# Abstract

 

## Background Aphasia affects one third of acute stroke patients. There is a considerable spontaneous recovery in aphasia, but impaired communication ability remains a great problem. Communication difficulties are an impediment to rehabilitation. Early treatment of the language deficits leading to increased communication ability would improve rehabilitation. The aim of this study is to elucidate the efficacy of very early speech and language therapy (SLT) in acute stroke patients with aphasia. 

## Methods A prospective, open, randomized, controlled trial was carried out with blinded endpoint evaluation of SLT, starting within 2 days of stroke onset and lasting for 21 days. 123 consecutive patients with acute, first-ever ischemic stroke and aphasia were randomized. The SLT treatment was Language Enrichment Therapy, and the aphasia tests used were the Norsk grunntest for afasi (NGA) and the Amsterdam-Nijmegen everyday language test (ANELT), both performed by speech pathologists, blinded for randomization. 

## Results The primary outcome, as measured by ANELT at day 21, was 1.3 in the actively treated patient group and 1.2 among controls. NGA led to similar results in both groups. Patients with a higher level of education (>12 years) improved more on ANELT by day 21 than those with \<12 years of education (3.4 vs. 1.0, respectively). In 34 patients in the treatment group and 19 in the control group improvement was ≥1 on ANELT (p < 0.05). There was no difference in the degree of aphasia at baseline except for fluency, which was higher in the group responding to treatment. 

## Conclusions Very early intensive SLT with the Language Enrichment Therapy program over 21 days had no effect on the degree of aphasia in unselected acute aphasic stroke patients. In aphasic patients with more fluency, SLT resulted in a significant improvement as compared to controls. A higher educational level of >12 years was beneficial. # Results 

## General Results We randomized 123 aphasic patients of which 114 (93%) completed the study and could be tested on day 21 (fig. [1](#)). Follow-up at 6 months could be performed in 99 patients (80%). There were no significant differences in baseline characteristics between the study groups, except for a history of myocardial infarction, which was more frequent in the intervention group (table [1](#)). At the follow-up at 6 months, 5 patients in the intervention group and 6 in the control group had died. Five patients in each group had recurrent stroke. All recurrent strokes occurred beyond the 3 weeks of intervention. 

## Primary and Secondary Outcomes The primary outcome in the whole group as measured by ANELT by day 21 was 1.3 among the SLT-treated patients and 1.2 among the controls (table [2](#)). The Diff Coeff was 8.5 in the SLT group and 9 in the control group. Also, per protocol analyses of ANELT by day 21 and for Diff Coeff revealed no statistical difference between the two study groups (table [2](#)). Patients with a higher level of education (>12 years) improved more in ANELT by day 21 than those with \<12 years of education [3.4 (1.0--4.8) vs. 1.0 (1.0--2.7); p < 0.01]. Diff Coeff improved more in patients with >12 years of education than in those with \<12 years of education [13 (8--26) vs. 8 (1--16); p < 0.01]. Higher values of ANELT, Coeff, fluency, and comprehension at baseline had a positive effect on ANELT by day 21 (p < 0.01), while worse neurological performance as indicated by higher NIHSS values at baseline and longer delay to inclusion had a negative effect on ANELT by day 21 (p < 0.01) and on Diff Coeff (p < 0.05). A multivariate analysis including baseline ANELT, Coeff, fluency, and NIHSS at baseline, as well as age, gender, delay to inclusion, intervention group, and level of education, confirmed that initial ANELT and length of education had an independent, significant impact on the primary outcome (i.e. ANELT by day 21). For secondary outcome (i.e. Diff Coeff), the impact of the initial NIHSS and educational level were significant. The types of aphasia are shown in figure [2](#). There were no differences in aphasia types between the two groups. Only 9 patients had a fluent type of aphasia at baseline, and there were no differences in fluent/non-fluent types of aphasia between the two groups. Best outcome according to ANELT at 3 weeks was seen in transcortical sensory aphasia, followed by isolation, conduction, and Wernicke type of aphasia. Patients with global aphasia had the poorest outcome. 

## Follow-Up at 6 Months At 6 months, ANELT and Coeff were similar in the two study groups (table [2](#)). The number of non-study SLT sessions after day 21 was 15 (4--38) in the treatment group and 10 (5--20) in the control group (p = 0.3). ANELT at 6 months of follow-up was 4.5 (1.9--5.0) among those with an education of >12 years and 1.5 (1.0--3.6) among those with less education (p < 0.01). For Coeff at 6 months, the corresponding results were 57 (39--59) and 39 (17--55) (p < 0.01). 

## Subgroup Analyses, Responders versus Non-Responders These analyses were performed post hoc. Results in the 53 aphasic stroke patients who improved ≥1 on ANELT (i.e. an improvement which was predetermined to be clinically relevant; responders) are presented in table [3](#). The 34 responders in the SLT treatment group were compared to those 25 patients who improved \<1 on ANELT (non-responders). NIHSS at baseline was lower in the responder group than in the non-responder group [5 (2--12) vs. 11 (7--20); p < 0.01]. Aphasia tests showed no difference at baseline except for fluency, which was 37 (30--64) words/min in the responder group and 8 (1.5--30) words/min in the non-responder group (p < 0.001). There were no differences in types of aphasia. The responders improved in all three parts of the NGA (comprehension, naming, and repetition), as compared to the non-responders (all p < 0.01). At 6 months of follow-up, a difference in ANELT remained between responders and non-responders [2.7 (1.2--4.9) vs. 1.1 (0.8--1.6); p < 0.01]. Among those with a fluency of >30 words/min (n = 51), more patients improved >1 on ANELT in the intervention group than among controls (18 vs. 6 patients; p < 0.05). ::::table-wrap

::: caption
Primary and secondary outcomes
:::

```
                                                                         Training group   Control group   p value
```

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Primary outcomes\
ANELT by day 21, intention-to-treat, n 59 55\
Median 1.3 (1--4.1) 1.2 (0--3.6) 0.37
ANELT by day 21, per protocol, n 54 49\
Median 1.5 (1--4.1) 1.0 (0--3.6) 0.16
Secondary outcomes\
Difference in coefficient at baseline and day 21, intention-to-treat, n 58 56\
Median 8.5 (1--17) 9 (3.3--16.8) 0.86
Difference in coefficient at baseline and day 21, per protocol, n 53 48\
Median 9 (1.5--17.5) 8.5 (2.3--16) 0.62
Follow-up at 6 months\
ANELT, n 50 49\
Median 1.8 (1--4.6) 3 (1--4.6) 0.49
Coefficient, n 50 49\
Median 40 (25--57) 49 (17--58) 0.62

Data are presented as median values and quartiles.:::: ::::table-wrap
::: caption
Effects of SLT at day 21 according to ANELT
:::

```
                                    SLT group (n=59)    Control group (n=55)   P
```

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Patients with a difference in ANELT\
≥1 from baseline to day 21 34 responders 19 \<0.01
\<1 from baseline to day 21 25 non-responders 36::::


Extracted trial result:
Outcome: improvment in ANELT by day 21 (continuous)
Intervention: higher level of education (>12 years)
Comparator: <12 years of education
Notes: Median is reported. Group sizes are only available in methods section.