(Stroke. 2000;31:2112.)
© 2000 American Heart Association, Inc.
Original Contribution |
Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients
From Max-Planck-Institute for Neurological Research (J.K., A.T., W.D.H.) and University Clinic of Neurology (H.K., W.D.H.), Cologne, Germany.
Correspondence to Prof Dr J. Kessler, Max-Planck-Institut für neurologische Forschung, Gleueler Str 50, D-50931 Köln, Germany. E-mail josef.kessler{at}pet.mpin-koeln.mpg.de
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Abstract |
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Background and Purpose—In a prospective, double-blind, placebo-controlled study, it was investigated whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and activation PET measurement of cerebral blood flow.
Methods—Twenty-four stroke patients with aphasia were randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were examined neuropsychologically and studied with H215O PET at rest and during activation with a word-repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface views from MRI coregistered to the PET images.
Results—Before treatment, both groups were comparable with respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of activation effect was significantly higher (P<0.05) in the left transverse temporal gyrus, left triangular part of inferior frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests.
Conclusions—Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and this effect is accompanied by a significant increase of task-related flow activation in eloquent areas of the left hemisphere.
Key Words: aphasia • piracetam • recovery of function • tomography, emission computed
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Whether the efficacy of rehabilitative measures can be enhanced by adjuvant pharmacotherapy in patients with cerebral disorders is still controversial. Trials relevant to this question were started in the 1940s and applied various agents in different neurological disorders. Early on, this strategy was targeted to language impairment, especially poststroke aphasia, but normally only single cases or small numbers of patients were reported. Positive effects observed in a few cases with various drugs acting by diverging mechanisms1 2 3 4 5 could usually not be replicated in large clinical trials.6 7 Piracetam, a
-aminobutyric acid
derivative with a potential effect on cognitive and mnestic
functions,8 was repeatedly used in the treatment of
aphasia: In small placebo-controlled trials, 4.8 g piracetam daily
over 6 to 12 weeks improved the performance in subtests of the
Aachen Aphasia Test,9 10 11 but the mechanism by which
piracetam enhances recovery from aphasia remained a matter of
speculation. Because infarcted tissue cannot regenerate, recovery from
poststroke aphasia must involve regions outside the morphologically
damaged area that regain or take over language functions lost in acute
stroke. It was repeatedly demonstrated that functional imaging
modalities can follow the improvement of neurological deficits in
changes of task-related activation patterns of flow or
metabolism in the course after stroke.12 13 14 15
The aim of this placebo-controlled double-blind study was to test the
effect of piracetam as an adjuvant to speech therapy on 2
levels—performance in aphasia tests and task-related flow
activation in eloquent brain regions—in a small group of patients with
poststroke aphasia. |
Subjects and Methods |
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Twenty-four right-handed patients (13 men, 11 women) were enrolled in the study. All patients suffered from acute aphasia of various types after ischemic stroke of the left hemisphere. All patients were native speakers, between the ages of 18 and 75 years, and without any cognitive or mnestic deficits before stroke. Diagnosis was based on neurological and medical examination, laboratory tests, EEG, Doppler ultrasonography of extracranial and large intracranial vessels, and CT early after stroke and MRI in the later course. Patients with previous ischemic events were excluded. Aphasia severity had to be mild to moderate and was measured with the Token test.16 To ensure sufficient performance of the word-repetition task during PET measurement, the patients had to reach a score of >50 of 150. Within 14 days after stroke, the patients were included in the study. Further exclusion criteria were clinically relevant hearing or sight disturbances, neurodegenerative disorders, psychiatric disease, drug-induced dementia, epilepsy, renal insufficiency, and treatment with other nootropics or with blood-flow-supporting medication before baseline testing. The patients were expected to have led an independent life before stroke event. At runtime of the study, we presupposed exclusion of patients in case of a suspect adverse reaction, a subsequent stroke, illicit drug taking, or by personal request.
The study protocol was approved by the ethics committee of the university and was performed according to European Guidelines for Good Clinical Practice. All patients or their close relatives gave informed consent.
Study Design
The study was prospective, randomized, double blind, and placebo
controlled. Patients received either piracetam 2x2400 mg/d or placebo
for 6 weeks. The regular administration of the drug/placebo was
supervised by drug counting. The randomization list was generated by a
software based on the uniform pseudo variates generated by the
"RANUNI" function (SAS Inc). The list was built by using blocks of
4. Treatment usually started 2 weeks after stroke. PET measurement
(during a word-repetition task) and language and
neuropsychological testing were usually done 2 to 3 days before. The
same procedures were repeated 8 weeks after the acute stroke. Treatment
together with extensive language therapy, occupational therapy, and
physiotherapy was identical for all patients. Speech therapy was
performed 5 times a week for 60 minutes, so that all patients had
received 30 sessions of language therapy at the end of treatment.
Neuropsychological Test Battery
The test battery included the following tests: a verbal fluency
task with the letters F, A, and S (1 minute for each
letter),17 Corsi’s block span test,18 a
modified laterally score after Oldfield,19 tests for
apraxia,20 progressive matrices of Raven,21
and the Benton test.22
For language testing the Aachen Aphasia Test was used,16 which consists of 6 rating scales for spontaneous speech (communicative verbal behavior, articulation and prosody, automated language, semantic structure, phonemic structure, and syntactic structure) and 5 subtests for the assessment of specific language impairments (repetition, written language, naming on confrontation, comprehension, and Token test).
Image Data Acquisition
PET studies were performed on a CTI/Siemens ECAT EXACT HR
scanner in 3-dimensional mode.23 Data acquisition started
with intravenous bolus injection of 370 MBq of
15O-labeled water and lasted for 90 seconds. At
each PET measurement (baseline at 2 weeks and follow-up at 8 weeks), 8
subsequent scans were obtained for each patient, with an interval of
approximately 8 minutes between scans. MRI scanning was performed with
1-T Magneton Impact (Siemens Medical Systems), using a fast, low-angle
shot sequence (flip angle 40°, repetition time 40 ms, echo time 15
ms) that produced 64 transaxial T1-weighted slices.
Activation Paradigm
The activation paradigm comprised 2 sets with 4 replications
each: a resting condition (dark room, eyes closed, and low ambient
noise) and a word-repetition task (repeating nouns read aloud)
presented in a balanced sequence (ABBABAAB, with A=rest and
B=word repetition). Patients were instructed to repeat and pronounce
simple, highly frequent German nouns aloud as quickly as
possible.24 For each run, a new list of nouns was used to
avoid recognition and habituation. Presentation of stimuli
started 5 seconds before tracer injection and ended 90 seconds after
injection. The rate of stimuli presentation was adapted to
the patient’s ability to repeat the word read aloud.
Image Processing
Each MRI data volume was aligned to the anterior-posterior
commissure line with an interactive 3-dimensional image registration
program.25 MRI data were segmented in brain and infarct
regions on transaxial T1-weighted slices with an interactive IDL
(Interactive Data Language, Research Systems Inc) and C-based image
analysis system,26 operating at a spatial
resolution of 1 mm3. After segmentation of
brain and infarcted tissue, a set of 14 volumes of interest (VOI) was
drawn on the MRI scans, as described in Table 1
. All PET scans were matched
interactively to MRI. Average images of the 4 scans belonging to each
task were calculated and normalized to mean global brain activity
(nCi/mL). In VOI sets transferred to the 2 average images, regional CBF
changes (r
CBF) were calculated as differences between resting and
activated condition. From task-induced regional changes
(rCBF) of each measurement before and after treatment, increase in
rCBF from 2 to 8 weeks was computed as (rCBF8
weeks-r CBF 2 weeks).
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Statistical Analysis
The significance of regional increase of rCBF was measured
for the regions across subjects in each of the 2 groups (placebo and
verum) was assessed by using t tests. Neuropsychological and
language data were analyzed with t tests for
dependent samples.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Twelve patients received piracetam and 12 received placebo. Both groups were comparable in age: the piracetam group was mean age 57.41 (SD 13.53) years, the placebo group 56.33 (9.95) years. Initial aphasia severity, as measured with the Token test, was mean 17.16 (SD 14.31) errors in the piracetam group and 17.91 (15.47) errors in the placebo group. In the piracetam group the treatment started 7.8 days after stroke, and in the placebo group it started 8.2 days after stroke. Infarct location was comparable in both groups, with 5 frontal, 3 subcortical, and 4 temporal lesions in each. Infarct volume was not significantly different in either group.
Neuropsychological Results
The results of language performance and the
neuropsychological tests are summarized in Table 2. Initially, both groups had mild to
moderate language impairment plus impairment in other
neuropsychological functions, such as visuospatial memory, recognition
memory, and reasoning,17 21 22 but there was no difference
in the neuropsychological profile. Both groups showed significant
reduction in the Token test error rate from the first to the second
testing. Whereas the placebo group showed improvement in written
language and in comprehension, the piracetam group showed significant
improvement not only in the subtests for written language, naming on
confrontation, and comprehension (see Table 2), but also in
spontaneous speech, especially in communicative verbal behavior, and in
the semantic and syntactic structure of their speech.
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PET Results
From the CBF changes at 2 and 8 weeks, relative increases
of rCBF were calculated for the language-related areas of the left
and right hemispheres (Table 1
). As shown in the
Figure and Table 3,
activation-induced flow changes increased in several left hemisphere
regions over the treatment period and reached significant levels
(P<0.05) in the left transverse temporal gyrus (Heschl’s
gyrus), the left superior temporal gyrus (BA 22, Wernicke’s region),
and the triangular part of the left frontal gyrus (BA 44, Broca’s
area) in the piracetam-treated group. The placebo group showed
significantly increased activation only in the inferior
part of the left precentral gyrus (vocalizing area). In neither group
were enhancements of the activation responses observed for right
hemispheric regions. In the piracetam group, a tendency but not a
significant suppression of rCBF in the right Broca area was
observed.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Most patients who survive the acute phase of an ischemic stroke regain some of the lost functions. In particular, the improvement of sensorimotor function is accompanied by increased blood flow and/or metabolism in impaired brain regions surrounding focal infarcts and in contralateral regions of the undamaged hemisphere,12 13 which might be a correlate to the functional remapping of the cortex demonstrated in experimental studies.27 Recovering from poststroke aphasia to a satisfactory level relies to a great extent on the functional reintegration of eloquent areas of the dominant hemisphere,15 28 whereas regions of the contralateral network contribute to improvement to a lesser extent and are not sufficient for recovery of full language function. Recovery after stroke is accelerated and facilitated by rehabilitation therapy, which might be supported by various drugs.29 Whereas the effect of physiotherapy for the improvement of sensorimotor deficits is unchallenged, the efficacy of speech therapy is still controversial, with several randomized controlled trials yielding no difference in outcome between treated and nontreated groups.7 Therefore, many trials were undertaken to enhance recovery from aphasia with use of pharmacological agents.30 31 32 In this context, amphetamines were applied for enhancing vigilance by increased noradrenaline levels in the brain, bromocriptine for the selective action of dopamine on language output,33 and cholinergic substances for the effect on naming.34 Piracetam improves learning and memory by facilitating release of acetylcholine and excitatory amino acids, and this effect might lead to increases in flow35 and energy metabolism.36 37 Several controlled studies10 11 have demonstrated a significant advantage of the piracetam-treated group in measures of aphasia, which did not persist over 24 weeks. In a large, multicenter trial, piracetam did not influence overall outcome when given within 12 hours of onset of acute ischemic stroke38 ; however, a significant improvement of language functions could be demonstrated with the Frenchay Aphasia Screening Test with piracetam in the subgroup of patients with poststroke aphasia.39 Our double-blind study in a small group of patients with poststroke aphasia supports these results and shows for the first time an action on the capacity to respond to a specific task related to the improved language function.
The mechanisms by which piracetam supports the beneficial effect of speech therapy and the relationship of this effect to increased blood-flow response to functional activation, however, is unclear. One might speculate that the actions of piracetam on transmitter release and functions40 41 as well as on pathologically altered neuronal membranes42 affect morphologically intact but functionally compromised tissue surrounding ischemic lesions and thereby enhance the capacity of these areas to be reintegrated into a functional network. This hypothesis is supported by findings on the importance of the state of tissue in the vicinity of infarcts for the recovery from aphasia43 ; the ability of these cortical areas to learn from specific rehabilitative measures, eg, speech therapy, might be enhanced by piracetam.44 Our results additionally point to the importance of the functional reactivation of temporal regions within the dominant hemisphere,15 which might be more efficient for recovery from aphasia than facilitation of transcallosal transfer45 and restitution of functions within a bilateral network.46 The results also emphasize the need to select patients who can benefit from drug treatment, especially in support of rehabilitative efforts targeted at relearning lost functionality. This learning process can be activated only as long as cortical areas specific or related to the impaired functions are morphologically intact and are not disconnected from the integrative network.
Our findings indicate a mechanism of action of piracetam in poststroke aphasia and support previous results. A large-scale clinical trial is justified by these data and is needed to prove the efficacy of piracetam as an adjuvant to speech therapy in poststroke aphasia.
Received April 3, 2000; revision received June 5, 2000; accepted June 6, 2000.
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References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Linn L. Sodium amytal in treatment of aphasia. Arch Neurol Psychiatry. 1947;58:357–358.
2. Billow BW. Observation of the use of sodium amytal in the treatment of aphasia. Med Rec. 1949;162:12–13.
3. Luria AR, Naydin VL, Tsvetkova LS. Restoration of higher cortical function following local brain damage. In: Vinken PJ, Bruyn GW, ed. Handbook of Clinical Neurology. Vol 3. Amsterdam, Netherlands: North Holland; 1969:368–433.
4. Jacobs DH, Shuren J, Gold M, Adair JC, Bowers D, Williamson DJG, Heilman KM. Physostigmine pharmacotherapy for aphasia. Neurocase. 1996;2:83–92.
5. Bachman L, Morgan A. The role of pharmacotherapy in the treatment of aphasia: preliminary results. Aphasiology. 1988;2:225–228.
6. Bergman PS, Green M. Aphasia: effect of intravenous sodium amytal. Neurology. 1951;1:471–475.
7. Ferro JM, Mariano G, Madureira S. Recovery from aphasia and neglect. Cerebrovasc Dis. 1999;9(suppl 5):6–22.
8. Giurgea C. Piracetam: nootropic pharmacology of neurointegrative activity. In: Current Developments in Psychopharmacology. New York, NY: Spectrum Publications; 1976;3:222–273.
9. Willmes K, Huber W, Poeck K, Poersch M. Die Wirkung von Piracetam bei der logopädischen Intensivtherapie von chronisch aphasischen Patienten. In: Helmchen H, ed. Wirkungen und Wirksamkeit von Nootropika. Berlin, Germany: Springer-Verlag; 1988:177–187.
10. Enderby P, Broeck J, Hospers W, Schildermans F, Deberdt W. Effect of piracetam on recovery and rehabilitation after stroke: a double-blind, placebo-controlled study. Clin Neuropharmacol. 1994;17:320–331.[Medline] [Order article via Infotrieve]
11. Huber W, Willmes K, Poeck KW, van Vleymen B, Deberdt W. Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study. Arch Phys Med Rehabil. 1997;78:245–250.[Medline] [Order article via Infotrieve]
12. Weiller C, Chollet F, Friston KJ, Wise RJS, Frackowiak RSJ. Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol. 1992;31:463–472.[Medline] [Order article via Infotrieve]
13.
Cramer SC, Nelles G, Benson RR, Kaplan JD, Parker RA,
Kong KK, Kennedy DN, Finklestein SP, Rosen BR. A functional MRI study
of subjects recovered from hemiparetic stroke. Stroke. 1997;28:2518–2527.
14. Heiss WD, Karbe H, Weber-Luxenburger G, Herholz K, Kessler J, Pietrzyk U, Pawlik G. Speech-induced cerebral metabolic activation reflects recovery from aphasia. J Neurol Sci. 1997;145:213–217.[Medline] [Order article via Infotrieve]
15. Heiss WD, Kessler J, Thiel A, Ghaemi M, Karbe H. Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia. Ann Neurol. 1999;45:430–438.[Medline] [Order article via Infotrieve]
16. Huber W, Poeck K, Weniger D, Willmes K. Der Aachener Aphasie Test. Göttingen, Germany: Hogrefe-Verlag; 1982.
17. Spreen O, Strauss E. A compendium of neuropsychological tests. New York, NY: Oxford University Press; 1991:221–229.
18. Milner B. Interhemispheric differences and psychological processes. Br Med Bull. 1971;27:273–277.
19. Salmaso D, Longoni AM. Problems in the assessment of hand preference. Cortex. 1985;21:533–549.[Medline] [Order article via Infotrieve]
20. Poeck K, ed. Klinische Neuropsychologie. Stuttgart, Germany: Thieme Verlag; 1989:89–310.
21. Raven JC, Court J, Raven J Jr. Standard Progressive Matrices (SPM). London, UK: JC Raven Ltd, 1976. German manual (2nd ed) by Kratzmeier H, Horn R. Weinheim, Germany: Beltz-Test Verlag; 1987.
22. Benton AL. Der Benton Test. Bern, Switzerland: Hans Huber Verlag; 1989.
23. Wienhard K, Dahlbom M, Eriksson L, Michel CH, Bruckbauer T, Pietrzyk U, Heiss WD. The ECAT EXACT HR: performance of a new high resolution positron scanner. J Comput Assist Tomogr. 1994;18:110–118.[Medline] [Order article via Infotrieve]
24. Hager W, Hasselborn M. Handbuch deutschsprachiger Wortnormen. Göttingen, Germany: Hogrefe-Verlag; 1994.
25.
Pietrzyk U, Herholz K, Fink GR, Jacobs A, Mielke R,
Slansky I, Würker M, Heiss WD. An interactive technique for
three-dimensional image registration: validation for PET, SPECT, MRI
and CT brain studies. J Nucl Med. 1994;35:2011–2018.
26. von Stockhausen HM, Pietrzyk U, Herholz K. Techniken zur Visualisierung funktioneller tomographischer Daten in der klinischen Forschung. In: Arnolds B, Müller H, Saupe D, Tolxdorff T, eds. Digitale Bildverarbeitung in der Medizin. Berlin, Germany: FU Berlin; 1996.
27. Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996;272:1791–1794.[Abstract]
28.
Cao Y, Vikingstad EM, George KP, Johnson AF. Cortical
language activation in stroke patients recovering from aphasia with
functional MRI. Stroke.. 1999;30:2331–2340.
29. Fisher M, Finklestein S. Pharmacological approaches to stroke recovery. Cerebrovasc Dis. 1999;9(suppl 5):29–32.
30. Small SL. Pharmacotherapy of aphasia: a critical review. Stroke. 1994;25:1282–1289.[Abstract]
31. Wallesch CW, Muller U, Hermann M. Aphasia: role of pharmacotherapy in treatment. CNS Drugs. 1997;7:203–213.
32. Walker-Batson D. Pharmacotherapy in the treatment of aphasia. In: Goldstein LB, ed. Restorative Neurology: Advances in Pharmacotherapy for Recovery After Stroke. Armonk, NY: Futura Publishing; 1998:257–270.
33.
Albert ML, Bachman D, Morgan A, Helm-Estabrooks N.
Pharmacotherapy for aphasia. Neurology. 1988;38:877–879.
34. Tanaka Y, Miyazaki M, Albert ML. Effects of increased cholinergic activity on naming in aphasia. Lancet. 1997;350:116–117.
35. Herrschaft H. The effect of piracetam on global and regional blood flow in acute cerebral ischemia of man. Med Klin. 1978;73:195–202.[Medline] [Order article via Infotrieve]
36. Heiss WD, Ilsen H, Wagner R, Pawlik G, Wienhard K. Remote functional depression of glucose metabolism in stroke and its alteration by activating drugs. In: Heiss WD, Phelps N, eds. Positron Emission Tomography of the Brain. Berlin, Germany: Springer; 1983:162–168.
37. Depresseux JC, Salmon E, Sadzot B, Cornette M, Franck G. Evaluation of the effect of piracetam on CBF and CMRO2 in acute stroke patients using PET and 15Oxygen. In: Bes A, ed. Senile Dementias: Proceedings of an International Symposium Organized by SIR International. Paris, France: Libby Eurotext; 1986.
38.
De Deyn PP, De Reuck J, Deberdt W, Vlietinck R,
Orgogozo JM. Treatment of the acute ischemic stroke with
piracetam. Stroke. 1997;28:2347–2352.
39. Orgogozo JM. Piracetam in the treatment of acute stroke. CNS Drugs. 1998;9(suppl 1):41–49.
40. Müller WE, Hartmann H, Koch S, Scheuer K, Stoll S. Neurotransmission in aging: therapeutic aspects. In: Racagni N, Brunello N, Langer SZ, eds. Recent Advances in the Treatment of Neurodegenerative Disorders and Cognitive Dysfunction. Basel, Switzerland: Karger; 1994:166–173.
41. Coq JO, Xerri C. Acute reorganization of the forepaw representation in the rat SI cortex after focal cortical injury: neuroprotective effects of piracetam treatment. Eur J Neurosci. 1999;11:2597–2608.[Medline] [Order article via Infotrieve]
42. Müller WE, Koch S, Scheuer K, Rostock A, Bartsch R. Effects of piracetam on membrane fluidity in the aged mouse, rat and human brain. Biochem Pharmacol. 1997;53:135–140.[Medline] [Order article via Infotrieve]
43.
Heiss WD, Kessler J, Karbe H, Fink GR, Pawlik G.
Cerebral glucose metabolism as a predictor of recovery from
aphasia in ischemic stroke. Arch Neurol. 1993;50:958–964.
44. Dimond S. Drugs to improve learning in man: implications and neuropsychological analysis. In: Knight R, Bakker O, eds. The Neuropsychology of Learning Disorders. London, UK: University Press; 1979:367–379.
45. Giurgea CE, Moyersoons FE. The pharmacology of callosal transmission: a general survey. In: Russell SE, ed. Structure and Function of Cerebral Commissures. London, UK: MacMillian Press; 1979:283–298.
46. Weiller C, Isensee C, Rijntjes M, Huber W, Müller S, Bier D, Dutschka K, Woods RP, Noth J, Diener HC. Recovery from Wernicke’s aphasia: a positron emission tomographic study. Ann Neurol. 1995;37:723–732.[Medline] [Order article via Infotrieve]
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