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Piracetam Treatment of Aphasia1
Running head: Piracetam Treatment of Aphasia
Piracetam Treatment of Aphasia of
Acute Stroke Victims
Eden M. Treadway
East Tennessee State University
Piracetam Treatment of Aphasia2
Abstract
Piracetam is a new drug that has been said to potentially improve speech in poststroke
aphasic patients. This paper reviews a study of Piracetam treatment of aphasia compared
to placebo. Several tests were utilized in order to measure language function, including
the Aachen Aphasia Test, Activities of Daily Living (ADL) rating scales (Barthel index,
Kuriansky Performance Test), and the Rivermead Perceptual Assessment Battery
(RPAB). Patients received either 4.8 g/day or placebo for 12 weeks. An improvement
was made in all five subtests of the AAT and an overall significant improvement in
aphasia. Increased cerebral blood flow was also found in three areas of the left
hemisphere (Heschl’s gyrus, Wernicke’s region, and Broca’s area) in the Piracetam group
compared to increased blood flow in only the left inferior precentral gyrus in placebo.
This study indicates that, in conjunction with speech therapy, Piracetam improves aphasia
of acute stroke victims.
Piracetam Treatment of Aphasia3
Introduction
According to a 2002 stroke testimony article by the National Institute of
Neurological Disorders and Stroke, "more than 600,000 people experience a stroke each
year." It also states that "of the more than four million stroke survivors alive today, many
experience permanent impairments of their ability to move, think, understand and use
language, or speak - losses that compromise their independence and quality of life.”
As the Baby Boomer generation ages, and because the possibility of stroke
increases with age, the likelihood of an enormous percentage of Americans suffering
from strokes continues to increase. A person may experience many possible neurological
problems after a stroke, one of the most common being aphasia (Greener, 2007).
Aphasia may be described as a "linguistic impairment associated with a brain
lesion" (Greener, 2007). Speech and language therapy remains the primary treatment of
aphasia following a stroke (Bakheit et al., 2007). However, "a number of drugs have been
utilized with the aim of ameliorating [poststroke] language functions" (Greener, 2007).
The drug demonstrating the most positive potential for such action is known as
Piracetam, a novelty drug discovered in the 1960's. Since its discovery, the importance of
Piracetam treatment specifically for stroke patients with aphasia has become a
concentrated area of research. Piracetam has since been used to treat many physical
disabilities, including poststroke aphasia, and recent studies have shown that Piracetam
may increase rehabilitation of aphasic patients. It has been shown to “improves higher
cerebral integrative functions,” such as learning and memory (Guirgea, 1976).
The means by which Piracetam performs such tasks is still uncertain, although
some researchers hypothesize that it increases cerebral blood flow (Kessler et al., 2000).
Piracetam Treatment of Aphasia4
Greener (2007) states "the role of pharmacotherapy is uncertain." Therefore, the goal of
this study is to assist in lessening this uncertainty.
.
Problem Statement
In this study I aim to prove that administering a specific type of pharmacotherapy
known as Piracetam as treatment of aphasia of acute stroke victims enhances recovery of
various language functions. Nearly everyone has been or will be affected by someone
they know and/or love dearly experiencing a stroke, and it is my assumption that
everyone wants the best, most proactive treatment for their loved ones.
Review of Literature
Recent studies regarding treatment of aphasic patients following stroke have
shown improvement when utilizing a nootropic drug known as Piracetam. Speech and
language therapy is currently the most common treatment of such disorder. However,
many pharmacological treatments have been tested, the most effective so far being
Piracetam (Greener, Enderby, Whurr, 2001, p. 8). According to Vernon (1991), this drug,
also known as UCB-6215, 2-oxo-pyrrolidone, or 2-oxo-1-pyrrolidone acetamide, was
first investigated in the 1960’s. Vernon also explains that the term “nootropic” was
coined by C.E. Guirgea from the Greek terms “noos” (mind) and “tropos” (turn towards).
Piracetam has since been noted to treat many disorders including, but not limited to,
schizophrenia, depression, congestive heart failure, arrhythmia, motion sickness, and
cerebral palsy (Vernon, 1991).
This particular study, however, focuses on Piracetam as treatment of all kinds of
aphasia following acute stroke. Aphasia, according to Greener et al. (2001), “describes
Piracetam Treatment of Aphasia5
linguistic impairment associated with a brain lesion.” Bakheit et al. (2007) further
explained that aphasia is “one of the most common neurological symptoms after stroke”
and that it “affects one-third of stroke survivors and usually has a poor prognosis.” They
continued to explain the severity of aphasia and its “significant negative impact on the
patient’s well-being, independence, social participation, and quality of life.”
Although many studies have been completed, the question of “whether the
efficacy of rehabilitative measures can be enhanced by adjuvant pharmacotherapy in
patients with cerebral disorders is still controversial” (Kessler, Thiel, Karbe, Heiss,
2000). Greener et al. (2001) concurred in stating that “role of pharmacotherapy is
uncertain.” However, recent studies have proposed that Piracetam has positive results on
mental and motor function in poststroke patients. The drug “affects various mental
functions” (Guirgea) and has been reported to increase cerebral blood flow and improve
overall clinical outcome (De Deyn, Reuck, Deberdt, Vlietinck, Orgogozo, 1997, p. 2348).
It has also been revealed that Piracetam improves learning and memory following a
stroke (Enderby, Broeckx, Hospers, Schildermans, Deberdt, 1994). Kessler et al. (2000)
explained that regions outside the specific damaged area of the brain that take over
language functions lost in stroke are heavily relied upon during recovery from aphasia
because the infracted tissue cannot rejuvenate. However, the exact means by which
Piracetam improves recovery from aphasia remains uncertain (Orgogozo, 1998).
Nevertheless, in conjunction with speech-language therapy Piracetam has shown positive
potential for improving poststroke aphasia (Huber, Willmes, Poeck, van Vleymen,
Deberdt, 1997).
There are multiple tests and scales that are useful in measuring language functions
Piracetam Treatment of Aphasia6
after stroke may be measured. Enderby et al. (1994) explained that many studies utilize
the Aachen Aphasia Test (AAT), “a psychometrically validated assessment developed
using linguistic principles, allowing the detail of language breakdown to be described.” In
a study conducted by W. Huber (1999), the AAT was used as a “validated and
standardized procedure to assess language function.” The AAT is used to assess mainly
language function and incorporates six rating scales for impulsive speech. These include
communicative verbal behavior, articulation and prosody, automated language, semantic
structure, phonemic structure, and syntactic structure. The AAT also includes five
subtests for the evaluation of precise language destruction including repetition, written
language, naming on confrontation, comprehension, and Token test (Enderby et al.,
1994).
Also, The Orgogozo scale was created for “clinical trial evaluation of middle
cerebral artery strokes” (Orgogozo, 1998). It measures 10 items including: vigilance,
verbal communication, elevation of the arm, finger and thumb movements, arm tone,
deviation of head and eyes, facial movements, elevation of the leg, dorsiflexion of the
foot, and leg tone. The Barthel Index has also been used to measure functional outcome
or “activities of daily living in the evaluation of a stroke” (Enderby et al., 1994). Some
studies use a combination of these three scales, as well as others, to assess functional
ability. Research studies show a positive correlation between Piracetam and higher scores
on these scales.
Greener et al. (2001) declare that Piracetam has been utilized in other
circumstances than treating aphasia such as improving reading ability and comprehension
in elderly patients with cognitive disorders. By reviewing the many uses for which
Piracetam Treatment of Aphasia7
Piracetam has been claimed one may see that overall it “improves higher cerebral
integrative functions, including those involved in cognitive processes such as learning
and memory” (Guirgea, 1976, p. 225). The precise mechanism by which Piracetam is
able to perform such a feat is uncertain, although some researchers have hypotheses that
involve increasing cerebral blood flow (Kessler et al., 2000) or “neuroprotective
properties mediated through effects on the cell membranes” (De Deyn et al., 1997). This
study focuses on the use of Piracetam to treat all kinds of aphasia including expressive
aphasia, receptive aphasia, global aphasia, mixed aphasia, dysphasia, and non-specific
aphasia (Greener et al., 2001, p. 3). While some researchers remain unsure and perplexed,
studies testing Piracetam regarding its use to treat poststroke aphasia have shown
positive, successful results. The goal of this study is to assist in becoming more certain of
these findings.
Methods
Piracetam and placebo were compared in a randomized, double-blind, placebocontrolled study. The subjects of this study were chosen from three local hospitals
including Johnson City Medical Center, Sycamore Shoals hospital, and Holston Valley
Medical Center.
This study adhered to all HIPPA guidelines in order to protect participant
confidentiality. All participants or their immediate relatives gave informed consent to
participate in the study. After presenting my method and Scales of Measurement the
ETSU VA IRB this study was approved, and it was concluded that it did not
unnecessarily expose the patients used at any risk or include any pervasive methods.
They also found that I discussed both benefits and risks of the study to the
Piracetam Treatment of Aphasia8
patients, that I informed them of the criteria for which I used to choose my patients for
the study, and that I would provide privacy to all patients involved.
A total of 137 patients were included in the study (within 14 days of a stroke) all
having suffered from acute aphasia of various types after stroke of the left hemisphere.
All patients were native speakers between 21 and 75 years of age. Patients had to have a
clinical deficit affecting motor, language, or perceptual functions and also be appropriate
for rehabilitative therapy (Enderby et al, 1994). Severity of aphasia had to be mild to
moderate and was measured with the Token Test (Kessler, 2000). Exclusion from the
study was permitted due to hearing or sight disturbances, neurodegenerative disorders,
medications that might interfere with cerebral function, a history of organic cerebral
disease, or a psychiatric disorder within the previous five years. Of the 137 patients, 70
received placebo while 67 patients received Piracetam treatment. Patients received either
Piracetam 4.8 g/day or placebo for a total of 12 weeks. Piracetam was given in a dosage
of 12 ml twice daily as a 20% solution while the placebo solution was identical in taste,
smell, and appearance (Enderby et al, 1994). The limits for the evaluation of efficacy
were total scores from several tests including Activities of Daily Living (ADL) rating
scales (Barthel index, Kuriansky Performance Test), the Aachan Aphasia Test (AAT),
and the Rivermead Perceptual Assessment Battery (RPAB). Patients were tested at the
beginning of the trial, during (week 5), and the end (week 12). The RPAB and AAT were
given only during week 12. Also, whenever possible, follow-up testing was performed 12
weeks following the end of the study. Language therapy, occupational therapy, and
physiotherapy were identical for all patients. (Kessler, 2000). This was nonparametric,
ordinal data that measured a difference in two related groups. Language tests were
Piracetam Treatment of Aphasia9
performed separately on the experimental and control groups both before and after the 12
week trial with Piracetam. The Wilcoxon signed ranked test was then used to determine
the significance of the difference between pre-test and post-test scores for individuals.
Results/Discussion
Both placebo and Piracetam groups were comparison in age: Piracetam group
was mean age 57.41 (SD 13.53) years and placebo group 56.33 (SD 9.95) years. Initial
aphasia severity (from the Token test) was mean 17.16 (SD 14.31) errors in the Piracetam
group and 17.91 (SD 15. 47) errors for placebo. Infarct location and volume were similar
in both groups, as well as the number of days after stroke which treatment began
(Piracetam- 7.8 days, placebo- 8.2 days).
In the Piracetam-treated group (n=67), cerebral blood flow increased in several
left hemisphere regions during the treatment period including Heschl’s gyrus, Wernicke’s
region, and Broca’s area and also reached significant levels (P<.05). However, in the
placebo group (n=70), increased blood flow was found only in left inferior precentral
gyrus. Neither group showed development in regions of the right hemisphere.
The Piracetam group showed improvement in five subtests of the AAT.
Piracetam Treatment of Aphasia10
Conclusion
The role of pharmacotherapy in poststroke aphasia is a popularly growing area of
research. Piracetam is a drug that has been said to treat or at least improve many cerebral,
learning, and memory malfunctions. However, the precise mechanism by which
Piracetam supports the beneficial effect of speech therapy and the relationship of this
effect to increased blood-flow remains unclear (Kessler, 2000). Nevertheless, the results
of this study show that there is a positive correlation between poststroke aphasic patients
treated with Piracetam within one week of stroke. This study supports previous results
that, if treated soon enough under the proper conditions, Piracetam may help a aphasic
patients regain some lost language functioning skills.
Piracetam Treatment of Aphasia11
References
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(2007). A prospective, randomized, parallel group, controlled study of the effect of
intensity of speech and language therapy on early recovery from poststroke aphasia.
Clinical Rehabilitation, 21(10):885-894.
De Deyn, P.P., Reuck, J.D., Deberdt, W., Vlietinck, R., Orgogozo, J.M. (1997).
Treatment of acute ischemic stroke with piracetam. Stroke, 28(2):2347-52.
Enderby P., Broeckx, J., Hospers, W., Schildermans, F., Deberdt, W. (1994). Efficacy of
piracetam on recovery and rehabilitation after stroke: A double blind, placebocontrolled study. Clinical Neuropharmacology, 17(4):320-331.
Greener, J., Enderby, P., Whurr, R. (2001). Pharmacological treatment for aphasia
following stroke. Cochrane Database of Systematic Reviews, 4:1-10.
Giurgea, C.E. (1976). Piracetam: nootropic pharmacology of neurointegrative activity.
Current Developments in Psychopharmacology, 3:222-273.
Huber, W. (1999). The role of piracetam in the treatment of acute and chronic aphasia.
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Huber, W., Willmes, K., Poeck, K.W., van Vleymen, B,. Deberdt, W. (1997). Piracetam
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Piracetam Treatment of Aphasia12
Orgogozo, J.M. (1998). Piracetam in the treatment of acute stroke. CNS Drugs, 9(suppl
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Vernon, M.W., Sorkin, E.M. (1991). Piracetam—an overview of its pharmacological
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