www.elsevier.com/locate/jns

Journal of the Neurological Sciences 217 (2004) 101–106

Global aphasia without hemiparesis: lesion analysis and its

mechanism in 11 Korean patients

Oh Young Banga, Kwang Gi Heoa, Yong Tae Kwakb, Phil Hyu Leea, In Soo Jooa, Kyoon Huha,*

aDepartment of Neurology, College of Medicine, Ajou University, Woncheon-dong San 5, Paldal-ku, Suwon, Kyungki-do 442-749, South KoreabDepartment of Neurology, Yong-in Hyoja Geriatric Hospital, South Korea

Received 21 March 2003; received in revised form 4 September 2003; accepted 8 September 2003

Abstract

Background: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome. This study localized the lesion and examined the

pathogenic mechanism in Korean patients with GAWH, and investigated whether areas of extensive hypoperfusion existed outside the

diffusion-weighted imaging (DWI) lesions seen in these patients. Material and methods: Eleven patients were diagnosed with aphasia using

the Western Aphasia Battery. To identify decreased perfusion, which might be functionally relevant to aphasia but not detected by DWI,

single photon emission tomography (SPECT) was performed in five patients. To uncover the possible pathogenic mechanisms of ischemic

stroke, vascular and cardiologic work-ups were performed in all of the patients. Results: The lesions seen on DWI varied, and included both

inferior frontal and superior temporal (three), isolated inferior frontal (four) or superior temporal (one), subcortical (two), and even parieto-

occipital (one) lesions. Brain SPECT did not reveal an extensive lesion of the peri-sylvian area outside the DWI lesion in any of the patients,

except one with the subcortical lesions. Conclusion: Our results indicate that a single lesion in different locations may be sufficient to produce

GAWH, and the lesion profile and stroke mechanism in GAWH are heterogeneous, suggesting that lesions to an area of complex functional

anatomy result in aphasia.

D 2003 Elsevier B.V. All rights reserved.

Keywords: Aphasia; Hemiparesis; Diffusion weighted imaging; Single photon emission; Tomogram

1. Introduction

Global aphasia without hemiparesis (GAWH) is a rare

and striking stroke syndrome, because of the unusual

dissociation between language and motor function. Global

language impairment typically occurs after large peri-syl-

vian lesions with infarction of both the frontal and temporal

branches of the left middle cerebral artery. Ordinarily,

contralateral hemiparesis occurs together with global apha-

sia, due to the proximity of the cortical language centers and

motor control areas [1].

Hanlon et al. [2] recently reviewed the lesion profile and

mechanisms of non-Asian cases of GAWH, including 10

patients of theirs, and suggested that a single lesion and non-

cardioembolic origin cause GAWH. Vignolo et al. [3] found

that only 59% of their patients with global aphasia with

0022-510X/$ - see front matter D 2003 Elsevier B.V. All rights reserved.

doi:10.1016/j.jns.2003.09.010

* Corresponding author. Tel.: +82-31-219-5175; fax: +82-31-219-

5178.

E-mail address: nmboy@unitel.co.kr (K. Huh).

hemiparesis had large left peri-sylvian lesions involving

both Broca’s and Wernicke’s areas, whereas 30% had either

anterior or posterior lesions and 11% had deep lesions of the

insula and lenticular nucleus.

Diffusion-weighted imaging (DWI) is the most sensi-

tive tool for detecting fresh ischemic lesions that cannot

be detected using conventional magnetic resonance imag-

ing (MRI), and it also provides information that differ-

entiates recent infarcts from chronic infarcts that are not

associated with clinical deficits like aphasia. In addition,

single photon emission tomography (SPECT) can identify

decreased flow that may be functionally relevant to

neurological symptoms that cannot be detected using

computed tomography (CT) or MRI. This is particularly

crucial for acute aphasia, when a defect detected by CT

and MRI cannot be reliably used to differentiate various

aphasia types [4]. Moreover, SPECT can be used to

identify the remote effects of vascular lesions [5]. There-

fore, DWI and SPECT together may provide instructive

clues for understanding the lesion profile of GAWH and

the functional anatomy of aphasia.

Fig. 1. DWI and brain SPECT findings in each group of patients. Black and white images, schematic drawings of the DWI lesions. Color images, brain SPECT

findings. Red lines represent the anterior and posterior margin of precentral gyrus.

O. Young Bang et al. / Journal of the Neurological Sciences 217 (2004) 101–106102

O. Young Bang et al. / Journal of the Neurological Sciences 217 (2004) 101–106 103

Fewer than 30 patients with GAWH have been described

previously [2]. To the best of our knowledge, no studies of

GAWH using DWI and SPECT have been reported. Further-

more, the pathogenic mechanismsmay vary depending on the

localization of the lesions and with ethnic group. The objec-

tives of this study were to localize the lesions and determine

the pathogenic mechanisms in Korean patients with GAWH,

and to investigate whether extensive areas of hypoperfusion

outside the DWI lesions existed in these patients.

Table 1

Characteristics of patients

Case Sex/age Handedness Work up for mechanisms of stroke

Angiographic Cardiologic

Classical lesion group

1 M/60 Right Normal MRA A-Fib, normal TTE

and TEE

2 M/79 Right Normal MRA A-Fib, normal TTE

3 F/59 Left Normal on TFCA Normal TEE

Non-classical lesion group

(1) Single lesion group

4a F/64 Right Left EC ICA

stenosis on TFCA

Normal TTE

5 M/62 Right Normal MRA A-Fib, akinetic left

ventricle segment

on TTE

6b F/43 Right Bilateral IC ICA

occlusion on TFCA

Normal TEE

7 F/80 Right Normal on MRA Normal TTE

8 M/79 Right Normal MRA Normal TTE

(2) Extra-sylvian lesion group

9c F/62 Right Left EC ICA

occlusion on TFCA

Normal TTE

10c F/75 Right Left EC ICA

occlusion on MRA

Normal TTE

11 F/58 Right Proximal MCA

stenosis on TFCA

Trivial valvular hear

disease on TEE

IC: intracranial, EC: extracranial, ICA: internal carotid artery, MCA: middle

cerebral artery, A-Fib: atrial fibrillation, MRA: magnetic resonance

angiography, TFCA: transfemoral conventional angiography, TTE: trans-

thoracic echocardiogram, TEE: transesophageal echocardiogram.a Asymptomatic old infarcts on right hemisphere.b Probable Moyamoya disease.c Previous right hemiparesis, but no sequale.

2. Materials and methods

We studied 11 consecutive patients with GAWH (4 men

and 7 women; age, 43–80 years; all but one were right-

handed). The Medical Research Council (MRC) scale was

used to assess their motor strength: on this scale, ‘0’

indicates no movement, ‘1’ movement only if gravity is

removed, ‘2’ weakness against gravity, ‘3’ weakness against

slight resistance, ‘4’ weakness against stronger resistance,

and ‘5’ normal strength. Each patient was also assessed

using the National Institutes of Health Stroke Scale (NIHSS)

[6]. All the subjects had normal scores bilaterally for the

upper extremity, hand, and lower extremity motor items of

the MRC and NIHSS. None had facial weakness. The

Western Aphasia Battery (WAB) [7,8] established the apha-

sic subtype and severity of aphasia, including subscales for

fluency, comprehension, repetition, and naming, during the

acute (within 3 days after stroke onset) and postacute (4 and

8 weeks after stroke onset) stages.

To uncover the possible pathogenic mechanisms of is-

chemic stroke, all the patients were examined using MRI (1.5

T, Sigma, GE), electro- and echocardiography, and conven-

tional or magnetic resonance angiography. DWI was per-

formed in the axial plane (TR: 10,000 ms, TE: 104 ms, slice

thickness: 7 mm, and no gap) within 3 days after stroke onset

in all of the patients. An extensive work-up, including

coagulopathy studies, was performed in two patients youn-

ger than 60 years old (patients 3 and 6). Using the results of

the work-up, the etiological subtypes of ischemic stroke were

classified using the criteria of Adams et al. [9]. To define

whether there was an extensive lesion outside the DWI

lesion, a Tc-99 m HMPAO brain SPECT study was also

performed in selected patients (within 7 days after stroke

onset). The existence and extent of the area of hypoperfusion

were determined by visual inspection by a neuroradiologist

who did not know the clinical status of the subjects.

Based on the cerebral lesions on DWI, we divided these

patients into three groups: (a) lesions in both the left

superior temporal and inferior frontal gyrus (the classical

lesion group), (b) a lesion in either the left inferior frontal

gyrus or the left superior temporal gyrus (the single lesion

group), and (c) a subcortical or cortical lesion outside the

peri-sylvian area (the extra-sylvian lesion group).

The SPECT patterns and possible mechanisms of stroke

were compared among the groups.

3. Results

All of the patients had large acute infarcts; however, the

locations of the infarcts on DWI varied (Fig. 1): three

(patients 1–3) were classified in the classical lesion group,

five (patients 4–8) in the single lesion group, and three

(patients 9–11) in the extra-sylvian lesion group. The

precentral gyrus was spared in all of the patients (Fig. 1).

However, two patients with subcortical lesions (patients 9

and 10) showed possible involvement of the motor pathway

in the deep brain structure on DWI, and were characterized

by the presence of a previous history of involvement of the

motor pathway and improvement without any motor deficit.

A SPECT study was performed in five patients who did not

show concurrent involvement of both the left inferior frontal

and left superior temporal gyrus (three of the single lesion

group, and one each of the extra-sylvian and classical lesion

groups). However, brain SPECT did not reveal any exten-

sive lesions of the peri-sylvian area outside the DWI lesions

in any of the patients, except one (patient 10) with the

subcortical lesions (Fig. 1).

Table 1 lists the demographic data and results of the

etiologic evaluation. Of the 11 patients, only three met the

criteria for cardioembolic ischemic stroke, and large artery

O. Young Bang et al. / Journal of the Neurological Sciences 217 (2004) 101–106104

disease of the relevant vessels was more prevalent (five

patients) in our patients with GAWH. Moreover, the path-

ogenic mechanism of stroke differed with the location of the

lesion on DWI. Two of the three patients with infarcts in

both the left superior temporal and inferior frontal gyrus (the

classical lesion group) had a potential source of cardioemb-

olism, whereas all the patients in the extra-sylvian lesion

group had large arterial occlusive lesions: two patients with

subcortical lesions (patients 9 and 10) had occlusive lesions

of the extracranial internal carotid artery and one patient

with an occipito-parietal lesion (patient 11) had a proximal

middle cerebral arterial occlusive lesion. One patient (pa-

tient 3 in the classical lesion group), a left-handed woman,

had a right hemispheric lesion, but no clear etiology. For the

single lesion group, the mechanisms of ischemic stroke were

variable: extracranial internal carotid arterial stenosis, atrial

Fig. 2. Follow up language profile of the patients. Perfect scores of fluency, com

Blackened square (n) indicates the patients of classical lesion group; open triang

fibrillation, and Moyamoya disease were found in one

patient each (patients 4, 5 and 6, respectively), while the

other two patients (patients 7 and 8) had no clear etiology.

Fig. 2 shows the WAB scores at the time of initial and

follow-up language assessments. All of the patients had

severe global aphasia, characterized by muteness or dense

non-fluent speech with severe speech initiation deficit,

marked impairment on both auditory and reading compre-

hension, no repetition, dysmorphic or dysgrammatical writ-

ing, and grossly defective naming. A follow-up language

assessment showed that all but three patients (patients 1, 2

and 6) showed minimal or no change in any of the language

domains and remained globally aphasic; most of the patients

had non-fluent spontaneous speech, moderate comprehen-

sion impairment, minimal capacity for naming monosyllabic

high frequency nouns, and limited repetition. As shown in

prehension, repetition, and naming were 20, 10, 10, and 10, respectively.

le (4), Single lesion group; and gray circle , extra-sylvian lesion group.

O. Young Bang et al. / Journal of the Neurological Sciences 217 (2004) 101–106 105

Fig. 2, there was a tendency to show more improvement in

comprehension and, in some patients (patients 1, 2 and 6) in

fluency, than in repetition or naming.

4. Discussion

Earlier reports suggest that multiple lesions involving the

anterior and posterior language area, but sparing the motor

cortex, are necessary to cause GAWH, and that GAWH is

highly indicative of embolic etiology [10,11]. However,

various lesion locations and pathogenic mechanisms have

been described in non-Asian cases of GAWH. Some reports

indicate that GAWH is not pathognomonic of embolism,

and that GAWH is also heterogeneous with respect to the

lesion profile [2,12].

In this study, similar variation in lesion location was

observed; only 3 of the 11 patients with GAWH had typical

classical lesions, and GAWH occurred more commonly with

a single lesion in the peri-sylvian area (either the inferior

frontal gyrus or superior temporal gyrus) or even the extra-

sylvian area. These results are in good agreement with

previously reported cases with global language impairment,

in which a single cortical lesion or deep brain lesion plus an

extensive lesion could cause global aphasia, suggesting the

highly heterogeneous location of the lesion in GAWH [3].

Moreover, with the help of SPECT, we attempted to

document possible extensive perfusion defects in the peri-

sylvian area in the patients with a single lesion, but failed to

do so. Therefore, our SPECT results strongly suggest that a

single lesion in either the left inferior frontal or superior

temporal gyrus can cause global aphasia. One case with a

subcortical lesion showed an extensive perfusion defect

outside the DWI lesions on brain SPECT. Cortical hypo-

perfusion in the peri-sylvian areas has been reported to be

crucial for the development of subcortical global aphasia

[13].

Our data, together with other reported cases [2,14],

suggest that GAWH cannot be considered pathognomic

for embolic stroke. In our study, atherosclerotic lesions

affecting either intra- or extra-cranial arteries were more

common than cardioembolic sources, although this might

have been caused by the low prevalence of cardioembolic

stroke (10.9%) among the stroke patients seen during the

study period. In this study, atherosclerotic disease was

found exclusively in the patients in the non-classical

lesion group, whereas most of the patients with the

classical lesion pattern on DWI had cardioembolic sour-

ces, suggesting that the location of the lesion on DWI

differs with the pathogenic mechanism of stroke. Al-

though only a small number of patients were included

in our study, in Korean patients with GAWH, there is a

tendency to the non-classical lesion pattern (73%, 8 of 11

patients) and a reduced association with a cardioembolic

source (27%, 3 of 11 patients), as compared to non-Asian

GAWH (about half of the patients had the classical lesion

pattern and a cardioembolic source) [2,10–12,14]. Further

studies with more patients are needed.

As shown in Fig. 1, none of our patients had involvement

of the precentral motor cortex. The DWI finding of subcor-

tical lesions in patients with GAWH (patients 9 and 10) was

unexpected. Using three-dimensional data on the lesions,

von Keyserlingk et al. [15] reported that parts of the deep

white matter were spared in patients with global aphasia, but

no hemiparesis. We do not know why the patients with a

subcortical lesion in our study (patients 9 and 10) did not

manifest hemiparesis, despite the likely involvement of the

motor pathway seen on DWI. A common finding in these

two patients was that they were thought to have had

previous involvement of the motor pathway and recovered.

Brain SPECT (patient 10) showed global left hemispheric

hypoperfusion (Fig. 1). Neuroimaging studies in stroke

patients indicate altered poststroke activation patterns,

which suggest functional reorganization or ‘‘brain plastici-

ty’’ [16]. An issue of particular interest is the role of the

motor cortex ipsilateral to the affected hand when patients

move this hand. Evidence for ipsilateral involvement, in

addition to contralateral activation, has been reported in

positron emission tomography (PET) [17,18] and functional

MRI studies [19–21], but with a focus of activity in the

ipsilateral premotor cortex [18,19,22]. Although we did not

perform functional imaging to document functional reorga-

nization, ‘cortical plasticity’, i.e., right hemispheric control

of right limb motor functions, could have played a role in

the development of GAWH in our patients.

Varying degrees of improvement after GAWH have been

reported; the improvement can be either rapid [11,12] or

poor [2]. Our patients could not be characterized by exten-

sive recovery of language function uniformly. Although the

language profile and recovery are reported to depend on the

location of the lesion [2], we could not confirm this finding,

probably due to the short interval of the follow-up assess-

ment of language function.

Our study has some limitations. First, we examined only

a small number of patients because of the rarity of this

syndrome. Second, due to the high frequency of vascular

death, fatal recurrent stroke, or myocardial infarction, espe-

cially in patients with large-artery disease (five patients), we

could not conduct a long-term follow-up examination.

Third, a more extensive work-up to deduce the mechanism,

such as a transesophageal echocardiogram, was not per-

formed in all of the patients, because of poor cooperation.

Conventional angiography was not performed in patients

older than 75 years or in those with sources of cardioemb-

olism, and hemostatic markers of prothrombotic tendency,

including protein C, protein S, antithrombin III, and anti-

phospholipid antibodies, were checked only in those youn-

ger than 60 years old. Finally, the brain SPECT study was

performed only in selected patients.

In conclusion, our results indicate that although the

patients with acute GAWH all appeared similar on neurolog-

ical examination, the lesion profile and stroke mechanism in

O. Young Bang et al. / Journal of the Neurological Sciences 217 (2004) 101–106106

GAWH are heterogeneous. A single lesion, in either a cortical

or subcortical area, in the absence of an extensive perfusion

defect, may cause GAWH, suggesting the complex functional

anatomy of aphasia. The localization of the lesions may also

differ depending on the pathogenic mechanism.

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