JOURNAL CLUB

Stroke: validation of the ABCD2 score, safety of tPA in strokemimics and effects of robot-assisted therapy

Michael Strupp

Published online: 21 May 2010

� Springer-Verlag 2010

This month’s Journal Club will focus on three recently

published studies on diagnosis, pharmacotherapy and

physiotherapy in patients with stroke. The ABCD2 score to

identify individuals at high risk of stroke after transient

ischemic attack has been evaluated in several studies since

its first description in 2005. The results concerning its

predictive value were conflicting. Therefore, Tsivgoulis

and co-workers performed a multicenter, external valida-

tion study which gave promising and solid results. The

second article focuses on the safety of IV thrombolysis in

patients with stroke mimics. This is of particular interest

because the use of IV thrombolysis has considerably

increased in recent years and quite often patients who

suffer from stroke-mimicking causes such as seizure,

migraine with aura or conversion disorder receive this

potentially harmful treatment. Therefore, the question of

whether IV thrombolysis may harm these patients is of

high clinical importance. The final article, published in the

New England Journal of Medicine, compares the efficacy

of intensive robot-assisted therapy with intensive compar-

ison therapy and usual care. It shows that machines are not

better than good physiotherapists.

Multicenter external validation of the ABCD2 score

Patients with a transient ischemic attack have a high risk

of developing early stroke and therefore a clinical score

that can estimate the risk would be very useful. Rothwell

and colleagues developed and further analysed the ABCD2

score. In this acronym, ‘‘A’’ stands for ‘‘age’’, ‘‘B’’ for

‘‘blood pressure’’, ‘‘C’’ for ‘‘clinical features’’ and ‘‘D’’ for

‘‘diabetes’’ and there is an additional item ‘‘I’’, which

means ‘‘imaging’’ from the admission CT scan (with leu-

koaraiosis or old/new ischemic lesions giving 1 point,

normal CT scan: 0 points). The ABCD2 score is a 7-point

score, with higher points indicating a higher risk. It is

calculated as follows: age C60 years: 1 point; blood

pressure [140 mm systolic or [90 mmHg diastolic: 1

point; clinical features: unilateral weakness: 2 points,

speech disturbance without weakness: 1 point, other

symptom: 0 points; duration of symptoms:\10 minutes: 0,

10–59 minutes: 1 point, C60 minutes: 2 points; diabetes

mellitus: yes: 1 point. Since its initial description in 2005,

however, conflicting studies on its predictive value have

been published, which might, as discussed below, have

methodological problems. Therefore, Tsivgoulis and co-

workers from Greece performed a multicenter external

validation study. They prospectively calculated the ABCD2

score in consecutive patients with a transient ischemic

attack who were hospitalised in three tertiary care neurol-

ogy departments; this included the analysis of two different

racial populations: white and Asian. The authors deter-

mined the 7-day and 90-day risk of stroke.

The major findings of this study were as follows: (1) In

the 148 patients the 7-day risk of stroke was 8% and the 90-

day risk was 16%. (2) The ABCD2 score correctly dis-

criminated between patients with a transient ischemic

attack with a high 7-day and a high 90-day risk of stroke.

Those with a score higher than 3 points had a 7-fold higher

90-day risk, i.e. 28% in the higher risk group suffered from

stroke compared to only 4% in those with 3 or fewer points.

(3) An ABCD2 score of more than 2 was associated with a

nearly 5-fold greater 90-day risk of stroke after statistical

M. Strupp (&)

Department of Neurology, Ludwig Maximilian University,

Klinikum Großhadern, Marchioninstr. 15, 81377 Munich,

Germany

e-mail: Michael.strupp@med.uni-muenchen.de

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J Neurol (2010) 257:1049–1051

DOI 10.1007/s00415-010-5595-3

adjustment had been performed for stroke risk factors, race,

history of previous transient ischemic attack and medica-

tion use before the attack.

Conclusions and comments: The authors conclude from

their state-of-the-art multicenter, external validation study

that the ABCD2 score is indeed clinically useful with a

high predictive value. These data also support the current

guidelines that patients with an ABCD2 score greater than

2 should be admitted immediately after the occurrence of

the neurological symptoms because of their high risk of

developing stroke.

In their careful discussion, the authors analyse the pros

and cons of previous studies and their own current study. In

previous studies there seemed to be an extremely varied

methodology which included a limited number of outcome

events, retrospective data collection, a lack of follow-up

after the first seven days, variation of the clinical specialty

of the initial evaluation, lack of baseline neuroimaging data

and reports from single-center only experience. The

strength of the current study was its prospective multi-

center design with an initial clinical assessment performed

by neurologists and negative CT scans in all patients with

transient ischemic attacks. Further, the outcome events

were all confirmed by neuroimaging or autopsy.

The authors also discuss the limitations of their study:

(1) Diffusion-weighted MRI was available in only 12% of

their patients. This is important because patients who have

pathological findings on diffusion-weighted imaging have a

substantially higher risk of stroke than those without

pathological findings. (2) The ABCD2 score was evaluated

in hospitalised patients, although the score was initially

designed for the outpatient setting. (3) There were differ-

ences in the secondary prevention strategies among the

different centers. (4) The diagnosis of transient ischemic

attack was made by an attending neurologist, whereas the

score was developed for use by non-neurologists, which

might cause bias. (5) Patients under the age of 80 were

evidently underrepresented in the cohort. (6) The sample

size was relatively small.

Nevertheless, this was a carefully performed study

which has clinical relevance and should further promote

the use of the simple ABCD2 score in clinical routine by

neurologists and non-neurologists.

Tsivgoulis G et al. (2010) Multicenter external valida-

tion of the ABCD2 score in triaging TIA patients. Neu-

rology 74:1351–1357 (e-mail: tsivgoulisgiorg@yahoo.gr)

Safety of tissue plasminogen activator in stroke mimics

and neuroimaging-negative cerebral ischemia

The use of intravenous tissue plasminogen activator

(tPA) has become increasingly popular over the last

10 years due to its proven efficacy if applied within the

first 4.5 hours after symptom onset. Clinical experience

shows that not all patients who receive IV thrombolysis

have actually had cerebrovascular ischemia. A certain

proportion may suffer from diseases mimicking stroke,

such as seizure, migraine with aura or a conversion

disorder. Therefore, we must question how safe IV

thrombolysis is in those patients who do not have a

cerebrovascular disease. Recent studies showed that about

3–7% of patients with IV tPA for assumed cerebral

ischemia have a stroke mimic. This relatively high

number can be explained by the situation in the emer-

gency room, where, on the basis of a quick history,

clinical examination and a CT scan to rule out hemor-

rhage, a quick decision has to be made so as not to delay

IV thrombolysis if indicated.

The safety and outcome of tPA was evaluated by

Chernyshev and co-workers from Houston in patients

treated with IV tPA who were identified from their stroke

registry from June 2004 to October 2008. They collected

the admission NIH Stroke Scale score, modified Rankin

score, length of stay, symptomatic intracerebral hemor-

rhage and the final discharge diagnosis.

The major findings were as follows: 21% of the 512

treated patients did not have evidence of a stroke on fol-

low-up examination. 14% of them had stroke mimics. The

average age of these patients with stroke mimics was

55 years, the average NIH Stroke Scale score was 7 at

admission, the average discharge score was 0, the median

length of stay was 3 days and in none of these cases was a

symptomatic intracerebral hemorrhage observed. In these

patients the most frequent etiologies were neurological

symptoms with seizure, migraine with aura and conversion

disorder. Seven percent had neuroimaging-negative cere-

bral ischemia. Their median admission NIH Stroke Scale

score, discharge score and length of stay were identical

and none of them also had symptomatic intracerebral

hemorrhage.

Conclusions and comments: There is a considerable

concern in those who treat patients with stroke that they

expose patients who do not have ischemic stroke to IV tPA,

which may lead to hemorrhage. Therefore, this current

clinical study and previous smaller case series are of

clinical importance. Giving tPA to patients who turn out

not to have ischemic stroke is evidently not associated with

a higher risk of intracerebral bleeding. This has further

consequences because it would take considerable time and

delay the administration of IV tPA if further examinations

in addition to taking history, clinical examination and a

cranial CT had to be performed to exclude other disorders.

All in all, this study should further increase our confidence

in the use of IV tPA in an acute emergency situation with

suspected stroke.

1050 J Neurol (2010) 257:1049–1051

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Chernyshev OY et al. (2010) Safety of tPA in stroke

mimics and neuroimaging-negative cerebral ischemia.

Neurology 74:1340–1345

Robot-assisted therapy for long-term upper-limb

impairment after stroke: no better than intensive

physiotherapy

There is an urgent need for further improvements to the

rehabilitation of patients who have suffered a stroke

because this is still a major burden for the affected subjects.

Therefore, new strategies need to be developed and eval-

uated to improve functioning and quality of life. One

approach is the use of robot-assisted therapy, in particular

since robotic rehabilitation devices can deliver high-

intensity, reproducible therapy. Further, due to an increased

understanding of the latent neurological potential for stroke

recovery and advances in robotics, the use of these

machines sounds quite promising. Based on these new

developments, Lo and co-workers from Providence, Rhode

Island performed a multicenter, randomised controlled trial

in patients with moderate to severe upper limb impairment

six months or more after stroke. The 127 patients were

randomly assigned to receive intensive robot-assisted

therapy, intensive comparison therapy or usual care.

Therapy consisted of 36 one-hour sessions over a period of

12 weeks. The primary efficacy outcome was a change in

motor function. This was measured on the Fugl-Meyer

Assessment of Sensorimotor Recovery after Stroke at

12 weeks. As secondary outcome measures the authors

used the Wolf Motor Function Test and the Stroke Impact

Scale. The latter were assessed after 36 weeks.

The major findings were as follows: (1) At 12 weeks the

Fugl-Meyer score was better for patients receiving robot-

assisted therapy compared to usual care, but worse than in

those receiving intensive comparison therapy without,

however, significant differences. (2) The results on the

Stroke Impact Scale were significantly better for patients

receiving robot-assisted therapy in comparison to the group

receiving usual care. (3) For the other secondary outcome

measures, there were no significant differences. In partic-

ular, robot-assisted therapy was not superior to intensive

comparison therapy. (4) The authors also performed a cross-

analysis, showing that the total costs for each of the three

therapies after 30 weeks amounted to about $15,000 with-

out any significant differences between the three groups.

Conclusions and comments: This state-of-the-art study

did not show any superiority of robot-assisted therapy

compared with intensive comparison therapy. The good

news is that the physiotherapy which is currently used

seems to be effective and that robot-assisted therapy has no

further benefit. This means that we can continue to apply

the successful physiotherapy, but should also look for other

treatment options beyond robot-assisted therapy.

This study also shows that, even in the highly ranked

New England Journal of Medicine, carefully performed

negative studies have the chance to be published.

Lo AC (2010) Robot-assisted therapy for long-term

upper-limb impairment after stroke. N Engl J Med (Epub

ahead of print) (e-mail: albert.lo@va.gov).

Summarising all three studies, the ultimate and major

goal in stroke is still prevention, prevention, prevention by

using, among other things, the ABCD2 score and, if stroke

occurs, IV thrombolysis, because we do not really have any

effective measures if damage occured to the brain tissue.

J Neurol (2010) 257:1049–1051 1051

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