Dystonia Treatment using Botulinum Toxin

Updated: Feb 04, 2016
  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Selim R Benbadis, MD  more...
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Overview

Overview

Introduction

Dystonia is a disorder characterized by involuntary sustained muscle contractions resulting in twisting and repetitive movements or abnormal postures. Despite an incomplete understanding of the neurological mechanisms underlying dystonia, relief of dystonic posturing and associated pain and discomfort has improved markedly since the introduction of botulinum toxin (BTX) therapy in the late 1980s, so much so, it has become the standard therapy for focal dystonias.

BTX is one of the most potent biologic substances known. The 7 distinct serotypes, A, B, C, D, E, F, and G, are of similar sizes and structures. However, the serotypes differ in their potency, duration of action, and cellular target sites. Types A and B have been shown to be safe and effective in double-blind clinical trials for the treatment of dystonia. One formulation of BTX-A is marketed worldwide under the name BOTOX® (Allergan Inc.) and another in Europe as Dysport (Speywood, UK). BOTOX® was approved in December 1989 by the US Food and Drug Administration (FDA) for "the treatment of strabismus, blepharospasm, and focal spasms including hemifacial spasm" and more recently for the treatment of cervical dystonia. A formulation of BTX-B was approved in December 2000 by the FDA for treatment of cervical dystonia, and will be marketed under the name Myobloc in the United States and Neurobloc in Europe (Elan Pharmaceuticals).

The clinician must recognize that the various commercial formulations of BTX differ in the dosages used clinically owing to differences in potency and diffusion (see next 2 sections).

The various botulinum toxins possess individual potencies, and care is required to assure proper use and avoid medication errors. Recent changes to the established drug names by the FDA were intended to reinforce these differences and prevent medication errors. The products and their approved indications include the following:

  • OnabotulinumtoxinA (Botox, Botox Cosmetic)
    • Botox - Cervical dystonia, severe primary axillary hyperhidrosis, strabismus, blepharospasm, upper and lower limb spasticity, overactive bladder, urinary incontinence, migraine headache
    • Botox Cosmetic - Moderate-to-severe glabellar lines, lateral canthal lines
  • AbobotulinumtoxinA (Dysport) - Cervical dystonia, upper limb spasticity, moderate-to-severe glabellar lines
  • IncobotulinumtoxinA (Xeomin) - Cervical dystonia, blepharospasm, upper limb spasticity, glabellar lines
  • RimabotulinumtoxinB (Myobloc) - Cervical dystonia

Botulinum toxin type A

BTX proteins have been studied since the early 1900s, initially to gain an understanding of botulism, a form of food poisoning. Later, they were studied because of the unique and specific muscle paralysis induced by minute amounts of the toxins. During the past 30 years of work on the use of the toxin for human treatment, selective procedures for the production, purification, and dispensing of the toxin have been developed to make it suitable for injection. Today BTX-A is employed and considered safe and effective for treatment of movement disorders and spasticity. One of the more common movement disorders treated with BTX-A is focal dystonia, the most frequently occurring types of which include cervical dystonia, blepharospasm, hand dystonia, oromandibular dystonia, occupational dystonia, and laryngeal dystonia.

The administration of BTX therapy for the focal dystonias requires a thorough understanding of the toxin itself, preparation of various dilutions, and practical knowledge of typical dosages and anatomy, along with basic electromyographic skills. The optimal dose of botulinum toxin (BTX) is the least amount of BTX needed to achieve a predetermined outcome (eg, decreased muscle tone, improved range of motion, improvement of certain active function, improved hygiene) without causing an adverse effect, weakness. [1]

BTX type A has the property of Ach release at the neuromuscular junction. Following local injection into muscles, the toxin enters the nerve terminal via endocytosis, interacts with intracellular proteins (soluble N -ethyl-maleimide sensitive factor attachment protein receptor [SNARE] proteins), and inhibits the vesicular release of the Ach neurotransmitter at the neuromuscular junction. [2, 3] This chemical denervation results in paralysis of the striated muscles, which usually peaks 2 weeks after the injection. Because of the molecular turnover within the neuromuscular junction and neuronal sprouting, neuronal activity begins to return at 3 months, with restoration of complete function at approximately 6 months. [4]

Many factors affect the dose of botulinum toxin including severity and chronicity of the disease, number of muscles involved, previous response, concurrent other medical therapy used, and also the experience of the person performing the injection. Smaller doses are used in children, proportionate to the body mass.

Structure

BTX is synthesized as a single-chain peptide with a molecular mass of 150 kilodaltons. This form has relatively little potency as a neuromuscular blocking agent, and activation requires a 2-step modification in the tertiary structure of the protein. This process converts the single-chain neurotoxin to a di-chain neurotoxin comprising a 100,000-dalton heavy chain (HC) linked by a disulfide bond to a 50,000-dalton light chain (LC). BTX acts at the neuromuscular junction where it exerts its effect by inhibiting the release of ACH from the presynaptic nerve terminal.

ACH is contained in vesicles, and several proteins (VAMP, SNAP-25, and syntaxin) are required to mediate fusion of these vesicles with the axon terminal membrane. BTX binds to the presynaptic terminal via the HC. The toxin is then internalized and the HC and LC are separated. The LC from BTX-A cleaves SNAP-25, the LCs from serotypes B and F cleave VAMP, and that from serotype C cleaves syntaxin. This disrupts ACH release and subsequent neuromuscular transmission, resulting in weakness of the injected muscle.

Medications used to treat focal dystonia

See the list below:

  • Botulinum toxin injections
  • Benzodiazepines
    • Clonazepam
    • Lorazepam
    • Diazepam
  • Baclofen
  • Anticholinergics
    • Trihexyphenidyl
    • Benztropine
  • Dopamine-depleting agents
    • Tetrabenazine
    • Clozapine

Optimum goals of treatment with botulinum toxin

The ideal of BTX treatment is to achieve a balance between weakness sufficient to reduce spasm but insufficient to interfere with function. The best combination of reduction in dystonia and pain with optimization of function should be sought.

Botulinum toxin type B for dystonia

Myobloc (Elan Pharmaceuticals) was approved by the FDA in December 2000 for treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia. BTX-B also has received marketing authorization from the European Union's Committee for Proprietary Medicinal Products and will be marketed as Neurobloc (Elan Pharmaceuticals).

Reported clinical studies have shown Myobloc/Neurobloc to be a safe and effective treatment for cervical dystonia in patients who have responded to BTX-A and in those who developed resistance to BTX-A. As with all the botulinum toxins, BTX-B acts at the neuromuscular junction inhibiting the release of ACh at the presynaptic membrane; however, the primary mechanism of action of BTX-B differs from that of BTX-A, as BTX-B inactivates a different protein involved in the release of ACh.

In a multicenter study of 100 patients with cervical dystonia, Jankovic et al examined the immunogenicity of botulinum toxin type B (BTX-B) and correlated the clinical response with the presence of blocking antibodies (Abs) using a novel mouse protection assay. One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit, suggesting that the high antigenicity of BTX-B limits its long-term efficacy. [5]

Relevant Anatomy

Most of the skeletal muscular system is arranged into groups of agonists and antagonist muscles that work in concert to provide efficient and controlled motion. This is achieved through the complex interaction of the musculoskeletal system with the pyramidal, extrapyramidal, and sensory components of the nervous system.

In gross anatomy, the nerves to skeletal muscles are branches of mixed peripheral nerves. The branches enter the muscles about one third of the way along their length, at motor points. Motor points have been identified for all major muscle groups for the purpose of functional electrical stimulation by physical therapists, in order to increase muscle power. Only 60% of the axons in the nerve to a given muscle are motor to the muscle fibers that make up the bulk of the muscle. The rest are sensory in nature, although the largest sensory receptors, the neuromuscular spindles, have a motor supply of their own.

A motor unit comprises a motor neuron in the spinal cord or brainstem together with the squad of muscle fibers it innervates. In large muscles (eg, the flexors of the hip or knee), each motor unit contains 1200 or more muscle fibers. In small muscles (eg, the intrinsic muscles of the hand), each unit contains 12 or fewer muscle fibers. Small units contribute to the finely graded contractions used for delicate manipulations.

For more information about the relevant anatomy, see Muscular System Anatomy.

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Indications

Applications of botulinum toxin injections

See the list below:

  • Focal dystonia
    • Focal limb dystonia
      • Blepharospasm
      • Cervical dystonia (torticollis)
      • Oromandibular-facial-lingual dystonia
    • Hemifacial spasm
    • Myoclonus
    • Dystonic tics
    • Tremors
    • Bruxism
    • Spasticity, upper and lower limb spasticity
    • Migraine headache
    • Overactive bladder, urinary incontinence

Treatment of focal dystonia with BTX is designed to improve the patient's posture and function and to relieve associated pain. As BTX-A has been studied most intensely and used most widely, this section outlines its structure, origin, and mechanism of action.

The toxin inhibits release of acetylcholine (ACH), a neurotransmitter responsible for activation of muscle contraction. Administration of the toxin results in weakness in the injected muscle. Some nerve terminals are not affected by the toxin, allowing the injected dystonic muscle to contract, but with less force. This weakness allows for improved posture and function of the dystonic muscle(s). The degree of weakness depends on the dose, and the duration of weakness is further dependent on the serotype employed.

In their study, Silberstein et al found that most patients treated with BTX-A in a specialty headache center presented with a chronic migraine diagnosis. Headache disability was correlated with measures of frequency and treatment utilization. Headache frequency and severity, failed prophylactic therapies, and greater number of coexisting medical conditions were all negatively associated with measures of health-related quality of life. [6, 7]

Moffat et al studied BTX treatment for axillary hyperhidrosis and found that axillary botulinum toxin treatment is durable. Patients experience gradual return of symptoms between 6 and 24 months. A minority do not require retreatment at this time. [8]

Lin et al report that corticosteroid is superior to BTX-A in relieving pain in tennis elbow at 4 weeks after injection. Because BTX injection did not relieve pain significantly but is associated with weakness, the muscle weakness caused by BTX is unlikely to be the sole mechanism of the pain relief observed in previous studies. [9]

Toffola et al found that BTX-A injection treatment was effective in reducing facial synkinesis, thus improving facial expression symmetry both at rest and in voluntary movements. [10]

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Contraindications

Contraindications

No absolute contraindications to the use of BTX-A are known. Relative contraindications include myasthenia gravis or motor neuron disease. Patients who are pregnant or lactating may not be appropriate candidates for BTX therapy.

Relative contraindications for clinical application of botulinum toxin

See the list below:

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Equipment

Preparation of botulinum toxin for injection

The toxin is produced by the gram-negative anaerobic bacterium Clostridium botulinum. It is harvested from a culture medium after fermentation of a toxin-producing strain of C botulinum, which lyses and liberates the toxin into the culture. The toxin is then extracted, precipitated, purified, and finally crystallized with ammonium sulfate. BTX-A should be diluted with preservative-free saline and the preparation used within 4 hours of reconstitution. Conditions for stability of the toxin in solution include pH 4.2-6.8 and temperature less than 20 degrees Celsius. Crystallized toxin is inactivated easily in solution by shaking.

Biological activity of the BTX-A distributed by Allergan Inc. onabotulinumtoxinA (BOTOX®) is different from that of the BTX-A produced by Speywood Pharmaceuticals in England abobotulinumtoxinA (Dysport) or Japan. The potency of BTX is expressed as mouse units, with 1 mouse unit equivalent to the median lethal dose (LD 50) for mice. BOTOX® is dispensed in small vials containing 100 units (U), while a vial of Dysport contains 500 U. The relative potency of BOTOX® units to Dysport units is approximately 1:4. BOTOX® units are used throughout this article. Most physicians dilute the vial of BOTOX® with 1-4 mL of saline, for a concentration of 2.5-10 U/0.1 mL.

Electromyographic (EMG) guidance of injections is generally advised with the exception of injections of muscles around the eye and some facial muscles. The dose of BOTOX® injected intramuscularly depends on the muscle size. Small muscles such as the vocal cords receive 0.75 U, whereas larger neck muscles may require 100-150 U and lower limb muscles may require 200-300 U to exert a desirable effect. After injection, BTX starts to weaken the muscle within 24-72 hours, and maximal effect occurs after about 14 days; benefit can last for 3-6 months.

IncobotulinumtoxinA (Xeomin), the most recently approved BTX-A product, is a lyophilized powder for injection that must be diluted for IM administration. Total dose is 120 units per treatment session. Higher doses did not provide additional efficacy and were associated with increased adverse effects. It is usually injected IM into sternocleidomastoid, splenius capitis, levator scapulae, scalenus, and/or trapezius muscle(s). [11, 12, 13]

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Technique

BTX should be administered only by trained specialists utilizing correct equipment, which includes EMG monitoring to help diagnose the underlying disorder and to identify appropriate muscles for injection. Prior to treatment with BTX, patients should undergo neurologic evaluation and examination. Secondary causes of dystonia such as drugs or Wilson disease should be ruled out. Physicians administering BTX must have a good understanding of both the anatomy of affected muscles and the resultant movement disorder. Patient education and counseling are essential components of a comprehensive therapeutic approach to all patients with dystonia. BTX can be used as sole therapy or as an adjunct to oral medications. Physical therapy may play a role as a supplement to BTX.

The injection techniques for individual clinical applications of botulinum toxin are described below.

Blepharospasm

See the list below:

  • Blepharospasm is characterized by involuntary, intermittent, forced eyelid closure. BTX is considered the treatment of choice for blepharospasm and has been used for this disorder since 1983. It has been used effectively in the treatment of blepharospasm induced by drugs such as L-dopa or neuroleptics, dystonic eyelid and facial tics in patients with Tourette syndrome, and "apraxia of eyelid opening."
  • Onset of improvement is seen in 4-7 days and benefit can last for up to 4 months.
  • Injection technique
    • Treatment may be started with 10 U of BOTOX® per eyelid, injecting a total of 20 U per patient. The most common effective dose is 25 U per eye. Diluting the BOTOX® with 4 mL of isotonic saline is recommended.
    • As the orbicularis oculi muscle lies superficially, intradermal injection with a 27- to 30-gauge needle is recommended.
    • Typically, 3-5 points around each eye are injected. The principle is to avoid the mid portion of the upper eyelid to avoid inadvertent diffusion into the levator palpebrae superiores, which would lead to undesirable ptosis. Injection into the medial lower lid also is avoided.

Focal hand dystonia

See the list below:

  • This condition typically presents with loss of speed and fluency of movement during a specific task. Neurologic evaluation is required to rule out radiculopathy or peripheral nerve entrapment for which specific treatment might be available. Nerve conduction studies may be required to exclude ulnar neuropathy or median entrapment neuropathy at the wrist. Examination of the forearm muscles should be performed during the specific task to determine which muscles are involved in the dystonia. Observations should be made at rest and during the provoking activity. The patient should be instructed to avoid compensating for the dystonia. The selection of muscles for injection depends on clinical examination, patient report of local pain or tightness, and/or EMG evidence of excessive activity.
  • Treatment may lead to an improvement in abnormal posture and pain and/or restoration of normal function. Benefit has been reported in as many as 80-90% patients and is usually apparent 5-7 days after injection. Symptomatic relief peaks about 2 weeks after treatment and may last for 3-4 months.
  • Injection technique
    • BTX is injected into the muscle belly; localizing muscles for injection in the forearm may be difficult, as many of the muscles are deep and overlapping.
    • EMG is recommended to help identify the target dystonic muscle. Once proper needle location is confirmed, BTX can be injected.
    • Common initial doses of BOTOX® for writer's cramp are 5 U for small muscles and 10-20 U for muscles in the forearm. Large doses into a single muscle are best given in multiple sites to aid diffusion of the toxin to a greater number of end plates. The dose of BTX is titrated over several injection sessions to the dose that maximizes relief from dystonia while minimizing muscle weakness.
    • Subsequent injections should be given at 2- to 4-month intervals. At each subsequent session, the patient should be examined for weakness that might indicate postponing treatment or reducing the dose. As the pattern of muscle contraction can change, the dystonia should be reevaluated at each session.

Cervical dystonia

See the list below:

  • Cervical dystonia (CD) is the most common form of focal dystonia and is characterized by sustained postures or contractions of the neck muscles. Deviation of the head can occur in multiple directions; turning of head (torticollis) is the most common subtype of cervical dystonia. Laterocollis (tilting) bends the head laterally, moving the ear toward the ipsilateral shoulder; anterocollis (forward flexion) deviates the chin downward toward the chest; and retrocollis (extension) produces upward extension of the chin. Cervical dystonia can involve any combination of these deviations.
  • Ninety percent of patients report some improvement in the postural deviation. In published reports 76-93% of patients experienced pain relief following treatment with BTX. In some studies, subjective pain relief is frequently more impressive than objective improvement in head posture. Latency between injections and onset of clinical benefit is around 7 days. Duration of effect is 3-4 months.
  • Examination of patient
    • CD is usually idiopathic but in some cases it follows trauma. A study including 300 patients at Baylor College of Medicine revealed that as many as 11% of patients had significant neck injury less than 1 year prior to the onset of CD. Exposure to neuroleptic drugs accounted for 6% of the cases of CD in the Baylor series. Neurologic examination is essential to rule out radicular processes or ophthalmologic disorders, which can present with abnormal posture of the head.
    • The anatomy of the neck is complex; a basic familiarity with anatomic landmarks, muscle origins and insertions, and vital structures in that region is necessary to use BTX injections effectively to treat these patients. The abnormal postures of CD usually result from abnormal activity of multiple muscles. Postures are complex, with combinations of turning, tilting, head flexion or extension, and shoulder elevation.
    • Proper selection of the involved muscles is the most important determinant of response to BTX treatment. Thus, careful examination of the patient in different positions is indicated; instruct the patient to position the head in a comfortable upright posture. Passively adjust the head and observe for additional extension, flexion, and rotation that may be compensated for by the patient and note any contractures. Palpate for contracting muscles and hypertrophy and any point tenderness. The patient should then be asked to walk and the head position observed and recorded. The head position that is most abnormal is used to select the muscles for injection. EMG is recommended to localize involved muscles.
  • Injection techniques
    • The most commonly injected muscles include sternocleidomastoid, trapezius, splenius capitis, levator scapulae, and scalene complex. Muscles involved in the abnormal posturing are isolated using standard anatomic landmarks.
    • EMG guidance is recommended for injection purposes. Once the EMG electrode is inserted, the patient is instructed to activate the muscle evoking a full recruitment pattern. The needle is held in position and the patient resumes a relaxed position.
    • The syringe is aspirated to ensure that the tip is not within a blood vessel and the appropriate amount of BTX is then injected directly through the electrode into the muscle.
    • BOTOX® treatment doses range from 10-600 U, with 200-300 U most commonly used.
    • Usually, 2-6 muscles are injected at multiple sites; the BTX should be injected along the belly of the muscle to allow for adequate diffusion.

Oromandibular dystonia

See the list below:

  • Oromandibular dystonia (OMD) is characterized by abnormal involuntary movements or spasms of lower face, jaw, and tongue muscles. Patients present with spasms of these muscles and jaw deviation.
  • Seventy to eighty percent of patients with OMD benefit from local injections of BTX into the inappropriately contracting muscles. Improvement is observed within the first week after BTX and the benefit can last for 3-4 months.
  • Injection technique
    • Treatment of this condition with BTX requires a detailed knowledge of the local anatomy.
    • Evaluation by both a neurologist and otolaryngologist is recommended.
    • OMD can involve different combinations of muscles including the masseter, lateral and medial pterygoids, and temporalis.
    • The recommended dose of BTX is 20 U in each muscle.

Laryngeal dystonia

See the list below:

  • Laryngeal dystonia, also called spasmodic dysphonia, is characterized by abnormal involuntary spasms of vocal muscles resulting in an abnormal voice pattern. This consists of 3 types; patients with adductor spasmodic dysphonia (strain-strangled voice), abductor spasmodic dysphonia (whispering voice), and adductor breathing dystonia (paradoxical vocal fold motion). It is a chronic neurologic disorder of central motor processing characterized by action-induced spasms of the vocal folds, typically resulting in dysphonia during speaking. It is often made worse by emotional stress and patients often use sensory tricks (eg, yawning or laughing when beginning to speak) to overcome their symptoms.
  • Seventy-five percent of patients note improvement in voice symptoms. Relief after BTX injection begins within 24-72 hours and lasts for an average of 4 months.
  • Injection technique
    • Before a patient can be considered as a potential candidate for BTX injections, the diagnosis of laryngeal dysphonia must be confirmed by neurologic, otolaryngologic, and voice assessment. Clinical findings should be documented by video and voice recording with fiberoptic laryngoscopy.
    • The thyroarytenoid muscles are located with EMG guidance, and percutaneous injections of BTX are administered through the cricothyroid membrane.
    • BTX dose ranges from 1.5-3 U.
    • Currently, a bilateral injection approach is the most frequently used technique.

Hemifacial spasm

See the list below:

  • Hemifacial spasm (HFS) is one of the more common craniofacial movement disorders. It is characterized by unilateral muscle contractions of the face. HFS may involve any combination of orbicularis oculi, frontalis, risorius, zygomaticus major, and platysmas muscles. This is not a form of focal dystonia but rather is caused most probably by irritation of cranial nerve VII by an artery compressing the nerve as it exits the brain stem.
  • Allam et al concluded that the clinical improvement induced by BTX in patients with cranial dystonia is largely symptomatic and does not seem to involve excitability changes of cortical motor areas from reorganization of inhibitory intracortical circuits. [14]
  • Injection technique: Injections of BTX are tailored to the facial muscles in spasm; the muscles affected differ from patient to patient.
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Complications

During injection, patients may report a stinging sensation, especially with treatment around the eyelids and face. Bruising at the site of injection may occur. In general, adverse effects usually are localized to the site of injection and are related to excess weakness of injected muscles, which is transient and well tolerated. Systemic adverse effects, though rare, consist of a flu-like syndrome that is transient and may last as long as a few weeks. Serious adverse effects are dysphagia and respiratory compromise, which may occur with injections into the neck, mouth region, and vocal cords. Intravascular injection is to be avoided, as this may cause generalized weakness. Pneumothorax is a rare, potentially serious complication, from pleural penetration when performing injections into the lower neck or back.

Most frequently reported adverse reactions in the treatment of cervical dystonia were dysphagia (19%), upper respiratory infections (12%), neck pains (11%), and headaches (11%). In patients treated with blepharospasm, the common adverse events included ptosis (20.8%), superficial keratitis (6.3%), and eye dryness (6.3%).

A number of cases of systemic botulism-like reaction to BTX-A injections have been reported recently. Generalized weakness including bulbar weakness developed in 2 cases and resolved over several weeks. One of these patients had been treated for torticollis for many years and the other had only one series of injections for spasticity.

The lethal dose of BOTOX® in humans is not known, although it has been estimated to be about 3000 U. The usual maximum total recommended dose at an injection session is about 600-800 U.

Development of antibodies

Botulinum neurotoxins may be immunogenic. Antibodies may develop, bind to the BTX, and inactivate it. The incidence of antibody-mediated resistance to BOTOX®, as determined by the mouse lethality assay, is reported between 3% and 10% and is accepted generally to be about 5%. The only apparent symptom of the development of antibodies is lack of response to further injections. The use of other serotypes (F or B) may benefit those who have developed antibody resistance. In a patient who no longer responds to BTX-A (secondary nonresponder) and in whom immunogenicity is suspected, the recommended approach is to inject 20 U BOTOX® into hypothenar or forehead muscles. If the patient is still responsive, transient weakness will develop in the muscle 1-2 weeks after injection. An alternative or adjunct is to take blood for antibody assay, but this usually is not covered by insurance.

Risk factors for the development of antibodies include higher doses, shorter intervals between injections, booster doses, and young age. Recommendations to help prevent development of antibodies include (1) use of smallest possible dose to achieve relief, (2) interval between injections of at least 1 month (preferred interval is 3 months), and (3) avoid "booster injection."

A patient who does not respond to the first injection of BTX-A is referred to as a "primary nonresponder," but reasons for nonresponse can include inappropriate site of injection and too low a dose. A person should not be considered a primary nonresponder until he or she has been injected by an expert using increasing doses or a lack of response has been demonstrated using one of the clinical tests discussed above.

Complications with particular clinical applications

See the list below:

  • Blepharospasm
    • Ten percent of patients develop ptosis, which improves spontaneously in less than 2 weeks.
    • Other complications include blurring of vision, tearing, and local hemorrhage.
  • Cervical dystonia
    • The most common adverse effects include neck weakness (20-30%), dysphagia (10-20%), and local pain. The occurrence of dysphagia appears to be related to the dose and the muscles injected.
    • Adverse effects are transient and usually resolve spontaneously within 2-3 weeks.
  • Oromandibular dystonia
    • Adverse effects are uncommon and include dysphagia and pain at the injection site.
    • Allam et al support the view that executive dysfunction in primary cranial dystonia (PCD) is secondary to the disrupting effects of the symptoms. Treatment with BTX alleviates the symptoms and, consequently, improves sustained attention. [15]
  • Laryngeal dystonia
    • Swallowing difficulties, which can last for 3-7 days, occur in 60% of patients.
    • Transient hypophonia and stridor also have been reported.
  • Hemifacial spasm
    • Adverse effects depend on location of injection.
    • Lower face injections may result in facial weakness and asymmetry, face and mouth droop, drooling, and loss of facial expression. Forehead injections can result in brow ptosis or loss of eyebrow elevation.
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