In this study, the significant improvement on language and cognitive function over continuous 16 weeks period could been observed in both SLT group and Memantine group. It is notable that after 8 to 12 weeks of treatment, the WAB-AQ scores increased more significantly in Memantine group, that represented the speech and recognition improvement in PSA patients. Memantine combined with SLT is an effective method in post-stroke aphasia.
The manifestations of aphasia is closely related to the location of ischemia or hemorrhage damage and the dominant hemisphere. From the pathophysiological mechanism, due to ischemia and hypoxia in the local brain tissue after ischemia and hemorrhage, edema, a large number of harmful substances are produced, such as free radicals and excitatory amino acids that was the primary mechanism for neuron death. The FDA approved memantine in 2003 for its use in moderate to severe Alzheimer’s disease. In the treatment of Alzheimer's disease in recent years, it has shown a relatively good effect, memantine can enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons caused by excitatory neurotransmitters [15]. Not only that, memantine hydrochloride has also shown good curative effects in basic studies of stroke animal models [16] [17].In stroke studies, memantine has been proven to provide post-ischemic neuroprotection via multiple mechanisms, including inhibition of apoptosis [18], NMDA inhibition mediated excitotoxicity [19], preserving intracellular ATP stores [18], and increasing tissue concentration of neuron-specific growth factors [20].
The main performance of aphasia is difficulty in comprehension and expression, their abilities of communicating are limited, which decrease the effectiveness of rehabilitation training. Aphasia examination mainly includes six basic aspects: oral comprehension, spontaneous language expression, repeating, naming, reading, and writing. For many years an effort has been made to target language therapy techniques that help the recovery of patients with aphasia [21]. Treatment guidelines for aphasia recommend intensive speech and language therapy for aphasia after stroke [22][23],but also with neuromodulation technology combined with speech therapy, Repetitive Transcranial Magnetic Stimulation(rTMS) and transcranial Direct Current Stimulation(tDCS) [24] [25] [26] [27] [28]. Drug treatment of large-scale, class 1 randomized controlled trials specifically for aphasia after stroke are scarce. In this study, we investigated the effects of SLT, memantine combined with SLT in patients with subacute PSA. The results showed that the mean WAB-AQ increased from visit 1 to visit 4, indicating both methods can improve overall language function after 4–16 weeks. But the improvement is more significant in Memantine group at week 8 to week 16. The effect of memantine was still continued during medicine washout period. The results of WAB-AQ subitem analysis showed that compared with SLT group, significant improvement in auditory comprehension-AQ at visit 1, auditory comprehension-AQ and spontaneous speech-AQ at visit 2,3,4 was observed in Memantine group. In the four follow-ups, the increase in MMSE scores was more obvious in the Memantine group, and there was a statistical difference compared with the control group at the second and third follow-up. We considered that there was no difference between groups in WAB-AQ at week 4 because the effect of memantine on aphasia recovery during a 3-week up-titration phase was unstable. These findings suggest that memantine combined with intensive speech and language therapy have a positive effect on the recovery of aphasia after subacute stroke, especially after eight weeks of continuous treatment.
Studies on stroke at different stages have shown controversial effects of drug therapy. In acute stroke studies, a case series study has shown that intravenous thrombolysis or endovascular therapy result in improvement of acute aphasia recovery[29]. A study consisted of 33 subacute stroke patients suggests that speech and language therapy, 30–60 minutes per day, 2 days a week, for 8 successive weeks, are effective in the treatment of subacute-stroke aphasic [30]. In chronic phase of stroke recovery, no study has provided evidence that pharmaceutical intervention results in significant improvement in chronic post-stroke aphasia in the absence of SLT [31]. However, several trials have provided primary evidence that some medications may augment the effects of speech therapy. A plausible mechanism is that language recovery depends on neuroplasticity. Medications that alter the availability of neurotransmitters could enhance neuroplasticity [32].In a study of 27 patients with chronic post-stroke aphasia, constraint-induced aphasia therapy was beneficial when used combined with memantine 10 mg twice daily [33]. Meanwhile, no insufficient evidence to recommend an optimal dosage that would result in maximum treatment outcome. [34]. In this RCT study, SLT was performed 30min/each time, once/day, 5 times/week, totally 12 weeks, combined with memantine, post-stroke aphasia would improve significantly at the treatment beginning of 4 weeks compared with baseline and showed differences between groups at week 8 and week 12, lasted to the drug washout period, providing strong evidence on aphasia recovery after stroke.
The shortcoming of this study is that this study is a single-center study. In the future, a larger multi-center study is needed to confirm its mechanism to help stroke patients recover their language function.