Efeitos da estimulação transcraniana por corrente contínua (ETCC) na recuperação do traumatismo cranioencefálico (TCE): uma revisão sistemática

Dement Neuropsychol dn Dementia & Neuropsychologia Dement. neuropsychol. 1980-5764 1980-5764 Associação de Neurologia Cognitiva e do Comportamento RESUMO. A lesão cerebral traumática (TCE) é uma das principais causas de incapacidade crônica. Menos de um quarto dos pacientes com TCE moderada e grave melhoraram sua cognição dentro de cinco anos. A estimulação cerebral não invasiva, incluindo a estimulação transcraniana por corrente contínua (ETCC), pode ajudar na reabilitação neurológica, aumentando a neuroplasticidade adaptativa e reduzindo as sequelas patológicas após o TCE. Métodos: pesquisamos os bancos de dados MEDLINE / PubMed e Web of Science. Usamos a escala de Jadad para avaliar os métodos utilizados nos ensaios clínicos. Resultados: os 14 artigos incluídos relataram diferentes desenhos de estudo; 2 estudos foram abertos, 9 foram ensaios clínicos randomizados (ECRs) cruzados e 3 foram ECR de grupos paralelos. A maioria dos estudos utilizou a ETCC anódica do córtex pré-frontal dorsolateral esquerdo, mas os parâmetros de montagem e estimulação variaram. Múltiplos estudos mostraram melhoras nas escalas de recuperação de coma em pacientes com distúrbios da consciência e melhora da cognição. Alguns estudos mostraram alterações nas medidas neurofisiológicas (eletroencefalografia (EEG) e estimulação magnética transcraniana (EMT)), correlacionando com os achados clínicos. Os principais vieses metodológicos foram a falta de relatos de cegamento e randomização. Conclusão: a ETCC é uma técnica neuromodulatória segura e não invasiva que pode ser administrada em monoterapia, mas a utilização da ETCC parece impulsionar os resultados clínicos quando combinada com outras estratégias terapêuticas (como reabilitação cognitiva e fisioterapia). O EEG e o EMT podem ajudar a orientar a pesquisa e tambem mensurar os ganhos clínicos por serem potenciais biomarcadores da neuroplasticidade. Traumatic brain injury (TBI) is a major cause of death and chronic disability in industrialized1 and developing countries,2 particularly for young and elderly patients. TBI can lead to transient or permanent physical, cognitive, affective and/or behavioral deficits. Even mild TBI may cause long-term sequalae such as post-concussion syndrome,3 potentially leading to neurological disorders and neurodegeneration.4,5 Memory loss is one of the most common deficits following TBI,6-12 and cognitive impairment can be persistent, especially after moderate and severe injury,12-16 resulting in lower functionality and quality of life.17,18 Only 23.7% of moderate and severe TBI patients (older than 16 years) that received inpatient rehabilitation improved in their cognition within 5 years according to the TBI Model Systems National Database, while 24% of the sample reported cognitive decline.19 Considering its high disease burden and the limited evidence of cognitive rehabilitation’s effectiveness in TBI,20 there is a great need for new and improved therapeutic strategies. Neuromodulation, such as non-invasive brain stimulation (NIBS) techniques, promotes adaptive neuroplasticity and may prevent or reduce pathological sequela following TBI.21,22 NIBS techniques may improve clinical recovery by facilitating functional and structural neuronal changes, by synaptic strengthening, and by increasing dendritic spines and their connections.23,24 NIBS techniques may potentially improve clinical outcomes beyond conventional rehabilitation and help patients who do not respond to typical therapies.25 Transcranial direct current stimulation (tDCS) is a safe NIBS technique studied in various disorders, including TBI.22 It involves the application of a low intensity electric current (usually 1 to 2 mA) often using two electrodes placed over the head to modulate cortical activity.26 TDCS alters neuronal resting membrane potentials, thereby raising the likelihood of depolarization and increased underlying cortical excitability, or of hyperpolarization and decreased cortical excitability.24,26 Anodal and cathodal tDCS are typically used to increase and decrease excitability respectively, and depending on the montage and stimulation parameters, tDCS can target different cerebral networks, including those involving cognition and motor activity.27,28 As tDCS is relatively safe and cost-effective (24) with only transient adverse effects,29,30 we aimed to systematically review its utility to improve TBI recovery. The rationale of this systematic review is that TBI is a complex disorder with limited therapeutic options, and that tDCS may be a potential adjuvant neurorehabilitation tool to improve clinical outcomes (e.g., cognitive, motor, and level of consciousness) in TBI. Our hypothesis is that tDCS may improve clinical and surrogate outcomes in TBI, depending on stimulation parameters. Our objective is to answer the following PICOS-based research question: does tDCS improve clinical or surrogate outcomes in adult TBI patients in clinical trials? METHODS Our initial online literature search was performed on MEDLINE/PubMed and Web of Science databases. On Pubmed we used the following MeSH terms: ((traumatic brain injury[MeSH Terms]) OR (tbi[MeSH Terms])) AND ((tDCS[MeSH Terms]) OR (Transcranial Direct Current Stimulation[MeSH Terms]) OR (tDCS[MeSH Terms])). We filtered by date (from 1/1/1900 to 9/15/2018), Species (Human), and Languages (English). On 9/17/2018 we searched Web of Science for the following search string and filters (TS means Topic): (TS=(traumatic brain injury OR tbi)); timespan: 1900-2018; indexes: SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI, CCR-EXPANDED, IC. We included experimental clinical trials, open label studies and case reports. Two independent researchers (AZ and MM) reviewed the titles and abstracts. Eligible studies fulfilled the following criteria: experimental studies on adult TBI patients who received tDCS for therapeutic purposes with the primary or exploratory aim of assessing clinical outcomes (e.g., cognitive, motor, or level of consciousness) or surrogate outcomes (e.g., electroencephalogram (EEG), transcranial magnetic stimulation (TMS)), over any duration of time compared to a pre-treatment baseline. We excluded studies that did not meet these criteria, screening first by title, then abstract, then by full text. We assessed studies for biases by evaluating funding sources. We used the Jadad score to assess publications based on the quality and reporting of the following methods: randomization (0,1, or 2 score); blinding (0,1, or 2 score); and patient flow (0 or 1 score); scores range from 0 to 5 and the higher the score the better the publication.31 There was generally no need to contact study authors as the necessary data was available, although we did contact one author to clarify blinding methods.32 Our methods follow PRISMA guidelines. RESULTS Of 115 search results (56 from Pubmed, 59 from Web of Science), we found 14 studies that used tDCS in TBI patients and fulfilled our eligibility criteria (Figure 1). Figure 1 Flow diagram following Prisma Statement. The 14 papers included in our review reported different study designs; 2 studies were open-label case-series33,34 and the rest were double-blind randomized clinical trials (RCTs) - 9 crossover RCTs32,35-42 one of which was semi-randomized,41 and 3 parallel group RCTs.43-45 Sample sizes were small, ranging from 5 to 55 participants, and often included other disorders (e.g., anoxia) or healthy controls in addition to TBI. A summary of the 14 papers is presented in Table 1. Table 1 Characteristics of studies using tDCS in patients with TBI. Author,year Study design Total samplesize (N) Electrode placement/polarity Sponge size Additionaltherapies Stimulationparameters Total number oftDCS sessions Primary outcome(s) Results Jadadscore Kangetal.2012 Double-blind,randomized,crossover N=9 F3 anodal; right supraorbital(Fp2) cathodal 5x5 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS;48-hour washout 2 Attention bycomputerized contrastreaction time task No significative improvementon RT after tDCS 3 Lesniaket al.2013 Double-blind,parallel group,pilot study N=26 F3 anodal; right supraorbital(Fp2) cathodal 5x7 cm Offline cognitivetraining 10 min of anodaltDCS, 1 mA;or sham tDCS 15 Episodic memory,working memory andattention Larger effect size after the interventioncompared to sham, but no significantdifference between groups 4 Angelakiset al.2014 Open-label, caseseries, blindeddose scalation N=10(DOC due to TBIn=5) C3 or F3 anodal; rightsupraorbital (Fp2) cathodal 5x5 cm None Week 1 - 20 min ofsham tDCS; Week2-20 min of anodaltDCS, 1 mA; Weeks3 and 4 - 20 min ofanodal tDCS, 2 mA 20 CRS-R Conflicting results. Some patientsimproved up to 2 weeks after stimulation.One patient received 10 extra sessionsof tDCS after 3 months and showedimprovement. Better improvement onpatients with MCS compared to PVS 2 Middletonetal.2014 Open-label, caseseries pilot study N= 5(n=2 TBI) Ipsilesional anodal at C3 or C4;and contralesional cathodal 5x5 cm 24 sessions ofonline physicaltherapy(3 times perweek) 15 min of anodaltDCS, 1.5 mA 24 Fugl-Meyer, PurduePegboard, Box andBlock, Stroke ImpactScale-16 Positive effects on motor performance upto 6 months after intervention 2 Thibautetal.2014 Double-blind,randomized,crossover N=55(n=32 DOC dueto TBI) F3 anodal;Fp2 cathodal 5x7 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS;48-hour washout 2 CRS-R, GOSe Improvements for MCS patients onCRS-R total scores. No effect of tDCSon any of the CRS-R subscales on VS/UWS groups 5 Ulametal.2015 Double blind,randomized,parallel group N=26(subacute TBI) F3 anodal; Fp2 cathodal 5x5.6 cm None 20 min of anodaltDCS, 1 mA;or sham tDCS 10 EEG,neuropsychologicalassessments Decreased theta with first session;decreased delta and increased alphaafter active tDCS. No changes in shamgroup. Correlation between decreaseddelta and improved cognitive tasks inactive group 3 Naroetal.2015 Cross-sectionalopen-label study N=45(n= 20 healthyand n=25 DOCdue to TBI oranoxia) SO anodal (between Fp1 andFp2); Cz cathodal 5x5 cmanode; 5x7cm referenceelectrode None 10 min of anodaltDCS, 1 mA;or sham tDCS 1 CRS-R, MEP, ICF, ICI,and SICI Significant effects in all physiologicalmeasurements in healthy controls afterthe tDCS, and on ICI and ICF in DOCpatients 2 Saccoetal.2016 Double-blind,randomized,parallel groups N=32 F3 or F4 anodal (anode onthe lesioned hemisphereand cathode on the otherhemisphere); bi-montage F3/F4 anodal in case of equalhemispheric lesion distribution 5x7 cm Offline cognitivetraining 20 min of anodaltDCS, 2 mA;or sham tDCS 10 (twice a day) TEA, BDI-II, RBANS,AES, fMRI Shorter reaction times and fewer errorscompared to baseline; decreased apathy 2 O'Neil-Pirozzietal.2017 Double-blind,crossover pilotstudy N=8(n=4 with chronicsevere TBI) F3 (anodal, cathodal orsham); right supraorbital (Fp2)reference electrode 5x7 cm None 20 min of anodal orcathodal tDCS,2 mA; or sham tDCS.48-hours washout 3 EEG alpha power, P300amplitude and latency,working memory test Positive effects on working memory afteranodal compared to cathodal tDCS in TBIand control group. No EEG changes 2 Wilkeetal.2017 Double-blind,semi-randomized,crossover study N=39(n=17 chronicmild TBI) C3 anodal; right supraorbital(Fp2) cathodal 5x7 cm anode,10x10cmcathode None 20 min of anodaltDCS, 1 mA; or sham tDCS. 7-day washout 2 MRS(GABAconcentration),TMS, PCS, cognitiveassessment No changes in any outcome 3 Martensetal.2018 Double-blind,crossover study N=27(n=12 DOC dueto TBI) F3 anodal, right supraorbital(Fp2) cathodal 5x7 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS;8-week washout 40 (2-4 weeksstimulation and8 weeks washout) Adverse eventsadherence, CRS-R Safety, feasibility andbehavioral effects - increase inCRS-R scores 5 Estraneoetal.2017 Double-blind,crossover study N=23(n=1 VS dueto TBI) F3 anodal, right supraorbital(Fp2) cathodal 5x7 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS.One-week washout 10 sessions(5 active and 5sham stimulation) CRS-R and EEG No changes on EEG or CRS-R 4 Thibautetal.2017 Double-blind,crossover study N=21(n=11 out of 16DOC due to TBI) F3 anodal, right supraorbital(Fp2) cathodal 5x7 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS.One-week washout 10 sessions(5 active and 5sham stimulation) CRS-R Positive treatment effect (CRS-R scores)after one week of anodal tDCScompared to sham 5 Baietal.2017 Double-blind,crossover study N=16(n=4 VS or MSCdue to TBI) F3 anodal, right supraorbital(Fp2) cathodal 5x5 cm None 20 min of anodaltDCS, 2 mA;or sham tDCS.3-day washout 2 TMS (MEP) and EEG Global cerebral excitability increased inearly time windows (0-100 and100-200 ms) for patients with MCSafter anodal tDCS 4 AES: Apathy Evolution Scale; BDI-II: Beck Depression Inventory (2nd edition); CRS-R: Coma Recovery Scale-Revised; DLPFC: dorsolateral prefrontal cortex (F3 on left, F4 on right); DOC: disorder of consciousness; EEG: electroencephalography; GABA: gamma-aminobutyric acid; GOSe: Glasgow Outcome Scale extended; ICF: intracortical facilitation; ICI: intracortical facilitation; M1: Primary Motor Cortex (C3 on left, C4 on right); MEP: motor evoked potential; MRS: magnetic resonance spectroscopy; MSC: Minimal State of Consciousness; PCS: post-concussion syndrome; PVS: persistent vegetative state; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; SICI: short-interval intracortical inhibition; SO: Supraorbital (orbitofrontal; FP1 on left, FP2 on right); PCS: post concussion syndrome; TEA: Test of Everyday Attention; tDCS: transcraniai direct current stimulation; TMS: transcranial magnetic stimulation; UWS: unresponsive wakefulness syndrome; VS: vegetative State. Type of outcomes The papers reported the use of tDCS in patients with TBI to improve clinical outcomes (mainly coma recovery and cognitive outcomes) and/or surrogate outcomes such as neurophysiological markers (electroencephalography (EEG) and transcranial magnetic stimulation (TMS)), magnetic resonance spectroscopy (MRS) and functional magnetic resonance imaging (fMRI). We found 7 studies that used tDCS to improve responsiveness in patients with disorders of consciousness (DOC) due to TBI and other brain injuries.33,35-39,42 The only strong evidence of tDCS’ effectiveness to improve functionality as measured by Coma Recovery Scale-Revised (CRS-R) came from the same group. All their studies were crossover RCTs using anodal tDCS (2 mA, current density 0.571 A/m2 for 20 minutes) over the left dorsolateral prefrontal cortex (DLPFC) with a right frontopolar reference electrode.35,37,38 A study using TMS-EEG (n=4/16 subjects had TBI) reported global excitability increases early on for MCS patients after anodal left DLPFC tDCS;39 the authors described significantly increased global mean field amplitudes of the TMS-evoked potentials with 200 ms of the TMS pulse in MCS patients overall, as opposed to VS patients who also had an increase at up to 100 ms, but a decrease at 300-400 ms. Estraneo et al.36 had no positive overall results following left DLPFC anodal tDCS (2 mA over 5 days) on functional (CRS-R) and surrogate (EEG) outcomes. However, this crossover RCT was more heterogeneous than the previous one,37 with a mix of subacute and chronic DOC patients. Six studies used tDCS to improve cognition,33,40,41,43-45 four of which showed no differences between outcomes pre and post-intervention.40,41,43,45 Two parallel-group sham-control RCTs used offline cognitive training after tDCS.44,45 The authors suggested that the combined intervention (tDCS + cognitive training) decreased abnormal hyperactivation, measured by fMRI, often seen in TBI patients.44 As to the other studies evaluating cognition, one crossover study40 found no improvements in RT using the same parameters as those used successfully by Sacco and colleagues44 and at a higher current density (due to smaller electrodes). However, they used only 2 sessions, a right orbitofrontal cathode, had no cognitive training and had a small sample size (n=9), which possibly underpowered the results. Two studies compared cognitive outcomes to EEG outcomes following left DLPFC tDCS: one parallel-group RCT on subacute TBI reported resting EEG power improvements after one anodal tDCS session (transiently decreased theta slowing at F3), at the end of 10 sessions and the following day (decreased delta plus increased alpha at both F3 and Fp2). It is important to note that this increased normalization (increased physiologic alpha, decreased pathologic delta) occurred under both the Fp2 “cathode” and the F3 “anode”. Additionally, the decreased delta power correlated with improved visual accuracy, color word interference, and brief visual memory task.43 Meanwhile, the second study was an exploratory crossover RCT, a single session of anodal tDCS increased word recall in both the TBI and control groups; it also increased P300 amplitude (for oddball task performance) in TBI patients. There was no effect on EEG theta or alpha power.33 A semi-randomized crossover study hypothesized that TBI patients would have worse cognition and higher GABA concentration and receptor activity than healthy controls, and that anodal left M1 tDCS would help ameliorate these findings. However, they found no changes in cognition, post-concussion syndrome, TMS or magnetic resonance spectroscopy measures,41 possibly due to tDCS response variability or variability in their methodology compared to previous studies. Finally, only one exploratory open-label study analyzed the effects of online tDCS on motor outcomes in patients with stroke and/or TBI.34 This study aimed to assess the feasibility and effectiveness of tDCS sessions. The results showed improvements up to 6 months after the intervention, but the interpretation was based on the effect size, which is not standard considering the small sample.34 The TBI patients had mixed results. Methodological scores for clinical trials: We analyzed the quality of the studies using the Jadad score.31 Only 3 papers scored 5 out of 5, having clearly reported the randomization and blinding methods as well as dropouts and withdrawals. Most other studies did not report the method used for randomization, or they were open label studies and scored zero for blinding. DISCUSSION When the brain is injured by trauma or other insults, it attempts to ameliorate the deficits resulting from its injury by forming new cortical and subcortical connections and by reorganizing neural networks. However, these compensatory mechanisms are often suboptimal, unable to fully restore function, and may lead to maladaptive effects and further complications such as cognitive impairment. Non-invasive brain stimulation (NIBS) techniques aim to utilize these neuroplastic mechanisms in ways that might target important functions and thereby improve clinical outcomes and quality of life. In other words, NIBS techniques such as tDCS aim to counteract maladaptive neuroplasticity and promote adaptive changes. The search for efficacious adjuvant therapies to improve outcomes in TBI is critical because rehabilitation techniques, and particularly cognitive rehabilitation, often do not lead to complete recovery. This review aimed to investigate the question: does tDCS improve clinical or surrogate outcomes in adult TBI patients in clinical trials? Most studies showed evidence of positive outcomes (surrogate and/or clinical) in TBI patients after tDCS32-35,37-39,42,44,45 albeit with some methodological variability. Limitations due to heterogeneous procedures are common to rehabilitation studies because the need for tailored therapy makes clinical trial design particularly challenging. Cognition can be especially difficult to target; the exact networks involved in cognitive performance are less clearly delineated than in motor function and are therefore are difficult to target with conventional rehabilitation techniques or with adjuvant therapies such as tDCS. Yet, cognitive problems are a major cause of diminished independence and quality of life in TBI patients,46 and they often coincide with - and are confounded by - behavioral and emotional deficits. Any hope for improvement is thus worth investigating. Motor outcomes are also important and merit further investigation in TBI. Overall the clinical and neurophysiologic results of this systematic review are preliminarily encouraging with regard to coma recovery, cognitive functions and motor recovery in TBI patients. However, further studies are needed to elicit the effects of tDCS parameters, including electrode placement, current density, stimulation duration and interval, as well as its effect on concomitant therapies (and vice versa). Additionally, further studies could help better identify potential tDCS protocol responders based on baseline characteristics. Considering the risks of polypharmacy in TBI, the potential of tDCS to reduce the need for - and perhaps to counteract the cognitive side effects of - some medications might be very useful. Combining tDCS with cognitive and/or physical training may enhance long-term potentiation (LTP)-like plasticity in the desired region beyond either treatment alone;47 however, it is important to understand how to use each of tDCS and other therapies to induce neurophysiologic effects individually before their combined effects can be delineated. This is important to avoid reaching a ceiling effect, which is probably what happened in one study.45 It may also be possible to obtain synergy by combining tDCS with another treatment, or to use each treatment to target different functions; conversely, targeting the wrong or opposing networks may cancel the therapeutic effects of each treatment. Improved biomarkers of neural damage due to TBI may help us better understand the mechanisms underlying tDCS and/or other therapies’ neurophysiologic effects and may also help clinicians predict their clinical effects and monitor therapy. Our review reveals how EEG and TMS markers preliminarily showed changes in some cases, which did - or did not - correlate to clinical outcomes. TBI is a heterogeneous disorder and anything that helps clinicians eventually tailor therapy or identify responders would be helpful, particularly considering the multiple comorbidities and different types of therapy TBI patients may receive. TMS can be used as NIBS to promote neuroplasticity when used in a repetitive way (rTMS) or as a biomarker to evaluate the integrity of the corticospinal tract. In our review, the TMS cortical silent period was used to investigate the GABAergic pathway in patients with mild TBI,41 and to evaluate DLPFC excitability in patients with disorders of consciousness.39 While such surrogate markers have limited generalizability to clinical applications, these measures are becoming increasingly correlated over the years. One example is a study published in 2015, in which the authors found a specific TMS threshold with reliable sensitivity to diagnose early stage amyotrophic lateral sclerosis (ALS).48 EEG is the other main biomarker used in our review to assess cortical activity after TBI. EEG is clinically used in TBI (especially when severe), in patients admitted to the intensive care unit, to rule out subclinical seizures, to monitor drug effects, and for other clinical purposes.49,50 However, it is not typically used in outpatient settings if there is no history suggestive of seizures. Yet, EEG can be used to follow clinical changes in patients over time even in the presence of medications, as the effects of certain neurological and psychiatric drugs on EEG (e.g., benzodiazepines, etc.) are known. In the context of our review, generalized slowing on EEG is consistent with encephalopathy (if the patient is not sleeping), while pathological focal slowing (especially in the delta range, but also often in the theta range) indicates dysfunction consistent with focal cortical lesions (e.g., stroke, subdural hematoma, abscess, neoplasm, etc.).51 Both generalized and focal slowing can variably be seen in TBI patients. Therefore, any decrease in pathological focal slowing is consistent with potentially improved cortical function; for example, in our systematic review, decreased delta power under the electrodes after active tDCS correlated with improved cognitive task performance. Decreased generalized slowing would indicate less or resolved encephalopathy. Eventually, a combination of clinical evaluations, EEG, TMS and/or other neurophysiologic assessments may aid in the development of higher quality tDCS studies in TBI. TMS may be particularly helpful to monitor motor responses. Overall, the effects of tDCS on clinical outcomes and neurophysiologic markers such as EEG and TMS in TBI patients need to be elucidated in future studies. These studies are worthwhile as heterogeneous disorders require tailored therapy, and tDCS lends itself well to tailoring and individualization based on patient need. In conclusion, TBI is an unfortunate phenomenon with frequently devastating and heterogeneous clinical outcomes. Cognitive outcomes in TBI are a major source of disability, and few therapeutic options are available. TDCS is a safe, non-invasive neuromodulatory technique that can be given alone (e.g., in comatose patients) but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. The desired outcomes will have a major impact on networks to target and thus tDCS stimulation parameters and concomitant therapies. The challenges of designing trials for heterogeneous TBI patients necessitate further development of neurophysiologic markers such as EEG and TMS to help track therapeutic progress and guide research. This study was conducted at the Speech and Feeding Disorders Lab, MGH Institute of Health Professions (MGH IHP), Boston, USA. References 1 1 Bruns J Jr., Hauser WA. The epidemiology of traumatic brain injury: a review. Epilepsia. 2003;44(s10):2-10. Bruns J Jr Hauser WA The epidemiology of traumatic brain injury: a review Epilepsia 2003 44 s10 2 10 2 2 de Almeida CER, de Sousa JL, Dourado JC, Gontijo PAM, Dellaretti MA, Costa BS. Traumatic Brain Injury Epidemiology in Brazil. World Neurosurgery. 2016;87:540-7. de Almeida CER de Sousa JL Dourado JC Gontijo PAM Dellaretti MA Costa BS Traumatic Brain Injury Epidemiology in Brazil World Neurosurgery 2016 87 540 547 3 3 Bramley H, Hong J, Zacko C, Royer C, Silvis M. Mild Traumatic Brain Injury and Post-concussion Syndrome: Treatment and Related Sequela for Persistent Symptomatic Disease. Sports Med Arthrosc Rev. 2016; 24(3):123-9. Bramley H Hong J Zacko C Royer C Silvis M Mild Traumatic Brain Injury and Post-concussion Syndrome: Treatment and Related Sequela for Persistent Symptomatic Disease Sports Med Arthrosc Rev 2016 24 3 123 129 4 4 Lima DPD, Simao C, Abib SDV, de Figueiredo LFP. Quality of life and neuropsychological changes in mild head trauma - Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission. Injury. 2008;39(5):604-11. Lima DPD Simao C Abib SDV de Figueiredo LFP Quality of life and neuropsychological changes in mild head trauma - Late analysis and correlation with S100B protein and cranial CT scan performed at hospital admission Injury 2008 39 5 604 611 5 5 Feltrin FS, Zaninotto AL, Guirado VMP, Macruz F, Sakuno D, Dalaqua M, et al. Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury. Brain Inj. 2018; 32(10):1208-17. Feltrin FS Zaninotto AL Guirado VMP Macruz F Sakuno D Dalaqua M Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury Brain Inj 2018 32 10 1208 1217 6 6 Sozda CN, Muir JJ, Springer US, Partovi D, Cole MA. Differential Learning and Memory Performance in OEF/OIF Veterans for Verbal and Visual Material. Neuropsychology. 2014;28(3):347-52. Sozda CN Muir JJ Springer US Partovi D Cole MA Differential Learning and Memory Performance in OEF/OIF Veterans for Verbal and Visual Material Neuropsychology 2014 28 3 347 352 7 7 Levin HS. Memory deficit after closed-head injury. J Clin Exp Neuropsychol. 1990;12(1):129-53. Levin HS Memory deficit after closed-head injury J Clin Exp Neuropsychol 1990 12 1 129 153 8 8 Tam SF, Man WK. Evaluating computer-assisted memory retraining programmes for people with post-head injury amnesia. Brain Inj. 2004; 18(5):461-70. Tam SF Man WK Evaluating computer-assisted memory retraining programmes for people with post-head injury amnesia Brain Inj 2004 18 5 461 470 9 9 Kim HJ, Burke DT, Dowds MM, George J. Utility of a microcomputer as an external memory aid for a memory-impaired head injury patient during in-patient rehabilitation. Brain Inj. 1999;13(2):147-50. Kim HJ Burke DT Dowds MM George J Utility of a microcomputer as an external memory aid for a memory-impaired head injury patient during in-patient rehabilitation Brain Inj 1999 13 2 147 150 10 10 Kelly JP. Traumatic brain injury and concussion in sports. JAMA. 1999; 282(10):989-91. Kelly JP Traumatic brain injury and concussion in sports JAMA 1999 282 10 989 991 11 11 Dikmen S, Machamer J, Fann JR, Temkin NR. Rates of symptom reporting following traumatic brain injury. J Int Neuropsychol Society. 2010;16(3):401-11. Dikmen S Machamer J Fann JR Temkin NR Rates of symptom reporting following traumatic brain injury J Int Neuropsychol Society 2010 16 3 401 411 12 12 Godefroy O. Frontal syndrome and disorders of executive functions. J Neurol. 2003;250(1):1-6. Godefroy O Frontal syndrome and disorders of executive functions J Neurol 2003 250 1 1 6 13 13 Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological assessment. 5 ed. New York, NY: Oxford University Press; 2012. Lezak MD Howieson DB Bigler ED Tranel D Neuropsychological assessment 5 ed 2012 New York, NY Oxford University Press 14 14 Costa TL, Zaninotto ALC, Benute GG, De Lucia MCS, Paiva WS, Wagemans J, et al. Perceptual organization deficits in traumatic brain injury patients. Neuropsychologia. 2015;78:142-52. Costa TL Zaninotto ALC Benute GG De Lucia MCS Paiva WS Wagemans J Perceptual organization deficits in traumatic brain injury patients Neuropsychologia 2015 78 142 152 15 15 Zaninotto AL, de Paula Guirado VM, Baldivia B, Nunes MD, Oliveira Amorim RL, Teixeira MJ, et al. Improvement of verbal fluency in patients with diffuse brain injury over time. Neuropsychiatr Dis Treat. 2014;10: 1155-60. Zaninotto AL de Paula Guirado VM Baldivia B Nunes MD Oliveira Amorim RL Teixeira MJ Improvement of verbal fluency in patients with diffuse brain injury over time Neuropsychiatr Dis Treat 2014 10 1155 1160 16 16 Zaninotto AL, Vicentini JE, Solla DJ, Silva TT, Guirado VM, Feltrin F, et al. Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study. Acta Neuropsychiatr. 2017;29(1):35-42. Zaninotto AL Vicentini JE Solla DJ Silva TT Guirado VM Feltrin F Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study Acta Neuropsychiatr 2017 29 1 35 42 17 17 Schacter LD, Glisky EL, McGlynn SM. The Neuropsychology of Everyday Life: Assessment and Basic Competencies. Boston: Martinus Nijhoff; 1990:231-57. Schacter LD Glisky EL McGlynn SM The Neuropsychology of Everyday Life: Assessment and Basic Competencies Boston Martinus Nijhoff 1990 231 257 18 18 Hoofien D, Gilboa A, Vakil E, Donovick PJ. Traumatic brain injury (TBI) 10-20 years later: a comprehensive outcome study of psychiatric symptomatology, cognitive abilities and psychosocial functioning. Brain Inj. 2001;15(3):189-209. Hoofien D Gilboa A Vakil E Donovick PJ Traumatic brain injury (TBI) 10-20 years later: a comprehensive outcome study of psychiatric symptomatology, cognitive abilities and psychosocial functioning Brain Inj 2001 15 3 189 209 19 19 Whiteneck GG, Eagye C, Cuthbert JP, Corrigan JD, Bell JM, et al. One and Five Year Outcomes After Moderate-to-Severe Traumatic Brain Injury Requiring Inpatient Rehabilitation: U.S. Department of Health and Human Services Centers for Disease Control and Prevention National Center for Injury Prevention and Control Administration for Community Living (ACL) National Institute on Disability, Independent Living and Rehabilitation Research (NIDILRR); 2018 [Available from: https://www.cdc.gov/traumaticbraininjury/pdf/CDC-NIDILRR-Self-Report-508.pdf. Whiteneck GG Eagye C Cuthbert JP Corrigan JD Bell JM One and Five Year Outcomes After Moderate-to-Severe Traumatic Brain Injury Requiring Inpatient Rehabilitation: U.S. Department of Health and Human Services Centers for Disease Control and Prevention National Center for Injury Prevention and Control Administration for Community Living (ACL) National Institute on Disability, Independent Living and Rehabilitation Research (NIDILRR) 2018 [Available from: https://www.cdc.gov/traumaticbraininjury/pdf/CDC-NIDILRR-Self-Report-508.pdf 20 20 Cognitive Rehabilitation Therapy for Traumatic Brain Injury: Evaluating the Evidence. http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2011/Cognitive-Rehabilitation-Therapy-for-Traumatic-Brain-Injury-Evaluating-the-Evidence/CRTforTBIreportbrief2.pdf Cognitive Rehabilitation Therapy for Traumatic Brain Injury: Evaluating the Evidence http://www.nationalacademies.org/hmd/~/media/Files/Report%20Files/2011/Cognitive-Rehabilitation-Therapy-for-Traumatic-Brain-Injury-Evaluating-the-Evidence/CRTforTBIreportbrief2.pdf 21 21 Villamar MF, Portilla AS, Fregni F, Zafonte R. Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury. Neuromodulation. 2012;15(4):326-38. Villamar MF Portilla AS Fregni F Zafonte R Noninvasive Brain Stimulation to Modulate Neuroplasticity in Traumatic Brain Injury Neuromodulation 2012 15 4 326 338 22 22 Li SS, Zaninotto AL, Neville IS, Paiva WS, Nunn D, Fregni F. Clinical utility of brain stimulation modalities following traumatic brain injury: current evidence. Neuropsychiatr Dis Treat. 2015;11:1573-86. Li SS Zaninotto AL Neville IS Paiva WS Nunn D Fregni F Clinical utility of brain stimulation modalities following traumatic brain injury current evidence Neuropsychiatr Dis Treat 2015 11 1573 1586 23 23 Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The plastic human brain cortex. Ann Rev Neurosci. 2005;28:377-401. Pascual-Leone A Amedi A Fregni F Merabet LB The plastic human brain cortex Ann Rev Neurosci 2005 28 377 401 24 24 Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, et al. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008;1(3):206-23. Nitsche MA Cohen LG Wassermann EM Priori A Lang N Antal A Transcranial direct current stimulation: State of the art 2008 Brain Stimul 2008 1 3 206 223 25 25 Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017; 128(1):56-92. Lefaucheur JP Antal A Ayache SS Benninger DH Brunelin J Cogiamanian F Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) Clin Neurophysiol 2017 128 1 56 92 26 26 Nitsche MA, Liebetanz D, Lang N, Antal A, Tergau F, Paulus W. Safety criteria for transcranial direct current stimulation (tDCS) in humans. Clin Neurophysiol. 2003;114(11):2220-2. Nitsche MA Liebetanz D Lang N Antal A Tergau F Paulus W Safety criteria for transcranial direct current stimulation (tDCS) in humans Clin Neurophysiol 2003 114 11 2220 2222 27 27 Miniussi C, Ruzzoli M. Transcranial stimulation and cognition. Hand Clin Neurol. 2013;116:739-50. Miniussi C Ruzzoli M Transcranial stimulation and cognition Hand Clin Neurol 2013 116 739 750 28 28 Miniussi C, Harris JA, Ruzzoli M. Modelling non-invasive brain stimulation in cognitive neuroscience. Neurosci Biobehav Rev. 2013;37(8):1702-12. Miniussi C Harris JA Ruzzoli M Modelling non-invasive brain stimulation in cognitive neuroscience Neurosci Biobehav Rev 2013 37 8 1702 1712 29 29 Antal A, Nitsche MA, Kruse W, Kincses TZ, Hoffmann KP, Paulus W. Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans. J Cogn Neurosci. 2004;16(4): 521-7. Antal A Nitsche MA Kruse W Kincses TZ Hoffmann KP Paulus W Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans J Cogn Neurosci 2004 16 4 521 527 30 30 Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, et al. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016;9(5):641-61. Bikson M Grossman P Thomas C Zannou AL Jiang J Adnan T Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016 Brain Stimul 2016 9 5 641 661 31 31 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12. Jadad AR Moore RA Carroll D Jenkinson C Reynolds DJ Gavaghan DJ Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996 17 1 1 12 32 32 O'Neil-Pirozzi TM, Doruk D, Thomson JM, Fregni F. Immediate memory and electrophysiologic effects of prefrontal cortex transcranial direct current stimulation on neurotypical individuals and individuals with chronic traumatic brain injury: a pilot study. Int J Neurosci. 2017;127(7): 592-600. O'Neil-Pirozzi TM Doruk D Thomson JM Fregni F Immediate memory and electrophysiologic effects of prefrontal cortex transcranial direct current stimulation on neurotypical individuals and individuals with chronic traumatic brain injury: a pilot study Int J Neurosci 2017 127 7 592 600 33 33 Angelakis E, Liouta E, Andreadis N, Korfias S, Ktonas P, Stranjalis G, et al. Transcranial Direct Current Stimulation Effects in Disorders of Consciousness. Arch Phys Med Rehabil. 2014;95(2):283-9. Angelakis E Liouta E Andreadis N Korfias S Ktonas P Stranjalis G Transcranial Direct Current Stimulation Effects in Disorders of Consciousness Arch Phys Med Rehabil 2014 95 2 283 289 34 34 Middleton A, Fritz SL, Liuzzo DM, Newman-Norlund R, Herter TM. Using clinical and robotic assessment tools to examine the feasibility of pairing tDCS with upper extremity physical therapy in patients with stroke and TBI: A consideration-of-concept pilot study. Neurorehabilitation. 2014;35(4):741-54. Middleton A Fritz SL Liuzzo DM Newman-Norlund R Herter TM Using clinical and robotic assessment tools to examine the feasibility of pairing tDCS with upper extremity physical therapy in patients with stroke and TBI A consideration-of-concept pilot study Neurorehabilitation 2014 35 4 741 754 35 35 Martens G, Lejeune N, O'Brien AT, Fregni F, Martial C, Wannez S, et al. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimul. 2018;11(5):982-90. Martens G Lejeune N O'Brien AT Fregni F Martial C Wannez S Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state Brain Stimul 2018 11 5 982 990 36 36 Estraneo A, Pascarella A, Moretta P, Masotta O, Fiorenza S, Chirico G, et al. Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study. J Neurol Sci. 2017;375:464-70. Estraneo A Pascarella A Moretta P Masotta O Fiorenza S Chirico G Repeated transcranial direct current stimulation in prolonged disorders of consciousness: A double-blind cross-over study J Neurol Sci 2017 375 464 470 37 37 Thibaut A, Bruno M-A, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness. Neurology. 2014;82(13):1112-8. Thibaut A Bruno M-A Ledoux D Demertzi A Laureys S tDCS in patients with disorders of consciousness Neurology 2014 82 13 1112 1118 38 38 Thibaut A, Wannez S, Donneau AF, Chatelle C, Gosseries O, Bruno MA, et al. Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state. Brain Inj. 2017;31(4):466-74. Thibaut A Wannez S Donneau AF Chatelle C Gosseries O Bruno MA Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state Brain Inj 2017 31 4 466 474 39 39 Bai Y, Xia XY, Kang JN, Yang Y, He JH, Li XL. TDCS modulates cortical excitability in patients with disorders of consciousness. Neuroimage Clin. 2017;15:702-9. Bai Y Xia XY Kang JN Yang Y He JH Li XL TDCS modulates cortical excitability in patients with disorders of consciousness Neuroimage Clin 2017 15 702 709 40 40 Kang EK, Kim DY, Paik NJ. Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: a pilot study. J Rehabil Med. 2012;44(4):346-50. Kang EK Kim DY Paik NJ Transcranial direct current stimulation of the left prefrontal cortex improves attention in patients with traumatic brain injury: a pilot study J Rehabil Med 2012 44 4 346 350 41 41 Wilke S, List J, Mekle R, Lindenberg R, Bukowski M, Ott S, et al. No Effect of Anodal Transcranial Direct Current Stimulation on Gamma-Aminobutyric Acid Levels in Patients with Recurrent Mild Traumatic Brain Injury. J Neurotrauma. 2017;34(2):281-290. Wilke S List J Mekle R Lindenberg R Bukowski M Ott S No Effect of Anodal Transcranial Direct Current Stimulation on Gamma-Aminobutyric Acid Levels in Patients with Recurrent Mild Traumatic Brain Injury J Neurotrauma 2017 34 2 281 290 42 42 Naro A, Calabro RS, Russo M, Leo A, Pollicino P, Quartarone A, et al. Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients? Restor Neurol Neurosci. 2015;33(2):159-76 Naro A Calabro RS Russo M Leo A Pollicino P Quartarone A Can transcranial direct current stimulation be useful in differentiating unresponsive wakefulness syndrome from minimally conscious state patients? Restor Neurol Neurosci 2015 33 2 159 176 43 43 Ulam F, Shelton C, Richards L, Davis L, Hunter B, Fregni F, et al. Cumulative effects of transcranial direct current stimulation on EEG oscillations and attention/working memory during subacute neurorehabilitation of traumatic brain injury. Clin Neurophysiol. 2015;126(3):486-96. Ulam F Shelton C Richards L Davis L Hunter B Fregni F Cumulative effects of transcranial direct current stimulation on EEG oscillations and attention/working memory during subacute neurorehabilitation of traumatic brain injury Clin Neurophysiol 2015 126 3 486 496 44 44 Sacco K, Galetto V, Dimitri D, Geda E, Perotti F, Zettin M, et al. Concomitant Use of Transcranial Direct Current Stimulation and Computer-Assisted Training for the Rehabilitation of Attention in Traumatic Brain Injured Patients: Behavioral and Neuroimaging Results. Front Behav Neurosci. 2016 31;10:57. Sacco K Galetto V Dimitri D Geda E Perotti F Zettin M Concomitant Use of Transcranial Direct Current Stimulation and Computer-Assisted Training for the Rehabilitation of Attention in Traumatic Brain Injured Patients: Behavioral and Neuroimaging Results Front Behav Neurosci 31 2016 10 57 57 45 45 Lesniak M, Polanowska K, Seniow J, Czlonkowska A. Effects of Repeated Anodal tDCS Coupled With Cognitive Training for Patients With Severe Traumatic Brain Injury: A Pilot Randomized Controlled Trial. J Head Trauma Rehabil. 2014;29(3):E20-E9. Lesniak M Polanowska K Seniow J Czlonkowska A Effects of Repeated Anodal tDCS Coupled With Cognitive Training for Patients With Severe Traumatic Brain Injury: A Pilot Randomized Controlled Trial J Head Trauma Rehabil 2014 29 3 E20 EE9 46 46 Pagulayan KF, Temkin NR, Machamer J, Dikmen SS. A longitudinal study of health-related quality of life after traumatic brain injury. Arch Phys Med Rehabil. 2006;87(5):611-8. Pagulayan KF Temkin NR Machamer J Dikmen SS A longitudinal study of health-related quality of life after traumatic brain injury Arch Phys Med Rehabil 2006 87 5 611 618 47 47 Rogers L. Transcranial Direct Current Stimulation (tDCS): Emerging Uses, Safety and Neurobiological Effects. Neuroscience research progression series: Nova Science Publishers, Incorporated;2016:104 Rogers L Transcranial Direct Current Stimulation (tDCS): Emerging Uses, Safety and Neurobiological Effects Neuroscience research progression series: Nova Science Publishers, Incorporated 2016 104 104 48 48 Menon P, Geevasinga N, Yiannikas C, Howells J, Kiernan MC, Vucic S. Sensitivity and specificity of threshold tracking transcranial magnetic stimulation for diagnosis of amyotrophic lateral sclerosis: a prospective study. Lancet Neurol. 2015;14(5):478-84. Menon P Geevasinga N Yiannikas C Howells J Kiernan MC Vucic S Sensitivity and specificity of threshold tracking transcranial magnetic stimulation for diagnosis of amyotrophic lateral sclerosis: a prospective study Lancet Neurol 2015 14 5 478 484 49 49 Schmitt S, Dichter MA. Electrophysiologic recordings in traumatic brain injury. Hand Clin Neurol. 2015;127:319-39. Schmitt S Dichter MA Electrophysiologic recordings in traumatic brain injury Hand Clin Neurol 2015 127 319 339 50 50 Tolonen A, Sarkela MOK, Takala RSK, Katila A, Frantzen J, Posti JP, et al. Quantitative EEG Parameters for Prediction of Outcome in Severe Traumatic Brain Injury: Development Study. Clin EEG Neurosci. 2018;49(4): 248-57. Tolonen A Sarkela MOK Takala RSK Katila A Frantzen J Posti JP Quantitative EEG Parameters for Prediction of Outcome in Severe Traumatic Brain Injury: Development Study Clin EEG Neurosci 2018 49 4 248 257 51 51 Benbadis S. Focal disturbances of brain function. In: Levin KH, Luders HO, editors. Comprehensive Clinical Neurophysiology. Philadelphia, PA.: Saunders; 2000:457-67. Benbadis S Focal disturbances of brain function Levin KH Luders HO Comprehensive Clinical Neurophysiology Philadelphia, PA Saunders 2000 457 467