Lower-extremity Dynamometry as a Novel Outcome Measure in a Double-blind, Placebo-controlled, Feasibility Trial of Intravenous Immunoglobulin (IVIG) for HIV-associated Myelopathy.

Objective: Open-label data suggest that intravenous immunoglobulin (IVIG) might improve lower-extremity strength in human immunodeficiency virus (HIV)-associated myelopathy (HIVM), a rare but debilitating neurologic complication of HIV. We sought to determine the feasibility of testing the efficacy of IVIG for HIVM more rigorously. Design: We conducted a randomized, double-blind, placebo-controlled feasibility trial of IVIG for HIVM, using dynamometry as an outcome measure (Clinical Trial No. NCT01561755). Setting: The study took place in an academic medical center in New York, New York Participants: Only 12 participants were enrolled in four years; critical impediments to the study were the rarity of patients with new HIVM diagnoses and prior exposure to IVIG in patients with an established diagnosis. Measurements: Dynamometry of hip flexion, knee flexion, and ankle dorsiflexion were measured; the HIV Dementia Motor Score (HDMS); and the two-minute timed walk test were utilized. Results: Recruitment was the major feasibility issue. Dynamometry was generally well-tolerated, had good test-retest reliability (r=0.71-0.86, p<0.02 for all muscle groups), and good inter-item reliability as judged by the correlations between the muscle groups (r=0.76-0.81, p=0.001-0.005). Dynamometry was valid and clinically meaningful based on its correlations with the HDMS and the two-minute timed walk test. Conclusion: We conclude that an adequately powered clinical trial of IVIG for HIVM would likely require a prolonged recruitment period and multiple participating sites. Lower limb dynamometry is a useful outcome measure for HIVM, which might also be useful in other HIV-related gait disorders.

Coupled Bimanual Training Using a Non-Powered Device for Individuals with Severe Hemiparesis: A Pilot Study.

BACKGROUND: Few options exist for training arm movements in participants with severe post-stroke hemiparesis who have little active range of motion. The purpose of this study was to test the safety and feasibility of training with a non-powered device, the Bimanual Arm Trainer (BAT), to facilitate motor recovery in individuals with severe hemiparesis. The BAT enabled coupled bimanual training of shoulder external rotation, which is reduced in individuals with severe post-stroke hemiplegia. The rationale for bimanual training was to harness contralesional cortical activity to drive voluntary movement in the affected arm in patients who could barely perform unimanual movements. METHODS: Nine participants with post-stroke hemiparesis, preserved passive range of motion and Modified Ashworth score of <3 in the shoulder and elbow joints, trained with the device for 45 minutes, twice a week for six weeks, and were assessed pre- and post-training. RESULTS: All participants tolerated the training and no adverse events were reported. Participants showed significant improvement in the upper extremity Fugl-Meyer score post-training with an effect size of 0.89. Changes in the flexor synergy pattern accounted for 64.7% of the improvement. Improvement in active range of motion in the paretic limb occurred for both trained and untrained movements. Some participants showed improvement in the time taken to perform selected tasks on the Wolf Motor Function Test post-training. CONCLUSION: The results demonstrate the safety and feasibility of using the Bimanual Arm Trainer to facilitate motor recovery in individuals with severe hemiparesis.

Contribution of Step Length to Increase Walking and Turning Speed as a Marker of Parkinson's Disease Progression.

When increasing ambulation speed in Parkinson's disease, step cadence increases more than stride length, indicating movement scaling difficulties that affect step generation in particular. We investigated whether step length variation when increasing ambulation speed was related to disease progression. Patients with Parkinson's disease (N = 39) and controls (N = 152) performed two timed ambulation tasks: at a 'free' (self-selected) pace and then at 'maximal' speed. The total number of steps (including during turns) and time to complete the task were clinically measured. The relative contribution of step length and cadence to increased ambulation speed was determined using two methods: the ratios of change in step length or in cadence to the change in ambulation speed, and the step length index. While the relative contribution of step length and cadence to increased ambulation speed was independent of age in both control and patient groups, in Parkinson's disease there was a negative correlation between time from diagnosis and the ratio of change in step length to change in ambulation speed (R = 0.54; p = 0.0004) and the step length index (R = 0.56, p = 0.0002). In parallel, there was a positive correlation between time since diagnosis and the ratio of change in cadence to change in ambulation speed (R = 0.57; p = 0.0002). The relative contribution of step length and cadence to increased ambulation speed is age invariant but a marker of Parkinson's disease advancement, and can be easily determined in the clinical setting.

Endovascular coil embolization of segmental arteries prevents paraplegia after subsequent thoracoabdominal aneurysm repair: an experimental model.

OBJECTIVES: To test a strategy for minimizing ischemic spinal cord injury after extensive thoracoabdominal aneurysm (TAAA) repair, we occluded a small number of segmental arteries (SAs) endovascularly 1 week before simulated aneurysm repair in an experimental model. METHODS: Thirty juvenile Yorkshire pigs (25.2 ± 1.7 kg) were randomized into 3 groups. All SAs, both intercostal and lumbar, were killed by a combination of surgical ligation of the lumbar SAs and occlusion of intercostal SAs with thoracic endovascular stent grafting. Seven to 10 days before this simulated TAAA replacement, SAs in the lower thoracic/upper lumbar region were occluded using embolization coils: 1.5 ± 0.5 SAs in group 1 (T13/L1), and 4.5 ± 0.5 SAs in group 2 (T11-L3). No SAs were coiled in the controls. Hind limb function was evaluated blindly from daily videotapes using a modified Tarlov score (0 = paraplegia, 9 = full recovery). After death, each segment of spinal cord was graded histologically using the 9-point Kleinman score (0 = normal, 8 = complete necrosis). RESULTS: Hind limb function remained normal after coil embolization. After simulated TAAA repair, paraplegia occurred in 6 of 10 control pigs, but in only 2 of 10 pigs in group 1; no pigs in group 2 had a spinal cord injury. Tarlov scores were significantly better in group 2 (control vs group 1, P = .06; control vs group 2, P = .0002; group 1 vs group 2, P = .05). A dramatic reduction in histologic damage, most prominently in the coiled region, was seen when SAs were embolized before simulated TAAA repair. CONCLUSIONS: Endovascular coiling of 2 to 4 SAs prevented paraplegia in an experimental model of extensive hybrid TAAA repair, and helped protect the spinal cord from ischemic histopathologic injury. A clinical trial in a selected patient population at high risk for postoperative spinal cord injury may be appropriate.

Spastic cocontraction in hemiparesis: effects of botulinum toxin.

INTRODUCTION: In this study of spastic hemiparesis we evaluated cocontraction during sustained agonist/antagonist efforts, before and after botulinum toxin (BoNT) injection in 1 agonist. METHODS: Nineteen hemiparetic subjects performed maximal isometric elbow flexion/extension efforts with the elbow at 100° (extensors stretched). Using flexor and extensor surface electromyography we calculated agonist recruitment/cocontraction indices from 500-ms peak voluntary agonist recruitment, before and 1 month after onabotulinumtoxinA injection (160 U) into biceps brachii. RESULTS: Before injection, agonist recruitment and cocontraction indices were higher in extensors than flexors [0.74 ± 0.15 vs. 0.59 ± 0.10 (P < 0.01) and 0.43 ± 0.25 vs. 0.25 ± 0.13 (P < 0.05), respectively]. Biceps injection decreased extensor cocontraction index (-35%, P < 0.05) while increasing flexor agonist recruitment and cocontraction indices. CONCLUSIONS: In spastic hemiparesis, stretch may facilitate agonist recruitment and spastic cocontraction. In the non-injected antagonist, cocontraction may be reduced by enhanced reciprocal inhibition from a more relaxed, and therefore stretched, agonist, or through decreased recurrent inhibition from the injected muscle.

Evolving compartment syndrome detected by loss of somatosensory- and motor-evoked potential signals during cervical spine surgery.

Neurologic injury is a rare but devastating complication of spinal surgery that can result in mild sensory to severe motor deficits. Surgeons increasingly use electrophysiological spinal cord function monitoring, including somatosensory- and motor-evoked potentials, intraoperatively to provide information about spinal cord function, aid in surgical decision making, improve outcomes, and reduce complication rates. By providing real-time information about the dorsal and anterior motor column function, somatosensory- and motor-evoked potentials signals allow surgeons to reverse noticeable changes and avoid devastating neurologic injuries. Recognizing changes in baseline signals in the setting of known risk factors enables surgeons to correct these risks. This article describes a case in which somatosensory- and motor-evoked potentials monitoring were lost in the setting of an impending right forearm compartment syndrome during 2-level anterior cervical diskectomy and fusion. To the authors' knowledge, this is the first reported case of spinal cord monitoring detecting an evolving compartment syndrome during cervical spine surgery. The early changes in signal intensity enabled the surgeon to search for a cause and remedy the situation by removing the infiltrated intravenous line. Without the observed changes in somatosensory- and motor-evoked potentials, it is likely that the compartment syndrome may have progressed to the point of requiring fasciotomy to prevent lasting neuromuscular injury. This article describes a new cause of changes in electrophysiological monitoring and further displays the usefulness of somatosensory- and motor-evoked potentials monitoring during even routine spinal surgery.

Pallidal deep brain stimulation for DYT6 dystonia.

BACKGROUND: Mutations of the THAP1 gene were recently shown to underlie DYT6 torsion dystonia. Little is known about the response of this dystonia subtype to deep brain stimulation (DBS) at the internal globus pallidus (GPi). METHODS: Retrospective analysis of the medical records of three DYT6 patients who underwent pallidal DBS by one surgical team. The Burke-Fahn-Marsden Dystonia Rating scale served as the primary outcome measure. Comparison is made to 23 patients with DYT1 dystonia also treated with GPi-DBS by the same team. RESULTS: In contrast with the DYT1 patients who exhibited a robust and sustained clinical response to DBS, the DYT6 patients exhibited more modest gains during the first 2 years of therapy, and some symptom regression between years 2 and 3 despite adjustments to the stimulation parameters and repositioning of one stimulating lead. Microelectrode recordings made during the DBS procedures demonstrated no differences in the firing patterns of GPi neurons from DYT1 and DYT6 patients. DISCUSSION: Discovery of the genetic mutations responsible for the DYT6 phenotype allows for screening and analysis of a new homogeneous group of dystonia patients. DYT6 patients appear to respond less robustly to GPi-DBS than their DYT1 counterparts, most likely reflecting differences in the underlying pathophysiology of these distinct genetic disorders. CONCLUSIONS: While early results of pallidal DBS for DYT6 dystonia are encouraging, further research and additional subjects are needed both to optimise stimulation parameters for this population and to elucidate more accurately their response to surgical treatment.

Fiducial registration with spoiled gradient-echo magnetic resonance imaging enhances the accuracy of subthalamic nucleus targeting.

BACKGROUND: A variety of imaging strategies may be used to derive reliable stereotactic coordinates when performing deep brain stimulation lead implants. No single technique has yet proved optimal. OBJECTIVE: To compare the relative accuracy of stereotactic coordinates for the subthalamic nucleus (STN) derived either from fast spin echo/inversion recovery (FSE/IR) magnetic resonance imaging MRI alone (group 1) or FSE/IR in conjunction with T1-weighted spoiled gradient-echo MRI (group 2). METHODS: A retrospective analysis of 145 consecutive STN deep brain stimulation lead placements (group 1, n = 72; group 2, n = 73) was performed in 81 Parkinson disease patients by 1 surgical team. From the operative reports, we recorded the number of microelectrode recording trajectories required to localize the desired STN target and the span of STN traversed along the implantation trajectory. In addition, we calculated the 3-dimensional vector difference between the initial MRI-derived coordinates and the final physiologically refined coordinates. RESULTS: The proportion of implants completed with just 1 microelectrode recording trajectory was greater (81% vs 58%; P < .001) and the 3-dimensional vector difference between the anatomically selected target and the microelectrode recording-refined target was smaller (0.6 ± 1.2 vs 0.9 ± 1.3; P = .04) in group 2 than in group 1. At the same time, the mean expanse of STN recorded along the implantation trajectory was 8% greater in group 2 (4.8 ± 0.6 vs 5.2 ± 0.6 mm; P < .001). CONCLUSION: A combination of stereotactic FSE/IR and spoiled gradient-echo MRI yields more accurate coordinates for the STN than FSE/IR MRI alone.

Transgressing the ventricular wall during subthalamic deep brain stimulation surgery for Parkinson disease increases the risk of adverse neurological sequelae.

BACKGROUND: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) is an effective treatment for the motor manifestations of advanced medically refractory Parkinson disease. Because of the medial location of the target, surgical trajectories to the STN may violate the ipsilateral lateral ventricle. OBJECTIVE: To determine whether violating the ventricle during STN DBS surgery is associated with postoperative confusion. METHODS: A retrospective chart review of all STN implantation procedures for Parkinson disease performed by 1 surgeon between January 2005 and September 2008 was performed. Postoperative magnetic resonance imaging was performed in all cases, and each scan was reviewed for evidence of ventricular wall violation. All charts were reviewed for postoperative confusion and/or increased length of hospital stay. RESULTS: A total of 145 leads were implanted in 81 patients over 102 admissions. Forty-three patients underwent contemporaneous bilateral lead implantation; 23 underwent unilateral implantation; and 18 underwent staged bilateral implantation. The cases of 8 patients were complicated by postoperative confusion and increased length of stay. Sixteen magnetic resonance imaging scans demonstrated evidence of ventricular wall violation including all 8 patients with postoperative confusion. The relative risk of having postoperative confusion after traversing the ventricle is 87 (P < .001). CONCLUSION: Violating the ventricular system during STN DBS surgery correlated significantly with postoperative altered mental status and subsequent increased length of hospital stay. This finding may explain why cognitive complications are observed more frequently in Parkinson disease patients undergoing DBS at the STN compared with the internal globus pallidus.

Pallidal deep brain stimulation for primary dystonia in children.

BACKGROUND: Deep brain stimulation (DBS) at the internal globus pallidus (GPi) has replaced ablative procedures for the treatment of primary generalized dystonia (PGD) because it is adjustable, reversible, and yields robust clinical improvement that appears to be long lasting. OBJECTIVE: To describe the long-term responses to pallidal DBS of a consecutive series of 22 pediatric patients with PGD. METHODS: Retrospective chart review of 22 consecutive PGD patients, ≤21 years of age treated by one DBS team over an 8-year period. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate symptom severity and functional disability, pre- and post-operatively. Adverse events and medication changes were also noted. RESULTS: The median follow-up was 2 years (range, 1-8 years). All 22 patients reached 1-year follow-up; 14 reached 2 years, and 11 reached 3 years. The BFMDRS motor subscores were improved 84%, 93%, and 94% (median) at these time points. These motor responses were matched by equivalent improvements in function, and the response to DBS resulted in significant reductions in oral and intrathecal medication requirements after 12 and 24 months of stimulation. There were no hemorrhages or neurological complications related to surgery and no adverse effects from stimulation. Significant hardware-related complications were noted, in particular, infection (14%), which delayed clinical improvement. CONCLUSION: Pallidal DBS is a safe and effective treatment for PGD in patients <21 years of age. The improvement appears durable. Improvement in device design should reduce hardware-related complications over time.

Patient characteristics and anesthetic technique are additive but not synergistic predictors of successful motor evoked potential monitoring.

BACKGROUND: Spinal cord monitoring is associated with a significantly lower rate of neurologic deficits after deformity surgery, and has been shown to have predictive value in cervical, thoracic, and lumbar surgery. Lower extremity motor evoked potentials (MEPs) are particularly sensitive to anesthetics and physiologic change, and can be difficult to obtain at baseline. The anesthesiologist is often required to modify the maintenance anesthetic to facilitate signal attainment. Although intuitive, the predictive significance of increasing age, body mass index (BMI), presence of diabetes and/or hypertension, surgical procedure, and anesthetic technique has not been well delineated. METHODS: We conducted a retrospective chart review of the anesthetic records of all patients who underwent spine surgery and MEP monitoring of the lower extremities from August 1, 2001 to December 31, 2005. Patients with preexisting paralysis of the lower extremities were excluded. Univariate analysis was performed to examine the distribution of diabetes, hypertension, anesthesia technique, age, gender, BMI, and surgical procedure. The chi(2) test and the 2-sample t test were used to test associations between MEP status and potential risk factors. Cochran-Armitage test was used to analyze trends in BMI and age by quartile. The effects of diabetes and hypertension, compared with patients with neither, were presented for each anesthetic technique. Bivariate analysis of the data was performed to analyze a potentially synergistic deleterious effect of diabetes, hypertension, and anesthetic technique using the Breslow-Day test for homogeneity of the odds ratios. Logistic regression analysis through stepwise selection was performed to form a model of the data. RESULTS: Two hundred fifty-six charts were reviewed. The univariate analysis showed that diabetes, hypertension, anesthesia technique, age, and BMI were significantly associated with failure to obtain MEP signals. None of the variables were found to have a synergistic effect on MEP signal attainment in the bivariate analysis. Hypertension, diabetes, and anesthetic technique were independent factors for MEP failure and their joint effects were additive not synergistic. CONCLUSIONS: Diabetes, hypertension, and anesthetic technique were the most important patient risk factors associated with failure to obtain lower extremity MEP signals. These results will improve anesthesiologists' ability to tailor anesthetic regimen to patient comorbidity when MEP monitoring is planned.

Botulinum toxin dilution and endplate targeting in spasticity: a double-blind controlled study.

OBJECTIVE: To determine the effects of botulinum neurotoxin type A (BTX-A) dilution and endplate-targeting in spastic elbow flexors. DESIGN: Double blind randomized controlled trial; 4-month follow-up after a 160-unit injection of BTX-A into spastic biceps brachii (4 sites). Randomization into: group 1: 100 mouse units (MU)/mL dilution, 0.4cc/site, 4-quadrant injection; group 2: 100MU/mL dilution, 0.4cc/site, 4 sites along endplate band; group 3: 20MU/mL dilution, 2cc/site, 4-quadrant injection (n=7 per group). SETTING: Institutional tertiary care ambulatory clinic. PARTICIPANTS: Referred sample of 21 adults with spastic hemiparesis. No participant withdrew due to adverse effects. INTERVENTION: A 160-unit injection of BTX-A of different dilutions and locations into biceps brachii. MAIN OUTCOME MEASURES: Primary: agonist and antagonist (cocontraction) mean rectified voltage (MRV) of elbow flexors/extensors during maximal isometric flexion/extension; secondary: maximal voluntary power of elbow flexion/extension; spasticity angle and grade in elbow flexors/extensors (Tardieu Scale); active range of elbow extension/flexion. RESULTS: BTX-A injection overall reduced agonist flexor MRV (-47.5%, P<0.0001), antagonist flexor MRV (-12%, P=.037), antagonist extensor MRV (-19%, P<.01), flexion maximal voluntary power (-33%, P<.001), elbow flexor spasticity angle (-30%, P<.001) and grade (-17%, P=.03), and increased extension maximal voluntary power (24%, P=.037) and active range of elbow extension (5.5%, 8 degrees , P=.002). Agonist and antagonist flexor MRV reductions in group 3 (-81% and -31%) were greater than in groups 1 and 2, whereas increase in active range of elbow extension was greater in group 2 (10%) than in groups 1 and 3 (P<.05, analysis of covariance [ANCOVA]). Elbow flexor spasticity was significantly reduced in groups 2 and 3 only (P<.05, ANCOVA). CONCLUSIONS: In spastic biceps, high-volume or endplate-targeted BTX-A injections achieve greater neuromuscular blockade, cocontraction and spasticity reduction, and active range of elbow extension improvement, than low volume, nontargeted injections.

Spinal cord blood flow and ischemic injury after experimental sacrifice of thoracic and abdominal segmental arteries.

OBJECTIVE: Spinal cord blood flow (SCBF) after sacrifice of thoracoabdominal aortic segmental arteries (TAASA) during thoracoabdominal aortic aneurysm (TAAA) repair remains poorly understood. This study explored SCBF for 72 h after sacrifice of all TAASA. METHODS: Fourteen juvenile Yorkshire pigs underwent complete serial TAASA sacrifice (T4-L5). Six control pigs underwent anesthesia and cooling to 32 degrees C with no TAASA sacrifice. In the experimental animals, spinal cord function was continuously monitored using motor evoked potentials (MEPs) until 1h after clamping the last TAASA. Fluorescent microspheres enabled segmental measurement of SCBF along the entire spinal cord before, and 5 min, 1 h, 5 h, 24 h and 72 h after complete TAASA sacrifice. A modified Tarlov score was obtained for 3 days after surgery. RESULTS: All the pigs with complete TAASA sacrifice retained normal cord function (MEP) until 1h after TAASA ligation. Seven pigs (50%) with complete TAASA sacrifice recovered after 72 h; seven pigs suffered paraparesis or paraplegia. Intraoperatively, and until 1h postoperatively, SCBF was similar among the three groups along the entire cord. Postoperatively, SCBF did not decrease in any group, but significant hyperemia occurred at 5h in controls and recovery animals, but did not occur in pigs that developed paraparesis or paraplegia in the T8-L2 segments (p=0.0002) and L3-S segments (p=0.0007). At 24h, SCBF remained marginally lower from T8 caudally; at 72h, SCBF was similar among all groups along the entire cord. SCBF in the segments T8-L2 at 5h predicted functional recovery (p=0.003). CONCLUSIONS: This study suggests that critical spinal cord ischemia after complete TAASA sacrifice does not occur immediately (intraoperatively), but is delayed 1-5h or longer after clamping, and represents failure to mount a hyperemic response to rewarming and awakening. The short duration of low SCBF associated with spinal cord injury suggests that hemodynamic and metabolic manipulation lasting only 24-72 h may allow routine preservation of normal cord function despite sacrifice of all TAASA secondary to surgical or endovascular repair of large TAAA.

Optimizing selective cerebral perfusion: deleterious effects of high perfusion pressures.

OBJECTIVE: Selective cerebral perfusion is a proven adjunct to hypothermia for neuroprotection in complex aortic surgery. The ideal conditions for the provision of selective cerebral perfusion, however, including optimal perfusion pressure, remain unknown. We investigated the effects of various perfusion pressures during selective cerebral perfusion on cerebral physiology and outcome in a long-term porcine model. METHODS: Thirty piglets (26.3 +/- 1.4 kg), cooled to 20 degrees C on cardiopulmonary bypass with alpha-stat pH management (mean hematocrit 23.6%), were randomly assigned to 90 minutes of selective cerebral perfusion at a pressure of 50 (group A), 70 (group B), or 90 (group C) mm Hg. With fluorescent microspheres and sagittal sinus sampling, cerebral blood flow and cerebral oxygen metabolism were assessed at baseline, after cooling, at two points during selective cerebral perfusion, and for 2 hours after cardiopulmonary bypass. Visual evoked potentials were monitored during recovery. Neurobehavioral scores were assessed blindly from standardized videotaped sessions for 7 postoperative days. RESULTS: Cerebral blood flow during selective cerebral perfusion was significantly increased by higher-pressure perfusion (P = .04), although all groups sustained similar levels of cerebral oxygen metabolism during selective cerebral perfusion (P = .88). After the end of cardiopulmonary bypass, the cerebral oxygen metabolism increased to above baseline in all groups, with the highest levels seen in group C (P = .06). Intracranial pressure was significantly higher during selective cerebral perfusion in group C (P = .0002); visual evoked potentials did not differ among groups. Neurobehavioral scores were significantly better in group A (P = .0002). CONCLUSION: Selective cerebral perfusion at 50 mm Hg provides neuroprotection superior to that at higher pressures. The increased cerebral blood flow with higher-pressure selective cerebral perfusion is associated with cerebral injury, reflected by high post-cardiopulmonary bypass cerebral oxygen metabolism and poorer neurobehavioral recovery.

Perfusing the cold brain: optimal neuroprotection for aortic surgery.

BACKGROUND: Selective cerebral perfusion (SCP) may enhance the neuroprotective benefits of hypothermia during aortic surgery. However, despite its widespread adoption, there is no consensus regarding optimal implementation of SCP. We used a survival porcine model to explore the physiologic characteristics and behavioral benefits of various protocols involving hypothermic circulatory arrest (HCA) and SCP. METHODS: Thirty pigs (26.3 +/- 1.4 kg), cooled to 15 degrees C on cardiopulmonary bypass, using alpha-stat pH management (mean hematocrit 30%), were randomly allocated to differing brain protection strategies: 90 minutes of HCA (group A); 30 minutes of HCA, then 60 minutes of SCP (group B); or 90 minutes of SCP (group C). Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF [mL x 100g(-1) x min(-1)]) and cerebral metabolic rate for oxygen (CMRO2 [mL x 100g(-1) x min(-1)]) were assessed at baseline, after cooling, during SCP (where applicable), and for 2 hours after cardiopulmonary bypass. Neurobehavioral scores were assessed blindly from standardized videotaped sessions for 7 days postoperatively. RESULTS: Cerebral blood flow was significantly higher (p = 0.0001) during SCP (60 and 90 minutes) if preceded by HCA. The CMRO2 was also significantly higher in group B versus group C (p = 0.016) at 60 minutes. The CMRO2 in all three groups rebounded promptly toward baseline after weaning from cardiopulmonary bypass. Postoperative neurobehavioral scores were significantly worse in group A. CONCLUSIONS: Continuous SCP provides the best brain protection overall. However, an initial period of HCA does not seem to impair late outcome; perhaps the elevated CBF and CMRO2 observed reflect a beneficial cerebral response to a recoverable insult. Clearly, 90 minutes of HCA induces permanent brain injury, even in this carefully controlled setting.

Preservation of spinal cord function after extensive segmental artery sacrifice: regional variations in perfusion.

BACKGROUND: Sacrifice of intercostal and lumbar arteries simplifies thoracoabdominal aneurysm surgery and enables endovascular stenting. Little is known about alterations in cord perfusion after extensive segmental artery sacrifice. We explored this question using hypothermia to reduce metabolism. METHODS: Twelve juvenile Yorkshire pigs (mean weight, 22.3 kg) were randomized to segmental artery sacrifice at 32 degrees C or 37 degrees C. Cord integrity was assessed with myogenic-evoked potential (MEP) monitoring. Stepwise craniocaudal sacrifice of segmental arteries was continued until MEP diminution occurred; the last segmental artery was then reopened. Fluorescent microspheres were used to measure spinal cord blood flow (SCBF) at baseline, 5 minutes, 1 hour, and 3 hours after segmental artery sacrifice. Hind limb function was monitored for 5 days. RESULTS: All animals recovered normal hind limb function. At 32 degrees C, more segmental arteries, 16.5 versus 15 (p = 0.03), could be sacrificed without MEP loss. Baseline SCBF at 32 degrees C was 50% that at 37 degrees C (p = 0.003) and remained fairly stable throughout. At 37 degrees C, SCBF to the craniocaudal extremes of the cord (C1 to T3 and L2 to L6) increased markedly (p = 0.01) at 1 hour and returned toward normal at 3 hours. Concomitantly, SCBF fell in the middle portion of the cord (T9 to T13) at 1 hour before returning to normal at 3 hours. CONCLUSIONS: Almost all segmental arteries can be sacrificed with preservation of spinal cord function. No major change occurs in the central cord in normothermic animals, but there is significant transient hyperemia in segments adjacent to extrasegmental vessels. Hypothermia reduces SCBF and abolishes this possible steal phenomenon. Metabolic and hemodynamic manipulation should enable routine sacrifice of all segmental arteries without spinal cord injury.

Avoidance of hemodilution during selective cerebral perfusion enhances neurobehavioral outcome in a survival porcine model.

INTRODUCTION: The ideal hematocrit (HCT) level during hypothermic selective cerebral perfusion (SCP)--to ensure adequate oxygen delivery without excessive perfusion--has not yet been determined. METHODS: Twenty pigs (26.0+/-2.6 kg) were randomized to low or high HCT management. The cardiopulmonary bypass (CPB) circuit was primed with crystalloid in the low HCT group (21+/-1%), and with donor blood in the high HCT group (30+/-1%). Pigs were cooled to 20 degrees C and SCP was carried out for 90 min. During rewarming, whole blood was added in the low HCT group and crystalloid in the high HCT group to produce equivalent HCT levels by the end of the procedure. Using fluorescent microspheres and sagittal sinus sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at baseline, after cooling, at two points during SCP (30 and 90 min), and at 15 min and 2 h post-CPB. In addition, a range of physiological and metabolic parameters, including intracranial pressure (ICP), were recorded throughout the procedure. The animals' behavior was videotaped and assessed blindly for 7 days postoperatively (maximum score=5). RESULTS: HCT levels were equivalent at baseline, 2 h post-CPB, and at sacrifice, but significantly different (p<0.0001) during cooling and SCP. Mean arterial pressure, pH and pCO2, and CMRO2 were equivalent between groups throughout. ICP was similar in the two groups throughout cooling, SCP, and rewarming, but was significantly higher in the low HCT animals after the termination of CPB. CBF was similar at baseline, but thereafter markedly higher in the low HCT group. Neurobehavioral performance was significantly better in the high HCT animals (median score 3.5 vs 4.5 on day 3, and 4.5 vs 4.75 on day 7, p=0.003). CONCLUSIONS: Higher HCT levels for SCP produced a significantly superior functional outcome, suggesting that the higher CBF with a lower HCT may be injurious, possibly because of an increased embolic load.

Spinal cord perfusion after extensive segmental artery sacrifice: can paraplegia be prevented?

OBJECTIVE: Understanding the ability of the paraspinal anastomotic network to provide adequate spinal cord perfusion pressure (SCPP) critical for both surgical and endovascular repair of thoracoabdominal aortic aneurysms (TAAA). METHODS: To monitor pressure in the collateral circulation, a catheter was inserted into the distal end of the divided first lumbar segmental artery (SA) of 10 juvenile Yorkshire pigs (28.9+/-3.8kg). SA pairs from T3 through L5 were serially sacrificed at 32 degrees C; SCPP and function - using motor-evoked potentials (MEPs) - were continuously monitored until 1h after clamping the last SA. Intermittent aortic and SCPP monitoring was continued for 5 days postoperatively, along with evaluation of motor function. RESULTS: A mean of 14.4+/-0.7 SAs were sacrificed without loss of MEP. SCPP (mmHg) dropped from 68+/-7 before SA clamping (77% of aortic pressure) to 22+/-6 at end clamping, and 21+/-4 after 1h, reaching its lowest point - 19+/-4 - after 5h. Postoperatively, SCPP recovered to 33+/-6 at 24h; 42+/-10 at 48h; 56+/-14 at 72h; 62+/-15 at 96h, returning to baseline (63+/-20) at 120h. Despite comparable SCPP patterns, four pigs did not fully regain the ability to stand. Six animals recovered: two could stand and four could walk. CONCLUSIONS: Interruption of all SAs at 32 degrees C in this pig model results in a spectrum of cord injury, with normal function in a majority of pigs postoperatively. The short duration of low SCPP suggests that hemodynamic manipulation lasting only 24-48h may allow routine complete preservation of normal cord function despite sacrifice of all SAs.