Cardiac & Resuscitation, Patient Care

An EMS Guide to Wake-Up Ischemic Strokes

Issue 12 and Volume 40.

It’s 7:15 a.m. when the tones go off. “Squad 83 and ALS 83, respond for a 65-year-old female with a possible stroke,” squawks the dispatcher. Why did the last crew leave the radio on so loud? It’s too early for loud noises. Apparently your partner didn’t get the memo about loud noises either; he flips the siren to wail as soon as the wheels start to roll.

You arrive to find Mrs. M, a pleasant older female who you’ve seen once or twice before for chest pain or palpitations. She seems to be staring into space, has an obvious facial droop, her arm drifts, her speech is slurred and the pleasant cheery lady you remember is certainly not normal.

You check her blood glucose, which is at 100 mg/dL.

Her husband is at her side. You’ve met him on your previous runs as well. Mr. M is always the attentive spouse who meets you at the door and follows behind the ambulance to the hospital after he hurriedly packs his wife’s overnight bag.

Today, he’s obviously distressed and urges you to hurry. He reports that Mrs. M was in her usual state of health yesterday. They went grocery shopping, spent some time gardening and watched late-night TV. They went to bed at approximately 10:30 p.m., and he woke up to find her in this state at 7 a.m. As he tells you this, your heart sinks. You know that when you get to the hospital you’re going to have to report Mrs. M’s last known normal time as nine hours ago. As with other patients with a prolonged time from the onset of their symptoms to their recognition, you realize the triage nurse is probably going to downgrade the urgency of your patient’s case because of this timeline. She’ll send you to a regular room rather than the high-acuity area or CT scanner. Mrs. M will ultimately be evaluated and admitted to the hospital with little hope of returning to the highly functional state she previously enjoyed. Mr. M may not be able to care for her and they’ll likely need to leave their home for a long-term care facility. This isn’t how you wanted to start your shift.

“Last known normal” is the last confirmed time the patient was symptom free, not the time symptoms were first noticed. In the case of a patient who wakes up symptomatic, the last known normal time is commonly when the patient went to bed. This time is used by emergency and stroke physicians to determine eligibility for treatment.


Each year, nearly 15 million people suffer from strokes worldwide—800,000 of those are in the United States.1,2 Approximately 20–25% (nearly 3 million) of these are termed “wake-up strokes.”1,3,4 This term describes strokes whose symptoms are first recognized upon waking from sleep, where the last known normal time was prior to going to bed.

Several trials have demonstrated that the morning hours are the most common time for a stroke to occur,”5,7 or it may simply be when the symptoms are first noticed.

However, there are suspected to be some physiologic changes in blood pressure and clotting factor activity that occur in the morning, which may be related to the number of strokes that present at this time of day.

These strokes are classically ineligible for acute thrombolytic therapy, because the exact time of the stroke onset is unknown. The last known normal time is critically important to determine due to the types of treatment that may be available to a patient.

Timing is important with stroke because for each minute a portion of the brain goes without blood flow, neurons and the surrounding supportive cells start to die at a rate of 1.9 million neurons per minute.8 It makes sense that earlier treatment results in more potential benefit for the patient by reducing neurons lost.

In addition to diminishing benefit, delays in treatment are accompanied by potential harm. As these areas of the brain become ischemic, their cellular structure changes and becomes weak. This unfortunately increases the likelihood that the patient may bleed into the area of ischemia, converting an ischemic stroke into a hemorrhagic stroke.

For this reason, emergency physicians and neurologists need to weigh the risk vs. benefit of treatment on an individual patient basis, and the time since last known normal is one of the most important factors.

Current treatments include thrombolysis (sometimes referred to as a “clot busting” medication) with tissue plasminogen activator (tPA), which is only approved for use within three hours after the patient was last seen normal in appropriately selected patients; in certain cases, therapy may be offered off-label up to 4.5 hours after last known normal.9,10 Clinical trials have suggested that approximately 1 in every 8 patients treated with tPA will have an excellent neurologic outcome they otherwise wouldn’t have had without it.11 It’s currently the only FDA-approved medication for the treatment of acute stroke.9,11

Because of our experiences with tPA in the setting of acute ischemic stroke, most areas in the country have chosen to designate primary and comprehensive stroke centers to help EMS crews choose the appropriate facility to transport these patients.

These specialized centers all have the ability to perform and interpret head CT scans 24 hours a day and have worked to make the system as efficient as possible. The systems usually include: facilitation of appropriate prehospital notification, rapid clinician exams, early CT and rapid administration of tPA when indicated.

Comprehensive stroke centers have additional advanced capabilities, including the ability to perform endovascular therapy for acute stroke. This is much like a cardiac catheterization for an ST elevation myocardial infarction (STEMI) where the patient is taken to an interventional radiologic lab where the embolic clot is located and removed or dissolved with intra-arterial tPA. This type of therapy isn’t available in all areas, but shows promise in patients with large vessel strokes when performed within six hours of stroke onset.10,12


The most important thing we can do when assessing these patients in the field is get a thorough history, focusing primarily on the last known normal time. Additional critical pieces of information include an urgent finger stick blood glucose as well as an accurate medication list.

Prehospital providers are known to be excellent at determining the last known normal time for a stroke that occurred while the patient was awake. But, wake-up strokes are more challenging.13

Rather than asking a patient, “When did these symptoms start?,” which will often get you an answer of, “I noticed them as soon as I woke up,” we need to focus on the last time the patient was known or witnessed to be symptom free.

Since the stroke may have occurred while the patient was sleeping, it may have occurred hours before they awoke or called for help. If patients have severe slurring of their speech, or their speech centers of the brain are affected by the stroke, they may not be able to reliably tell you when they were last symptom free.

A witness is usually our most reliable method of determining the last time the patient was symptom free. If one is available, gather as much information from them as possible and strongly consider transporting them with the patient to help provide the hospital staff with these important details.

Unfortunately, witnesses aren’t always available or may only be able to tell us the patient was symptom free when they went to bed last night.

Sometimes, there are other clues that we can use from the scene that may benefit the patient. Look to see what the patient has done that morning. If Mrs. M woke up, got dressed, brushed her teeth, walked downstairs, made coffee and is now seated at the kitchen table aphasic with a flaccid arm and leg, it’s possible these symptoms began after she awoke. These details are important to report to the ED because they may impact the decision-making for treatment after her evaluation at the ED.

Prehospital providers should perform a validated EMS stroke exam like the Cincinnati Prehospital Stroke Scale

In addition to focusing our history on the last known normal time, you should perform a validated EMS stroke exam like the Cincinnati Prehospital Stroke Scale, which includes assessing for facial droop, arm drift and slurred speech.14 (See Table 1,above.) You should also rule out symptomatic hypoglycemia, which can mimic a stroke, by checking blood sugar. A full set of vital signs should be obtained.

Not all stroke patients need oxygen, but if they’re hypoxic (< 94%), provide supplemental oxygen. It’s common for stroke patients to be acutely hypertensive. Hypertension should never be treated in the field in an acute stroke patient, because it may be compensatory to drive cerebral perfusion to the ischemic brain; as always, refer to your local protocols or online medical control for your area.

Hypotension (systolic blood pressure < 90 mmHg), on the other hand, should be aggressively treated with IV fluids. Symptomatic hypotension can appear like an acute ischemic stroke or worsen the outcomes of an acute stroke.

Finally, as in other time-dependent diseases, scene time should be minimized as much as possible. Delays on scene will only cause delays in treatment. A reasonable goal is to keep on-scene time to 10–15 minutes.


The importance of hospital pre-notification can’t be understated; it’s important to provide the hospital with notification well before your arrival. Briefly provide your exam findings, vitals and last known normal time.12 This will help the ED team prepare for your arrival, facilitate the time-sensitive workup and activate a stroke team if one is available.

Patients with a wake-up stroke should be transported to a stroke-capable hospital— one with 24-hour CT and tPA capabilities. Other hospital capabilities may vary quite a bit depending on your region.

Some hospitals utilize a telemedicine system to allow specialized stroke physicians to assess the patient and review the imaging via video conferencing. Others have stroke physicians available in person or by telephone. Even if the last known normal time was more than six hours ago, a timely head CT scan and consultation with a stroke physician is important for the best possible outcome.

The concept of stroke triage (similar to trauma triage) is currently being explored in many regions. Since 2013, the American Heart Association has advocated transporting stroke patients to the highest level of care possible (comprehensive stroke center > primary stroke center > stroke-ready hospital), as long as transport time isn’t increased by more than 15 minutes.10

This concept makes sense for patients who would qualify for endovascular therapy or research trials, but there’s no widely accepted triage tool for EMS to make this decision. As these tools are being developed,19 recommendations are likely to rapidly change, and all EMS providers should take an active role in regional stroke systems of care.


Currently, wake-up strokes shouldn’t get treated with tPA due to the high risk of secondary intracranial hemorrhage. However, there’s emerging data that indicates we may be able to treat some patients who wake up with symptoms and thus have an extended period of time since they were last seen normal.4,15,16

Some radiology trials have shown some wake-up strokes appear much like strokes that are known to be < 6 hours old on initial head CT and rapid magnetic resonance imaging (MRI).2,17

In combination with our knowledge about the circadian rhythm of strokes that commonly occur early in the morning, this may suggest that many wake-up strokes are occurring shortly before the patient awoke rather than in the middle of the night. These trials will need to be validated on a larger scale, and aren’t standard of care at this time.

New research is focusing on advanced imaging studies to help better characterize the age of a stroke when a reliable last known normal can’t be determined. There’s currently a large multicenter, multinational randomized trial in Europe called WAKE-UP, which is assessing a mismatch in visibility of an acute ischemic lesion between diffusion-weighted MRI and fluid-attenuated inversion recovery MRI.1 These MRI findings are consistent with ischemia < 4.5 hours old, suggesting they may benefit from treatment. Patients are being randomized to either IV lytic therapy (tPA) or placebo and followed for favorable neurologic outcome.

Prehospital providers should perform a validated EMS stroke exam like the Cincinnati Prehospital Stroke Scale

Prehospital providers should perform a validated EMS stroke exam like the Cincinnati Prehospital Stroke Scale, which includes assessing for facial droop, arm life and slurred speech.


As of the writing of this article, approximately 290 patients have been randomized with a goal of enrolling 800. Additional research is looking at CT scans with IV dye since CTs are more readily available in most EDs.18

If there’s imaging data that suggests the ischemia is very young, some patients may be eligible for either tPA or interventional therapy after a wake-up stroke. As this data emerges, the possibility for treating patients with wake-up strokes will hopefully increase.

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1. Thomalla G, Fiebach JB, Ostergaard L, et al. A multicenter, randomized, double-blind, placebo-controlled trial to test efficacy and safety of magnetic resonance imaging-based thrombolysis in wake-up stroke (WAKE-UP). Int J Stroke. 2014;9(6):829–836.

2. Rimmele DL, Thomalla G. Wake-up stroke: Clinical characteristics, imaging findings, and treatment option-an update. Front Neurol. 2014;5(35):1–7.

3. Rubin MN, Barrett KM. What to do with wake-up stroke. Neurohospitalist.2015;5(3):161–172.

4. Buck D, Shaw LC, Price CI, et al. Reperfusion therapies for wake-up stroke: Systematic review. Stroke. 2014;45(6):1869–1875.

5. Mackey J, Kleindorfer D, Sucharew H, et al. Population-based study of wake-up strokes. Neurology. 2011;76(19):1662–1667.

6. Chaturvedi S, Adams HP, Woolson RF. Circadian variation in ischemic stroke subtypes. Stroke. 1999;30(9):1793–1795

7. Serena J, Davalos A, Segura T, et al. Stroke on awakening: Looking for a more rational management. Cerebrovasc Dis. 2003;16(2):128–133.

8. Saver JL. Time is brain—quantified. Stroke. 2006;37(1):263–266.

9. American College of Emergency Physicians Clinical Policies Subcommittee. Clinical policy: Use of intravenous tissue plasminogen activator for the management of acute ischemic stroke in the emergency department. Ann Emerg Med. 2015;66(3):322–333.

10. Jauch EC, Saver JL, Adams HP. Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke. 2013;44(3):870–947.

11. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke.NEJM. 1995;333(24):1581–1587.

12. Powers WJ, Derdeyn CP, Biller J, et al. 2015 AHA/ASA focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: : A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46(10):3020–3035.

13. Curfman D, Connor LT, Moy HP, et al. Accuracy of emergency medical services-reported last known normal times in patients suspected with acute stroke. Stroke. 2014;45(5):1275–1279.

14. Kotari RU, Pancioli A, Liu T, et al. Cincinnati Prehospital Stroke Scale: Reproducibility and validity. Ann Emerg Med. 1999;33(4):373–378.

15. Manawadu D, Bodla S, Keep J, et al. An observational study of thrombolysis outcomes in wake-up ischemic stroke patients. Stroke. 2013;44(2):427–431.

16. Thomalla G, Gerloff C. Treatment concepts for wake-up stroke and stroke with unknown time of symptom onset. Stroke. 2015;46(9):2707–2713.

17. Todo K, Moriwaki H, Saito K, et al. Early CT findings in unknown-onset and wake-up strokes. Cerebrovasc Dis. 2006;21(5–6):367–371.

18. Campbell BCV, Weir L, Desmond PM, et al. CT perfusion improves accuracy and confidence in acute ischaemic stroke. J Neurol Neurosurg Psychiatry. 2013;84(6):613–618.

19. Katz BS, McMullan JT, Sucharew H, et al. Design and validation of a prehospital scale to predict stroke severity: Cincinnati prehospital stroke severity scale. Stroke. 2015;46(6):1508–1512.


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