Recovery of rat muscle size but not function more than 1 year after a single botulinum toxin injection.

INTRODUCTION: Neurotoxin injection is used to treat a wide variety of neuromuscular disorders. The purpose of this study was to measure the functional and structural properties of botulinum toxin-injected adult rat skeletal muscle over nearly the entire lifespan. METHODS: Ten groups of animals were subjected to either neurotoxin injection [Botox, Type A (BT-A); Allergan, Irvine, California] or saline solution injection. Neurotoxin-injected animals (n = 90) were analyzed at different time-points: 1 week; 1 month; 3 months; 6 months; 12 months; or 18 months. RESULTS: In spite of the recovery of structural features, such as muscle mass and fiber area, dorsiflexion torque production remained significantly depressed by 25%, even at 12 months after neurotoxin injection. DISCUSSION: The data demonstrate that, after a single BT-A injection, although gross muscle morphology recovered over a 12-month time period, loss of contractile function did not recover. Muscle Nerve 57: 435-441, 2018.

Systematic test of neurotoxin dose and volume on muscle function in a rat model.

INTRODUCTION: Onabotulinum toxin serotype A (BT-A) is used for a variety of motor and sensory disorders related to abnormal muscle activity. METHODS: We developed a high-resolution rodent model to allow precise determination of the effect of BT-A dose (measured in units) and injectate volume (measured in µl) on the efficacy of the injection and systemic side effects. Dorsiflexion is the best indicator of injected and contralateral muscle function. RESULTS: One month after injection, dorsiflexion torque of BT-A-injected limbs was decreased significantly in all experimental groups compared with saline controls (P < 0.05). Torque was also compared among the BT-A groups, which demonstrated a significant effect of dose (P < 0.001), but no effect of volume (P > 0.2) and no dose × volume interaction (P > 0.3). Similar results were observed for other parameters measured. CONCLUSIONS: These data demonstrate that injection dose and not volume or concentration is the primary determinant of neurotoxin efficacy in a rodent model.

The effect of payer type on clinical outcomes in total knee arthroplasty.

This was a retrospective cohort analysis of 112 patients undergoing primary total knee arthroplasty, wherein baseline demographics, resource utilization, and outcomes were compared by insurance type: Medicaid, Medicare, or private. At the time of surgery, Medicaid patients were younger (P<.0001) and had lower preoperative Knee Society Scores than Medicare and private patients (P=.0125). Medicaid postoperative scores were lower than those of private patients (P=.0223). The magnitude of benefit received by Medicaid patients was similar to Medicare and private patients. Medicaid patients had a higher number of cancelled (P=.01) and missed (P=.0022) appointments relative to Medicare and private patients. Medicaid patients also had shorter average follow-up periods compared to private patients (P=.0003). Access to care and socioeconomic factors may be responsible for these findings.

Acetabular distraction: an alternative for severe defects with chronic pelvic discontinuity?

BACKGROUND: Stabilization of a pelvic discontinuity with a posterior column plate with or without an associated acetabular cage sometimes results in persistent micromotion across the discontinuity with late fatigue failure and component loosening. Acetabular distraction offers an alternative technique for reconstruction in cases of severe bone loss with an associated pelvic discontinuity. QUESTIONS/PURPOSES: We describe the acetabular distraction technique with porous tantalum components and evaluate its survival, function, and complication rate in patients undergoing revision for chronic pelvic discontinuity. METHODS: Between 2002 and 2006, we treated 28 patients with a chronic pelvic discontinuity with acetabular reconstruction using acetabular distraction. A porous tantalum elliptical acetabular component was used alone or with an associated modular porous tantalum augment in all patients. Three patients died and five were lost to followup before 2 years. The remaining 20 patients were followed semiannually for a minimum of 2 years (average, 4.5 years; range, 2-7 years) with clinical (Merle d'Aubigné-Postel score) and radiographic (loosening, migration, failure) evaluation. RESULTS: One of the 20 patients required rerevision for aseptic loosening. Fifteen patients remained radiographically stable at last followup. Four patients had early migration of their acetabular component but thereafter remained clinically asymptomatic and radiographically stable. At latest followup, the average improvement in the patients not requiring rerevision using the modified Merle d'Aubigné-Postel score was 6.6 (range, 3.3-9.6). There were no postoperative dislocations; however, one patient had an infection, one a vascular injury, and one a bowel injury. CONCLUSIONS: Acetabular distraction with porous tantalum components provides predictable pain relief and durability at 2- to 7-year followup when reconstructing severe acetabular defects with an associated pelvic discontinuity. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Passive mechanical properties and related proteins change with botulinum neurotoxin A injection of normal skeletal muscle.

The effects of botulinum neurotoxin A on the passive mechanical properties of skeletal muscle have not been investigated, but may have significant impact in the treatment of neuromuscular disorders including spasticity. Single fiber and fiber bundle passive mechanical testing was performed on rat muscles treated with botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers was determined by gel electrophoresis. Muscle collagen content was determined using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic modulus was reduced compared to control fibers (53.00 kPa vs. 63.43 kPa). Fiber stiffness and slack sarcomere length were also reduced compared to control fibers and myosin heavy chain composition shifted from faster to slower isoforms. Average titin molecular weight increased 1.77% after treatment. Fiber bundle passive elastic modulus increased following treatment (168.83 kPa vs. 75.14 kPa). Bundle stiffness also increased while collagen content per mass of muscle tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on the passive mechanical properties of normal muscle that is opposite to the changes observed in spastic muscles.

Biopsy of osteoporotic vertebral compression fractures during kyphoplasty: unsuspected histologic findings of chronic osteitis without clinical evidence of osteomyelitis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate biopsy results obtained during vertebral augmentation (kyphoplasty) for presumed/confirmed osteoporotic vertebral compression fractures (VCFs). SUMMARY OF BACKGROUND DATA: Kyphoplasty to augment vertebrae in osteoporotic VCFs is well established. When VCF etiology is in question, bone biopsy can be performed at that time. Biopsy results, however, can be misleading without careful clinical correlation. METHODS: From July 2003 to July 2006, 94 vertebral biopsies were obtained from 66 patients during kyphoplasty for VCFs. Average patient age was 73 (range, 22-99), including 47 females and 19 males. There were 48 one-level, 17 two-level, and 4 three-level biopsies. Biopsy levels included: T6 (3), T7 (7), T8 (7), T9 (3), T10 (3), T11 (8), T12 (21), L1 (18), L2 (13), L3 (8), L4 (2), L5 (1). Histologic/immunohistochemical evaluations were performed. RESULTS: All specimens showed features of fracture in various stages of bony healing. Initially, 13 of 66 (19.7%) cases were read by a surgical pathologist as chronic inflammation, with 6 having features suggestive of chronic osteomyelitis, including polyclonal plasma cells, necrosis, and lymphoplasmacytic infiltrate. For this study, these biopsies were evaluated by an independent surgical pathologist (N.W.). Re-review showed 7 of the 13 cases were consistent with osteoporotic VCF healing in various stages with adjacent trilineage hematopoiesis. Six of 13 (46%), were read as containing fragmented bony spicules, fibrotic and fatty marrow, lymphoplasmacytic inflammation, and aggregates of mature, polyclonal plasma cells, suggesting the possibility of chronic osteomyelitis. However, at average follow-up of 37 months (range, 21-57 months), no patient demonstrated clinical and/or laboratory evidence of infection. Additionally, biopsies from 4 patients confirmed suspected or unsuspected malignancy, or confirmed no recurrence of malignant disease. CONCLUSION: Patients undergoing first-time vertebral augmentation should be considered for vertebral biopsy. Tissue examination is useful and may reveal pathologic fracture or possible infection. However, if infection is reported, clinical and laboratory correlation are important to make a diagnosis of osteomyelitis.

Increased efficacy and decreased systemic-effects of botulinum toxin A injection after active or passive muscle manipulation.

The effect of physical manipulation on the outcome of neurotoxin (NT) injection was studied in a rat tibialis anterior (TA) model system where dorsiflexion torque could be measured precisely. After determination of initial torque, all rats received a one-time botulinum toxin A (BTX-A) injection (dose 6.0 units/kg in a volume of 100 microL) into the TA midbelly. Four experimental groups were studied: one group was subjected to BTX-A injection alone (BTX-A only, n=8), one was subjected to BTX-A injection followed immediately by 10 isometric contractions (ISO; n=9), and the third was subjected to BTX-A followed immediately by 10 muscle passive stretch/release cycles (PS; n=10). After 1 month, maximum dorsiflexion torque of the injected and contralateral legs was determined followed by quantification of TA fiber area. Post-injection torque was significantly reduced by around 80% in all NT-treated extremities 1 month after injection (p<0.05). While all NT-treated extremities demonstrated a significant torque decrease relative to their pre-injection levels, ISO and PS groups demonstrated significantly lower torques compared with the BTX-A only group which received no physical manipulation (p<0.05) indicating greater efficacy. Perhaps even more surprising was that the ISO and PS groups both demonstrated a significantly smaller contralateral effect compared with the BTX-A only group that received no manipulation (p<0.05) indicating a decreased systemic-effect. Muscle fiber size generally correlated with dorsiflexion torque. These data demonstrate that both neuromuscular activity (seen in the ISO group) and muscle movement (seen in the PS group) increased the efficacy of BTX-A and decreased the systemic side effects.