Peripheral nerve at extreme low temperatures 2: pharmacologic modulation of temperature effects.

Changes in temperature have profound and clinically important effects on the peripheral nerve. In a previous paper, the effects of temperature on many properties of the peripheral nerve action potential (NAP) were explored including the NAP amplitude, conduction velocity and response to paired pulse stimulation. In this paper, the effects of pharmacologic manipulations on these parameters were explored in order to further understand the mechanisms of these effects. The reduction in conduction velocity with temperature was shown to be independent of the ionic composition of the perfusate and was unaffected by potassium or sodium channel blockade. This implies that the phenomenon of reduced conduction velocities at low temperature may be related to changes in the passive properties of the axon with temperature. Blockade of sodium channels and chronic membrane depolarization produced by high perfusate potassium concentrations or high dose 4-aminopyridine impair the resistance of the nerve to hypothermia and enhance the injury to the nerve produced by cycles of cooling and rewarming. This suggests the possibility that changes in the sodium inactivation channel may be responsible for the changes in the NAP amplitude with temperature and that prolonged sodium inactivation may lead more permanent changes in excitability.

Peripheral nerve at extreme low temperatures 1: effects of temperature on the action potential.

Hypothermia is an important means of neuroprotection. Understanding the effects of temperature on a physiologic measurement such as the nerve action potential (NAP) is important in monitoring its effects. The effects of hypothermia on the NAP amplitude, conduction velocity, and response to paired pulse stimulation were quantified in a rat sciatic nerve preparation from 37 to 10 degrees C. The time course of temperature related changes and the effect of repeated cycles of cooling and rewarming are explored using the following measures of the NAP: peak-to-peak amplitude, conduction velocity, duration, area under the curve and response to paired pulse stimuli. The NAP amplitude initially increases as temperature is reduced to 27 degrees C and then drops to roughly 50% of its baseline value by 16 degrees C while the area under the curve increases gradually until it begins to decline at 16 degrees C. Permanent loss of the NAP appears only after cooling below 10 degrees C for extended periods. Although the dependence of amplitude on temperature is approximately sigmoidal, the conduction velocity declines linearly at a rate of 2.8m/s/ degrees C. The response to paired pulse stimulation is strongly dependent on both temperature and the interstimulus interval with the responses at shorter interstimulus intervals being more temperature sensitive. With repetitive cycles of cooling and rewarming, the NAP amplitude declines by roughly 4% with every cycle without changes in the temperature at which the NAP amplitude reaches 50% of baseline. Only minor differences in conduction velocity are seen during cooling and rewarming.

Predictive model of length of stay and discharge destination in neuroscience admissions.

BACKGROUND: The purpose of this study was to try and determine the best predictors of hospital length of stay and discharge destination in patients admitted to a neuroscience service. METHODS: Valid data was collected for 170 patients. Variables included age, gender, location prior to admission, principle diagnosis, various physiological measurements upon admission, comorbidity, independence in various activities of daily living prior to admission, length of stay, and disposition upon discharge. Study design was a correlational descriptive study performed through the analysis of data and the development and validation of statistically significant factors in determining the length of stay. RESULTS: All factors with a strong (P < 0.05) relationship with the length of stay were entered into a forward stepwise linear regression with length of stay as the dependent variable. The three most significant variables in predicting length of stay in this study were admission from an outpatient setting, modified Rankin score on admission, and systolic blood pressure on admission. CONCLUSIONS: Functional status at admission, specifically, a higher modified Rankin score and a lower systolic blood pressure along with the acquisition of deep vein thrombosis, catheter associated urinary tract infections, intubation, and admission to an intensive care unit all have a statistically significant effect on the hospital length of stay.

Anoxia-induced changes in optimal substrate for peripheral nerve.

Hyperglycemia accentuates the injury produced by anoxia both in the central and peripheral nervous system. To understand whether this is a consequence of changes in metabolic pathways produced by anoxia, the effect of the metabolic substrate used by the rat peripheral nerve on the nerve action potential (NAP) was studied in the presence and absence of anoxia. In the continuously oxygenated state, the NAP was well preserved with glucose, lactate, as well as with high concentrations of sorbitol and fructose but not ß-hydroxybutyrate, acetate or galactose. With intermittent anoxia, the pattern of substrate effects on the NAP changed markedly so that low concentrations of fructose became able to support neurophysiologic activity but not high concentrations of glucose. These alterations occurred gradually with repeated episodes of anoxia as reflected by the progressive increase in the time needed for the NAP to disappear during anoxia when using glucose as substrate. This "preconditioning" effect was not seen with other substrates and an opposite effect was seen with lactate. In fact, the rate at which the NAP disappeared during anoxia was not simply related to degree of recovery after anoxia. These are distinct phenomena. For example, the NAP persisted longest during anoxia in the setting of hyperglycemia but this was the state in which the anoxic damage was most severe. Correlating the results with existing literature on the metabolic functions of Schwann cells and axons generates testable hypotheses for the mechanism of hyperglycemic damage during anoxia and lead to discussions of the role for a metabolic shuttle between Schwann cells and axons as well as a potential important role of glycogen.

Ventricular asystole during vagus nerve stimulation for epilepsy in humans.

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.

Technetium-99m-HMPAO SPECT in partial status epilepticus.

UNLABELLED: In this paper we correlate the findings on 99mTc-HMPAO brain SPECT with the results of clinical examinations and electroencephalography to determine the utility of SPECT in the evaluation of patients with suspected status epilepticus. METHODS: Thirteen patients with suspected status epilepticus underwent serial neurologic examinations, serial electroencephalograms, CT/MRI scanning and 99mTc-HMPAO SPECT. Seven patients were diagnosed with status epilepticus and six patients received other neurological diagnoses. RESULTS: All patients with status epilepticus at the time of the brain SPECT scan demonstrated focal hyperperfusion on SPECT in an area concordant with that suggested by EEG. One patient with status epilepticus demonstrated a persistent area of hyperperfusion on SPECT 24 hr after the cessation of status with no evidence of breakdown in the blood-brain barrier demonstrated by 99mTc-DTPA SPECT. No patient in this study without a diagnosis of status epilepticus had focal areas of hyperperfusion on SPECT. CONCLUSION: We suggest that a 99mTc-HMPAO SPECT scan demonstrating focal hyperperfusion in a patient being evaluated for partial status epilepticus is nonspecific. Even in the absence of a structural lesion causing local breakdown in the blood-brain barrier, it may indicate either ongoing status epilepticus or recently terminated status. However, a SPECT scan demonstrating no area of focal hyperperfusion argues against the diagnosis of partial status.

Detection of stroke during cardiac operations with somatosensory evoked responses.

OBJECTIVES: The objectives of this study were to determine if monitoring of intraoperative somatosensory evoked potentials could be used to detect stroke during cardiac operations and to establish indicators of cerebral ischemia based on changes in these potentials. METHODS: Twenty-five patients undergoing cardiac operations underwent preoperative and postoperative neurologic examinations as well as intraoperative recording of somatosensory evoked potentials. Detailed analysis of the waveforms of these potentials was performed. RESULTS: Two of the 25 patients had intraoperative strokes. These patients and only these patients had changes in their somatosensory evoked potentials during the operation suggesting cerebral ischemia. The unilateral disappearance of the cortical somatosensory evoked potential waves correlated significantly with the clinical outcome of stroke (p < 0.004). Ischemic changes were detected in real time and were related to the removal of the aortic crossclamp in one patient and to the initiation of cardiopulmonary bypass in the other. CONCLUSIONS: Somatosensory evoked potentials can detect intraoperative stroke during cardiac operations. Acute, unilateral decreases in amplitude of the cortical potential are more useful than changes in latency in detecting intraoperative stroke.

Acute type A aortic dissection: retrograde perfusion with left superior vena cava.

Retrograde cerebral perfusion with hypothermic circulatory arrest confers additional cerebral protection during repair of type A aortic dissection. We present a 42-year-old man with acute type A aortic dissection and a persistent, left superior vena cava. Cannulation of the right and left superior vena cava is used for retrograde perfusion of both hemispheres with bilateral monitoring of electroencephalogram and somatosensory-evoked potentials during and after the hypothermic circulatory arrest interval.

Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials.

BACKGROUND: Deep hypothermia is an important cerebral protectant and is critical in procedures requiring circulatory arrest. The purpose of this study was to determine the factors that influence the neurophysiologic changes during cooling before circulatory arrest, in particular the occurrence of electrocerebral silence. METHODS: In 109 patients undergoing hypothermic circulatory arrest with neurophysiologic monitoring, five electrophysiologic events were selected for detailed study. RESULTS: The mean nasopharyngeal temperature when periodic complexes appeared in the electroencephalogram after cooling was 29.6 degrees C +/- 3 degrees C, electroencephalogram burst-suppression appeared at 24.4 degrees C +/- 4 degrees C, and electrocerebral silence appeared at 17.8 degrees C +/- 4 degrees C. The N20-P22 complex of the somatosensory evoked response disappeared at 21.4 degrees C +/- 4 degrees C, and the somatosensory evoked response N13 wave disappeared at 17.3 degrees C +/- 4 degrees C. The temperatures of these various events were not significantly affected by any patient-specific or surgical variables, although the time to cool to electrocerebral silence was prolonged by high hemoglobin concentrations, low arterial partial pressure of carbon dioxide, and by slow cooling rates. Only 60% of patients demonstrated electrocerebral silence by either a nasopharyngeal temperature of 18 degrees C or a cooling time of 30 minutes. CONCLUSIONS: With the high degree of interpatient variability in these neurophysiologic measures, the only absolute predictors of electrocerebral silence were nasopharyngeal temperature below 12.5 degrees C and cooling longer than 50 minutes.

Deep hypothermic circulatory arrest: II. Changes in electroencephalogram and evoked potentials during rewarming.

BACKGROUND: Electrophysiologic studies during rewarming after deep hypothermic circulatory arrest probe the state of the brain during this critical period and may provide insight into the neurological effects of circulatory arrest and the neurologic outcome. METHODS: Electroencephalogram (EEG) and evoked potentials were monitored during rewarming in 109 patients undergoing aortic surgery with hypothermic circulatory arrest. RESULTS: The sequence of neurophysiologic events during rewarming did not mirror the events during cooling. The evoked potentials recovered first followed by EEG burst-suppression and then continuous EEG. The time to recovery of the evoked potentials N20-P22 complex was significantly correlated with the time of circulatory arrest even in patients without postoperative neurologic deficits (r = 0.37, (p = 0.002). The nasopharyngeal temperatures at which continuous EEG activity and the N20-P22 complex returned were strongly correlated (r = 0.44, p = 0.0002; r = 0.41, p = 0.00003) with postoperative neurologic impairment. Specifically, the relative risk for postoperative neurologic impairment increased by a factor of 1.56 (95% CI 1.1 to 2.2) for every degree increase in temperature at which the EEG first became continuous. CONCLUSIONS: No trend toward shortened recovery times or improved neurologic outcome was noted with lower temperatures at circulatory arrest, indicating that the process of cooling to electrocerebral silence produced a relatively uniform degree of cerebral protection, independent of the actual nasopharyngeal temperature.

Postoperative neurologic assessment and management of the cardiac surgical patient.

The neurologic evaluation of patients in the immediate postoperative period and postanesthetic state is unique and challenging. Neurologic assessment is complicated by the lingering residual effects of anesthetics as well as by the effects of narcotic analgesics, anxiolytics, and muscle relaxants, especially in ventilated patients. In this review we examine the suspected causes, clinical manifestations, diagnostic options, and intervention schemes for the common neurologic syndromes seen after cardiac operations.

Spinal dural arteriovenous malformations. Intraoperative evoked potential evidence for pathophysiology. A case report.

STUDY DESIGN: This case report details intraoperative evoked potential changes during surgical removal of a T8 dural arteriovenous malformation. OBJECTIVES: The pattern of changes in somatosensory-evoked responses during surgical correction of spinal dural at arteriovenous malformation can illuminate the pathophysiologic process behind the clinical symptoms. SUMMARY OF BACKGROUND DATA: Arteriovenous malformation of the spinal dura can manifest with multiple symptoms, including progressive myelopathy and pain. The pathophysiologic process behind these symptoms could be either direct compression of the spinal cord by the arteriovenous malformation, ischemia resulting from the cord, or increased venous pressure. METHODS: To investigate these hypotheses further, the results of posterior tibial evoked potentials obtained during surgical removal of a T8 dural arteriovenous malformation were analyzed. RESULTS: At baseline, the cortical (P40) potential was markedly prolonged bilaterally. During surgery, just after the dura was opened, a marked increase was observed in the latencies of the P40 and P60 components of the evoked response on the right, which began to resolve as soon as the arteriovenous malformation was occluded. Only minimal changes were seen on the left. CONCLUSIONS: These results are most consistent with the increased venous pressure hypothesis for the pathogenesis of neurologic symptoms in dural arteriovenous malformations.

Generalized averaging and noise levels in evoked responses.

A formal relationship between the mean square noise level in an evoked potential experiment, the number of averages and the autocorrelation function of the noise is derived. The generalized averaging process is recast as a filter applied to the noise signal. This filter is computed for a number of different types of evoked potential experiments in which various weighting factors and stochastic stimulation times are allowed. Although the variance in noise level estimates can be large, there is a general trend for noise reduction to occur more slowly than the expected 1/N when the total time over which averaging occurs is small in comparison to the correlation time of the noise. When the total averaging time exceeds the temporal extent of the autocorrelation function, the expected 1/N behavior is observed.

Physiologic study of pressure point techniques used in the martial arts.

BACKGROUND: Study physiologic changes occurring during "knockouts" produced by application of pressure point techniques during martial arts demonstrations. EXPERIMENTAL DESIGN: prospective analysis of physiologic variables during and immediately following an acute event. SETTING: martial arts demonstration carried out at a medical center hospital. SUBJECTS: 12 normal volunteers participating in a martial arts demonstration. INTERVENTIONS: application of various pressure point techniques that have been observed to produce states of unresponsiveness in volunteers. MEASURES: continuous ECG and video/EEG monitoring with measurements of blood pressure and oxygen saturation. Qualitative analysis of EEG and ECG recordings and quantitative comparison of heart rate, blood pressure, and oxygen saturation measurements before during and after the period of induced unconsciousness. RESULTS: No significant changes in blood pressure, oxygen saturation, cardiac rate or rhythm, or electroencephalogram are noted during the knockouts produced by application of pressure point techniques. There was only variable inability for subjects to remember words spoken to them during the episode of apparent unresponsiveness. CONCLUSIONS: The mechanism for the state of unresponsiveness produced by application of pressure point techniques is not related to a significant cardiac or pulmonary process. There is no evidence of reduced cerebral blood flow during this time or of other dangerous physiologic changes. The exact mechanism for this phenomenon remains uncertain.

Paradoxical response to valproic acid in a patient with a hypothalamic hamartoma.

OBJECTIVE: To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy. CASE SUMMARY: A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital. DISCUSSION: Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.

Strategies for minimizing 60 Hz pickup during evoked potential recording.

Electrical interference at mains power supply frequency can adversely affect the recording of evoked potentials and can be especially destructive in an operating room setting. We investigated 60 Hz interference in electrode cables running from subject to preamplifier and further examined methods to eliminate such interference. We conclude that braiding electrode wires is highly efficacious in such interference reduction, presumably by reducing the magnetic flux enclosed by the wires. We further indicate that the use of flexible metal hose fabricated from Permalloy 80 may effect further interference reduction.

Viral encephalitis masquerading as a fulminant anticholinergic toxidrome.

CASE REPORT: Emergency physicians are well versed in the recognition and management of certain poisonings which present with characteristic toxidromes. We present a case of a young pharmacy student who presented with altered mental status, tachycardia, facial flushing, dilated pupils, and dry skin and mucous membranes presumably due to anticholinergic poisoning. She improved with a combination of benzodiazepines and the acetylcholinesterase inhibitor physostigmine. However, following resolution of her initial symptoms, she became ill again and the subsequent neurologic evaluation revealed a diencephalic lesion consistent with a viral encephalitis. The acute anticholinergic signs and symptoms resulted from this lesion in an area of large cholinergic outflow. Although recognition and management of her acute anticholinergic findings were appropriate, they were not the manifestations of an acute anticholinergic ingestion.

Vascular transit times in calcarine cortex: kinetic analysis of R2* changes observed using localized 1H spectroscopy.

A kinetic analysis of water signal intensity changes measured in human visual cortex by PRESS localized 1H spectroscopy at 500 ms resolution with light-emitting diode (LED) goggle stimulation was used to determine vascular transit times for transitions between rest and activation. Monoexponential curve fitting was used to determine both R2* values for each free induction decay and the time constants for R2* changes with activation and deactivation. Measured transit time values were in general agreement with the literature, and were significantly shorter for "Off-->On" than for "On-->Off" transitions, consistent with known alterations in blood flow with activation and deactivation. The differences in transit times between "Off-->On" and "On-->Off" also varied with stimulus frequency in accordance with known physiology. This type of analysis may provide a useful means of analyzing functional activation data and for quantitatively comparing functional activation results from differing subjects and imaging sessions.

Neurophysiologic effects of retrograde cerebral perfusion used for aortic reconstruction.

OBJECTIVE: The results of neurophysiologic monitoring using somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were analyzed to determine if retrograde cerebral perfusion (RCP) supported central nervous system electrical function during surgery that required temporary interruption of antegrade cerebral perfusion (IACP). DESIGN: A prospective, observational study. SETTING: A university hospital. PARTICIPANTS: Fifteen adult patients who underwent aortic reconstruction using RCP and three patients who underwent thoracic aortic operations using hypothermic circulatory arrest without RCP. INTERVENTIONS: SSEPs and EEG were monitored continuously throughout the operation. Regression analysis was performed to determine the factors that affected the rate of decrease in SSEP amplitudes during IACP and the time required for SSEP and EEG activity to recover after antegrade cerebral perfusion (ACP) was restored. MEASUREMENTS AND MAIN RESULTS: The amplitude of SSEPs that were elicited decreased over time after IACP. The mean +/- standard deviation (SD) time required for the brachial plexus (Erb's point), cervicomedullary junction (N13), and brainstem (N18) SSEPs to decrease to 0.5 of their original amplitude after IACP were 30 +/- 2, 19 +/- 2, and 16 +/- 2 minutes, respectively. The rate of decrease in the N18 SSEP amplitude after IACP correlated positively to the fraction of no-flow time (p = 0.01). CONCLUSION: RCP attenuated the rate of decay in SSEP amplitudes during IACP. This suggested that RCP had a measurable physiologic effect on central nervous system function and may increase the time that ACP can be safely interrupted.