L. Andrew Koman

Management of cerebral palsy with botulinum-A toxin: preliminary investigation.

Summary: Use of intramuscular botulinum-A toxin (Botox) to produce neuromuscular blockade has been effective in treating certain ocular and facial muscular imbalances as well as spasmodic torticollis. In this preliminary open study, the effectiveness of intramuscularly injected Botox on the muscular imbalances of cerebral palsy was assessed in 27 pediatric patients. Each patient had “dynamic deformities” unresponsive to other treatment, and operation was the only other realistic alternative. The dose of Botox was calculated on a unit/body weight basis. In ambulatory patients, clinical changes in gait were assessed by a physicians rating scale. Reduction in spasticity became apparent in 12–72 h after injection; the effect of Botox after target threshold was reached lasted 3–6 months. No major side effects occurred. Botox may prove a useful adjuvant in conservative management of the spasticity of cerebral palsy. Successful management with these injections may allow delay of surgical intervention until the child is older and at less risk of possible complications, including the need for repeated surgical procedures.

Botulinum Toxin Type A Neuromuscular Blockade in the Treatment of Lower Extremity Spasticity in Cerebral Palsy: A Randomized, Double-Blind, Placebo-Controlled Trial

Increased gastrocnemius/soleus muscle tone in children with cerebral palsy may cause an equinus of the ankle. Botulinum toxin type A (BTX), a neuromuscular blocking agent, reduces muscle tone in various neuromuscular disorders. The safety and short-term efficacy of BTX injections were evaluated in a prospective, 3-month, double-blind, randomized clinical trial involving 114 children with cerebral palsy and dynamic equinus foot deformity. Outcome was determined by observational gait analysis, ankle range-of-motion measurements, and quantification of muscle denervation by nerve conduction. Patients in the BTX group demonstrated improved gait function and partial denervation of the injected muscle. No serious adverse events were reported.

Acute pain following musculoskeletal injuries and orthopaedic surgery: mechanisms and management.

The undertreatment of acute pain associated with musculoskeletal conditions and surgical procedures is a focus of growing concern to orthopaedic surgeons. Fortunately, the armamentarium now includes recent advances in the understanding of how undertreated acute pain can lead to chronic pain, the development of new therapeutic agents, and new approaches to pain management. The concept of neuronal plasticity (the ability of neurons to profoundly alter their structure, function, or biochemical profile in response to repeated afferent sensory input) is now central to the understanding of the development of chronic pain from acute pain. Local inflammation in injured tissue increases the sensitization of specialized peripheral sensory neurons (nociceptors), leading to repeated afferent input into the central nervous system. Resolving inflammation before these events occur may prevent modifications in the central nervous system that lead to chronic pain. Therefore, it is important to reduce pain and inflammation at both the central and peripheral level. In addition to traditional agents (aspirin, nonspecific nonsteroidal anti-inflammatory drugs, opioids, local anesthetics, and regional blocks), more recently developed agents, such as cyclooxygenase-2 specific inhibitors, are now available. Combinations of these agents, as well as combinations of pharmacologic and nonpharmacologic approaches, are being used as multimodal therapy to treat the multiple sources of acute pain. Clinical practice guidelines for the management of acute pain now emphasize the incorporation of new knowledge into solid, evidence-based practice. This knowledge, combined with further understanding of the anatomic, physiologic, cellular, and molecular basis of pain, will provide the basis forfuture approaches to the management of acute pain in orthopaedic practice.

Peripheral Nerve Regeneration Using a Keratin-Based Scaffold: Long-Term Functional and Histological Outcomes in a Mouse Model

PURPOSE The management of peripheral nerve injuries with segmental defects is a challenge to both patient and surgeon. Repairs under tension have a poor prognosis; sensory nerve allografts have donor site morbidity and suboptimal motor recovery, but remain the gold standard. The development of conduit-based repair strategies has evolved and these are promising for sensory nerves and short defects; however, no conduit filler is clinically available that improves motor recovery equivalent to sensory autografts. In this study, motor recovery using keratin-based hydrogel filler was compared with that for sensory nerve autografts and empty conduits. METHODS Fifty-four mice were randomized into 3 treatment groups: empty conduit, sural nerve autograft, and keratin hydrogel-filled conduit. Animals were followed for 6 weeks, 3 months, and 6 months. Outcomes included compound motor action potential (CMAP), nerve area, myelinated axon number and density, and myelinated axon diameter. RESULTS Neuromuscular recovery with keratin was greater than with empty conduits in most outcome measures. Nerves that regenerated through the keratin hydrogel had lower conduction delays, greater amplitudes, more myelinated axons, and larger axons than nerves that regenerated through empty conduits. Sensory nerve autografts and keratin hydrogel were statistically equivalent in CMAP measurements at 6 months. Moreover, keratin-filled conduits demonstrated greater axon density and larger average axon diameter than both empty conduits and autograft at 6 months. CONCLUSIONS In a mouse tibial nerve model, keratin hydrogels significantly improved electrophysiological recovery, compared with empty conduits and sensory nerve autografts, at an early time point of regeneration. Keratin hydrogels also produce long-term electrical and histological results superior to empty conduits and equivalent to sensory nerve autografts.

Spasticity associated with cerebral palsy in children: Guidelines for the use of botulinum A toxin

Botulinum A toxin produces selective and reversible chemodenervation that can be employed to balance muscle forces across joints in children with cerebral palsy (CP). Currently, there are two commercially available botulinum A toxin formulations (BOTOX® and Dysport®). The amount of botulinum A toxin required depends upon the number of muscles that are targeted, and the size of the patient. In order to achieve adequate chemodenervation with botulinum A toxin, the following conditions must be met: (i) a sufficient number of units of toxin must be injected in order to neutralize neuromuscular junction (NMJ) activity; (ii) an appropriate drug volume is required in order to optimize the delivery of the toxin to the NMJs; and (iii) localization of the injecting needle through the fascia of the target muscle is necessary. Localization of the injection may be facilitated by active electromyography, ultrasonography, palpation of the muscle belly, and/or use of anatomic landmarks.Botulinum A toxin injections are indicated for use in pediatric patients with CP to: (i) improve motor function by balancing muscle forces across joints; (ii) improve health-related quality of life by decreasing spasticity and/or decreasing caregiver burden; (iii) decrease pain from spasticity; (iv) enhance self-esteem by diminishing inappropriate motor responses; and (v) provide a presurgical diagnostic tool.Following intramuscular injections of botulinum A toxin, short-term benefits of reduced spasticity are observed in approximately 70–82% of children. The intermediate term (1–2 years) efficacy rate is approximately 50%. The most common deformity treated with toxin injections in pediatric patients with CP is equinus foot deformity. However, efficacy of toxin injections for the management of crouched gait, pelvic flexion contracture, cervical spasticity, seating difficulties, and upper extremity deformity also has been documented. In addition, toxin injections have been shown to manage painful muscle spasticity associated with surgery or application of casts and painful cervical spasticity with or without dystonia. Toxin injections can also be used as a diagnostic tool to determine the appropriateness of other interventions by observing the muscle response to the injection in order to gain additional information for the development of a treatment plan. Botulinum A toxin, when used in appropriate doses, is well tolerated.

The microcirculatory effects of peripheral sympathectomy

Microvascular physiology following peripheral artery sympathectomy was evaluated in seven hands with refractory pain (n = 7) and ulceration (n = 7) by serial isolated cold stress testing, which measures digital temperature and cutaneous perfusion (laser Doppler fluxmetry). All patients (n = 6) had vasospasm (secondary Raynauds phenomenon) and arteriographically proven digital and palmar occlusive disease. Microcirculatory flow responses were correlated with symptoms and signs (including ulcer healing) before and after (2-8 weeks, 12-15 weeks, and 24 weeks) peripheral sympathectomy. Baseline data were compared with those of controls (n = 7 extremities). Following surgery, all seven hands had diminished pain; six had ulcer healing and one had ulcer reduction. Isolated cold stress testing demonstrated abnormalities in temperature and laser Doppler fluxmetry response between patients and controls. Although total flow (reflected by temperature) was not significantly increased after surgery, peripheral sympathectomy increased nutritional flow in these patients with combined vasospastic vessels and occlusive injury. The clinical changes observed following peripheral sympathectomy appear to be related to postsurgical correction of abnormal arteriovenous shunting and to improved nutritional blood flow to ischemic areas. This accounts for the resultant diminution of pain and healing of ulcers observed in these patients after surgery.

The vascularized cutaneous scapular flap.

Five cases of cutaneous free tissue transfer using the cutaneous and circumflex scapular vessels are presented. The free scapular flap is an excellent choice when intermediate-sized (6 to 10 by 10 to 16 cm) uninnervated flap coverage is necessary and cannot be achieved by conventional methods. The flap is exposed easily and has a constant artery and venous system, 2- to 3-mm-diameter vessels, and a 4- to 6-cm vascular pedicle. The shoulder donor site can be closed primarily. Like all shoulder wounds, it has a tendency to spread, but not functional deficit exists at the shoulder or on the posterior chest wall.

Reflex sympathetic dystrophy of the knee after sensory nerve injury

Reflex sympathetic dystrophy (RSD) of the knee is an extremely difficult problem to treat. This study examined the possible relationship between isolated injury to the infrapatellar branch of the saphenous nerve (IPBSN) and the etiology and natural course of RSD. Thirty-five patients with clinically significant sympathetic dystrophy of the knee were examined retrospectively. All patients (100%) had clinical evidence of insult to the IPBSN. Thirty-three patients (94%) were found to have vasomotor instability as measured by isolated cold stress testing (ICST). All patients in this population of 33 were treated with vasoactive therapies. Subjective improvement was noted in 20 patients (p = NS). Initial ICSTs of improved and unimproved patients were compared. Baseline temperatures were significantly warmer in patients who improved with therapy (p less than 0.05), and a warmer trend was evident throughout all phases of the test in those who improved compared with those who did not. Eighty percent of patients treated within 1 year improved with one or more vasoactive therapies, whereas only 44 percent improved when treatment was started after 1 year, indicating a significant population difference (p less than 0.05).

Arterial shunting as an adjunct to major limb revascularization.

Temporary arterial and venous shunting lias been employed to reduce warm ischemia in major limb replantation and revascularization on eight occasions. This has allowed identification of vital structures, thorough debridement, and rigid internal or external skeletal fixation prior to definitive arterial repair. Arterial shunting has not been associated with any significant complications and has improved our operative technique in these severe vascular injuries.

Quantification of upper extremity function and range of motion in children with cerebral palsy

This study evaluated the hypothesis that upper extremity function and range of motion can be quantified reliably in children with cerebral palsy (CP) in a busy clinical setting. The specific aim was to determine the inter‐ and intrarater reliability of a modified House Functional Classification (MHC) system to evaluate upper extremity function and a standardized instrument to document upper extremity range of motion (Upper Extremity Rating Scale [UERS]). Sixty‐five children with CP (43 males, 22 females, mean age 9y 2mo, SD 4y 1mo) with spasticity involving the upper extremity (quadriplegia n=22; hemiplegia n=36; diplegia n=7; Gross Motor Functional Classification System Levels I n=41, II n=6, III n=3, IV n=5, V n=10) were evaluated independently by occupational therapists and orthopedic surgeons using both instruments at several visits. Inter‐ and intrarater reliability were determined for both instruments by calculating measures of agreement (weighted kappa values and intraclass correlation coefficients [ICCs]). Interrater agreement (ICC=0.94) and intrarater agreement (ICC=0.96) on the MHC were good to excellent. Similarly, inter‐rater agreement (kappa 0.66–0.81) and intrarater agreement (kappa 0.64–0.88) on the UERS was either good or excellent. The MHC and the UERS provide standardized, reliable, reproducible, and efficient instruments that can be used by occupational therapists and orthopedic surgeons to evaluate the upper extremities of children with CP.