.

“Optimizing Prediction Scores for Poor Outcome After Intra-Arterial Therapy in Anterior Circulation Acute Ischemic Stroke”
www.ncbi.nlm.nih.gov/pubmed/23929748

HINTS vs. ABCD2 in Dizziness

Dizziness in the Emergency Department sends everyone down their favorite diagnostic algorithm, with outcomes ranging from utterly benign to impending permanent disability. I’ve covered the repurposing of the ABCD2 score for risk-stratification in dizziness before, showing it had some utility in predicting posterior circulation stroke.

However, unsurprisingly, these authors demonstrate examination maneuvers specifically targeted at evaluating cerebellar function outperform risk-stratification. The HINTS (head impulse, nystagmus type, test of skew) evaluation compared with the ABCD2 (age, blood pressure, clinical features, duration, diabetes) in a convenience sample of 190 prospectively collected patients with acute vestibular syndrome. Of these 190 patients, 124 had a central cause for their vertigo (stroke, hemorrhage, space-occupying lesion). The sensitivity and specificity of the ABCD2 score in predicting a central lesion was 58.1% and 60.6%, respectively, while the HINTS score resulted in 96.8% and 98.5%, respectively.

It’s a bit of a straw-man comparison – considering the ABCD2 score was never designed to detect posterior circulation stroke, only to affect probability estimates for cerebrovascular disease. The prevalence of disease in this sample probably also leads to an overestimation of the specificity of the HINTS exam, but it has otherwise been found to have very good test characteristics.

Visit EMCrit for more information and video footage of the HINTS test, if you’re not already using it.

“HINTS Outperforms ABCD2 to Screen for Stroke in Acute Continuous Vertigo and Dizziness”
http://www.ncbi.nlm.nih.gov/pubmed/24127701