A Stroke of Error
- Spotlight Case
- State the key clinical factors to assess in a patient with suspected stroke.
- Appreciate the relationship between elevated blood pressure and stroke in the acute setting.
- Identify strategies to compress treatment times for patients eligible to receive rtPA for acute ischemic stroke.
- Describe the current timing parameters, risks, and benefits for rtPA administration in acute ischemic stroke.
- Define the necessary steps to become certified as a primary stroke center by The Joint Commission.
Case & Commentary—Part 1
A 67-year-old man with a history of untreated hypertension presented to the emergency department (ED) after a fall. On presentation, he was noted to have a systolic blood pressure of 220 mm Hg and word-finding difficulties of unclear duration. Laboratory results were notable for an elevated troponin of 0.2 μg/L and an elevated creatinine of 1.9 mg/dL (but there was no baseline comparison for the latter). To further evaluate his neurologic deficit, the ED obtained a CT scan of his brain without contrast before admitting him to the cardiology service with a working diagnosis of hypertensive emergency. The head CT demonstrated extensive white matter hypoattenuation, which was greater than expected for his age, but no focal findings. The cardiology team ordered an MRI to further characterize these findings, but the patient was unable to tolerate it due to his altered mental status. Neurology was not formally consulted.
The initial neurologic evaluation of a patient with suspected stroke necessitates a rapid and focused assessment. The history should center on establishing the time of symptom onset or the time the patient was last known to be neurologically normal if the time of symptom onset cannot be confidently established. The interval between symptom onset and clinical assessment will determine whether acute reperfusion therapy for ischemic stroke can be considered. The neurologic examination should focus on identifying signs of lateralized hemispheric or brainstem dysfunction consistent with stroke. The National Institutes of Health Stroke Scale (NIHSS) is a validated 15-item scale (Table) that assesses key components of the standard neurologic examination (1) and has been widely adopted into routine clinical practice. Brain imaging is the only reliable means to differentiate between ischemic and hemorrhagic stroke.(2,3) Non-contrast head computed tomography (CT) is the imaging modality most readily available in most stroke centers. CT is sensitive to intracranial hemorrhage and may be rapidly performed as part of the acute stroke evaluation.
Blood pressure is commonly elevated in patients with acute stroke and may be related to the stress of cerebral infarction, pre-existing hypertension, or a response to increased intracranial pressure.(4) Arterial blood pressure spontaneously declines in most patients with ischemic stroke within the first 24 hours of admission.(5) Extreme elevations of blood pressure can result in end-organ damage manifesting as cerebral, cardiac, or renal dysfunction. In this case, the elevated serum troponin and creatinine may have indicated cardiac and renal involvement secondary to uncontrolled systolic blood pressure. Disturbances of cerebral function due to hypertension typically result in diffuse symptoms that may include headache, change in mental status, or seizures. Focal symptoms are less common. In the acute setting, it may be difficult to differentiate between blood pressure elevation as the primary cause of end-organ dysfunction or as a secondary consequence of stroke. Framing effects, anchoring, and overreliance on test results are potential sources of diagnostic error.(6)
Neurological consultation in the emergency department can be considered when signs or symptoms of central or peripheral nervous system dysfunction are evident. Many common neurological presentations, such as migraine headache, can be reliably diagnosed and effectively treated by emergency department providers without neurological consultation. Patients with transient or persistent symptoms suggestive of hemispheric, brainstem, cerebellar, or retinal dysfunction warrant neurological consultation. In this case, the presentation was sufficiently complex to warrant neurological consultation in the emergency department. Detailed neurological examination by an experienced neurologist may identify subtle localizing signs suggestive of a vascular event and reduce the risk of missing an opportunity to offer acute reperfusion therapy to a potentially eligible patient. In hospitals without timely access to on-site neurological expertise, telemedicine has been leveraged to provide remote teleneurological evaluation.(7)
Case & Commentary—Part 2
Two days into his hospitalization, and after spontaneous resolution of his hypertensive emergency and initial neurologic symptoms, the patient became acutely unresponsive and was noted to have new right hand weakness. The cardiology team called a "Code Stroke." The consulting neurology team examined the patient and found dysarthria, aphasia, right arm and face weakness, and a right homonymous hemianopsia. A head CT without contrast again demonstrated white matter hypoattenuation without hemorrhage. The team administered intravenous tPA [tissue plasminogen activator] for presumed ischemic stroke 100 minutes after the acute deficit. Three hours later, the patient developed new ataxia and nystagmus, prompting an emergent head CT, which demonstrated post-tPA intracerebral hemorrhage in several areas. After careful monitoring and several additional days in the intensive care unit, the patient ultimately was transferred to a rehabilitation facility with moderate persistent neurologic deficits.
Clinical outcomes are strongly associated with time to treatment in acute ischemic stroke patients treated with intravenous rtPA [recombinant tissue plasminogen activator].(8) Pre-hospital notification of acute stroke teams, group notification through paging systems, standardized order sets, early measurement of body weight, obtaining non-contrast head CT immediately upon emergency department arrival, and ready availability of rtPA can compress treatment times for eligible patients. Written protocols for the use of intravenous rtPA in acute stroke have been shown to be a key step in enhancing the administration and reducing complications of this therapy.(9) Periodic review of performance metrics and continuing stroke education of neurology and emergency department staff can facilitate ongoing quality improvement projects and augment outcomes. Through streamlined systems of care, a rapid and coordinated response can be achieved when a stroke patient arrives to the emergency department.
Rapid and timely treatment can be harder to achieve in hospitalized patients that develop stroke symptoms following admission for an unrelated problem. As in this case, inpatients may be located in diverse areas of the hospital including general medical or surgical wards, step-down units, or intensive care units. Immediate neurological evaluation may be limited during nights and weekends in some hospitals. Nursing staff on non-neurological floors often have less familiarity with stroke assessment and the clinical data necessary to make a decision regarding acute reperfusion therapy. Drawing labs and patient transport to the radiology department for non-contrast head CT may introduce additional treatment delays. Availability of rtPA and experience with reconstitution and administration of the drug may be limited on general medical and surgical wards. Development of "in-house" stroke protocols that parallel established emergency department protocols may overcome some of the challenges associated with diagnosis and treatment of stroke in hospitalized patients.
Intravenous rtPA is the only FDA-approved treatment for acute ischemic stroke. Approval was based on the results of the National Institute of Neurological Disorders and Stroke rtPA stroke study, which randomized 624 patients with acute ischemic stroke within 3 hours of symptom onset to treatment with either placebo or intravenous rtPA (0.9 mg/kg, maximum dose 90 mg).(10) Favorable outcomes at 3 months were achieved in the 31%–50% of patients treated with rtPA compared to 20%–38% of patients in the placebo group. This difference was statistically and clinically significant. Patients treated within 90 minutes of onset achieved better outcomes than those who were treated between 90 and 180 minutes, although there was still benefit in the latter group. The major risk of treatment was symptomatic intracranial hemorrhage, which occurred in 6.4% of patients in the treatment group within 36 hours compared to 0.6% of patients in the placebo group. There was no significant difference in 3-month mortality which occurred in 17% of patients in the treatment group compared to 21% in the placebo group. The safety and efficacy of rtPA in routine clinical use has been subsequently confirmed in a large cohort of patients.(11) As in this case, most symptomatic intracerebral hemorrhages occur within 24–36 hours after initiation of treatment.(12)
Strict adherence to inclusion and exclusion criteria for rtPA administration is necessary to achieve the best possible outcomes. Exclusion criteria may be more common in hospitalized patients who have undergone recent interventional or surgical procedures that may increase the risk of bleeding. The growing use of novel oral anticoagulants such as direct thrombin inhibitors and factor Xa inhibitors pose a unique challenge in the setting of acute ischemic stroke. Unlike warfarin where the intensity of anticoagulation can be rapidly measured with the international normalized ratio (INR), the novel oral anticoagulants require measurement of the thrombin time or ecarin clotting time; laboratory assays are often not processed quickly enough to make therapeutic decisions. Therefore, patients taking direct thrombin inhibitors or factor Xa inhibitors are often ineligible for treatment with intravenous rtPA. Despite persistent fears regarding the potential hemorrhagic complications associated with rtPA use, the majority of medicolegal outcomes related to rtPA are for failure to treat.(13)
Primary stroke centers certified by The Joint Commission have emerged as an effective mechanism to standardize and centralize stroke care in the United States.(14) Various state-based agencies, the Healthcare Facilities Accreditation Program, and other organizations also recognize a smaller number of primary stroke centers. Primary stroke centers are capable of delivering care to most patients with stroke, can offer intravenous rtPA, and admit patients to a stroke unit. An important element of initial certification and maintenance of certification is measurement of the quality of care for stroke patients. Stroke centers should have a database or registry capable of tracking the number and type of stroke patients seen, their treatments, timelines for receiving treatments, and measurement of clinical outcomes.(15) A system should be in place whereby data can be systematically collected, reviewed by stakeholders, and acted on for performance and quality improvement. Specific benchmarks for comparisons should be established for evidence-based recommendations such as the door-to-needle time for the use of intravenous rtPA should not exceed 60 minutes.(16) A primary stroke center is expected to select at least two relevant patient-care parameters for benchmarking each year with review and alteration of practice patterns (if needed) at least twice per year.(15) If hospitals adopt these recommendations it is expected that patients will achieve more accurate diagnoses, more timely therapies, and improved overall outcomes.
- Timely neurological assessment of patients with suspected stroke increases the probability of identifying patients who may benefit from acute reperfusion therapy.
- Written stroke protocols and coordinated acute stroke teams can reduce onset-to-treatment times and facilitate the best possible outcomes for ischemic stroke patients treated with recombinant tissue plasminogen activator (rtPA).
- Many hospitals are better organized to provide timely, evidence-based stroke care for patients presenting to the ED than for those whose symptoms begin in the hospital. Hospital-based protocols can help to narrow this gap.
- Periodic review of performance metrics and ongoing quality improvement projects can enhance stroke systems of care.
- Certification of primary stroke centers has proven effective in improving stroke-related outcomes and identifies hospitals that adhere to current evidence-based practices.
Kevin M. Barrett, MD, MSc
Associate Professor of Neurology
Director, Neurohospitalist Fellowship Program
Faculty Disclosure: Dr. Barrett has declared that neither he, nor any immediate member of his family, have a financial arrangement or other relationship with the manufacturers of any commercial products discussed in this continuing medical education activity. In addition, the commentary does not include information regarding investigational or off-label use of pharmaceutical products or medical devices.
1. Lyden P, Lu M, Jackson C, et al. Underlying structure of the National Institutes of Health Stroke Scale: results of a factor analysis. NINDS tPA Stroke Trial Investigators. Stroke. 1999;30:2347-2354. [go to PubMed]
2. Besson G, Robert C, Hommel M, Perret J. Is it clinically possible to distinguish nonhemorrhagic infarct from hemorrhagic stroke? Stroke. 1995;26:1205-1209. [go to PubMed]
3. Mader TJ, Mandel A. A new clinical scoring system fails to differentiate hemorrhagic from ischemic stroke when used in the acute care setting. J Emerg Med. 1998;16:9-13. [go to PubMed]
4. Phillips SJ. Pathophysiology and management of hypertension in acute ischemic stroke. Hypertension. 1994;23:131-136. [go to PubMed]
5. Heitsch L, Jauch ED. Management of hypertension in the setting of acute ischemic stroke. Curr Hypertens Rep. 2007;9:506-511. [go to PubMed]
6. Vickrey BG, Samuels MA, Ropper AH. How neurologists think: a cognitive psychology perspective on missed diagnoses. Ann Neurol. 2010;67:425-433. [go to PubMed]
7. Wang S, Gross H, Lee SB, et al. Remote evaluation of acute ischemic stroke in rural community hospitals in Georgia. Stroke. 2004;35:1763-1768. [go to PubMed]
8. Balami J, Hadley G, Sutherland BA, Karbalai H, Buchan AM. The exact science of stroke thrombolysis and the quiet art of patient selection. Brain. 2013;136:3528-3553. [go to PubMed]
9. Jeng JS, Tang SC, Deng IC, Tsai LK, Yeh SJ, Yip PK. Stroke center characteristics which influence the administration of thrombolytic therapy for acute ischemic stroke: a national survey of stroke centers in Taiwan. J Neurol Sci. 2009;281:24-27. [go to PubMed]
10. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-1587. [go to PubMed]
11. Gumbinger C, Reuter B, Stock C, et al. Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials. BMJ. 2014;348:g3429. [go to PubMed]
12. Derex L, Nighoghossian N. Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update. J Neurol Neurosurg Psychiatry. 2008;79:1093-1099. [go to PubMed]
13. Liang BA, Lew R, Zivin JA. Review of tissue plasminogen activator, ischemic stroke, and potential legal issues. Arch Neurol. 2008;65:1429-1433. [go to PubMed]
14. Alberts MJ, Hademenos G, Latchaw RE, et al. Recommendations for the establishment of primary stroke centers. Brain Attack Coalition. JAMA. 2000;283:3102-3109. [go to PubMed]
15. Alberts MJ, Latchaw RE, Jagoda A, et al. Revised and updated recommendations for the establishment of primary stroke centers: a summary statement from the Brain Attack Coalition. Stroke. 2011;42:2651-2665. [go to PubMed]
16. Jauch EC, Saver JL, Adams HP Jr, et al. 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;44:870-947. [go to PubMed]
Table. NIH Stroke Scale.
|1a. Level of Consciousness: The investigator must choose a response if a full evaluation is prevented by such obstacles as an endotracheal tube, language barrier, orotracheal trauma/bandages. A 3 is scored only if the patient makes no movement (other than reflexive posturing) in response to noxious stimulation.||0 = Alert; keenly responsive.
1 = Not alert; but arousable by minor stimulation to obey, answer, or respond.
2 = Not alert; requires repeated stimulation to attend, or is obtunded and requires strong or painful stimulation to make movements (not stereotyped).
3 = Responds only with reflex motor or autonomic effects or totally unresponsive, flaccid, and are flexic.
|1b. LOC Questions: The patient is asked the month and his/her age. The answer must be correct - there is no partial credit for being close. Aphasic and stuporous patients who do not comprehend the questions will score 2. Patients unable to speak because of endotracheal intubation, orotracheal trauma, severe dysarthria from any cause, language barrier, or any other problem not secondary to aphasia are given a 1. It is important that only the initial answer be graded and that the examiner not "help" the patient with verbal or non-verbal cues.||0 = Answers both questions correctly.
1 = Answers one question correctly.
2 = Answers neither question correctly.
|1c. LOC Commands: The patient is asked to open and close the eyes and then to grip and release the non-paretic hand. Substitute another one step command if the hands cannot be used. Credit is given if an unequivocal attempt is made but not completed due to weakness. If the patient does not respond to command, the task should be demonstrated to him or her (pantomime), and the result scored (i.e., follows none, one or two commands). Patients with trauma, amputation, or other physical impediments should be given suitable one-step commands. Only the first attempt is scored.||0 = Performs both tasks correctly.
1 = Performs one task correctly.
2 = Performs neither task correctly.
|2. Best Gaze: Only horizontal eye movements will be tested. Voluntary or reflexive (oculocephalic) eye movements will be scored, but caloric testing is not done. If the patient has a conjugate deviation of the eyes that can be overcome by voluntary or reflexive activity, the score will be 1. If a patient has an isolated peripheral nerve paresis (CN III, IV or VI), score a 1. Gaze is testable in all aphasic patients. Patients with ocular trauma, bandages, pre-existing blindness, or other disorder of visual acuity or fields should be tested with reflexive movements, and a choice made by the investigator. Establishing eye contact and then moving about the patient from side to side will occasionally clarify the presence of a partial gaze palsy.||0 = Normal.
1 = Partial gaze palsy; gaze is abnormal in one or both eyes, but forced deviation or total gaze paresis is not present.
2 = Forced deviation, or total gaze paresis not overcome by the oculocephalic maneuver.
|3. Visual: Visual fields (upper and lower quadrants) are tested by confrontation, using finger counting or visual threat, as appropriate. Patients may be encouraged, but if they look at the side of the moving fingers appropriately, this can be scored as normal. If there is unilateral blindness or enucleation, visual fields in the remaining eye are scored. Score 1 only if a clear-cut asymmetry, including quadrantanopia, is found. If patient is blind from any cause, score 3. Double simultaneous stimulation is performed at this point. If there is extinction, patient receives a 1, and the results are used to respond to item 11.||0 = No visual loss.
1 = Partial hemianopia.
2 = Complete hemianopia.
3 = Bilateral hemianopia (blind including cortical blindness).
|4. Facial Palsy: Ask – or use pantomime to encourage – the patient to show teeth or raise eyebrows and close eyes. Score symmetry of grimace in response to noxious stimuli in the poorly responsive or non-comprehending patient. If facial trauma/bandages, orotracheal tube, tape or other physical barriers obscure the face, these should be removed to the extent possible.||0 = Normal symmetrical movements.
1 = Minor paralysis (flattened nasolabial fold, asymmetry on smiling).
2 = Partial paralysis (total or near-total paralysis of lower face).
3 = Complete paralysis of one or both sides (absence of facial movement in the upper and lower face).
|5. Motor Arm: The limb is placed in the appropriate position: extend the arms (palms down) 90 degrees (if sitting) or 45 degrees (if supine). Drift is scored if the arm falls before 10 seconds. The aphasic patient is encouraged using urgency in the voice and pantomime, but not noxious stimulation. Each limb is tested in turn, beginning with the non-paretic arm. Only in the case of amputation or joint fusion at the shoulder, the examiner should record the score as untestable (UN), and clearly write the explanation for this choice.||0 = No drift; limb holds 90 (or 45) degrees for full 10 seconds.
1 = Drift; limb holds 90 (or 45) degrees, but drifts down before full 10 seconds; does not hit bed or other support.
2 = Some effort against gravity; limb cannot get to or maintain (if cued) 90 (or 45) degrees, drifts down to bed, but has some effort against gravity.
3 = No effort against gravity; limb falls.
4 = No movement.
UN = Amputation or joint fusion, explain: ________________
5a. Left Arm
5b. Right Arm
|6. Motor Leg: The limb is placed in the appropriate position: hold the leg at 30 degrees (always tested supine). Drift is scored if the leg falls before 5 seconds. The aphasic patient is encouraged using urgency in the voice and pantomime, but not noxious stimulation. Each limb is tested in turn, beginning with the non-paretic leg. Only in the case of amputation or joint fusion at the hip, the examiner should record the score as untestable (UN), and clearly write the explanation for this choice.||0 = No drift; leg holds 30-degree position for full 5 seconds.
1 = Drift; leg falls by the end of the 5-second period but does not hit bed.
2 = Some effort against gravity; leg falls to bed by 5 seconds, but has some effort against gravity.
3 = No effort against gravity; leg falls to bed immediately.
4 = No movement.
UN = Amputation or joint fusion, explain: ________________
6a. Left Leg
6b. Right Leg
|7. Limb Ataxia: This item is aimed at finding evidence of a unilateral cerebellar lesion. Test with eyes open. In case of visual defect, ensure testing is done in intact visual field. The finger-nose-finger and heel-shin tests are performed on both sides, and ataxia is scored only if present out of proportion to weakness. Ataxia is absent in the patient who cannot understand or is paralyzed. Only in the case of amputation or joint fusion, the examiner should record the score as untestable (UN), and clearly write the explanation for this choice. In case of blindness, test by having the patient touch nose from extended arm position.||0 = Absent.
1 = Present in one limb.
2 = Present in two limbs.
UN = Amputation or joint fusion, explain: _______________
|8. Sensory: Sensation or grimace to pinprick when tested, or withdrawal from noxious stimulus in the obtunded or aphasic patient. Only sensory loss attributed to stroke is scored as abnormal and the examiner should test as many body areas (arms [not hands], legs, trunk, face) as needed to accurately check for hemisensory loss. A score of 2, "severe or total sensory loss," should only be given when a severe or total loss of sensation can be clearly demonstrated. Stuporous and aphasic patients will, therefore, probably score 1 or 0. The patient with brainstem stroke who has bilateral loss of sensation is scored 2. If the patient does not respond and is quadriplegic, score 2. Patients in a coma (item 1a=3) are automatically given a 2 on this item.||0 = Normal; no sensory loss.
1 = Mild-to-moderate sensory loss; patient feels pinprick is less sharp or is dull on the affected side; or there is a loss of superficial pain with pinprick, but patient is aware of being touched.
2 = Severe to total sensory loss; patient is not aware of being touched in the face, arm, and leg.
|9. Best Language: A great deal of information about comprehension will be obtained during the preceding sections of the examination. For this scale item, the patient is asked to describe what is happening in the attached picture, to name the items on the attached naming sheet and to read from the attached list of sentences. Comprehension is judged from responses here, as well as to all of the commands in the preceding general neurological exam. If visual loss interferes with the tests, ask the patient to identify objects placed in the hand, repeat, and produce speech. The intubated patient should be asked to write. The patient in a coma (item 1a=3) will automatically score 3 on this item. The examiner must choose a score for the patient with stupor or limited cooperation, but a score of 3 should be used only if the patient is mute and follows no one-step commands.||0 = No aphasia; normal.
1 = Mild-to-moderate aphasia; some obvious loss of fluency or facility of comprehension, without significant limitation on ideas expressed or form of expression. Reduction of speech and/or comprehension, however, makes conversation about provided materials difficult or impossible. For example, in conversation about provided materials, examiner can identify picture or naming card content from patient's response.
2 = Severe aphasia; all communication is through fragmentary expression; great need for inference, questioning, and guessing by the listener. Range of information that can be exchanged is limited; listener carries burden of communication. Examiner cannot identify materials provided from patient response.
3 = Mute, global aphasia; no usable speech or auditory comprehension.
|10. Dysarthria: If patient is thought to be normal, an adequate sample of speech must be obtained by asking patient to read or repeat words from the attached list. If the patient has severe aphasia, the clarity of articulation of spontaneous speech can be rated. Only if the patient is intubated or has other physical barriers to producing speech, the examiner should record the score as untestable (UN), and clearly write an explanation for this choice. Do not tell the patient why he or she is being tested.||0 = Normal.
1 = Mild-to-moderate dysarthria; patient slurs at least some words and, at worst, can be understood with some difficulty.
2 = Severe dysarthria; patient's speech is so slurred as to be unintelligible in the absence of or out of proportion to any dysphasia, or is mute/anarthric.
3 = UN = Intubated or other physical barrier, explain:___________
|11. Extinction and Inattention (formerly Neglect): Sufficient information to identify neglect may be obtained during the prior testing. If the patient has a severe visual loss preventing visual double simultaneous stimulation, and the cutaneous stimuli are normal, the score is normal. If the patient has aphasia but does appear to attend to both sides, the score is normal. The presence of visual spatial neglect or anosagnosia may also be taken as evidence of abnormality. Since the abnormality is scored only if present, the item is never untestable.||0 = No abnormality.
1 = Visual, tactile, auditory, spatial, or personal inattention or extinction to bilateral simultaneous stimulation in one of the sensory modalities.
2 = Profound hemi-inattention or extinction to more than one modality; does not recognize own hand or orients to only one side of space.