Longitudinal whole-brain analysis of multi-subject diffusion data in diffuse axonal injury.

BACKGROUND: Diffuse axonal injury occurs with high acceleration and deceleration forces in traumatic brain injury (TBI). This lesion leads to disarrangement of the neuronal network, which can result in some degree of deficiency. The Extended Glasgow Outcome Scale (GOS-E) is the primary outcome instrument for the evaluation of TBI victims. Diffusion tensor imaging (DTI) assesses white matter (WM) microstructure based on the displacement distribution of water molecules. OBJECTIVE: To investigate WM microstructure within the first year after TBI using DTI, the patient's clinical outcomes, and associations. METHODS: We scanned 20 moderate and severe TBI victims at 2 months and 1 year after the event. Imaging processing was done with the FMRIB software library; we used the tract-based spatial statistics software yielding fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) for statistical analyses. We computed the average difference between the two measures across subjects and performed a one-sample t-test and threshold-free cluster enhancement, using a corrected p-value < 0.05. Clinical outcomes were evaluated with the GOS-E. We tested for associations between outcome measures and significant mean FA clusters. RESULTS: Significant clusters of altered FA were identified anatomically using the JHU WM atlas. We found increasing spotted areas of FA with time in the right brain hemisphere and left cerebellum. Extensive regions of increased MD, RD, and AD were observed. Patients presented an excellent overall recovery. CONCLUSIONS: There were no associations between FA and outcome scores, but we cannot exclude the existence of a small to moderate association.

Longitudinal assessment of magnetization transfer ratio, brain volume, and cognitive functions in diffuse axonal injury.

BACKGROUND: Diffuse axonal injury (DAI) is a frequent mechanism of traumatic brain injury (TBI) that triggers a sequence of parenchymal changes that progresses from focal axonal shear injuries up to inflammatory response and delayed axonal disconnection. OBJECTIVE: The main purpose of this study is to evaluate changes in the axonal/myelinic content and the brain volume up to 12 months after TBI and to correlate these changes with neuropsychological results. METHODS: Patients with DAI (n = 25) were scanned at three time points after trauma (2, 6, and 12 months), and the total brain volume (TBV), gray matter volume, and white matter volume (WMV) were calculated in each time point. The magnetization transfer ratio (MTR) for the total brain (TB MTR), gray matter (GM MTR), and white matter (WM MTR) was also quantified. In addition, Hopkins verbal learning test (HVLT), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure test were performed at 6 and 12 months after the trauma. RESULTS: There was a significant reduction in the mean TBV, WMV, TB MTR, GM MTR, and WM MTR between time points 1 and 3 (p < .05). There was also a significant difference in HVLT-immediate, TMT-A, and TMT-B scores between time points 2 and 3. The MTR decline correlated more with the cognitive dysfunction than the volume reduction. CONCLUSION: A progressive axonal/myelinic rarefaction and volume loss were characterized, especially in the white matter (WM) up to 1 year after the trauma. Despite that, specific neuropsychological tests revealed that patients' episodic verbal memory, attention, and executive function improved during the study. The current findings may be valuable in developing long-term TBI rehabilitation management programs.

Effects of transcranial direct current stimulation (tDCS) and concurrent cognitive training on episodic memory in patients with traumatic brain injury: a double-blind, randomised, placebo-controlled study.

INTRODUCTION: Deficits in episodic memory following traumatic brain injury (TBI) are common and affect independence in activities of daily living. Transcranial direct current stimulation (tDCS) and concurrent cognitive training may contribute to improve episodic memory in patients with TBI. Although previous studies have shown the potential of tDCS to improve cognition, the benefits of the tDCS applied simultaneously to cognitive training in participants with neurological disorders are inconsistent. This study aims to (1) investigate whether active tDCS combined with computer-assisted cognitive training enhances episodic memory compared with sham tDCS; (2) compare the differences between active tDCS applied over the left dorsolateral prefrontal cortex (lDLPFC) and bilateral temporal cortex (BTC) on episodic memory and; (3) investigate inter and intragroup changes on cortical activity measured by quantitative electroencephalogram (qEEG). METHODS AND ANALYSIS: A randomised, parallel-group, double-blind placebo-controlled study is conducted. Thirty-six participants with chronic, moderate and severe closed TBI are being recruited and randomised into three groups (1:1:1) based on the placement of tDCS sponges and electrode activation (active or sham). TDCS is applied for 10 consecutive days for 20 min, combined with a computer-based cognitive training. Cognitive scores and qEEG are collected at baseline, on the last day of the stimulation session, and 3 months after the last tDCS session. We hypothesise that (1) the active tDCS group will improve episodic memory scores compared with the sham group; (2) differences on episodic memory scores will be shown between active BTC and lDLPFC and; (3) there will be significant delta reduction and an increase in alpha waves close to the location of the active electrodes compared with the sham group. ETHICS AND DISSEMINATION: This study was approved by Hospital das Clínicas, University of São Paulo Ethical Institutional Review Border (CAAE: 87954518.0.0000.0068). TRIAL REGISTRATION NUMBER: NCT04540783.

Dynamic changes in white matter following traumatic brain injury and how diffuse axonal injury relates to cognitive domain.

Objective: The goal is to evaluate longitudinally with diffusion tensor imaging (DTI) the integrity of cerebral white matter in patients with moderate and severe DAI and to correlate the DTI findings with cognitive deficits.Methods: Patients with DAI (n = 20) were scanned at three timepoints (2, 6 and 12 months) after trauma. A healthy control group (n = 20) was evaluated once with the same high-field MRI scanner. The corpus callosum (CC) and the bilateral superior longitudinal fascicles (SLFs) were assessed by deterministic tractography with ExploreDTI. A neuropschychological evaluation was also performed.Results: The CC and both SLFs demonstrated various microstructural abnormalities in between-groups comparisons. All DTI parameters demonstrated changes across time in the body of the CC, while FA (fractional anisotropy) increases were seen on both SLFs. In the splenium of the CC, progressive changes in the mean diffusivity (MD) and axial diffusivity (AD) were also observed. There was an improvement in attention and memory along time. Remarkably, DTI parameters demonstrated several correlations with the cognitive domains.Conclusions: Our findings suggest that microstructural changes in the white matter are dynamic and may be detectable by DTI throughout the first year after trauma. Likewise, patients also demonstrated improvement in some cognitive skills.

The Effects of Repetitive Transcranial Magnetic Stimulation on Anxiety in Patients With Moderate to Severe Traumatic Brain Injury: A Post-hoc Analysis of a Randomized Clinical Trial.

Background: Traumatic brain injury (TBI) is one of the leading causes of neuropsychiatric disorders in young adults. Repetitive Transcranial Magnetic Stimulation (rTMS) has been shown to improve psychiatric symptoms in other neurologic disorders, such as focal epilepsy, Parkinson's disease, and fibromyalgia. However, the efficacy of rTMS as a treatment for anxiety in persons with TBI has never been investigated. This exploratory post-hoc analyzes the effects of rTMS on anxiety, depression and executive function in participants with moderate to severe chronic TBI. Methods: Thirty-six participants with moderate to severe TBI and anxiety symptoms were randomly assigned to an active or sham rTMS condition in a 1:1 ratio. A 10-session protocol was used with 10-Hz rTMS stimulation over the left dorsolateral prefrontal cortex (DLPFC) for 20 min each session, a total of 2,000 pulses were applied at each daily session (40 stimuli/train, 50 trains). Anxiety symptoms; depression and executive function were analyzed at baseline, after the last rTMS session, and 90 days post intervention. Results: Twenty-seven participants completed the entire protocol and were included in the post-hoc analysis. Statistical analysis showed no interaction of group and time (p > 0.05) on anxiety scores. Both groups improved depressive and executive functions over time, without time and group interaction (p s < 0.05). No adverse effects were reported in either intervention group. Conclusion: rTMS did not improve anxiety symptoms following high frequency rTMS in persons with moderate to severe TBI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02167971.

Cognitive Assessment in Patients with Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health problem inWestern countries. ATBI brings many negative consequences, including behavioral and cognitive changes, which affect social adjustment and the performance of functional activities. Cognitive evaluation after TBI is a complex issue in what pertains to definition of the most appropriate questionnaires for clinical use in a comprehensive analysis of the condition of the patient. In this paper, we described a critical review of the main cognitive assessment tests currently used in clinical and research settings in patients with TBI.

Transcranial magnetic stimulation for the treatment of anxiety disorder.

Anxiety is currently one of the main mood changes and can impair the quality of life of the individual when associated with other neurological or psychiatric disorders. Neuromodulation has been highlighted as a form of treatment of several pathologies, including those involving anxiety symptoms. Among the neuromodulatory options with the potential to improve mood changes, we highlight repetitive transcranial magnetic stimulation (rTMS). rTMS is a viable therapeutical option for neuropsychiatric dysfunctions of high prevalence and is important for the understanding of pathological and neuropsychological adaptation processes. Even with this potential, and high relevance of intervention, we observe the scarcity of literature that covers this subject. The objective of this study was to carry out a survey of the current literature, using scientific databases for the last five years. We found 32 studies reporting the effects of rTMS on anxiety, 7 on anxiety disorders and 25 on anxiety symptoms as comorbidities of neurological or psychiatric disorders. This survey suggests the need for further studies using TMS for anxiety in order to seek strategies that minimize these anxiety effects on the quality of life of the victims of this disorder.

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review.

Traumatic brain injury (TBI) is a major cause of chronic disability. Less than a quarter of moderate and severe TBI patients improved in their cognition within 5 years. Non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), may help neurorehabilitation by boosting adaptive neuroplasticity and reducing pathological sequelae following TBI. METHODS: we searched MEDLINE/PubMed and Web of Science databases. We used Jadad scale to assess methodological assumptions. RESULTS: the 14 papers included reported different study designs; 2 studies were open-label, 9 were crossover randomized clinical trials (RCTs), and 3 were parallel group RCTs. Most studies used anodal tDCS of the left dorsolateral prefrontal cortex, but montages and stimulation parameters varied. Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments. Some studies showed changes in neurophysiologic measures (electroencephalography (EEG) and transcranial magnetic stimulation (TMS), correlating with clinical findings. The main methodological biases were lack of blinding and randomization reports. CONCLUSION: tDCS is a safe, non-invasive neuromodulatory technique that can be given as monotherapy but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. EEG and TMS may help guide research due to their roles as biomarkers for neuroplasticity.

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.

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review / Efeitos da estimulação transcraniana por corrente contínua (ETCC) na recuperação do traumatismo cranioencefálico (TCE): uma revisão sistemática

ABSTRACT. Traumatic brain injury (TBI) is a major cause of chronic disability. Less than a quarter of moderate and severe TBI patients improved in their cognition within 5 years. Non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), may help neurorehabilitation by boosting adaptive neuroplasticity and reducing pathological sequelae following TBI. Methods: we searched MEDLINE/PubMed and Web of Science databases. We used Jadad scale to assess methodological assumptions. Results: the 14 papers included reported different study designs; 2 studies were open-label, 9 were crossover randomized clinical trials (RCTs), and 3 were parallel group RCTs. Most studies used anodal tDCS of the left dorsolateral prefrontal cortex, but montages and stimulation parameters varied. Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments. Some studies showed changes in neurophysiologic measures (electroencephalography (EEG) and transcranial magnetic stimulation (TMS), correlating with clinical findings. The main methodological biases were lack of blinding and randomization reports. Conclusion: tDCS is a safe, non-invasive neuromodulatory technique that can be given as monotherapy but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. EEG and TMS may help guide research due to their roles as biomarkers for neuroplasticity.

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.

Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury.

BACKGROUND AND OBJECTIVE: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. METHODS: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. RESULTS: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. CONCLUSIONS: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Effects of transcranial LED therapy on the cognitive rehabilitation for diffuse axonal injury due to severe acute traumatic brain injury: study protocol for a randomized controlled trial.

BACKGROUND: Photobiomodulation describes the use of red or near-infrared light to stimulate or regenerate tissue. It was discovered that near-infrared wavelengths (800-900 nm) and red (600 nm) light-emitting diodes (LED) are able to penetrate through the scalp and skull and have the potential to improve the subnormal cellular activity of compromised brain tissue. Different experimental and clinical studies were performed to test LED therapy for traumatic brain injury (TBI) with promising results. One of the proposals of this present study is to develop different approaches to maximize the positive effects of this therapy and improve the quality of life of TBI patients. METHODS/DESIGN: This is a double-blinded, randomized, controlled trial of patients with diffuse axonal injury (DAI) due to a severe TBI in an acute stage (less than 8 h). Thirty two patients will be randomized to active coil helmet and inactive coil (sham) groups in a 1:1 ratio. The protocol includes 18 sessions of transcranial LED stimulation (627 nm, 70 mW/cm2, 10 J/cm2) at four points of the frontal and parietal regions for 30 s each, totaling 120 s, three times per week for 6 weeks, lasting 30 min. Patients will be evaluated with the Glasgow Outcome Scale Extended (GOSE) before stimulation and 1, 3, and 6 months after the first stimulation. The study hypotheses are as follows: (1) transcranial LED therapy (TCLT) will improve the cognitive function of DAI patients and (2) TCLT will promote beneficial hemodynamic changes in cerebral circulation. DISCUSSION: This study evaluates early and delayed effects of TCLT on the cognitive rehabilitation for DAI following severe acute TBI. There is a paucity of studies regarding the use of this therapy for cognitive improvement in TBI. There are some experimental studies and case series presenting interesting results for TBI cognitive improvement but no clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03281759 . Registered on 13 September 2017.

Altered Intracortical Inhibition in Chronic Traumatic Diffuse Axonal Injury.

BACKGROUND: Overactivation of NMDA-mediated excitatory processes and excess of GABA-mediated inhibition are attributed to the acute and subacute phases, respectively, after a traumatic brain injury (TBI). However, there are few studies regarding the circuitry during the chronic phase of brain injury. OBJECTIVE: To evaluate the cortical excitability (CE) during the chronic phase of TBI in victims diagnosed with diffuse axonal injury (DAI). METHODS: The 22 adult subjects were evaluated after a minimum of 1 year from the onset of moderate or severe TBI. Each of the subjects first had a comprehensive neuropsychological assessment to evaluate executive functions-attention, memory, verbal fluency, and information processing speed. Then, CE assessment was performed with a circular coil applying single-pulse and paired-pulse transcranial magnetic stimulation over the cortical representation of the abductor pollicis brevis muscle on M1 of both hemispheres. The CE parameters measured were resting motor threshold (RMT), motor-evoked potentials (MEPs), short-interval intracortical inhibition (SIICI), and intracortical facilitation (ICF). All data were compared with that of a control group that consisted of the healthy age-matched individuals. RESULTS: No significant differences between the left and right hemispheres were detected in the DAI subjects. Therefore, parameters were analyzed as pooled data. Values of RMT, MEPs, and ICF from DAI patients were within normal limits. However, SIICI values were higher in the DAI group-DAI SIICI = 1.28 (1.01; 1.87) versus the control value = 0.56 (0.33; 0.69)-suggesting that they had a disarranged inhibitory system (p < 0.001). By contrast, the neuropsychological findings had weak correlation with the CE data. CONCLUSION: As inhibition processes involve GABA-mediated circuitry, it is likely that the DAI pathophysiology itself (disruption of axons) may deplete GABA and contribute to ongoing disinhibition of these neural circuits of the cerebrum during the chronic phase of DAI.

Photobiomodulation using low-level laser therapy (LLLT) for patients with chronic traumatic brain injury: a randomized controlled trial study protocol.

BACKGROUND: Photobiomodulation using low-level laser therapy (LLLT) has been tested as a new technique to optimize recovery of patients with traumatic brain injury (TBI). The aim of this study is to evaluate inhibitory attentional control after 18 sessions of active LLLT and compare with the placebo group (sham LLLT). Our exploratory analysis will evaluate the efficacy of the active LLLT on verbal and visuospatial episodic memory, executive functions (working memory, verbal and visuospatial fluency, attentional processes), and anxiety and depressive symptoms compared to the sham group. METHODS/DESIGN: A randomized double-blinded trial will be made in 36 patients with moderate and severe TBI. The active LLLT will use an optical device composed of LEDs emitting 632 nm of radiation at the site with full potency of 830 mW. The cranial region with an area of 400 cm2 will be irradiated for 30 min, giving a total dose per session of 3.74 J/cm2. The sham LLLT group contains only an LED device with power < 1 mW, only serving to simulate the irradiation. Each patient will be irradiated three times per week for six weeks, totaling 18 sessions. Neuropsychological assessments will be held one week before the beginning of the sessions, after one week, and three months after the end of LLLT sessions. Memory domain, attention, executive functioning, and visual construction will be evaluated, in addition to symptoms of depression, anxiety, and social demographics. DISCUSSION: LLLT has been demonstrated as a safe and effective technique in significantly improving the memory, attention, and mood performance in healthy and neurologic patients. We expect that our trial can complement previous finds, as an effective low-cost therapy to improve cognitive sequel after TBI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393079 . Registered on 20 February 2015.

Hepatitis C virus eradication improves immediate and delayed episodic memory in patients treated with interferon and ribavirin.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is associated with impairment of cognitive function and mood disorders. Our aim was to evaluate the impact of sustained virological response (SVR) on cognitive function and mood disorders. METHOD: A prospective exploratory one arm study was conducted. Adult clinically compensated HVC patients were consecutively recruited before treatment with interferon and ribavirin for 24 to 48 weeks, according to HCV genotype. Clinical, neurocognitive and mood assessments using the PRIME-MD and BDI instruments were performed at baseline, right after half of the expected treatment has been reached and 6 months after the end of antiviral treatment. Exclusion criteria were the use of illicit psychotropic substances, mental confusion, hepatic encephalopathy, hepatocellular carcinoma, severe anemia, untreated hypothyroidism, Addison syndrome and major depression before treatment. RESULTS: Thirty six patients were enrolled and 21 completed HCV treatment (n = 16 with SVR and n = 5 without). Regardless of the viral clearance at the end of treatment, there was a significant improvement in the immediate verbal episodic memory (p = 0.010), delayed verbal episodic memory (p = 0.007), selective attention (p < 0.001) and phonemic fluency (p = 0.043). Patients with SVR displayed significant improvement in immediate (p = 0.045) and delayed verbal episodic memory (p = 0.040) compared to baseline. The baseline frequency of depression was 9.5%, which rose to 52.4% during treatment, and returned to 9.5% 6 months after the end of treatment, without significant difference between patients with and without SVR. Depressive symptoms were observed in 19.1% before treatment, 62% during (p = 0.016) and 28.6% 6 months after the end of treatment (p = 0.719). CONCLUSIONS: Eradication of HCV infection improved cognitive performance but did not affect the frequency of depressive symptoms at least in the short range.

Transcranial Direct Current Stimulation for Post-Concussion Syndrome: Study Protocol for a Randomized Crossover Trial.

BACKGROUND: Mild traumatic brain injury (MTBI) represents 70-80% of all treated brain injuries. A considerable proportion of MTBI patients experience post-concussion symptoms for a prolonged period after MTBI, and these symptoms are diagnosed as persistent post-concussion syndrome (PPCS). PPCS is defined as a range of physical, cognitive, and emotional symptoms. However, memory and executive dysfunction seems to be one of the most debilitating symptoms. Recently, non-invasive brain stimulation has been studied as a potential treatment method for traumatic brain injury (TBI) patients. Therefore, our primary goal is to verify the effects of transcranial direct current stimulation (tDCS) in patients with PPCS who demonstrate cognitive deficits in long-term episodic memory, working memory, and executive function following MTBI. METHODS/DESIGN: This is a randomized crossover trial of patients with a history of MTBI with cognitive deficits in memory and executive function. Thirty adult patients will be randomized in a crossover manner to receive three weekly sessions of anodal tDCS (2 mA) at left dorsolateral prefrontal cortex, left temporal cortex, and sham stimulation that will be performed at 7-day intervals (washout period). The clinical diagnosis of PPCS will be determined using the Rivermead Post-Concussion Symptoms Questionnaire. Patients who meet the inclusion criteria will be assessed with a neuropsychological evaluation. A new battery of computerized neuropsychological tests will be performed before and immediately after each stimulation. Statistical analysis will be performed to determine trends of cognitive improvement. DISCUSSION: There is paucity of studies regarding the use of tDCS in TBI patients, and although recent results showed controversial data regarding the effects of tDCS in such patients, we will address specifically patients with PPCS and MTBI and no brain abnormalities on CT scan other than subarachnoid hemorrhage. Moreover, due to the missing information on literature regarding the best brain region to be studied, we will evaluate two different regions to find immediate effects of tDCS on memory and executive dysfunction. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02292589 (https://register.clinicaltrials.gov).

Hypnosis as a Valuable Tool for Surgical Procedures in the Oral and Maxillofacial Area.

Hypnosis is a valuable tool in the management of patients who undergo surgical procedures in the maxillofacial complex, particularly in reducing and eliminating pain during surgery and aiding patients who have dental fear and are allergic to anesthesia. This case report demonstrates the efficacy of hypnosis in mitigating anxiety, bleeding, and pain during dental surgery without anesthesia during implant placement of tooth 14, the upper left first molar.

Visuospatial memory improvement in patients with diffuse axonal injury (DAI): a 1-year follow-up study.

OBJECTIVE: Diffuse axonal injury (DAI) is prevalent in traumatic brain injury (TBI), and is often associated with poor outcomes and cognitive impairment, including memory deficits. Few studies have explored visual memory after TBI and its relationship to executive functioning. Executive functioning is crucial for remembering an object's location, operating devices, driving, and route finding. We compared visual memory performance via the Rey-Osterrieth Complex Figure (ROCF) test 6 and 12 months after DAI. METHOD: In total, 40 patients (mean age 28.7 years; 87.5% male) with moderate-to-severe DAI following a road traffic accident completed the 1-year follow-up. There was a three-phase prospective assessment. In phase 1 (1-3 months after trauma), patients completed the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI). In phases 2 (6 months) and 3 (12 months), they completed the BDI, STAI, and a neuropsychological battery [ROCF copy and recall, digit span forward/backward, Grooved Pegboard test, intelligence quotient (IQ) by Wechsler Adult Intelligence Scale-III (WAIS-III)]. RESULTS: There was an improvement in ROCF recall over time (p=0.013), but not ROCF copy (p=0.657).There was no change in executive function (Savage scores) copy (p=0.230) or recall (p=0.155). Age, years of education, severity of the trauma, and IQ did not influence ROCF recall improvement. CONCLUSION: There are time-dependent improvements in visual memory in patients with DAI. Neuroplasticity in the 1st months after trauma provides an opportunity for visuospatial memory learning. The present findings may be useful to formulate management plans for long-term TBI rehabilitation.