Stroke, Thrombolysis, NIHSS .....

We've recently had a Great Thrombolysis Debate in our ED.

But would like to summarise (I've cut and pasted the rev bits) what I read in sev EM papers some time back on some controversial area together with the references below:

A.  Acute Stroke, Neuroimaging, and Thrombolysis

    MRI is at least equal in efficacy to CT for detection of ICH in the hyperacute stroke patient, and both appear to have very high sensitivity and specificity. MRI is superior to CT for demonstration of subacute and chronic hemorrhage and hemorrhagic transformation of an acute ischemic stroke.

    MR-DWI (diffusion weighted imaging MR) is far superior to unenhanced CT and routine MRI in the detection of acute ischemia, with very high sensitivity and specificity. For a patient within 3 hours of symptom onset, MRI can be used if it does not unduly delay the timely administration of IV tPA since a more definitive diagnosis will be obtained with MR-DWI and it is far more effective than CT for excluding some mimics of acute cerebral ischemia.

    For patients beyond 3 hours from onset of symptoms, either MR-DWI or CTA should be performed, especially if mechanical thrombectomy or intra-arterial thrombolytic therapy is contemplated.

    Frank hypointensity on CT, particularly if it involves more than one third of an MCA territory, is a strong contraindication to treatment with thrombolysis. Early signs of infarct on CT, regardless of their extent, are not a contraindication to treatment.

    Gradient-echo MR can detect microhemorrhage, both old and new, better than CT, indicating the presence of amyloid angiopathy, hypertension, small vascular malformations, and other vascular diseases. The presence of a small number of these microhemorrhages (< 5) does not contraindicate intravenous thrombolysis.

Reference: Latchaw RE,et al. Recommendations for imaging of acute ischemic stroke: a scientific statement from the American Heart Association Stroke 2009;40(11):3646-78.

B.  Stroke Thrombolysis: Unique Exclusion Criteria for the 3 - 4.5 Hour Window

Exclusion criteria unique to the 3 -4.5 hour window:

    Age > 80 years
    History of prior stroke AND diabetes
    Oral anticoagulant treatment prior to admission (even if INR <1.7)
    Severe stroke: NIHSS >25
    CT findings involving stroke > 1/3 of the MCA territory

(1) Carpenter CR, et al. Thrombolytic Therapy for Acute Ischemic Stroke beyond Three Hours J Emerg Med 2010 Jun 23. [Epub ahead of print]
(2) Wahlgren N, et al. Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study Lancet 2008;372:1303–1309.
(3) Hacke W, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke N Engl J Med 2008;359:1317–1329.
(4) Massachusetts General Hospital Stroke Service Protocols:

C.  Early CT Signs of Ischemic Stroke

The NINDS Study found a 31% sensitivity for early signs of ischemic stroke on noncontrast CT within 3 hours of symptom onset. The rate of detection increased to 82% at 6 hours (1).

Early signs of cerebral ischemia on CT:

    Hypoattenuation of brain tissue - with ischemia, cytotoxic edema develops resulting in increased brain water content. There is a loss of gray-white differentiation because of the increase in the relative water concentration within the ischemic tissues.

    With edema, swelling of the gyri produces sulcal effacement, which may lead to ventricular compression.

    Hyperdense MCA sign - a result of thrombus or embolus in the MCA.

    Obscuration of the lentiform nucleus (also called blurred basal ganglia) is seen in MCA infarction and is one of the most frequently seen signs.

    Insular Ribbon sign refers to hypodensity and swelling of the insular cortex (the center of the cerebral cortex deep between the temporal lobe and the frontal lobe).

The sooner these signs become evident, the more profound is the degree of ischemia (1,2). Typically, at 6-12 hours sufficient edema is recruited into the stroke area to produce significant regional hypodensity on CT; a large hypodense area present within 3 hours of reported symptom onset should prompt careful review regarding the time of stroke symptom onset.

There is controversy as to whether early signs of infarct on CT are a contraindication to thrombolysis. The presence of CT evidence of infarction early in presentation has been associated with poor outcome and increased propensity for hemorrhagic transformation after thrombolytics in some studies (3,4).  In the NINDS trial, there was no interaction between early infarction signs and tPA treatment for any clinical outcomes. Currently early signs of ischemia on CT are not generally considered to be a contraindication to use of tPA.  However, "frank hypointensity" on CT, particularly if it involves more than one third of an MCA territory, is a strong contraindication to treatment (1).

(1 ) Latchaw et al.  Recommendations for imaging acute ischemic stroke:  A scientific statement from the American Heart Association  Stroke 2009;40:3646-78.
(2) Patel SC, et al. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Lack of clinical significance of early ischemic changes on computed tomography in acute stroke JAMA. 2001;286: 2830–2838.
(3) von Kummer R, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy Radiology 1997;205(2):327-33.
(4) Dzialowski I, et al. Extent of early ischemic changes on computed tomography (CT) before thrombolysis: prognostic value of the Alberta Stroke Program Early CT Score in ECASS II Stroke 2006;37(4):973-8.

D.  Acute Stroke with NIHSS Score of 0

Physicians rely on the National Institutes of Health Stroke Scale (NIHSS) to evaluate patients with suspected acute stroke and to make decisions about acute treatment. The NIHSS correlates with infarct size, clinical severity, and long-term outcome. It is important to recognize, however, that ischemic stroke may cause symptoms that are not captured by the NIHSS scale.

The NIHSS scale is highly weighted toward deficits caused by anterior circulation strokes, whereas deficits caused by posterior circulation strokes receive fewer points (1-3). Within the anterior circulation, the scale underestimates the degree of right versus left hemisphere injury (1,4). It is possible that some patients with persistent symptoms on arrival to ED and an NIHSS score of 0 still have an infarct (1).

In a recent study, stroke patients with an NIHSS score of 0 most commonly presented with nausea, vomiting, and headache, all of which are associated with posterior circulation ischemia (1). Midline lesions of the cerebellum cause truncal ataxia, which is not part of the NIHSS. In addition, decreased visual acuity, Horner's syndrome, and memory impairments are neurologic deficits not captured by the NIHSS. Subtle limb weakness (4/5) in an upper motor neuron pattern (extensors of the arms or flexors of the legs) may not be observed on the motor component of the NIHSS.

These data reinforce that the NIHSS cannot replace history and a thorough neurologic exam to diagnose acute stroke and that the NIHSS alone cannot be used to rule out a stroke in patients with acute persistent symptoms.

(1) Martin-Schild S, et al. Zero on the NIHSS Does Not Equal the Absence of Stroke Ann Emerg Med 2011 Jan;57(1):42-5.
(2) Libman RB, et al. Differences between anterior and posterior circulation stroke in TOAST Cerebrovasc Dis 2001;11:311-316.
(3) Sato S, et al. Baseline NIH stroke scale score predicting outcome in anterior and posterior circulation strokes Neurology 2008;70:2371-2377.
(4) Fink JN, et al. Is the association of National Institutes of Health Stroke Scale scores and acute magnetic resonance imaging stroke volume equal for patients with right- and left-hemisphere ischemic stroke? Stroke 2002;33:954-958.


  1. Hi RG this is your buddie TL from the emerald isle reverting to the blog site as requested. As mentioned thrombolysis can kill. This needs to be spelled out. As a physician a patient is easily scared depending on the language used so packaging the information is paramount. Too much talk of death and haemorrhage will turn all if them off and no talk of cons will turn them all on. For me dealing with the long term consequences of stroke supervising stroke rehab is a real eye opener. Leaving the Ed alive without a haemorrhage over the age if 80 is not necessarily a success for these people. People if that age have alot of life experience and have taken most of the s&€t life can throw at then. Some are more than willing to risk death to improve. Definitely not best to dismiss as just a bit if a stroke when you'll have a long term expressive dysphasia be a hoist transfer in a nursing home with a dense hemi afterwards. Also physician must not treat thyself but thy patients. I very much enjoy the challenge of this field but it's not easy.

  2. Welcome Tom. Always good to have other perspectives. Here's some thoughts:

    1. We're not vehemently against it. We thrombolyse daily in our ED. We're for more scrutiny and against wantonly calling it standard of care (it's definitely not in Oz where I trained)

    2. Consent may be clear cut in Eire but language and culture play a large part in decision making around the world.

    3. Evidence is getting shakier. Here's a good run down:

    4. Our stroke unit and neurological institute are gathering more numbers as we speak so more info to come I am sure.

    Keep visiting and spread the conversation.