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.

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.

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.

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.

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.

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.

Optimal temperature for selective cerebral perfusion.

OBJECTIVE: Although combinations of hypothermic circulatory arrest and antegrade selective cerebral perfusion are used for cerebral protection during arch surgery, there is no consensus regarding the optimal temperature during selective cerebral perfusion. This study explored the effect of different temperatures during selective cerebral perfusion on cerebral metabolism and neurologic outcome. METHODS: In this blinded study, 40 pigs (19-21 kg) were randomized into 4 groups after 30 minutes of hypothermic circulatory arrest at 20 degrees C. During a 60-minute interval of selective cerebral perfusion, with flow regulated to maintain a perfusion pressure of 50 mm Hg, pigs were perfused at 10 degrees C, 15 degrees C, 20 degrees C, and 25 degrees C. Fluorescent microspheres enabled calculation of cerebral blood flow during perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular resistance, and oxygen consumption were also monitored. Behavioral scores were obtained for 7 days after surgery. RESULTS: Cerebral blood flow decreased significantly ( P < .002) during cooling in all groups: it was significantly higher throughout selective cerebral perfusion in the 20 degrees C to 25 degrees C versus the 10 degrees C to 15 degrees C group ( P = .0001) and remained higher during recovery ( P = .0001). Oxygen consumption decreased significantly with cooling ( P = .0001), remained low during perfusion, and rebounded with rewarming but was significantly lower at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C throughout selective cerebral perfusion ( P = .003) and after CPB was discontinued ( P = .001). Postoperative behavioral scores were significantly better after selective cerebral perfusion at 10 degrees C to 15 degrees C than at 20 degrees C to 25 degrees C ( P = .001). CONCLUSIONS: This study suggests that selective cerebral perfusion at 10 degrees C to 15 degrees C provides better cerebral protection than selective cerebral perfusion at 20 degrees C to 25 degrees C, even though oxygen consumption remains low for hours after selective cerebral perfusion at 10 degrees C to 15 degrees C. Prompt return of metabolism to baseline levels after hypothermic circulatory arrest/selective cerebral perfusion does not necessarily predict superior behavioral outcome.

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.

Cooling to 10 degrees C and treatment with Cyclosporine A improve cerebral recovery following prolonged hypothermic circulatory arrest in a chronic porcine model.

OBJECTIVE: This study was undertaken to assess whether cooling to 10 degrees C and/or treatment with Cyclosporine A (CsA) can reduce neurological injury during prolonged hypothermic circulatory arrest (HCA) in a chronic animal model. METHODS: In this blinded study, 24 pigs (20-23 kg) were randomized to HCA for 90 min at 20 degrees C (n=8), at 10 degrees C (n=8), or at 10 degrees C with 5 mg/kg CsA (n=8). CsA (or placebo) were given intravenously before and for 3 days after HCA. Hemodynamics and neurophysiological data were monitored periodically throughout the experiment and for 3 h after HCA, as well as intracranial pressure (ICP), which has been shown to correlate with outcome. Daily neurological/behavioral evaluation (mental status, coordination and appetite; 12=normal and 0=coma or death) was carried out until sacrifice on postoperative day (POD) 3. RESULTS: Overall survival rate was 83.3%: one 20 degrees C control, two 10 degrees C controls, and one 10 degrees C/CsA pig died and were replaced. Basic hemodynamic data revealed no significant differences between groups. ICP differed significantly among the groups during the first 3 h postoperatively (P=0.003 by repeated measures ANOVA); it was higher in the 20 degrees C group than in the 10 degrees C/CsA or 10 degrees C control groups. Recovery of visual evoked potentials was significantly better in the 10 degrees C/CsA group than in the 10 degrees C control group; no recovery was seen by 3 h in the 20 degrees C control group. Postoperative behavioral scores also differed significantly between the groups, P=0.03: a good behavioral outcome--a score >9 on POD3--was more prevalent among CsA-treated pigs (75%) than among 10 degrees C controls (50%), or 20 degrees C controls (12.5%, P=0.06). CONCLUSIONS: The data suggest that cooling to 10 degrees C and CsA treatment are both of benefit in improving cerebral recovery after HCA when compared with untreated 20 degrees C controls, and may be synergistic.

Effect of hypothermia on cerebral blood flow and metabolism in the pig.

BACKGROUND: The pig has become an increasingly popular model for the study of cerebral protection during cardiothoracic surgery in recent years, but little information is available concerning hypothermic porcine physiology. Because the efficacy of cerebral protection depends largely upon metabolic suppression, we studied cerebral oxygen metabolism at various temperatures using two different methods to assess cerebral blood flow (CBF). MATERIAL AND METHODS: Twelve pigs (7 to 13 kg) underwent cooling on cardiopulmonary bypass to 8 degrees C as recorded by an electrode placed deep in the parenchyma of the brain. CBF was measured in 6 animals using radioactive microspheres and in the other 6 using fluorescent microspheres. CBF, cerebral oxygen consumption, and cerebral vascular resistance were determined at 37 degrees C, 28 degrees C, 18 degrees C, and 8 degrees C. RESULTS: Both methods produced very similar data. CBF fell steadily with decrease in temperature to 18 degrees C but failed to drop further with more profound hypothermia. With both groups combined, mean cerebral oxygen metabolism was 2.63 mL/100 g per minute at 37 degrees C. Metabolic activity was 50% of base line values at 28 degrees C, 19% at 18 degrees C, and 11% at 8 degrees C. The Q10 value in the pig--the degree of metabolic suppression achieved by a 10 degrees C drop in temperature--is 2.46 (95% confidence interval 2.1 to 2.9); this value is consistent with similar studies in humans. CONCLUSIONS: The presence of significant residual metabolic activity at 18 degrees C suggests that this degree of hypothermia may provide incomplete cerebral protection during prolonged interruption of CBF. This study demonstrates that cooling to temperatures below 18 degrees C in the pig can achieve greater metabolic suppression although it may be associated with loss of cerebral autoregulation.

Cerebral physiology and outcome after hypothermic circulatory arrest followed by selective cerebral perfusion.

BACKGROUND: This study explored the impact of an interval of hypothermic circulatory arrest (HCA) preceding selective cerebral perfusion (SCP) on cerebral physiology and outcome. This protocol allows use of SCP during aortic surgery without the threat of embolization inherent in balloon catheterization of often severely atherosclerotic cerebral vessels. METHODS: In this blinded study, 30 pigs (20 to 22 kg) were randomized after cooling to 20 degrees C. Pigs in the HCA-CPB group (n = 10) underwent 30 minutes of HCA followed by 60 minutes of total body perfusion (CPB); HCA-SCP pigs (n = 10) underwent 30 minutes of HCA followed by 60 minutes of SCP, and SCP pigs (n = 10) had 90 minutes of SCP without prior HCA. Fluorescent microspheres enabled calculation of cerebral blood flow during perfusion and recovery. Hemodynamics, intracranial pressure, cerebrovascular resistance, and cerebral oxygen consumption were also monitored. Daily behavioral scores were obtained for 7 days postoperatively. RESULTS: In all groups, cerebral oxygen consumption fell significantly with cooling (p < 0.0001), remained low during perfusion, and rebounded promptly with rewarming; cerebral oxygen consumption was significantly (p = 0.027) greater during SCP than during HCA-CPB. Cerebral blood flow was significantly higher throughout SCP in the HCA-SCP group (p < 0.0001) than with CPB. Cerebrovascular resistance during SCP and HCA-SCP was significantly lower (p = 0.036) than during CPB. Behavioral scores were significantly better with SCP than with HCA-CPB throughout recovery, but did not differ between SCP and HCA-SCP. CONCLUSIONS: This study suggests that a short period of HCA preceding SCP provides global cerebral protection comparable to continuous SCP, implying that in clinical practice, a short period of HCA to reduce risk of embolization will not compromise the superior cerebral protection provided by SCP.

Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a double-blind 12-month evaluation study.

OBJECT: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been established as an effective treatment for Parkinson disease (PD). Nevertheless, bilateral surgical procedures can be associated with frequent and severe complications. The aim in the present study was to assess the safety and efficacy of unilateral STN stimulation, and the need for a second procedure. METHODS: Twelve patients with PD underwent unilateral DBS of the STN and were followed up for 12 months. Patients were assessed at baseline and at each visit in a double-blind fashion by analyzing the Unified PD Rating Scale (UPDRS), ambulation speed, and home diaries. Levodopa-off/stimulation-on UPDRS motor scores were improved by 26 +/- 8% (p < 0.05, mean +/- standard deviation [SD]) compared with the baseline levodopa-off score; there was a 50% improvement in contralateral features, a 17% improvement ipsilaterally, and a 36% improvement in axial features. The mean ambulation speed increased by 83 +/- 44% (p < 0.01, mean +/- SD). The medication-on time with dyskinesias was significantly reduced (p < 0.01) and the daily levodopa dose was reduced by 19 +/- 6% (p < 0.05, mean +/- SD). There were no clinically significant side effects. CONCLUSIONS: Unilateral DBS of the STN is safe and well tolerated, and may provide sufficient benefit so that additional surgery is not required.

Mild hypothermia protects the spinal cord from ischemic injury in a chronic porcine model.

OBJECTIVES: During thoracoabdominal aortic aneurysm repair, prolonged compromise of spinal cord blood supply can result in irreversible spinal cord injury. This study investigated the impact of mild hypothermia during aortic cross-clamping on postoperative paraplegia in a chronic porcine model. METHODS: The thoracic aorta was exposed and cross-clamped in 30 juvenile pigs (20-22 kg) for different intervals at normothermia (36.5 degrees C), and during mild hypothermia (32.0 degrees C). Three pigs were evaluated at each time and temperature. Myogenic motor-evoked potentials (MEPs) were monitored, and postoperative recovery evaluated using a modified Tarlov score. RESULTS: There were no significant hemodynamic or metabolic differences between individual animals, and the groups had equivalent arterial pressures (mean 64.3+/-3.6 mmHg). Time to recovery of MEPs correlated with severity of injury; all animals with irreversible MEP loss suffered postoperative paraplegia. At normothermia, animals with 20 min of aortic cross-clamping emerged with normal motor function, but those cross-clamped for 30 min suffered paraplegia. With mild hypothermia, animals tolerated 50 min of aortic cross-clamping without evidence of neurologic injury, but were all paraplegic after 70 min of ischemia. Animals appeared to recover normal motor function after 60 min of aortic cross-clamping at hypothermia initially, but exhibited delayed-onset paraplegia 36 h postoperatively. CONCLUSIONS: Our observations indicate that mild hypothermia dramatically increases the tolerance of the spinal cord to ischemia in the pig, and therefore suggests that cooling to 32.0 degrees C should be encouraged during surgery which may compromise spinal cord blood supply. An ischemic insult of borderline severity may result in delayed paraplegia.

Impact of hypothermic selective cerebral perfusion compared with hypothermic cardiopulmonary bypass on cerebral hemodynamics and metabolism.

OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for cerebral protection during aortic arch surgery, but the effect of the absence of systemic perfusion on cerebrovascular dynamics it has never been established. This study explored the physiology of prolonged SCP compared to hypothermic cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29 juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass (CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were injected during perfusion and recovery, enabling calculation of total and regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF decreased significantly (P=0.0001) during cooling, but remained at significantly higher levels with SCP than with HCPB throughout perfusion and recovery (P<0.0001). CVR was significantly lower with SCP than with HCPB throughout perfusion (P=0.04). Oxygen consumption fell significantly with cooling (P=0.0001), remained low during perfusion, and rebounded promptly with rewarming; with SCP it was significantly higher than with HCPB throughout the perfusion interval (P=0.03), and remained higher thereafter. ICP rose significantly less with SCP than with HCPB (P=0.02). CONCLUSION: We conclude that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as evidenced by significantly higher CBF and oxygen consumption during SCP, by prompt recovery of oxygen consumption after rewarming, and by significantly lower ICP during perfusion and in the post-bypass period.