Shi-Uk Lee

Mild to Moderate Early Exercise Promotes Recovery from Cerebral Ischemia in Rats

OBJECTIVE We examined the effects of various exercise intensities on recovery from middle cerebral artery occlusion (MCAO) in rats. METHODS First, we administered a 120-minute left MCAO to male Sprague-Dawley rats and randomly assigned them to one of four groups: no exercise (Group 1), mild exercise (Group 2), moderate exercise (Group 3), and severe exercise (Group 4). Then, we trained the rats for 30 min per day for one week or two weeks. We used a five-point neurological evaluation scale to measure neurological deficits 1-day, 4-days, 7-days, 10-days and 14-days after MCAO and measured infarct volume by use of 2% 2,3,4-triphenyltetrazolium chloride in exercised brains. We also performed immunohistochemistry analysis of the brain to observe reactive astrocytosis at the peri-infarct region. RESULTS Neurological examination indicated that Group 2 and 3 recovered better than Group 1 after one week and two weeks (p < 0.05). Moreover, Group 2 and 3 had reduced brain infarct volume compared with Group 1 after one week (p < 0.05). There were no significant differences between Group 4 and Group 1. The thickness of the peri-infarct astrocytosis was significantly reduced in Group 4 relative to Group 1 after one week. There was a significant negative correlation between the extent of reactive astrocytosis and neurological recovery (r = -0.648, p < 0.01). CONCLUSION This study demonstrates that mild to moderate exercise that begins soon after induced cerebral ischemia promotes recovery and that astrocytes may have an important role in the recovery process.

Changes in posterior disc bulging and intervertebral foraminal size associated with flexion-extension movement: a comparison between L4-5 and L5-S1 levels in normal subjects

BACKGROUND CONTEXT No previous study has used magnetic resonance imaging (MRI) to evaluate changes of posterior disc bulging and intervertebral foraminal size in the normal spine with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. PURPOSE To determine changes in posterior disc bulging and intervertebral foraminal size with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels. STUDY DESIGN An in vivo study of magnetic resonance kinematics with spine flexion extension. METHODS Spines of three volunteers with no history of low back pain were scanned in neutral, flexion, and extension positions in a vertically open MRI system. MRI was repeated after 6 hours of normal activity and an additional 4 hours of heavy activity with a weighted vest. Posterior bulging of the intervertebral disc and the size of intervertebral foramen were measured at the L4-5 and L5-S1 levels. RESULTS With spine flexion, posterior bulging of the discs increased at L4-5 in eight of nine measurements (three different spine-loading states for each of three subjects) and L5-S1 discs in six of nine measurements. In most cases, posterior bulging decreased with extension. No significant difference was noted in the degree of disc bulge between levels. Foraminal size at L4-5 increased with flexion and decreased with extension, and the extent of these changes was greater at the L4-5 level than at L5-S1. CONCLUSIONS This pilot study demonstrates two distinct behavior characteristics of the normal spine with flexion-extension movement.

Stochastic Linkage Modeling for Mechanical Error Analysis of Planar Mechanisms

This paper addresses stochastic linkage modeling for mechanical error analysis of planar mechanisms. Considering the effects of joint angle variations, the effective link length model is generalized. The generalized model produces more accurate predictions of mechanical errors than the effective link length model. However, the generalization requires more complicated mechanical error analysis. This paper proposes a stochastic model to intuitively consider the effects of tolerances and clearances, based on the clearance vector concept. Stochastic models are applied to typical mechanisms and their results are compared with those of Monte Carlo simulations. The comparison shows that the proposed stochastic model is effective for mechanical error analysis. The clearance vector model yields more accurate results and is easier to use than the generalized effective link length model.

Efficacy and safety of NABOTA in post-stroke upper limb spasticity: a phase 3 multicenter, double-blinded, randomized controlled trial.

Botulinum toxin A is widely used in the clinics to reduce spasticity and improve upper limb function for post-stroke patients. Efficacy and safety of a new botulinum toxin type A, NABOTA (DWP450) in post-stroke upper limb spasticity was evaluated in comparison with Botox (onabotulinum toxin A). A total of 197 patients with post-stroke upper limb spasticity were included in this study and randomly assigned to NABOTA group (n=99) or Botox group (n=98). Wrist flexors with modified Ashworth Scale (MAS) grade 2 or greater, and elbow flexors, thumb flexors and finger flexors with MAS 1 or greater were injected with either drug. The primary outcome was the change of wrist flexor MAS between baseline and 4weeks post-injection. MAS of each injected muscle, Disability Assessment Scale (DAS), and Caregiver Burden Scale were also assessed at baseline and 4, 8, and 12weeks after the injection. Global Assessment Scale (GAS) was evaluated on the last visit at 12weeks. The change of MAS for wrist flexor between baseline and 4weeks post-injection was -1.44±0.72 in the NABOTA group and -1.46±0.77 in the Botox group. The difference of change between both groups was 0.0129 (95% confidence interval -0.2062-0.2319), within the non-inferiority margin of 0.45. Both groups showed significant improvements regarding MAS of all injected muscles, DAS, and Caregiver Burden Scale at all follow-up periods. There were no significant differences in all secondary outcome measures between the two groups. NABOTA demonstrated non-inferior efficacy and safety for improving upper limb spasticity in stroke patients compared to Botox.

Feasibility of 18F-FDG PET as a Noninvasive Diagnostic Tool of Muscle Denervation: A Preliminary Study

The purpose of this study was to confirm glucose hypermetabolism in denervated muscle and investigate the feasibility of 18F-FDG PET scanning for the detection of muscle denervation. Method: A sciatic neuropathy model in rats was created by nerve resection of the left sciatic nerve and sham operation on the other side. Eight days after denervation, small-animal PET/CT scans of the hindlimbs were acquired. Muscle denervation was confirmed by electrophysiologic and histologic study. Results: All rats showed increased 18F-FDG uptake in the muscles of the left (denervated) lower legs. The calculated maximum lesion-to-normal counts ratio of the left lower leg anterolateral (left, 11.02 ± 2.08; right, 1.81 ± 0.40, n = 6, P < 0.01) and posterior (left, 9.81 ± 4.58; right, 1.87 ± 0.44, n = 6, P < 0.01) compartment were significantly increased. The electrophysiologic and histologic study verified muscle denervation. Conclusion: Glucose hypermetabolism in muscle denervation is an obvious phenomenon. 18F-FDG PET scanning can be used to visualize muscle denervation.

Neuronox versus BOTOX in the Treatment of Post-Stroke Upper Limb Spasticity: A Multicenter Randomized Controlled Trial.

Background Botulinum toxin type A is widely used for treating spasticity. Neuronox (Neu-BoNT/A), a newly manufactured botulinum toxin a, has not yet been investigated for its efficacy and safety in the treatment of post-stroke upper limb spasticity. Objective We evaluated the efficacy and safety of Neuronox (Neu-BoNT/A) compared with BOTOX (onabotulinum toxin A) for treating post-stroke upper limb spasticity. Methods In total, 196 stroke patients with moderate to severe upper limb spasticity were randomly assigned to either Neuronox or BOTOX intervention. The wrist flexors were mandatory and elbow, finger, and thumb flexors were optional muscles to be injected. Assessments were performed at baseline and 4, 8, and 12 weeks after the intervention. The primary outcome measure was the change from baseline of the Modified Ashworth Scale (MAS) at the wrist flexors at week 4. Secondary outcome measures included the change of MAS at each visit, response rate, Disability Assessment Scale (DAS), Carer Burden Scale, and Global Assessment of treatment benefit. Results Primary outcome measures were -1.39±0.79 and -1.56±0.81 in the Neuronox and BOTOX groups, respectively. The difference was within the noninferiority margin of 0.45 (95% upper limit=0.40). There were no significant differences between the groups in the secondary outcome and safety measures, except the change of the MAS at the elbow flexors at week 12 (-0.88±0.75 in the Neuronox group, -0.65±0.74 in the BOTOX group; P=0.0429). Both groups showed significant improvements in the MAS, DAS, and Carer Burden Scale at weeks 4, 8, and 12. Conclusion Neuronox showed equivalent efficacy and safety compared with BOTOX for treating post-stroke upper limb spasticity. Trial Registration ClinicalTrials.gov NCT01313767

MR and MR arthrography to identify degenerative and posttraumatic diseases in the shoulder joint.

MR imaging provides a comprehensive evaluation of a wide spectrum of both intraarticular and extraarticular pathology of the shoulder. MR imaging enables the detection or exclusion of degenerative and posttraumatic diseases of the shoulder with a reasonable accuracy. MR arthrography is useful in the visualization of subtle anatomic details and further improves the differentiation. In this article, findings of MR imaging and MR arthrography of degenerative and posttraumatic shoulder diseases (impingement syndrome, rotator cuff tears, and glenohumeral instability) has been reviewed.

Clinical Outcomes of Conservative Treatment and Arthroscopic Repair of Rotator Cuff Tears: A Retrospective Observational Study

Objective To compare the clinical outcomes following conservative treatment and arthroscopic repair in patients with a rotator cuff tear. Methods In this retrospective study, patients aged >50 years with a symptomatic rotator cuff tear were reviewed. The rotator cuff tendons were evaluated using ultrasonography, shoulder magnetic resonance imaging or MR arthrography, and the patients with either a high-grade partial-thickness or small-to-medium-sized (≤3 cm) full-thickness tear were included in this study. The primary outcome measures were a pain assessment score and range of motion (ROM) at 1-year follow-up. The secondary outcomes were the rate of tear progression or retear along with the rate of symptom aggravation after the treatments. Results A total of 357 patients were enrolled, including 183 patients that received conservative treatment and 174 patients who received an arthroscopic repair. The pain assessment score (p<0.001) and the ROM in forward flexion (p<0.001) were significantly improved in both groups. The ROM in internal rotation did not significantly change after conservative treatment and arthroscopic repair. The pain assessment score and ROM were not significantly different between the two groups. Retear was observed in 9.6% of patients who had an arthroscopic repair and tear progression was found in 6.7% of those who underwent conservative treatment. The proportion of aggravation for pain and ROM did not significantly differ between the two groups. Conclusion The effectiveness of conservative treatment is not inferior to arthroscopic repair for patients >50 years old with a less than medium-sized rotator cuff tear in a 1-year follow-up period. Further study is warranted to find the optimal combination of conservative treatment for a symptomatic rotator cuff tear.

Safety of Low-Dose Oral Dantrolene Sodium on Hepatic Function

OBJECTIVE To investigate the incidence of hepatobiliary dysfunction after administration of low-dose dantrolene sodium. DESIGN A retrospective survey of medical records. SETTING One secondary and 2 tertiary hospitals. PARTICIPANTS Patients (N=243; 144 men, 27 children; mean age ± SD, 47.8 ± 19.7y) who were administered dantrolene at a daily dose of 12.5 to 400mg for more than 4 weeks. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Liver function test (LFT) results, including serum total bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase, were recorded before and at least 1 month after the initial dose of dantrolene. In cases of treatment cessation, the reason was investigated. Significantly elevated LFT levels were defined as ≥ to 2 times the upper limit of the normal range. RESULTS Treatment duration was 268.0 ± 428.5 days with a daily dose of 65.2 ± 44.7 mg. At the end of the investigation, 95 patients (39.1%) had been lost to follow-up, and 105 (43.2%) had stopped treatment. The reasons for cessation were improved spasticity (42.9%), no effect of the medication (27.6%), weakness (6.7%), and other medical problems (5.7%). Patients with weaknesses did not have elevated LFT values. A 32-year-old man with head injuries and multiple trauma developed hepatic dysfunction 82 days after the initial dose and 43 days after a dose increment to 400mg/d. Other patients did not experience significant LFT abnormalities. CONCLUSIONS One case of hepatic dysfunction was recorded in 243 cases after at least 4 weeks of low-dose oral dantrolene administration. Low-dose dantrolene can be used safely with meticulous clinical and laboratory monitoring.

Changes in Posterior Lumbar Disk Contour Abnormality with Flexion-Extension Movement in Subjects with Low Back Pain and Degenerative Disk Disease

To determine whether posterior lumbar disk contour dimensions differ in the flexed seated, upright seated, and extended seated positions.