Acid-Ion Sensing Channel 1a Deletion Reduces Chronic Brain Damage and Neurological Deficits after Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) causes long-lasting neurodegeneration and cognitive impairments; however, the underlying mechanisms of these processes are not fully understood. Acid-sensing ion channels 1a (ASIC1a) are voltage-gated Na+- and Ca2+-channels shown to be involved in neuronal cell death; however, their role for chronic post-traumatic brain damage is largely unknown. To address this issue, we used ASIC1a-deficient mice and investigated their outcome up to 6 months after TBI. ASIC1a-deficient mice and their wild-type (WT) littermates were subjected to controlled cortical impact (CCI) or sham surgery. Brain water content was analyzed 24 h and behavioral outcome up to 6 months after CCI. Lesion volume was assessed longitudinally by magnetic resonance imaging and 6 months after injury by histology. Brain water content was significantly reduced in ASIC1a-/- animals compared to WT controls. Over time, ASIC1a-/- mice showed significantly reduced lesion volume and reduced hippocampal damage. This translated into improved cognitive function and reduced depression-like behavior. Microglial activation was significantly reduced in ASIC1a-/- mice. In conclusion, ASIC1a deficiency resulted in reduced edema formation acutely after TBI and less brain damage, functional impairments, and neuroinflammation up to 6 months after injury. Hence, ASIC1a seems to be involved in chronic neurodegeneration after TBI.

Is bimanual interference affected in the case of a central proprioceptive loss? New insight from a left-brain-damaged single-case study.

OBJECTIVE: It was suggested that the bimanual coupling effect might be linked to motor intentionality and planning, which are the top-down components of motor execution. However, previous results in pathological and healthy individuals have also underlined the pivotal role of bottom-up sensorimotor information. METHOD: In this single-case study, the Circles-Lines Coupling Task was administered to a left-parietal-brain-damaged individual. The cerebral lesion caused a central proprioceptive loss, relative to the impaired right hand, when out of the visual control. For the 1st time in literature, we sought to investigate whether the movement of the unaffected hand induced an efficient coupling effect on the movement of the affected one. The bimanual task was performed in the presence and absence of visual input. The patient's performance was compared with that of healthy controls. RESULTS: We observed the traditional bimanual coupling effect in healthy controls. Moreover, we also replicated the effect when they performed the task blindfolded. In the case of the patient, both hands showed the typical ovalization of the line trajectory when the task was performed in visual modality. It is interesting that when the patient performed the task blindfolded, the trajectories of the impaired right hand seemed to be not influenced by the concomitant circular movement of the spared left hand. CONCLUSIONS: The movement of the unaffected hand induced a bimanual coupling effect on the movement of the affected one only when the visual input was available. In absence of a visual feedback, the aberrant proprioceptive information might preclude the emerging of bimanual coupling, even in the case of a preserved motor intentionality and planning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

High occurrence of sleep problems in survivors of a childhood brain tumor with neurocognitive complaints: The association with psychosocial and behavioral executive functioning.

BACKGROUND: Survivors of childhood brain tumors are prone to sleep and neurocognitive problems. Effective interventions to improve neurocognitive functioning are largely lacking. In general, sleep problems are negatively related to neurocognitive functioning, but this relationship is unclear in survivors of childhood brain tumors. Therefore, the occurrence of sleep problems, potential risk factors, and the relation between sleep and executive functioning were evaluated. PROCEDURE: Baseline data of a randomized controlled trial on the effectiveness of neurofeedback were used. Childhood brain tumor survivors 8-18 years of age with parent-reported neurocognitive complaints ≥2 years after treatment were eligible. Parents completed the Sleep Disturbance Scale for Children. Executive functioning was assessed by parents and teachers (Behavior Rating Inventory of Executive Functioning). Multiple linear regression analyses were used to examine sociodemographic and medical characteristics and emotional difficulties and hyperactivity/inattention (Strength and Difficulties Questionnaire) as potential risk factors for sleep problems, and to assess the association between sleep and executive functioning. RESULTS: Forty-eight percent of survivors (n = 82, 7.0 ± 3.6 years post diagnosis, age 13.8 ± 3.2 years) had sleep problems and scored significantly worse than the norm on the subscales Initiating and Maintaining Sleep, Excessive Somnolence, and the total scale (effect sizes 0.58-0.92). Emotional problems and/or hyperactivity/inattention were independent potential risk factors. Sleep problems were associated with worse parent-reported executive functioning. CONCLUSIONS: Sleep problems occur among half of childhood brain tumor survivors with neurocognitive problems, and are associated with worse executive functioning. Future studies should focus on the development of sleep interventions for this population, to improve sleep as well as executive functioning.

[Infantile acquired brain injury, a personal experience. Demands from the socio-familial point of view]. / Daño cerebral sobrevenido infantil, una experiencia personal. Reclamaciones desde el punto de vista sociofamiliar.

We report on the experience of a family in which the youngest child has acquired brain injury and the struggle undertaken by the family to improve the neurorehabilitation resources in the public health service. The article outlines the main demands, from the socio-familial point of view, as regards the improvement of neurological rehabilitation and the resources needed to deliver it.

TITLE: Daño cerebral sobrevenido infantil, una experiencia personal. Reclamaciones desde el punto de vista sociofamiliar.Se describe la experiencia de una familia en la que el hijo menor tiene daño cerebral sobrevenido y la lucha emprendida por la familia para mejorar los recursos neurorrehabilitadores de la sanidad publica. Se recogen las principales reclamaciones, desde el punto de vista sociofamiliar, en cuanto a la mejora en la atencion neurorrehabilitadora y los recursos necesarios.

[Clinical utility and psychometric properties of Prefrontal Symptoms Inventory (PSI) in acquired brain injury and degenerative dementias]. / Utilidad clínica y propiedades psicométricas del inventario de síntomas prefrontales (ISP) en el daño cerebral adquirido y las demencias degenerativas.

INTRODUCTION: The cognitive, emotional and behavioural alterations secondary to acquired brain injury and degenerative dementias can be quantitatively and quantitatively appraised by administering self-reports that ask both patients and reliable informants about the difficulties patients have in their everyday life. SUBJECTS AND METHODS: The Prefrontal Symptoms Inventory (PSI) and the Modified Memory Failures in Everyday Life Questionnaire (MFE-30) were administered to 174 paired participants: 87 patients with brain damage or degenerative dementias and their 87 reliable informants. In addition to the psychometric goodness of the tests, the study also explored the clinical usefulness of applying these questionnaires to patients and their informants in order to obtain a rate of discrepancy in the scores as a measure of anosognosia. RESULTS: The results show how applying the PSI-20 (20 items) or the PSI (46 items), whether administered together with the MFE-30 (30 items) or not, is a very useful procedure for assessing the symptoms in individuals with acquired brain injury or degenerative dementias, since it yields a great deal of information about patients' difficulties in their daily life. CONCLUSIONS: We recommend that, in addition to the compulsory neuropsychological assessment, questionnaires or inventories of symptoms like those proposed here should be carried out, due to the fact that they offer a number of advantages from the clinical point of view, as well as being efficacious and effective in economic terms.

TITLE: Utilidad clinica y propiedades psicometricas del inventario de sintomas prefrontales (ISP) en el daño cerebral adquirido y las demencias degenerativas.Introduccion. Las alteraciones cognitivas, emocionales y comportamentales secundarias al daño cerebral adquirido y las demencias degenerativas pueden valorarse cuantitativa y cualitativamente mediante la administracion de autoinformes que interroguen ­a pacientes e informadores fiables­ sobre las dificultades de los pacientes en la vida cotidiana. Sujetos y metodos. Se administro el inventario de sintomas prefrontales (ISP) y el cuestionario de fallos de memoria en la vida cotidiana modificado (MFE-30) a 174 participantes emparejados: 87 pacientes con daño cerebral o demencias degenerativas y sus 87 informadores fiables. Se exploro, junto con la bondad psicometrica de las pruebas, la utilidad clinica de la aplicacion de estos cuestionarios a pacientes e informadores para obtener un indice de discrepancia de las puntuaciones como medida de la anosognosia. Resultados. Los resultados muestran como aplicar el ISP-20 (20 items) o el ISP (46 items), sean o no administrados conjuntamente con el MFE-30 (30 items), resulta un procedimiento muy util para la valoracion de la sintomatologia en los individuos con daño cerebral adquirido o demencias degenerativas, al proporcionar una gran cantidad de informacion sobre las dificultades de los pacientes en la vida cotidiana. Conclusiones. Se recomienda, junto con la obligada evaluacion neuropsicologica, la cumplimentacion de cuestionarios o inventarios de sintomas como los propuestos, dado que presentan ventajas desde el punto de vista clinico, ademas de resultar eficaces, efectivos y eficientes en terminos economicos.

Isolated linear skull fractures in children with blunt head trauma.

BACKGROUND AND OBJECTIVE: Children and adolescents with minor blunt head trauma and isolated skull fractures are often admitted to the hospital. The objective of this study was to describe the injury circumstances and frequency of clinically important neurologic complications among children with minor blunt head trauma and isolated linear skull fractures. METHODS: This study was a planned secondary analysis of a large prospective cohort study in children <18 years old with blunt head trauma. Data were collected in 25 emergency departments. We analyzed patients with Glasgow Coma Scale scores of 14 or 15 and isolated linear skull fractures. We ascertained acute neurologic outcomes through clinical information collected during admission or via telephone or mail at least 1 week after the emergency department visit. RESULTS: In the parent study, we enrolled 43,904 children (11,035 [25%] <2 years old). Of those with imaging studies, 350 had isolated linear skull fractures. Falls were the most common injury mechanism, accounting for 70% (81% for ages <2 years old). Of 201 hospitalized children, 42 had computed tomography or MRI repeated; 5 had new findings but none required neurosurgical intervention. Of 149 patients discharged from the hospital, 20 had repeated imaging, and none had new findings. CONCLUSIONS: Children with minor blunt head trauma and isolated linear skull fractures are at very low risk of evolving other traumatic findings noted in subsequent imaging studies or requiring neurosurgical intervention. Hospital admission for neurologically normal children with isolated linear skull fractures after minor blunt head trauma for monitoring is typically unnecessary.

Opportunities, threats and limitations of neuroscience data in forensic psychiatric evaluation.

PURPOSE OF REVIEW: In the last decade, a number of studies have been published to shed light on the interaction between neuroscience and the law, notably on the introduction of neuroscience data in forensic psychiatric evaluation (FPE). Even if there is a growing consensus on the relevance of neuroscience in clinical practice, the role of neuroscience in FPE is still controversial. RECENT FINDINGS: The use of neuroscience data in FPE can support the detection of psychopathological disabilities (e.g. deficit of self-control, aggressiveness) that may be involved in criminal action. Traumatic brain injury-related clinical disorders that may lead to misconduct have a relevant role in the debate. Traditionally, literature refers also to rare and weird cases in which brain tumours, infections and morphological abnormalities were supposed to be significantly associated with disorders leading to criminal action. SUMMARY: After reviewing recent literature from both legal and neuroscientific perspectives, we consider a broader range of clinical conditions (e.g. disorders of consciousness in sleepwalking, dopamine replacement therapy in Parkinson's disease, misattributions of self in delusional experience) that may have implications in legal settings. Obviously, it would be possible to consider also different clinical conditions. We conclude by suggesting further experimental and theoretical analysis.

Neuronal damage and functional deficits are ameliorated by inhibition of aquaporin and HIF1α after traumatic brain injury (TBI).

The present study, using a rodent model of closed-head diffuse traumatic brain injury (TBI), investigated the role of dysregulated aquaporins (AQP) 4 and 9, as well as hypoxia inducible factor -1α(HIF-1α) on brain edema formation, neuronal injury, and functional deficits. TBI was induced in adult (400-425 g), male Sprague-Dawley rats using a modified Marmarou's head impact-acceleration device (450 g weight dropped from 2m height). Animals in each treatment group were administered intravenous anti-AQP4 or -AQP9 antibodies or 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α) 30 min after injury. At 24h post-TBI, animals (n=6 each group) were sacrificed to examine the extent of brain edema by water content, as well as protein expression of AQP and HIF-1α by Western immune-blotting. At 48-hours post-TBI, neuronal injury (n=8 each group) was assessed by FluoroJade (FJ) histochemistry. Spatial learning and memory deficits were evaluated by radial arm maze (n=8 each group) up to 21 days post-TBI. Compared to non-injured controls, significant (p<0.05) increases in the expression of AQP4 and -9 were detected in the brains of injured animals. In addition, significant (p<0.05) brain edema after TBI was associated with increases (p <0.05) both in neuronal injury (FJ labeling) and neurobehavioral deficits. Selective inhibition of either AQP4 or -9, or HIF-1α significantly (p<0.05) decreased the expression of the proteins. In addition, inhibition of the AQPs and HIF-1α significantly (p<0.05) ameliorated brain edema, as well as the number of injured neurons in cortical layers II/III and V/VI, striatum and hippocampal regions CA1/CA3. Finally, compared to the non-treated TBI animals, AQP or HIF-1α inhibition significantly (p<0.01) improved neurobehavioral outcomes after TBI. Taken together, the present data supports a causal relation between HIF-AQP mediated cerebral edema, secondary neuronal injury, and tertiary behavioral deficits post-TBI. The data further suggests that upstream modulation of the molecular patho-trajectory effectively ameliorates both neuronal injury and behavioral deficits post-TBI.

The no smoking sign--insular infarction.

BACKGROUND: Cigarette smoking is the most common preventable cause of morbidity and mortality in developed countries. Smokers with brain damage involving the insula are 136 times more likely to stop smoking immediately after the injury than smokers with brain injuries elsewhere. METHODS: Case Report. RESULTS: A 58-year-old woman with a history of hypertension, coronary artery disease, and 40 pack-year history (1 pack per day for 40 years) of smoking presented with sudden confusion and word-finding difficulty. Initial neurological examination showed disorientation to time, difficulty following commands, and perseveration. No focal motor, sensory, or visual deficit was present. Noncontrast head CT showed a new insular ischemic stroke. Five months after discharge from the hospital, the patient reported that she had not resumed smoking cigarettes, had not used any smoking cessation aids, and had not intended to stop smoking. Her daughter reported that "it was as if she forgot that she used to smoke." CONCLUSION: Unintentional abrupt smoking cessation serves as a unique lesion localizer. Insular hypocretin transmission plays a permissive role in the motivational properties of nicotine in animals. Whether the mechanism of smoking cessation relates to hypocretin secretion has yet to be proven in humans.

SenseCam as a rehabilitation tool in a child with anterograde amnesia.

We present the case of a 13-year-old boy, CJ, with profound episodic memory difficulties following the diagnosis of a metastatic intracranial germ cell tumour and subsequent treatment with radiotherapy and chemotherapy. At the core of this study is the first application of SenseCam to a child with severe memory impairment. CJ was taken for a walk while he was wearing SenseCam. This included visiting four different locations. We manipulated the number of locations he could review on SenseCam "films" and then tested recognition memory (forced choice) for both reviewed and non-reviewed locations. We also collected his justifications for the choices he made. Our results indicate that repeated viewings of SenseCam images support the formation of personal semantic memories. Overall our results suggest that the use of SenseCam in memory rehabilitation extends beyond supporting episodic memory and recollection, and supports the feasibility of its use with children who have marked memory difficulties.

Early emergence of behavior and social-emotional problems in very preterm infants.

OBJECTIVE: Children born very preterm are reported to have an increased frequency of social, emotional, and behavioral problems at school age compared with their peers born at term. The primary aim of this study was to compare social-emotional difficulties and competencies of very preterm and full-term children at 2 years' corrected age. In addition, the relation between perinatal variables and early behavior problems was also examined to help identify those very preterm children most at risk. METHOD: At 2 years' corrected age, the parents of 188 very preterm (gestational age <30 weeks or birth weight <1,250 g) and 70 full-term (gestational age >or=37 weeks) children completed the Infant Toddler Social and Emotional Assessment to determine externalizing, internalizing, and dysregulation problems and social-emotional competencies. For the very preterm sample, extensive perinatal data were collected including sex, birth weight, gestational age, chronic lung disease, and postnatal steroids, as well as neonatal cerebral white matter abnormalities detected by magnetic resonance imaging. RESULTS: The very preterm children at 2 years demonstrated significantly higher internalizing and dysregulation scores and lower competence scores than peers born at term. There was no significant difference in externalizing scores between groups. Female sex, lower birth weight z score, white matter abnormalities, and postnatal corticosteroids were significantly associated with lower competence scores in the very preterm group. CONCLUSIONS: Very preterm children exhibit higher rates of behavior problems early in development, in particular internalizing and dysregulation problems and poorer competence.

The quality of preterm infants' spontaneous movements: an early indicator of intelligence and behaviour at school age.

BACKGROUND: The quality of very preterm infants' spontaneous movements at 11 to 16 weeks post-term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience. METHODS: Spontaneous movement quality was assessed, using Prechtl's method, at 11 to 16 weeks post-term in 65 infants born at

The role of neuropsychological functioning in cancer survivors' return to work one year after diagnosis.

OBJECTIVE: The objective of this study was to investigate the relationship between neuropsychological functioning and the ability to work in cancer survivors. METHODS: The study involved a consecutive cohort of 45 patients who had received a primary diagnosis of cancer, were gainfully employed at baseline, and had been treated with curative intent. Twelve months after the first day of sick leave, they underwent a neuropsychological assessment that included executive function and verbal memory tests. Other clinical, person-related, and work-related factors were also assessed by questionnaire at this time. Ability to work was measured as perceived workability (0-10) and work status at 12 months of sick leave. RESULTS: Fifteen participants (33%) showed neuropsychological impairments covering various domains. The mean workability score of cancer survivors with neuropsychological impairment was 4.9, whereas those without impairments had a mean score of 6.0 (raw beta = -0.19: 95% CI = -2.9 to 0.7; adjusted beta = -0.15; 95% CI = -2.5 to 0.8). More cancer survivors with neuropsychological impairments (7/15, 47%) than without (9/30, 30%) had not yet returned to work (raw OR 0.5: 95% CI: 0.1-1.8; adjusted OR 0.5; 95% CI: 0.1-2.1). CONCLUSIONS: To date, this is the largest study to assess neuropsychological functioning objectively in combination with perceived workability and work status. Impaired neuropsychological functioning was found in one-third of the cancer survivors and was related to a lower vocational functioning, but the relationship was not statistically significant. More research is needed to test the relevance of neuropsychological impairments for vocational functioning.

Revisiting the legal standards that govern requests to sterilize profoundly incompetent children: in light of the "Ashley Treatment," is a new standard appropriate?

This Note discusses the recent controversy surrounding a six-year-old girl named Ashley, whose parents chose to purposefully stunt her growth and remove her reproductive organs for nonmedical reasons. A federal investigation determined that Ashley's rights had been violated because doctors performed the procedure, now referred to as the "Ashley Treatment," without first obtaining a court order. However, the investigation did not make any conclusions regarding whether the "Ashley Treatment" could present a legally permissible treatment option in the future. After discussing the constitutional rights that the "Ashley Treatment" implicates and the current legal standards in place, this Note examines how courts have applied these legal standards to cases involving extreme requests. Drawing upon legal commentators, this Note concludes that a court could approve a request for the "Ashley Treatment" in appropriate and limited cases where the parents have presented clear and convincing evidence before a court that the benefits that the "Ashley Treatment" would provide to the child and her family outweigh the risks associated with the procedure. This Note argues that those benefits may include extrinsic considerations, but courts should remain cautious when considering such evidence and be sure that the evidence as a whole supports their conclusions.

Neurodevelopmental sequelae of pediatric acute lymphoblastic leukemia and its treatment.

This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research. It is concluded that neurocognitive outcomes for the majority of children with standard-risk ALL treated according to current chemotherapy protocols is relatively good, but subgroups of children are more significantly compromised. As medical treatments advance and survival rates continue to improve, neurocognitive outcomes and other quality of life indicators will become increasingly important. Preventing or ameliorating treatment-related neuropsychological sequelae represents the next major challenge in pediatric ALL.

Developmental perspectives on optimizing educational and vocational outcomes in child and adult survivors of cancer.

Over the last few decades, long-term survival rates of children diagnosed with the two most common forms of childhood cancer, acute lymphoblastic leukemia (ALL) and brain tumors have improved substantially. Neurodevelopmental and psychosocial sequelae resulting from these diseases and their treatment have a direct impact on the developing brain and on the quality of life of these children and their families. The focus of this article is on optimizing neuropsychological and adaptive outcomes for children who have been successfully treated for these cancers and whose prospects for long-term survival are increasingly encouraging. We present a model for understanding systemic interactions among the multiple factors that influence the child's development over time and take into account contextual variables. Strategies for optimizing cognitive and psychosocial outcomes or ameliorating late effects need to consider treatment histories, specific stages of development, the contextual demands/developmental challenges associated with each, and the resources (internal and external to the child) available to meet these challenges. The challenges faced by survivors at the early childhood, middle childhood, adolescent, and emerging adulthood stages are discussed. We review different types of interventions and discuss how these can contribute to optimal functioning in survivors of childhood ALL and brain tumors.

Neurodevelopmental outcomes of children with low-grade gliomas.

As a group, children with low-grade gliomas (LGGs) enjoy a high rate of long-term survival and do not require the intensity of neurotoxic treatments used with higher risk pediatric brain tumors. Because they are generally considered to have favorable neurobehavioral outcomes, they have not been studied as thoroughly as higher-grade brain tumors by late-effects researchers. In this article, we review the literature on the neurobehavioral effects associated with low-grade gliomas and conclude that, (1) this is a large, understudied group of survivors of pediatric brain tumors; (2) recent small- and large-scale studies document increased risk in multiple cognitive-behavioral domains after treatment for LGGs compared with healthy peers; (3) such risk is not uniform but varies with tumor location and treatments; and (4) a life span development perspective is essential to a complete understanding of the risks faced by these children. More research on the most efficacious biopsychosocial treatment models for improving the outcomes of survivors of low-grade glioma is recommended, informed by a better understanding of theireducational needs. Investigations of genetic influences on outcome as well as prospective studies of these patients as they age are also recommended.