Piracetam Improves Activated Blood Flow and Facilitates Rehabilitation of Poststroke Aphasic Patients Effect of Piracetam on Recovery and Rehabilitation After Stroke: A Double‐Blind, Placebo‐Controlled Study Does long term use of piracetam improve speech disturbances due to ischemic cerebrovascular diseases? Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study. No effects of anodal transcranial direct stimulation on language abilities in early rehabilitation of post-stroke aphasic patients. Treatment of acute ischemic stroke with piracetam. Members of the Piracetam in Acute Stroke Study (PASS) Group. Restitution of alpha-topography by piracetam in post-stroke aphasia. Interaction between psychological and pharmacological treatment in cognitive impairment. Transcranial direct current stimulation effects on neural processing in post‐stroke aphasia Anodal transcranial direct current stimulation in early rehabilitation of patients with post-stroke non-fluent aphasia: a randomized, double-blind, sham-controlled pilot study. Transcranial direct current stimulation in post-stroke sub-acute aphasia: study protocol for a randomized controlled trial Transcranial Magnetic Stimulation Combined with Speech and Language Training in Early Aphasia Rehabilitation: A Randomized Double-Blind Controlled Pilot Study Cathodal transcranial direct current stimulation of the right Wernicke’s area improves comprehension in subacute stroke patients Aphasia in acute stroke: Incidence, determinants, and recovery
Background and Purpose In a prospect i ve , 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 r and omly 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 Summary : The nootropic agent piracetam has been shown to improve learning and memory , and it may , by this means , facilitate recovery and rehabilitation after a stroke . We report the results of a pilot study exploring its effects in patients undergoing rehabilitation after acute cerebral infa rct ion in the carotid artery territory . We compared piracetam and placebo , each given for 12 weeks , in a multicenter , double-blind , r and omized trial of parallel-group design ; testing was performed at baseline ( 6–9 weeks poststroke ) , weeks 5 and 12 , and , in fewer patients , 12 weeks after termination of treatment . St and ardized tests of activities of daily living ( Barthel Index , Kuriansky Test ) , aphasia ( Aachen Aphasia Test ) , and perception ( Rivermead Perception Assessment Battery ) were the primary efficacy variables . Of 158 patients , 137 ( 81 males , 56 females ) were studied after treatment and 88 at 24-week follow-up . Thirty patients on piracetam ( 45 % ) and 37 on placebo ( 53 % ) were aphasic on entry . Both groups , including the subgroups with aphasia , were well matched at baseline for demographic data , stroke sequelae , type and severity of aphasia , and prognostic parameters . Multivariate analysis of Aachen Aphasia subtest scores showed a significant overall improvement relative to baseline in favor of piracetam ( p = 0.02 ) at 12 weeks . This was not seen at 24 weeks when , however , fewer patients were available for evaluation so that we could neither confirm nor deny whether improvement was maintained after cessation of piracetam . We were unable to demonstrate an effect on tests of activities of daily living and could neither confirm nor exclude an effect on perceptual deficit . We have shown an improvement in aphasia in patients undergoing rehabilitation after a stroke after 12 weeks ' treatment with piracetam that requires confirmation in further studies Aphasia causes significant disability and h and icap among stroke survivors . Language therapy is recommended for aphasic patients , but not always available . Piracetam , an old drug with novel properties , has been shown to have mild beneficial effects on post-stroke aphasia . In the current study , we investigated the effects of 6 months treatment with piracetam on aphasia following stroke . Thirty patients with first-ever ischemic strokes and related aphasia were enrolled in the study . The scores for the National Institutes of Health Stroke Scale ( NIHSS ) , Barthel Index ( BI ) , modified Rankin Scale ( mRS ) , and Gülhane Aphasia Test were recorded . The patients were scheduled r and omly to receive either 4.8 g piracetam daily or placebo treatment for 6 months . At the end of 24 weeks , clinical assessment s and aphasia tests were repeated . The level of improvement in the clinical parameters and aphasia scores was compared between the two groups . All patients had large lesions and severe aphasia . No significant difference was observed between the piracetam and placebo groups regarding the improvements in the NIHSS , BI and mRS scores at the end of the treatment . The improvements observed in spontaneous speech , reading fluency , auditory comprehension , reading comprehension , repetition , and naming were not significantly different in the piracetam and placebo groups , the difference reached significance only for auditory comprehension in favor of piracetam at the end of the treatment . Piracetam is well-tolerated in patients with post-stroke aphasia .  Piracetam taken orally in a daily dose of 4.8 g for 6 months has no clear beneficial effect on post-stroke language disorders OBJECTIVE To determine whether piracetam 4.8 g/day together with intensive language therapy improved language function more than language therapy alone . DESIGN Double-blind , placebo-controlled parallel group study . SETTING Referral speech and language clinic of a university department of neurology . PATIENTS Sixty-six in patients with aphasia present between 4 weeks and 36 months . INTERVENTIONS Intensive language therapy for 6 weeks in all patients . Thirty-two patients received piracetam 4.8 g daily and 34 patients received placebo . MAIN OUTCOME MEASURE The Aachen Aphasia Test ( AAT ) , a st and ardized procedure for evaluating the severity of aphasia , was performed at baseline and after 6 weeks ' treatment . RESULTS In 50 patients evaluated for efficacy , a trend toward improvement in the active group was observed in all subtests of the AAT . This trend was statistically significant for absolute differences in recovery of " written language " and " profile level . " CONCLUSION Piracetam appears to have a positive adjuvant effect on the recovery of aphasia in patients receiving intensive language therapy BACKGROUND AND PURPOSE Recent research suggests that an increased level of stroke-affected left hemisphere cortical ( especially frontal ) excitability is associated with better language improvement in aphasic patients .  Anodal transcranial direct current stimulation ( A-tDCS ) , increasing cortical activity , may facilitate perilesional left hemisphere recruitment to subserve language processing and enhance effects of behavioural therapy . The aim of the study ( r and omized , double-blind , sham-controlled ) was to evaluate the effectiveness of repeated A-tDCS over Broca area as a strategy to enhance aphasia recovery during early post-stroke rehabilitation . MATERIAL AND METHODS Thirty-seven participants with moderate or severe aphasia were r and omized to receive 15 consecutive daily sessions of A-tDCS ( 1 mA , 10 min ; experimental group , n = 18 ) or sham stimulation ( 1 mA , 25 s ; control group , n = 19 ) followed by language therapy .  Effects of tDCS were assessed using the Boston Diagnostic Aphasia Examination , performed before and after the rehabilitation , and three months later . RESULTS The results did not confirm a positive impact of repeated A-tDCS , preceding language therapy , on language abilities in our patients . Although both groups improved after the therapy , there were no statistically significant differences between groups in either short-term or long-term tDCS effects . Effect sizes for the experimental group , at post-treatment and the 3-month follow-up , were slightly higher than in controls but insufficient to infer any beneficial influence of the applied intervention . CONCLUSIONS The findings do not support  A-tDCS functional benefits during early rehabilitation of post-stroke aphasia . Further research is needed to explore the effectiveness of this kind of neuromodulation BACKGROUND AND PURPOSE Piracetam , a nootropic agent with neuroprotective properties , has been reported in pilot studies to increase compromised regional cerebral blood flow in patients with acute stroke and , given soon after onset , to improve clinical outcome . We performed a multicenter , r and omized , double-blind trial to test whether piracetam conferred benefit when given within 12 hours of the onset of acute ischemic stroke to a large group of patients . METHODS Patients received placebo or 12 g piracetam as an initial intravenous bolus , 12 g daily for 4 weeks and 4.8 g daily for 8 weeks . The primary end point was neurologic outcome after 4 weeks as assessed by the Orgogozo scale . Functional status at 12 weeks as measured by the Barthel Index was the major secondary outcome . CT scan was performed within 24 hours of the onset of stroke but not necessarily before treatment . Analyses based on the intention to treat were performed in all r and omized patients ( n = 927 ) and in an " early treatment " population specified in the protocol as treatment within 6 hours of the onset of stroke but subsequently redefined as less than 7 hours after onset ( n = 452 ) . RESULTS In the total population , outcome was similar with both treatments ( the mean Orgogozo scale after 4 weeks : piracetam 57.7 , placebo 57.6 ; the mean Barthel Index after 12 weeks : piracetam 55.8 , placebo 53.1 ) . Mortality at 12 weeks was 23.9 % ( 111/464 ) in the piracetam group and 19.2 % ( 89/463 ) in the placebo group ( relative risk 1.24 , 95 % confidence interval , 0.97 to 1.59 ; P = .15 ) . Deaths were fewer in the piracetam group in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke . Post hoc analyses in the early treatment subgroup showed differences favoring piracetam relative to placebo in mean Orgogozo scale scores after 4 weeks ( piracetam 60.4 , placebo 54.9 ; P = .07 ) and Barthel Index scores at 12 weeks ( piracetam 58.6 , placebo 49.4 ; P = .02 ) . Additional analyses within this subgroup , confined to 360 patients with moderate and severe stroke ( initial Orgogozo scale score < 55 ) , showed significant improvement on piracetam in both outcomes ( P < .02 ) . CONCLUSIONS Piracetam did not influence outcome when given within 12 hours of the onset of acute ischemic stroke . Post hoc analyses suggest that piracetam may confer benefit when given within 7 hours of onset , particularly in patients with stroke of moderate and severe degree . A r and omized , placebo-controlled , multicenter study , the Piracetam Acute Stroke Study II ( PASS II ) will soon begin OBJECTIVE Electroencephalographic and clinical effects of piracetam in post-stroke aphasia were evaluated in a prospect i ve , r and omized , double-blind , placebo-controlled trial . METHODS In 24 patients with mild to moderate aphasia after ischemic stroke , quantitative topographic EEG at rest was studied before and after a 6-week treatment period . RESULTS In the active treatment group , a significant shift in the alpha-rhythm from frontal to occipital regions was observed which may be due to a restitution of corticothalamic circuits involved in the generation of alpha-activity . CONCLUSION Neuropsychological scores improved significantly and markedly in various domains of speech during piracetam treatment , whereas improvements were less marked and restricted to a few categories in the placebo group In contrast to other kinds of psychotropic drugs , nootropics or cognition enhancing drugs may be indicated , not for the direct treatment of the pathology itself , but for improving or restoring the remaining brain functions . Brain functions are normally trained during various kinds of non-medical therapy , such as physiotherapy , speech therapy , occupational therapy , memory training etc ... In research little attention has been paid to the combination of both kinds of therapeutic approaches , probably because of the important method ological difficulties . This combination however , offers various interesting perspectives : L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum ( GBE ) or piracetam 2.4 or 4.8 g/d , combined with a memory training program , in nondemented patients complaining of memory problems . The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and , hence , are complementary . Some functions , like attention/perception in the GBE study and learning in the piracetam study , seem to benefit from both treatments , suggesting a mutually potentiating effect of drug treatment and training . This potentiation is very clear in the treatment of dyslexic children : in a placebo-controlled study piracetam 3.3 g/d , in combination with normal school teaching and more specific logopedic therapy , allowed a normal progression during the full school year in reading accuracy and reading comprehension , while the placebo treated children getting a similar training progressed only with 50 % . Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d , especially when given during the first months after the stroke , or otherwise in combination with an intensive speech training . In both double-blind studies the piracetam treated group improved about 60 % more than the group who only got speech therapy and placebo . All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions . E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals , most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity Non‐invasive transcranial direct current stimulation ( tDCS ) can enhance recovery after stroke . However , fundamental knowledge about how tDCS impacts neural processing in the lesioned human brain is currently lacking . In the present study , it was investigated how tDCS modulates brain function in patients with post‐stroke language impairment ( aphasia ) . In a cross‐over , r and omized trial , patients named pictures of common objects during functional magnetic resonance imaging ( fMRI ) . Concurrently , excitatory ( anodal‐ ) or sham‐tDCS ( 1 mA , 20 min , or 30 s , respectively ) was administered to the left primary motor cortex , a montage with demonstrated potential to improve aphasic language . By choosing stimuli that could reliable be named by the patients , the authors aim ed to derive a pure measure of stimulation effects that was independent of treatment or performance effects and to assess how tDCS interacts with the patients ' residual language network . Univariate fMRI data analysis revealed reduced activity in domain‐general regions mediating high‐level cognitive control  during anodal‐tDCS . Independent component functional network analysis demonstrated selectively increased language network activity and an inter‐correlated shift from higher to lower frequency b and s , indicative of increased within‐network communication . Compared with healthy controls , anodal‐tDCS result ed in overall “ normalization ” of brain function in the patients . These results demonstrate for the first time how tDCS modulates neural processing in stroke patients . Such information is crucial to assure that behavioral treatments targeting specific neural circuits overlap with regions that are modulated by tDCS , thereby maximizing stimulation effects during therapy . Hum Brain Mapp 38:1518–1531 , 2017 . © 2016 Wiley Periodicals , PURPOSE Recent research in patients with chronic aphasia shows an association between excitatory anodal transcranial direct current stimulation ( A-tDCS ) of the stroke-affected left hemisphere coupled with speech and language therapy ( SLT ) and better language performance . The present study aim ed to investigate this association during the early post-stroke rehabilitation period , when adaptive changes are most possible on neurophysiological and behavioral levels . METHODS We r and omized 24 patients with non-fluent aphasia to receive 15 consecutive sessions ( 5 days/week for 3 weeks ) of A-tDCS ( 1 mA , 10 min ; n = 14 ) or sham tDCS ( S-tDCS : 1 mA , 25 sec ; n = 10 ) over Broca 's area followed by 45-min SLT . Naming ability was assessed before the rehabilitation , after its completion , and three months later . RESULTS Both groups significantly improved after the therapy . There were no statistically significant between-group differences in the short-term or long-term tDCS effects on naming accuracy and naming time . The A-tDCS group obtained higher effect sizes in naming time , both post-treatment and at the 3-month follow-up , suggesting potential benefits of the stimulation . CONCLUSIONS The findings provide only weak evidence for A-tDCS-related language gains during early neurorehabilitation of post-stroke aphasia . Further research is needed to explore the effectiveness of this kind of neuromodulation Background Transcranial direct current stimulation ( tDCS ) is a promising new technique to optimize the effect of regular Speech and Language Therapy ( SLT ) in the context of aphasia rehabilitation . The present study focuses on the effect of tDCS provided during SLT in the sub-acute stage after stroke . The primary aim is to evaluate the potential effect of tDCS on language functioning , specifically on word-finding , as well as generalization effects to verbal communication . The secondary aim is to evaluate its effect on social participation and quality of life , and its cost-effectiveness . Methods We strive to include 58 stroke patients with aphasia , enrolled in an inpatient or outpatient stroke rehabilitation program , in a multicenter , double-blind , r and omized controlled trial with two parallel groups and 6 months ’ follow-up . Patients will participate in two separate intervention weeks , with a pause of 2 weeks in between , in the context of their regular aphasia rehabilitation program . The two intervention weeks comprise daily 45-minute sessions of word-finding therapy , combined with either anodal tDCS over the left inferior frontal gyrus ( 1 mA , 20 minutes ; experimental condition ) or sham-tDCS over the same region ( control condition ) . The primary outcome measure is word-finding . Secondary outcome measures are verbal communication , social participation , quality of life , and cost-effectiveness of the intervention . Discussion Our results will contribute to the discussion on whether tDCS should be implemented in regular aphasia rehabilitation programs for the sub-acute post-stroke population in terms of (cost-)effectiveness . Trial registration Nederl and s Trail Register : NTR4364 . Registered on 21 February 2014 Abstract Background : Functional neuroimaging studies with poststroke aphasia patients have shown increased activation of the unaffected hemisphere , which hypothetically reflects a maladaptive strategy of brain reorganization . Objective : We investigated whether repetitive transcranial magnetic stimulation ( rTMS ) inhibiting the right-hemisphere homologue of Broca ’s area improves language restitution if combined with speech/ language therapy . Methods : Forty aphasic patients during the subacute phase of ischemic stroke were r and omized to a 3-week aphasia rehabilitation protocol in combination with real or sham rTMS .  Naming , repetition , and comprehension were assessed using the Boston Diagnostic Aphasia Examination at baseline , immediately after therapy , and 15 weeks after completing treatment . Results : Although language functions improved in both experimental and control groups after 3 weeks , only slight group differences in degree of recovery were revealed between patients receiving rTMS and control participants . Follow-up revealed that severely aphasic rTMS patients demonstrated significantly greater improvement than patients receiving sham stimulation in repetition . Conclusions : Inhibitory rTMS applied to the right frontal language homologue is not effective for all poststroke aphasia patients , although it might benefit selected patients Previous studies have shown the appearance of right-sided language -related brain activity in right-h and ed patients after a stroke .  Non-invasive brain stimulation such as transcranial direct current stimulation ( tDCS ) and repetitive transcranial magnetic stimulation ( rTMS ) have been shown to modulate excitability in the brain . Moreover , rTMS and tDCS have been found to improve naming in non-fluent post-stroke aphasic patients . Here , we investigated the effect of tDCS on the comprehension of aphasic patients with subacute stroke . We hypothesized that tDCS applied to the left superior temporal gyrus ( Wernicke 's area ) or the right Wernicke 's area might be associated with recovery of comprehension ability in aphasic patients with subacute stroke . Participants included right-h and ed subacute stroke patients with global aphasia due to ischemic infa rct of the left M1 or M2 middle cerebral artery . Patients were r and omly divided into three groups : patients who received anodal tDCS applied to the left superior temporal gyrus , patients who received cathodal tDCS applied to the right superior temporal gyrus , and patients who received sham tDCS . All patients received conventional speech and language therapy during each period of tDCS application . The Korean-Western Aphasia Battery ( K-WAB ) was used to assess all patients before and after tDCS sessions . After intervention , all patients had significant improvements in aphasia quotients , spontaneous speech , and auditory verbal comprehension . However , auditory verbal comprehension improved significantly more in patients treated with a cathode , as compared to patients in the other groups . These results are consistent with the role of Wernicke 's area in language comprehension and the therapeutic effect that cathodal tDCS has on aphasia patients with subacute stroke , suggesting that tDCS may be an adjuvant treatment approach for aphasia rehabilitation therapy in patients in an early stage of stroke Knowledge of the frequency and remission of aphasia is essential for the rehabilitation of stroke patients and provides insight into the brain organization of language . We studied prospect ively and consecutively an unselected and community‐based sample of 881 patients with acute stroke .  Assessment of aphasia  was done at admission , weekly during the hospital stay , and at a 6‐months follow‐up using the aphasia score of the Sc and inavian Stroke Scale .  Thirty‐eight percent had aphasia at the time of admission ; at discharge 18 % had aphasia .  Sex was not a determinant of aphasia in stroke , and no sex difference in the anterior‐posterior distribution of lesions was found . The remission curve was steep : Stationary language function in 95 % was reached within 2 weeks in those with initial mild aphasia , within 6 weeks in those with moderate , and within 10 weeks in those with severe aphasia . A valid prognosis of aphasia could be made within 1 to 4 weeks after the stroke depending on the initial severity of aphasia . Initial severity of aphasia was the only clinical ly relevant predictor of aphasia outcome . Sex , h and edness , and side of stroke lesion were not independent outcome predictors , and the influence of age was minimal
Conclusions Piracetam plays a limited role in the rehabilitation of overall language impairment and only benefits written language ability at the end of trials .
Its effect on overall linguistic level and written language tends to emerge within a short period and declines thereafter
Background Aphasia is a common symptom in post-stroke patients .
Piracetam is a commonly used nootropic agent that promises various benefits to brain function , including language improvement .
Objective We performed a systematic review and meta- analysis to assess whether piracetam facilitates the rehabilitation of language performance in post-stroke patients .