Cause Of Cerebral Palsy Research Articles

Cerebral palsy and brain cooling

This month in The Journal there are 3 articles that discuss cerebral palsy (CP) and the use of hypothermia to decrease brain injury in newborns. Garfinkel et al used a Canadian CP registry to estimate that about 5% of CP could be prevented with the effective use of therapeutic hypothermia of asphyxiated term infants delivered in Canada. This low effectiveness results from the multiple factors pointed out in the editorial by Berg. Most cases of CP are not the result of the acute sentinel asphyxial events associated with deliveries, and many of the infants do not qualify for hypothermia treatment. Furthermore, the therapy is not highly effective. This discouraging overall effect of therapeutic hypothermia is compounded in low and middle-income countries (LMIC) as pointed out by the Commentary by Tagin et al. Hypoxic ischemic encephalopathy is responsible for an estimated 25% of all neonatal deaths worldwide, and asphyxia is responsible for a large number of fresh stillborns in LMIC countries. Although therapeutic hypothermia is an effective therapy in high resource environments, it has not been demonstrated to be effective in LMIC in a few trials. Although the therapy is relatively simple to deliver in any modern neonatal intensive care unit, there are multiple obstacles to its effective use in LMIC. Identification of the infant that qualifies for hypothermia treatment by the criteria used in high resource environments requires trained personnel and infrastructure, and, thus, is not easily accomplished. More lives could be saved by upgrading obstetric services to decrease stillborns and providing effective resuscitation, than by developing the infrastructure necessary for the rapid identification and treatment of the asphyxiated infant with hypothermia. Therapies to improve outcomes that are effective in one environment may not work in another. Even though therapeutic hypothermia is a major advance as the first treatment that can decrease brain injury in asphyxiated term infants, its overall impact on the incidence of CP and birth asphyxia will be small within the context of worldwide infant mortality. Article page 25▶ Article page 58▶ Editorial page 8▶ Cerebral Palsy after Neonatal Encephalopathy: How Much Is Preventable?The Journal of PediatricsVol. 167Issue 1PreviewTo determine the expected proportion of term cerebral palsy (CP) after neonatal encephalopathy (NE) that could theoretically be prevented by hypothermia and elucidate the perinatal factors associated with CP after NE in those who do not meet currently used clinical criteria required to qualify for hypothermia (“cooling criteria”). Full-Text PDF Neuroprotection for Perinatal Hypoxic Ischemic Encephalopathy in Low- and Middle-Income CountriesThe Journal of PediatricsVol. 167Issue 1PreviewPerinatal hypoxic ischemic encephalopathy (HIE) is associated with approximately one-quarter of global neonatal deaths.1 In 2010, there were an estimated 1.15 million cases of neonatal encephalopathy, of which 96% of were from low- and middle-income (LMI) countries.2 In the developed world, therapeutic hypothermia is now widely accepted as the standard of care for treating newborns with moderate to severe HIE.3 Therapeutic hypothermia has been found to reduce the risk of death or major neurodevelopmental disability at age 18 months (risk ratio [RR], 0.76; 95% CI, 0.69-0.84) and to increase survival with normal neurologic function (RR, 1.63; 95% CI, 1.36-1.95). Full-Text PDF Prevention of Cerebral Palsy: Which Infants Will Benefit from Therapeutic Hypothermia?The Journal of PediatricsVol. 167Issue 1PreviewCan cerebral palsy (CP) be prevented? The answer depends on the etiology of CP. Although the causes of CP are largely related to early brain injury, both the nature of that injury and the later manifestations can differ based on the gestational and postnatal ages at which the injury occurs, as well as its source. Full-Text PDF

Abbreviated exposure to hypoxia is sufficient to induce CNS dysmyelination, modulate spinal motor neuron composition, and impair motor development in neonatal mice.

Neonatal white matter injury (nWMI) is an increasingly common cause of cerebral palsy that results predominantly from hypoxic injury to progenitor cells including those of the oligodendrocyte lineage. Existing mouse models of nWMI utilize prolonged periods of hypoxia during the neonatal period, require complex cross-fostering and exhibit poor growth and high mortality rates. Abnormal CNS myelin composition serves as the major explanation for persistent neuro-motor deficits. Here we developed a simplified model of nWMI with low mortality rates and improved growth without cross-fostering. Neonatal mice are exposed to low oxygen from postnatal day (P) 3 to P7, which roughly corresponds to the period of human brain development between gestational weeks 32 and 36. CNS hypomyelination is detectable for 2–3 weeks post injury and strongly correlates with levels of body and brain weight loss. Immediately following hypoxia treatment, cell death was evident in multiple brain regions, most notably in superficial and deep cortical layers as well as the subventricular zone progenitor compartment. PDGFαR, Nkx2.2, and Olig2 positive oligodendrocyte progenitor cell were significantly reduced until postnatal day 27. In addition to CNS dysmyelination we identified a novel pathological marker for adult hypoxic animals that strongly correlates with life-long neuro-motor deficits. Mice reared under hypoxia reveal an abnormal spinal neuron composition with increased small and medium diameter axons and decreased large diameter axons in thoracic lateral and anterior funiculi. Differences were particularly pronounced in white matter motor tracts left and right of the anterior median fissure. Our findings suggest that 4 days of exposure to hypoxia are sufficient to induce experimental nWMI in CD1 mice, thus providing a model to test new therapeutics. Pathological hallmarks of this model include early cell death, decreased OPCs and hypomyelination in early postnatal life, followed by dysmyelination, abnormal spinal neuron composition, and neuro-motor deficits in adulthood.

The thrombin receptor is a critical extracellular switch controlling myelination.

Hemorrhagic white matter injuries in the perinatal period are a growing cause of cerebral palsy yet no neuroprotective strategies exist to prevent the devastating motor and cognitive deficits that ensue. We demonstrate that the thrombin receptor (protease-activated receptor 1, PAR1) exhibits peak expression levels in the spinal cord at term and is a critical regulator of the myelination continuum from initiation to the final levels achieved. Specifically, PAR1 gene deletion resulted in earlier onset of spinal cord myelination, including substantially more Olig2-positive oligodendrocytes, more myelinated axons, and higher proteolipid protein (PLP) levels at birth. In vitro, the highest levels of PAR1 were observed in oligodendrocyte progenitor cells (OPCs), being reduced with differentiation. In parallel, the expression of PLP and myelin basic protein (MBP), in addition to Olig2, were all significantly higher in cultures of PAR1-/- oligodendroglia. Moreover, application of a small molecule inhibitor of PAR1 (SCH79797) to OPCs in vitro increased PLP and MBP expression. Enhancements in myelination associated with PAR1 genetic deletion were also observed in adulthood as evidenced by higher amounts of MBP and thickened myelin sheaths across large, medium, and small diameter axons. Enriched spinal cord myelination in PAR1-/- mice was coupled to increases in extracellular-signal-regulated kinase 1/2 and AKT signaling developmentally. Nocturnal ambulation and rearing activity were also elevated in PAR1-/- mice. These studies identify the thrombin receptor as a powerful extracellular regulatory switch that could be readily targeted to improve myelin production in the face of white matter injury and disease.

Single Photon Emission Computed Tomography Scan as a Diagnostic Tool in Children with Cerebral Palsy Treated with Human Embryonic Stem Cells

Introduction: Cerebral palsy (CP) is caused by abnormalities in the developing brain leading to an impairment of muscle coordination and movement control in the body. Neonatal hypoxic-ischemic brain injury and hypoxic ischemic encephalopathy (HIE) are major causes of CP. Neurodegenerative disorders can be treated with human embryonic stem cells (hESC). Magnetic resonance imaging (MRI), positron emission tomography and single photon emission computed tomography (SPECT) scan are some of the imaging modalities for CP, but among all SPECT scan is more sensitive in detecting abnormalities in the brain. SPECT scan is an effective tool for the detection of cerebral blood flow, cerebral impairment and local brain metabolism. The present study was conducted to evaluate the diagnostic modality of SPECT scan that can assess the patient with CP before and after hESC therapy. Methodology: The study included the patients with CP for whom SPECT scan was performed before and after the therapy. Technetium-hexa methyl propylene aminoxime (Tc-HMPAO) SPECT scan was analyzed to assess the number of hypoperfused lesions/ areas in the brain and the percentage of improvement by hESC treatment. The patients were scored clinically using GMFCS scores. Results: Overall, 88 patients aged 2 months to 18 years with clinical manifestations of CP had SPECT scan performed before and after the therapy. The total treatment days varied from 31 to 310 days. All the subjects showed improvement in SPECT scan. Majority of subjects (n=58) had significant SPECT scan (>60%) change, followed by moderate SPECT scan (>30% 10% <30%) change in 3 subjects. These patients also showed a clinical improvement as reflected in their GMFCS scores. Conclusion: SPECT scan can be a crucial diagnostic modality to assess patients with CP.

Cerebral palsy: Phenotypes and risk factors in term singletons born small for gestational age

Background and objectivesChildren born small for gestational age (SGA) are at increased risk of developing cerebral palsy (CP). The pathophysiology behind this association remains unclear. We compare the clinical profile of children with CP born SGA to other children with CP. We hypothesize that differences noted will support antenatal causes of CP in children born SGA. MethodsWe conducted a retrospective cohort study of term singletons with CP, extracting data from the Canadian Cerebral Palsy Registry. SGA was determined as birth weight for gestational age and sex below the tenth percentile. ResultsMothers of children with CP born SGA were more likely to be of African-American ethnicity (RR 2.54, 95% CI 1.20–5.39), have intrauterine infections (RR 2.22, 95% CI 1.09–4.50) and have gestational hypertension (RR 1.78, 95% CI 1.06–3.00). Children with CP born SGA had smaller head circumferences at birth (p < 0.001) and higher frequencies of emergency cesarean-section (RR 1.53, 95% CI 1.22–1.92), birth asphyxia (RR 1.53, 95% CI 1.0–2.32), and placental abnormalities (RR 1.45, 95% CI 1.00–2.10). Children with CP born SGA had greater fine motor (RR 1.46, 95% CI 1.02–2.11), gross motor (RR 1.53, 95% CI 1.12–2.10) and communication impairment (RR 1.24, 95% CI 1.10–1.40), and a higher frequency of cognitive impairment (RR 1.33, 95% CI 1.06–1.69). ConclusionChildren with CP born SGA have different clinical factors and phenotypic profiles than other children with CP. These differences support the hypothesis of antenatal and perinatal causes of CP in children born SGA. Future case control studies would be desired to further define this causal pathway.

Transplanted glial restricted precursor cells improve neurobehavioral and neuropathological outcomes in a mouse model of neonatal white matter injury despite limited cell survival.

Neonatal white matter injury (NWMI) is the leading cause of cerebral palsy and other neurocognitive deficits in prematurely-born children, and no restorative therapies exist. Our objective was to determine the fate and effect of glial restricted precursor cell (GRP) transplantation in an ischemic mouse model of NWMI. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal-Day 5 (P5). At P22, intracallosal injections of either enhanced green fluorescent protein (eGFP) + GRPs or saline were performed in control and ligated mice. Neurobehavioral and postmortem studies were performed at 4 and 8 weeks post-transplantation. GRP survival was comparable at 1 month but significantly lower at 2 months post-transplantation in NWMI mice compared with unligated controls. Surviving cells showed better migration capability in controls; however, the differentiation capacity of transplanted cells was similar in control and NWMI. Saline-treated NWMI mice showed significantly altered response in startle amplitude and prepulse inhibition (PPI) paradigms compared with unligated controls, while these behavioral tests were completely normal in GRP-transplanted animals. Similarly, there was significant increase in hemispheric myelin basic protein density, along with significant decrease in pathologic axonal staining in cell-treated NWMI mice compared with saline-treated NWMI animals. The reduced long-term survival and migration of transplanted GRPs in an ischemia-induced NWMI model suggests that neonatal ischemia leads to long-lasting detrimental effects on oligodendroglia even months after the initial insult. Despite limited GRP-survival, behavioral, and neuropathological outcomes were improved after GRP-transplantation. Our results suggest that exogenous GRPs improve myelination through trophic effects in addition to differentiation into mature oligodendrocytes.

Familial risk of cerebral palsy: population based cohort study

Objective To investigate risks of recurrence of cerebral palsy in family members with various degrees of relatedness to elucidate patterns of hereditability.Design Population based cohort study.Setting Data from the Medical...

White matter damage in the preterm neonate

Abstract The most common form of brain injury in preterm infants is periventricular leukomalacia (PVL). PVL is also the most common cause of cerebral palsy in the smallest and most vulnerable preterm infant. The core theme in its pathogenesis is the effect of hypoxia, ischaemia, and inflammation on the vulnerable white matter of the developing brain. Over the last decade, with improved laboratory and imaging techniques, the complex relationships between the known associated factors involved in causation of PVL is becoming increasingly known. A better understanding of its pathogenesis provides the basis for future protective strategies against PVL.

Congenital cytomegalovirus is associated with severe forms of cerebral palsy and female sex in a retrospective population‐based study

Congenital cytomegalovirus (cCMV) infection can result in poor outcomes including cerebral palsy (CP). The aim of this study was to describe the incidence and comorbidities of CP reported to the Australian Cerebral Palsy Register (ACPR) as attributed to cCMV infection. This was a retrospective population-based study. Cases were drawn from Australian state CP registers with population level ascertainment, 1993 to 2003 (n=2265; 56.4% males, Gross Motor Function Classification System [GMFCS] ratings available for Victorian cases only: 70% GMFCS levels I to III and 30% GMFCS levels IV to V). Clinical data were extracted and cases with cCMV reported as a known cause were compared with cases where cCMV was not reported. Children with cCMV (n=34; 12 males, 22 females; mean [SD] gestational age, 36.4 wk [4.4], range 24-41 wk) accounted for 1.5% of CP cases; 2.9 per 100,000 live births, (95% confidence intervals 1.9-3.9). When compared with CP cases where cCMV was not reported, proportionally, more CP cases with cCMV were born to younger mothers (p<0.001), were female (64% vs 43%, p=0.014), had spastic quadriplegia (73% vs 21%, p<0.001), required wheeled mobility i.e. GMFCS IV or V (78% vs 28%, p<0.001), had epilepsy (70% vs 30%, p<0.001), deafness (40% vs 2%, p<0.001), functional blindness (20% vs 5%, p<0.001), and severe communication impairment (71% vs 25%, p<0.001). cCMV is an important potentially preventable cause of CP and is associated with severe disability and female sex in cases reported to the ACPR. Future studies utilising prospective sample collection for cCMV testing are needed to confirm these findings.

Development, Reliability, and Validity of the Alberta Perinatal Stroke Project Parental Outcome Measure

BackgroundPerinatal stroke is a leading cause of cerebral palsy and lifelong disability, although parent and family outcomes have not yet been studied in this specific population. The Alberta Perinatal Stroke Project Parental Outcome Measure was developed as a 26-item questionnaire on the impact of perinatal stroke on parents and families. MethodsThe items were derived from expert opinion and scientific literature on issues salient to parents of children with perinatal stroke, including guilt and blame, which are not well captured in existing measures of family impact. Data were collected from 82 mothers and 28 fathers who completed the Parental Outcome Measure and related questionnaires (mean age, 39.5 years; mean child age, 7.4 years). Analyses examined the Parental Outcome Measure's internal consistency, test-retest reliability, validity, and factor structure. ResultsThe Parental Outcome Measure demonstrated three unique theoretical constructs: Psychosocial Impact, Guilt, and Blame. The Parental Outcome Measure has excellent internal consistency (Cronbach α = 0.91) and very good test-retest reliability more than 2-5 weeks (r = 0.87). Regarding validity, the Parental Outcome Measure is sensitive to condition severity, accounts for additional variance in parent outcomes, and strongly correlates with measures of anxiety, depression, stress, quality of life, family functioning, and parent adjustment. ConclusionsThe Parental Outcome Measure contributes to the literature as the first brief measure of family impact designed for parents of children with perinatal stroke.

Umbilical arterial pH in patients with cerebral palsy

BackgroundUmbilical arterial pH (UApH) in severe cerebral palsy (CP) is not fully understood. AimsThis work aims to determine the relationship between fetal acidemia and clinical features of severe CP. Study designA retrospective study design is used. SubjectsA review was conducted unti1 April 2013 among 218 infants with CP diagnosed to be caused by antenatal and/or intrapartum conditions determined by the Japan Council for Quality Health Care. After excluding patients in whom the causes of CP were thought to be due to events after delivery, 168 infants born at over 34weeks of gestation that both Apgar score and UApH were measured were selected. Outcome measuresSevere fetal acidemia was defined as a pH of less than 7.0. ResultsSix major factors were found to be associated with CP: placental abruption (A, n=42), traumatic delivery with an abnormal FHR pattern (B, n=29), an abnormal FHR pattern during labor (C, n=27), chorioamnionitis with an abnormal FHR pattern (D, n=17), an abnormal FHR pattern before labor (E, n=14), and cord prolapse (F, n=10). The UApH was less than 7.0 in 114 cases (67.9%) and more than 7.20 in 20 cases (11.9%). The UApH values were lowest in group A (median 6.7, 6.43–6.99) and highest in group E (7.18, 6.92–7.45). The distribution of the UApH values was significantly different in these groups. ConclusionPlacental abruption was a factor most associated with low pH. Even among the infants with severe CP, over 10% of patients exhibited a non-acidemic status at birth.

Impact of an Educational Film on Parental Knowledge of Children with Cerebral Palsy

Parents of children with cerebral palsy (CP) must have knowledge about the disease and its management to improve the outcome. This uncontrolled interventional trial was carried out to evaluate the parental knowledge of CP and assess the impact of an educational programme on it. Preset questionnaires were filled before and 1 week after a single session educational programme using an educational film. Out of a total of 53 subjects, majority (75.5%) were from lower socioeconomic status. Initially, none knew the correct name of child's illness; afterwards 45.3% could name it. When compared to previous status, there occurred significant improvement in the knowledge of parents after viewing the film with regard to knowing the cause of CP, knowing that motor involvement was predominant in CP, knowledge regarding curability of the disease, and knowledge about special schooling (P < 0.05). Change in knowledge was not related to socioeconomic or educational status (P > 0.05). Majority (94.3%) found the film useful and 96.2% learned how they could help in the management of their children. Parental knowledge of CP is inadequate which can be improved by incorporating such educational programmes in special clinics to improve management.

The Estimated Cost of Early Cord Clamping at Birth Within Europe

Early cord clamping has been a common although variable practice at all births throughout Europe for the past 40 years. It is known to result in a variable degree of hypovolemia, reduced cardiac output, reduced cerebral circulation, and an immediate loss of placental oxygenated blood. Hypoxic ischemia of the brain at birth is recognized to be a major underlying cause of cerebral palsy. Using very conservative estimates of the adverse effects of early cord clamping in a proportion of births according to the survey of its use in Europe and an estimate of the cost of care for an individual with cerebral palsy, we have calculated a possible cost for the intervention which is unnecessary and continued practice is largely the result of habit and poor understanding of the physiology of transition.

Effect of early intervention in the developmental outcome of hypoxic ischemic encephalopathy infants

Background: Neonatal brain injury due to intrapartum asphyxia is a significant cause of cerebralpalsy, mental retardation, and epilepsy. Despite advances in perinatal care over the pastthree decades, the incidence of cerebral palsy attributed to birth asphyxia has not changed. Indeveloping countries, the incidence of post asphyxiate neurological damage is particularly high. Objectives: To study the developmental outcomes of hypoxic ischemicencephalopathy infants by early physiotherapy intervention till one year Methodology: This study had conducted on 48 asphyxiated full term newborn infants who developed HypoxicIschemic Encephalopathy (HIE) admitted in Neonatal Intensive Care Unit (NICU) of Rajah Muthiah Medical College &hospital. The studied infants have classified on the basis of Sarnat and Sarnat staging of HIE into 3 stages, and they were given early intervention. Denver developmental screening test have administered to infants every four months till one year. The level of achievement of various developmental domains in among various stages of HIE early intervention infants were compared. Results: We found improvement in the level of achievement of developmental domains in various stages of birth asphyxia infants with a better outcome in stage I HIE infants. Conclusion: The early interventional program on HIE infants in the neurodevelopmentaloutcome after one year of age investigated in this study was efficacious in infants who participated in thestudy.

Mutations in gamma adducin are associated with inherited cerebral palsy

ObjectiveCerebral palsy is estimated to affect nearly 1 in 500 children, and although prenatal and perinatal contributors have been well characterized, at least 20% of cases are believed to be inherited. Previous studies have identified mutations in the actin-capping protein KANK1 and the adaptor protein-4 complex in forms of inherited cerebral palsy, suggesting a role for components of the dynamic cytoskeleton in the genesis of the disease.MethodsWe studied a multiplex consanguineous Jordanian family by homozygosity mapping and exome sequencing, then used patient-derived fibroblasts to examine functional consequences of the mutation we identified in vitro. We subsequently studied the effects of adducin loss of function in Drosophila.ResultsWe identified a homozygous c.1100G>A (p.G367D) mutation in ADD3, encoding gamma adducin in all affected members of the index family. Follow-up experiments in patient fibroblasts found that the p.G367D mutation, which occurs within the putative oligomerization critical region, impairs the ability of gamma adducin to associate with the alpha subunit. This mutation impairs the normal actin-capping function of adducin, leading to both abnormal proliferation and migration in cultured patient fibroblasts. Loss of function studies of the Drosophila adducin ortholog hts confirmed a critical role for adducin in locomotion.InterpretationAlthough likely a rare cause of cerebral palsy, our findings indicate a critical role for adducins in regulating the activity of the actin cytoskeleton, suggesting that impaired adducin function may lead to neuromotor impairment and further implicating abnormalities of the dynamic cytoskeleton as a pathogenic mechanism contributing to cerebral palsy.

Encefalopatía por Kernicterus: Serie clínica

Kernicterus (bilirubin encephalopathy): case reports Introduction: Jaundice is common in newborn babies (NB). Bilirubin levels of 20 mg/dL or higher may cause choreoathetoid cerebral palsy, sensorineural hearing loss, eye disorders and enamel dysplasia in term infants; clinical picture compatible with kernicterus. Objective: To describe five cases of kernicterus treated at a Neu - rology Unit between 2002 and 2012. Case reports: Five cases of babies with gestational ages between 35 and 39 weeks, birth-weight ranging from 2580 to 4250 grams and bilirubin levels between 24 and 47 mg/dL are presented. Two infants were at home when acute encephalopathy developed, all were treated with photothera- py and 3 of them underwent exchange transfusion. The age of diagnosis of kernicterus was between 12 days to 10 years; three patients were diagnosed in neonatal period through MRI that revealed basal ganglia impregna- tion. All patients evolved presenting movement disorders of varying severity. Three of them were diagnosed with sensorineural hearing impairments and two presented eye disorders. Psychometric tests showed cogni- tive delay in three patients and normal development in the remaining children. Conclusion: Kernicterus in a devastating disease present in the national reality. It is a preventable cause of cerebral palsy; therefore, it is necessary to educate parents, population and health care professionals about neonatal hyperbilirubinemia early detection and treatment. (Key words: Kernicterus, bilirubin, basal ganglia, cerebral palsy, hearing loss). Rev Chil Pediatr 2013; 84 (6): 659-666

White matter loss in a mouse model of periventricular leukomalacia is rescued by trophic factors.

Periventricular leukomalacia (PVL) is the most frequent cause of cerebral palsy and other intellectual disabilities, and currently there is no treatment. In PVL, glutamate excitotoxicity (GME) leads to abnormal oligodendrocytes (OLs), myelin deficiency, and ventriculomegaly. We have previously identified that the combination of transferrin and insulin growth factors (TSC1) promotes endogenous OL regeneration and remyelination in the postnatal and adult rodent brain. Here, we produced a periventricular white matter lesion with a single intracerebral injection of N-methyl-d-aspartate (NMDA). Comparing lesions produced by NMDA alone and those produced by NMDA + TSC1 we found that: NMDA affected survival and reduced migration of OL progenitors (OLPs). In contrast, mice injected with NMDA + TSC1 proliferated twice as much indicating that TSC1 supported regeneration of the OLP population after the insult. Olig2-mRNA expression showed 52% OLP survival in mice receiving a NMDA injection and increased to 78% when TSC1 + NMDA were injected simultaneously and ventricular size was reduced by TSC1. Furthermore, in striatal slices TSC1 reduced the inward currents induced by NMDA in medium-sized spiny neurons, demonstrating neuroprotection. Thus, white matter loss after excitotoxicity can be partially rescued as TSC1 conferred neuroprotection to preexisting OLP and regeneration via OLP proliferation. Furthermore, we showed that early TSC1 administration maximizes neuroprotection.

Thyroxin Treatment Protects Against White Matter Injury in The Immature Brain via Brain-Derived Neurotrophic Factor

Low level of thyroid hormone is a strong independent risk factor for white matter (WM) injury, a major cause of cerebral palsy, in preterm infants. Thyroxin upregulates brain-derived neurotrophic factor during development. We hypothesized that thyroxin protected against preoligodendrocyte apoptosis and WM injury in the immature brain via upregulation of brain-derived neurotrophic factor. Postpartum (P) day-7 male rat pups were exposed to hypoxic ischemia (HI) and intraperitoneally injected with thyroxin (T4; 0.2 mg/kg or 1 mg/kg) or normal saline immediately after HI at P9 and P11. WM damage was analyzed for myelin formation, axonal injury, astrogliosis, and preoligodendrocyte apoptosis. Neurotrophic factor expression was assessed by real-time polymerase chain reaction and immunohistochemistry. Neuromotor functions were measured using open-field locomotion (P11 and P21), inclined plane climbing (P11), and beam walking (P21). Intracerebroventricular injection of TrkB-Fc or systemic administration of 7,8-dihydroxyflavone was performed. On P11, the HI group had significantly lower blood T4 levels than the controls. The HI group showed ventriculomegaly and marked reduction of myelin basic protein immunoreactivities in the WM. T4 (1 mg/kg) treatment after HI markedly attenuated axonal injury, astrocytosis, and microgliosis, and increased preoligodendrocyte survival. In addition, T4 treatment significantly increased myelination and selectively upregulated brain-derived neurotrophic factor expression in the WM, and improved neuromotor deficits after HI. The protective effect of T4 on WM myelination and neuromotor performance after HI was significantly attenuated by TrkB-Fc. Systemic 7,8-dihydroxyflavone treatment ameliorated hypomyelination after HI injury. T4 protects against WM injury at both pathological and functional levels via upregulation of brain-derived neurotrophic factor-TrkB signaling in the immature brain.

Psychological impact of cerebral palsy on families: The African perspective

Background:Psychological stress associated with cerebral palsy (CP) is known to be one of the most depressing conditions of families. In the traditional African society, some peculiar factors may contribute to the stress.Aims:The aims of this study were to identify and describe, from the African perspective, the psychological impact of CP on families and determine the strategies adopted by families in coping with it.Settings and Design:The study was a cross-sectional descriptive survey conducted in the Physiotherapy Department of a tertiary hospital.Materials and Methods:Participants were 52 parents of children with CP. They completed a questionnaire designed to determine the degree of psychological stress on the families and strategies adopted to cope with the stress.Statistical Analysis:Descriptive statistics were used to show responses in graphical formats.Results:Respondents agreed that having adequate knowledge of CP would help them cope well with the demands of taking care of children with CP. 38.5% of respondents said that people in the society accused them of some wrongdoing that has made their children to have CP. Personal problems experienced include loss of job, lack of concentration at work, loss of family joy, and derangement of financial affairs of the family. 26 (50%) of them resort to religious/spiritual intervention as an alternative or complementary mode of treatment for their children while 28% resort to dependence on the extended family system for support.Conclusion:Families caring for children with CP generally have a positive attitude towards their children. However, there is need to educate the public on the causes of CP and treatment options available to families.

Fetal Asphyxia: A Case Study of Translational Research

Translational research is a high priority for the Canadian Institutes of Health Research and the National Institutes of Health in the United States. The history of the significance of fetal asphyxia as a cause of brain damage and cerebral palsy reflects the challenge for translational research. An antepartum and intrapartum cause of cerebral palsy was proposed in the 19th century Our current understanding that fetal asphyxia beyond a certain threshold will cause brain damage is built on the foundation of laboratory studies conducted over the last 50 years. However, many questions remain to be answered. Clinical studies have confirmed a similar response of the human fetus to fetal asphyxia in vivo. Translation of this knowledge into patient care during the intrapartum period has been achieved to some degree.The emphasis on translational research relates to the political, public, and professional desire to improve patient care. The challenges for translational research have been highlighted in recent publications and are evident in fetal asphyxia The goals of translational research will only be achieved with a continuing commitment to both laboratory and clinical research.