Cerebral Palsy

In this study, we examined whether rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, is neuroprotective in focal ischemic brain injury, and whether rosiglitazone can enhance the protective action of tissue plasminogen activator (tPA), an agent used clinically for thrombolytic therapy. Rats were subjected to ischemic brain injury by embolizing preformed clots into the middle cerebral artery (MCA). Treatment with rosiglitazone reduced infarction and improved functional recovery; it also enhanced the neuroprotective action of tPA and lengthened the time window for initiating tPA treatment. Occlusion of MCA resulted in a loss of collagen type IV, a major structural protein of the microvascular basal lamina, and tPA treatment worsened this loss. Rosiglitazone treatment prevented the reduction of collagen type IV in the ischemic injured brain by inhibiting the activation of matrix metallopeptidase-9 (MMP-9). In addition, rosiglitazone treatment reduced inflammatory reactions in the ischemic injured brain. Rosiglitazone either alone or in combination with tPA is an effective agent in the reduction of ischemic brain injury. The reduction of microvascular damage and inflammation contributes to the beneficial actions of rosiglitazone.Journal of Cerebral Blood Flow & Metabolism advance online publication, 24 June 2009; doi:10.1038/jcbfm.2009.87.

Recovery after stroke and other types of brain injury is restricted in part by the limited ability of undamaged neurons to form compensatory connections. Inosine, a naturally occurring purine nucleoside, stimulates neurons to extend axons in culture and, in vivo, enhances the ability of undamaged neurons to form axon collaterals after brain damage. The molecular changes induced by inosine are unknown, as is the ability of inosine to restore complex functions associated with a specific cortical area. Using a unilateral injury model limited to the sensorimotor cortex, we show that inosine triples the number of corticospinal tract axons that project from the unaffected hemisphere and form synaptic bouton-like structures in the denervated half of the spinal cord. These changes correlate with improved recovery in animals’ ability to grasp and consume food pellets with the affected forepaw. Studies using laser-capture microdissection and microarray analysis show that inosine profoundly affects gene expression in corticospinal neurons contralateral to the injury. Inosine attenuates transcriptional changes caused by the stroke, while upregulating the expression of genes associated with axon growth and the complement cascade. Thus, inosine alters gene expression in neurons contralateral to a stroke, enhances the ability of these neurons to form connections on the denervated side of the spinal cord, and improves performance with the impaired limb.

Physiological evidence indicates that several brain regions, including the medial temporal lobes and prefrontal cortex (PFC), are involved in processing events that are novel or distinctive in their immediate context. However, behavioral studies that investigate whether these regions are critical for producing stimulus novelty advantages in memory are limited. For example, evidence from an animal lesion study indicated that the PFC is involved in stimulus novelty effects, but this has not been examined in humans. In the current study, we used a von Restorff novelty paradigm to test a large cohort of lateral PFC patients (n = 16). We found that patients with lateral PFC damage were impaired in recollection- and familiarity-based recognition, and they did not exhibit a normal memory advantage for novel compared with non-novel items. These results provide neuropsychological evidence supporting a key role for the lateral PFC in producing stimulus novelty advantages in memory.

AIM: This paper provides an overview of the epidemiology of rugby league injuries and associated costs in New Zealand requiring medical treatment. Method: New Zealand national Accident Compensation Corporation injury data for the period 1999 to 2007 were searched for rugby league injury cases. Data were analysed by demographics, body region, nature/severity of injury, and medical procedure and costs. RESULTS: A total of 5,941 injury entitlement claims were recorded over the study period with a significant decrease observed in the injury rate between the 1999-00 and 2002-03 reporting years. The total cost of the injuries for the study period was $42,822,048 [ pound15,916,072]. The mean (+/-SD) number of injury entitlement claims per year was 743 (+/-271) and yearly cost was $5,352,760 [ pound1,989,880] (+/-$2,485,535 [ pound923,994]). The knee was the most commonly reported injury site (225 per 1,000 entitlement claims; $8,750,147 [ pound3,252,020]) and soft tissue injuries were the most common injury types (474 per 1,000 entitlement claims; $17,324,214 [ pound6,438,599]). Accounting for only 1.8% of total injury entitlement claims, concussion/brain injuries accounted for 6.3% of injury entitlement costs and had the highest mean cost per claim ($25,347 [ pound9,420]). The upper and lower arm recorded the highest mean injury site claim cost of $43,096 [ pound16,016] per claim. The 25-29 age group recorded 27.7% of total injury entitlement claims and 29.6% of total injury entitlement costs which was slightly more than the 20-24 age group (27.3% claims; 24.7% costs). Nearly 15% of total MSC injury entitlement claims and 20% of total costs were recorded from participants 35 years or older. DISCUSSION: This study identified that the knee was the most common injury site and soft tissue injuries were the most common injury type requiring medical treatment, which is consistent with other international studies on rugby league epidemiology. This study also highlighted that both the rate of injury and the average age of injured rugby league players increased over time. The high cost of concussion/brain injuries is a cause for concern as it reflects the severity of the injuries. CONCLUSION: Injury prevention programmes for rugby league should focus on reducing the risk of concussion/brain injury and knee and soft tissue injury, and should target participants in the 20-30 year age range. More longitudinal epidemiological studies with specific details on injury mechanisms and participation data are warranted to further identify the injury circumstances surrounding participation in rugby league activities.

Effects of caffeic acid phenethyl ester (CAPE) on the serum S-100B levels were studied as an index for brain damage after permanent middle cerebral artery (MCA) occlusion in rabbits. Twenty rabbits were divided into four groups (n=5): control, sham, non-treatment and CAPE. The right MCA was occluded using a microsurgical procedure with bipolar coagulation and was then transected in non-treatment and CAPE groups. The rabbits in the sham group underwent a surgical procedure but the MCA was not occluded. No surgery was performed in the control group. CAPE was administered after MCA occlusion at the dose of 10mug/kg, once a day intraperitoneally for 7 days in the CAPE group. Serum S-100B levels were determined on days 1, 2, 4 and 7. Serum S-100B level was significantly increased following permanent MCA occlusion. Posttreatment of CAPE significantly reduced the serum S-100B level. This study demonstrated that CAPE is capable of attenuating increased serum S-100B level induced by MCA occlusion in rabbits. CAPE may be useful as a neuroprotective agent.

Fever in the neurocritical care setting is common and has a negative impact on outcome of all disease types. Meta-analyses have demonstrated that fever at onset and in the acute setting after ischemic brain injury, intracerebral hemorrhage, and cardiac arrest has a negative impact on morbidity and mortality. Data support that the impact of fever is sustained for longer durations after subarachnoid hemorrhage and traumatic brain injury. Recent advances have made eliminating fever and maintaining normothermia feasible. However, there are no prospective randomized trials demonstrating the benefit of fever control in these patient populations, and important questions regarding indications and timing remain. The purpose of this review is to analyze the data surrounding the impact of fever across a range of neurologic injuries to better understand the optimal timing and duration of fever control. Prospective randomized trials are needed to determine whether the beneficial impact of secondary injury prevention is outweighed by the potential risks of prolonged fever control.

Dyspnea is the unpleasant awareness of breathing while healthy persons will hardly sense their own breath at rest. Dyspnea is comparable to pain because both caution the organism that will activate protective mechanisms to avoid further damage. Dyspnea results from central nervous processing of respiratory feed back signals. Feed back from respiratory muscles, the chest wall, the airways and the lung reach the brain while partial pressure of oxygen and carbon dioxide is continuously monitored and arterial blood gases are permanently stabilized. Sensation of breathlessness depends on its origin. Main qualities of dyspnea include air hunger during hypercapnia, laboured breathing during increased minute ventilation and chest tightness in asthma. During chronic dyspnea, respiratory control aims for a new breathing pattern that will ease breathlessness. Since respiratory control includes both autonomic regulation and cortical modulation of breathing, voluntarily guided respiration can be employed to influence other autonomic regulated systems and pain perception.

OBJECTIVE: Supernumerary phantom limb (SPL) is a rare neurological manifestation where patients with a severe stroke-induced sensorimotor deficit experience the illusory presence of an extra limb that duplicates a real one. The illusion is most often experienced as a somesthetic phantom, but rarer SPLs may be intentionally triggered or seen. Here, we report the case of a left visual, tactile, and intentional SPL caused by right subcortical damage in a nondeluded woman. METHODS: Using functional magnetic resonance imaging, we investigated the multimodal nature of this phantom, which the patient claimed to be able see, use, and move intentionally. The patient participated in a series of sensorimotor and motor imagery tasks involving the right, the left plegic, and the SPL’s hand. RESULTS: Right premotor and motor regions were engaged when she imagined that she was scratching her left cheek with her left plegic hand, whereas when she performed the same task with the SPL, additional left middle occipital areas were recruited. Moreover, comparison of responses induced by left cheek (subjectively feasible) versus right cheek scratching (reportedly unfeasible movement) with the SPL demonstrated significant activation in right somesthetic areas. INTERPRETATION: These findings demonstrate that intentional movements of a seen and felt SPL activate premotor and motor areas together with visual and sensory cortex, confirming its multimodal dimension and the reliability of the patient’s verbal reports. This observation, interpreted for cortical deafferentation/disconnection caused by subcortical brain damage, constitutes a new but theoretically predictable entity among disorders of bodily awareness. Ann Neurol 2009;65:698-705.

Objective. The aim of this study is to investigate whether a high concentration of interleukin-6 (IL)-6 in the amniotic fluid is associated to a higher risk of preterm delivery, premature rupture of the membranes (PROM), and periventricular leucomalacia (PVL) in preterm infants; we have further investigated whether the levels of IL-6 are related to the presence of vaginal infection by mycoplasms. Methods. One hundred eight patients were screened by vaginal swab, sonography, amniocentesis, and dosage of IL-6 in the amniotic fluid during the second trimester of pregnancy. Results. High levels of IL-6 and vaginal mycoplasms are related to preterm birth and PROM. We had no case of PLV. Conclusion. In order to achieve a good therapeutic purpose and get to an efficient strategy, the patients have to be elected by a number of criteria, which may include anamnesis elements, vaginal swab, then cytokines dosage in selected women, thus excluding the low-risk cases. Further studies are expected in order to plan guidelines including the dosage of ILs and principally of IL-6 as a main marker of preterm birth, above all during the second trimester.

Primary objective: To examine the hospitalization costs and discharge outcomes of US children with TBI and to evaluate a severity measure, the predictive mortality likelihood level. Research design: Data from the 2006 Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID) were used to report the national estimates and characteristics of TBI-associated hospitalizations among US children </=20 years of age. The percentage of children with TBI caused by motor vehicle crashes (MVC) and falls was calculated according to the predictive mortality likelihood levels (PMLL), death in hospital and discharge into long-term rehabilitation facilities. Associations with the PMLL, discharge outcomes and average hospital charges were examined. Results: In 2006, there were an estimated 58 900 TBI-associated hospitalizations among US children, accounting for $2.56 billion in hospital charges. MVCs caused 38.9% and falls caused 21.2% of TBI hospitalizations. The PMLL was strongly associated with TBI type, length of hospital stay, hospital charges and discharge disposition. About 4% of children with fall or MVC related TBIs died in hospital and 9% were discharged into long-term facilities. Conclusion: The PMLL may provide a useful tool to assess characteristics and treatment outcomes of hospitalized TBI children, but more research is still needed.