Introduction

Focal hand dystonia (FHD) is characterized by dystonic hand contractions that are often aggravated by purposeful actions and may be specific to a particular task. For example, a patient may have dystonia when using the hand for writing but not for other tasks such as eating or typing. The term “occupational dystonia” is used when dystonia affecting performance of the job arises in individuals with a particular occupation, usually an occupation requiring repetitive and excessive fine motor activity. The occupations particularly prone to have focal task-specific dystonia are listed in Table 10.1. Most of these hand dystonias fall under the rubric of primary focal dystonias.

This chapter discusses writer’s cramp and musician’s dystonia (cramp) in detail, the two most common occupational dystonias, followed by a discussion of other focal occupational dystonias.

Pathogenesis

The exact cause of FHD is not yet elucidated. A consistent physiological finding is excessive activation of antagonists and overflow and prolongation of muscle activation. Both of these are thought to reflect deficiency of inhibition at multiple levels of the motor system circuitry (Hallett, 2000, 2006a,b). Dopamine dysfunction has also been implicated. Although FHD is a movement disorder, somatosensory dysfunction is also present, including distorted sensory maps of the affected hand (Bara-Jimenez et al., 1998) and impaired sensory discrimination (Sanger et al., 2001). Structural MRI analyses have shown increased gray matter volume in the basal ganglia of musicians (Granert et al., 2011) and writers (Garraux et al., 2004) with FHD. Functional MRI has shown impaired activation of the primary sensorimotor and supplementary motor cortex during voluntary muscle relaxation and contraction (Oga et al., 2002). A genetic factor in the development of hand dystonia is possible, as up to 20% of patients with writer’s cramp have family members with dystonia.

The injection of botulinum neurotoxin (BoNT) for cosmetic purposes is the most commonly performed cosmetic procedure in the USA, with 4 million such procedures performed in 2011 alone (American Society for Aesthetic Plastic Surgery, 2011).

With time, overlying skin loses both its elasticity and thickness. This, coupled with repeated pleating and contraction of the skin over many years, will result in wrinkles. Cosmetically, the primary function of BoNT is to paralyze the muscles of facial expression. By relaxing the relevant underlying muscles of facial expression, BoNT will eliminate the so-called “dynamic” rhytids (wrinkles). Over time, even the appearance of static rhytids may be improved. In a 2007 study, patients reported looking 3 years’ younger than baseline 4 weeks after receiving BoNT to the upper face (Carruthers and Carruthers, 2007)

Currently (2012), there are three BoNT type A (BoNT-A) formulations with a cosmetic indication available in the USA: onabotulinumtoxinA (Botox, Allergan. Irvine, CA, USA), abobotulinumtoxinA (Dysport, Ipsen, Slough, UK) and incobotulinumtoxinA (Xeomin, Merz, Frankfurt/M, Germany). All are approved for the treatment of glabellar lines.

Introduction

Visible scars, particularly on the face, may have important social and psychological implications and are a significant concern for patients before undergoing surgery. Many new developments in science and medicine have been driven by the desire to minimize or eliminate scars, including endoscopic, minimally invasive and robotic surgeries. Despite these innovations, many procedures still require open incisions, resulting in visible scars, and research into scarless healing continues.

To optimize healing and minimize scarring, an understanding of the wound-healing process is of critical importance. The first phase of wound healing, the inflammatory phase, generally lasts a few days and is characterized by vasodilation and cellular response. The wound must be thoroughly irrigated and meticulously cleaned to maintain asepsis and discourage the persistence of macrophages and other inflammatory cells that prolong inflammation.

The second phase of wound healing, the proliferative phase, is characterized by epithelial regeneration and collagen synthesis. This phase lasts several weeks and may overlap the inflammatory phase. Epithelial regeneration is greatly improved if wounds are closed by primary intention; wounds that heal by secondary intention take much longer for this process.

Introduction

Hyperhidrosis may generally be defined as excessive sweating or sweating beyond physiological needs. It may be divided into generalized, regional and localized/focal types and, according to whether the cause is known or not, into primary/idiopathic and secondary forms. Secondary hyperhidrosis can be induced by a number of infectious, endocrine, metabolic, cardiovascular, neurological, psychiatric and malignant conditions; it can also be caused by certain drugs and poisoning. The prevalence of hyperhidrosis in the US population has been calculated at 2.8% (Strutton et al., 2004). Of those, primary axillary hyperhidrosis appears to be the most frequent type, severely affecting 0.5%.

Box 22.1 gives the diagnosis of primary focal hyperhidrosis set out by a multispecialty working group (Hornberger et al., 2004). It usually starts in childhood or adolescence and mainly involves the armpits, palms, soles and craniofacial region, either alone or in various combinations. There are well-known, particularly emotional, triggers of sweating episodes, but the exact pathogenesis of the sympathetic overstimulation of eccrine sweat glands is still poorly understood apart from a clear genetic background.

Clinical aspects of headache disorders

Headache affects more than 45 million individuals in the USA, which makes it one of the most common nervous system disorders (National Institute of Neurological Disorders and Stroke, 2002). The International Headache Society’s diagnostic criteria for headache disorders (ICHD-II, Headache Classification Committee, 2004) classifies primary headache disorders as those in which headache itself is the illness, with no other etiology diagnosed. Examples include migraine and tension-type headache (TTH). Headache disorders can be further classified as episodic (<15 headache days per month) or chronic (≥15 headache days per month for more than 3 months).

Migraine is a primary headache disorder characterized by enhanced sensitivity of the nervous system (Silberstein, 2000) associated with a combination of neurological, gastrointestinal and autonomic disturbances (Silberstein, 2004). The ICHD-II has provided criteria for a total of seven subtypes of migraine (including migraine with and migraine without aura). The ICHD-II diagnostic criteria for migraine without aura (Headache Classification Committee, 2004) include

• headache associated with at least two of the following: unilateral location, pulsating quality, moderate or severe pain intensity and aggravation by or causing avoidance of routine physical activities

• at least one of the following during headache: nausea and/or vomiting, photophobia and phonophobia

• headache not attributable to another disorder.

It is estimated that 28 million Americans, including 18% of women and 7% of men, are afflicted with severe, disabling migraines (Lipton et al., 2001). The World Health Organization (2012) ranked migraine as one of the world’s most disabling illnesses, profoundly impacting quality of life and causing functional impairment and disruption of household or social activities. The economic burden of the disease to society is also considerable. In the USA, the yearly medical costs exceed 1 billion dollars, and costs to employers due to migraine-related absenteeism and reduced productivity is 13 billion dollars (Hu et al., 1999).

Cricopharyngeal dysphagia

The cricopharyngeal muscle, or upper esophageal sphincter (UES), corresponds to the most inferior portion of the inferior constrictor muscle. It creates a sphincter separating the hypopharynx from the esophagus, preventing the inlet of air into the esophagus during inspiration and esophageal reflux into the pharynx. It is myoelectrically silent at rest and active during swallowing.

Cricopharyngeal dysphagia arises from dysfunction of the cricopharyngeal muscle, which can be primary or secondary to a number of pathological conditions, including cerebrovascular accidents, amyotrophic lateral sclerosis, oculopharyngeal muscular dystrophy and skull basal lesion. Oropharyngeal dysphagia is the clinical presentation and possibly correlates with aspiration or penetration of liquid or food into the upper airways. During manometry, incomplete relaxation of the UES or an increase in intrabolus pressure may be demonstrated (Fig. 32.1).

Cricopharyngealmuscle dysfunction has been traditionally treated with surgical myotomy, mechanical dilatation or plexus neurectomy. Localized injections of botulinum neurotoxin (BoNT) into the dorsomedial or ventrolateral parts of the muscle have also been successfully performed endoscopically, percutaneously (Fig. 32.1a) and eventually under CT or fluoroscopic control, with or without electromyographic (EMG) guidance (Fulmer et al., 2011). Unfortunately, there are no standards or guidelines and the administered dose reported ranges widely between 10 and 120 U onabotulinumtoxinA, usually selected on the basis of symptom severity.

Introduction

Plantar fasciitis (PF) is the most common cause of chronic heel pain and is a major health issue in runners and long-distance walkers. It affects 2 million people in the USA and results in approximately 1 million visits to the physician office, 62% of which are to primary care physicians. The annual cost of treatments is estimated to be between $192 and $376 million (Tu and Bytomski, 2011). Overuse injury may lead to repetitive microtears of the plantar fascia near the calcaneus, irritating pain fibers and producing secondary inflammation. Other risk factors include obesity, flat or overarched feet and improper shoes. The pain usually involves the inferior and medial aspect of the heel (calcaneus), at the medial aspect of the calcaneal tubercle. However, the entire course of the plantar fascia may be involved. Patients typically have intense heel pain, described as aching, jabbing or burning pain, with the first couple of steps in the morning. Pain is reproduced by palpation of the median tubercle of the calcaneum and with dorsiflexion of the toes (Windlass test) (Young, 2012). In many patients, the application of ice and/or the use of heel cup orthosis activity modification and a stretching/strengthening exercise program reduce the pain satisfactorily. Further measures include deep-tissue massage therapy, night splints and periods of immobilization. Persistent problems may respond to treatment with posterior night splints, ultrasound, iontophoresis, phonophoresis, extracorporal shock wave therapy or even local corticosteroid injections (Goff and Crawford, 2011). Where medical approaches fail, surgery is advocated but has modest results. Approximately 10–12% of patients fail to achieve pain relief from medical and/or surgical treatment.

Introduction

Cervical dystonia (CD), originally known as spasmodic torticollis and first described by Foltz in 1959, is a neurological syndrome characterized by abnormal head and neck posture caused by tonic involuntary contractions in a set of cervical muscles. However, CD and spasmodic torticollis are not interchangeable: CD is the preferred term when referring to idiopathic focal dystonia of the neck. Spasmodic torticollis is now considered to be one of four types of CD. Cervical dystonia is classified into four types based on the principal direction of head posture:

• torticollis: abnormal rotation of the head to the right or to the left in the transverse plane

• laterocollis: the head tilts toward the right or left shoulder

• antecollis: the head pulls forward with neck flexion

• retrocollis: the head pulls back with the neck hyperextended.

Cervical dystonia is slightly more common in females, with a male to female ratio of 1:1.2 (Kessler et al., 1999). Onset is usually insidious, although in some patients the onset has been reported as sudden. Cervical dystonia may develop in patients of all age groups, but the peak age of onset is 41 years (Kessler et al., 1999). Idiopathic CD usually progresses in severity over the first 5 years until it reaches a plateau, after which it remains fairly constant and becomes a lifelong condition. Although remission can occur, it is rare and the dystonia usually returns after a period of time. The cervical component may also exist as part of a more extensive form of dystonia, in which the dystonia can spread to involve adjacent structures such as the face or the arm(s). When dystonia involves several contiguous body parts, it is considered segmental dystonia. When it involves several parts of the body that are not contiguous, such as the neck and foot, it is called multifocal, and when it involves the majority of the body, it is referred to as generalized dystonia.

Introduction

Spasticity is part of the upper motor neuron syndrome produced by conditions such as stroke, multiple sclerosis, traumatic brain injury, spinal cord injury or cerebral palsy that affect upper motor neurons or their efferent pathways in the brain or spinal cord. It is characterized by increased muscle tone, exaggerated tendon reflexes, repetitive stretch reflex discharges (clonus) and released flexor reflexes (great toe extension; flexion at the ankle, knee and hip) (Lance, 1981). Late sequelae may include contracture, pain, fibrosis and muscle atrophy.

Chemodenervation by intramuscular injection of botulinum neurotoxin (BoNT) can reduce spastic muscle tone (usually measured by the Ashworth Scale or Modified Ashworth Scale), normalize limb posture, ameliorate pain, modestly improve motor function (measured by performance of standardized motor tasks or activities of daily living) and prevent contractures. Such efficacy is best documented for the upper limbs (Bhakta et al., 2000; Sheean, 2001; Brashear et al., 2002; Childers et al., 2004; Suputtitada and Suwanwela, 2005; Bergfeldt et al., 2006; Kaňovský et al., 2009; Barnes et al., 2010; Ryuji et al., 2010a; Shaw et al., 2011). In the lower limbs, efficacy is more limited, although rectification of plantar-flexed foot posture is documented (Baricich et al., 2008), and there is a modicum of evidence for amelioration of gait (Bleyenheuft et al., 2009; Ryuji et al., 2010b). In 2008, a large evidence-based review concluded that BoNT should be offered for treatment of spasticity in adults, with level A evidence for improvement of muscle tone and level B for improvement of motor function (Simpson et al., 2008; Elia et al., 2009).

Introduction

Justinus Kerner, a German medical doctor and poet, was the first to describe botulism in detail in the nineteenth century (see Chapter 1). However, it took another 150 years until botulinum neurotoxin (BoNT) was first used for therapeutic measures. This was done by Alan Scott, a co-author of this chapter, who examined a number of chemical substances in order to find one that could lengthen an extrinsic eye muscle in order to have an alternative to surgery for squint. In animal tests, BoNT proved to be the only substance that showed the desired paralytic effect and was locally and systemically well tolerated in a very low dose (Scott et al., 1973). The first patients were treated in 1978. It is evident that this method is safe but cannot replace surgery for most patients with strabismus because the long-term effect is often not stable (Fig. 20.1).

This book illustrates that strabismus has been joined by a wide range of disorders for which BoNT has emerged as an important or even first-line treatment, in addition to cosmetic indications. Around the eye/orbit, a number of diseases can be treated with BoNT: predominantly essential blepharospasm and hemifacial spasm (Chapters 8 and 13; for both BoNT is the first choice treatment) but also to lengthen retracted lids and to overcome double vision in Graves’ disease, to reduce oscillopsia and improve vision in nystagmus, to produce protective ptosis in lagophthalmos or corneal diseases, to reduce tearing through injections into the lacrimal gland, and to treat special cases of spastic entropion.

Introduction

Botulinum neurotoxin (BoNT) serotype A (BoNT-A) is the treatment of choice for cervical dystonia (CD). Treatment outcome can vary with the presentation of CD and is significantly dependent on the correct assessment of the muscle involved.

There are “simple” (movement disorders in one plane) and “complex” (movement disorder in two or more levels) forms of CD. The most common presentation is the rotation and tilting of the head. The difficulty lies in the treatment of complex CD. In large studies, rates of patient satisfaction with the BoNT therapy range from 50 to 60% (Comella et al., 2000; Haussermann et al., 2004; Truong et al., 2010). The most common cause of unsatisfactory treatment is the selection of the wrong muscle. The selection of the treated muscles is most effective if the actual clinical picture of complex CD in a patient is considered as an individual situation.

In a large study with imaging (MRI, CT) in patients with CD, it was noted that the previous phenomenological classification of CD in four groups (torticollis, laterocollis, antecollis and retrocollis) is inadequate. There are clinical cases of CD in which only muscles that act on the head are involved, and others involving only muscles that act on the cervical spine (Reichel, 2009, 2012). Therefore, a more extensive complex cervical movement disorder clinical analysis beyond the four traditional groups is required. The objective is a precise delineation of an optimal individualized treatment strategy in the selection of muscle involved. As the selection of the treated muscles and finding the individual BoNT dose can be difficult, different diagnostic methods are used. They include ultrasound, CT neck soft tissue imaging (particularly the deep muscles of the neck), electromyography (EMG) of neck muscles and standardized photographs of patients with measurements of angles (head, neck, thorax). The presence of a lateral shift or forward sagittal shift (very rarely backward) suggests a combination of two clinical pictures: lateral shift occurs when a laterocollis is combined with a laterocaput to the opposite side (Fig. 6.1a). A sagittal shift forward occurs when an antecollis is combined with a retrocaput. A sagittal shift to the rear is also possible (combination of retrocollis and antecaput) but occurs very rarely isolated, most likely with generalized dystonia.

Introduction

Botulinum neurotoxins (BoNTs) are used to treat a large number of muscle hyperactivity disorders including dystonia, spasticity, tremor and autonomic disorders (e.g. hyperhidrosis and hypersalivation), as well as facial wrinkles. Commercially available products differ with respect to serotype, formulation and purity. Not all products are approved in all countries. Serotype A-containing products are Botox (onabotulinumtoxinA), Dysport (abobotulinumtoxinA) and Xeomin (incobotulinumtoxinA), whereas NeuroBloc/MyoBloc (rimabotulinumtoxinB) contains serotype B. The active ingredient in all products is BoNT, a two-chain protein with a molecular weight of 150 kDa. BoNT type A (BoNT-A) inhibits release of the neurotransmitter acetylcholine by cleaving synaptosomal associated protein-25, a SNARE protein, while BoNT type B (BoNT-B) cleaves synaptobrevin (vesicle-associated membrane protein-2).

Since BoNTs are foreign proteins, the human immune system may respond to them with the production of specific anti-BoNT antibodies. The probability of developing such antibodies increases with the BoNT doses applied (Göschel et al., 1997; Lange et al., 2009). Whether other drug-related factors might contribute to immune responses is discussed below. Patient-related factors may also be involved in triggering antibody formation to BoNT. Recently, a patient was reported who was treated with abobotulinumtoxinA for several years with good results until he developed anti-BoNT-induced therapy failure after he received BoNT following a wasp sting (Paus et al., 2006). Since components of wasp poison are effective immunostimulants, a preactivation of lymphocytes may have triggered antibody formation against BoNT-A. In the following, a method is presented for the quantification of anti-BoNT in sera; the immune cell reactions to antigens are described and drug-related immune responses are discussed.

Introduction

Primary blepharospasm is a common adult-onset focal dystonia, characterized by involuntary contractions of the periocular muscles that result in forceful eye closure and impaired opening and closing of the eyes (Marsden, 1976; Berardelli et al., 1985; Defazio et al., 2007). The severity of blepharospasm can vary from repeated frequent blinking, causing only minor discomfort, to persistent forceful closure of the eyelids leading to functional blindness (Fig. 8.1). Blepharospasm can be caused by tonic or phasic contractions of the orbicularis oculi muscles and may also be associated with levator palpebrae muscle inhibition (apraxia of eyelid opening) or involuntary movements in the lower face and masticatory muscles (Meige’s syndrome). In most cases, blepharospasm is considered primary and is only occasionally secondary to structural brain lesions or drug therapy (Jankovic, 2006).

Pathophysiology

Neurophysiological recordings of the blink reflex have given important insights into the pathophysiology of blepharospasm. In patients with blepharospasm, the recovery cycle of the R2 component of the blink reflex is enhanced, presumably owing to a lack of brainstem interneuronal inhibition (Berardelli et al., 1985, 1998). Blepharospasm is also associated with an abnormal responsiveness of the blink reflex to sensory stimuli. Studies using magnetic brain stimulation also suggest a loss of inhibition and increased plasticity in the central nervous system of patients with blepharospasm (Defazio et al., 2007; Quartarone et al., 2008).

Introduction

This chapter describes aspects of tics and tremors including clinical features, oral medication treatment and the utility of botulinum neurotoxin (BoNT) injections as a therapeutic modality.

Tics

Tics are brief, sudden, movements (motor tics) or sounds (phonic tics) that are intermittent but may be repetitive and stereotypic (Jankovic and Kurlan, 2011). When motor tics and phonic tics coexist without other neurological abnormalities, the diagnosis of Tourette’s syndrome should be considered. Most patients with Tourette’s syndrome have also a variety of comorbid disorders such as attention deficit disorder, obsessive compulsive disorder and impulse control disorders. Tourette’s syndrome is considered a genetic neurodevelopmental disorder but its pathogenesis is not well understood (Jankovic and Kurlan, 2011). Although Tourette’s syndrome is the most common cause of childhood-onset tics, there are many other causes of tics, including autistic disorder and various insults to the brain and basal ganglia (infection, stroke, head trauma, drugs and neurodegenerative disorders).

Introduction

The primary focus of this chapter is to provide a review of the technical requirements and techniques for performing brightness mode (B-mode) ultrasound (US) to guide botulinum neurotoxin (BoNT) injections for cervical dystonia (CD). A brief review of the advantages and disadvantages of various guidance techniques and the supporting literature is also presented.

Cervical dystonia

Idiopathic CD is the most common form of focal dystonia worldwide (Defazio et al., 2004; Jankovic, 2004). It is characterized by sustained muscle contraction leading to abnormal postures and twisting movements of the head and neck. Patients with CD report functional limitations and pain associated with the muscle pulling or twisted postures. The combination of pain and posturing affect many activities of daily living and quality of life and limit participation in work, family life and avocational interests. A full review of the diagnosis, patterns of muscle involvement and range of therapies for CD is covered elsewhere in this text.

Introduction

Cerebral palsy is not a specific disease but a clinical syndrome caused by a non-progressive injury to the developing brain that results in a disorder of movement and posture that is permanent but not unchanging. It is the most common cause of physical disability affecting children in developed countries. The incidence is steady in most countries at approximately 2 per 1000 live births. The prevalence of cerebral palsy is much higher in children with birth weight under 1500 g and in those born earlier than 28 weeks of gestation. The location, timing and severity of the brain lesion are extremely variable, which results in many different clinical presentations. Despite the static nature of the brain injury, the majority of children with cerebral palsy develop progressive musculoskeletal problems such as posturing and muscle contractures (Koman et al., 2004). Additionally, as pointed out in an expert consensus on cerebral palsy, it is important to recognize that there are also frequent yet inconsistent disturbances of sensation, cognition, communication and perception; abnormalities of behavior; and seizures (Bax et al., 2005).

Classification

Cerebral palsy may be classified according to the cause of the brain lesion (when this is known), and the location of the brain lesion as noted on imaging such as MRI or CT. Clinically more useful classification schemes are based on the type of movement disorder, the distribution of the movement disorder (Box 15.1) and the gross motor function of the child.

Introduction

Botulinum neurotoxin (BoNT) has been used effectively to alleviate pain in many pain disorders and has been proven to be a good choice for treatment of neuropathic pain. There have been no major side effects, only minor local infection. Randomized controlled studies and open-label studies indicate BoNT is beneficial in diabetic neuropathic pain, trigeminal neuralgia and postherpetic neuralgia (Piovesan et al., 2005; Ranoux et al., 2008; Yuan et al., 2009; Xiao et al., 2010). This chapter discusses the putative mechanisms of BoNT action and injection methodology for these three conditions.

Peripheral and central sensitization processes are involved in the pathophysiology of neuropathic pain (Baron, 2006; Pace et al., 2006). Abnormal muscle contraction, released substance P and calcitonin gene-related peptide also play significant roles in hyperalgesia of neuropathic pain. An ideal therapy for neuropathic pain should block these pain-inducing pathways as completely as possible. Muscle paralytic mechanisms, vasodilatation, pain-related neurotransmitter blockage, peripheral inflammatory pain inhibition and the inhibition of central pain perception contribute to the effectiveness of BoNT for neuropathic pain (Ranoux et al., 2008; Yuan et al., 2009; Neumeister et al., 2009).

Introduction

Botulinum neurotoxins (BoNTs) are proteins derived from the bacterium Clostridium botulinum that have been formulated as drug products for clinical use. These biologics are typically injected into muscles where they act locally to inhibit the release of acetylcholine at the neuromuscular junction. Botulinum neurotoxins can also act on cholinergic autonomic terminals following injection into smooth muscle, where they inhibit contractions, or nearby glands, where they inhibit glandular secretions. Additionally, they can inhibit release of inflammatory peptides at pain endings.

Synthesis and structure

C. botulinum produces BoNTs as protein complexes that contain non-toxin hemagglutinin and non-hemagglutinin proteins in addition to the neurotoxin itself. The type and number of non-toxin proteins are determined by the strain of the bacteria, and these proteins form complexes with the neurotoxin that range in molecular weight from approximately 300 kDa to approximately 900 kDa (Sakaguchi et al., 1984). Seven different BoNTs serotypes are produced by different clostridial strains, A, B, C1, D, E, F and G. Only types A and B are commercially available; types C and F have been tried in humans on an experimental basis only.

Introduction

Botulinum neurotoxin type A (BoNT-A) injections are established as a standard procedure for the treatment of functional shortening of different muscles in spastic or dystonic children. Preconditions for beneficial effects are:

• a functional problem resulting from dynamic hyperactive muscle shortening without major structural changes

• a focal problem caused by hyperactivity of a few muscles

• application of the BoNT in the target muscle close to the neuromuscular junctions

• a sufficient dose

• no antibodies to BoNT-A.

Muscles that are superficial and palpable are easy to inject. In contrast, exact placement of the needle is more difficult and less controllable in muscles that are not palpable and deeply situated (e.g. iliopsoas) or are small and difficult to selectively identify (such as forearm muscles). Exact needle placement is, however, essential for optimal functional result, avoidance of side effects and evaluation of therapeutic failures.

To localize the target muscle and to control the placement of the injection needle several techniques are available:

• orientation at anatomical landmarks and palpation supported by moving the distal joint to observe the motion of the needle placed in the target muscle (Buchthal technique)

• electromyography

• electrical stimulation

• real-time ultrasound

• CT.

Clinical application of BoNT has been shown to be inaccurate except for the gastrocsoleus complex (Chin et al., 2005). Electromyography is good, but many muscles may be simultaneously active. Control by electrical stimulation is quite uncomfortable and painful and often requires anesthesia. Guidance under CT is not appropriate for routine use because of the exposure to radiation and high costs. By comparison, the advantages of the ultrasound-guided technique are clear:

• real-time observation of the injection

• readily available

• easily applicable after a manageable learning period

• cost effective

• no serious side effects.

Introduction

Thoracic outlet syndrome (TOS) is a rare, often perplexing disorder caused by compression of neurovascular structures, leading to cervicogenic–brachial pain and other symptoms in neck and upper limb. Thoracic outlet syndrome is a group of disorders, not a single disorder, and patients may present with a wide variety of signs and symptoms. The wide range of symptoms and signs in TOS may confound clinicians unfamiliar with this condition (Sanders et al., 2008; Ferrante, 2012; Foley et al., 2012). Again, because TOS is a group of disorders, there is no “gold standard” to establish the diagnosis. This may lead to misdiagnosis or overdiagnosis of TOS in patients who present with symptoms suggesting TOS but who have other causes for their symptoms. It is, therefore, imperative that physicians be familiar with the range of symptoms and signs of TOS and testing that either supports or refutes this diagnosis. It is also critical that the diagnosis be correctly established before proceeding to invasive interventions for a presumed diagnosis of TOS, including botulinum neurotoxin (BoNT) injections.

One of the many emerging applications for BoNT therapy is for the treatment of musculoskeletal pain disorders, including TOS. While the efficacy of BoNT on decreasing pain associated with cervical dystonia and chronic migraine is established, the antinocioceptive mechanism of action of BoNT is not fully understood (Mense, 2004; Aoki, 2005). Reports of reduced pain with BoNT have been reported in various musculoskeletal pain disorders, including joint pain, myofascial pain and cerebral palsy (Barwood et al., 2000; Gobel et al., 2006; Singh et al., 2009). Although there are numerous reports in the literature citing the efficacy of BoNT for pain and other symptoms associated with TOS, additional research is needed to establish the role of BoNT in TOS and other pain disorders (Jordan et al., 2007; Danielson and Odderson, 2008; Torriani et al., 2010; Foley et al., 2012). The proposed mechanism of action includes reduced muscle spasm leading to decreased compression of neurovascular structures (Jordan et al., 2007; Tsao, 2007; Danielson and Odderson, 2008). Injection of BoNT into muscles also leads to denervation atrophy, which may reduce compression and neurogenic or vasogenic symptoms. It has also been reported that BoNT reduces the release of nocioceptive neurotransmitters, which could also be a contributing factor in reduced pain in TOS.