146 results on '"Leff AP"'
Search Results
2. Phantasia, aphantasia, and hyperphantasia: Empirical data and conceptual considerations
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Larner, AJ, Leff, AP, and Nachev, PC
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- 2024
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- View/download PDF
3. RELEASE: a protocol for a systematic review based, individual participant data, meta- and network meta-analysis, of complex speech-language therapy interventions for stroke-related aphasia
- Author
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Brady, MC, Ali, M, VandenBerg, K, Williams, LJ, Williams, LR, Abo, M, Becker, F, Bowen, A, Brandenburg, C, Breitenstein, C, Bruehl, S, Copland, DA, Cranfill, TB, Pietro-Bachmann, MD, Enderby, P, Fillingham, J, Galli, FL, Gandolfi, M, Glize, B, Godecke, E, Hawkins, N, Hilari, K, Hinckley, J, Horton, S, Howard, D, Jaecks, P, Jefferies, E, Jesus, LMT, Kambanaros, M, Kang, EK, Khedr, EM, Kong, APH, Kukkonen, T, Laganaro, M, Ralph, MAL, Laska, AC, Leemann, B, Leff, AP, Lima, RR, Lorenz, A, MacWhinney, B, Marshall, RS, Mattioli, F, Maviş, İ, Meinzer, M, Nilipour, R, Noé, E, Paik, NJ, Palmer, R, Papathanasiou, I, Patricio, BF, Martins, IP, Price, C, Jakovac, TP, Rochon, E, Rose, ML, Rosso, C, Rubi-Fessen, I, Ruiter, MB, Snell, C, Stahl, B, Szaflarski, JP, Thomas, SA, Van De Sandt-Koenderman, M, Van Der Meulen, I, Visch-Brink, E, Worrall, L, Wright, HH, Brady, MC [0000-0002-4589-7021], Ali, M [0000-0001-5899-2485], VandenBerg, K [0000-0001-5035-9650], Williams, LJ [0000-0002-6317-1718], Williams, LR [0000-0003-2430-1142], Abo, M [0000-0001-6701-4974], Becker, F [0000-0002-0857-0628], Bowen, A [0000-0003-4075-1215], Brandenburg, C [0000-0002-6992-7790], Breitenstein, C [0000-0002-6408-873X], Bruehl, S [0000-0003-4826-1990], Copland, DA [0000-0002-2257-4270], Cranfill, TB [0000-0001-7608-6443], Pietro-Bachmann, MD [0000-0001-8027-2337], Enderby, P [0000-0002-4371-9053], Fillingham, J [0000-0002-0363-8021], Galli, FL [0000-0001-9244-9179], Gandolfi, M [0000-0002-0877-4807], Glize, B [0000-0001-9618-2088], Hawkins, N [0000-0002-7210-1295], Hilari, K [0000-0003-2091-4849], Hinckley, J [0000-0002-4052-1420], Horton, S [0000-0002-2133-1410], Howard, D [0000-0001-9141-5751], Jaecks, P [0000-0002-5878-1327], Jefferies, E [0000-0002-3826-4330], Jesus, LMT [0000-0002-8534-3218], Kambanaros, M [0000-0002-5857-9460], Kang, EK [0000-0001-5315-1361], Khedr, EM [0000-0001-5679-9833], Kong, APH [0000-0002-6211-0358], Kukkonen, T [0000-0002-8189-0337], Laganaro, M [0000-0002-4054-0939], Ralph, MAL [0000-0001-5907-2488], Laska, AC [0000-0002-7330-940X], Leemann, B [0000-0003-2226-6777], Leff, AP [0000-0002-0831-3541], Lima, RR [0000-0002-9914-4789], Lorenz, A [0000-0002-0200-1977], MacWhinney, B [0000-0002-4988-1342], Marshall, RS [0000-0001-9313-5454], Mattioli, F [0000-0002-4912-5520], Maviş, İ [0000-0003-3924-1138], Meinzer, M [0000-0003-1370-3947], Nilipour, R [0000-0003-4180-7989], Noé, E [0000-0002-2547-8727], Paik, NJ [0000-0002-5193-8678], Palmer, R [0000-0002-2335-7104], Papathanasiou, I [0000-0003-0999-696X], Patricio, BF [0000-0002-2619-470X], Martins, IP [0000-0002-9611-7400], Price, C [0000-0003-0111-9364], Jakovac, TP [0000-0002-5018-9556], Rochon, E [0000-0001-5521-0513], Rose, ML [0000-0002-8892-0965], Rosso, C [0000-0001-7236-1508], Rubi-Fessen, I [0000-0002-9775-3812], Ruiter, MB [0000-0001-6147-5235], Snell, C [0000-0001-8606-7801], Stahl, B [0000-0003-3957-1495], Szaflarski, JP [0000-0002-5936-6627], Thomas, SA [0000-0003-0704-9387], van de Sandt-Koenderman, M [0000-0002-8104-6937], van der Meulen, I [0000-0002-6156-3873], Visch-Brink, E [0000-0001-7833-0112], Worrall, L [0000-0002-3283-7038], Wright, HH [0000-0001-6922-6364], and Apollo - University of Cambridge Repository
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Stroke ,IPD ,meta-analysis ,stroke, aphasia, complex intervention, IPD, meta-analysis ,genetic structures ,aphasia ,complex intervention - Abstract
Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis.\ud \ud Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke.\ud \ud Methods and procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions.\ud \ud Outcomes and results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains.\ud \ud Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke.\ud \ud Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947)
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- 2020
4. Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients
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Nardo, D., Holland, R., Leff, AP, Price, CJ, Crinion, JT, Nardo, Davide, Holland, Rachel, Leff, Alexander P, Price, Cathy J, and Crinion, Jennifer T
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Adult ,Male ,anomia treatment ,Anomia ,Young Adult ,Reaction Time ,Aphasia ,Humans ,Nervous System Physiological Phenomena ,word retrieval ,Aged ,picture naming ,phonemic cueing ,Original Articles ,Middle Aged ,Magnetic Resonance Imaging ,aphasia ,Semantics ,Stroke ,Treatment Outcome ,Chronic Disease ,Female ,Cues ,Photic Stimulation ,Human - Abstract
See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Naming in aphasia can be facilitated by phonemic cueing, both as an immediate retrieval strategy and as a long-term treatment. Nardo et al. report that immediate and long-term facilitation of naming rely on common neural networks, while whole words and partial cues promote naming via different networks., See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted—for the first time—a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol—a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients’ naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen’s d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patients.
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- 2017
5. Auditory training changes temporal lobe connectivity in ‘Wernicke’s aphasia’: a randomised trial
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Woodhead, ZVJ, Crinion, J, Teki, S, Penny, W, Price, CJ, and Leff, AP
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Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex.
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- 2017
6. Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable
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Boyd, LA, Hayward, KS, Ward, NS, Stinear, CM, Rosso, C, Fisher, RJ, Carter, AR, Leff, AP, Copland, DA, Carey, LM, Cohen, LG, Basso, DM, Maguire, JM, Cramer, SC, Boyd, LA, Hayward, KS, Ward, NS, Stinear, CM, Rosso, C, Fisher, RJ, Carter, AR, Leff, AP, Copland, DA, Carey, LM, Cohen, LG, Basso, DM, Maguire, JM, and Cramer, SC
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© 2017, © 2017 World Stroke Organization. The most difficult clinical questions in stroke rehabilitation are “What is this patient’s potential for recovery?” and “What is the best rehabilitation strategy for this person, given her/his clinical profile?” Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.
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- 2017
7. Auditory STM Capacity Correlates with Gray Matter Density in the Left Posterior STS in Cognitively Normal and Dyslexic Adults
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Richardson, FM, Ramsden, S, Ellis, C, Burnett, S, Megnin, O, Catmur, C, Schofield, TM, Leff, AP, and Price, CJ
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A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using whole-brain statistics, we identified a region in the left posterior STS where gray matter density was positively correlated with forward digit span, backward digit span, and performance on a "spoonerisms" task that required both auditory STM and phoneme manipulation. Across tasks and participant groups, the correlation was highly significant even when variance related to reading and auditory nonword repetition was factored out. Although the dyslexics had poorer phonological skills, the effect of auditory STM capacity in the left STS was the same as in the cognitively normal group. We also illustrate that the anatomical location of this effect is in proximity to a lesion site recently associated with reduced auditory STM capacity in patients with stroke damage. This result, therefore, indicates that gray matter density in the posterior STS predicts auditory STM capacity in the healthy and damaged brain. In conclusion, we suggest that our present findings are consistent with the view that there is an overlap between the mechanisms that support language processing and auditory STM.
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- 2011
8. The neuronal dynamics of speech sound processing
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Schofield, TM, primary, Iverson, P, additional, Kiebel, SJ, additional, Stephan, KE, additional, Kilner, JM, additional, Frison, KJ, additional, Crinion, JT, additional, Price, CJ, additional, and Leff, AP, additional
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- 2009
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9. Patients with impaired auditory comprehension activate the ‘dorsal' temporo-frontal stream when listening to intelligible speech
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Leff, AP, primary, Stephan, KE, additional, Seghier, M, additional, Friston, KJ, additional, Price, CJ, additional, and Schofield, TM, additional
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- 2009
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10. Rehabilitation of hemianopia.
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Schofield TM and Leff AP
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- 2009
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11. Treatment of reading impairment after stroke.
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Leff AP and Behrmann M
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- 2008
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12. Optokinetic therapy improves text reading in patients with hemianopic alexia: a controlled trial.
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Spitzyna GA, Wise RJ, McDonald SA, Plant GT, Kidd D, Crewes H, Leff AP, Spitzyna, G A, Wise, R J S, McDonald, S A, Plant, G T, Kidd, D, Crewes, H, and Leff, A P
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- 2007
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13. Jargon dyslexia: a single case study of intact reading comprehension in a jargon dysphasic.
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Warrington EK and Leff AP
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- 2000
14. Is central nervous system processing altered in patients with heart failure?
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Stuart D. Rosen, Richard J.S. Wise, Andrew J.S. Coats, Lewis Adams, Vincent J. Cunningham, Paolo G. Camici, Alexander P. Leff, Kevin Murphy, Rosen, Sd, Murphy, K, Leff, Ap, Cunningham, V, Wise, Rj, Adams, L, Coats, Aj, and Camici, Paolo
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Male ,Cardiac output ,Heart disease ,Cardiac Output, Low ,Hemodynamics ,Physical exercise ,Central Nervous System Diseases ,Hyperventilation ,medicine ,Humans ,Exercise ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Autonomic nervous system ,Dyspnea ,Cerebral blood flow ,Cerebrovascular Circulation ,Anesthesia ,Heart failure ,Perception ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Tomography, Emission-Computed - Abstract
Aims Breathlessness is a cardinal symptom of heart failure and the altered regulation of breathing is common. The contribution of abnormal central nervous system activity has not previously been investigated directly, although abnormal autonomic responses have been described. Our aim was to assess whether heart failure patients exhibit different patterns of regional brain activation after exercise stress. Methods We used positron emission tomography with (H2O)-O-15, to measure changes in regional cerebral blood flow (rCBF) and absolute global cerebral blood flow (gCBF) in 6 mate class II/III heart failure patients and 6 normal controls. Breathlessness (0-5 visual analogue scale) and respiratory parameters were measured at rest, after horizontal bicycle exercise and during isocapnic hyperventilation. CBF was measured in each condition in all subjects. Results Both groups were similarly breathless after exercise and the respiratory parameters were comparable. rCBF differences for the main comparison (exercise vs; hyperventilation) were: activation of the right frontal medial. gyrus (P < 0.001, Z = 4.90) and left precentral gyrus (P < 0.03, Z = 4.66) in controls but not in patients. Both groups had rCBF increases in the left anterior cingulate (P < 0.05, Z = 4.67) and right dorsal cingulate cortex (P < 0.05, Z = 4.66). The gCBF did not differ between exercise, isocapnic hyperventilation and rest in patients but, in controls, gCBF was greater after exercise compared to either isocapnic hyperventilation or rest. Conclusion Heart failure patients had a distinct pattern of regional cortical activity with exercise-induced breathlessness but unvarying CBF values between conditions. These central neural differences in activity may contribute to some features of heart failure, such as variability in symptoms and autonomic dysregulation. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
- Published
- 2004
15. The impact of speech rhythm and rate on comprehension in aphasia.
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Robson H, Thomasson H, Upton E, Leff AP, and Davis MH
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Background: Speech comprehension impairment in post-stroke aphasia is influenced by speech acoustics. This study investigated the impact of speech rhythm (syllabic isochrony) and rate on comprehension in people with aphasia (PWA). Rhythmical speech was hypothesised to support comprehension in PWA by reducing temporal variation, leading to enhanced speech tracking and more appropriate sampling of the speech stream. Speech rate was hypothesised to influence comprehension through auditory and linguistic processing time., Methods: One group of PWA (n = 19) and two groups of control participants (n = 10 and n = 18) performed a sentence-verification. Sentences were presented in two rhythm conditions (natural vs isochronous) and two rate conditions (typical, 3.6 Hz vs slow, 2.6 Hz) in a 2 × 2 factorial design. PWA and one group of controls performed the experiment with clear speech. The second group of controls performed the experiment with perceptually degraded speech., Results: D-prime analyses measured capacity to detect incongruent endings. Linear mixed effects models investigated the impact of group, rhythm, rate and clarity on d-prime scores. Control participants were negatively affected by isochronous rhythm in comparison to natural rhythm, likely due to alteration in linguistic cues. This negative impact remained or was exacerbated in control participants presented with degraded speech. In comparison, PWA were less affected by isochronous rhythm, despite producing d-prime scores matched to the degraded speech control group. Speech rate affected all groups, but only in interactions with rhythm, indicating that slow-rate isochronous speech was more comprehendible than typical-rate isochronous speech., Conclusions: The comprehension network in PWA interacts differently with speech rhythm. Rhythmical speech may support acoustic speech tracking by enhancing predictability and ameliorate the detrimental impact of atypical rhythm on linguistic cues. Alternatively, reduced temporal prediction in aphasia may limit the impact of deviation from natural temporal structure. Reduction of speech rate below the typical range may not benefit comprehension in PWA., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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16. Prevalence, patterns, and predictors of patient-reported non-motor outcomes at 30 days after acute stroke: Prospective observational hospital cohort study.
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Ozkan H, Ambler G, Banerjee G, Browning S, Leff AP, Ward NS, Simister RJ, and Werring DJ
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- Humans, Female, Aged, Male, Cohort Studies, Quality of Life, Prevalence, Cerebral Hemorrhage epidemiology, Cerebral Hemorrhage complications, Hospitals, Patient Reported Outcome Measures, Pain, Fatigue epidemiology, Fatigue complications, Stroke epidemiology, Stroke complications, Ischemic Stroke complications
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Background: Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains., Aims: We aimed to identify the prevalence, patterns, and the factors associated with non-motor outcomes 30 days after stroke., Methods: This prospective observational hospital cohort study-Stroke Investigation in North and Central London (SIGNAL)-identified patients with acute ischemic stroke or intracerebral hemorrhage (ICH) admitted to the Hyperacute Stroke Unit (HASU) at University College Hospital (UCH), London, between August 1, 2018 and August 31, 2019. We assessed non-motor outcomes (anxiety, depression, fatigue, sleep, participation in social roles and activities, pain, bowel function, and bladder function) at 30-day follow-up using the Patient-Reported Outcome Measurement Information System-Version 29 (PROMIS-29) scale and Barthel Index scale., Results: We obtained follow-up data for 605/719 (84.1%) eligible patients (mean age 72.0 years; 48.3% female; 521 with ischemic stroke, 84 with ICH). Anxiety (57.0%), fatigue (52.7%), bladder dysfunction (50.2%), reduced social participation (49.2%), and pain (47.9%) were the commonest adverse non-motor outcomes. The rates of adverse non-motor outcomes in ⩾ 1, ⩾ 2 and ⩾ 3 domains were 89%, 66.3%, and 45.8%, respectively; in adjusted analyses, stroke due to ICH (compared to ischemic stroke) and admission stroke severity were the strongest and most consistent predictors. There were significant correlations between bowel dysfunction and bladder dysfunction (κ = 0.908); reduced social participation and bladder dysfunction (κ = 0.844); and anxiety and fatigue (κ = 0.613). We did not identify correlations for other pairs of non-motor domains., Conclusion: Adverse non-motor outcomes were very common at 30 days after stroke, affecting nearly 90% of evaluated patients in at least one health domain, about two-thirds in two or more domains, and almost 50% in three or more domains. Stroke due to ICH and admission stroke severity were the strongest and most consistent predictors. Adverse outcomes occurred in pairs of domains, such as with anxiety and fatigue. Our findings emphasize the importance of a multi-domain approach to effectively identify adverse non-motor outcomes after stroke to inform the development of more holistic patient care pathways after stroke., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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17. Predicting Online Behavioural Responses to Transcranial Direct Current Stimulation in Stroke Patients with Anomia.
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Hope TMH, Ondobaka S, Akkad H, Nardo D, Pappa K, Price CJ, Leff AP, and Crinion JT
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Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks' performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it.
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- 2024
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18. Advances in the Rehabilitation of Hemispatial Inattention.
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Singh NR and Leff AP
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- Humans, Transcranial Direct Current Stimulation methods, Transcranial Magnetic Stimulation methods, Mental Disorders rehabilitation, Virtual Reality Exposure Therapy
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Purpose of Review: There continue to be a plethora of approaches to the rehabilitation of hemispatial inattention, from different forms of sensory stimulation (visual, auditory and somatosensory feedback), through all major modes of non-invasive brain stimulation to drug therapies. Here we summarise trials published in the years 2017-2022 and tabulate their effect sizes, with the aim of drawing on common themes that may serve to inform future rehabilitative studies., Recent Findings: Immersive virtual reality approaches to visual stimulation seem well tolerated, although they have yet to yield any clinically relevant improvements. Dynamic auditory stimulation looks very promising and has high potential for implementation. Robotic interventions are limited by their cost and are perhaps best suited to patients with a co-occurring hemiparesis. Regarding brain stimulation, rTMS continues to demonstrate moderate effects but tDCS studies have yielded disappointing results so far. Drugs, primarily aimed at the dopaminergic system, often demonstrate beneficial effects of a medium size, but as with many of the approaches, it seems difficult to predict responders and non-responders. Our main recommendation is that researchers consider incorporating single-case experimental designs into their studies as rehabilitation trials are likely to remain small in terms of patient numbers, and this is the best way to deal with all the factors that cause large between-subject heterogeneity., (© 2023. The Author(s).)
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- 2023
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19. Systematic evaluation of high-level visual deficits and lesions in posterior cerebral artery stroke.
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Robotham RJ, Rice GE, Leff AP, Lambon Ralph MA, and Starrfelt R
- Abstract
Knowledge about the consequences of stroke on high-level vision comes primarily from single case studies of patients selected based on their behavioural profiles, typically patients with specific stroke syndromes like pure alexia or prosopagnosia. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical behavioural and lesion profiles of impairments in high-level vision after posterior cerebral artery stroke. We present behavioural and lesion data from the Back of the Brain project, to date the largest ( N = 64) and most detailed examination of patients with cortical posterior cerebral artery strokes selected based on lesion location. The aim of the current study was to relate behavioural performance with faces, objects and written words to lesion data through two complementary analyses: (i) a multivariate multiple regression analysis to establish the relationships between lesion volume, lesion laterality and the presence of a bilateral lesion with performance and (ii) a voxel-based correlational methodology analysis to establish whether there are distinct or separate regions within the posterior cerebral artery territory that underpin the visual processing of words, faces and objects. Behaviourally, most patients showed more general deficits in high-level vision ( n = 22) or no deficits at all ( n = 21). Category-selective deficits were rare ( n = 6) and were only found for words. Overall, total lesion volume was most strongly related to performance across all three domains. While behavioural impairments in all domains were observed following unilateral left and right as well as bilateral lesions, the regions most strongly related to performance mainly confirmed the pattern reported in more selective cases. For words, these included a left hemisphere cluster extending from the occipital pole along the fusiform and lingual gyri; for objects, bilateral clusters which overlapped with the word cluster in the left occipital lobe. Face performance mainly correlated with a right hemisphere cluster within the white matter, partly overlapping with the object cluster. While the findings provide partial support for the relative laterality of posterior brain regions supporting reading and face processing, the results also suggest that both hemispheres are involved in the visual processing of faces, words and objects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2023
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20. Colour perception deficits after posterior stroke: Not so rare after all?
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Munk AH, Starup EB, Lambon Ralph MA, Leff AP, Starrfelt R, and Robotham RJ
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- Humans, Color Perception, Brain, Color Vision Defects complications, Color Vision Defects diagnosis, Stroke complications
- Abstract
Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury, and is generally considered to be rare. Both hemispheres are thought to contribute to colour perception, but most published cases have had bilateral or right hemisphere lesions. In contrast to congenital colour blindness that affects the discrimination between specific hues, cerebral achromatopsia is often described as affecting perception across all colours. Most studies of cerebral achromatopsia have been single cases or case series of patients with colour perception deficits. Here, we explore colour perception deficits in an unbiased sample of patients with stroke affecting the posterior cerebral artery (N = 63) from the Back of the Brain project. Patients were selected based on lesion location only, and not on the presence of a given symptom. All patients were tested with the Farnsworth D-15 Dichotomous Colour Blindness Test and performance compared to matched controls (N = 45) using single case statistics. In patients with abnormal performance, the patterns of colour difficulties were qualitatively analysed. 22% of the patients showed significant problems with colour discrimination (44% of patients with bilateral lesions, 28% with left hemisphere lesions and 5% with right hemisphere lesions). Lesion analyses identified two regions in ventral occipital temporal areas in the left hemisphere as particularly strongly related to impaired performance in colour perception, but also indicated that bilateral lesions are more strongly associated with impaired performance that unilateral lesions. While some patients only had mild deficits, colour perception impairments were in many cases severe. Many patients had selective deficits only affecting the perception of some hues. The results suggest that colour perception difficulties following PCA stroke are common, and that they vary in severity and expression. In addition, the results point towards bilateral processing of colour perception with a left hemispheric domination, contradicting previous reports., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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21. Mapping spoken language and cognitive deficits in post-stroke aphasia.
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Akkad H, Hope TMH, Howland C, Ondobaka S, Pappa K, Nardo D, Duncan J, Leff AP, and Crinion J
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- Adult, Humans, Magnetic Resonance Imaging adverse effects, Cognition, Aphasia, Stroke complications, Cognition Disorders complications
- Abstract
Aphasia is an acquired disorder caused by damage, most commonly due to stroke, to brain regions involved in speech and language. While language impairment is the defining symptom of aphasia, the co-occurrence of non-language cognitive deficits and their importance in predicting rehabilitation and recovery outcomes is well documented. However, people with aphasia (PWA) are rarely tested on higher-order cognitive functions, making it difficult for studies to associate these functions with a consistent lesion correlate. Broca's area is a particular brain region of interest that has long been implicated in speech and language production. Contrary to classic models of speech and language, cumulative evidence shows that Broca's area and surrounding regions in the left inferior frontal cortex (LIFC) are involved in, but not specific to, speech production. In this study we aimed to explore the brain-behaviour relationships between tests of cognitive skill and language abilities in thirty-six adults with long-term speech production deficits caused by post-stroke aphasia. Our findings suggest that non-linguistic cognitive functions, namely executive functions and verbal working memory, explain more of the behavioural variance in PWA than classical language models imply. Additionally, lesions to the LIFC, including Broca's area, were associated with non-linguistic executive (dys)function, suggesting that lesions to this area are associated with non-language-specific higher-order cognitive deficits in aphasia. Whether executive (dys)function - and its neural correlate in Broca's area - contributes directly to PWA's language production deficits or simply co-occurs with it, adding to communication difficulties, remains unclear. These findings support contemporary models of speech production that place language processing within the context of domain-general perception, action and conceptual knowledge. An understanding of the covariance between language and non-language deficits and their underlying neural correlates will inform better targeted aphasia treatment and outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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22. Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis.
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Brady MC, Ali M, VandenBerg K, Williams LJ, Williams LR, Abo M, Becker F, Bowen A, Brandenburg C, Breitenstein C, Bruehl S, Copland DA, Cranfill TB, Pietro-Bachmann MD, Enderby P, Fillingham J, Lucia Galli F, Gandolfi M, Glize B, Godecke E, Hawkins N, Hilari K, Hinckley J, Horton S, Howard D, Jaecks P, Jefferies E, Jesus LM, Kambanaros M, Kyoung Kang E, Khedr EM, Pak-Hin Kong A, Kukkonen T, Laganaro M, Lambon Ralph MA, Charlotte Laska A, Leemann B, Leff AP, Lima RR, Lorenz A, MacWhinney B, Shisler Marshall R, Mattioli F, Maviş İ, Meinzer M, Nilipour R, Noé E, Paik NJ, Palmer R, Papathanasiou I, Patricio B, Pavão Martins I, Price C, Prizl Jakovac T, Rochon E, Rose ML, Rosso C, Rubi-Fessen I, Ruiter MB, Snell C, Stahl B, Szaflarski JP, Thomas SA, van de Sandt-Koenderman M, van der Meulen I, Visch-Brink E, Worrall L, and Harris Wright H
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- Aged, Female, Humans, Infant, Newborn, Male, Language, Speech Therapy methods, Aphasia rehabilitation, Stroke complications, Stroke Rehabilitation
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Background: Stroke rehabilitation interventions are routinely personalized to address individuals' needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias., Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database., Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori . Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild-moderate/ moderate-severe based on language outcomes' median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness., Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants' greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3-4 SLT-h/week; ⩾ 50 hours). For moderate-severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild-moderate participants' greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males' greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week., Conclusions: We observed a treatment response in most subgroups' overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild-moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate-severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.
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- 2022
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23. Better long-term speech outcomes in stroke survivors who received early clinical speech and language therapy: What's driving recovery?
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Roberts S, Bruce RM, Lim L, Woodgate H, Ledingham K, Anderson S, Lorca-Puls DL, Gajardo-Vidal A, Leff AP, Hope TMH, Green DW, Crinion JT, and Price CJ
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- Humans, Language Therapy, Speech, Speech Therapy, Survivors, Aphasia etiology, Stroke complications, Stroke therapy
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Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy ( n = 79), versus those who did not ( n = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy.
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- 2022
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24. Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis
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Brady MC, Ali M, VandenBerg K, Williams LJ, Williams LR, Abo M, Becker F, Bowen A, Brandenburg C, Breitenstein C, Bruehl S, Copland DA, Cranfill TB, di Pietro-Bachmann M, Enderby P, Fillingham J, Galli FL, Gandolfi M, Glize B, Godecke E, Hawkins N, Hilari K, Hinckley J, Horton S, Howard D, Jaecks P, Jefferies E, Jesus LMT, Kambanaros M, Kang EK, Khedr EM, Kong APH, Kukkonen T, Laganaro M, Lambon Ralph MA, Laska AC, Leemann B, Leff AP, Lima RR, Lorenz A, MacWhinney B, Shisler Marshall R, Mattioli F, Maviş İ, Meinzer M, Nilipour R, Noé E, Paik NJ, Palmer R, Papathanasiou I, Patrício BF, Martins IP, Price C, Jakovac TP, Rochon E, Rose ML, Rosso C, Rubi-Fessen I, Ruiter MB, Snell C, Stahl B, Szaflarski JP, Thomas SA, van de Sandt-Koenderman M, van der Meulen I, Visch-Brink E, Worrall L, and Wright HH
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Background: People with language problems following stroke (aphasia) benefit from speech and language therapy. Optimising speech and language therapy for aphasia recovery is a research priority., Objectives: The objectives were to explore patterns and predictors of language and communication recovery, optimum speech and language therapy intervention provision, and whether or not effectiveness varies by participant subgroup or language domain., Design: This research comprised a systematic review, a meta-analysis and a network meta-analysis of individual participant data., Setting: Participant data were collected in research and clinical settings., Interventions: The intervention under investigation was speech and language therapy for aphasia after stroke., Main Outcome Measures: The main outcome measures were absolute changes in language scores from baseline on overall language ability, auditory comprehension, spoken language, reading comprehension, writing and functional communication., Data Sources and Participants: Electronic databases were systematically searched, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Linguistic and Language Behavior Abstracts and SpeechBITE (searched from inception to 2015). The results were screened for eligibility, and published and unpublished data sets (randomised controlled trials, non-randomised controlled trials, cohort studies, case series, registries) with at least 10 individual participant data reporting aphasia duration and severity were identified. Existing collaborators and primary researchers named in identified records were invited to contribute electronic data sets. Individual participant data in the public domain were extracted., Review Methods: Data on demographics, speech and language therapy interventions, outcomes and quality criteria were independently extracted by two reviewers, or available as individual participant data data sets. Meta-analysis and network meta-analysis were used to generate hypotheses., Results: We retrieved 5928 individual participant data from 174 data sets across 28 countries, comprising 75 electronic (3940 individual participant data), 47 randomised controlled trial (1778 individual participant data) and 91 speech and language therapy intervention (2746 individual participant data) data sets. The median participant age was 63 years (interquartile range 53–72 years). We identified 53 unavailable, but potentially eligible, randomised controlled trials (46 of these appeared to include speech and language therapy). Relevant individual participant data were filtered into each analysis. Statistically significant predictors of recovery included age (functional communication, individual participant data: 532, n = 14 randomised controlled trials) and sex (overall language ability, individual participant data: 482, n = 11 randomised controlled trials; functional communication, individual participant data: 532, n = 14 randomised controlled trials). Older age and being a longer time since aphasia onset predicted poorer recovery. A negative relationship between baseline severity score and change from baseline ( p < 0.0001) may reflect the reduced improvement possible from high baseline scores. The frequency, duration, intensity and dosage of speech and language therapy were variously associated with auditory comprehension, naming and functional communication recovery. There were insufficient data to examine spontaneous recovery. The greatest overall gains in language ability [14.95 points (95% confidence interval 8.7 to 21.2 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.78 points (95% confidence interval 0.48 to 1.1 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with receiving speech and language therapy 4 to 5 days weekly; for auditory comprehension [5.86 points (95% confidence interval 1.6 to 10.0 points) on the Aachen Aphasia Test-Token Test], the greatest gains were associated with receiving speech and language therapy 3 to 4 days weekly. The greatest overall gains in language ability [15.9 points (95% confidence interval 8.0 to 23.6 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.77 points (95% confidence interval 0.36 to 1.2 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with speech and language therapy participation from 2 to 4 (and more than 9) hours weekly, whereas the highest auditory comprehension gains [7.3 points (95% confidence interval 4.1 to 10.5 points) on the Aachen Aphasia Test-Token Test] were associated with speech and language therapy participation in excess of 9 hours weekly (with similar gains notes for 4 hours weekly). While clinically similar gains were made alongside different speech and language therapy intensities, the greatest overall gains in language ability [18.37 points (95% confidence interval 10.58 to 26.16 points) on the Western Aphasia Battery-Aphasia Quotient] and auditory comprehension [5.23 points (95% confidence interval 1.51 to 8.95 points) on the Aachen Aphasia Test-Token Test] were associated with 20–50 hours of speech and language therapy. Network meta-analyses on naming and the duration of speech and language therapy interventions across language outcomes were unstable. Relative variance was acceptable (< 30%). Subgroups may benefit from specific interventions., Limitations: Data sets were graded as being at a low risk of bias but were predominantly based on highly selected research participants, assessments and interventions, thereby limiting generalisability., Conclusions: Frequency, intensity and dosage were associated with language gains from baseline, but varied by domain and subgroup., Future Work: These exploratory findings require confirmatory study designs to test the hypotheses generated and to develop more tailored speech and language therapy interventions., Study Registration: This study is registered as PROSPERO CRD42018110947., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research ; Vol. 10, No. 28. See the NIHR Journals Library website for further project information. Funding was also provided by The Tavistock Trust for Aphasia., (Copyright © King’s Printer and Controller of HMSO 2022. This work was produced by Brady et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)
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- 2022
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25. A simple intervention for disorders of consciousness- is there a light at the end of the tunnel?
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Yelden K, James LM, Duport S, Kempny A, Farmer SF, Leff AP, and Playford ED
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Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30-71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low ( M : 31%, Range: 13-66.4%, SD : 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant ( p = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant ( p = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level ( p = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC., (Copyright © 2022 Yelden, James, Duport, Kempny, Farmer, Leff and Playford.)
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- 2022
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26. Go, COMPARE!
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Leff AP and Crinion J
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Competing Interests: Competing interests: None declared.
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- 2022
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27. Richard Wolfgang Semon (1859-1918).
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Larner AJ, Leff AP, and Nachev PC
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- 2022
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28. The impact of the UK COVID-19 pandemic on patient-reported health outcomes after stroke: a retrospective sequential comparison.
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Ozkan H, Ambler G, Banerjee G, Chan E, Browning S, Mitchell J, Perry R, Leff AP, Simister RJ, and Werring DJ
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- Adult, Humans, Outcome Assessment, Health Care, Pandemics, Patient Reported Outcome Measures, Retrospective Studies, SARS-CoV-2, United Kingdom epidemiology, COVID-19, Stroke epidemiology, Stroke therapy
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Background and Purpose: The COVID-19 pandemic and related social isolation measures are likely to have adverse consequences on community healthcare provision and outcome after acute illnesses treated in hospital, including stroke. We aimed to evaluate the impact of the COVID-19 pandemic on patient-reported health outcomes after hospital admission for acute stroke., Methods: This retrospective study included adults with acute stroke admitted to the University College Hospital NHS Foundation Trust Hyperacute Stroke Unit. We included two separate cohorts of consecutively enrolled patients from the same geographical population at two time points: 16th March-16th May 2018 (pre-COVID-19 pandemic); and 16th March-16th May 2020 (during the COVID-19 pandemic). Patients in both cohorts completed the validated Patient Reported Outcomes Measurement Information System-29 (PROMIS-29 version 2.0) at 30 days after stroke., Results: We included 205 patients who were alive at 30 days (106 admitted before and 99 admitted during the COVID-19 pandemic), of whom 201/205 (98%) provided patient-reported health outcomes. After adjustment for confounding factors, admission with acute stroke during the COVID-19 pandemic was independently associated with increased anxiety (β = 28.0, p < 0.001), fatigue (β = 9.3, p < 0.001), depression (β = 4.5, p = 0.002), sleep disturbance (β = 2.3, p = 0.018), pain interference (β = 10.8, p < 0.001); and reduced physical function (β = 5.2, p < 0.001) and participation in social roles and activities (β = 6.9, p < 0.001)., Conclusion: Compared with the pre-pandemic cohort, patients admitted with acute stroke during the first wave of the COVID-19 pandemic reported poorer health outcomes at 30 day follow-up in all domains. Stroke service planning for any future pandemic should include measures to mitigate this major adverse impact on patient health., (© 2021. The Author(s).)
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- 2022
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29. Neuro-Rehabilitation OnLine (N-ROL): description and evaluation of a group-based telerehabilitation programme for acquired brain injury.
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Beare B, Doogan CE, Douglass-Kirk P, Leff AP, and Ward N
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- Aged, Female, Humans, Male, Middle Aged, Surveys and Questionnaires, Brain Injuries rehabilitation, Neurological Rehabilitation methods, Telerehabilitation methods
- Abstract
Competing Interests: Competing interests: None declared.
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- 2021
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30. Clinical Effectiveness of the Queen Square Intensive Comprehensive Aphasia Service for Patients With Poststroke Aphasia.
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Leff AP, Nightingale S, Gooding B, Rutter J, Craven N, Peart M, Dunstan A, Sherman A, Paget A, Duncan M, Davidson J, Kumar N, Farrington-Douglas C, Julien C, and Crinion JT
- Subjects
- Chronic Disease, Communication, Comprehension, Female, Follow-Up Studies, Handwriting, Humans, Language Tests, Male, Middle Aged, Quality of Life, Reading, Speech, Speech Therapy, Treatment Outcome, Aphasia etiology, Aphasia therapy, Stroke complications, Stroke Rehabilitation
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Background and Purpose: Poststroke aphasia has a major impact on peoples’ quality of life. Speech and language therapy interventions work, especially in high doses, but these doses are rarely achieved outside of research studies. Intensive Comprehensive Aphasia Programs (ICAPs) are an option to deliver high doses of therapy to people with aphasia over a short period of time., Methods: Forty-six people with aphasia in the chronic stage poststroke completed the ICAP over a 3-week period, attending for 15 days and averaging 6 hours of therapy per day. Outcome measures included the Comprehensive Aphasia Test, an impairment-based test of the 4 main domains of language (speaking, writing, auditory comprehension, and reading) which was measured at 3 time points (baseline, immediately posttreatment at 3 weeks and follow-up at 12-week post-ICAP); and, the Communicative Effectiveness Index, a carer-reported measure of functional communication skills collected at baseline and 12 weeks., Results: A 2-way repeated measures multivariate ANOVA was conducted. We found a significant domain-by-time interaction, F=12.7, P<0.0005, indicating that the ICAP improved people with aphasia’s language scores across all 4 domains, with the largest gains in speaking (Cohen’s d=1.3). All gains were maintained or significantly improved further at 12-week post-ICAP. Importantly, patients’ functional communication, as indexed by changes on the Communicative Effectiveness Index, also significantly improved at 12-week post-ICAP, t=5.4, P<0.0005, also with a large effect size (Cohen’s d=0.9)., Conclusions: People with aphasia who participated in the Queen Square ICAP made large and clinically meaningful gains on both impairment-based and functional measures of language. Gains were sustained and in some cases improved further over the subsequent 12 weeks.
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- 2021
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31. Brain regions that support accurate speech production after damage to Broca's area.
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Lorca-Puls DL, Gajardo-Vidal A, Oberhuber M, Prejawa S, Hope TMH, Leff AP, Green DW, and Price CJ
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Broca's area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca's area. Importantly, contemporary evidence suggests that, within Broca's area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca's area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca's area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca's area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca's area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca's area., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2021
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32. Lesion site and therapy time predict responses to a therapy for anomia after stroke: a prognostic model development study.
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Hope TMH, Nardo D, Holland R, Ondobaka S, Akkad H, Price CJ, Leff AP, and Crinion J
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- Anomia diagnosis, Brain pathology, Disease Management, Female, Humans, Male, Prognosis, Anomia etiology, Anomia therapy, Stroke complications
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Stroke is a leading cause of disability, and language impairments (aphasia) after stroke are both common and particularly feared. Most stroke survivors with aphasia exhibit anomia (difficulties with naming common objects), but while many therapeutic interventions for anomia have been proposed, treatment effects are typically much larger in some patients than others. Here, we asked whether that variation might be more systematic, and even predictable, than previously thought. 18 patients, each at least 6 months after left hemisphere stroke, engaged in a computerised treatment for their anomia over a 6-week period. Using only: (a) the patients' initial accuracy when naming (to-be) trained items; (b) the hours of therapy that they devoted to the therapy; and (c) whole-brain lesion location data, derived from structural MRI; we developed Partial Least Squares regression models to predict the patients' improvements on treated items, and tested them in cross-validation. Somewhat surprisingly, the best model included only lesion location data and the hours of therapy undertaken. In cross-validation, this model significantly out-performed the null model, in which the prediction for each patient was simply the mean treatment effect of the group. This model also made promisingly accurate predictions in absolute terms: the correlation between empirical and predicted treatment response was 0.62 (95% CI 0.27, 0.95). Our results indicate that individuals' variation in response to anomia treatment are, at least somewhat, systematic and predictable, from the interaction between where and how much lesion damage they have suffered, and the time they devoted to the therapy., (© 2021. The Author(s).)
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- 2021
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33. NUVA: A Naming Utterance Verifier for Aphasia Treatment.
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Barbera DS, Huckvale M, Fleming V, Upton E, Coley-Fisher H, Doogan C, Shaw I, Latham W, Leff AP, and Crinion J
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Anomia (word-finding difficulties) is the hallmark of aphasia, an acquired language disorder most commonly caused by stroke. Assessment of speech performance using picture naming tasks is a key method for both diagnosis and monitoring of responses to treatment interventions by people with aphasia (PWA). Currently, this assessment is conducted manually by speech and language therapists (SLT). Surprisingly, despite advancements in automatic speech recognition (ASR) and artificial intelligence with technologies like deep learning, research on developing automated systems for this task has been scarce. Here we present NUVA, an utterance verification system incorporating a deep learning element that classifies 'correct' versus' incorrect' naming attempts from aphasic stroke patients. When tested on eight native British-English speaking PWA the system's performance accuracy ranged between 83.6% to 93.6%, with a 10-fold cross-validation mean of 89.5%. This performance was not only significantly better than a baseline created for this study using one of the leading commercially available ASRs (Google speech-to-text service) but also comparable in some instances with two independent SLT ratings for the same dataset., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)
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- 2021
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34. The cost to see the Wizard: buy-ins and trade-offs in neurological rehabilitation.
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Doogan C and Leff AP
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- Humans, Neurological Rehabilitation
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- 2021
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35. The clinical effectiveness of Eye-Search therapy for patients with hemianopia, neglect or hemianopia and neglect.
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Szalados R, Leff AP, and Doogan CE
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- Humans, Prospective Studies, Treatment Outcome, Visual Fields, Hemianopsia complications, Perceptual Disorders
- Abstract
We investigated the clinical effectiveness of Eye-Search, a web-based therapy app designed to improve visual search times, in a large group of patients with either hemianopia, neglect or both hemianopia and neglect. A prospective, interventional cohort design was used. For the main, impairment-based outcome measure (average visual search time), the within-subject control was affected vs. unaffected side. Four hundred and twenty-six participants who fitted the inclusion criteria completed all 4 time points (1200 therapy trials). We found a significant three-way interaction between therapy, side and group. Eye-Search therapy improved search times to the affected visual field of patients with either hemianopia alone or neglect and hemianopia, but not those with neglect alone. Effect sizes were moderate to large and consistent with previous studies. We found a similar significant interaction between therapy and group for the patient-reported outcome measure "finding things" that most closely matched the impairment-based outcome (visual search). Eye-Search therapy improves both impairment-based and patient-reported outcome measures related to visual search in patients with hemianopia alone or hemianopia and neglect.
- Published
- 2021
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36. Category-selective deficits are the exception and not the rule: Evidence from a case-series of 64 patients with ventral occipito-temporal cortex damage.
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Rice GE, Kerry SJ, Robotham RJ, Leff AP, Lambon Ralph MA, and Starrfelt R
- Subjects
- Humans, Brain, Temporal Lobe diagnostic imaging
- Abstract
The organisational principles of the visual ventral stream are still highly debated, particularly the relative association/dissociation between word and face recognition and the degree of lateralisation of the underlying processes. Reports of dissociations between word and face recognition stem from single case-studies of category selective impairments, and neuroimaging investigations of healthy participants. Despite the historical reliance on single case-studies, more recent group studies have highlighted a greater commonality between word and face recognition. Studying individual patients with rare selective deficits misses (a) important variability between patients, (b) systematic associations between task performance, and (c) patients with mild, severe and/or non-selective impairments; meaning that the full spectrum of deficits is unknown. The Back of the Brain project assessed the range and specificity of visual perceptual impairment in 64 patients with posterior cerebral artery stroke recruited based on lesion localization and not behavioural performance. Word, object, and face processing were measured with comparable tests across different levels of processing to investigate associations and dissociations across domains. We present two complementary analyses of the extensive behavioural battery: (1) a data-driven analysis of the whole patient group, and (2) a single-subject case-series analysis testing for deficits and dissociations in each individual patient. In both analyses, the general organisational principle was of associations between words, objects, and faces even following unilateral lesions. The majority of patients either showed deficits across all domains or in no domain, suggesting a spectrum of visuo-perceptual deficits post stroke. Dissociations were observed, but they were the exception and not the rule: Category-selective impairments were found in only a minority of patients, all of whom showed disproportionate deficits for words. Interestingly, such selective word impairments were found following both left and right hemisphere lesions. This large-scale investigation of posterior cerebral artery stroke patients highlights the bilateral representation of visual perceptual function., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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37. Damage to Broca's area does not contribute to long-term speech production outcome after stroke.
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Gajardo-Vidal A, Lorca-Puls DL, Team P, Warner H, Pshdary B, Crinion JT, Leff AP, Hope TMH, Geva S, Seghier ML, Green DW, Bowman H, and Price CJ
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Stroke complications, Aphasia, Broca pathology, Broca Area pathology, Frontal Lobe pathology, Stroke pathology
- Abstract
Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2021
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38. Lesions that do or do not impair digit span: a study of 816 stroke survivors.
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Geva S, Truneh T, Seghier ML, Hope TMH, Leff AP, Crinion JT, Gajardo-Vidal A, Lorca-Puls DL, Green DW, and Price CJ
- Abstract
Prior studies have reported inconsistency in the lesion sites associated with verbal short-term memory impairments. Here we asked: How many different lesion sites can account for selective impairments in verbal short-term memory that persist over time, and how consistently do these lesion sites impair verbal short-term memory? We assessed verbal short-term memory impairments using a forward digit span task from the Comprehensive Aphasia Test. First, we identified the incidence of digit span impairments in a sample of 816 stroke survivors (541 males/275 females; age at stroke onset 56 ± 13 years; time post-stroke 4.4 ± 5.2 years). Second, we studied the lesion sites in a subgroup of these patients ( n = 39) with left hemisphere damage and selective digit span impairment-defined as impaired digit span with unimpaired spoken picture naming and spoken word comprehension (tests of speech production and speech perception, respectively). Third, we examined how often these lesion sites were observed in patients who either had no digit span impairments or digit span impairments that co-occurred with difficulties in speech perception and/or production tasks. Digit span impairments were observed in 222/816 patients. Almost all (199/222 = 90%) had left hemisphere damage to five small regions in basal ganglia and/or temporo-parietal areas. Even complete damage to one or more of these five regions was not consistently associated with persistent digit span impairment. However, when the same regions were spared, only 5% (23/455) presented with digit span impairments. These data suggest that verbal short-term memory impairments are most consistently associated with damage to left temporo-parietal and basal ganglia structures. Sparing of these regions very rarely results in persistently poor verbal short-term memory. These findings have clinical implications for predicting recovery of verbal short-term memory after stroke., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2021
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39. Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging.
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Fleming V, Brownsett S, Krason A, Maegli MA, Coley-Fisher H, Ong YH, Nardo D, Leach R, Howard D, Robson H, Warburton E, Ashburner J, Price CJ, Crinion JT, and Leff AP
- Abstract
Objective: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, 'Listen-In', and examined the relation between brain structure and therapy response., Methods: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T
1 ), therapy (T2 -T4 ) and maintenance (T5 ) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2 -T4 ) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry., Results: Thirty-five participants completed, on average, 85 hours (IQR=70-100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen's d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes., Conclusions: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay., Trial Registration Number: NCT02540889., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2020
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40. RELEASE: a protocol for a systematic review based, individual participant data, meta- and network meta-analysis, of complex speech-language therapy interventions for stroke-related aphasia.
- Author
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Brady MC, Ali M, VandenBerg K, Williams LJ, Williams LR, Abo M, Becker F, Bowen A, Brandenburg C, Breitenstein C, Bruehl S, Copland DA, Cranfill TB, Pietro-Bachmann MD, Enderby P, Fillingham J, Galli FL, Gandolfi M, Glize B, Godecke E, Hawkins N, Hilari K, Hinckley J, Horton S, Howard D, Jaecks P, Jefferies E, Jesus LMT, Kambanaros M, Kang EK, Khedr EM, Kong AP, Kukkonen T, Laganaro M, Ralph MAL, Laska AC, Leemann B, Leff AP, Lima RR, Lorenz A, MacWhinney B, Marshall RS, Mattioli F, Maviş I, Meinzer M, Nilipour R, Noé E, Paik NJ, Palmer R, Papathanasiou I, Patricio BF, Martins IP, Price C, Jakovac TP, Rochon E, Rose ML, Rosso C, Rubi-Fessen I, Ruiter MB, Snell C, Stahl B, Szaflarski JP, Thomas SA, van de Sandt-Koenderman M, van der Meulen I, Visch-Brink E, Worrall L, and Wright HH
- Abstract
Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis., Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke., Methods and Procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions., Outcomes and Results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains., Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke., Systematic Review Registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947).
- Published
- 2020
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41. The Architect Who Lost the Ability to Imagine: The Cerebral Basis of Visual Imagery.
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Thorudottir S, Sigurdardottir HM, Rice GE, Kerry SJ, Robotham RJ, Leff AP, and Starrfelt R
- Abstract
While the loss of mental imagery following brain lesions was first described more than a century ago, the key cerebral areas involved remain elusive. Here we report neuropsychological data from an architect (PL518) who lost his ability for visual imagery following a bilateral posterior cerebral artery (PCA) stroke. We compare his profile to three other patients with bilateral PCA stroke and another architect with a large PCA lesion confined to the right hemisphere. We also compare structural images of their lesions, aiming to delineate cerebral areas selectively lesioned in acquired aphantasia. When comparing the neuropsychological profile and structural magnetic resonance imaging (MRI) for the aphantasic architect PL518 to patients with either a comparable background (an architect) or bilateral PCA lesions, we find: (1) there is a large overlap of cognitive deficits between patients, with the very notable exception of aphantasia which only occurs in PL518, and (2) there is large overlap of the patients' lesions. The only areas of selective lesion in PL518 is a small patch in the left fusiform gyrus as well as part of the right lingual gyrus. We suggest that these areas, and perhaps in particular the region in the left fusiform gyrus, play an important role in the cerebral network involved in visual imagery., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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42. Cognition in Stroke Rehabilitation and Recovery Research: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable.
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McDonald MW, Black SE, Copland DA, Corbett D, Dijkhuizen RM, Farr TD, Jeffers MS, Kalaria RN, Karayanidis F, Leff AP, Nithianantharajah J, Pendlebury S, Quinn TJ, Clarkson AN, and O'Sullivan MJ
- Subjects
- Cognitive Dysfunction etiology, Humans, Stroke complications, Stroke Rehabilitation methods, Stroke Rehabilitation standards, Biomedical Research standards, Cognitive Dysfunction rehabilitation, Consensus, Neurological Rehabilitation methods, Neurological Rehabilitation standards, Practice Guidelines as Topic standards, Stroke therapy, Translational Research, Biomedical standards
- Abstract
Cognitive impairment is an important target for rehabilitation as it is common following stroke, is associated with reduced quality of life and interferes with motor and other types of recovery interventions. Cognitive function following stroke was identified as an important, but relatively neglected area during the first Stroke Recovery and Rehabilitation Roundtable (SRRR I), leading to a Cognition Working Group being convened as part of SRRR II. There is currently insufficient evidence to build consensus on specific approaches to cognitive rehabilitation. However, we present recommendations on the integration of cognitive assessments into stroke recovery studies generally and define priorities for ongoing and future research for stroke recovery and rehabilitation. A number of promising interventions are ready to be taken forward to trials to tackle the gap in evidence for cognitive rehabilitation. However, to accelerate progress requires that we coordinate efforts to tackle multiple gaps along the whole translational pathway.
- Published
- 2019
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43. Neuroplasticity and aphasia treatments: new approaches for an old problem.
- Author
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Crosson B, Rodriguez AD, Copland D, Fridriksson J, Krishnamurthy LC, Meinzer M, Raymer AM, Krishnamurthy V, and Leff AP
- Subjects
- Aphasia diagnostic imaging, Aphasia etiology, Aphasia physiopathology, Brain diagnostic imaging, Brain physiopathology, Functional Neuroimaging, Humans, Stroke complications, Stroke Rehabilitation, Aphasia rehabilitation, Language Therapy, Neuronal Plasticity, Stroke physiopathology, Transcranial Direct Current Stimulation, Transcranial Magnetic Stimulation
- Abstract
Given the profound impact of language impairment after stroke (aphasia), neuroplasticity research is garnering considerable attention as means for eventually improving aphasia treatments and how they are delivered. Functional and structural neuroimaging studies indicate that aphasia treatments can recruit both residual and new neural mechanisms to improve language function and that neuroimaging modalities may hold promise in predicting treatment outcome. In relatively small clinical trials, both non-invasive brain stimulation and behavioural manipulations targeting activation or suppression of specific cortices can improve aphasia treatment outcomes. Recent language interventions that employ principles consistent with inducing neuroplasticity also are showing improved performance for both trained and novel items and contexts. While knowledge is rapidly accumulating, larger trials emphasising how to select optimal paradigms for individualised aphasia treatment are needed. Finally, a model of how to incorporate the growing knowledge into clinical practice could help to focus future research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
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44. How Does iReadMore Therapy Change the Reading Network of Patients with Central Alexia?
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Kerry SJ, Aguilar OM, Penny W, Crinion JT, Leff AP, and Woodhead ZVJ
- Subjects
- Adult, Aged, Cross-Over Studies, Dyslexia diagnostic imaging, Dyslexia etiology, Female, Humans, Magnetoencephalography methods, Male, Middle Aged, Photic Stimulation methods, Stroke complications, Stroke diagnostic imaging, Stroke therapy, Stroke Rehabilitation methods, Computer-Assisted Instruction methods, Dyslexia therapy, Nerve Net physiology, Occipital Lobe physiology, Prefrontal Cortex physiology, Reading
- Abstract
Central alexia (CA) is an acquired reading disorder co-occurring with a generalized language deficit (aphasia). The roles of perilesional and ipsilesional tissue in recovery from poststroke aphasia are unclear. We investigated the impact of reading training (using iReadMore, a therapy app) on the connections within and between the right and left hemisphere of the reading network of patients with CA. In patients with pure alexia, iReadMore increased feedback from left inferior frontal gyrus (IFG) region to the left occipital (OCC) region. We aimed to identify whether iReadMore therapy was effective through a similar mechanism in patients with CA. Participants with chronic poststroke CA ( n = 23) completed 35 h of iReadMore training over 4 weeks. Reading accuracy for trained and untrained words was assessed before and after therapy. The neural response to reading trained and untrained words in the left and right OCC, ventral occipitotemporal, and IFG regions was examined using event-related magnetoencephalography. The training-related modulation in effective connectivity between regions was modeled at the group level with dynamic causal modeling. iReadMore training improved participants' reading accuracy by an average of 8.4% (range, -2.77 to 31.66) while accuracy for untrained words was stable. Training increased regional sensitivity in bilateral frontal and occipital regions, and strengthened feedforward connections within the left hemisphere. Our data suggest that iReadMore training in these patients modulates lower-order visual representations, as opposed to higher-order, more abstract representations, to improve word-reading accuracy. SIGNIFICANCE STATEMENT This is the first study to conduct a network-level analysis of therapy effects in participants with poststroke central alexia. When patients trained with iReadMore (a multimodal, behavioral, mass practice, computer-based therapy), reading accuracy improved by an average 8.4% on trained items. A network analysis of the magnetoencephalography data associated with this improvement revealed an increase in regional sensitivity in bilateral frontal and occipital regions and strengthening of feedforward connections within the left hemisphere. This indicates that in patients with CA iReadMore engages lower-order, intact resources within the left hemisphere (posterior to their lesion locations) to improve word reading. This provides a foundation for future research to investigate reading network modulation in different CA subtypes, or for sentence-level therapy., (Copyright © 2019 the authors.)
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- 2019
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45. Safety of Tattoos in Persons Undergoing MRI.
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Callaghan MF, Negus C, Leff AP, Creasey M, Burns S, Glensman J, Bradbury D, Williams E, and Weiskopf N
- Subjects
- Healthy Volunteers, Humans, Prospective Studies, Risk Factors, Magnetic Resonance Imaging adverse effects, Tattooing
- Published
- 2019
- Full Text
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46. ReadClear: An Assistive Reading Tool for People Living with Posterior Cortical Atrophy.
- Author
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Suarez-Gonzalez A, Ocal D, Pavisic I, Peacock A, Naessens M, Ahmed S, Butler CR, Leff AP, Yong KXX, and Crutch SJ
- Subjects
- Atrophy, Cross-Over Studies, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Outcome Assessment, Health Care, Pattern Recognition, Visual physiology, Reading, Cerebral Cortex pathology, Dyslexia diagnosis, Dyslexia etiology, Dyslexia rehabilitation, Neurodegenerative Diseases pathology, Neurodegenerative Diseases psychology, Neurodegenerative Diseases therapy, Self-Help Devices
- Abstract
Background: Progressive reading impairment is an early and debilitating symptom of posterior cortical atrophy (PCA) arising from the progressive deterioration of visual processing skills., Objective: The goal of this study was to test the effectiveness of a purpose-built reading app (ReadClear) co-produced with people living with PCA and designed to reduce the reading difficulties experienced by this population (e.g., getting lost in the page and missing words when reading)., Methods: Twenty subjects with PCA were included in a cross-over design home-based study aimed at determining whether ReadClear could 1) enhance the subjective reading experience (reading pleasantness) and 2) improve reading accuracy (reducing the number of reading errors) compared with a sham condition (a standard e-reader)., Results: Reading using ReadClear provided a better subjective reading experience than sham (p = 0.018, d = 0.5) and significantly reduced the percentage of reading errors (p < 0.0001, r = 0.82), particularly errors due to omissions (p = 0.01, r = 0.50), repeated words (p = 0.002, r = 0.69), and regressions in the text (p = 0.003, r = 0.69). We found that different kinds of reading errors were related to specific neuropsychological profiles., Conclusion: ReadClear can assist reading in people living with PCA by reducing the number of reading errors and improving the subjective reading experience of users.
- Published
- 2019
- Full Text
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47. Recovery after stroke: not so proportional after all?
- Author
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Hope TMH, Friston K, Price CJ, Leff AP, Rotshtein P, and Bowman H
- Subjects
- Humans, Recovery of Function, Statistics as Topic methods, Stroke
- Abstract
The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the variance in the patients' recoveries, are rapidly accumulating. Here, we show that these headline effect sizes are likely inflated. The key effects in this literature are typically expressed as, or reducible to, correlation coefficients between baseline scores and recovery (outcome scores minus baseline scores). Using formal analyses and simulations, we show that these correlations will be extreme when outcomes are significantly less variable than baselines, which they often will be in practice regardless of the real relationship between outcomes and baselines. We show that these effect sizes are likely to be over-optimistic in every empirical study that we found that reported enough information for us to make the judgement, and argue that the same is likely to be true in other studies as well. The implication is that recovery after stroke may not be as proportional as recent studies suggest.
- Published
- 2019
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48. How right hemisphere damage after stroke can impair speech comprehension.
- Author
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Gajardo-Vidal A, Lorca-Puls DL, Hope TMH, Parker Jones O, Seghier ML, Prejawa S, Crinion JT, Leff AP, Green DW, and Price CJ
- Subjects
- Female, Functional Laterality, Humans, Language Disorders etiology, Linguistics, Male, Memory, Short-Term, Middle Aged, Comprehension, Frontal Lobe pathology, Language Disorders pathology, Language Disorders psychology, Speech Perception, Stroke complications
- Abstract
Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.
- Published
- 2018
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49. Lesion-site-dependent responses to therapy after aphasic stroke.
- Author
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Aguilar OM, Kerry SJ, Ong YH, Callaghan MF, Crinion J, Woodhead ZVJ, Price CJ, Leff AP, and Hope TMH
- Subjects
- Dyslexia, Acquired complications, Dyslexia, Acquired therapy, Humans, Stroke complications, Stroke therapy, Therapy, Computer-Assisted methods, Treatment Outcome, Brain pathology, Dyslexia, Acquired pathology, Speech Therapy methods, Stroke pathology
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2018
- Full Text
- View/download PDF
50. Late recovery of awareness in prolonged disorders of consciousness -a cross-sectional cohort study.
- Author
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Yelden K, Duport S, James LM, Kempny A, Farmer SF, Leff AP, and Playford ED
- Subjects
- Adult, Age Factors, Aged, Cohort Studies, Cross-Sectional Studies, Disability Evaluation, Disabled Persons rehabilitation, Female, Humans, Male, Middle Aged, Recovery of Function, Risk Factors, Severity of Illness Index, Time, Awareness physiology, Brain Injuries complications, Brain Injuries rehabilitation, Consciousness Disorders etiology, Consciousness Disorders psychology, Consciousness Disorders rehabilitation, Persistent Vegetative State etiology, Persistent Vegetative State psychology, Persistent Vegetative State rehabilitation
- Abstract
Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term., Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised., Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76)., Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.
- Published
- 2018
- Full Text
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