Top Issues in Emergency Neurology Today

Standards of care in emergency neurology

Mobile stroke units

Mobile stroke units have gotten a lot of press recently, and rightfully so. A mobile stroke unit is an ambulance that is equipped with neuroimaging capabilities, point-of-care laboratory testing, telemedicine capabilities, and medications such as intravenous tissue plasminogen activator (IV tPA) and anticoagulant reversal capabilities.

The goal of these units is to bring swift treatment to where a stroke patient might be, as opposed to waiting for the patient to arrive in the hospital. The safety, efficacy, and cost-effectiveness of these units is currently being evaluated at various centers in different countries, but because “time is brain,” these units may have the potential to influence what we view as standard of care in emergency neurology down the road.¹

Large vessel occlusion

A hot topic of discussion in the stroke world is how patients who are suspected of having a large vessel occlusion (LVO) should be triaged. Traditionally, many stroke patients have been initially triaged to the nearest stroke unit to be evaluated for IV tPA and then transferred to a comprehensive stroke center if an evaluation for endovascular therapy is needed. In the context of all the positive trials for endovascular therapy over the past couple of years, the thought is that stroke patients who are identified as having an LVO in the field should be transferred to a center with endovascular therapy capabilities immediately, to reduce the time to revascularization.

Clinical scales are being developed to help clinicians discern patients with LVOs in the field. Changes in ambulance triage and patient flow potentially have practical implications for neurologists in different practice settings and for Emergency Medical Services staff everywhere.²

Intracranial hemorrhage

As direct oral anticoagulants (DOACs) aside from warfarin become more popular, we are seeing more patients with intracranial hemorrhage who are on these medications (eg, dabigatran, rivaroxaban). The best methods of reversing DOACs for patients with intracranial hemorrhage are an actively evolving field of research. Intravenous idarucizumab, a humanized antibody, has emerged as a reversal agent for dabigatran, although data regarding safety and efficacy for its use in patients with intracranial hemorrhage are needed. For the time being, prothrombin complex concentrates remain the method of choice for rivaroxaban reversal; newer agents-such as andexanet alfa, which is a “decoy” binder of factor Xa inhibitors, are undergoing the drug approval process.³

Cardiac arrest

In the world of immediate post–cardiac-arrest management, the proper target for temperature management is a much-discussed topic, and great hospital-to-hospital variability currently exists with regards to formal protocols. As a nod to landmark trials published in the early 2000s, the most recent AAN practice guideline summary on the topic advocates for therapeutic hypothermia to 32 to 34 degrees Celsius for patients initially presenting with a shockable rhythm. However, taking more recent trials into account, the summary also acknowledges that for all patients with out-of-hospital cardiac arrest, targeted temperature management to 36 degrees Celsius is likely acceptable as well.⁴ Judging by recent discussions on this topic amongst the members of the Critical Care and Emergency Neurology Section of the AAN, there is a range of opinions on the right target, even among specialists.

Status epilepticus

Continuous EEG (cEEG) has become a mainstay for management of patients with status epilepticus, especially for those who do not recover their mental status very soon after emergent treatment. As prevalent as cEEG is in practice, the management of patterns that fall in the so-called “ictal-interictal” continuum is still a source of uncertainty, even amongst experienced specialists.

How such patterns for any individual patient should be treated is often debated amongst emergency neurology and epilepsy teams, with the potential risks of both under-treatment and overtreatment in mind. More research is needed to understand situations in which such intermediate patterns, if left untreated, may promote further neuronal injury.⁵

The CHARM phase 3 trial

The CHARM phase 3 trial (Cirara in Large Hemispheric Infarction Analyzing Modified Rankin and Mortality) will be looking at intravenous glyburide, which inhibits Sur1-Trpm4 channels in the brain. These channels are upregulated following ischemia for certain patients and can lead to increased cerebral edema; treatment of patients with large strokes with IV glyburide may decrease cerebral edema formation.

The field of emergency neurology does not have great therapies for preventing and treating cerebral edema following large hemispheric ischemic stroke, so any potential therapies are certainly worth keeping an eye on! My friend and colleague at Yale, Dr. Kevin Sheth, was one of the leaders of the team that recently published the GAMES-RP study, the phase 2 trial.⁶

Challenges and notables

Over the past few years there have been a number of high-profile multicenter trials in emergency neurology that have had negative results. HeadPoST looked at head position for acute stroke⁷; ATACH II looked at intensive blood pressure management for intracerebral hemorrhage⁸; Eurotherm 3235 examined hypothermia for traumatic brain injury (TBI)⁹; PROTECT looked at progesterone for severe TBI.¹⁰ Hopefully the collective message of such trials to neurologists is not simply that we lack effective management strategies for emergent situations but that our field needs to double down on future research and not get discouraged!

The results of the DAWN study, on the other hand, are quite positive and exciting. The results were recently presented at the 3rd European Stroke Organisation Conference and demonstrated that endovascular thrombectomy can reduce disability in selected stroke patients presenting as far out as 24 hours after initial symptom onset.

The idea of selecting stroke patients for endovascular therapy based on favorable core/penumbral imaging characteristics as opposed strictly to time criteria has always been appealing to neurologists, but it is great to see this approach to extend the intervention window having an impressive impact on long-term outcome. Such studies will have a big effect on how stroke codes are called in emergency rooms and the urgency and frequency with which many LVO patients are transferred to centers with endovascular capability.

The importance of aggressive management

Despite attention in the literature, patients LVO or similar situations are still at high-risk for being susceptible to self-fulfilling prophecies of emergent care. While clinicians understandably do not want to inappropriately offer aggressive therapy to patients with poor chance at reasonable recovery, the fact is that for many situations in emergency neurology, our tools for predicting ultimate outcome are limited. Moreover, research has shown that early prognostic estimates among clinicians can vary greatly. Where uncertainty exists, it is best to pursue aggressive management up front and engage patients and their families in a shared decision-making process regarding goals of care, as prognosis becomes clearer with treatment.

Disclosures:

Dr Hwang is Assistant Professor of Neurology, Division of Neurocritical Care and Emergency Neurology, Yale School of Medicine, New Haven, CT.

References:

1. Fassbender K, Grotta JC, Walter S, et al. Mobile stroke units for prehospital thrombolysis, triage, and beyond: benefits and challenges. Lancet Neurol. 2017;16:227-237.

2.  Schlemm E, Ebinger M, Nolte CH, et al. Optimal transport destination for ischemic stroke patients with unknown vessel status: use of prehospital triage scores. Stroke. 2017;48:2184-2191.

3. Steiner T, Weitz JI, Veltkamp R. Anticoagulant-associated intracranial hemorrhage in the era of reversal agents. Stroke. 2017;48):1432-1437.

4.  Geocadin RG, Wijdicks E, Armstrong MJ, et al. Practice guideline summary: reducing brain injury following cardiopulmonary resuscitation. Neurology. 2017;88:2141-2149.

5. Sivaraju A, Gilmore EJ. Understanding and managing the ictal-interictal continuum in neurocritical care. Curr Treat Options Neurol. 2016;18:8.

6. Sheth KN, Elm JJ, Molyneaux BJ, et al. Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2016;15:1160-1169.

7. Anderson CS, Arima H, Lavados P, et al. Cluster-randomized, crossover trial of head positioning in acute stroke. N Eng J Med. 2017;376:2437-2447.

8. Qureshi AI, Palesch YY, Barsan WG, et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. N Eng J Med. 2016;375:1033-1043.

9. Andrews PJ, Sinclair HL, Rodriguez A, et al. Hypothermia for intracranial hypertension after traumatic brain injury. N Eng J Med. 2015;374:1385.

10. Wright DW, Yeatts SD, Silbergleit R, et al. Very early administration of progesterone for acute traumatic brain injury. New Eng J Med. 2014;371:2457-2466.