DTI-derived parameters differ between moderate and severe traumatic brain injury and its association with psychiatric scores.

BACKGROUND AND AIM: Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. METHODS: Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12 months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. RESULTS: Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p < 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p < 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p < 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI. CONCLUSION: DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.

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.

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.

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.

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.

Non-invasive Intracranial Pressure Waveform Analysis in Chiari Malformation Type 1: A Pilot Trial.

OBJECTIVE: This pilot study aimed to investigate the role of Posterior Fossa Decompression (PFD) on the intracranial pressure (ICP) waveform in patients with Chiari Malformation type 1 (CM1). It also sought to explore the relationship between symptom improvement and ICP waveform behavior. METHODS: This exploratory cohort study evaluated adult patients diagnosed with CM1. The patients underwent PFD using a standard technique at our institution, which involved a 3 × 3 cm posterior craniectomy and excision of the posterior arch of C1. The ICP waveform was measured using an external strain-gauge device connected to a pin attached to the skull. Measurements were collected pre- and post-PFD, and the P2/P1 ratio was calculated pre- and postoperatively. RESULTS: The pilot study comprised 6 participants, 3 men and 3 women, with ages ranging from 39 to 68 years. The primary symptoms were cerebellar ataxia and typical headaches. The study found that most patients who showed clinical improvement, as judged by the Gestalt method, had a postoperative decrease in the P2/P1 ratio. However, 1 patient did not show an improvement in the P2/P1 ratio despite a good clinical outcome. CONCLUSIONS: This study suggests that the P2/P1 ratio may decrease after PFD. However, we highlight the need for further research with a larger sample size to confirm these preliminary results.

Speech motor impairment in ALS is associated with multiregional cortical thinning beyond primary motor cortex.

Introduction: Cortical thinning is well-documented in individuals with amyotrophic lateral sclerosis (ALS), yet its association with speech deterioration remains understudied. This study characterizes anatomical changes in the brain within the context of speech impairment patterns in individuals with ALS, providing insight into the disease's multiregional spread and biology. Methods: To evaluate patterns of cortical thickness in speakers with ALS with and without functional speech changes compared to healthy controls (HCs) using whole-brain and region of interest (ROI) analyses. Forty individuals with ALS and 22 HCs underwent a T1-weighted 3-Tesla magnetic resonance imaging (MRI). Individuals with ALS were divided into two groups based on the preserved speech [ps-ALS] (n = 18) or deteriorated speech [ds-ALS] (n = 22) as measured by the ALSFRSF-R speech subscore (=4 or <4 points, respectively). Sixteen a priori-defined and automatically segmented cortical and subcortical brain ROIs were selected based on their previously documented roles in speech production. Two cortical thickness analyses were performed: (1) group-level whole-brain surface-based analyses and (2) group-level ROI analyses. A case study of 6 ALS individuals examined the cortical thickness, and their speech was characterized using quantitative and qualitative measures. Results: Based on the group-level whole-brain surface-based analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in the left primary motor and somatosensory cortices and the right inferior parietal lobe with its adjacent lateral occipital cortical regions. The ps-ALS group demonstrated no significant cortical thinning compared to HCs. Based on the group-level ROI analyses, the ds-ALS group demonstrated significant cortical thinning compared to HCs in bilateral middle motor cortices, right posterior dorsal premotor cortex, and left anterior cingulate cortex. The case study analysis revealed that ALS speakers with speech features characteristic of spastic dysarthria exhibited cortical thinning, while those with speech features characteristic of flaccid dysarthria did not. Discussion: Individuals with ALS have anatomical changes involving multiregional neocortical areas beyond the primary motor cortex that may manifest as subjective (i.e., clinical judgment) and objective (i.e., speaking rate) changes in speech production. Further longitudinal work in ALS is needed to better understand the link between MRI cortical thickness changes and bulbar dysfunction.

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.

Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic epileptic spasms.

A five-and-a-half-year-old girl started experiencing progressive left hemiparesis at age two and a half years. At age five years and four months she started presenting clusters of asymmetric periodic epileptic spasms with no hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped complexes. Serial brain imaging revealed progressive atrophy of the right hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy, and histological examination showed signs of inflammation and features of focal cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is unique in the following aspects: the presence of typical Rasmussen encephalitis features of progressive unilateral brain involvement without seizures, a delay of almost three years prior to seizure onset; an atypical seizure type presentation with periodic epileptic spasms and the presence of FCD associated with inflammatory changes. [Published with video sequences].

Speech and swallowing deficits in X-Linked Dystonia-Parkinsonism.

INTRODUCTION: X-linked Dystonia-Parkinsonism (XDP) is a progressive, disabling disease characterized by the devastating impairment of bulbar function, including speech and swallowing. Despite these detrimental impacts, bulbar impairments in this population are not well characterized. OBJECTIVES: To identify impairments in the bulbar system measured by oromotor performance in individuals with XDP relative to healthy controls. Secondarily, to detect diagnostic bulbar markers that are sensitive and specific to the initial years of XDP. METHODS: This case-control study included 25 healthy controls and 30 participants with XDP, divided into two subgroups based on the median of their disease length. Multiple clinical and instrumental oromotor tasks and measures were used to evaluate bulbar motor function. RESULTS: Differences were found between both the subgroups with XDP and healthy controls on almost all measures, including maximum performance tasks such as tongue strength, alternating motion rate (AMR), and sequential motion rate (SMR) (p < 0.05). Differences were found between the XDP subgroups and the control group for the percentage of pause time during the speech, a rating of speech severity, and a swallowing task (ps < 0.05). Scores on self-reported questionnaires, tongue strength, the number of repetitions produced during an AMR, percent pause, and speech severity demonstrated good sensitivity and specificity to differentiate the initial years of XDP onset from healthy controls. CONCLUSIONS: Our findings revealed impairments across bulbar functions in participants within the first 7 years of the XDP onset. Highly sensitive and specific bulbar impairment measures were detected in instrumental and self-reported measures that are fundamental for monitoring disease.

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.

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.

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.

Repetitive TMS does not improve cognition in patients with TBI: A randomized double-blind trial.

OBJECTIVE: To determine whether high-frequency repetitive transcranial magnetic stimulation (rTMS) improves cognition in patients with severe traumatic brain injury. METHODS: A single-center, randomized, double-blind, placebo-controlled study of rTMS was conducted in patients aged 18-60 years with chronic (>12 months postinjury) diffuse axonal injury (DAI). Patients were randomized to either a sham or real group in a 1:1 ratio. A 10-session rTMS protocol was used with 10-Hz stimulation over the left dorsolateral prefrontal cortex (DLPFC). Neuropsychological assessments were performed at 3 time points: at baseline, after the 10th rTMS session, and 90 days after intervention. The primary outcome was change in executive function evaluated using the Trail Making Test Part B. RESULTS: Thirty patients with chronic DAI met the study criteria. Between-group comparisons of performance on TMT Part B at baseline and after the 10th rTMS session did not differ between groups (p = 0.680 and p = 0.341, respectively). No significant differences were observed on other neuropsychological tests. No differences in adverse events between treatment groups were observed. CONCLUSIONS: Cognitive function in individuals with chronic DAI is not improved by high-frequency rTMS over the left DLPFC, though it appears safe and well-tolerated in this population. CLINICALTRIALSGOV IDENTIFIER: NCT02167971. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for individuals with chronic DAI, high-frequency rTMS over the left DLPFC does not significantly improve cognition.

Longitudinal Clinical Trial Recruitment and Retention Challenges in the Burn Population: Lessons Learned From a Trial Examining a Novel Intervention for Chronic Neuropathic Symptoms.

Long-term trials are key to understanding chronic symptoms such as pain and itch. However, challenges such as high attrition rates and poor recruitment are common when conducting research. The aim of this work was to explore these issues within a long-term randomized control trial using transcranial direct current stimulation to treat pain and itch. This parallel double blinded, placebo-controlled randomized trial was comprised of 15 transcranial direct current stimulation visits and 7 follow-up visits. Participants were over the age of 18, had a burn injury that occurred at least 3 weeks before enrollment, and reported having pain and/or itch that was moderate to severe in intensity. A total of 31 subjects were randomized into either an active or sham transcranial direct current stimulation groups. There were no significant differences between the groups in terms of age, race, education, baseline depression, or anxiety. The median dropout time was at visit 19 (visit 16 [SE = 1.98] for the sham group and visit 19 [SE = 1.98] for the active group). Analysis showed no differences in the dropout rate between groups [χ2(1) = 0.003, P = .954]. The dropout rate was 46.7% for the sham group and 43.8% for the active group. Overall, 45.2% of the subjects dropped out of the trial. Long-term clinical trials are an essential part of evaluating interventions for symptoms such as chronic pain and itch. However, as seen in this trial, long-term studies in the burn population often face recruitment and adherence challenges.

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.