RIPK1 or RIPK3 deletion prevents progressive neuronal cell death and improves memory function after traumatic brain injury.

Traumatic brain injury (TBI) causes acute and subacute tissue damage, but is also associated with chronic inflammation and progressive loss of brain tissue months and years after the initial event. The trigger and the subsequent molecular mechanisms causing chronic brain injury after TBI are not well understood. The aim of the current study was therefore to investigate the hypothesis that necroptosis, a form a programmed cell death mediated by the interaction of Receptor Interacting Protein Kinases (RIPK) 1 and 3, is involved in this process. Neuron-specific RIPK1- or RIPK3-deficient mice and their wild-type littermates were subjected to experimental TBI by controlled cortical impact. Posttraumatic brain damage and functional outcome were assessed longitudinally by repetitive magnetic resonance imaging (MRI) and behavioral tests (beam walk, Barnes maze, and tail suspension), respectively, for up to three months after injury. Thereafter, brains were investigated by immunohistochemistry for the necroptotic marker phosphorylated mixed lineage kinase like protein(pMLKL) and activation of astrocytes and microglia. WT mice showed progressive chronic brain damage in cortex and hippocampus and increased levels of pMLKL after TBI. Chronic brain damage occurred almost exclusively in areas with iron deposits and was significantly reduced in RIPK1- or RIPK3-deficient mice by up to 80%. Neuroprotection was accompanied by a reduction of astrocyte and microglia activation and improved memory function. The data of the current study suggest that progressive chronic brain damage and cognitive decline after TBI depend on the expression of RIPK1/3 in neurons. Hence, inhibition of necroptosis signaling may represent a novel therapeutic target for the prevention of chronic post-traumatic brain damage.

Cluster analysis of impairment measures to inform an evidence-based classification structure in RaceRunning, a new World Para Athletics event for athletes with hypertonia, ataxia or athetosis.

RaceRunning enables athletes with limited or no walking ability to propel themselves independently using a three-wheeled frame that has a saddle, handle bars and a chest plate. For RaceRunning to be included as a para athletics event, an evidence-based classification system is required. This study assessed the impact of trunk control and lower limb impairment measures on RaceRunning performance and evaluated whether cluster analysis of these impairment measures produces a valid classification structure for RaceRunning. The Trunk Control Measurement Scale (TCMS), Selective Control Assessment of the Lower Extremity (SCALE), the Australian Spasticity Assessment Scale (ASAS), and knee extension were recorded for 26 RaceRunning athletes. Thirteen male and 13 female athletes aged 24 (SD = 7) years participated. All impairment measures were significantly correlated with performance (rho = 0.55-0.74). Using ASAS, SCALE, TCMS and knee extension as cluster variables in a two-step cluster analysis resulted in two clusters of athletes. Race speed and the impairment measures were significantly different between the clusters (p < 0.001). The findings of this study provide evidence for the utility of the selected impairment measures in an evidence-based classification system for RaceRunning athletes.

Gait Performance in People with Symptomatic, Chronic Mild Traumatic Brain Injury.

There is a dearth of knowledge about how symptom severity affects gait in the chronic (>3 months) mild traumatic brain injury (mTBI) population despite up to 53% of people reporting persisting symptoms after mTBI. The aim of this investigation was to determine whether gait is affected in a symptomatic, chronic mTBI group and to assess the relationship between gait performance and symptom severity on the Neurobehavioral Symptom Inventory (NSI). Gait was assessed under single- and dual-task conditions using five inertial sensors in 57 control subjects and 65 persons with chronic mTBI (1.0 year from mTBI). The single- and dual-task gait domains of Pace, Rhythm, Variability, and Turning were calculated from individual gait characteristics. Dual-task cost (DTC) was calculated for each domain. The mTBI group walked (domain z-score mean difference, single-task = 0.70; dual-task = 0.71) and turned (z-score mean difference, single-task = 0.69; dual-task = 0.70) slower (p < 0.001) under both gait conditions, with less rhythm under dual-task gait (z-score difference = 0.21; p = 0.001). DTC was not different between groups. Higher NSI somatic subscore was related to higher single- and dual-task gait variability as well as slower dual-task pace and turning (p < 0.01). Persons with chronic mTBI and persistent symptoms exhibited altered gait, particularly under dual-task, and worse gait performance related to greater symptom severity. Future gait research in chronic mTBI should assess the possible underlying physiological mechanisms for persistent symptoms and gait deficits.

Impaired cerebral blood flow regulation in chronic traumatic brain injury.

Baroreflex sensitivity (BRS) and cerebral autoregulation (CA) play an important role in maintaining constant cerebral blood flow (CBF) during systemic changes in blood pressure (BP). Impaired BRS and CA have been reported in acute traumatic brain injury (TBI) which may also contribute to secondary injury and poorer recovery after acute TBI; however, their status during chronic stages remains elusive. Thus, the goal of this study is to determine whether cardiac BRS and dynamic CA (dCA) were impaired during the chronic stage in patients with single TBI and persistent neurological symptoms. Twenty-two subjects with blunt head TBI ≥ 6 months prior to the study (13 mild and 9 moderate to severe TBI) and persistent symptoms on Rivermead Post-Concussion Symptoms Questionnaire at enrollment were compared to 22 age/sex/fitness level-matched healthy control subjects. Beat-to-beat changes in heart rate, BP, and CBF velocity were measured at rest and during a repeated sit-stand maneuver. Hemodynamic variability, dCA, and cardiac BRS were calculated using spectral and transfer function analyses. We found dCA phase in low frequency (LF) range of 0.07-0.20 Hz was lower in subjects with TBI than in control subjects (0.51 ± 0.19 vs. 0.63 ± 0.26, p = 0.043) during the resting condition. Among subjects with TBI, the lower dCA phase in LF was correlated with poorer performance on measures of cognitive function (all p < 0.05). These findings suggested that subjects with chronic TBI showed impaired dCA which may contribute to persistent cognitive impairment. Cerebrovascular measures may provide a physiological measure to evaluate interventions for chronic TBI and accompanying functional deficits.

Relationship of Cerebral Blood Flow to Cognitive Function and Recovery in Early Chronic Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of morbidity worldwide, for which biomarkers are needed to better understand the underlying pathophysiology. Microvascular injury represents a subset of pathological mechanisms contributing to cognitive dysfunction after TBI, which may also impair subsequent neural repair thereby inhibiting cognitive recovery. Magnetic resonance imaging (MRI)-based measurement of cerebral blood flow (CBF) by arterial spin labeling (ASL) provides an appealing means of assessing microvascular disruption in TBI; however, the relationship between CBF alterations in the early chronic post-TBI setting and cognitive dysfunction as well as subsequent cognitive recovery remain poorly understood. Structural MRI and ASL were performed in 42 TBI subjects 3 months post-injury and 35 matched healthy controls. Neuropsychological testing was performed in each subject, as well as in a subset of TBI patients (n = 33) at 6 and/or 12 months post-injury. TBI and control subject CBF data were compared between groups in a voxel-wise fashion while controlling for the effects of structural atrophy. A region-of-interest approach was then used to compare CBF to clinical and neuropsychological measures within the TBI group in a cross-sectional fashion, as well as to the degree of subsequent cognitive recovery among subjects with follow-up testing. At 3 months post-injury, the TBI group demonstrated lower performance in each cognitive domain (p < 0.05), as well as widespread reductions in gray matter CBF independent of structural atrophy (p < 0.05). Within the TBI group, CBF was moderately correlated with injury severity (r = -0.43; p = 0.009) and executive function (r = 0.43; p = 0.01). In the longitudinal analysis, there was a positive correlation between initial CBF and processing speed recovery (r = 0.43; p = 0.015) independent of age, education level, and initial test score. Early chronic TBI is associated with widespread gray matter CBF deficits, which are correlated with injury severity and cognitive dysfunction. CBF may predict subsequent recovery in some cognitive domains.

A novel repetitive head impact exposure measurement tool differentiates player position in National Football League.

American-style football participation poses a high risk of repetitive head impact (RHI) exposure leading to acute and chronic brain injury. The complex nature of symptom expression, human predisposition, and neurological consequences of RHI limits our understanding of what constitutes as an injurious impact affecting the integrity of brain tissue. Video footage of professional football games was reviewed and documentation made of all head contact. Frequency of impact, tissue strain magnitude, and time interval between impacts was used to quantify RHI exposure, specific to player field position. Differences in exposure characteristics were found between eight different positions; where three unique profiles can be observed. Exposure profiles provide interpretation of the relationship between the traumatic event(s) and how tissue injury is manifested and expressed. This study illustrates and captures an objective measurement of RHI on the field, a critical component in guiding public policy and guidelines for managing exposure.

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.

Pulsed Transcranial Red/Near-Infrared Light Therapy Using Light-Emitting Diodes Improves Cerebral Blood Flow and Cognitive Function in Veterans with Chronic Traumatic Brain Injury: A Case Series.

Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Background: Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. Materials and methods: Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). Results: Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21-21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. Conclusions: Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.

Chronic Traumatic Encephalopathy.

PURPOSE OF REVIEW: This article provides a discussion on the current state of knowledge of chronic traumatic encephalopathy (CTE), with an emphasis on clinical features and emerging biomarkers of the condition. RECENT FINDINGS: The results of several large brain bank case series among subjects with a history of contact sports or repetitive head trauma have indicated that a high frequency of CTE may exist in this population. However, the true prevalence of CTE among individuals with a history of head trauma remains unknown, given that individuals who experienced cognitive, behavioral, and mood symptoms during life are more likely to have their brains donated for autopsy at death and epidemiologic studies of the condition are lacking. Neuropathologic consensus criteria have been published. Research-based clinical criteria have been proposed and are beginning to be applied, but the definitive diagnosis of CTE in a living patient remains impossible without effective biomarkers for the condition, which is an active area of study. SUMMARY: The field of CTE research is rapidly growing and parallels many of the advances seen for other neurodegenerative conditions, such as Alzheimer disease decades ago.

Balance in chronic traumatic brain injury: correlations between clinical measures and a self-report measure.

OBJECTIVE: To assess associations among commonly used self-report and clinical measures of balance in chronic TBI. DESIGN: Cross-sectional analysis of balance in a convenience sample of individuals at least one year post TBI. MAIN OUTCOME MEASURES: Activities-Specific Balance Confidence Scale (ABC) (self-reported balance impairment), Community Balance and Mobility Scale (CB&M) (clinical measure validated in TBI), and Balance Evaluation Systems Test (BESTest) (clinical measure not validated in TBI). METHODS: Fifty-nine individuals (64% male, mean age 48.2 years) ambulating independently within the home participated in testing. Pearson correlation coefficients were used to quantify the direction and magnitude of the relationships among the three balance impairment measures. RESULTS: A significant positive correlation was noted between the ABC and CB&M (r = 0.42, p = 0.0008), between the ABC and BESTest (r = 0.46, p = 0.0002), and between the CB&M and BESTest (r = 0.86, p < 0.0001). CONCLUSIONS: This is the first study we are aware of in the chronic moderate to severe TBI population directly comparing patient's self-reported balance impairment with clinical measures. Positive correlations were found between the self-report measure and both clinical measures. Overall, individuals with chronic TBI tend to self-report less impaired balance than clinical measures indicate. These results provide preliminary evidence to support the need for validation of the BESTest in this population. ABBREVIATIONS: ABC: Activities-specific balance confidence scale; BESTest: balance evaluation systems test; BOS: base of support; COM: center of mass; CB&M: community balance and mobility scale; CI: confidence interval; IQR: interquartile range; PTs: physical therapists; SD: standard deviation; SE: standard error; TBI: traumatic brain injury.

High Systolic Blood Pressure Induces Cerebral Microvascular Endothelial Dysfunction, Neurovascular Unit Damage, and Cognitive Decline in Mice.

A chronic and gradual increase in pulse pressure (PP) is associated with cognitive decline and dementia in older individuals, but the mechanisms remain ill-defined. We hypothesized that a chronic elevation of PP would cause brain microvascular endothelial mechanical stress, damage the neurovascular unit, and ultimately induce cognitive impairment in mice, potentially contributing to the progression of vascular dementia and Alzheimer disease. To test our hypothesis, male control wild-type mice and Alzheimer disease model APP/PS1 (amyloid precursor protein/presenilin 1) mice were exposed to a transverse aortic constriction for 6 weeks, creating a PP overload in the right carotid (ipsilateral). We show that the transverse aortic constriction procedure associated with high PP induces a cascade of vascular damages in the ipsilateral parenchymal microcirculation: in wild-type mice, it impairs endothelial dilatory and blood brain barrier functions and causes microbleeds, a reduction in microvascular density, microvascular cell death by apoptosis, leading to severe hypoperfusion and parenchymal cell senescence. These damages were associated with brain inflammation and a significant reduction in learning and spatial memories. In APP/PS1 mice, that endogenously display severe cerebral vascular dysfunctions, microbleeds, parenchymal inflammation and cognitive dysfunction, transverse aortic constriction-induced high PP further aggravates cerebrovascular damage, Aß (beta-amyloid) accumulation, and prevents learning. Our study, therefore, demonstrates that brain microvessels are vulnerable to a high PP and mechanical stress associated with transverse aortic constriction, promoting severe vascular dysfunction, disruption of the neurovascular unit, and cognitive decline. Hence, chronic elevated amplitude of the PP could contribute to the development and progression of vascular dementia including Alzheimer disease.

Mirror Movements are Linked to Executive Control in Healthy and Brain-injured Adults.

It has been shown that brain-injured patients (BIP) have exacerbated mirror movements (MM). MM are involuntary contractions occurring in homologous muscles contralateral to voluntary movements, particularly in distal upper limb muscles. Attentional and inhibitory processes have been proposed as key factors to explain the level of MM. However, the link between MM and attentional/inhibitory processes has never been formally tested. The present study aims to test this link in 24 right-handed healthy adults and eight chronic BIP. We investigated the link between the amount/intensity of MM and attentional/inhibitory functions. For each participant, MM produced on each limb were assessed with two tasks, and the attentional and inhibitory functions were assessed with six neuropsychological tests. Our results showed (1) a greater amount and intensity of MM and (2) a selective deficit in sustained attention in BIP compared to healthy adults. Moreover, (3) in all participants - independent of the type of task used to evaluate MM - the amount and intensity of MM was predicted by the level of executive control, assessed by the Trail Making Test. High level of MM was associated with weak executive control abilities. This study is the first to highlight the link between MM and executive functioning, which may have implications for rehabilitation in BIP.

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.

Imaging of Cerebrovascular Function in Chronic Traumatic Brain Injury.

Traumatic cerebrovascular injury (TCVI) is a common pathologic mechanism of traumatic brain injury (TBI) and presents an attractive target for intervention. The aims of this study were to assess cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) to assess their value as biomarkers of TCVI in chronic TBI, characterize the spatial distribution of TCVI, and assess the relationships between each biomarker and neuropsychological and clinical assessments. Forty-two subjects (27 chronic TBI, 15 age- and gender-matched healthy volunteers) were studied cross-sectionally. CBF was measured by arterial spin labeling and CVR by assessing the MRI-blood oxygen level-dependent signal with hypercapnia challenge. A focused neuropsychological battery adapted from the TBI Common Data Elements and neurobehavioral symptom questionnaires were administered at the time of the imaging session. Chronic TBI subjects showed a significant reduction in mean global, gray matter (GM), and white matter (WM) CVR, compared with healthy volunteers (p < 0.001). Mean GM CVR had the greatest effect size (Cohen's d = 0.9). CVR maps in chronic TBI subjects showed patchy, multifocal CVR deficits. CBF discriminated poorly between TBI subjects and healthy volunteers and did not correlate with CVR. Mean global CVR correlated best with chronic neurobehavioral symptoms among TBI subjects. Global, GM, and WM CVR are reliable and potentially useful biomarkers of TCVI in the chronic stage after moderate-to-severe TBI. CBF is less useful as biomarker of TCVI. CVR correlates best with chronic TBI symptoms. CVR has potential as a predictive and pharmacodynamic biomarker for interventions targeting TCVI.

A Clinical Framework for Functional Recovery in a Person With Chronic Traumatic Brain Injury: A Case Study.

BACKGROUND AND PURPOSE: This case study describes a task-specific training program for gait walking and functional recovery in a young man with severe chronic traumatic brain injury. CASE DESCRIPTION: The individual was a 26-year-old man 4 years post-traumatic brain injury with severe motor impairments who had not walked outside of therapy since his injury. He had received extensive gait training prior to initiation of services. His goal was to recover the ability to walk. INTERVENTION: The primary focus of the interventions was the restoration of walking. A variety of interventions were used, including locomotor treadmill training, electrical stimulation, orthoses, and specialized assistive devices. A total of 79 treatments were delivered over a period of 62 weeks. OUTCOMES: At the conclusion of therapy, the client was able to walk independently with a gait trainer for approximately 1km (over 3000 ft) and walked in the community with the assistance of his mother using a rocker bottom crutch for distances of 100m (330 ft). DISCUSSION: Specific interventions were intentionally selected in the development of the treatment plan. The program emphasized structured practice of the salient task, that is, walking, with adequate intensity and frequency. Given the chronicity of this individual's injury, the magnitude of his functional improvements was unexpected.Video Abstract available for additional insights from the Authors (see Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A175).

It's Not All Fun and Games: Sports, Concussions, and Neuroscience.

Few items grab the public's attention like sports, from extremes of great victory to injury and defeat. No injury currently arouses stronger interest than concussion. Giza et al., discuss how neuroscience can provide balance between physical activity and TBI, and guide thoughtful discourse and policy.

Efecto de la lesión electrolítica del estriado dorsomedial sobre la conducta sexual y actividad locomotora de la rata / Effect of electrolytic lesion of the dorsomedial striatum on sexual behaviour and locomotor activity in rats

Introducción: Las áreas motoras corticales no solo son influenciadas por aferencias sensitivas periféricas y áreas de asociación prefrontales, sino también por los ganglios basales, específicamente el estriado. El estriado dorsomedial (EDM) y el estriado dorsolateral están involucrados en el aprendizaje espacial y el aprendizaje estímulo-respuesta; sin embargo, cada una de estas zonas pudiera mediar distintos componentes del aprendizaje. El propósito del estudio es determinar el efecto de la lesión electrolítica del EDM sobre el aprendizaje y ejecución de la conducta locomotora y sexual en ratas macho. Método: Una vez que los sujetos aprendieron a ejecutar las pruebas motoras de equilibrio, laberinto, rampa de ascenso y la conducta sexual, se realizó la lesión electrolítica del EDM. Cinco días después se realizaron las pruebas en 2 ocasiones más y se compararon las latencias de ejecución de cada prueba. Resultados: Después de la lesión, los valores promedio de latencia, incrementaron durante la ejecución de las pruebas de laberinto y equilibrio. Sin embargo, los valores promedio en la prueba rampa y conducta sexual, no aportaron efectos contrastantes entre los grupos. Conclusiones: La lesión electrolítica del EDM modifica la ejecución de la actividad locomotora (prueba de laberinto y equilibrio), pero no la ejecución de la conducta sexual (AU)

Introduction: Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Method: Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Results: Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Conclusions: Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behavior (AU)

Encefalopatía crónica postraumática: aquella gran desconocida / Chronic traumatic encephalopathy: the unknown disease

La encefalopatía crónica postraumática es una enfermedad neurodegenerativa fruto de la acumulación de numerosos traumatismos craneoencefálicos, para la cual no existe un diagnóstico premórtem definitivo ni un tratamiento específico. Entre los factores de riesgo asociados con la encefalopatía crónica postraumática se encuentran: la exposición a deportes de contacto, la presencia de la apolipoproteína E4 y la edad avanzada. Histopatológicamente, aunque comparte ciertas características con la enfermedad de Alzheimer, tiene una presentación más específica (depósito de proteína tau fosforilada en forma de ovillos neurofibrilares, asociados a acúmulo de elementos del neuropilo, acompañados en ocasiones de placas de beta-amiloide). Clínicamente se caracteriza por un curso lento que se inicia con síntomas cognitivos leves y emocionales, y progresa hacia la aparición de síntomas parkinsonianos y demencia. A pesar de que existen elementos diagnósticos prometedores, no son, actualmente, una realidad, y la clave en el manejo de esta enfermedad es la prevención y la detección precoz de sus primeros síntomas (AU)

Chronic traumatic encephalopathy is a neurodegenerative disease produced by accumulated minor traumatic brain injuries; no definitive premortem diagnosis and no treatments are available for chronic traumatic encephalopathy. Risk factors associated with chronic traumatic encephalopathy include playing contact sports, presence of the apolipoprotein E4, and old age. Although it shares certain histopathological findings with Alzheimer disease, chronic traumatic encephalopathy has a more specific presentation (hyperphosphorylated tau protein deposited as neurofibrillary tangles, associated with neuropil threads and sometimes with beta-amyloid plaques). Its clinical presentation is insidious; patients show mild cognitive and emotional symptoms before progressing to parkinsonian motor signs and finally dementia. Results from new experimental diagnostic tools are promising, but these tools are not yet available. The mainstay of managing this disease is prevention and early detection of its first symptoms (AU)

Inventario de Síntomas Prefrontales (ISP) en el daño cerebral adquirido: concordancia entre puntuaciones de paciente, familiar y profesional / The Prefrontal Symptoms Inventory (PSI) in acquired brain injury: agreement between the scores of patients, relatives and professionals

Introducción. El uso de autoinformes sobre síntomas de mal funcionamiento en la vida diaria derivados de déficits funcionales de origen prefrontal se ha generalizado en la práctica clínica, dado que permiten aportar validez ecológica incremental a otras pruebas específicas. Sin embargo, queda por determinar si la autoevaluación es suficiente por sí misma o es preferible la participación de un evaluador externo. Sujetos y métodos. Se administró el inventario de síntomas prefrontales (ISP) a 115 sujetos en tratamiento por diversas patologías cerebrales. La misma prueba, referida al paciente, se administró a algún profesional que siguiera estrechamente la evolución del caso y, cuando fue posible (n = 88), a un familiar o cuidador. Se exploró la bondad psicométrica del ISP en las tres muestras y se estimó el grado de correlación y concordancia entre las tres evaluaciones. Resultados. Las tres evaluaciones mostraron correlación significativa, aunque los pacientes declararon menos síntomas que sus familiares y cuidadores en funcionamiento ejecutivo. Las evaluaciones de familiares y pacientes se superpusieron y mostraron un alto grado de concordancia en perfil y magnitud. Conclusiones. Se recomienda, junto con la obligada evaluación neuropsicológica, la cumplimentación de cuestionarios o inventarios de síntomas como el ISP, con probada robustez psicométrica, que permitan explorar el impacto de las disfunciones cerebrales en el funcionamiento cotidiano. Dado que muchas de estas disfunciones se acompañan de diversos grados de anosognosia, se recomienda su administración a observadores externos, familiares o profesionales, de cara a obtener una evaluación más adecuada de la magnitud de las dificultades funcionales (AU)

Introduction. The use of self-reports about symptoms of malfunctioning in daily life derived from functional deficits of a prefrontal origin has become widespread in clinical practice, since they allow incremental ecological validity to be added to other specific tests. Yet it remains to be determined whether self-assessment is sufficient on its own or if the participation of an external evaluator would be preferable. Subjects and methods. The Prefrontal Symptoms Inventory (PSI) was administered to 115 subjects being treated for a range of brain pathologies. The same test, referring to the patient, was administered to one of the professionals closely following the development of the case and, whenever possible (n = 88), a relative or caregiver. The psychometric goodness of the PSI was explored in the three samples, and the degree of correlation and agreement among the three assessments was estimated. Results. The three assessments showed significant correlation, although the patients reported fewer symptoms than their relatives and caregivers in terms of executive functioning. The assessments of relatives and patients were superposed and showed a high degree of agreement as regards both profile and magnitude. Conclusions. In addition to the mandatory neuropsychological assessment, we recommend the administration of questionnaires or inventories about symptoms such as the PSI, with proven psychometric robustness, that make it possible to explore the impact of brain dysfunctions in daily functioning. Since many of these dysfunctions are accompanied by different degrees of anosognosia, they should be administered to external observers, relatives or professionals, with the intention of obtaining a more adequate assessment of the magnitude of the functional difficulties (AU)

Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG-PET metabolism)-structure (MRI-diffusion-weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill-defined. FDG-PET and MRI-DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function-structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function-structure relationship was present in brain-damaged patients between functional metabolism of inferior-parietal, precuneus, and frontal regions and structural integrity of the frontal-inferiorparietal, precuneus-inferiorparietal, thalamo-inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo-inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function-structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707-3720, 2016. © 2016 Wiley Periodicals, Inc.