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.

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.

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.

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.

Impact of high intracranial pressure on neurophysiological recovery and behavior in a chronic porcine model of hypothermic circulatory arrest.

OBJECTIVE: This review was undertaken to determine whether high intracranial pressure (ICP) during reperfusion after hypothermic circulatory arrest (HCA) correlates with evidence of suboptimal cerebral protection in a chronic porcine model. METHODS: In concurrent studies of cerebral protection, 48 control pigs (24-31 kg) underwent 90 min of HCA at 20 degrees C using a strictly standardized protocol. Hemodynamic measurements, ICP and neurophysiological data (EEG, SSEP) were assessed before HCA and until 3 h postoperatively. ICP was measured using a Codman microtip catheter inserted directly into brain parenchyma. Neurological/behavioral evaluation (9=full recovery) was carried out daily through postoperative day (POD) 3. RESULTS: There were no significant hemodynamic or metabolic differences between individual animals. ICP (mmHg) increased significantly for the first 3 h after HCA: from baseline levels of 6.2+/-2.1 to 10+/-2.6 at 1 h, 11+/-3.2 at 2 h and 10+/-3.6 mmHg at 3 h; P<0.001 for the trend. EEG recovery 3 h after HCA was observed in 13 animals (27%), and correlated with lower ICP during reperfusion (P<0.001): with each 1 mmHg increase in ICP at 3 h, the odds of early EEG recovery decreased by a factor of 0.72. Lower ICP during reperfusion was also significantly associated with higher behavioral scores on POD 1 and 2, P<0.001. CONCLUSIONS: A significant rise in ICP may help explain the prolonged obtundation and confusion often seen clinically after HCA. If these small but consistent increases in ICP contribute to rather than reflect ischemic neuronal damage, simple maneuvers to reduce ICP may improve cerebral recovery after HCA.

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.

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.

Thoracic and thoracoabdominal aneurysm repair: is reimplantation of spinal cord arteries a waste of time?

BACKGROUND: The impact of different strategies for management of intercostal and lumbar arteries during repair of thoracic and thoracoabdominal aortic aneurysms (TAA/A) on the prevention of paraplegia remains poorly understood. METHODS: One hundred consecutive patients with intraoperative monitoring of motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) during TAA/A repair involving serial segmental artery sacrifice (October 2002 to December 2004) were reviewed. RESULTS: Operative mortality was 6%. The median intensive care unit stay was 2.5 days (IQ range: 1-4 days), and the median hospital stay 10.0 days (IQ range: 8-17 days). Potentials remained unchanged during the course of serial segmental artery sacrifice, or could be returned to baseline levels by anesthetic and blood pressure manipulation, in 99 of 100 cases. An average of 8.0 +/- 2.6 segmental artery pairs were sacrificed overall, with an average of 4.5 +/- 2.1 segmental pairs sacrificed between T7 and L1, where the artery of Adamkiewicz is presumed to arise. Postoperative paraplegia occurred in 2 patients. In 1, immediate paraplegia was precipitated by an intraoperative dissection, resulting in 6 hours of lower body ischemia. A second ambulatory patient had severe paraparesis albeit normal cerebral function after resuscitation from a respiratory arrest. CONCLUSIONS: With monitoring of MEP and SSEP, sacrifice--without reimplantation--of as many as 15 intercostal and lumbar arteries during TAA/A repair is safe, resulting in acceptably low rates of immediate and delayed paraplegia. This experience suggests that routine surgical implantation of segmental vessels is not indicated, and that, with evolving understanding of spinal cord perfusion, endovascular repair of the entire thoracic aorta should ultimately be possible without spinal cord injury.

Use of a maze to detect cognitive dysfunction in a porcine model of hypothermic circulatory arrest.

BACKGROUND: Hypothermic circulatory arrest (HCA) can result in cognitive impairment not reflected by histopathology or gross neurologic observation. We tested the sensitivity of two multi-room maze tasks in detecting cerebral dysfunction after HCA in pigs. METHODS: Twenty-seven pigs were studied, divided between two tasks. 13 underwent 90 minutes HCA at 20 degrees C and were trained from postoperative day (POD) 7; 14 were unoperated controls. The maze includes a holding area, 8 rooms, and a center hallway. One piece of apple is placed in each baited room on each of 10 days of learning evaluation. After a pig enters a room, doors to all other rooms close, and the pig must return to the holding area. In task 1, 6 of 8 rooms were baited, and each day's session ended when each baited room had been entered, or after 20 trials. In task 2, initially only the right- or left-sided rooms were baited. Pigs were evaluated each day until they entered 4 baited rooms, or for 15 trials; the process was then repeated, baiting the other side. RESULTS: Intraoperative physiology and postoperative recovery showed no differences between task 1 or 2 pigs. Task 1 did not distinguish between control and HCA groups (p = 0.5), but task 2 revealed significantly (p = 0.04) better learning in controls. CONCLUSIONS: The significantly poorer performance of pigs after HCA suggests that the reversal of baited rooms in task 2 provides the sensitivity to detect cognitive dysfunction. The maze is a promising tool to investigate in pigs the mild cerebral damage often seen after HCA.