Functional outcomes after selective dorsal rhizotomy followed by minimally invasive tendon lengthening procedures in children with spastic cerebral palsy.

Many surgical options have been proposed to improve the ambulatory status of children with spastic cerebral palsy (CP), but none have focused on addressing both spasticity and lower extremity tendon contractures. The purpose of this study is to evaluate the results of selective dorsal rhizotomy (SDR) followed by minimally invasive tendon lengthening allowing immediate return to ambulation. Two hundred fifty-five spastic CP patients (who received SDR procedure at an average age of 6.9±2.6 years and tendon lengthening procedure at an average age of 7.2±2.5 years) were retrospectively reviewed. Patients were grouped by the gross motor function classification system (GMFCS) 1-3 and 4-5. Kaplan-Meier analysis and Cox proportional hazard model using a requirement for additional tendon lengthening as an end point were conducted. Tendon lengthening followed SDR at an average of 4.3±10.7 months. On an average of 4.9±1.2 years after tendon lengthening, GMFCS was improved in 28 and maintained in 213 patients, respectively. There was no difference of variables and joint angles between the two GMFCS groups. A repeat tendon lengthening was required in 19 patients. The Kaplan-Meier analysis showed 81% success rate. Cox proportional hazard model identified age at tendon lengthening [hazards ratio (HR), 0.53; 95% confidence interval (CI), 0.37-0.76] and duration between SDR and tendon lengthening of more than 6 months (HR, 2.96; 95% CI, 1.05-8.33) associated with need for a repeat tendon lengthening procedure. Our novel approach of SDR/tendon lengthening results in improved joint angles as well as stable or improved GMFCS. Longer follow-up is necessary to determine if this approach could prolong ambulatory ability and reduced need for more invasive orthopedic surgeries.

Biopsy of the superficial cortex: predictors of effectiveness and outcomes.

BACKGROUND: Brain biopsies of superficial cortex are performed for diagnosis of neurological diseases, but preoperative predictors of successful diagnosis and risks are lacking. OBJECTIVE: We evaluated effectiveness and outcomes of superficial cortical biopsies and determined preoperative predictors of diagnosis, outcomes, morbidities, and mortality. METHODS: A single-institution retrospective analysis of 170 patients who underwent open brain biopsies of superficial cortex was performed. Clinical predictors of effectiveness and outcomes were determined using univariate/multivariate analyses and a system for risk-benefit stratification was created and tested. RESULTS: Brain biopsies led to successful diagnosis in 122 of 170 (71.8%) and affected management in 97 of 170 (57.1%) cases. Factors increasing the odds of diagnostic pathology included age older than 45 years (odds ratio [OR]: 2.67, 95% confidence interval [CI]: 1.34-5.27, P < .01), previous cancer diagnosis (OR: 3.64, 95% CI: 1.69-7.85, P < .001), focal (OR: 3.90, 95% CI: 1.91-8.00, P < .001) and enhancing (OR: 5.03, 95% CI: 2.41-10.52, P < .001) lesions on magnetic resonance imaging, biopsy of specific lesions on magnetic resonance imaging (OR: 9.34, 95% CI: 4.29-20.33, P < .001), and use of intraoperative navigation (OR: 6.59, 95% CI: 3.04-14.28, P < .001). Brain biopsies led to symptomatic intracranial hemorrhage, seizures, other significant morbidities, and perioperative mortality in 12.4%, 16.2%, 37.1%, and 8% of cases, respectively. Risk of postoperative intracranial hemorrhage was increased by a history of aspirin use (OR: 2.51, 95% CI: 1.23-5.28, P < .05) and age older than 60 years (OR: 2.66, 95% CI: 1.36-5.18, P < .01). CONCLUSION: Effectiveness and risk of morbidity/mortality can be estimated preoperatively for patients undergoing open brain biopsies of the superficial cortex. Older age and specific imaging characteristics increase the odds of diagnostic biopsy. Conversely, older age and aspirin use increases the risk of postoperative complications.

Peri-operative pain management in children with cerebral palsy: comparative efficacy of epidural vs systemic analgesia protocols.

INTRODUCTION: Selective Dorsal Rhizotomy (SDR) is the only surgical intervention with class I evidence supporting permanent reduction in spasticity for children with cerebral palsy (Paediatr Anaesth, 12, 2002, 296; Neurosurg Focus, 21, 2006, e2). Postoperatively, adequate analgesia can be difficult to achieve (J Neurosurg, 105, 2006, 8; Childs Nerv Syst, 17, 2001, 556; Pediatr Neurosurg, 43, 2007, 107; Anesth Analg, 79, 1994, 340; Reg Anesth Pain Med, 24, 1999, 438; Pediatr Anesth, 19, 2009, 1213). This study examines a novel regimen utilizing the combination of epidurally infused ropivacaine - hydromorphone and scheduled ketorolac. This regimen was compared to a protocol utilizing systemic fentanyl and diazepam. METHODS: Following IRB approval, 31 patients receiving epidural analgesia were compared with 41 patients who received systemic analgesia. All surgeries were performed by one surgeon with standardized anesthetic and nursing care. Studied outcomes included: pain scores; episodes of severe pain; nausea, itching; oxygen desaturation; and ICU admission. Data were analyzed using Mann-Whitney U-test, CHI square, and Fisher exact test where indicated with P < 0.05 considered significant. RESULTS: Studied groups had similar demographics, biometrics and disease burdens. Patients in the epidural group had statistically and clinically significant reductions in peak recorded pain scores for each 4-h period in the first 24 postoperative hours. Severe pain (score >5) was markedly reduced in the epidural group with 9% of epidural patients vs. 68% of systemic patients experiencing at least one episode. Fewer epidural patients experienced oxygen desaturation during the first two postoperative days (6.5% vs. 41%, 6.5% vs. 39%). CONCLUSION: Epidural analgesia resulted in substantial improvements in pain control and safety. The data supports the superiority of a multimodal analgesia approach centered on epidural analgesia. A similar protocol should be considered following simple laminectomies or procedures associated with lower-extremity muscle spasm.

Glioblastoma in children: a single-institution experience.

PURPOSE: Current treatment recommendations for pediatric glioblastoma include surgery, chemotherapy, and radiation therapy. However, even with this multispecialty approach, overall survival remains poor. To assess outcome and evaluate treatment-related prognostic factors, we retrospectively reviewed the experience at our institution. METHODS AND MATERIALS: Twenty-four glioblastoma patients under the age of 21 were treated with radiation therapy with curative intent at Washington University, St. Louis, from 1970 to 2008. Patients underwent gross total resection, subtotal resection or biopsy alone. Fourteen (58%) of the patients received chemotherapy. All patients received radiation therapy. Radiation consisted of whole-brain radiation therapy in 7 (29%) patients with a median dose of 50.4 Gy. Seventeen (71%) patients received three-dimensional conformal radiation therapy with a median dose of 54 Gy. RESULTS: Median follow-up was 12.5 months from diagnosis. One and 2-year overall survival rates were 57% and 32%, respectively. Median overall survival was 13.5 months. There were no differences in overall survival based on patients' age, race, gender, tumor location, radiation volume, radiation dose, or the use of chemotherapy. There was a significant improvement in overall survival for patients in whom gross total resection was achieved (p = 0.023). Three patients were alive 5 years after gross total resection, and 2 patients were alive at 10 and 24 years after diagnosis. CONCLUSIONS: Survival for children with glioblastoma remains poor. Data from this and other studies demonstrate the importance of achieving a gross total resection. Continued investigation into new treatment options is needed in an attempt to improve outcome for these patients.

Neutrophil elastase and neurovascular injury following focal stroke and reperfusion.

Neutrophil elastase (NE) degrades basal lamina and extracellular matrix molecules, and recruits leukocytes during inflammation; however, a basic understanding of the role of NE in stroke pathology is lacking. We measured an increased number of extravascular NE-positive cells, as well as increased levels of tissue elastase protein and activity, following transient middle cerebral artery occlusion (tMCAo). Both pharmacologic inhibition of NE with ZN200355 (ZN), and genetic deletion of NE, significantly reduced infarct volume, blood-brain barrier disruption, vasogenic edema, and leukocyte-endothelial adherence 24 h after tMCAo. ZN also reduced infarct volume in MMP9-null mice following tMCAo. There were, however, no reductions in infarct volume or vasogenic edema in NE-null mice in two models of permanent middle cerebral artery occlusion. Our findings confirm the involvement of NE in neurovascular stroke pathology, when reperfusion allows neutrophils access to vulnerable brain, with pharmacologic or genetic inhibition of NE being both neuro- and vasculo-protective in this setting.

Hypoxic preconditioning protects human brain endothelium from ischemic apoptosis by Akt-dependent survivin activation.

Preconditioning-induced ischemic tolerance is well documented in the brain, but cell-specific responses and mechanisms require further elucidation. The aim of this study was to develop an in vitro model of ischemic tolerance in human brain microvascular endothelial cells (HBMECs) and to examine the roles of phosphatidylinositol 3-kinase (PI3-kinase)/Akt and the inhibitor-of- apoptosis protein, survivin, in the ability of hypoxic preconditioning (HP) to protect endothelium from apoptotic cell death. Cultured HBMECs were subjected to HP, followed 16 h later by complete oxygen and glucose deprivation (OGD) for 8 h; cell viability was quantified at 20 h of reoxygenation (RO) by the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay. HBMECs were examined at various times after HP or OGD/RO using immunoblotting and confocal laser scanning immunofluorescence microscopy for appearance of apoptotic markers and expression of phosphorylated (p)-Akt and p-survivin. Causal evidence for the participation of the PI3-kinase/Akt pathway in HP-induced protection and p-survivin upregulation was assessed by the PI3-kinase inhibitor LY-294002. HP significantly reduced OGD/RO-induced injury by 50% and also significantly reduced the OGD-induced translocation of apoptosis-inducing factor (AIF) from mitochondria to nucleus and the concomitant cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). PI3-kinase inhibition blocked HP-induced increases in Akt phosphorylation, reversed the effects of HP on OGD-induced AIF translocation and PARP-1 cleavage, blocked HP-induced survivin phosphorylation, and ultimately attenuated HP-induced protection of HBMECs from OGD. Thus HP promotes an antiapoptotic phenotype in HBMECs, in part by activating survivin via the PI3-kinase/Akt pathway. Survivin and other phosphorylation products of p-Akt may be therapeutic targets to protect cerebrovascular endothelium from apoptotic injury following cerebral ischemia.

Ballistocardiogram artifact removal from EEG signals using adaptive filtering of EOG signals.

We estimated ballistocardiogram (BCG) components in EEG signals recorded inside an MRI magnet using the electro-oculogram (EOG) signals recorded simultaneously with the EEG signals. Since the EOG signals are measured near the EEG measuring points, it is thought that the BCG components in the EOG signals resemble the BCG components in the EEG signals. To estimate the BCG components in the EEG signals, we applied the Kalman filter to the EOG and EEG signals recorded inside a 3.0 T MRI magnet. After removing the estimated BCG components from the EEG signals, we extracted the visual-evoked potentials (VEPs) from the BCG-removed EEG signals. To validate the efficacy of Kalman filtering in the BCG artifact removal, we have compared three types of VEPs of eight healthy subjects: one extracted from the raw EEG signals measured outside the magnet and the others extracted from the BCG-removed EEG signals measured inside the magnet. The BCG artifacts have been removed with Kalman filtering as well as with the conventional BCG template subtraction method for the sake of comparison. No significant difference in waveforms, latencies and amplitudes has been found between the two types of VEPs extracted from the two kinds of BCG-removed EEG signals.

Selective decrease of chick embryonic primordial germ cells in vivo and in vitro by soft X-ray irradiation.

The feasibility of soft (low-energy) X-ray irradiation as a means of depleting the endogenous primordial germ cell(s) (PGC) of chicken embryos, to improve the efficiency of germ cell-mediated transgenesis, was investigated. Eggs were subjected to a non-irradiated control treatment and embryos were exposed for 40s to soft X-ray at 15, 16.5, or 18 kV ( approximately 1.5, 1.65, and 1.8 Gy, respectively). Exposure of stage X embryos to each dose of X-ray resulted in a reduction of approximately 50% in the number of PGC apparent at stage 28, whereas the total number of gonadal cells was unaffected. Irradiation (16.5 kV) of embryos at stage 9 or 14 also resulted in similar decreases in the number of PGC with no effect on the total number of gonadal cells. Irradiation did not affect embryo hatchability, compared with the non-irradiated control treatment, although the hatch rate increased with the age of embryos at the time of irradiation. Exposure of gonadal cells isolated from stage 28 embryos to X-ray (16.5 kV, approximately 0.8 Gy) prevented the increase in PGC number during subsequent culture for 10 days; the increase in the total number of gonadal cells was not affected. In conclusion, exposure of chicken embryos to a low dose of soft X-rays is effective for depleting the endogenous PGC population without affecting embryo hatchability or somatic cell viability.

Cerebral endothelial cell apoptosis after ischemia-reperfusion: role of PARP activation and AIF translocation.

Cerebral ischemia-reperfusion leads to vascular dysfunction characterized by endothelial cell injury or death. In the present study, we used an in vitro model to elucidate mechanisms of human brain microvascular endothelial cell (HBMEC) injury after episodic ischemia-reperfusion. Near-confluent HBMEC cultures were exposed to intermittent hypoxia-reoxygenation (HX/RO) and, at different recovery time points, cell viability was assessed by the MTT assay, apoptotic death by fluorescence microscopy of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL)-positive cells, and nuclear translocation of apoptosis-inducing factor (AIF) and cleavage of poly(ADP-ribose) polymerase-1 (PARP-1) by immunoblotting of subcellular fractions. Reductions in HBMEC viability were proportional to the number of HX/RO cycles, and not the total duration of hypoxia. Using four cycles of 1-h HX with 1 h of intervening normoxic RO, cell viability was reduced 30% to 40% between 12 and 48 h. Treatment with the PARP-1 inhibitors 3-aminobenzamide or 4-amino-1,8-naphthalimide during the insult improved HBMEC viability at 24 h after insult, and resulted in dose-dependent reductions in TUNEL-positivity at 16 h after insult, but not if these treatments were delayed by 4 h. HX/RO-induced increases in nuclear AIF translocation, as well as PARP-1 cleavage, were also reduced dose-dependently at 4 h after insult by the inhibitors. The caspase inhibitor z-VAD-fmk blocked PARP-1 cleavage, but did not affect AIF translocation and was only modestly cytoprotective. These findings indicate that PARP-1 activation and a PARP-1-dependent, caspase-independent, nuclear translocation of AIF contribute to apoptotic cerebral endothelial cell death after ischemia-reperfusion, underscoring the potential for ischemic microvascular protection by inhibiting PARP activation or preventing AIF translocation.

Effect of nerve cell currents on MRI images in snail ganglia.

We performed extracellular potential recording with dissected snail ganglia inside an MRI scanner to investigate correlation between neuronal activity and MR image intensity. To increase neuronal activity we applied a nitric oxide donor, sodium-nitrosocystein, to the ganglia. The MR image intensity change in the ganglia region is correlated with the neuronal activity and was up to 5.49+/-1.94%. Since the snail has non-magnetic hemocyanins as oxygen carrying protein, it seems that the image intensity change is mainly due to the local magnetic fields produced by the neuronal currents.

An interclass nuclear transfer between fowl and mammal: in vitro development of chicken-to-cattle interclass embryos and the detection of chicken genetic complements.

An attempt was made to develop an interclass somatic cell nuclear transfer method as an alternative means of establishing chicken embryonic stem cells. Chicken-to-cattle interclass embryos that activated calcium ionophore, cycloheximide, and cytochalasin D were developed into blastocysts, and the developing interclass embryos had chicken genetic complements.

Magnetic resonance electrical impedance tomography at 3 Tesla field strength.

Magnetic resonance electrical impedance tomography (MREIT) is a recently developed imaging technique that combines MRI and electrical impedance tomography (EIT). In MREIT, cross-sectional electrical conductivity images are reconstructed from the internal magnetic field density data produced inside an electrically conducting object when an electrical current is injected into the object. In this work we present the results of electrical conductivity imaging experiments, and performance evaluations of MREIT in terms of noise characteristics and spatial resolution. The MREIT experiment was performed with a 3.0 Tesla MRI system on a phantom with an inhomogeneous conductivity distribution. We reconstructed the conductivity images in a 128 x 128 matrix format by applying the harmonic B(z) algorithm to the z-component of the internal magnetic field density data. Since the harmonic B(z) algorithm uses only a single component of the internal magnetic field data, it was not necessary to rotate the object in the MRI scan. The root mean squared (RMS) errors of the reconstructed images were between 11% and 35% when the injection current was 24 mA.