Cerebral Palsy

CONTEXT: Traumatic experiences in early childhood are associated with increased risk of developing stress-related disorders, which are linked to structural brain abnormalities. However, it is unclear whether these volumetric brain changes are present before disease onset or reflect the consequences of disease progression. OBJECTIVE: To identify structural abnormalities in the nonhuman primate brain that may predict increased risk of stress-related neuropsychiatric disorders in human beings. DESIGN: Rhesus monkeys were divided into 2 groups at birth: a group raised with their mothers and other juvenile and adult animals (mother reared) and a group raised with 3 age-matched monkeys only (peer reared) for the first 6 months of life. Anatomical brain images were acquired in juvenile male and female rhesus monkeys using magnetic resonance imaging. SETTING: National Institutes of Health Animal Center in Poolesville, Maryland. Subjects Twenty-eight rhesus monkeys (Macaca mulatta) aged 24 to 30 months were used for the study. MAIN OUTCOME MEASURES: Volumetric measures of the anterior cingulate cortex, medial prefrontal cortex, hippocampus, corpus callosum, and cerebellar vermis were compared between mother-reared (n = 15) and peer-reared animals (n = 13). RESULTS: Compared with mother-reared monkeys, we found an enlarged vermis, dorsomedial prefrontal cortex, and dorsal anterior cingulate cortex in peer-reared monkeys without any apparent differences in the corpus callosum and hippocampus. CONCLUSIONS: Peer-rearing during infancy induces enlargement in stress-sensitive brain regions. These changes may be a structural phenotype for increased risk of stress-related neuropsychiatric disorders in human beings.

Using real-time 3D-speckle-tracking in the clinical course of Tako-Tsubo turned out as a quick and feasible tool for recognition and follow-up of wall motion abnormalities.

Pediatric acquired brain injury (BI) not only affects the child with the injury, but also greatly impacts their family. Studies suggest there are higher rates of caregiver and sibling psychological distress after a child in the family has sustained a BI. Also, family functioning after BI impacts the child’s recovery. In reviewing the literature, we identified seven theoretical clinical guidelines for working with families of children and adolescents with BI. These clinical guidelines are as follows: (1) select developmentally appropriate interventions, (2) match the intervention to the family, (3) provide advocacy, (4) provide injury education, (5) focus on family realignment, (6) appropriately adjust the child’s environment, and (7) provide skills training to the family and child. The existing research on family interventions for BI is reviewed within the context of these theoretical guidelines, and the empirical support for each guideline is subsequently evaluated using specific criteria for empirically supported treatments. Unfortunately, very few randomized controlled studies exist, and continued research is needed to classify all clinical guidelines as “efficacious.” In addition, continued research will aid in informing professionals of specific approaches to utilize when working with a family of a child with BI. Currently, clinicians and researchers can turn to the existing clinical guidelines to help address the numerous barriers posed by implementing and studying family interventions for pediatric BI. (c) 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:159-166.

Neuronal plasticity allows the central nervous system to learn skills and remember information, to reorganize neuronal networks in response to environmental stimulation, and to recover from brain and spinal cord injuries. Neuronal plasticity is enhanced in the developing brain and it is usually adaptive and beneficial but can also be maladaptive and responsible for neurological disorders in some situations. Basic mechanisms that are involved in plasticity include neurogenesis, programmed cell death, and activity-dependent synaptic plasticity. Repetitive stimulation of synapses can cause long-term potentiation or long-term depression of neurotransmission. These changes are associated with physical changes in dendritic spines and neuronal circuits. Overproduction of synapses during postnatal development in children contributes to enhanced plasticity by providing an excess of synapses that are pruned during early adolescence. Clinical examples of adaptive neuronal plasticity include reorganization of cortical maps of the fingers in response to practice playing a stringed instrument and constraint-induced movement therapy to improve hemiparesis caused by stroke or cerebral palsy. These forms of plasticity are associated with structural and functional changes in the brain that can be detected with magnetic resonance imaging, positron emission tomography, or transcranial magnetic stimulation (TMS). TMS and other forms of brain stimulation are also being used experimentally to enhance brain plasticity and recovery of function. Plasticity is also influenced by genetic factors such as mutations in brain-derived neuronal growth factor. Understanding brain plasticity provides a basis for developing better therapies to improve outcome from acquired brain injuries. (c) 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:94-101.

Multiple sclerosis (MS) is commonly regarded as an inflammatory disease, but it also has a neurodegenerative component, which represents an additional target for treatment. The use of MRI to evaluate the inflammatory disease component in ‘proof-of concept’ clinical trials is well established, but no systematic assessment of imaging outcomes to evaluate neuroprotection or repair in MS has been performed. In this Review, we examine the potential of traditional and novel imaging parameters to serve as primary outcomes in phase II clinical trials of neuroprotective and reparative strategies in MS. We present the conclusions of an international meeting of imaging, clinical and statistical experts, as well as a review of relevant literature. The available imaging techniques are appraised in five categories of performance: pathological specificity, reproducibility, sensitivity to change, clinical relevance, and response to treatment. At present, the three most promising primary outcomes in phase II trials of neuroprotective and/or reparative strategies in MS are: changes in whole-brain volume to gauge general cerebral atrophy; T1 hypointensity and magnetization transfer ratio to monitor the evolution of lesion damage; and optical coherence tomography findings to evaluate the anterior visual pathway. Power calculations show that these outcome measures can be applied with attainable sample sizes.

There are only few strategic and therapeutic options to improve the functional outcome of patients after cardiac arrest and resuscitation(CPR). The pathophysiology of reperfusion injury following global ischemia is not completely understood. We present here a murine model of cardiac arrest and resuscitation which allows an analysis of the pathophysiology of reperfusion injury, especially focusing on survival, tissue damage and functional neurological parameters. Under systemic hemodynamic monitoring, male C57BL/6J mice were subjected to 3 minutes of a potassium-induced cardiac arrest. After resuscitation under controlled conditions, mice were observed and neurologically scored for 72 hours post-CPR. As a control sham-treated animals were provided. Also blood samples were drawn and organs were removed for a histological analysis. Here global ischemia and reperfusion led to functional and histological reperfusion damage. The overall mortality up to day 3 post CPR was 54%. Resuscitated animals developed marked functional neurologic deficits, as assessed by Rotarod and elevated plus-maze testing. Histological examinations and blood analyses of CPR-animals revealed significant leukocyte tissue infiltration and morphological damage of brain, lung and kidneys. In summary, mice undergoing CPR after cardiac arrest present distinct neurological deficits, marked organ damage and a 54% mortality rate. Our highly standardized and reproducible model of mice resuscitation provides a means for a better understanding of the post-CPR pathophysiology and thus opens new perspectives to develop relevant therapeutic approaches to minimize global ischemia/reperfusion injury.

OBJECTIVE: An animal model of concussions in National Football League players has been described in a previous study. It involves a freely moving 300-g Wistar rat impacted on the side of the head at velocities of 7.4 to 11.2 m/s with a 50-g impactor. The impact causes a 6% to 28% incidence of meningeal hemorrhages and 0.1- to 0.3-mm focal petechiae depending on the impact velocity. This study addresses the immunohistochemical responses of the brain. METHODS: Twenty-seven tests were conducted with a 50-g impactor and velocities of 7.4, 9.3, or 11.2 m/s. The left temporal region of the helmet-protected head was hit 1 or 3 times. Thirty-one additional tests were conducted with a 100-g impactor. Diffuse axonal injury in distant regions of the brain was assessed with immunohistochemistry for NF-200, the heaviest neurofilament subunit, and glial fibrillary acidic protein, an intermediate filament protein in astrocytes. Hemorrhages were analyzed by unspecific peroxidase. There were 10 controls. RESULTS: A single impact at 7.4 and 9.3 m/s velocity with the 50-g impactor causes minimal neuronal injury and astrocytosis. Repeat impacts with 11.2 m/s velocity and more than 9.3-m/s impacts with 100 g cause diffuse axonal injury and distant injury bilaterally in the cerebral cortex, the subcortical, the white matter, the hippocampus CA1, the corpus callosum, and the striatum, as indicated by NF-200 accumulation in neuronal perikarya 10 days after impact. It also causes reactive astrocytosis in the midline regions of the cerebral cortex and periventricularly. Regions with erythrocyte-loaded blood capillaries indicated brain edema in regions of the cerebral cortex, the brainstem, and the cerebellum. CONCLUSION: When the immunohistochemical results are extrapolated to professional football players, concussions result in no or minimal brain injury. Repeat impacts at higher velocity or with a heavier mass impactor cause extensive and distant diffuse axonal injury. Based on this model, the threshold for diffuse axonal injury is above even the most severe conditions for National Football League concussion.

OBJECTIVE: A concussion model was developed to study injury mechanisms, functional effects, treatment, and recovery. Concussions in National Football League football involve high-impact velocity (7.4-11.2 m/s) and rapid change in head velocity (DeltaV) (5.4-9.0 m/s). Current animal models do not simulate these head impact conditions. METHODS: One hundred eight adult male Wistar rats weighing 280 to 350 g were used in ballistic impacts simulating 3 collision severities causing National Football League-type concussion. Pneumatic pressure accelerated a 50 g impactor to velocities of 7.4, 9.3, and 11.2 m/s at the left side of the helmet-protected head. A thin layer of padding on the helmet controlled head acceleration, which was measured on the opposite side of the head, in line with the impact. Peak head acceleration, DeltaV, impact duration, and energy transfer were determined. Fifty-four animals were exposed to single impact, with 18 each having 1, 4, or 10 days of survival. Similar tests were conducted on another 54 animals, which received 3 impacts at 6-hour intervals. An additional 72 animals were tested with a 100g impactor to study more serious brain injuries. Brains were perfused, and surface injuries were identified. RESULTS: The 50 g impactor matches concussion conditions scaled to the rat. Impact velocity and head DeltaV were within 1% and 3% of targets on average. Head acceleration reached 450 g to 1750 g without skull fracture. The test is repeatable and robust. Gross pathology was observed in 11%, 28%, and 33% of animals in the 7.4-, 9.3-, and 11.2-m/s single impacts, respectively. At 7.4 m/s, a single diameter area of less than 0.5 mm of fine petechial hemorrhage occurred on the brain surface in the parenchyma and meninges nearest the point of impact. At higher velocities, there were larger areas of bleeding, sometimes with subdural hemorrhage. When the 50 g impactor tests were examined by logistic regression, greater energy transfer increased the probability of injury (odds ratio, 5.83; P = 0.01), as did 3 repeat impacts (odds ratio, 4.72; P = 0.002). The number of survival days decreased the probability of observing injury (odds ratio, 0.25 and 0.11 for 4 and 10 days, respectively, compared with 1 day). The 100g impactor produced more severe brain injuries. CONCLUSION: A concussion model was developed to simulate the high velocity of impact and rapid head DeltaV of concussions in National Football League players. The new procedure can be used to evaluate immediate and latent effects of concussion and more severe injury with greater impact mass.

INTRODUCTION: The relationship between visual perception and visual mental imagery are at the center of a lively theoretical debate between those postulating common neurocognitive processes between perception and imagery and those who emphasize the differences between these two entities. Neuropsychology can make an important contribution to this debate, by assessing associations and dissociations between perceptual and imaginal deficits in patients with brain damage. However, currently there is no standardized test battery available for such assessments. MATERIAL AND METHODS: Here we present a battery of paper-and-pencil tests assessing different domains of visual mental imagery and visual perception abilities: object form and color, animals, orthographic material, numbers, faces, and space. We also explored the effects of age, educational level and gender on performance on a group of 103 participants free of neurological damage. RESULTS: The battery includes two parts: one composed of 14 tests assessing mental imagery and the second part composed of eight tests assessing the abilities of visual perception. We calculated the correlations between the tests, and found that, with the exception of orthographic material, there were generally poor correlations between imagery and perceptual tests. CONCLUSION: This result seems inconsistent with hypotheses postulating a strict correspondence between perceptual and imagery abilities.

INTRODUCTION: Few data are available about the epidemiology and injury characteristics in staircase falls. The available literature mainly concerns children and autopsy studies. OBJECTIVE: To describe the epidemiology and injury characteristics of staircase falls, and to identify high-risk groups for these falls. METHODS: All patients who reported to an academic Accident & Emergency (A&E) department in 2005 after a staircase fall were selected in the Dutch Injury Surveillance System These data were linked to the hospital Trauma Registry database. RESULTS: Four hundred and sixty-four patients (42% male, p=0.001), with a median age of 35 years were included. Children under five suffered significantly more head injuries. Male patients showed significantly more thoracic injuries than female patients. Spinal column fractures were only seen in patients over 25 years of age. Older patients tended to accumulate more rib fractures and lower extremity fractures and were admitted more frequently than the younger patients. Sixty-one patients (13%) required admission. Two patients, both with severe traumatic brain injury (TBI), died. National data on staircase falls were comparable with our hospital data. However, in comparison to the national population data, senior citizens in this study had an incidence that was markedly higher than in the younger patients. CONCLUSION: Injuries due to staircase falls occur in all age groups, however, children under five years are relatively over-represented with higher rates of head injury. Senior citizens showed a markedly higher incidence than younger patients. Most injuries occur to the distal extremities and are relatively mild.