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Objective: Quantify how temperature and age modulate the effects of multiple periods of anoxia on peripheral nerve., Methods: Nerve action potentials (NAP) recorded from rat sciatic nerve in vitro. Effects of multiple cycles of anoxia on the NAP are evaluated as functions of temperature and age. In some experiments, the nerve was held at constant temperature and others the nerve was hypothermic only during anoxia and returned to 36°C with restoration of oxygen., Results: Hypothermia mitigates the effect of anoxia on the NAP, an effect that increases with multiple cycles of anoxia. Preservation of the NAP waveform after 5 cycles of anoxia is best when hypothermia is delivered only during anoxia. Hypothermia reduces the rate at which the NAP disappears during anoxia but has a limited effect on the rate of recovery. With intermittent hypothermia the amplitude of the NAP is best preserved with temperatures of 15-22°C. Velocity and duration are best preserved below 25°C. The loss of the NAP during anoxia is slower in the older nerves., Conclusions: Lower temperatures improve the recovery of the NAP from anoxia and increase the time it takes for the NAP to disappear during anoxia as does increasing age., Significance: Document the effects of hypothermia on the anoxia response as a step toward understanding its nerve protectant effect., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Determine the effects of serial episodes of anoxia in an in vitro peripheral nerve preparation., Methods: The nerve action potential (NAP) from rat sciatic nerve was recorded during 5 cycles of anoxia and reperfusion. Multiple NAP parameters were analyzed as well as stimulus response curves., Results: The amplitude of the NAP declined to half baseline in 865 s on the first cycle of anoxia and recovered to half baseline during recovery in 470 s. These times increased with successive cycles of anoxia. The current required to produce a half maximal NAP showed a variable initial decrease before increasing with anoxia. The paired-pulse response showed a decline at 2-3 ms interstimulus interval during anoxia but was less dependent of interstimulus interval during recovery. NAP amplitude and velocity decrease over successive cycles of anoxia at a rate greater than in the absence of anoxia., Conclusions: The NAP declines slowly when peripheral nerve is exposed to anoxia but returns at least twice as quickly when re-exposed to oxygen. Short periods of anoxia produce long lasting changes in the nerve suggesting greater resistance to anoxia. With serial episodes of anoxia there is gradual NAP amplitude reduction and increase in duration and latency., Significance: Anoxic-preconditioning appears in isolated peripheral nerve., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The extracellular matrix of peripheral nerve is formed from a diverse set of macromolecules, including glycoproteins, collagens and proteoglycans. Recent studies using knockout animal models have demonstrated that individual components of the extracellular matrix play a vital role in peripheral nerve development and regeneration. In this study we identified fibrillin-1 and fibrillin-2, large modular structural glycoproteins, as components of the extracellular matrix of peripheral nerve. Previously it was found that fibrillin-2 null mice display joint contractures, suggesting a possible defect of the peripheral nervous system in these animals. Close examination of the peripheral nerves of fibrillin-2 deficient animals described here revealed some structural abnormalities in the perineurium, while general structure of the nerve and molecular composition of nerve extracellular matrix remained unchanged. We also found that in spite of the obvious motor function impairment, fibrillin-2 null mice failed to display changes of nerve conduction properties or nerve regeneration capacity. Based on the data obtained we can conclude that peripheral neuropathy should be excluded as the cause of the impairment of locomotory function and joint contractures observed in fibrillin-2 deficient animals., (Copyright (c) 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

Objective: Determine whether EEG findings could be used as an independent prognostic indicator of outcomes in a general patient population., Methods: A large electronic medical record was used to merge the results of EEG studies with the results of medical evaluations including: medications prescribed, medical diagnoses, blood test results, imaging results, and outcomes in 3193 patients. Univariable and multivariable analyses were undertaken to determine whether the EEG had a role in predicting outcomes independent of other factors in a clinic population., Results: Patients with abnormal EEG's had significantly higher mortalities, greater cost of healthcare and more evaluation visits than patients with normal EEG's in every age range independent of the presence other medical conditions. The costs associated with caring for a patient with an abnormal EEG were roughly three times that of a patient with a normal EEG. The risk of death in the multivariable analysis was 3.7 times higher in patients with an abnormal EEG than in patients with a normal EEG., Conclusions: In addition to its traditional diagnostic implications, the EEG may convey information about general level of illness and the cost of caring for patients., Significance: Certain EEG findings may identify high risk patients and thus may open the door to possible interventions.

Background: Although the neurologic status of patients undergoing cardiac operations has been well studied at other times, there are few studies of neurologic status in the immediate postoperative state. This study used standardized nursing neurologic evaluations to describe the sequence of neurologic changes during the first few hours after cardiac operations and the factors that influence them., Methods: In this prospective study, patients arriving in the intensive care unit after cardiac operations were serially assessed using the using the Neurologic Intensive Care Evaluation (NICE) for up to 24 hours postoperatively. The study evaluated the effects on outcome of various preoperative and intraoperative variables, as well as the NICE scores., Results: Recovery of brainstem reflexes occurred at 1.4 +/- 1.4 hours, and the fully alert state occurred at a mean of 5.1 +/- 3.8 hours after admission to the intensive care unit in patients without a new neurologic deficit. Patients with new neurologic deficits or patients discharged to supervised care settings took longer to reach each neurologic milestone. Older patients, patients with more complex surgical procedures, and patients with higher cardiovascular risk factors took longer to become fully alert. The time to reach the highest NICE score was a strong predictor of the duration of intubation but only weakly predicted other outcome variables in a multivariable analysis., Conclusions: Standardized, serial nursing neurologic assessments of postoperative cardiac patients provide insight into the immediate postoperative period and may be a useful tool for early identification of patients at risk for adverse outcomes.

The response to transcranial electrical stimulation of the brain is an important means of assessing motor pathways in the anesthetized patient. The purposes of this study were to elucidate the pattern of axonal excitation produced by transcranial stimulation and to demonstrate how this pattern is affected by changes in the conductivity or geometry of the skull-CSF-brain complex. To this end, analytic solutions to the problem of electrodes placed on a three shell spherical model were obtained under constant current conditions. The potentials, currents and fields generated were computed and the "activating function" was computed for an idealized set of radially organized axons in order to estimate the degree of membrane depolarization produced by stimulation. The degree to which electromagnetic/radiation effects change these solutions was also estimated. The pattern of stimulation was only slightly dependent on the conductivity and the thickness of the CSF layer. Axons very close to the anode were stimulated with lowest threshold at the brain surface. Axons further away were stimulated with higher thresholds and the point of maximum stimulation moved nearer the center of the sphere. Near the cathode, stimulation was maximal about 5-7 degrees away from the edge of the electrode but the peak magnitude of the activating function was generally 20 times lower than over the anode.

Differences between constant current and constant voltage nerve stimulation are controversial. To elucidate this controversy, exact solutions are found for the electrical potential and current of a conducting electrode of finite size placed near a boundary of altered conductivity. Substantial differences in the effects of a finite and a point stimulator are predicted. This was strongly dependent on the stimulator-boundary distance, the conductivity of the media, and the curvature of the boundary. The difference between constant voltage and constant current stimulation was smaller than the effects of changes in medium conductivity and electrode distance. A poorly conducting boundary layer surrounding the stimulator minimized these differences.

Although seizures can be a manifestation of paraneoplastic disorders, there are few descriptions of the association between the anti-Hu paraneoplastic syndrome and epilepsia partialis continua. A new case of refractory complex partial status epilepticus in a patient with a paraneoplastic syndrome associated with a poorly differentiated mediastinal tumor that expressed Hu antigen is described clinically, pathologically, and electrographically. We discuss the presentation of focal seizures in a disease that is characterized by diffuse pathologic involvement of the brain. The progression of EEG, MRI, and clinical findings during the course of the illness is also discussed. To our knowledge, this is the first description of paraneoplastic epilepsia partialis continua associated with diffuse pathologic abnormalities.

A case of an older patient with the Angelman syndrome due to a deletion at the 15q11-q13 region is presented. The patient demonstrated generalized prolonged myoclonus severe enough to produce temperatures of 41.4 degrees C and CPK elevations to 7281 U/l. This myoclonus was unresponsive to benztropine, clonazepam and worsened with bromocriptine. It resolved with sleep induced by either lorazepam or diphenhydramine and during treatment with reserpine. Once discharged from the hospital and treated with reserpine, there were much less frequent recurrences of the myoclonus that responded well to concomitant treatment with clonazepam. Later attempts to reduce the reserpine resulted in worsening of the myoclonus. Older patients with Angelman syndrome may display a wide variety of neurologic syndromes. This severe myoclonus in this patient worsened with dopamine agonist treatment and initially improved with dopamine depletion therapy while in the long-term responding best to a combination of clonazepam and reserpine.

Background: Delayed postoperative paraplegia is a recognized complication of thoracic (TAA) or thoracoabdominal aortic aneurysm (TAAA) repair. The purpose of this study was to evaluate the effectiveness of interventions to treat delayed-onset paraplegia., Methods: Between January 1, 2000 and August 31, 2001, 99 patients underwent surgical repair of TAA, Crawford type I, II, or III TAAA. Standard intraoperative management included distal aortic perfusion and cerebrospinal fluid (CSF) drainage unless contraindicated. Therapeutic interventions to treat delayed paraplegia included lumbar CSF drainage and vasopressor therapy., Results: Three of the 99 patients had paraplegia upon awakening. Delayed-onset paraplegia occurred in 8 patients, 2 of whom had recurrent episodes. In those 8 patients, the initial episode occurred at a median of 21.6 hours (range 6.4 to 110.0 hours) after surgery and the second episode averaged 176 hours after surgery. At the onset of paraplegia, the average mean arterial pressure was 74 mm Hg and CSF pressure was 14 mm Hg. Three of the 8 patients had a functioning CSF catheter at the onset and the other 5 patients had catheters subsequently placed. Therapeutic interventions increased blood pressure to a mean arterial pressure of 95 mm Hg and decreased CSF pressure to 10 mm Hg. Five of the 8 patients with delayed-onset paraplegia made a full neurologic recovery and 3 had partial recovery., Conclusions: Patients with delayed-onset paraplegia had an increased chance of recovery as compared with those patients in whom paraplegia was diagnosed upon emergence from anesthesia. Acute interventions directed to increase spinal cord perfusion by increasing systemic blood pressure and decreasing CSF pressure were effective for the reversal of delayed onset of paraplegia after TAA or TAAA repair, resulting in an overall 3% incidence of permanent paraplegia and 3% incidence of residual paraparesis.

An analysis of the effects of automatic artifact rejection on the evoked potential recordings is made using both a theoretical analysis and computer simulations. It is demonstrated that when the noise at each measurement point is independently distributed with maximum probability near zero amplitude, the bias and changes in variance induced by the automatic artifact rejection are small unless more than 80% of traces are rejected. When high-amplitude noise transients occur, there can be significant bias in the evoked potential when the artifact rejection threshold is set near the amplitude of the noise transients. Even more substantial distortions in the evoked potential occur when the noise is not independently distributed at each measurement point. It is important to recognize the possibility of these effects during clinical evoked potential recording.

Background: The available techniques for intravascular gene delivery to the heart are inefficient and not organ-specific. Yet, effective treatment of heart failure will likely require transgene expression by the majority of cardiac myocytes. To address this problem, we developed a novel cannulation technique that achieves efficient isolation of the heart in situ using separate cardiopulmonary bypass (CPB) circuits for the heart and body in dogs., Methods: The arterial inflow and venous effluent from the two circuits were physically isolated. The efficiency of separation was 98% to 99% in three preliminary experiments using Evans Blue dye-labeled albumin. In 6 dogs, the cardiac circuit was perfused with oxygenated crystalloid cardioplegia at 37 degrees C containing approximately 4 x 10(11) particles of an adenovirus encoding LacZ (AdCMVLacZ) with a perfusion pressure of 170 to 200 mm Hg for 15 minutes allowing virus to recirculate through the heart approximately 15 times. Cross-clamp time was 26 +/- 2 minutes and CPB time was 90 +/- 3 minutes., Results: Five animals survived and were euthanized at 7 days. Beta-galactosidase activities measured using a chemiluminescent assay were three orders of magnitude higher in all areas of the heart than in the liver. Histological analyses revealed heterogeneous X-Gal staining of myocytes in all areas of the myocardium., Conclusions: Despite using a constitutive promoter, this technique yields relatively cardiac-specific transgene expression and is potentially translatable to clinical applications. Future studies will allow for further optimization of the conditions necessary for vector-mediated gene delivery to the heart.