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Epidemiology of Aphasia Attributable to First

Ischemic Stroke
Incidence, Severity, Fluency, Etiology, and Thrombolysis
Stefan T. Engelter, MD; Michal Gostynski, MD, MPH; Susanna Papa; Maya Frei; Claudia Born;
Vladeta Ajdacic-Gross DrSc; Felix Gutzwiller, MD, DrPH; Phillipe A. Lyrer, MD
Background and PurposeIn a geographically defined population, we assessed incidence and determinants of aphasia
attributable to first-ever ischemic stroke (FEIS).
MethodsA 1-year prospective, population-based study among the permanent residents of the canton Basle City,
Switzerland, was performed using multiple overlapping sources of information.
ResultsAmong 188 015 inhabitants, 269 patients had FEIS, of whom 80 (30%; 95% CI, 24 to 36) had aphasia. The
overall incidence rate of aphasia attributable to FEIS amounted to 43 per 100 000 inhabitants (95% CI, 33 to 52).
Aphasic stroke patients were older than nonaphasic patients. The risk of aphasia attributable to FEIS increased by 4%
(95% CI, 1% to 7%), and after controlling for atrial fibrillation, by 3% (95% CI, 1% to 7%) with each year of patients
age. Gender had no effect on incidence, severity, or fluency of aphasia. Cardioembolism was more frequent in aphasic
stroke patients than in nonaphasic ones (odds ratio [OR], 1.85; 95% CI, 1.07 to 3.20). Aphasic patients sought medical
help earlier than nonaphasic stroke patients. Still, after controlling for stroke onsetassessment interval, aphasic stroke
patients were more likely to receive thrombolysis than nonaphasics (OR, 3.5; 95% CI, 1.12 to 10.96).
ConclusionAnnually, 43 of 100 000 inhabitants had aphasia resulting from first ischemic stroke. Advancing age and
cardioembolism were associated with an increased risk for aphasia. Severity and fluency of aphasia were not affected
by demographic variables. (Stroke. 2006;37:1379-1384.)
Key Words: aphasia epidemiology stroke thrombolysis

phasia in stroke patients is associated with increased


mortality,1 decreased rates of functional recovery,2,3 and
reduced probability to return to work4 compared with nonaphasic stroke patients. High-intensity speech therapy has been
shown recently to improve outcome5 but requires the availability
of a sufficient number of qualified therapists. Thus, for planning
stroke rehabilitation processes and resource allocation, epidemiological data about frequency and severity of aphasia in stroke
patients are crucial. The frequency of aphasics among stroke
patients ranged from 21% to 38%.6 10 However, these numbers
are based on studies with different methodological approaches
entailing specific limitations. Some used a retrospective design.11 Some were based on surveys,7 in-hospital stroke registries,9 stroke unit cohorts,1,12 or patients of neurological departments.10,13 Most of these studies assessed only patients admitted
to a hospital,1,6,9,12,14 thus introducing a potential bias because
the presence of aphasic symptoms may increase the probability
of admission.7,15 Furthermore, aphasia studies meeting current
standards for epidemiological studies16 are lacking to the best of
our knowledge.

Some groups reported that demographic factors like age and


gender influence the occurrence,10,17 severity,18 and fluency9,18,19
of aphasia, whereas other studies could not confirm these
findings.6,20 22
Aphasia was predominantly attributed to cardioembolic stroke
etiology,23 whereas other case series reported multiple underlying stroke mechanisms.24 Population-based studies about stroke
etiology stratified to the presence or absence of aphasia are
lacking. Furthermore, it had yet to be studied whether there is an
association between aphasia as stroke symptom and treatment
with thrombolysis. With these considerations in mind, we
designed a 1-year prospective, population-based study to determine the incidence and the determinants of aphasia resulting
from first-ever ischemic stroke (FEIS), including an adjustment
to European standard population.25

Patients and Methods


Study Population and Data Acquisition
As a joint initiative of the Stroke Unit Basel, the Institute of Social
and Preventive Medicine, Zurich, and the Swiss Aphasia Society, we

Received January 4, 2006; final revision received March 6, 2006; accepted March 9, 2006.
From the Neurological Clinic and Stroke Unit (S.T.E., S.P., P.A.L.), University Hospital Basle, Switzerland; Institute of Social and Preventive Medicine
(M.G., V.A.-G., F.G.), University of Zurich, Switzerland; Institute of Speech Therapy (M.F.), University Hospital Basel, Switzerland; and Institute for
Specific Pedagogics and Psychology (C.B.), Basel, Switzerland.
Correspondence to S.T. Engelter, MD, Neurological Clinic and Stroke Unit, University Hospital Basle, Petersgraben 4, CH 4031 Basel, Switzerland.
E-mail [email protected]
2006 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org

DOI: 10.1161/01.STR.0000221815.64093.8c

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designed a prospective bipartite study about the epidemiology of:


FEIS26 and of aphasia attributable to FEIS. The canton Basle City,
Switzerland, was considered an appropriate model for such a study
because of its geographically well-defined catchment area and the
advanced degree of organized stroke care available for all inhabitants. After ethical approval, we prospectively recorded all FEIS
patients among the residents of the canton Basle City in between
June 1, 2002, and May 31, 2003 (188 015 inhabitants, census 2002).
Multiple, overlapping sources of information were used, as suggested by Sudlow and Warlow16 (1). The stroke register of the local
university hospital, which is the only hospital providing stroke unit
care not only in Basle City but in the whole region, enabled us to
ascertain all stroke patients on a daily basis (2). The register of the
only neurorehabilitation unit of Basle City, which is located outside
the university hospital, was used to identify all patients with
in-hospital neurorehabilitation, regardless of the place of acute stroke
treatment (3). The records of speech therapists within all hospitals in
Basle City were used to identify all stroke patients with aphasia (4).
All hospitals in Basle City received mailings every 3 months to
provide data about their stroke patients treated (5). All physicians
practicing in Basle City, taking care of nursing home residents, or
filling in death certificates were contacted by mail every 3 months,
to report on all stroke patients they have encountered. This approach
was chosen to retrieve patients who were managed outside hospitals
or who died because of stroke before hospitalization (6). The records
of a stroke neurologist who made stroke ward rounds in a nearby
hospital outside Basle City were checked on a weekly basis for
possible study patients (7). For identification of pediatric strokes, the
only pediatric hospital was contacted. The distribution of data
sources and the manner in which our study population was assembled are shown in the Figure.

Diagnosis and Assessment of Aphasia


In all stroke patients hospitalized in the university hospital, the
diagnosis of aphasia was made by a stroke unit neurologist on
admission. A bedside language examination27 was done. It includes
the use of the standardized items for language testing of the National
Institutes of Health Stroke Scale,28 which have a good inter-rater
reliability ( value 0.68 to 0.71).28 Additionally, within the next 3
days, evaluation by a speech therapist started in all patients with
abnormalities of speech, language, or swallowing, and the Basel

Minnesota Test for the differential diagnosis of aphasia29,30 was


applied by the speech therapist to confirm or disapprove of the
diagnosis of aphasia. In cases of disagreement between initial
neurologist ratings and speech therapist assessments, consensus was
reached by comparing the source data of both raters.
In patients hospitalized in primary care hospitals lacking stroke
unit treatment, diagnosis of aphasia was made by a speech therapist.
In patients not hospitalized, presence or absence of aphasia relied on
the assessment of the treating primary care physician and a speech
therapist, if such a therapy was implemented.
Patients with pre-existing aphasia caused by a nonstroke etiology
were excluded, as were all patients who had aphasia resulting from
ischemic stroke but in whom this event was a recurrent rather than
the first ischemic stroke (n9). Native languages other than German
were no exclusion criterion.
Severity of aphasia was graded into 3 categories (ie, 1 mild, 2
moderate, and 3 severe) applying the aphasia subscale of the
Scandinavian Stroke Scale.31 This scale was used in a previous
community-based aphasia study6 and was shown to have a high
inter-rater reliability ( value 0.86). Aphasia was dichotomized as
fluent or nonfluent aphasia based on the initial bedside language
assessment.27 In cases of 1 severity or fluency ratings, the earliest
assessment was used for further analysis.

Verification of Diagnosis and Determination


of Stroke Etiology
Diagnoses FEIS and aphasia were verified by a single, experienced stroke neurologist (S.T.E.), who reviewed all available source
data of reported patients. Source data check was performed for all
patients who were either treated in the university hospital or in the
rehabilitation unit, or both, and in selected cases for those assessed
or treated elsewhere. For nonhospitalized patients, diagnoses of FEIS
and aphasia were solely based on the information provided by the
physicians in charge. Stroke etiology was determined by the same
stroke neurologist according to the Trial of Org 10172 in Acute
Stroke Treatment TOAST.32 Data about the risk factor profile,
clinical symptoms and syndromes, and the findings of etiological
investigations were reviewed. The latter comprised extracranial and
transcranial Doppler/duplex sonography (n189), computed tomography scan (n228), MRI with magnetic resonance angiogram
(n128), digital subtraction angiogram (n11), 24-hour ECG

Epidemiology of aphasia attributable to first ischemic stroke in Basle City. Flowchart summarizing data sources and composition of the
study population.

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Engelter et al
(n130), and echocardiography (n162). High-risk or medium-risk
sources for cardiac embolism had to be present for cardioembolic
stroke etiology. Patients with 2 possible stroke pathomechanisms
(eg, high-grade carotid stenosis and atrial fibrillation) were classified
as having undetermined stroke etiology, as were those with incomplete workup.32 Patients with missing data were excluded from this
part of the study (ie, comparison between stroke etiology and
presence versus absence of aphasia). These were 23 of 269 patients
(8.6%) of the entire population or 11 of 80 (13.8%) of the aphasic
subgroup, respectively.

Epidemiology of Ischemic Aphasia

unknown) and the clinical assessment of stroke and aphasia. In


addition, we compared the rates of thrombolysis between both
groups based on the Basle thrombolysis databank, in which data of
all thrombolyzed stroke patients have been prospectively ascertained
since 1997.

Data Analysis
All ages were included in the analysis. Overall, gender- and
age-specific incidence rates of aphasia attributable to FEIS were
calculated per 100 000 population with 95% CI. In addition, a direct
standardization to the European standard population was performed.25
Furthermore, we assessed the frequency of aphasia in FEIS patients
across ages and gender. Bivariate analysis was performed with the 2
test for dichotomous/polytomous variables. Analyses of continuous
variables were done with the t test. The associations between aphasia
and age (unadjusted and adjusted for atrial fibrillation), aphasia
and gender (adjusted for age), aphasia and smoking (adjusted for
age), and aphasia and thrombolysis (controlling for stroke onset
assessment interval and age) were examined using logistic regres-

Aphasic Versus Nonaphasic Stroke Patients


We compared aphasic with nonaphasic stroke patients in respect of
stroke etiology, demographic characteristics, stroke risk factors
according to criteria used by other epidemiological studies,33 type of
stroke care provider (ie, stroke unit, other hospital, or primary care
physician), and stroke onsetassessment interval. The latter was
defined as the time delay between first stroke symptoms (or the time
the patient was last seen without symptoms if exact onset was

TABLE 1. Clinical Characteristics, Stroke Etiology, and Treatment With


Thrombolysis Among Aphasic Vs Nonaphasic Stroke Patients
Patients With First Ischemic Stroke (n269)

Clinical Characteristics

Aphasics
(n80; 100%)

Nonaphasics
(n189; 100%)

OR (95% CI)
1.03 1.011.07

Demographic data
Age, mean (range)

80 (4598)

75 (3796)

81

77

66 (53)

54 (102)

1.67 (0.972.89)

13 (1336)

22 (11008)

0.99 (0.980.99)

Stroke unit

80 (64)

82 (155)

0.87 (0.451.70)

Other hospital

11 (9)

15 (29)

0.70 (0.321.55)

9 (7)

3 (5)

3.5 (0.4511.48)

11 (9)

3 (5)

3.51 (1.1210.96)

Median, y
Female gender % (n)
Stroke onsetassessment interval
Median (range; h)
Type of stroke care provider, % (n)

Primary care physician


Treatment with thrombolysis, % (n)
Stroke risk factors, % (No.)

Aphasics

Nonaphasics

(n69; 100%)

(n177; 100%)

Hypertension

74 (51)

67 (119)

1.38 (0.742.57)

Smoking (current)

12 (8)

23 (41)

0.62 (0.261.48)

Diabetes mellitus

16 (11)

23 (41)

0.63 (0.301.31)

Hypercholesterolemia

19 (13)

30 (53)

0.54 (0.271.08)

Atrial fibrillation

42 (29)

23 (41)

2.41 (1.334.35)

Coronary heart disease

32 (22)

32 (57)

0.99 (0.541.79)

Stroke etiology, % (No.)


Cardioembolism

48 (33)

29 (52)

1.85 (1.073.20)

Large artery atherosclerosis

7 (5)

15 (26)

0.42 (0.151.13)

Small artery occlusion

0 (0)

22 (38)

Other determined etiology$

4 (3)

11 (20)

0.33 (0.011.14)

41 (28)

23 (41)

1.94 (1.093.46)

Undetermined etiology

1381

Stroke onsetassessment interval was defined as time interval between stroke onset (or time
patient was last seen without symptoms) until clinical stroke assessment took place. In 5 patients
(1.9%), data were missing. They were excluded from this part of the study.
In 23 (8.6%) patients, data about risk factor profile and etiological workup were missing. They
were excluded from this part of the study; stroke etiology according to TOAST;32 $this category
includes dissection, vasculitis, and other uncommon causes of stroke; including patients with 2
etiologies.
Adjusted for atrial fibrillation, age, or stroke onsetassessment interval.

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TABLE 2. Incidence Rate of Aphasia Attributable to First Ischemic Stroke in
Basel, Switzerland
Gender
Males

Females

Age, y

n/N

64

3/74 444

6574

7/7958

88

7584

8/5059

158

24/9173

9/1509

596

17/4392

27/88 970

30 (1942)

85
Total (95% CI)

IR

n/N

Total
IR

4/74 698

8/10 782

IR
5

74

15/18 740

80

262

32/14 232

225

387

53/99 045

n/N
7/149 142

54 (3968)

26/5901

441

80/188 015

43 (3352)

SR (95% CI)

20 (1228)
22 (1529)
21 (1328)

n indicates No. of patients with aphasia attributable to first-ischemic stroke; N, No. of population at risk; IR,
incidence rate (per 100 000 population per year); SR, standardized incidence rate adjusted to the European standard
population.25

increased steeply with age from 5 per 100 000 population among
the 65 years of age group to 441 for those 85 years of age.
After adjustment for age to the European standard population,
the overall incidence rate was 21 per 100 000 population (95%
CI, 13 to 28). It was similar in females (22; 95% CI, 15 to 29)
and males (20; 95% CI, 12 to 28).

sion analyses. To examine the relationship between severity or


fluency of aphasia and age or gender, nonparametric tests (Kruskall
Wallis H test and MannWhitney U test) were performed. Values of
P0.05 (2-sided test) were considered statistically significant. Descriptive and inferential analyses were performed using the SPSS
statistical package (SPSS for Windows; version 9).34 Data were
presented as odds ratios (ORs) or percentages with 95% CIs unless
otherwise stated.

Effect of Age and Gender

Results

Aphasic FEIS patients were older than their nonaphasic peers


(mean age 80 years versus 75 years; P0.002). The risk of
experiencing aphasia resulting from FEIS increased by 4%
(95% CI, 1% to 7%) and after controlling for atrial fibrillation
by 3% (95% CI, 1% to 7%) with each year of stroke patient
age. Frequency of aphasia among FEIS patients increased
from 15% (95% CI, 5% to 26%) in patients 65 years of age
to 43% (95% CI, 30% to 56%) among those 85 years of age
(P0.002; Table 3). Female FEIS patients showed a nonsignificant trend toward a higher risk of aphasia compared with
males (OR, 1.67 [95% CI, 0.97 to 2.34]). Adjusted for age,
the OR was 1.40 (95% CI, 0.80 to 2.46).

Study Population
Among 269 FEIS patients, 80 patients had aphasia, yielding an
overall 30% (95% CI, 24% to 36%) prevalence of aphasia in
FEIS. Clinical stroke assessment took place after a median of 20
hours (range 30 minutes to 6 weeks). The 25/50/75 percentiles of
the stroke onsetassessment interval were 5/20/60 hours. Aphasic FEIS patients had a shorter median onsetassessment interval
(13 hours) than their nonaphasic peers (22 hours). Atrial fibrillation was more common in aphasic (42%) than in nonaphasic
(23%) FEIS patients, yielding an OR of 2.41 (95% CI, 1.33 to
4.35). Other stroke risk factors and the type of stroke care did not
differ significantly between both groups (Table 1).

Incidence of Aphasia Attributable to FEIS

Aphasia Severity and Fluency Stratified by


Gender and Age

The overall crude incidence rate of aphasia attributable to FEIS


amounted to 43 per 100 000 population (95% CI, 33 to 52; Table
2). The age-specific incidence rates of FEIS-related aphasia

Aphasia was mild in 35 (44%), moderate in 24 (30%), and


severe in 21 (26%) patients, respectively. Aphasia was fluent
in 23 (29%) and nonfluent in 48 (60%) of the patients (in 9,

TABLE 3. Gender and Age Effects on the Frequency of Aphasia Attributable to First
Ischemic Stroke
Aphasics
Gender
Males

Females

Total

Age, y

Aphasics/FEIS

Aphasics/FEIS

Aphasics/FEIS

% (95% CI)

65

3/27

11

4/19

21

7/46

15 (526)

6574

7/33

21

8/29

28

15/62

24 (1436)

7584

8/36

22

24/64

38

32/100

32 (2342)

85
Total (95% CI)

9/18

50

17/43

40

26/61

43 (3056)

27/114

24 (1633)

53/155

35 (2742)

80/269

30 (2436)

No. of patients with FEIS; No. of FEIS patients presenting with aphasia.

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Engelter et al
or 11%, patients fluency ratings were unclassified or missing). There were no statistically significant differences between females and males with regard to aphasia severity
(P0.31) and fluency (P0.32). The same holds true for the
relationship between age and aphasia severity (P0.26) as
well as fluency (P0.86).

Stroke Etiology
Cardioembolism was more frequent in aphasic than in nonaphasic FEIS patients (OR, 1.85; 95% CI, 1.07 to 3.20;
P0.03). In aphasic FEIS patients, cardioembolism was the
underlying stroke etiology in about one half of the patients
(48%), and it represents the main determined stroke etiology
for this cohort. In turn, small vessel occlusion accounted for
22% of the strokes among nonaphasic FEIS patients but was
not present in the aphasic FEIS cohort (P0.001; Table 1).

Thrombolysis
Fourteen of 269 patients had thrombolysis (5.2%). Aphasic
patients (9 of 80) were more likely to receive thrombolysis
than nonaphasic (5 of 189), even after adjustment for stroke
onsetassessment interval (OR, 3.51; 95% CI, 1.12 to 10.96;
P0.031) or after controlling for onsetassessment interval
and age (OR, 4.74; 95% CI, 1.41 to 15.95; P0.012; Table 1)

Discussion
This prospective, population-based study about the epidemiology of aphasia attributable to FEIS showed the main
findings: 33 to 52 of 100 000 inhabitants are affected per
year, and advancing age and cardioembolism are associated
with an increased risk for aphasia.
The risk of aphasia increased by 1% to 7% per each year of
age of stroke patients. Every seventh FEIS patient 65 years
of age had aphasia, whereas the proportion nearly tripled for
subjects 85 years of age. So far, an age-dependent increase
in the occurrence of aphasia has been noticed only in one10
among several aphasia studies without such an association.6,9,17 However, our finding is corroborated by data from
multicenter, hospital-based stroke registries in which aphasia
was significantly more frequent among older than among
younger stroke patients.35,36
Female gender was not an independent risk factor for
aphasia resulting from FEIS. This finding is in line to the
majority of aphasia studies13,20,37 but is in contrast to 2 stroke
databank studies.17,38
Neither gender nor age had an influence on severity or
fluency of aphasia, which is in line with the majority of
aphasia studies.6,20 22 Some studies had suggested that nonfluent aphasia is more common in men9 and that severity18,19
and fluency of aphasia11,13 increase with advancing age.
Cardioembolism was present in nearly one half of the
aphasic FEIS patients and represents the most important
etiology in the aphasic cohort. The impact of atrial fibrillation as
major contributor to cardioembolic stroke increases steadily with
age.39 The age gradient was also noticed for the likelihood of
aphasia as stroke symptom in the current study and may suggest
a causal relationship. Thus, cardioembolism may disproportionately frequently cause aphasia. For Wernickes aphasia, such a

Epidemiology of Ischemic Aphasia

1383

relationship was indeed shown.23 Our results indicate that this


association may be extended to ischemic aphasia per se.
Aphasic stroke patients sought medical help earlier than
nonaphasic patients, possibly because stroke diagnosis was
easier or loss of speech caused more fear than other symptoms in the patients. After controlling for the (shorter) stroke
onsetassessment interval, still, the presence of aphasia was
associated with a higher likelihood of thrombolysis. However, the small sample size and the wide 95% CI urge toward
a cautious interpretation of this observation, which might
have occurred by chance. It has been reported recently that
patients with right-hemisphere strokes were less likely to
receive intravenous thrombolysis than those with lefthemisphere strokes.40 Thus, both observations might support
the hypothesis that left-hemispheric symptoms increase the
odds for thrombolysis.
As strengths, the present study made incidence estimates
based on hospitalized as well as nonhospitalized aphasia
patients from a well-defined catchment area. Furthermore,
multiple overlapping sources of information were used to
ascertain preferably all FEIS regardless of where acute stroke
care took place. Such an approach is recommended for
epidemiological stroke studies16 but is novel in aphasia
studies to the best of our knowledge.
A weakness of this approach is that the extent of language
assessment and the level of expertise of the raters differed
across the study population. Thus, the probability of falsepositive or false-negative aphasia diagnoses is likely to vary
across the data sources. The highest rates of misdiagnosis are
expected among nonhospitalized patients for whom aphasia
diagnosis is solely based on the assessment of primary care
physicians. This subgroup contributes to 4% of FEIS and to
9% of the aphasic FEIS patients, respectively, whereas 90%
of the FEIS patients were evaluated by either an experienced
neurologist with training and expertise in stroke and aphasia,
by a speech therapist, or both. Exclusion of all patients exclusively assessed by primary care physicians would amount to an
incidence rate of 39 (95% CI, 30 to 48), which is not
substantially different from that of the entire population (43;
95% CI, 33 to 52). Thus, significant alterations of our results
resulting from misclassification are unlikely. As another
limitation, information about risk factor profile was obtained
retrospectively, and etiological investigations were not done
thoroughly in all patients. Therefore, the association between
presence of aphasia and cardioembolism as underlying stroke
etiology requires confirmation. As a caveat, we excluded
patients with new aphasia resulting from recurrent stroke and
those with aphasia caused by mechanisms other than ischemic stroke. Thus, our data must not be interpreted as an
overall estimate of the incidence of aphasia per se.

Acknowledgments
The study was supported by the Basel-Hirnschlag-[Stroke]-Fonds
and aphasie suisse.

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Epidemiology of Aphasia Attributable to First Ischemic Stroke: Incidence, Severity,


Fluency, Etiology, and Thrombolysis
Stefan T. Engelter, Michal Gostynski, Susanna Papa, Maya Frei, Claudia Born, Vladeta
Ajdacic-Gross, Felix Gutzwiller and Phillipe A. Lyrer
Stroke. 2006;37:1379-1384; originally published online May 11, 2006;
doi: 10.1161/01.STR.0000221815.64093.8c
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2006 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628

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