|Year : 2014 | Volume
| Issue : 7 | Page : 703-706
Recent advances in the treatment of post-stroke aphasia
Anna Zumbansen1, Alexander Thiel2
1 School of Speech Pathology and Audiology, Université de Montréal; Jewish General Hospital, McGill University, Montreal, QC, Canada
2 Jewish General Hospital, McGill University, Montreal, QC, Canada
|Date of Acceptance||15-May-2014|
|Date of Web Publication||29-May-2014|
Jewish General Hospital, 3755 Chemin de la Côte Ste-Catherine, Montreal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Zumbansen A, Thiel A. Recent advances in the treatment of post-stroke aphasia. Neural Regen Res 2014;9:703-6
Aphasia is an impairment of language use following brain damage. There is no consensual definition of aphasia beyond this general description (Code and Petheram, 2011). In a more restricted definition, however, aphasia is an impairment of linguistic processing at the phonological, morphological, lexical semantic or syntactic level which is usually caused by lesions of the left cerebral hemisphere. This impairment can affect language reception and expression depending on the various aphasic syndromes (McNeil and Pratt, 2001). Aphasia results in restrictions in those activities of daily living which rely on communication. In terms of the International Classification of Functioning, Disability and Health (WHO, 2001), limitations in functional communication pose significant challenges to social participation (Davidson et al., 2008) and reduce the patients' quality of life (Kauhanen et al., 1999; Shadden, 2005). Recent data on the incidence of aphasia following stroke range between 0.02 and 0.06 % with a prevalence between 0.1 and 0.4 % in the developed world (Code and Petheram, 2011). Spontaneous behavioral recovery usually occurs to some degree in the weeks to months after stroke and depends on many factors such as the infarct size and location and the severity of initial stroke deficits (Cramer, 2008). Traditionally, proposed mechanisms of the neurological intrinsic recovery are the resolution of edema surrounding the infarcted area (Katzman et al., 1977; Lo, 1986) and reperfusion of incompletely damaged, but highly vulnerable perilesional tissue (see Donnan et al., 2013). These local mechanisms are supposed to support early recovery (in days to weeks after stroke) and do not depend on behavioral experience but have been targeted by pharmacological treatments: of more than a thousand drugs tested in animal models, 114 have been studied in clinical trials (Pérez de la Ossa and Davalos, 2007) and to date none of these potentially neuroprotective agents was found to be effective in humans. Only rapid reperfusion with recombinant tissue plasminogen activator (rTPA) does improve functional outcome after ischemic stroke, but its use is limited by a short therapeutic window (4.5 hours following stroke), the risk of hemorrhage and potential ischemia/reperfusion injury (Lakhan et al., 2009). In contrast, neuronal network reorganization, which also occurs spontaneously, has been related to later recovery and can be influenced by environmental and behavioral factors (Cramer, 2008; Nudo, 2011, 2013). On the molecular level, regulation of gene expression in the unaffected peri-infarct tissue seems to favour the synthesis of growth promoting and to suppress the synthesis of growth inhibiting proteins thus creating a permissive environment for axonal/dendritic sprouting and may thus offer a window of opportunity for behavioural interventions to be effective (Carmichael, 2006).
Even after standard treatments provided by the health care systems, the majority of people with aphasia have a chronic communication disability. Speech and language therapy (SLT) is the current standard of care for aphasia treatment but supplemental therapeutic strategies are emerging. The aim of this short review is to give an overview of current advances in research on behavioural, pharmacological and electrophysiological treatments for post-stroke aphasia.
Research on SLT efficacy in post-stroke aphasia has accelerated dramatically in the last decade. Until 1999, only 12 trials fulfilled the rigorous Cochrane criteria for inclusion into a systematic Cochrane review (Greener et al., 1999). This initial review was updated in 2011 based on 39 randomized controlled trials (RCT) involving 2,518 randomized patients (Brady et al., 2012) and came to the conclusion that the analyzed studies gave some evidence of the effectiveness of SLT for the improvement of functional communication, receptive and expressive language after stroke. Notably, they found a significant effect in the meta-analysis of nineteen randomized comparisons (1,414 participants) of SLT versus no SLT on patients' functional communication (standardised mean difference 0.30, 95% CI 0.08 to 0.52, P = 0.008). The molecular mode of action of SLT is still largely unknown.
Traditionally, SLT consists of impairment-based therapies, which aim at improving functional communication in targeting the underlying linguistic deficits. For example, an SLT targeting semantic deficits will use semantic decision tasks at the word, sentence or text level to improve linguistic semantic processing whereas in the case of phonological deficits, SLT will train phonological input and output processing (Doesborgh et al., 2004). A few impairment-based therapies are designed to be used as a holistic treatment program to improve language in daily communication. Examples are the melodic intonation therapy (Sparks et al., 1974; AAN, 1994) which uses a specific singing-speech technique that presumably engages language capable areas in the right hemisphere (but see Zumbansen et al., 2014, for a critical review) and the constraint induced language therapy (Pulvermόller et al., 2001) that extends principles of constraint-induced movement therapies to language rehabilitation by setting intensive stimulation training of the impaired linguistic functions while supressing compensatory behaviors such as gestures. To date, however, there is no conclusive evidence that one SLT approach is better than another on functional communication outcomes (Brady et al., 2012).
In clinical practice, SLT clinicians commonly use combinations of different therapeutic approaches on an attempt to tailor the language treatment to each patient's clinical profile (Rose et al., 2014). In order to document therapeutic efficacy, Beeson and Robey (2006) recommend using outcome measures based on untrained test material and assessment of connected natural speech or similar evaluation tools for functional communication. Although these latter measures have rarely been reported in efficacy studies, as already mentioned, impairment-based therapies have shown some effectiveness on functional communication in patients with aphasia after stroke (Brady et al., 2012) and the most recent RCTs have reinforced the level of evidence of these approaches (Godecke et al., 2012; Sickert et al., 2014; van der Meulen et al., 2014).
However, despite the efficacy of these therapies the majority of stroke survivors do not recover completely from their language impairment, necessitating a quest for alternative therapeutic approaches in SLT practice to help patients regaining a better quality of life with aphasia (Rose et al., 2014). So-called functional-based approaches do not aim at improving language per se but focus instead on the larger level of functional communication. Functional communication refers to the ability to communicate in real world settings (Brady et al., 2012) and includes both linguistic and extra-linguistic means (Worrall and Frattali, 2000; Holland and Hinckley, 2004). Those treatments target non-linguistic communicative skills which can be optimized to improve daily communication activities relevant to the patient (e.g., mimic and gestures). It also involves training of the patient's relatives to make them better communication partners. Because functional-based approaches are relatively new in comparison to their impairment-based counterparts, the available evidence of their efficacy is weaker to date and more well-designed studies are needed to document the efficacy of these interesting new therapeutic strategies.
In sum, there is good evidence that SLT benefits patients' functional communication, receptive and expressive language compared to no SLT and it is likely that results are better with intensive rather than low-frequency treatment. There is no evidence that any of the discussed therapies is superior to the others (Brady et al., 2012). Aphasia treatment is usually provided at the intensity of one to five hours per week on average. Recent studies seem to suggest that treatment of such intensity is likely insufficient and it is estimated that almost twice this intensity is required to achieve significant treatment effects beyond spontaneous recovery (Code and Petheram, 2011). However increasing treatment intensity often is not feasible due to economic limitations in most public health systems but also due to the lack of various other resources, such as time and space (Rose et al., 2014). Thus, research on non-behavioral supplementary treatments is needed, which may potentiate the effectiveness of SLT, particularly in acute and subacute stages where the SLT is currently provided with highest intensity (Katz et al., 2000; Verna et al., 2009). Such possible adjuvant strategies may comprise pharmacological approaches as well as non-invasive brain stimulation (NIBS).
Adjuvant pharmacotherapy for enhancement of SLT effects
As for any other post-stroke deficits, adequate acute stroke management according to current guidelines (Jauch et al., 2013) to minimize primary (e.g., by reperfusion therapies) and secondary brain damage (e.g., through treatment of edema, neuroprotection, etc.) is also fundamental for aphasia recovery. In this review, we only focus on pharmacological therapies which have specifically been investigated in conjunction with SLT and may have the potential to enhance SLT efficacy. A number of drugs have been studied for possible SLT enhancing effects (Berthier et al., 2011; Salter et al., 2013; Cahana-Amitay et al., 2014). Here, we briefly present those substances which have been tested in RCTs for their presumed neuromodulatory effect on various neurotransmitters systems.
Piracetam, a cyclic derivative of γ-aminobutiric acid (GABA), has been considered as promising in conjunction with intensive SLT in the acute and sub-acute phases (Greener et al., 2001; Liepert, 2008; Berthier et al., 2011). In one study, 2,400 mg taken twice daily had a positive effect on several expressive and receptive language subtests as well as spontaneous speech (Kessler et al., 2000). The specific mechanisms of action of Piracetam are not well understood. Kessler and colleagues (2000) found increases in cerebral blood flow in key language areas which were positively correlated with language recovery. Other mechanisms might involve modulation of cholinergic, glutamatergic and possibly GABAergic neurotransmitter systems.
Donepezil and other cholinergic agents (e.g., Galantamine, Bifelemane and Physostigmine) have shown some positive therapeutic effects in post-stroke aphasia (Berthier et al., 2011; Berthier, 2014). Notably, 10 mg of Donepezil per day in combination with only two hours of SLT per week improved picture naming (Cohen's d = 0.92, large effect size) and the severity of aphasia (Cohen's d = 0.87, large effect size) in a RCT with 26 participants (Berthier et al., 2006). By inhibiting acetylcholinesterase, Donepezil is thought to facilitate neurotransmission in cerebral cholinergic connections to language brain areas (Kasa et al., 2000). These pathways play an important role for practice-related plasticity based on long-term potentiation enhancing attention, learning and memory (Sarter et al., 2005).
Memantine (10 mg twice daily) was tested in one RCT only and seemed to be associated with long-lasting effects on outcome measures of language function and functional communication. In this study, pharmacotherapy was combined with intensive SLT administrated as group therapy to patients with chronic aphasia (Berthier et al., 2009). As NMDA receptor agonist, Memantine is supposed to act on glutamatergic transmissions and enhance the activity of preserved neural networks. Further studies are needed to support these promising results.
Several cathecholaminergic drugs have been investigated in conjunction with SLT with inconclusive results. To date, two dopaminergic agents (Bromocriptine and Levodopa) have been tested in two RCTs each (Gill and Leff, 2014). Bromocriptine showed no treatment effect (Sabe et al., 1995; Ashtary et al., 2006) but no SLT treatment was provided during these studies. In contrast, Seniσw et al. (2009) found L-dopa to be effective when paired with intensive SLT over three weeks during the sub-acute phase, particularly in patients with frontal lesions. However, Leemann et al. (2011) found no effect of Levodopa over placebo with intensive SLT over two weeks.
The effect of amphetamines was subject to one RCT with aphasic patients in the sub-acute phase post-stroke. 10 STL sessions over five weeks preceded by intakes of 10 mg of Dextroamphetamine improved language recovery (Walker-Batson et al., 2001). However, for now, the use of amphetamines for improving recovery after stroke is not recommended in clinical practice (Martinsson et al., 2007).
In summary, following the criteria for the evidence based review in stroke rehabilitation (Salter et al., 2013), the level of evidence supporting the general use of these drugs to improve aphasia recovery is moderate. Strongest evidence to date exists for the efficacy of Piracetam in combination with SLT and strongest evidence for inefficacy exists for Bromocriptine. For now, none of the drug is recommended for routine use in aphasia rehabilitation and further research are warranted both to support clinical pharmacological treatment for post-stroke aphasia and to better understand the mechanisms by which the different drugs act on language and communication recovery.
Noninvasive brain stimulation (NIBS) as adjuvant therapy for SLT
NIBS can modulate the excitability and activity of targeted cortical regions. With increasing knowledge and improved understanding of the roles of the dominant (usually left) and nondominant (usually right) hemisphere language networks in brain reorganization after stroke, repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have emerged as new electrophysiological approaches to aphasia rehabilitation [Table 1]. Aphasia recovery can be supported by reactivation of perilesional cortical areas (intrahemispheric compensation) or by transfer of language functions into the nondominant, nonaffected hemisphere (interhemispheric compensation) (Heiss and Thiel, 2006).
Interhemispheric compensation is thought to occur by unmasking of possibly language related areas in the right hemisphere (RH) through reduction of transcallosal inhibition by a lesion in the left hemisphere (LH) (Winhuisen et al., 2005). There is an on-going debate on whether this released activity in those RH networks is beneficial for recovery of language function (Anglade et al., 2014). In post-stroke aphasia, regions of the RH that are homologue to the language areas in the damaged left hemisphere (LH) can support some language recovery, however, the best rehabilitation results have so far been observed with intrahemispheric rather than interhemispheric compensation (Heiss et al., 1999; Rosen et al., 2000). Therefore, the majority of NIBS studies have tried to facilitate recruitment of perilesonal cortex in the damaged hemisphere (Torres et al., 2013). Excitatory NIBS (high-frequency rTMS > 1 Hz; intermittent theta burst stimulation; anodal tDCS) has been used to augment cortical excitability of the left hemispheric language network, whereas inhibitory NIBS (low-frequency rTMS ≤ 1Hz; cathodal tDCS) aims at reducing RH over-activations (Heiss and Thiel, 2012). Both approaches are based on the idea that re-establishing left hemisphere language network activity results in better rehabilitation results (Crosson et al., 2007).
To date, RCTs using inhibitory rTMS have shown some evidence of effectiveness on language and functional communication outcomes in chronic post-stroke aphasia even without SLT (Barwood et al., 2011; Medina et al., 2012). However, patients in the acute stages undergoing SLT seem to benefit more from this type of brain stimulation (Kindler et al., 2012). In fact, several recent RCTs involving right-handed patients with sub-acute aphasia support the enhancing effect of inhibitory rTMS on language recovery when combined with SLT (Weiduschat et al., 2011; Kindler et al., 2012; Heiss et al., 2013; Seniσw et al., 2013; Thiel et al., 2013). Because not all patients seem to benefit equally from this treatment (Waldowski et al., 2012; Heiss et al., 2013; Seniów et al., 2013), there is a need to refine the criteria identifying those patients which are likely to best respond to this kind of therapy. For example, Seniów and colleagues (2013) report better efficacy in participants with severe aphasia and Heiss and colleagues (2013) showed that left handers might not respond to the treatment in the same way as right handers. Recently, language improvements have been related to SLT in combination with inhibitory and excitatory rTMS in patients with subacute non-fluent aphasia (Khedr et al., 2014). Some positive results on anomia (as measured by picture naming and semantic fluency tasks) have also been reported in case series with excitatory rTMS (Cotelli et al., 2011; Szaflarski et al., 2011), but no RCT testing this stimulation mode has been published to date.
In comparison to rTMS, available evidence for tDCS in aphasia rehabilitation is scarce. In 2013, a Cochrane review included four randomized controlled cross-over trials with a total of 33 patients with chronic aphasia (Monti et al., 2008; Flöel et al., 2011; Kang et al., 2011; Marangolo et al., 2011) and one RCT with 21 patients with subacute aphasia (You et al., 2011). This was the first systematic review of this stimulation modality and it was concluded that at present there is insufficient evidence to support the view that tDCS enhances SLT outcomes, contrary to the conclusion of many published trials (Elsner et al., 2013). However, the authors found some indication of positive effects with cathodal tDCS (i.e., inhibitory NIBS) over the non-lesioned hemisphere based on three studies (Flöel et al., 2011; Kang et al., 2011; You et al., 2011) and advocated further randomized controlled trials with a parallel group design and sample-size estimation.
Beyond improved clinical trial design future RCTs on NIBS efficacy also need to investigate alternate stimulation sites for tDCS (Baker et al., 2010; Fiori et al., 2013; Marangolo et al., 2014) and for rTMS (Heiss et al., 2013), possibly neuroimaging guided and should control for lesion location and premorbid hemispheric speech dominance.
SLT is the best treatment to improve language and functional communication in post-stroke aphasia. However, even well studied impairment-based approaches show limited effects on language recovery. Pharmacological (in particular Piracetam) and NIBS strategies (mainly inhibitory rTMS over the contralesional hemisphere) offer promising new ways to optimize SLT effects and clearly merit further research.
| References|| |
|1.||AAN (1994) Assessment: melodic intonation therapy. Neurology 44:566-568. |
|2.||Anglade C, Thiel A, Ansaldo AI (2014) The complementary role of the cerebral hemispheres in recovery from aphasia after stroke: a critical review of literature. Brain Inj 28:138-145. |
|3.||Ashtary F, Janghorbani M, Chitsaz A, Reisi M, Bahrami A (2006) A randomized, double-blind trial of bromocriptine efficacy in nonfluent aphasia after stroke. Neurology 66:914-916. |
|4.||Baker JM, Rorden C, Fridriksson J (2010) Using transcranial direct-current stimulation to treat stroke patients with aphasia. Stroke 41:1229-1236. |
|5.||Barwood CH, Murdoch BE, Whelan B-M, Lloyd D, Riek S, O'Sullivan J, Coulthard A, Wong A, Aitken P, Hall G (2011) The effects of low frequency Repetitive Transcranial Magnetic Stimulation (rTMS) and sham condition rTMS on behavioural language in chronic non-fluent aphasia: Short term outcomes. NeuroRehabilitation 28:113-128. |
|6.||Beeson PM, Robey RR (2006) Evaluating single-subject treatment research: lessons learned from the aphasia literature. Neuropsychol Rev 16:161-169. |
|7.||Berthier ML (2014) Cognitive enhancing drugs in aphasia: A vote for hope. Aphasiology 28:128-132. |
|8.||Berthier ML, Pulvermüller F, Dávila G, Casares NG, Gutiérrez A (2011) Drug therapy of post-stroke aphasia: a review of current evidence. Neuropsychol Rev 21:302-317. |
|9.||Berthier ML, Green C, Higueras C, Fernandez I, Hinojosa J, Martin M (2006) A randomized, placebo-controlled study of donepezil in poststroke aphasia. Neurology 67:1687-1689. |
|10.||Berthier ML, Green C, Lara JP, Higueras C, Barbancho MA, Dávila G, Pulvermüller F (2009) Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia. Ann Neurol 65:577-585. |
|11.||Brady MC, Kelly H, Godwin J, Enderby P (2012) Speech and language therapy for aphasia following stroke. Cochrane Database Syst Rev 5: CD000425. |
|12.||Cahana-Amitay D, Albert ML, Oveis A (2014) Psycholinguistics of aphasia pharmacotherapy: Asking the right questions. Aphasiology 28:133-154. |
|13.||Carmichael ST (2006) Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann Neurol 59:735-742. |
|14.||Code C, Petheram B (2011) Delivering for aphasia. Int J Speech Lang Pathol 13:3-10. |
|15.||Cotelli M, Fertonani A, Miozzo A, Rosini S, Manenti R, Padovani A, Ansaldo AI, Cappa SF, Miniussi C (2011) Anomia training and brain stimulation in chronic aphasia. Neuropsychol Rehabil 21:717-741. |
|16.||Cramer SC (2008) Repairing the human brain after stroke: I. Mechanisms of spontaneous recovery. Ann Neurol 63:272-287. |
|17.||Crosson B, McGregor K, Gopinath KS, Conway TW, Benjamin M, Chang YL, Moore AB, Raymer AM, Briggs RW, Sherod MG (2007) Functional MRI of language in aphasia: a review of the literature and the methodological challenges. Neuropsychol Rev 17:157-177. |
|18.||Davidson B, Howe T, Worrall L, Hickson L, Togher L (2008) Social participation for older people with aphasia: the impact of communication disability on friendships. Top Stroke Rehabil 15:325-340. |
|19.||Doesborgh SJ, van de Sandt-Koenderman MW, Dippel DW, van Harskamp F, Koudstaal PJ, Visch-Brink EG (2004) Effects of semantic treatment on verbal communication and linguistic processing in aphasia after stroke a randomized controlled trial. Stroke 35:141-146. |
|20.||Donnan GA, Baron JC, Davis SM, Sharp FR (2013) The ischemic penumbra: CRC Press. |
|21.||Elsner B, Kugler J, Pohl M, Mehrholz J (2013) Transcranial direct current stimulation (tDCS) for improving aphasia in patients after stroke (Review). Cochrane Database Syst Rev 6:CD009760. |
|22.||Fiori V, Cipollari S, Di Paola M, Razzano C, Caltagirone C, Marangolo P (2013) tDCS stimulation segregates words in the brain: evidence from aphasia. Front Hum Neurosci 7:269. |
|23.||Flöel A, Meinzer M, Kirstein R, Nijhof S, Deppe M, Knecht S, Breitenstein C (2011) Short-term anomia training and electrical brain stimulation. Stroke 42:2065-2067. |
|24.||Gill SK, Leff AP (2014) Dopaminergic therapy in aphasia. Aphasiology 28: 155-170. |
|25.||Godecke E, Hird K, Lalor EE, Rai T, Phillips MR (2012) Very early poststroke aphasia therapy: a pilot randomized controlled efficacy trial. Int J Stroke 7:635-644. |
|26.||Greener J, Enderby P, Whurr R (1999) Speech and language therapy for aphasia following stroke. Cochrane Database Syst Rev 4:CD000425. |
|27.||Greener J, Enderby P, Whurr R (2001) Pharmacological treatment for aphasia following stroke. Cochrane Database Syst Rev 4:CD000424. |
|28.||Heiss WD, Thiel A (2006) A proposed regional hierarchy in recovery of post-stroke aphasia. Brain Lang 98:118-123. |
|29.||Heiss WD, Thiel A (2012) Is transcranial magnetic stimulation an effective therapy for aphasia? Clinical Practice 9:473-482. |
|30.||Heiss WD, Kessler J, Thiel A, Ghaemi M, Karbe H (1999) Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia. Ann Neurol 45:430-438. |
|31.||Heiss WD, Hartmann A, Rubi-Fessen I, Anglade C, Kracht L, Kessler J, Weiduschat N, Rommel T, Thiel A (2013) Noninvasive brain stimulation for treatment of right-and left-handed poststroke aphasics. Cerebrovasc Dis 36:363-372. |
|32.||Holland AL, Hinckley JJ (2004) Communication disorders in adults: functional approaches to aphasia. In: The MIT encyclopedia of communication disorders (Kent RD, ed), pp 283-285: MIT Press. |
|33.||Jauch E, Saver J, Adams Jr H, Bruno A, Connors J, Demaerschalk B, Khatri P, McMullan Jr P, Qureshi A, Rosenfield K (2013) on behalf of the American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Peripheral Vascular Disease, and Council on Clinical Cardiology Guidelines for the Early Management of Patients With Acute Ischemic Stroke. A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44:870-947. |
|34.||Kang EK, Kim YK, Sohn HM, Cohen LG, Paik NJ (2011) Improved picture naming in aphasia patients treated with cathodal tDCS to inhibit the right Broca's homologue area. Restor Neurol Neurosci 29:141-152. |
|35.||Kasa P, Papp H, Kasa Jr P, Torok I (2000) Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain. Neuroscience 101:89-100. |
|36.||Katz RC, Hallowell B, Code C, Armstrong E, Roberts P, Pound C, Katz L (2000) A multinational comparison of aphasia management practices. I Int J Lang Commun Disord 35:303-314. |
|37.||Katzman R, Clasen R, Klatzo I, Meyer JS, Pappius HM, Waltz AG (1977) Report of joint committee for stroke resources. IV. brain edema in stroke. Stroke 8:512-540. |
|38.||Kauhanen ML, Korpelainen JT, Hiltunen P, Brusin E, Mononen H, Määttä R, Nieminen P, Sotaniemi KA, Myllylä VV (1999) Poststroke depression correlates with cognitive impairment and neurological deficits. Stroke 30:1875-1880. |
|39.||Kessler J, Thiel A, Karbe H, Heiss W (2000) Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients. Stroke 31:2112-2116. |
|40.||Khedr EM, El-Fetoh NA, Ali AM, El-Hammady DH, Khalifa H, Atta H, Karim AA (2014) Dual-hemisphere repetitive transcranial magnetic stimulation for rehabilitation of poststroke aphasia a randomized, double-Blind clinical trial. Neurorehabil Neural Repair In Press. |
|41.||Kindler J, Schumacher R, Cazzoli D, Gutbrod K, Koenig M, Nyffeler T, Dierks T, Müri RM (2012) Theta burst stimulation over the right Broca's homologue induces improvement of naming in aphasic patients. Stroke 43:2175-2179. |
|42.||Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7. |
|43.||Leemann B, Laganaro M, Chetelat-Mabillard D, Schnider A (2011) Crossover trial of subacute computerized aphasia therapy for anomia with the addition of either levodopa or placebo. Neurorehabil Neural Repair 25: 43-47. |
|44.||Liepert J (2008) Pharmacotherapy in restorative neurology. Curr Opin Neurol 21:639-643. |
|45.||Lo RC (1986) Recovery and rehabilitation after stroke. Can Fam Physician 32:1851-1853. |
|46.||Marangolo P, Marinelli C, Bonifazi S, Fiori V, Ceravolo M, Provinciali L, Tomaiuolo F (2011) Electrical stimulation over the left inferior frontal gyrus (IFG) determines long-term effects in the recovery of speech apraxia in three chronic aphasics. Behav Brain Res 225:498-504. |
|47.||Marangolo P, Fiori V, Campana S, Antonietta Calpagnano M, Razzano C, Caltagirone C, Marini A (2014) Something to talk about: Enhancement of linguistic cohesion through tdCS in chronic non fluent aphasia. Neuropsychologia 53:246-256. |
|48.||Martinsson L, Hardemark H, Eksborg S (2007) Amphetamines for improving recovery after stroke. Cochrane Database Syst Rev 1:CD002090. |
|49.||McNeil MR, Pratt SR (2001) Defining aphasia: Some theoretical and clinical implications of operating from a formal definition. Aphasiology 15:901-911. |
|50.||Medina J, Norise C, Faseyitan O, Coslett HB, Turkeltaub PE, Hamilton RH (2012) Finding the right words: transcranial magnetic stimulation improves discourse productivity in non-fluent aphasia after stroke. Aphasiology 26:1153-1168. |
|51.||Monti A, Cogiamanian F, Marceglia S, Ferrucci R, Mameli F, Mrakic-Sposta S, Vergari M, Zago S, Priori A (2008) Improved naming after transcranial direct current stimulation in aphasia. J Neurol Neurosurg Psychiatry 79: 451-453. |
|52.||Nudo RJ (2011) Neural bases of recovery after brain injury. J Commun Disord 44:515-520. |
|53.||Nudo RJ (2013) Recovery after brain injury: mechanisms and principles. Front Hum Neurosci 7:887. |
|54.||Pérez de la Ossa N, Davalos A (2007) Neuroprotection in cerebral infarction: the opportunity of new studies. Cerebrovasc Dis 24:153-156. |
|55.||Pulvermüller F, Neininger B, Elbert T, Mohr B, Rockstroh B, Koebbel P, Taub E (2001) Constraint-induced therapy of chronic aphasia after stroke. Stroke 32:1621-1626. |
|56.||Rose M, Ferguson A, Power E, Togher L, Worrall L (2014) Aphasia rehabilitation in Australia: Current practices, challenges and future directions. Int J Speech Lang Pathol 16:169-180. |
|57.||Rosen H, Petersen S, Linenweber M, Snyder A, White D, Chapman L, Dromerick A, Fiez J, Corbetta M (2000) Neural correlates of recovery from aphasia after damage to left inferior frontal cortex. Neurology 55:1883-1894. |
|58.||Sabe L, Salvarezza F, Cuerva AG, Leiguarda R, Starkstein S (1995) A randomized, double-blind, placebocontrolled study of bromocriptine in nonfluent aphasia. Neurology 45:2272-2274. |
|59.||Salter K, Teasell R, Foley N, Allen L (2013) Aphasia. In: The evidence-based review of stroke rehabilitation (EBRSR) - 16th edition (Teasell R, Foley N, Salter K, Richardson M, Allen L, Hussein N, Bhogal S, Jutai J, Speechley M, eds). www.ebrsr.com. |
|60.||Sarter M, Hasselmo ME, Bruno JP, Givens B (2005) Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res Rev 48:98-111. |
|61.||Seniów J, Litwin M, Litwin T, Le?niak M, Członkowska A (2009) New approach to the rehabilitation of post-stroke focal cognitive syndrome: Effect of levodopa combined with speech and language therapy on functional recovery from aphasia. J Neurol Sci 283:214-218. |
|62.||Seniów J, Waldowski K, Le?niak M, Iwañski S, Czepiel W, Członkowska A (2013) Transcranial Magnetic Stimulation combined with speech and language training in early aphasia rehabilitation: a randomized double-blind controlled pilot study. Top Stroke Rehabil 20:250-261. |
|63.||Shadden B (2005) Aphasia as identity theft: Theory and practice. Aphasiology 19:211-223. |
|64.||Sickert A, Anders LC, Münte TF, Sailer M (2014) Constraint-induced aphasia therapy following sub-acute stroke: a single-blind, randomised clinical trial of a modified therapy schedule. J Neurol Neurosurg Psychiatry 85: 51-55. |
|65.||Sparks RW, Helm NA, Albert ML (1974) Aphasia rehabilitation resulting from melodic intonation therapy. Cortex 10:303-316. |
|66.||Szaflarski JP, Vannest J, Wu SW, DiFrancesco MW, Banks C, Gilbert DL (2011) Excitatory repetitive transcranial magnetic stimulation induces improvements in chronic post-stroke aphasia. Med Sci Monit 17:CR132-139. |
|67.||Thiel A, Hartmann A, Rubi-Fessen I, Anglade C, Kracht L, Weiduschat N, Kessler J, Rommel T, Heiss WD (2013) Effects of noninvasive brain stimulation on language networks and recovery in early poststroke aphasia. Stroke 44:2240-2246. |
|68.||Torres J, Drebing D, Hamilton R (2013) TMS and tDCS in post-stroke aphasia: Integrating novel treatment approaches with mechanisms of plasticity. Restor Neurol Neurosci 31:501-515. |
|69.||van der Meulen I, van de Sandt-Koenderman WME, Heijenbrok-Kal MH, Visch-Brink EG, Ribbers GM (2014) The efficacy and timing of melodic intonation therapy in subacute aphasia. Neurorehabil Neural Repair In Press. |
|70.||Verna A, Davidson B, Rose T (2009) Speech-language pathology services for people with aphasia: A survey of current practice in Australia. Int J Speech-Lang Pa 11:191-205. |
|71.||Waldowski K, Seniów J, Le?niak M, Iwañski S, Cz³onkowska A (2012) Effect of low-frequency repetitive transcranial magnetic stimulation on naming abilities in early-stroke aphasic patients: a prospective, randomized, double-blind sham-controlled study. ScientificWorldJournal 2012:518568. |
|72.||Walker-Batson D, Curtis S, Natarajan R, Ford J, Dronkers N, Salmeron E, Lai J, Unwin DH (2001) A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 32:2093-2098. |
|73.||Weiduschat N, Thiel A, Rubi-Fessen I, Hartmann A, Kessler J, Merl P, Kracht L, Rommel T, Heiss WD (2011) Effects of repetitive transcranial magnetic stimulation in aphasic stroke a randomized controlled pilot study. Stroke 42:409-415. |
|74.||WHO (2001) ICF: International Classification of Functioning, Disability, and Health. In. Geneva, Switzerland. |
|75.||Winhuisen L, Thiel A, Schumacher B, Kessler J, Rudolf J, Haupt WF, Heiss WD (2005) Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia A combined repetitive transcranial magnetic stimulation and positron emission tomography Study. Stroke 36:1759-1763. |
|76.||Worrall L, Frattali C (2000) Neurogenic Communication Disorders: A Functional Approach. New-York: Thieme. |
|77.||You DS, Kim DY, Chun MH, Jung SE, Park SJ (2011) Cathodal transcranial direct current stimulation of the right Wernicke's area improves comprehension in subacute stroke patients. Brain Lang 119:1-5. |
|78.||Zumbansen A, Peretz I, Hébert S (2014) Melodic intonation therapy: back to basics for future research. Front Neurol 5:7. |
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