Cerebral Palsy

Object Medial pectoral nerve (MPN) to musculocutaneous nerve (MCN) neurotization for recovery of elbow flexion by biceps reinnervation is a valid option following traumatic injury to the upper brachial plexus. A major criticism of the application of this technique in infants is the smaller size of the MPN and mismatch of viable axons. We describe our institutional experience utilizing this procedure and critically examine functional outcomes. Methods Office charts and hospital records of children from over an 11-year period beginning January 1997 were reviewed. Of the 53 children of various ages undergoing brachial plexus exploration for traumatic injury of any nature, 20 underwent MPN to MCN neurotization as a part of an overall procedure in the first year of life to treat birth-related brachial plexus palsy and had at least 9 months’ follow-up. Medial pectoral nerve to MCN neurotization was chosen if the results of clinical examination and intraoperative electrophysiological evidence were consistent with medial cord function. Functional recovery was defined as the ability of the child to bring their hand to their mouth. Results Sixteen patients (80%) gained functional recovery. The median age at surgery was 7 months. Median time to first clinic visit documenting recovery was 11.5 months and median overall follow up was 21.5 months. Preoperative hand function was a useful predictor of recovery of elbow flexion. Conclusions Medial pectoral nerve to MCN neurotization is a valid surgical option for the reinnervation of the biceps muscle for birth-related brachial plexus palsy when the hand is functional preoperatively. Useful elbow flexion can be expected in the majority of these children.

OBJECTIVE: To investigate neonatal outcome after breech presentation in term pregnancies. STUDY DESIGN: Data from 1345 term breech deliveries over a 12-year study period were retrospectively reviewed. Neonatal morbidity and mortality were compared by route of delivery. RESULTS: We investigated 1345 term breech deliveries. A total of 1041 patients (77.4%) attempted a vaginal delivery; of these, 808 (60.1%) were delivered vaginally and 233 patients (17.3%) who failed at vaginal birth underwent cesarean section. The other 304 women (22.6%) were delivered by a planned cesarean section. No statistical differences were found in the incidence of low 5-minute Apgar scores and arterial cord blood pH values<or=7. Admission to neonatal units was higher after vaginal delivery than after elective cesarean section (55.0% vs. 20.0%). The difference between vaginal delivery and cesarean section in the rate of severe plexus injuries was statistically significant (P=0.0025). Two neonatal deaths occurred at term after a trial of labor. No perinatal death of a term breech infant occurred in the cesarean section group. CONCLUSION: The increased risk of birth trauma and admission to a neonatal intensive care unit after vaginal delivery emphasizes the advantages of a planned cesarean section for a breech presentation.

OBJECTIVE: To compare the rate of serious adverse perinatal outcomes of term labour between private and public maternity hospitals in Australia. DESIGN, SETTING AND PARTICIPANTS: A population-based study of 789 240 term singleton births in public and private hospitals in 2001-2004, using data from the National Perinatal Data Collection. MAIN OUTCOME MEASURES: Third- and fourth-degree perineal injury, requirement for high level of neonatal resuscitation, Apgar score < 7 at 5 minutes, admission to neonatal intensive care unit or special care nursery, and perinatal death. RESULTS: 31.4% of the term singleton births occurred in private hospitals. After adjusting for maternal age, Indigenous status, parity, smoking status, diabetes, hypertension, remoteness of usual residence, and method of birth, the rates of all adverse outcomes studied were higher for public hospital births. For women, the adjusted odds ratio (AOR) for third- or fourth-degree perineal injury was 2.28 (95% CI, 2.16-2.40). For babies, the odds of a high level of resuscitation (AOR, 2.37; 95% CI, 2.17-2.59), low Apgar score (AOR, 1.75; 95% CI, 1.65-1.84), intensive care requirement (AOR, 1.48; 95% CI, 1.45-1.51) and perinatal death (AOR, 2.02; 95% CI, 1.78-2.29) were all higher in public hospitals. CONCLUSION: For women delivering a single baby at term in Australia, the prevalence of adverse perinatal outcomes is higher in public hospitals than in private hospitals.

Aim Cerebral palsy (CP) is frequently linked to white matter injury in children born preterm. Diffusion tensor imaging (DTI) is a powerful technique providing precise identification of white matter microstructure. We investigated the relationship between DTI-observed thalamocortical (posterior thalamic radiation) injury, motor (corticospinal tract) injury, and sensorimotor function. Method Twenty-eight children born preterm (16 males, 12 females; mean age 5y 10mo, SD 2y 6mo, range 16mo-13y; mean gestational age at birth 28wks, SD 2.7wks, range 23-34wks) were included in this case-control study. Twenty-one children had spastic diplegia, four had spastic quadriplegia, two had hemiplegia, and one had ataxic/hypotonic CP; 15 of the participants walked independently. Normative comparison data were obtained from 35 healthy age-matched children born at term (19 males, 16 females; mean age 5y 9mo, SD 4y 4mo, range 15mo-15y). Two-dimensional DTI color maps were created to evaluate 26 central white matter tracts, which were graded by a neuroradiologist masked to clinical status. Quantitative measures of touch, proprioception, strength (dynamometer), and spasticity (modified Ashworth scale) were obtained from a subset of participants. Results All 28 participants with CP had periventricular white-matter injury on magnetic resonance imaging. Using DTI color maps, there was more severe injury in the posterior thalamic radiation pathways than in the descending corticospinal tracts. Posterior thalamic radiation injury correlated with reduced contralateral touch threshold, proprioception, and motor severity, whereas corticospinal tract injury did not correlate with motor or sensory outcome measures. Interpretation These findings extend previous research demonstrating that CP in preterm children reflects disruption of thalamocortical connections as well as descending corticospinal pathways.

Pituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential risk factors for pituitary tumors in Southeast England. Information on medical and reproductive history, female sex hormones, and cigarette smoking was collected by personal interview from 299 cases and 630 controls aged 18 to 59 years. Tumor risk was reduced in subjects reporting a past diagnosis of hay fever [odds ratio (OR), 0.7; 95% confidence interval (CI), 0.5-1.0] but not asthma or eczema. Risk was raised in women who were postmenopausal 1 year before diagnosis (OR, 3.2; 95% CI, 1.6-6.2), especially if menopause was surgically induced (OR, 6.7; 95% CI, 2.2-19.9) or occurred under age 40 years (OR, 7.5; 95% CI, 2.6-21.4). This effect remained when evaluating menopausal status 10 years before diagnosis. There was no association with parity overall, but risk was increased for first childbirth under age 20 years compared with nulliparity (OR, 3.4; 95% CI, 1.4-8.4). No significant association was observed with ever use of oral contraceptives or hormone replacement therapy, nor with cigarette smoking, past head injury, past diagnosis with epilepsy, or birth characteristics, except for an inverse association of risk with maternal age. This study suggests a raised risk of pituitary tumors in relation to surgically induced menopause, early postmenopausal age, and young age at childbirth, and possibly a reduced risk with hay fever and increasing maternal age. Reasons for these associations need further investigation, but some associations might be due to hormonal effects of an undiagnosed pituitary tumor. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1492-500).

AIM: To assess the regional vulnerability to ischemic damage and perfusion/metabolism mismatch of reperfused brain following restoration of spontaneous circulation (ROSC) after cardiac arrest. METHOD: We used positron emission tomography (PET) to map cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in brain of young pigs at intervals after resuscitation from cardiac arrest. After obtaining baseline PET recordings, ventricular fibrillation of 10min duration was induced, followed by mechanical closed-chest cardiopulmonary resuscitation (CPR) in conjunction with i.v. administration of 0.4U/kg of vasopressin. After CPR, external defibrillatory shocks were applied to achieve restoration of spontaneous circulation (ROSC). CBF and CMRO(2) were mapped and voxelwise maps of OEF were calculated at times of 60, 180, and 300min after ROSC. RESULTS: There was hypoperfusion throughout the telencephalon at 60min, with a return towards baseline values at 300min. In contrast, there was progressively increasing CBF in cerebellum throughout the observation period. The magnitude of CMRO(2) decreased globally after ROSC, especially in cerebral cortex. The magnitude of OEF in cerebral cortex was 60% at baseline, tended to increase at 60min after ROSC, and declined to 50% thereafter, thus suggesting transition to an ischemic state. CONCLUSION: The cortical regions tended most vulnerable to the ischemic insult with an oligaemic pattern and a low CMRO(2) whereas the cerebellum instead showed a pattern of luxury perfusion.

Hypoxia-inducible transcription factors (HIF)-1 and HIF-2, composed of an oxygen-dependent alpha-subunit and a constitutive beta-subunit, have been characterized as the most important regulators of oxygen homeostasis during physiological and pathological conditions. During embryonic, fetal and postnatal brain development, HIFs and specific HIF target genes are involved in early and highly active maturational processes by modulating cell differentiation, vascular development, angiogenesis and metabolic homeostasis. Under hypoxic conditions, activation of the HIF system reflects an immediate and cell-specific response to acute brain hypoxia. In a complementary fashion, both HIF-1 and HIF-2 modulate cerebral hypoxic stress responses and activate endogenous neuroprotective systems during acute and late stages of hypoxic/ischemic (HI) damage of the developing brain. Therefore, HIFs and their specific target genes that are expressed during brain injury are of particular interest for future diagnostic and therapeutic options in HI injury of the developing nervous system.

Hypothermia is an effective method for reducing the neuronal damage induced by hypoxia-ischemia (HI) but the underlying mechanism remains unclear. To investigate the effects of post-HI hypothermia on the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 2hours. They were divided into a hypothermia group (rectal temperature 32-33 degrees C for 24h) and a normothermia group (36-37 degrees C for 24h) immediately after hypoxia-ischemia. Animals were sacrificed at 12, 24 and 72h for gene analysis and 0, 1, 3 and 7 days for protein analysis after HI. There was a significant decrease in infarct volume in the hypothermia group at 7 days after HI compared with that in the normothermia group. The hypothermia group had more Neuronal Nuclei (NeuN) positive neurons and lower levels of glial fibrillary acidic protein (GFAP) mRNA and immunoreactivity in the hippocampus CA1 region than the normothermia group. Real-time PCR showed no significant difference in glial cell line-derived neurotrophic factor (GDNF) mRNA expression in the hippocampus in the two groups at various time points after HI. However, GDNF protein level was significantly increased in the hypothermia group. On the other hand, mRNA and protein levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were dramatically decreased in the hypothermia compared with the normothermia group. The present findings highlight an apparent association between inhibition of hippocampal neuron loss by hypothermia and decreased astrocytosis and inflammatory cytokine release after hypoxia-ischemia in the developing brain.

No effective therapy is currently available to promote recovery following ischemic stroke. Stem cells have been proposed as a potential source of new cells to replace those lost due to central nervous system injury, as well as a source of trophic molecules to minimize damage and promote recovery. We undertook a detailed review of data from recent basic science and preclinical studies to investigate the potential application of endogenous and exogenous stem cell therapies for treatment of cerebral ischemia. To date, spontaneous endogenous neurogenesis has been observed in response to ischemic injury, and can be enhanced via infusion of appropriate cytokines. Exogenous stem cells from multiple sources can generate neural cells that survive and form synaptic connections after transplantation in the stroke-injured brain. Stem cells from multiple sources cells also exhibit neuroprotective properties that may ameliorate stroke deficits. In many cases, functional benefits observed are likely independent of neural differentiation, although the exact mechanisms remain poorly understood. Future studies of neuroregeneration will require the demonstration of function in endogenously born neurons following focal ischemia. Further, methods are currently lacking to demonstrate definitively the therapeutic effect of newly introduced neural cells. Increased plasticity following stroke may facilitate the functional integration of new neurons, but the loss of appropriate guidance cues and supporting architecture in the infarct cavity will likely impede the restoration of lost circuitry. Thus careful investigation of the mechanisms underlying trophic benefits will be essential. Evidence to date suggests that continued development of stem cell therapies may ultimately lead to viable treatment options for ischemic brain injury. J. Comp. Neurol. 515:125-144, 2009. (c) 2009 Wiley-Liss, Inc.

Ischemic brain is highly vulnerable to free radicals mediated secondary neuronal damage especially mitochondrial dysfunctions. Present study investigated the neuroprotective effect of S-allyl L-cysteine (SAC), a water soluble compound from garlic, against cerebral ischemia/reperfusion (I/R)-induced mitochondrial dysfunctions in hippocampus (HIP). We used transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia. SAC (300 mg/kg) was given twice intraperitoneally: 15 min pre-occlusion and 2 h post-occlusion at the time of reperfusion. SAC significantly restored ATP content and the activity of mitochondrial respiratory complexes in SAC treated group which were severely altered in MCAO group. A marked decrease in calcium swelling was observed as a result of SAC treatment. Western blot analysis showed a marked decrease in cytochrome c release as a result of SAC treatment. The status of mitochondrial glutathione (GSH) and glucose 6-phosphate dehydrogenase (G6-PD) was restored by SAC treatment with a significant decrease in mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) and H2O2 content. SAC significantly improved neurological deficits assessed by different scoring methods as compared to MCAO group. Also, the brain edema was significantly reduced. The findings of this study suggest the ability of SAC in functional preservation of ischemic neurovascular units and its therapeutic relevance in the treatment of ischemic stroke.