Stroke Rehabilitation: The Medical Measures That Support Recovery
Stroke is one of the most common causes of death and disability worldwide. It is estimated that a new stroke occurs every 40 seconds in the United States [1]. Globally, approximately 16.9 million people experience a stroke each year. Of these, 5.9 million die, while survivors often remain disabled [2]. Patients who have experienced a stroke frequently develop speech and motor impairments. Speech disorders are identified in one-third of cases, while motor impairments affect up to 80 percent of patients [3, 4].
Rehabilitation procedures help reduce these impairments. However, even after completing a rehabilitation program, neurological deficits causing moderate to severe disability persist in 25–50 percent of patients [5]. Speech impairments are particularly difficult to correct and respond less effectively to interventions than motor deficits [6].
The effectiveness of rehabilitation may be enhanced by pharmacological interventions. Although studies in this field remain limited, several medications have shown potential benefits in neurorehabilitation.
Levodopa
The role of dopamine in the motor system has prompted research into the use of levodopa during rehabilitation. However, the results obtained so far have been conflicting.
Several studies have found that levodopa, administered at a dose of 100 mg/day, may support motor recovery. Positive effects on fine hand movement accuracy and gait have been observed [5, 7, 8]. However, the number of patients included in these studies was small, and many other studies did not confirm these findings [5, 7, 9].
One study found that levodopa may also be beneficial in correcting speech impairments. Patients who received the medication demonstrated improvements in speech fluency and repetition [7].
Levodopa was well tolerated in the studies. Therefore, the main obstacle to its use during rehabilitation remains the insufficient evidence and inconsistent study findings [5, 7].
Acetylcholinesterase Inhibitors (AChEIs)
Acetylcholinesterase inhibitors are used to treat the symptoms of Alzheimer’s disease. Their potential to improve speech impairments in patients after stroke has also been investigated.
Donepezil has been shown to improve scores on scales assessing the severity of aphasia. However, no significant difference was observed between patients receiving the medication and those receiving placebo when instruments evaluating spoken language in daily life were used [5, 10]. In addition, improvement in speech function was observed only while the medication was being taken and disappeared after treatment was discontinued [6].
A small study also found a positive effect of donepezil on sensorimotor function [10].
It is important to note that the medication was not well tolerated. Adverse effects occurred significantly more often in patients taking donepezil, affecting 61 percent of participants, compared with 23 percent of those receiving placebo [10].
Selective Serotonin Reuptake Inhibitors (SSRIs)
Fluoxetine at a dose of 20 mg/day and citalopram at a dose of 40 mg/day were used in individual studies to improve motor function.
According to the authors, these medications improved gait, performance of daily activities, and the accuracy of fine movements. Improvement in motor function correlated with increased activity in the cerebral cortex during functional magnetic resonance imaging studies [5, 7, 10].
SSRIs were well tolerated. However, it has been suggested that these medications may be associated with an increased risk of hemorrhagic stroke. Therefore, further studies are required to evaluate their safety [7].
Piracetam and Pramiracetam
Piracetam, or pyrrolidone acetamide, and similar medications, such as the piracetam derivative pramiracetam, are classified as nootropics.
Their precise mechanism of action remains unclear. However, because of their structural similarity to gamma-aminobutyric acid (GABA), they are believed to have GABAergic effects [11]. Pramiracetam has also been shown to exert an additional effect on the cholinergic system by increasing the activity of cholinergic neurons in the hippocampus [11].
Studies using brain cell cultures have shown that these medications have protective effects during ischemia. They reduce the extent of damage caused by hypoxia-reoxygenation and improve cell viability [12, 13].
Studies involving patients who had experienced a stroke found that piracetam, administered at doses of up to 4,800 mg/day, had a positive effect on the recovery of speech function. These findings were confirmed using objective neuroimaging methods. During positron emission tomography scans, patients receiving piracetam showed increased activity in the brain regions responsible for speech, including Broca’s and Wernicke’s areas [5, 10, 14].
Further studies suggested that piracetam use might be associated with increased mortality. However, this increase was not consistently statistically significant across all studies [10]. A Cochrane review noted that these findings may have been related not to the effect of the medication but to differences in the clinical condition of patients in the study groups. After the results were adjusted for stroke severity, increased mortality was no longer observed among patients receiving piracetam [15].
Despite the positive effects of piracetam on aphasia identified in clinical studies, its use in patients after stroke is limited by inconvenient administration. Because of its relatively weak effect and short duration of action, the medication must be taken frequently and at high doses. In all studies in which a positive effect on speech function was observed, the administered dose was 4,800 mg/day.
Pramiracetam is one of the most potent medications in this class. Because of its high bioavailability and longer duration of action, it can be administered at much lower doses than piracetam, at 600 mg twice daily, making it considerably more convenient to use [11]. In addition, pramiracetam is the only medication discussed in this article that is reimbursed in Lithuania for up to three months after a stroke. This makes it a well-tolerated, convenient, and accessible option for supporting pharmacological rehabilitation, particularly in patients with cognitive impairments.
Conclusions
Neurological deficits often persist after stroke, even following rehabilitation. Speech function is particularly difficult to restore and is more challenging to improve than motor impairment [14]. Because aphasia is associated with higher rates of depression and mortality, as well as poorer quality of life, efforts are being made to identify pharmacological interventions that may improve the recovery of speech function after stroke [6].
At present, evidence supporting pharmacological neurorehabilitation remains limited. Nevertheless, studies of certain medications have produced promising results, and further research may allow these treatments to be incorporated into routine clinical practice.
NERVOUS AND MENTAL DISORDERS
Dr. Eglė Audronytė
Vilnius University Hospital Santaros Klinikos, Clinic of Neurology and Neurosurgery
2015 No. 1 (68)
Reg. No. LT/Pra/2015/01
