Journal of Geriatric Cardiology December 2007 Vol 4 No 4

225

Clinical Research

Prediction of acute stroke progression by the National

Institutes of Health Stroke Scale
Vinh Phuong, Tran Van Huy
Department of Geriatric Cardiology, Khanh Hoa Hospital,Vietnam
Objective To determine the occurrence of neurological changes during the first 48 hours after acute stroke as it relates to the initial
stroke severity assessment. Methods The assessment with the National Institutes of Health Stroke Scale (NIHSS) was performed
serially for the first 48 hours on 68 consecutive ischemic stroke patients admitted to the Department of Geriatric Cardiology at the
Khanh Hoa Hospital, Nha Trang, Vietnam. Incidence of stroke progression (a 3-point increase on the NIHSS) was recorded and
analysis performed to determine its association with initial stroke severity and other demographic and physiological variables. Deficit
resolution by 48 hours, defined as an NIHSS score of 0 or 1, measured the frequency of functional recovery predicted by the initial deficit.
Results Overall progression was noted in 28% of events (19/68). Applying Bayes solution to the observed frequency of worsening, the
greatest likelihood of predicting future patient progression occurred with NIHSS score of =7 and >7. Patients with an initial NIHSS score
of =7 experienced a 13% (6/47) worsening rate versus those of an initial score of >7 with a 62% (13/21) worsening rate (P<0.01). 42.5%
(20/47) of those with an initial score of =7 were functionally normal at 48 hours, whereas only 4.7% (1/21) of those with scores of >7
returned to a normal examination within this period (2, P<0.05). Conclusions This study suggests that the early clinical course of
neurological deficit after acute stroke be dependent on the initial stroke severity and that a dichotomy in early outcome exist surrounding
an initial NIHSS score of 7. These findings may have significant implications for the design and patient stratification in treatment
protocols with respect to primary clinical outcome.(J Geriatr Cardiol 2007;4:225-228.)
Key Word stroke; prediction

Introduction
Clinical observations suggest that the first 48 hours
after an ischemic stroke be associated with potential instability and secondary worsening.1-3 Recent researches have
demonstrated that much of the cell death from stroke results
from a complex series of biochemical events (often termed
the ischemic cascade) that occur over a period of hours or
even days after the initial stroke. 4- 6 In addition, components of the inflammatory pathways, which are considered
to be the hallmarks of reperfusion injury, can result in secondary tissue injury and further vascular compromise.7-9
The National Institutes of Health Stroke Scale (NIHSS)
of the USA is widely used in the assessment of initial and
final neurological deficits in all acute stroke studies.10 It was
one of multiple variables analyzed for its capacity to predict
progression and improvement of the patient suffering from
stroke.10
The objective of this study was to determine the characteristics of patients likely to show neurological changes
during the first 48 hours after the onset of acute cerebral
ischemia by NIHSS in the setting of a stroke- patient-admitCorresponding author: Dr. Vinh Phuong. Department of Geriatric
Cardiology, Khanh Hoa Hospital. 19 Yersin Nha Trang, Vietnam.
Tel: 8458-812344. E-mail: npvinhphuong@dng.vnn.vn

ting department.

Subjects & methods

Subjects
The study include all patients > 18 years admitted to
the Department of Geriartic Cardiology at Khanh Hoa
Hospital, Nha Trang, Vietnam from June 2005 to September
2006 with the diagnosis of acute ischemic stroke. The NIHSS
was performed at presentation and every 8 hours for 48
hours on all patients.
Inclusion criteria: 1) Ischemic stroke onset within 24
hours of enrollment, 2) identifiable time of onset, 3) stable
deficit lasting longer than 1 hour without rapid improvement.
Exclusion criteria: 1) Hemorrhagic stroke, 2) prior neurological deficit that obscured the ability to follow the neurological examination from the most recent infarct, 3) Coma.
NIHSS scoring
NIHSS is short for National Institutes of Health Stroke
Scale. It was a commonly used yardstick for measuring the
outcome of neurological deficits in stroke patients. Raters
are well trained and given detailed instructions from the
NIH Stroke Scale Training Digital Video Disk provided by
the National Institute of Neurological Disorders and Stroke.10
The scale consists of 11 items, and each item includes a

Journal of Geriatric Cardiology December 2007 Vol 4 No 4

226
scale of several scores, with a total score of 42 .10

Imaging classification
Computer tomography (CT) scan was performed on
all patients to confirm the location and size of the infarct.
Imaging classifications of the strokes were divided into the
following 5 categories: 1) lacunar infarcts (subcortical lesions =1 cm), 2) small to moderate cortical or subcortical
infarcts [>1cm and <1/3 of the mid-cerebral artery (MCA)
distribution], 3) moderate to large cortical or subcortical
infarcts (>1/3 MCA distribution), 4) brain stem, and 5) normal.
Monitoring: Patients were monitored carefully for clinical changes: 1) neurological worsening was defined as a 3point or greater increase on the NIHSS during the first 48
hours. 2) patients were classified as having improved if
they had a normal examination at the end of 48 hours (NIHSS
score of 0 or 1).
Statistical analysis: Bayes solution rule16 was applied to identify a threshold initial NIHSS score. The probability is that a patient with a score below the threshold who
is predicted to improve in 48 hours and the probability that
a patient with a score above the threshold who is predicted
to worsen in 48 hours. A 2 test was performed to determine
whether the rates of worsening and improvement were different between the groups of patients above and below the
initial stroke scale threshold. A stepwise logistic regression
analysis was performed to assess which variables were associated with stroke progression. The demographic data,
baseline characteristics, and risk factors for stroke were
compared between those who showed progression and
those who did not by the Studentst test and Mann-Whitney
rank sum as appropriate.

7, who worsened in only 6 of 47 cases (13%) (2 = 8,790, P<

0.01). In addition, 20 of 47 patients (42.5%) with an initial
NIHSS score 7 were normal (NIHSS score of 0 or 1) at 48
hours, whereas only 1 of 21 (4,7%) of those with scores >7
were normal at the same time point (2 = 5.883, P<0.05) (Figure
1 Table 2).
Stepwise logistic regression of the factors tested for
association with stroke progression [demographic data: age,
sex, baseline characteristics: completed blood count (CBC),
atrial fibrillation, initial NIHSS score, mean arterial pressure
(MAP), and risk factors for stroke: hypertenion (HTN),
smoking, hypercholesterolemia, diabetes] revealed that only
the initial neurological score, MAP and atrial fibrillation were
useful in predicting which patients would worsen (Table 3).
Atrial fibrillation and mean arterial blood pressure
Table 1 Demographic data & baseline characteristics of
patients
Characteristics

Frequency

44
24

65
35

No. of patients worsened(n)

No. of pts without progression(n)

19
49

28
72

Average age(yr)
Average time from onset to admission (hr)

66.2
15

Sex
Male(n)
Female(n)

Average progression time (hr)

Average initial NIHSS score
90
80
70
60
50
40
30
20
10
0

Results
From June 2004 to September 2005, sixty eight patients
were admitted, and among those, forty four (65%) were men
and twenty four (35%) were women. The average patient
age was 66.2 years. The average time from onset of stroke
symptoms to enrollment into the study was 15 hours, and
the average initial NIHSS score was 6.5. Overall, progression of neurological deficits occurred in 19 of the 68 events
(28%)(Table 1).
Patients with an NIHSS of score>7 worsened in 13 of
21 cases (62%) compared with those with an initial score of

34.913.2
6.5

83%

60%
50%

43%

13%

10%
0%

1-7

8 - 14
Improved

0%

15 - 21

> 21

Worsened

Figure 1 Neurological progression related to the NIHSS score

Table 2 Neurological worsening or return to normal related to the NIHSS score

Neurological changes

Score:1-7

Score:8-14

Score:15-21

Improvement

20 (43%)

1 (10%)

0 (0%)

0 (%)

21 (31%)

Without progression

21 (45%)

4 (40%)

2 (40%)

1 (17%)

28 (41%)

6 (13%)

5 (50%)

3 (60%)

5 (83%)

19 (28%)

10

68 (100%)

Worsening
Total

47

Score:>21

Total

Journal of Geriatric Cardiology December 2007 Vol 4 No 4

(MAP) in the first 48 hours were significant factors associated with patients who worsened (P=0.014 & P=0.012).
Especially, the initial neurological score strongly tended
toward association with worsening neurological progression (P<0.001). There was no significant association with
other factors such as age, sex, CBC on admission, as well as
HTN, smoking, diabetes, and high LDL-cholesterol.
Analysis of stroke subtypes by CT demonstrated a
significantly greater likelihood of progression in patients
with large to moderate cortical and subcortical infarcts,
whereas patients with lacunar and small subcortical infarcts
or normal scans had significantly fewer episodes of neurological deterioration (Table 4).

Discussion
Our study demonstrates the potential value of the initial NIHSS score in identifying those patients who are likely
to progress as well as those likely to improve over the first
48 hours. A sharp demarcation in the occurrence of improvement was also seen at a threshold of 7. The observed frequency of clinical worsening sharply increased above an
initial NIHSS score of 7, with the probability of worsening
being 5 times greater with a score of >7 (62%) than with a

227

score of =7 (13%). With a score of =7 on admission, a patient was 9 times more likely to be normal in 48 hours than
those presenting with higher scores.
Other recent prospective studies of progression in
acute stroke have highlighted the high frequency of change
in the neurological examination that can occur in the first
several hours to days after ischemic injury, and that delayed edema may play a role in symptom progression. 3, 13-17
Early deterioration has been noted in as many as 22-40% of
patients in the first 48 hours, 3 and major neurological improvement has been reported in 22-28% of acute stroke
victims during the same time frame. 14,16 This may allow therapies targeting the ischemic penumbra to be instituted during the phase of lesion extension in these patient subgroups
with greater chances of stroke progression.
The importance of understanding the frequency of
alterations in the clinical condition after acute stroke is illustrated by the data that show the predictive value of early
changes on long-term outcome. Toni, et al 3,15 reveals that
patients with early deterioration have an increased mortality of 35% to 50%. Conversely, patients with early improvement have been reported to have a high frequency of good
outcome (79%) at 30 days.3 In addition, it has been shown
that the clinical course of recovery stabilizes beyond day 4,

Table 3. The factors tested for associations with stroke progression

No

Factors

Progression (n=19)

1 2

Nonprogression (n=49)

Age

67.6

66.0

0.237

2
3

Sex, M/F
Hypertension

13/6
16(84.2%)

31/18
31(63.2%)

0.690
0.093

4
5

Smoking
Hypercholesterolemia

11(57.9%)
9 (47.3%)

18(36.7%)
12 (24.5%)

0.113
0.067

6
7

Diabetes
Atrial fibrillation 1

3 (15.8%)
6(31.5%)

9 (18.4%)
4 (8.2%)

0.802
0.014

8
9

Initial NIHSS score 1 2

White blood cell1 2

8.95
9.105

5.57
9.285

<0.001
0.724

10
11

Platelet 1 2
MAP 1

198.9
114.2

207.3
108.2

0.303
0.012

Note:1 Stepwise logistic regression analysis

2
Mann-Whitney rank-sum test.

Table 4. Stroke progression related to stroke subtype by CT

Stroke subtype
() Lacunar/small subcortical infarction

Progression (n=19)

Nonprogression (n=49)

p value

1 (5.3%)

21(42.9%)

<0.05

12 (63.2%)

7(14.3%)

<0.01

() Small cortical / subcortical infarcts(<1/3 MCA)

2 (10.5%)

5(10.2%)

0.61

() Brain stem

1 (5.3%)

5(10.2%)

0.32

() Normal

3 (15.8%)

11(22.4%)

0.30

() Moderate to large cortical

/subcortical infarcts(>1/3 MCA)

Journal of Geriatric Cardiology December 2007 Vol 4 No 4

228

with improvement becoming more linear from that time on. 3

We found that infarct size was closely associated with
neurological changes, as previously noted by some
investigators.15 Patients with lacunar infarcts were 10 times
more likely to remain stable or improve than to experience
neurological deterioration. Conversely, patients with moderate to large cortical and subcortical infarcts (>1/3 of the
MCA territory) were significantly more likely to progress
than any other imaging-defined subgroup.
In addition, our study demonstrated that strokes occurring in patients with atrial fibrillation are more likely to
progress. Whether this is due to larger strokes (more commonly seen with cardioembolic ischemic events) or re-embolization is unknown. Of those with atrial fibrillation who
progressed, 5 of 6 had moderate to large cortical or subcortical infarcts. Of those who did not progress, 50% had small
cortical or subcortical infarcts.

3.

Conclusion

10.

This study strongly suggests that the course of neurological deficit following acute stroke is dependent on the
initial stroke severity and that a dichotomy in early outcome
exists with respect to the initial NIHSS scores when patients are stratified to =7 and >7.
Additionally, MAP and atrial fibrillation were found
to be useful in predicting neurological worsening.
These findings may have significant implications for
the design and patient stratification in treatment protocols
with respect to primary clinical outcome.

11.

References

16.

1.

2.

Johnston KC, Li JY, Lyden PD, et al. Medical and neurological

complications of ischemic stroke: experience from the
RANTTAS trial. Stroke 1998;29:44753.
Davalos A, Cendra E, Teruel J, et al. Deteriorating ischemic
stroke: risk factors and prognosis. Neurology 1990; 40:18659.

4.
5.

6.

7.

8.

9.

12.
13.
14.

15.

17.

Toni D, Fiorelli M, Bastianello S, et al. Acute ischemic strokes

improving during the first 48 hours of onset: predictability,
outcome, and possible mechanisms. Stroke 1997;22:10-14.
Choi D. Cerebral hypoxia: some new approaches and unanswered questions. J Neurosci 1990;10:2493-501.
Kuroda S, Siesju BK. Reperfusion damage following focal
ischemia: pathophysiology and therapeutic windows. Clin
Neurosci 1997;4:199-212.
Chalmers-Redman RME, Fraser AD, Ju WYH, et al. Mechanisms of nerve cell death: apoptosis or necrosis after cerebral
ischemia. Int Rev Neurobiol 1997;40:1-25.
Hallenbeck JM. Inflammatory reactions at the blood-endothelial interface in acute stroke. Adv Neurol 1996;71:281300.
DeGraba TJ. The role of inflammation following acute stroke:
utility of pursuing anti-adhesion molecule therapy. Neurology 1998;51(Suppl 3):S62-8.
Bjork J, Hedqvist P, Arfors KE. Increase in vascular permeability induced by leukotriene B4 and the role of polymorphonuclear leukocytes. Inflammation 1982;6:189-200.
Lyden P, Raman R, Liu L, et al. NIHSS training and certification using a new digital video disk is reliable. Stroke 2005; 36:
2446-9.
Goldstein LB, Bertels C, PA-C, Davis JN. Interrelatel reliability of the NIH Stroke Scale. Arch Neurol 1989;46:660-2.
Rao CR. Linear Statistical Inference and Its Applications.
New York, NY: John Wiley & Sons; 1965: 413-9, 487-93.
Biller J, Love BB, Marsh EE, et al. Spontaneous improvement after acute ischemic stroke. Stroke 1990; 21:1008-12.
Toni D, Fiorelli M, Zanette EM, et al. Early spontaneous
improvement and deterioration of ischemic stroke patients.
Stroke 1998; 29:1144-48.
Toni D, Fiorelli M, Gentile M, et al. Progressing neurological
deficit secondary to acute ischemic stroke. Arch Neurol 1995;
52:670-5.
Wityk RJ, Pessin MS, Kaplan RF, et al. Serial assessment of
acute stroke using the NIH Stroke Scale. Stroke 1994; 25:
362-5.
Fiorelli M, Alperovitch A, Argentino C, et al. Prediction of
long-term outcome in the early hours following acute ischemic
stroke. Arch Neurol 1995;52:250-5.