Cerebral Palsy

Abstract Objective: The fetal inflammatory response syndrome (FIRS) is present in a fraction of fetuses exposed to intra-amniotic infection and is associated with the impending onset of labor and multisystem organ involvement. Neonates born with funisitis, the histologic counterpart of fetal systemic inflammation, are at increased risk for cerebral palsy and bronchopulmonary dysplasia. The aim of this study was to determine whether fetal and maternal granulocytes and monocytes have the phenotypic and metabolic characteristics of activation in cases with FIRS. Study design: A case-control study was conducted with umbilical cord and maternal blood samples obtained from patients who delivered preterm with (n=30) and without funisitis (n=15). The phenotypic characteristics of granulocytes and monocytes were examined using flow cytometry and monoclonal antibodies including CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were measured at the basal state and after stimulation (oxidative burst). A P<0.01 was considered statistically significant. Results: (1) Funisitis was associated with a significant increase in the median mean channel brightness (MCB) of CD14, CD64, and CD66b on granulocytes and the MCB of CD64 on monocytes collected from umbilical cord blood. (2) The basal iROS production and oxidative burst were higher in the umbilical cord monocytes of neonates with funisitis than in those without funisitis. (3) There were no differences in the immunophenotype, basal iROS production, and oxidative burst in maternal granulocytes or monocytes between the study groups. Conclusion: Fetal systemic inflammation is associated with phenotypic and metabolic changes consistent with activation in fetal immune cells but not in maternal blood.

Untreated hip joint in cerebral palsy children leads to subluxation or dislocation caused by muscle imbalance often with associated painful arthritis. The very strong hip joint flexors and adductors muscles overpower the abductors and extensors muscles, moving the hip joint’s rotation center to shift from center of the femoral head to the lesser trochanter. The forces gradually change the shape of the acetabulum, which becomes more elliptical. Between 1994 and 2000, 136 cerebral palsy children were treated by multilevel soft tissue surgery. Among them 95 children required surgical interventions for hip problems. In 18 cases (7 girls, 11 boys) with average adduction of 10 degrees and migration index over 60%, osteotomy of proximal femur (varus and derotation osteotomy) combine with Dega pelvic osteotomy was performed. Mean age at the time of surgery was 11.2 years. The study was based on clinical examination, parents’ questionnaire and radiological findings (mean follow up 8 years). The functional improvement was observed. Correction of the position of femoral head into acetabulum allowed for sufficient abduction of the leg with mean increase of 18 degrees. In ambulatory patients, gait pattern had change to less energy. In non-ambulatory patients improved ability of perineal care. Migration index decreased to an average of 25%. Hip pain decreased in all. The unsatisfactory results were noted in two cases, redislocation. Dega’s acetabular osteotomy allows for correction deficiency of the acetabulum with a good coverage of femoral head. With a properly planned approach, bone surgery can bring good clinical and functional results.

Objectives: To evaluate the feasibility and the ability to recruit and retain children with severe traumatic brain injury or cerebral palsy, and their families, to a simple home-based exercise programme and to assess the immediate and short-term effects of such intervention on reducing impairment and improving function. STUDY DESIGN: Randomized clinical trial.Participants: Twenty children aged 7-13 years, with traumatic brain injury (N = 10) or cerebral palsy (N = 10) who were independent ambulators. Five children from each group were randomly assigned to a control group – regular daily activities, or to an experimental group – regular daily activities plus a home-based task-oriented exercise programme of sit-to-stand and step-up exercise, for six weeks. OUTCOME MEASURES: Feasibility: The number of participants who completed the programme protocol. Efficacy: Timed Up and Go Test and Functional Reach Test were used as functional balance tests. Maximal isometric strength was assessed by using a hand-held dynamometer; walking performance was assessed by the 10 m walk test, 2-minute walk test and Energy Expenditure Index.Results: Nine children completed all parts of the training programme. At the end of the intervention period an increase of 3-4 cm in the mean Functional Reach Test and a reduction of 1.6 +/- 2.1 seconds in the Timed Up and Go Test were noted (P < 0.01) in the experimental group while no changes were noted in the control group. In all other outcomes assessed no significant differences were noted between groups. The positive change in balance performance in the experimental group was maintained during a six-week follow-up period.Conclusions: A home-based task-oriented exercise programme can improve balance performance in children with spastic cerebral palsy or severe traumatic brain injury.

Alcohol consumption during pregnancy is a significant public health problem and may result in a wide range of adverse outcomes for the child. The developing central nervous system (CNS) is particularly susceptible to ethanol toxicity. Children with fetal alcohol spectrum disorders (FASD) have a variety of cognitive, behavioral, and neurological impairments. FASD currently represents the leading cause of mental retardation in North America ahead of Down syndrome and cerebral palsy. Ethanol exposure during development causes multiple abnormalities in the brain such as permanent loss of neurons, ectopic neurons, and alterations in synaptogenesis and myelinogenesis. These alcohol-induced structural alterations in the developing brain underlie many of the behavioral deficits observed in FASD. The cellular and molecular mechanisms of ethanol neurotoxicity, however, remain unclear. Ethanol elicits cellular stresses, including oxidative stress and endoplasmic reticulum stress. Glycogen synthase kinase 3beta (GSK3beta), a multifunctional serine/threonine kinase, responds to various cellular stresses. GSK3beta is particularly abundant in the developing CNS, and regulates diverse developmental events in the immature brain, such as neurogenesis and neuronal differentiation, migration, and survival. Available evidence indicates that the activity of GSK3beta in the CNS is affected by ethanol. GSK3beta inhibition provides protection against ethanol neurotoxicity, whereas high GSK3beta activity/expression sensitizes neuronal cells to ethanol-induced damages. It appears that GSK3beta is a converging signaling point that mediates some of ethanol’s neurotoxic effects.

Mediastinoscopy is a minimum invasive investigation representing a reference in mediastinum exploration and having a major role regarding therapeutic strategies in patients with lung cancer or other mediastinal pathology. Research studies show that this surgical intervention, although having in reality low morbidity and mortality (0.6-3.7% morbidity and 0.2% mortality), is potentially dangerous in non properly trained hands. Mediastinoscopical related complications appear as a consequence of the following: (1) incision and access path; (2) surgical maneuvers and are also general complications as in any other surgical approach related to anesthesiology act or postoperative recovery course. The most frequent complications are surgical-related: hemorrhage, recurrent palsy, pneumothorax, tracheal laceration, esophageal lesions, wound dehiscence or anesthesiology-related such as: cardiac arrest and respiratory hypoxia, various arrhythmias, cerebral insufficiency, amaurozis fugax. From all the complications only 0.1-0.5% have clinical significance, the most dreadful remaining massive hemorrhage, which requires a trained team with a very well equipped operating theatre for thoracic, vascular and cardiac surgery. Frequently in cure and prevention of such disastrous events a close cooperation between radiologist, oncologist, surgeon is required (for method limits) and anesthesiologist and from a different perspective with the bronchologist, pneumologist and gastro-enterologist. In trained hands and in teaching hospitals mediastinoscopy remains the golden standard in mediastinal evaluation, a simple procedure, with low morbidity and mortality.

The prevalence of open oval window (OOW) in patients with different types of ischemic insult and the possibility of independent pathogenetic contribution of OOW to brain injury were evaluated by examining 85 patients (mean age 53 +/- 14 yr) with cardioembolic (CES), lacunar (LS), and other subtypes of ischemic insult. CT and MRT of the head, duplex scanning of head arteries, contrast transcranial monitoring middle cerebral arteries, standard and contrast transthoracic and transoesophageal echocardiography revealed OOW in 40% of the patients. It had small anatomic and functional size and a tunnel-like shape. The presence of an interatrial shunt was unrelated to the degree of neurologic deficit, the size and location of brain injuries, the number of ischemic foci. It is concluded that OOW has no pathogenetic significance of its own and makes no contribution to brain injury in stroke-affected patients.

BACKGROUND: There is a heightened focus on postexplosion functional outcomes in combat casualties. Previously, we reported a high prevalence of posttraumatic stress disorder (PTSD) (32%) and mild traumatic brain injury (mTBI) (41%) in patients with explosion-related burns. We hypothesized that the prevalence of PTSD in patients with burn was associated with primary blast injuries (PBIs) and mTBI. METHODS: We reviewed the records of 333 patients admitted consecutively to the United States Army Institute of Surgical Research burn center for explosion-related injuries between March 2003 and March 2006. By using the Posttraumatic Checklist, Military Version (PCL-M), patients were evaluated for PTSD symptoms (PCL-M score >or=44). Loss of consciousness defined mTBI. Patient data were analyzed in groups based on PTSD (yes or no), mechanism of injury (improvised explosive device [IED] vs. other explosive), PBI (yes or no), and mTBI (yes or no). RESULTS: Of 333 patients, 119 had PTSD assessments. Overall, PTSD was 22% (26 of 119). The prevalence of PTSD differed between mechanism of injury groups (p = 0.03). In the IED group (n = 105), 25% had PTSD symptoms and 18% had mTBI; patients injured by other explosive devices (n = 14) had no PTSD symptoms and one had mTBI (p = 0.04; p = 0.69, respectively). Also in the IED group, in patients with PBI, PTSD was 45% (9 of 20) compared with 20% (17 of 85) without PBI (odds ratio=3.27; 95% confidence interval, 1.17-9.16). More patients with PBI and mTBI (4 of 6; 67%) had PTSD symptoms compared with other patients (22 of 99; 22%) (odds ratio, 7.00; 95% confidence interval, 1.20-40.78). No other associations were found between PBI and mTBI. CONCLUSION: IED-wounded burn patients with PBI and mTBI have a greater prevalence of PTSD. Patients who did not have IED-related injuries did not have PTSD and only one had mTBI.

Mitochondrial dysfunction and oxidative stress are increasingly implicated in the pathophysiology of schizophrenia. The brain is the body’s highest energy consumer, and the glutathione system is the brain’s dominant free radical scavenger. In the current paper, we review the evidence of central and peripheral nervous system anomalies in the oxidative defences of individuals with schizophrenia, principally involving the glutathione system. This is reflected by evidence of the manifold consequences of oxidative stress that include lipid peroxidation, protein carboxylation, DNA damage and apoptosis – all potentially part of the process of neuroprogression in the disorder. Importantly, oxidative stress is amenable to intervention. We consider the clinical potential of some possible interventions that help reduce oxidative stress, via augmentation of the glutathione system, particularly N-acetyl cysteine. We argue that a better understanding of the mechanisms and pathways underlying oxidative stress will assist in developing the therapeutic potential of this area.

PURPOSE.: The purpose of this study was to determine the frequencies of visual impairment and dysfunction among combat-injured Polytrauma Rehabilitation Center (PRC) inpatient and Polytrauma Network Site (PNS) outpatient military personnel with traumatic brain injury (TBI). METHODS.: A retrospective analysis of data from vision screenings of 68 PRC-inpatients with moderate to severe levels of TBI and 124 PNS-outpatients with mild TBI at the VA Palo Alto Health Care System was conducted. RESULTS.: Eighty-four percent of PRC-inpatients and 90% of PNS-outpatients had TBIs associated with a blast event. The majority of patients in both the PRC and PNS populations had visual acuities of 20/60 or better (77.8% PRC, 98.4% PNS). Visual dysfunctions (e.g., convergence, accommodative, and oculomotor dysfunction) were common in both PRC and PNS populations. In the PRC-inpatient population, acuity loss of 20/100 to no light perception (13%) and visual field defects (32.3%) were found. In the PNS-outpatient population, acuity loss of 20/100 to no light perception (1.6%) and visual field defects (3.2%) were infrequently found. In both the PRC and PNS populations, visual field defects were more often associated with blast than non-blast events. CONCLUSIONS.: Blast events were the most frequent mechanism of injury associated with TBI in combat-injured servicemembers. The vision findings suggest that combat troops exposed to blast with a resulting mild TBI are at risk for visual dysfunction, and combat troops with polytrauma injuries are at risk for visual dysfunction and/or visual impairment. The visual consequences of such injuries necessitate further study and support the need for appropriate evaluation and treatment in all severities of TBI.

BACKGROUND AND PURPOSE: Spreading depolarizations, characterized by large propagating, slow potential changes, have been demonstrated with electrocorticography in patients with cerebral hemorrhage and ischemic stroke. Whereas spreading depolarizations are harmless under normal conditions in animals, they cause or augment damage in the ischemic brain. A fraction of spreading depolarizations is abolished by N-methyl-D-aspartate receptor antagonists. Summary of Case-In 2 patients with severe acute brain injury (traumatic and spontaneous intracranial hemorrhage), spreading depolarizations were inhibited by the noncompetitive N-methyl-D-aspartate receptor antagonist ketamine. This restored electrocorticographic activity. CONCLUSIONS: These anecdotal electrocorticographic findings suggest that ketamine has an inhibitory effect on spreading depolarizations in humans. This is of potential interest for future neuroprotective trials.