Montserrat Bernabeu

NONINVASIVE BRAIN STIMULATION IN TRAUMATIC BRAIN INJURY

Objective:To review novel techniques of noninvasive brain stimulation (NBS), which may have value in assessment and treatment of traumatic brain injury (TBI). Methods:Review of the following techniques: transcranial magnetic stimulation, transcranial direct current stimulation, low-level laser therapy, and transcranial Doppler sonography. Furthermore, we provide a brief overview of TMS studies to date. Main findings:We describe the rationale for the use of these techniques in TBI, discuss their possible mechanisms of action, and raise a number of considerations relevant to translation of these methods to clinical use. Depending on the stimulation parameters, NBS may enable suppression of the acute glutamatergic hyperexcitability following TBI and/or counter the excessive GABAergic effects in the subacute stage. In the chronic stage, brain stimulation coupled to rehabilitation may enhance behavioral recovery, learning of new skills, and cortical plasticity. Correlative animal models and comprehensive safety trials seem critical to establish the use of these modalities in TBI. Conclusions:Different forms of NBS techniques harbor the promise of diagnostic and therapeutic utility, particularly to guide processes of cortical reorganization and enable functional restoration in TBI. Future lines of safety research and well-designed clinical trials in TBI are warranted to determine the capability of NBS to promote recovery and minimize disability.

Cerebral response to speech in vegetative and minimally conscious states after traumatic brain injury

Primary objective: To study cerebral response in a functional magnetic resonance imaging (fMRI) task of speech perception in a sample of patients in vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury. Methods: Three patients in VS, four patients in MCS and 19 healthy volunteers were enrolled for the study. All subjects underwent an fMRI task of passive listening of narratives played forward and backward, alternated with periods of silence. This study analysed cerebral response to language and to complex sound processing in the healthy subjects’ group and in each patient, using SPM5. Results: One patient in VS and one in MCS showed cerebral responses to language and to complex sound very similar to those shown by the healthy volunteers. Two more patients, one in VS and one in MCS, showed significant responses to complex sound only. Finally, one patient in VS and one patient in MCS failed to show significant activation in response to either stimulus. Conclusions: Some patients in VS and MCS can preserve cerebral responses to language and auditory stimuli. fMRI may be useful to identify these responses, which may pass unnoticed in a bedside examination.

A longitudinal fMRI study of working memory in severe TBI patients with diffuse axonal injury.

Traumatic brain injury (TBI) patients have working memory deficits and altered patterns of brain activation during this function. The evolution of the impairment has not been examined to date. This study investigated longitudinal changes in brain activation during a working memory task. Twelve patients with severe and diffuse TBI and ten healthy matched controls were fMRI scanned twice at a 6-month interval during an n-back task (0-, 2- and 3-back). All the TBI patients selected presented signs of diffuse axonal injury on CT but had no evidence of focal lesions on MRI clinical examination. Significant changes in brain activation over time were observed in patients, but not in controls. During the first examination, though both groups engaged bilateral fronto-parietal regions known to be involved in working memory, activation of the right superior frontal gyrus was low in the TBI group. However, the difference between TBI and controls had decreased significantly after 6 months. A factor analysis confirmed the greater increase in activation in the right superior frontal cortex in the TBI group than in healthy controls, leading to normalization of the brain activation pattern. In conclusion, this longitudinal study provides evidence of a progressive normalization of the working memory activation pattern after diffuse axonal injury in severe TBI, coinciding with an improvement in performance on this function.

Frontal Hypoactivation on Functional Magnetic Resonance Imaging in Working Memory after Severe Diffuse Traumatic Brain Injury

Working memory is frequently impaired after traumatic brain injury (TBI). The present study aimed to investigate working memory deficits in patients with diffuse axonal injury and to determine the contribution of cerebral activation dysfunctions to them. Eighteen patients with severe TBI and 14 healthy controls matched for age and gender were included in the study. TBI patients were selected according to signs of diffuse axonal injury on computed tomography (CT) and without any evidence of focal lesions on MRI clinical examination. Functional magnetic resonance (fMRI) was used to assess brain activation during n-back tasks (0-, 2-, and 3-back). Compared to controls, the TBI group showed significant working memory impairment on the Digits Backwards (p=0.022) and Letter-Number Sequencing subtests from the WAIS-III (p<0.001) under the 2-back (p=0.008) and 3-back (p=0.017) conditions. Both groups engaged bilateral fronto-parietal regions known to be involved in working memory, although patients showed less cerebral activation than did controls. Decreased activation in TBI patients compared to controls was observed mainly in the right superior and middle frontal cortex. The correlation patterns differed between patients and controls: while the control group showed a negative correlation between performance and activation in prefrontal cortex (PFC), TBI patients presented a positive correlation in right parietal and left parahippocampus for the low and high working memory load, respectively. In conclusion, severe TBI patients with diffuse brain damage show a pattern of cerebral hypoactivation in the right middle and superior frontal regions during working memory tasks, and also present an impaired pattern of performance correlations.

Developing Core Sets for Persons With Traumatic Brain Injury Based on the International Classification of Functioning, Disability, and Health:

The authors outline the process for developing the International Classification of Functioning, Disability, and Health (ICF) Core Sets for traumatic brain injury (TBI). ICF Core Sets are selections of categories of the ICF that identify relevant categories of patients affected by specific diseases. Comprehensive and brief ICF Core Sets for TBI should become useful for clinical practice and for research. The final definition of the ICF Core Sets for TBI will be determined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies. The development of ICF Core Sets is an inclusive and open process and rehabilitation professionals are invited to participate.

Reductions of Thalamic Volume and Regional Shape Changes in the Vegetative and the Minimally Conscious States

The thalamus is known to play a key role in arousal regulation and support of human consciousness. Neuropathological studies have identified thalamic damage as one of the most common abnormalities present in the brains of patients who were in a vegetative state (VS) or a minimally-conscious state (MCS) state at the time of their deaths. Nonetheless, no in vivo studies of thalamic abnormalities in these patients have been conducted. Using high-resolution T1-weighted magnetic resonance images and a novel approach to shape analysis, we investigated thalamic global and regional changes in a sample of patients in a VS or an MCS. Group comparisons and correlations with clinical variables were performed for the total thalamic volume and for each surface vertex. Total thalamic volume was significantly lower in patients than in healthy volunteers. Shape analysis revealed significant bilateral regional atrophy in the dorso-medial body in patients compared to controls; this atrophy was more widespread in VS than in MCS patients. Lower thalamic volume was significantly correlated with worse Disability Rating Scale scores. Shape analysis suggested that the dorso-medial nucleus and the internal medullar lamina were the main regions responsible for this correlation. Our findings suggest that MCS and VS patients present different patterns of regional thalamic abnormalities, and that these differences partially explain their clinical profile.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

BackgroundThe rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness.MethodsfMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits.ResultsfMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus.ConclusionsThese results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

What domains of the International Classification of Functioning, Disability and Health are covered by the most commonly used measurement instruments in traumatic brain injury research?

OBJECTIVE To identify the most frequently used outcome measurement instruments reported in clinical studies on TBI and to provide a content comparison in the framework of the International Classification of Functioning, Disability and Health (ICF). PATIENTS AND METHODS A systematic literature review of clinical studies in TBI was performed using Medline, EMBASE and PsychINFO. The items of the measurement instruments present in more than 20% of the studies were linked to the ICF language. RESULTS 193 papers fulfilled the eligibility criteria. The frequency analysis identified six instruments: Functional Independence Measure (50%), Glasgow Outcome Scale (34%), Disability Rating Scale (32%), Wechsler Adult Intelligence Scale (29%), Trail Making Test (26%) and Community Integration Questionnaire (22%). The analysed instruments focus on different aspects of body functions (especially DRS, WAIS and TMT) and aspects of activities and participation in life (especially CIQ and FIM). Inter-researcher agreement for the ICF linking process was 0.83. CONCLUSIONS Translating the items of different measurement instruments into the ICF language provides a practical tool to facilitate content comparisons among different outcome measures. The comparison can assist clinical researchers to integrate information acquired from different studies and different tools.

An observational report of intensive robotic and manual gait training in sub-acute stroke

BackgroundThe use of automated electromechanical devices for gait training in neurological patients is increasing, yet the functional outcomes of well-defined training programs using these devices and the characteristics of patients that would most benefit are seldom reported in the literature. In an observational study of functional outcomes, we aimed to provide a benchmark for expected change in gait function in early stroke patients, from an intensive inpatient rehabilitation program including both robotic and manual gait training.MethodsWe followed 103 sub-acute stroke patients who met the clinical inclusion criteria for Body Weight Supported Robotic Gait Training (BWSRGT). Patients completed an intensive 8-week gait-training program comprising robotic gait training (weeks 0-4) followed by manual gait training (weeks 4-8). A change in clinical function was determined by the following assessments taken at 0, 4 and 8 weeks (baseline, mid-point and end-point respectively): Functional Ambulatory Categories (FAC), 10 m Walking Test (10 MWT), and Tinetti Gait and Balance Scales.ResultsOver half of the patients made a clinically meaningful improvement on the Tinetti Gait Scale (> 3 points) and Tinetti Balance Scale (> 5 points), while over 80% of the patients increased at least 1 point on the FAC scale (0-5) and improved walking speed by more than 0.2 m/s. Patients responded positively in gait function regardless of variables gender, age, aetiology (hemorrhagic/ischemic), and affected hemisphere. The most robust and significant change was observed for patients in the FAC categories two and three. The therapy was well tolerated and no patients withdrew for factors related to the type or intensity of training.ConclusionsEight-weeks of intensive rehabilitation including robotic and manual gait training was well tolerated by early stroke patients, and was associated with significant gains in function. Patients with mid-level gait dysfunction showed the most robust improvement following robotic training.

Do traditional executive measures tell us anything about daily-life functioning after traumatic brain injury in Spanish-speaking individuals?

Primary objective: To examine the relationship between traditional executive function measures and everyday competence in Spanish-speaking individuals with moderate-to-severe traumatic brain injury (TBI). Methods and procedures: Thirty-two TBI patients (24 men, eight women) with an age range of 17–59 years (mean age = 30.73 years; SD = 13.34) were administered a battery of performance-based executive function measures. Such measures included the Trail Making Test part B, Wisconsin Card Sorting Test, Stroop Colour Word Interference Test, Controlled Oral Word Association Test and Letter-Number Sequencing. Behavioural manifestations of executive deficits were assessed by the Behaviour Rating Inventory of Executive Function-Adult version (BRIEF-A). Patients everyday functioning was examined with the Patient Competency Rating Scale (PCRS). Main outcomes and results: Traditional performance-based executive measures correlated significantly, although moderately, with the PCRS; this relationship was more significant in the Controlled Oral Word Association Test and Trail Making Test part B. A significant correlation was obtained between the BRIEF-A clinical scales and patients everyday competence as measured by the PCRS. Conclusions: The current findings suggest that traditional performance-based executive measures reveal some degree of ecological validity or real-world relevance, providing relevant information for predicting everyday competence after moderate-to-severe TBI.