Recent neuropsychological studies of patients with amyotrophic lateral sclerosis (ALS) have demonstrated that some patients have aphasic symptoms, including impaired syntactic comprehension. However, it is not known if syntactic comprehension disorder is related to executive and visuospatial dysfunction. In this study, we evaluated syntactic comprehension using the Syntax Test for Aphasia (STA) auditory comprehension task, frontal executive function using the Frontal Assessment Battery (FAB), visuospatial function using Raven’s Coloured Progressive Matrices (RCPM), and dementia using the Hasegawa Dementia Scale-Revised (HDS-R) in 25 patients with ALS. Of the 25 patients, 18 (72%) had syntactic comprehension disorder (STA score < IV), nine (36%) had frontal executive dysfunction (FAB score < 14), six (24%) had visuospatial dysfunction (RCPM score < 24), and none had dementia (HDS-R score < 20). Nine of the 18 patients with syntactic comprehension disorder (50%) passed the FAB and RCPM. Although sample size was small, these patients had a low STA score but normal FAB and RCPM score. All patients with bulbar onset ALS had syntactic comprehension disorder. These results indicate that it might be necessary to assess syntactic comprehension in patients with bulbar onset ALS. The implications of these findings are discussed in relation to the pathological continuum of ALS.
Amyotrophic lateral sclerosis (ALS) has historically been considered a neurodegenerative disease characterized by the progressive involvement of upper and lower motor neurons at the bulbar and spinal level. However, the consensus criteria have changed, and ALS is now considered a multisystem disorder in which motor system deficits are prominent but nonmotor deficits can also be observed [
The frontal lobe contributes to executive function, language function, and elementary motor function. Executive function refers to higher-level cognitive functions that contribute to the control and direction of lower-level functions such as language, cognition, behavior, and memory [
Patients with motor neuron disease (MND) and ALS also exhibit language dysfunction, including aphasic symptoms, such as Broca’s aphasia, due to frontal lobe deterioration [
Bak et al. [
Despite these reports, it remains unclear how syntactic comprehension disorder is related to executive and visuospatial dysfunction in ALS. The purpose of this study was to investigate the prevalence and profile of syntactic comprehension in ALS and to investigate the relation of syntactic comprehension with executive and visuospatial function. In addition, single-photon emission computed tomography (SPECT) was performed for two patients to investigate the pathological continuum of ALS.
Seventy-five Japanese ALS patients visited the Department of Speech Therapy at Kitasato University East Hospital from May 1, 2010, to August 31, 2011. All fulfilled the El Escorial criteria for definite ALS [
Flowchart showing the sequence of participant selection.
Patients were classified with bulbar, upper limb, or lower limb onset ALS by a neurologist according to self-reported initial symptoms. Subscales of the Japanese version of the revised ALS functional rating scale (ALSFRS-R) [
We evaluated syntactic comprehension, frontal executive function, visuospatial function, and dementia in all patients. Each of the tests used is characterized by brevity and was selected to minimize the burden on participants.
The STA auditory comprehension task includes four levels, with eight sentences in each level. Level I consists of nonreversible, active sentences with regular word order; Level II consists of reversible, active sentences with regular word order; Level III consists of reversible, active sentences with regular and nonregular word order; and Level IV consists of reversible, passive sentences with regular and nonregular word order (Table
Each stage and examples of Syntax Test for Aphasia.
Level | Strategy | Definition | Sample of Japanese (English) |
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I | The meaning of a word | Nonreversible, active sentences in regular word order | otokonoko (n) ga (p) aruiteiru (v) |
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II | The word order | Reversible, active sentences in regular word order | onnanoko (n) ga (p) otosan (n) ni (p) purezento (n) wo (p) ageteiru (v) |
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III | The particle without complementizer | Reversible, active sentences in regular and nonregular word order | otousan (n) wo (p) onnanoko (n) ga (p) ositeiru (v) |
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IV | The particle with complementizer | Reversible, passive sentences in regular and nonregular word order | otosan (n) ga (p) onnanoko (n) ni (p) rinngo (n) wo (p) moratteiru (v) |
(n): noun; (v): verb; (p): particle.
For each sentence, patients are presented with four to six pictures and are required to point to the picture that corresponds to the sentence read by the examiner. Seven sentences within a level have to be answered correctly to pass that level. Failure to pass all four levels (STA score < IV) was classed as failure of the STA auditory comprehension task and was considered indicative of syntactic comprehension disorder.
In Japanese grammar, particles are short words that follow the modified noun, verb, or adjective and can indicate various functions and meanings within a sentence. Some particles are equivalent to English prepositions, but others have a unique usage that is not found in English. For example, the sentences in Level III (Table
In two patients (patients 7 and 22) who had consented to go through neuroimaging test in writing, we performed 123I-isopropyl amphetamine SPECT (IMP-SPECT). Both patients selected for IMP-SPECT had similar clinical characteristics: they were both women aged between 70 and 80 years with upper limb onset ALS. The disease duration was between 1 and 2 years. Regional cerebral blood flow (r-CBF) was assessed using three-dimensional stereotactic surface projection.
Relations between syntactic comprehension (STA auditory comprehension score), frontal executive function (FAB score), visuospatial function (RCPM score) and demographic variables (age, disease duration, severity of dysarthria (ALSFRS-R1 score), and severity of upper limb impairment (ALSFRS-R5a score) were assessed using Pearson’s correlation. Correlations among the neuropsychological tests (STA auditory comprehension, FAB, RCPM, and HDS-R) were calculated with Spearman rank correlation coefficient. All analyses were performed using SPSS version 10.0 J software for Windows. Data are presented as mean ± standard deviation unless otherwise stated.
Results are presented from 25 patients (16 men, 9 women) aged 67.9 ± 9.0 years. Disease duration was 23.9 ± 15.5 months (range, 6–61 months). The ALSFRS-R1 score was 3.5 ± 0.8 and the ALSFRS-R5a score was 3.6 ± 0.5. Eleven patients were classified with bulbar onset ALS, 10 with upper limb onset ALS, and four with lower limb onset ALS. The clinical and neuropsychological characteristics of patients are summarized in Table
Patient characteristics and the results of neuropsychological assessments.
Patient |
Age |
Gender | handedness | Subtype | Disease duration (months) | ALS FRS-R1 |
ALS FRS-R5a score | HDS-R |
STA achieved |
FAB |
RCPM |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 53 | F | R | Spinal (u) | 41 | 3 | 4 | 30 | IV | 18 | 30 |
2 | 79 | F | R | Spinal (l) | 6 | 3 | 3 | 29 | IV | 16 | 27 |
3 | 61 | M | R | Spinal (u) | 24 | 4 | 3 | 30 | IV | 17 | 35 |
4 | 59 | M | R | Spinal (l) | 59 | 4 | 3 | 30 | IV | 18 | 32 |
5 | 48 | M | R | Spinal (u) | 32 | 4 | 3 | 30 | IV | 17 | 32 |
6 | 50 | M | R | Spinal (l) | 9 | 4 | 4 | 30 | IV | 18 | 33 |
7 | 74 | F | R | Spinal (u) | 21 | 3 | 3 | 29 | IV | 16 | 27 |
8 | 73 | M | R | Spinal (u) | 24 | 4 | 3 | 29 | III | 18 | 30 |
9 | 74 | M | R | Bulbar | 18 | 4 | 4 | 22 | III | 16 | 30 |
10 | 74 | M | R | Spinal (l) | 12 | 4 | 4 | 28 | III | 16 | 34 |
11 | 74 | M | R | Bulbar | 10 | 4 | 4 | 28 | III | 17 | 34 |
12 | 68 | M | R | Bulbar | 14 | 4 | 3 | 28 | III | 17 | 30 |
13 | 59 | M | R | Spinal (u) | 33 | 4 | 3 | 30 | III | 16 | 36 |
14 | 71 | M | R | Bulbar | 9 | 4 | 4 | 30 | III | 17 | 29 |
15 | 71 | M | R | Bulbar | 61 | 2 | 4 | 27 | III | 16 | 34 |
16 | 73 | F | L | Bulbar | 20 | 2 | 4 | 29 | III | 14 | 31 |
17 | 75 | F | R | Bulbar | 26 | 3 | 4 | 29 | II | 11 | 25 |
18 | 63 | F | R | Bulbar | 46 | 4 | 3 | 23 | III | 13 | 26 |
19 | 72 | M | R | Bulbar | 10 | 2 | 4 | 30 | II | 11 | 25 |
20 | 68 | F | R | Spinal (u) | 10 | 4 | 4 | 25 | III | 13 | 24 |
21 | 59 | F | R | Spinal (u) | 11 | 4 | 4 | 25 | II | 12 | 18 |
22 | 75 | F | R | Spinal (u) | 13 | 4 | 3 | 26 | I | 11 | 24 |
23 | 82 | M | R | Bulbar | 41 | 3 | 4 | 22 | III | 12 | 24 |
24 | 73 | M | R | Bulbar | 28 | 2 | 4 | 23 | I | 8 | 23 |
25 | 69 | M | R | Spinal (u) | 20 | 4 | 4 | 21 | I | 5 | 14 |
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Average | 67.9 | 23.9 | 3.5 | 3.6 | 27.3 | 14.4 | 28.2 | ||||
SD | 9.0 |
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15.5 | 0.8 | 0.5 | 3.0 |
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3.5 | 5.4 |
ALS FRS-R: revised amyotrophic lateral sclerosis functional rating scale; HDS-R: Hasegawa Dementia Scale-revised; STA: Syntax Test for Aphasia; FAB: Frontal Assessment Battery; RCPM: Raven’s Coloured Progressive Matrices; R: right; L: left; (u): upper limb; (l): lower limb.
Eighteen out of the 25 patients (72%) failed to complete all four levels of the STA auditory comprehension task (score < IV; Table
Patients were divided into four groups (Table
The distribution of patients according to the initial symptoms and the results of STA, FAB, and RCPM.
Group | Initial symptoms | ||
---|---|---|---|
Upper limb | Lower limb | Bulbar | |
A (STA+, FAB+, RCPM+) | 4 | 3 | 0 |
B (STA−, FAB+, RCPM+) | 2 | 1 | 6 |
C (STA−, FAB−, RCPM+) | 0 | 0 | 3 |
D (STA−, FAB−, RCPM−) | 4 | 0 | 2 |
STA: Syntax Test for Aphasia; FAB: Frontal Assessment Battery; RCPM: Raven’s Coloured Progressive Matrices; +: pass, −: failure.
The scores on the STA auditory comprehension task, the FAB, and the RCPM were not correlated with age, disease duration, ALSFRS-R1 score, or ALSFRS-R5a score (Table
Correlation between demographic variables and results of STA, FAB, and RCPM.
Pearson’s correlation | |
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Age | |
STA score | −0.390 |
FAB score | −0.311 |
RCPM score | −0.258 |
Disease duration | |
STA score | 0.199 |
FAB score | 0.123 |
RCPM score | 0.210 |
ALSFRS-R1 score | |
STA score | 0.168 |
FAB score | 0.258 |
RCPM score | 0.087 |
ALSFRS-R5a score | |
STA score | −0.332 |
FAB score | −0.348 |
RCPM score | −0.251 |
ALS FRS-R: revised amyotrophic lateral sclerosis functional rating scale; STA: Syntax Test for Aphasia; FAB: Frontal Assessment Battery; RCPM: Raven’s Coloured Progressive Matrices.
Spearman rank correlation coefficient among neuropsychological assessments.
rs |
| |
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STA score | ||
FAB score | 0.791 | <0.05 |
RCPM score | 0.600 | <0.05 |
HDS-R score | 0.574 | <0.05 |
FAB score | ||
RCPM score | 0.734 | <0.05 |
HDS-R score | 0.637 | <0.05 |
RCPM score | ||
HDS-R score | 0.565 | n.s. |
STA: Syntax Test for Aphasia; FAB: Frontal Assessment Battery; RCPM: Raven’s Coloured Progressive Matrices; HDS-R: Hasegawa Dementia Scale-revised; n.s.: not significant.
Patient 7 passed all four levels of the STA auditory comprehension task and passed the FAB, the RCPM, and the HDS-R (Group A). IMP-SPECT revealed that she had mildly reduced r-CBF in the bilateral frontal lobes. Patient 22 passed the HDS-R but failed the STA auditory comprehension task, the FAB, and the RCPM (Group D) and had moderately reduced r-CBF in the bilateral frontotemporal lobes (Figure
3D-SSP Analysis. Case A. IMP-SPECT images revealed mildly reduced r-CBF in the bilateral frontal lobes of patient 7, who was within normal limits at all of three tests. Case B. IMP-SPECT images revealed moderately reduced r-CBF in the bilateral frontotemporal lobes of patient 22, who failed all three tests.
The majority (72.0%) of ALS patients tested in this study had syntactic comprehension disorder, which is one of the linguistic characteristics of ALS with aphasic symptoms [
Previous reports of the frequency of syntactic comprehension disorders in amyotrophic lateral sclerosis and motor neuron disease.
Study | Tests | Frequency |
---|---|---|
Doran et al. (1995) [ |
The test of the reception of grammar (TROG) and the shortened version of the token test | 3/5 (60.0%) |
Rakowicz and Hodges (1998) [ |
The test of the reception of grammar (TROG) | 5/18 (27.8%) |
Cobble (1998) [ |
The test of auditory comprehension of sentences (PALPA) | 5/9 (55.6%) |
Bak et al. (2001) [ |
The test of the reception of grammar (TROG) | 5/6 (83.3%) |
Taylor et al. (2013) [ |
The test of the reception of grammar (TROG) | 18/51 (35.3%) |
Current results | Syntax test for aphasia (STA) | 18/25 (72.0%) |
The syntax test used in this study evaluated the strategy level (use of word meaning, word order, or particle) of syntactic comprehension [
Bak et al. [
Neuropsychological and neuroimaging studies have reported that Broca’s area (left inferior frontal gyrus, Brodmann’s areas 44 and 45) is involved in the processing of sentence structure [
Broca’s area is adjacent to the lower precentral gyrus, which is the motor center for the face, lips, tongue, and pharynx. Therefore, we propose that, in patients with bulbar onset ALS, neurodegeneration may have progressed from the medulla oblongata and pons to the precentral gyrus and inferior frontal gyrus. Six of 10 (60.0%) patients with upper limb onset ALS had syntactic comprehension disorder, and 1 of 4 (25.0%) patients with lower limb onset ALS had syntactic comprehension disorder (Table
Taylor et al. [
Ichikawa et al. [
In this study we investigated the prevalence and profile of syntactic comprehension in ALS and the relation of syntactic comprehension with executive and visuospatial function. There was a high prevalence of syntactic comprehension disorder, especially in patents with bulbar onset ALS. These results raise the possibility that neurodegeneration in ALS may sequentially progress from Broca’s area to the prefrontal lobe and occipital lobe.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors would like to acknowledge all the patients who kindly agreed to participate in this study.