New indications for botulinum toxin in rheumatology

Joint Bone Spine 73 (2006) 667–671 http://france.elsevier.com/direct/BONSOI/

Review

New indications for botulinum toxin in rheumatology Guy Monnier*, Laurent Tatu, Fabrice Michel Neuromuscular Diseases and Investigations, Jean-Minjoz Teaching Hospital, 3, boulevard Fleming, 25030 Besancon cedex, France Received 24 October 2005; accepted 21 March 2006 Available online 30 August 2006

Abstract Previously known only as a deadly bacterial poison responsible for severe paralysis, botulinum toxin is now a well-recognized therapeutic agent used to relieve involuntary movements, dystonia-related functional impairments, spasticity, and autonomic disorders such as hyperhidrosis. Musculoskeletal pain in patients with rheumatic disorders is among the emerging indications for botulinum toxin therapy. Preliminary data have been obtained in patients with cervical or thoracolumbar myofascial pain syndrome, chronic low back pain, piriformis muscle syndrome, tennis elbow, and stiff person syndrome. At present, the effects of botulinum toxin and its use for pain relief remain controversial. Carefully designed prospective trials are needed to investigate the efficacy and safety of botulinum toxin in pain disorders. © 2006 Elsevier Masson SAS. All rights reserved. Keywords: Botulinum toxin; Rheumatology; Chronic myofascial pain

1. Introduction The indications for botulinum toxin (BTX) therapy are expanding and will probably include a number of musculoskeletal diseases in the near future. Several muscle and joint diseases managed by rheumatologists may benefit from the muscle-inhibiting effects of BTX. Furthermore, recent data suggest that BTX may exert specific analgesic effects. 2. Botulinum toxin 2.1. Properties BTX is the most potent neurotoxin identified to date. By inhibiting the release of acetylcholine (ACh) at the neuromuscular junction, BTX causes paralysis and muscle wasting. This effect can be used to treat disorders characterized by muscle overactivity. The effect fades after a few weeks as a result of the growth of new nerve endings, so that the injections must be repeated at intervals of a few months. When injected intramuscularly, the toxin diffuses to about 45 mm from the injection site. It may also act at a greater distance either by antidromic * Corresponding

author. E-mail address: [email protected] (G. Monnier).

1297-319X/$ - see front matter © 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2006.03.005

diffusion along the motor neuron axons to the ventral horn, without crossing the blood-brain barrier, or via the bloodstream. Diffusion into the bloodstream may explain some of the side effects that are discussed later in this article. 2.2. Pharmacology Seven botulinum neurotoxin serotypes, labeled A through G, have been identified. Serotypes A through F are produced by different Clostridium botulinum strains and serotype G by Clostridium argentinense. The neurotoxin complexed with nonneurotoxic proteins constitutes BTX, which is the form used as a therapeutic agent [1]. In humans, serotypes A, B, E, F, and G exert pharmacological effects, whereas C and D are inactive. 2.3. Therapeutic uses 2.3.1. Products The most widely used BTX is type A (Botox® and Dysport®), although a few indications for type B (Neurobloc®) have emerged. These products have slightly different marketing authorizations but their specific characteristics and bioequivalence will not be discussed in this article [2].

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2.3.2. Indications BTX was first used in 1977 to treat esotropia in children. Its indications were rapidly expanded to include blepharospasm, hemifacial spasm, and spasmodic torticollis. BTX was then found to be effective in other dystonic disorders, involuntary movement disorders, and focal spasticity, as well as in autonomic function disorders such as hyperhidrosis and sialorrhea in patients with neurological disorders. Contraindications include pregnancy and lactation, myasthenia, Lambert–Eaton syndrome, and amyotrophic lateral sclerosis. Extreme caution is in order in patients who have peripheral neurological disorders with neurogenic manifestations (e.g. facial spasm after facial palsy). The effects of BTX are potentiated by aminoglycosides and cyclosporine and diminished by aminoquinolines. A history of allergic disorders indicates an increased risk for adverse events. BTX therapy in the past is associated with increased sensitivity to neuromuscular blockers, requiring close monitoring in situations that require neuromuscular blockade. 2.3.3. Practical modalities The practical modalities of BTX therapy vary somewhat according to the underlying condition. In patients with blepharospasm or hemifacial spasm, the toxin should be injected into the deep subcutaneous tissue of the muscles involved in the abnormal movements. Good knowledge of local anatomy is essential. Among the other disorders treated with BTX, esotropia is managed by ophthalmologists, laryngeal and orofacial dystonia by otorhinolaryngologists, and hyperactive bladder by neurourologists. In patients with dystonia or muscle spasm, BTX diminishes the muscle overactivity, thereby improving motor function. Guidelines for the use of BTX in cerebral palsy [3] indicate that BTX therapy should be reserved for the treatment of focal spasticity or for achieving focal improvements in patients with generalized abnormalities, in the absence of fixed contractures. A reasonable treatment goal should be developed with the patient and incorporated into a multidisciplinary management program. The muscles to be injected vary according to the treatment goal. The maximum dose, which depends on body weight and toxin type, governs the number of muscles that can be injected. The number of injection sites per muscle is relatively consistent in adults but varies in children with body size and muscle development. Electrophysiological testing is generally used to identify the target muscles. Although large superficial muscles can be easily palpated, electrophysiological testing is the best means of identifying the target neuromuscular junctions of deep muscles and of muscles located in complex environments. Hollow needles are used for electromyogram (EMG) recording, electrical stimulus delivery, and BTX injection. The sound produced by motor unit activity and transmitted through the recording device loudspeaker can be used to guide needle placement. Alternatively, electrical stimuli can be delivered while moving the needle to locate the site of greatest mechanical effectiveness at a given threshold intensity. Mechanical effectiveness is assessed based on contraction amplitude if the muscle is superficial and on joint motion amplitude if the muscle itself

is not visible. Side effects are uncommon and usually benign. They include local diffusion, transient injection site pain or hematoma, short-lived asthenia, increased sensitivity to cold, vertigo, flu-like syndrome, and gastrointestinal symptoms. One death has been reported, in a patient with chronic obstructive lung disease who received BTX injections into the neck, as well as two cases of botulism-like syndrome. BTX is the main therapeutic tool in conditions such as blepharospasm, hemifacial spasm, or orofacial dystonia. In many situations, however, BTX is a component of a complex treatment program in which rehabilitation therapy plays a central role. BTX can be used in combination with a number of medications, including baclofen, benzodiazepines, anticholinergic agents, and dopamine agonists. However, BTX is often used as a medication of last resort in patients who fail to respond to other treatment options. In France, both BTX-A products (Botox® and Dysport®) were initially licensed for the treatment of blepharospasm, spasmodic torticollis, and hemifacial spasm; Botox® was also approved for ocular motility disorders in pediatric patients. Approved indications were subsequently expanded to include dynamic pes equinus in cerebral palsy patients older than 2 years of age, upper limb spasticity in stroke patients, and axillary hyperhidrosis. BTX injection was restricted at first to a few categories of specialists but can now be performed by all “specialists who have a good level of experience with BTX therapy in their field” [4]. BTX is available only at hospitals, by restricted prescription, and can be administered by “specialists who work in specialized departments of private healthcare facilities” or by “prescribing physicians who work in specialized departments under the responsibility of the department head in public healthcare facilities” [4]. 3. Effects of botulinum toxin on pain The muscle-relaxing effect of BTX alleviates the pain due to cervical dystonia or spasticity [5]. Only recently has pain emerged as an indication for BTX therapy [6]. The mechanism underlying the analgesic effect of BTX has not been fully elucidated. Wissel et al. [7] suggested that pain relief occurred only when the pain was caused by muscle overactivity. However, the decreased strength and amplitude of abnormal movements fails to fully explain the analgesic effect of BTX [8]. Rosales et al. [9] showed that BTX acted on intrafusal and extrafusal fibers, thus reducing the activity of neuromuscular spindles. Filippi et al. [10] reported evidence that BTX blocks the gamma motor endings, thereby diminishing input to the alpha-motoneurons and decreasing reflex muscular tone. Evidence suggesting antidromic diffusion of BTX has been reported [11,12]. Using labeled BTX, Aoki [13] showed reuptake by the central nervous system of BTX metabolites that might affect the exocytosis of neurotransmitters and neuropeptides involved in pain. Peripheral chemodenervation may not be the only mechanism by which BTX affects nociception [14]. Inhibition of inflammatory processes via incompletely understood mechanisms may contribute to the analgesic effect of BTX [15]. In rats, BTX was found to inhibit substance P, a

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potent neurotransmitter capable of activating neurogenic inflammation [16,17], or to stimulate naturally occurring analgesics such as enkephalin [18]. Much work remains to be done before widespread use of BTX can be recommended as a means of obtaining pain relief. In several studies [19,20], the patients reported discomfort, particularly when deep muscles were injected. Injection site pain occurred in 38% of patients in one study [19]. 4. Botulinum toxin in rheumatology BTX may hold promise for the treatment of cervical and thoracolumbar myofascial pain, chronic low back pain, piriformis muscle syndrome, epicondylitis, and stiff person syndrome. In addition, new indications such as thoracic outlet syndrome are generating debate [23]. The rapid expansion of indications for BTX therapy is in sharp contrast to the initial attitude of prudent insistence on the need for standardized evidence-based protocols [3]. Clinical proof that BTX therapy effectively relieves chronic musculoskeletal pain is lacking [22–24]. Studies are needed to determine the total dose, dose per injection point, number of injection points per site, injection routes, and follow-up modalities [23]. Analgesic effects of BTX were reported in 1986 by Tsui et al. [25] in patients with spasmodic torticollis. The first evidence of efficacy in chronic myofascial pain came from two 1994 reports, one on a single patient [26] and the other on six patients [27]. The first large case-series was an open-label trial reported by Alo et al. in 1997 [28]. The long-term effects of BTX were investigated in 52 patients with myofascial pain of the neck and shoulder girdle or of the thoracolumbar paraspinal and pelvic muscles [28]. The injection sites were determined individually based on the physical findings. Needle placement was guided by fluoroscopic monitoring of contrast agent diffusion. There were many side effects, which were probably caused in part by the contrast agent. In later review De Seze et al. (2003) [29] found only six articles on the use of BTX to treat chronic neck pain. In addition, the symptoms varied widely [27,30], and the underlying causes ranged from whiplash injury [31,32] to fibromyalgia [21]. The Botox® doses varied from 50 to 230 units. The trapezius muscle was the most common injection site. The results were inconsistent; for instance, two studies conducted by the same groups yielded contradictory results [33,34]. The largest studies of BTX therapy in myofascial pain were conducted by Lang [35] in 72 patients and by Royal et al. [36] in 104 patients. The results were encouraging, indicating a need for controlled trials. Few studies of BTX therapy for chronic low back pain have been reported. Foster et al. [37] conducted a randomized double-blind placebo-controlled trial in 31 patients. Botox® was used in 15 patients, in a dose of 200 units divided among five points in the lumbar paraspinal muscles on the side of greatest pain. The 16 remaining patients received saline injections. Significant improvements in pain and function were noted in the BTX group 3 and 8 weeks after the injections. No benefits were apparent after 6 months. No side effects were reported in the BTX group. Difazio and Jabbari [38] underlined

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the impact of pain severity, duration, and underlying cause on treatment decisions and reviewed data indicating that BTX provided local relief at the site of pain without inducing systemic effects. These authors, together with Jost et al. [39], emphasized the need for controlled trials in larger populations of patients with nonsymptomatic back pain refractory to conventional treatment, in the absence of contraindications to BTX use. Piriformis muscle syndrome is an uncommon condition whose treatment with BTX has generated strong interest over the last few years. Of the five studies published between May 2001 and January 2004, three used BTX-A [40–42] and two used BTX-B [43,44]. In a study of 30 patients, Fanucci et al. [40] used computed tomography guidance; in addition, 3 months after the injection, nine patients underwent magnetic resonance imaging, which showed piriformis muscle wasting and denervation-related signal changes. Of the 30 patients, 26 reported symptom relief within 5–7 days and four had a similarly excellent result after a second injection. A randomized placebo-controlled cross-over trial by Childers et al. [42] showed pain relief after intramuscular injection of 100 IU of Botox® at a single site. Fishman et al. [41] reported that BTX used as an adjunct to physical therapy induced greater pain relief than a mixture of lidocaine and methylprednisolone. A dose-finding study conducted 2 years later by the same group [44] investigated the effects of 5000, 7500, 10,000, and 12,500 IU of BTX-B in 27 patients with piriformis muscle syndrome. The evaluation done 2 weeks post-injection showed better results in the group given 12,500 IU as an adjunct to physical therapy. Lang [43] investigated the effects of BTX-B in 20 patients with piriformis muscle syndrome. BTX-B in a dose of 5000 IU per site was injected unilaterally or bilaterally. Good or excellent results were noted in 90% of patients. In most studies of piriformis syndrome, EMG was used to guide needle placement [41–44]. An open uncontrolled study of 16 patients with tennis elbow showed good results after BTX injection into the tendons of the epicondylar muscles [45]. In a randomized controlled trial, 20 patients received 50 IU of BTX-A injected 5 cm distal to the point of maximum tenderness upon palpation of the lateral epicondyle [46]. Saline was injected at the same site in the 20 controls. No differences were noted between the two groups 3 months after the injection. However, another randomized study indicated that BTX was as effective as surgery [47], producing good or excellent 12-month outcomes in 65% of patients. Scant data are available on the effects of BTX in stiff person syndrome. In 1993, Davis and Jabbari [48] reported dramatic improvements in pain, stiffness, gait, and radiographic lumbar hyperlordosis in a patient given a total dose of 560 IU of BTXA (probably Dysport®) in three sessions spaced 1 week apart (160 IU during the first session and 200 IU during each of the two other sessions). BTX-A was injected at five sites in the lumbar paraspinal muscles, from L1 to L5, on both sides, in a dose of 16–20 IU per site. Thigh muscle overactivity improved after the paraspinal injections. In 1997, Liguori et al. [49] reported that BTX-A injections improved rigidity and spasms

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in two patients with stiff person syndrome. One patient received 700 IU of BTX-A (Dysport®) into the quadriceps, adductor muscles, hamstring muscles, and calf muscles, whereas the other patient received 1000 IU of the same product into the proximal upper limb muscles. In both patients, BTX-A was injected on one side of the body and saline on the other; the patient and evaluator were unaware of the order of the injections. After 6–9 days, the rigidity was substantially improved and the spasms had stopped. A significant decrease in spasm frequency was also noted on the side treated with saline injections. 5. Discussion The indications for BTX therapy are expanding at a rapid pace. However, new uses for BTX should rest on sound scientific evidence, and physicians who perform BTX injections should be thoroughly conversant with the advantages and drawbacks of this treatment modality. Evidence that BTX is safe has accumulated over the years, and the cost of BTX has decreased. Nevertheless, further controlled studies in large numbers of patients are needed to determine the optimal indications and modalities of BTX therapy. In chronic myofascial pain, further evidence of efficacy is needed [27,32–35]. Several studies recommend that BTX be injected at trigger points, which are tender points located in hypertonic muscles or their fascias [14,50,51]. However, additional work is needed to standardize the injection site distribution, total dose, dose per injection site, and frequency of injection sessions. The mechanism by which BTX may alleviate chronic myofascial pain remains unknown. Pain relief is not obtained consistently. Carefully designed prospective trials of BTX therapy in chronic myofascial pain are awaited. In chronic low back pain and piriformis muscle syndrome, a plausible mechanism of action of BTX is decreased muscle overactivity related to inhibition of ACh release. In addition, specific muscles are involved and can be identified to ensure that the injections reach their targets. We agree with Comella et al. [52] that EMG guidance is the simplest and fastest method. In addition, in experienced hands and with proper equipment, EMG guidance is extremely reliable. We do not have experience with CT guidance [40] or ultrasound guidance, with or without fluoroscopic monitoring; both methods are more cumbersome than EMG guidance. Piriformis muscle syndrome shares similarities with focal spasticity or dystonia. The diagnosis rests on a thorough, reproducible, and comparative physical examination. Typical findings include external rotation of the limb on the involved side [53] and contraction of the piriformis muscle [53]. Specific maneuvers that passively stretch the muscle or cause it to contract should be performed in the standing position [54], in the seated position [55], in the supine position [56], and in the lateral decubitus position [57]. Similar to magnetic resonance imaging, electrophysiological testing may assist in the diagnosis. Of particular interest is investigation of proximal conduction in the ischiatic nerve via recording of delayed latency responses, most notably the H-reflex delay induced by flexion, adduction, and internal rotation of the

lower limb [58]. The injection site should be determined on the basis of well-defined landmarks and EMG findings. We use landmarks that differ slightly from those described by Benzon et al. [59]. Physical therapy is used in addition to BTX in most cases. Potential mechanisms by which BTX may improve tennis elbow remain speculative. BTX may relax tension on the tendons by inducing partial paralysis of the wrist and/or finger extensors, thereby replicating the effects of surgical tenotomy [47]. BTX may not have any advantages over surgery [45]. At present, BTX is considered only in patients who fail to respond to other nonsurgical treatments [46,60]. The role for BTX therapy in stiff person syndrome remains unclear. BTX induces focal changes, whereas stiff person syndrome is characterized by widespread muscle overactivity. The muscles to be injected should be identified according to the goals of treatment in terms of pain relief and functional gains. BTX should be incorporated into a well-defined treatment program. Spreading the maximum dose over a large number of muscles reduces treatment efficacy. The two reports of BTX therapy in patients with stiff person syndrome [48,49] point out that improvements occurred at a distance from the BTX injection sites: in one patient, overactivity of the ipsilateral thigh muscles decreased after injection into the lumbar paraspinal muscles [48], and in two patients bilateral improvements occurred although BTX was injected on one side and saline on the other [49]. These findings may suggest hematogenous diffusion of BTX. However, in our experience with over 1000 patients treated for dystonia or spasticity, we have not observed improvements on the untreated side after unilateral BTX injections. In sum, further work is needed to determine the efficacy, mechanisms of action, and modalities of use of BTX therapy. References [1] Poulain B, Humeau Y. Le mode d’action des neurotoxines botuliques : aspects pathologiques, cellulaires et moléculaires. Ann Readapt Med Phys 2003;46:286–95. [2] Gury C. Aspects pharmacologiques et médicoéconomiques. In: Ranoux D, Gury C, editors. Manuel d’utilisation pratique de la toxine botulique. Marseille: Solal; 2002. p. 13–32. [3] Graham HK, Aoki KR, Autti-Rämö I, Boyd RN, Delgado MR, GaeblerSpina DJ, et al. Recommendations for the use of botulinum toxin type A in the management of cerebral palsy. Gait Posture 2000;11:67–79. [4] Gury C, Duneau M, Ranoux D. Aspects réglementaires. In: Ranoux D, Gury C, editors. Manuel d’utilisation pratique de la toxine botulique. Marseille: Solal; 2002. p. 263–70. [5] Jankovic J, Schwartz K. Botulinum toxin injections for cervical dystonia. Neurology 1990;40:277–80. [6] Thant ZS, Tan EK. Emerging therapeutic applications of botulinum toxin. Med Sci Monit 2003;9:RA40–RA48. [7] Wissel J, Muller J, Dressnandt J, Heinen F, Naumann M, Topka H. Management of spasticity associated pain with botulinum toxin A. J Pain Symptom Manage 2000;20:44–9. [8] Simon O, Raibaut P, Faucher M, Sheik-Ismael S, Amarenco G. Toxine botulique et céphalées. Ann Readapt Med Phys 2003;46:312–8. [9] Rosales RL, Arimura K, Takenaga S, Osame M. Extrafusal and intrafusal muscle effects in experimental botulinum toxin-A injection. Muscle Nerve 1996;19:488–96.

G. Monnier et al. / Joint Bone Spine 73 (2006) 667–671 [10] Filippi GM, Errico P, Santarelli R, Bagolini B, Manni E. Botulinum A toxin effects on rat jaw muscle spindles. Acta Otolaryngol 1993;113: 400–4. [11] Wiegand H, Erdmann G, Wellhoner HH. 125 I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. Naunyn Schmiedebers Arch Pharmacol 1976;292:161–5. [12] Wiegand H, Wellhoner HH. The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex. Naunyn Schmiedebergs Arch Pharmacol 1977;298:235–8. [13] Aoki KR. Pharmacology and immunology of botulinum toxin serotypes. J Neurol 2001;248(Suppl 1):3–10. [14] Göbel H, Lindner V, Krack P, Heinze A, Gaartz N, Deuschl G. Treatment of chronic tension-type headache with botulinum toxin. Cephalalgia 1999;19:455. [15] Borodic GE, Acquadro M, Johnson EA. Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects. Expert Opin Investig Drugs 2001;10:1531–44. [16] Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon 2000;38:245–58. [17] Cui M, Aoki R. Botulinum toxin A inhibits the inflammatory pain in the rat formalin model. Cephalalgia 2000;20:20–41. [18] Humm AM, Pabst C, Lauterburg T, Burgunder JM. Enkephalin and aFGF are differentially regulated in rat spinal motoneurons after chemodenervation with botulinum toxin. Exp Neurol 2000;161:361–72. [19] Lorentz IT, Subramaniam SS, Yiannikas C. Treatment of idiopathic spasmodic torticollis with botulinum toxin A: a double blind study on twenty-three patients. Mov Disord 1991;6:145–50. [20] Ceballos-Baumann AO. Evidence-based medicine in botulinum toxin therapy for cervical dystonia. J Neurol 2001;248(Suppl 1):14–20. [21] Paulson GW, Gill W. Botulinum toxin is unsatisfactory therapy for fibromyalgia. Mov Disord 1996;11:459. [22] Sheean G. Botulinum toxin for the treatment of musculoskeletal pain and spasm. Curr Pain Headache Rep 2002;6:460–9. [23] Lang AM. Botulinum toxin type A therapy in chronic pain disorders. Arch Phys Med Rehabil 2003;84(Suppl 1):69–73. [24] Borodic GE, Acquadro MA. The use of botulinum toxin for the treatment of chronic facial pain. J Pain 2002;3:21–7. [25] Tsui JK, Eisen A, Stoessl AJ, Calne S, Calne DB. Double-blind study of botulinum toxin in spasmodic torticollis. Lancet 1986;2:245–7. [26] Acquadro MA, Borodic GE. Treatment of myofascial pain with botulinum A toxin. Anesthesiology 1994;80:705–6. [27] Cheshire WP, Abashian SW, Mann JD. Botulinum toxin in the treatment of myofascial pain syndrome. Pain 1994;59:65–9. [28] Alo KM, Yland MJ, Kramer DL. Botulinum toxin in the treatment of myofascial pain. Pain Clin 1997;10:107–16. [29] De Seze MP, DE Seze M, Dehail P, Joseph PA, Lavignolle B, Barat M. Toxine botulique A et douleurs musculosquelettiques. Ann Readapt Med Phys 2003;46:329–32. [30] Wheeler AH, Goolkasian P, Gretz SS. Botulinum toxin A for the treatment of chronic neck pain. Pain 2001;94:255–60. [31] Freund BJ, Schwartz M. Treatment of whiplash associated neck pain with botulinum toxin-A: report of 8 cases. J Rheumatol 1999;26:756–8. [32] Freund BJ, Schwartz M. Treatment of whiplash associated neck pain (corrected) with botulinum toxin-A: a pilot study. J Rhumatol 2000;27: 481–4. [33] Wheeler AH, Goolkasian P, Gretz SS. A randomized double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine 1998;23: 1662–6. [34] Wheeler AH, Goolkasian P. Open label assessment of botulinum toxin A for pain treatment in a private outpatient setting. J Musculoskeletal Pain 2001;9:67–82. [35] Lang AM. A pilot study of botulinum toxin type A (Botox®), administered using a novel injection technique, for the treatment of myofascial pain. Am J Pain Manage 2000;10:108–12. [36] Royal MA, Gunyea I, Bhakta B, Movva V, Ward S, Jenson M. Botulinum toxin type A in the treatment of refractory myofascial pain. Neurology 2001;56(Suppl 3):350 [abstract].

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[37] Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double-blind study. Neurology 2001;56:1290–3. [38] Difazio M, Jabbari B. A focused review of the use of botulinum toxins for low back pain. Clin J Pain 2002;18(6 Suppl):155–62. [39] Jost WH, Reilich P, Pongratz D. Botulinum toxin in low back pain. In: Jost WH, editor. Botulinum toxin in painful diseases Pain headache, vol. 14. Basel: Karger; 2003. p. 159–69. [40] Fanucci E, Masala S, Sodani G, Varrucciu V, Romagnoli A, Squillaci E. CT guided injection of botulinic toxin for percutaneous therapy of piriformis muscle syndrome with preliminary MRI results about denervative process. Eur Radiol 2001;11:2543–8. [41] Fishman LM, Anderson C, Rosner B. Botox and physical therapy in the treatment of piriformis syndrome. Am J Phys Med Rehabil 2002;81:936– 42. [42] Childers MK, Wilson DJ, Gnatz SM, Conway RR, Sherman AK. Botulinum toxin type A use in piriformis muscle syndrome: a pilot study. Am J Phys Med Rehabil 2002;81:751–9. [43] Lang AM. Botulinum toxin type B in piriformis syndrome. Am J Phys Med Rehabil 2004;83:198–202. [44] Fishman LM, Konnoth C, Rozner B. Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: a dose finding study. Am J Phys Med Rehabil 2004;83:42–50. [45] Placzek R, Lindner MS, Deuretzbacher G. Therapy for chronic radial epicondylitis with botulinum toxin A. Z Orthop Ihre Grenzgeb 2004;142: 701–5 [switch these two references]. [46] Hayton MJ, Santini AJ, Hugues PJ, Frostick SP, Trail JA, Stanley JK. Botulinum toxin injection in the treatment of tennis elbow. A doubleblind, randomized, controlled, pilot study. J Bone Joint Surg Am 2005; 87:503–7. [47] Keizer SB, Rutten HP, Pilot P, Morre HH, Vos JJ, Verburg AD. Botulinum toxin injection versus surgical treatment for tennis elbow: a randomized pilot study. Clin Orthop Relat Res 2002;401:125–31. [48] Davis D, Jabbari B. Significant improvement of stiff-person syndrome after para-spinal injection of botulinum toxin A. Mov Disord 1993;8: 371–3. [49] Liguori R, Cordivari C, Lugaresi E, Montagna P. Botulinum toxin A improves muscle spasms and rigidity in stiff-person syndrome. Mov Disord 1997;12:1060–3. [50] Simons DG, Travell JG, Simons LS. Travell and Simons’myofascial pain and dysfunction: the trigger point manual, vol. I: Upper half of body, ed. 2. Baltimore: Williams and Wilkins; 1999. [51] Wolfe F, Simons DG, Fricton J. The fibromyalgia and myofascial pain syndromes: a preliminary study of tender points and trigger points in persons with fibromyalgia, myofascial pain syndrome and no disease. J Rheumatol 1992;19:944–51. [52] Comella CL, Buchman AS, Tanner CM, Brown-Toms NC, Goetz G. Botulinum toxin injections for spasmodic torticollis: increased magnitude of benefits with electromyographic assistance. Neurology 1992;42:878– 82. [53] Brown JA, Braun MA, Namey TC. Piriformis syndrome in a 10-year-old boy as a complication of operation with the patient in the sitting position. Neurosurgery 1988;23:117–9. [54] Goussard JC. Le syndrome du pyramidal. Aspects cliniques et traitement. Rev Med Orthoped 1990;19:27–31. [55] Pace JB, Nagle D. Piriform syndrome. West J Med 1976;47:1144–6. [56] Freiberg AH. The fascial elements in associated low-back and sciatic pain. J Bone Joint Surg 1934;16:126–36. [57] Beatty RA. The piriformis muscle syndrome: a simple diagnostic manoeuver. Neurosurgery 1994;34:512–4. [58] Fishman LM, Zybert PA. Electrophysiologic evidence of piriformis syndrome. Arch Phys Med Rehabil 1992;73:359–64. [59] Benzon HT, Katz JA, Benzon HA. Piriformis syndrome: anatomic considerations, a new injection technique, and a review of the literature. Anesthesiology 2003;98:1442–8. [60] Boisaubert B, Brousse C, Zaoui A, Montigny JP. Les traitements non chirurgicaux de la tendinopathie des épicondyliens. Ann Readapt Med Phys 2004;47:346–55.