7 Botulinum Neurotoxin for Cervical Dystonia

10.1055/b-0040-175230

7 Botulinum Neurotoxin for Cervical Dystonia

Tanya K. Meyer, Joel Guss, and Ronda E. Alexander

Summary

Cervical dystonia (CD) is the most common focal dystonia and causes significant functional deficits. The pathophysiology is poorly understood, although there is a genetic component in some individuals. The efficacy of oral medications is limited. The mainstay of treatment is the injection of botulinum neurotoxin into the affected cervical musculature. Deep brain stimulation has been shown to have success for certain cases of dystonia and tremor. This chapter discusses the appropriate workup required and the injection technique for CD.

7.1 Introduction

Cervical dystonia or CD is the most common focal dystonia. ¹ It results in the sustained contraction of the cervical musculature, leading to abnormal posturing of the neck, head, and shoulder. The injection of botulinum neurotoxin (BoNT) into the overactive muscles of CD patients can effectively treat the abnormal neck movements and pain caused by this disorder. The abnormal movements of the neck and head can result in twisting (torticollis), tilting (laterocollis), flexion (anterocollis), or extension (retrocollis). Additional movements are shoulder elevation and lateral movement of the head/neck with relation to the chest wall.

7.2 Epidemiology

The incidence of CD is 9 to 30 per 100,000 people in the United States, and the prevalence may vary among ethnic groups. ¹ ^, ² Studies have shown a higher incidence among women, with an approximate 2:1 female-to-male ratio. ³ In greater than 70% of cases, the disease begins between the fourth and sixth decades of life, with a peak incidence in the fifth decade. ⁴ A family history of dystonia is seen in 12%. Progression of dystonia to other anatomic areas is seen in up to one-third of cases. ³

Symptoms typically worsen over the course of the first 5 years before stabilizing. Spontaneous remission is seen in 10 to 20% of individuals lasting days to years, although these are temporary and most patients eventually relapse. ³ ^, ⁵ Employment status is significantly affected by CD, with over 30% requiring reduced work hours or reduced responsibilities and 19% resulting in loss of employment. ⁶

7.3 Pathophysiology

As in all dystonia, the pathophysiology of idiopathic CD is not well understood, although it is generally thought to be an abnormality in central motor processing. There is a genetic component to the development of dystonia, but trauma and drug exposure can also be a precedent to focal dystonia. ⁷ The use of neuroleptics or metoclopramide can be associated with acute onset of dystonia or tardive dystonia, which can be accompanied by other more typical tardive movements such as orofacial dyskinesia and akathisia. ⁸ Currently, the main theories are decreased central inhibition, sensory deficit with sensorimotor mismatch, aberrant neuroplasticity, and abnormal basal ganglia discharge. ⁹ ^, ¹⁰ ^, ¹¹ ^, ¹² ^, ¹³ ^, ¹⁴ Although any muscle in the neck may be involved, Table 7‑1 lists the common muscles with the associated head/neck movements. There may be multiple muscles involved with co-contraction of agonist and antagonist muscles.

**Table 7.1** Typical muscles involved in cervical dystonia
Movement	Muscles involved
Rotational: torticollis	Ipsilateral semispinalis cervicis
	Ipsilateral levator scapulae
	Ipsilateral splenius cervicis
Rotational: torticaput	Ipsilateral splenius capitis
	Ipsilateral obliquus capitis inferior
	Contralateral sternocleidomastoid
	Contralateral trapezius
	Contralateral semispinalis capitis
Laterocollis	Ipsilateral sternocleidomastoid
	Ipsilateral splenius capitis
	Ipsilateral scalene complex
	Ipsilateral levator scapulae
	Ipsilateral trapezius
Shoulder elevation	Ipsilateral levator scapulae
Shoulder elevation	Ipsilateral trapezius
Retrocollis	Bilateral splenius capitis^a
	Bilateral semispinalis capitis^a
	Bilateral upper trapezius^a
Anterocollis	Bilateral sternocleidomastoid^a
	Bilateral scalene complex^a
	Bilateral submental complex^a
Source: Data from Brashear A. The botulinum toxins in the treatment of cervical dystonia. Semin Neurol 2001;21(1):85–90; and from Walker FO. Botulinum toxin therapy for cervical dystonia. Phys Med Rehabil Clin N Am 2003;14:749–766; and from Jost WH, Tatu L. Selection of muscles for botulinum toxin injections in cervical dystonia. Mov Disord Clin Pract 2015;2:224–226. ^aFor bilateral injections, decrease the individual dose by 50 to 60% to avoid unwanted dysphagia in the anterior injections or neck weakness and difficulty holding the head straight in the posterior injections.

7.4 Clinical Manifestation

Idiopathic CD usually begins with abnormal head/neck movements before progressing to other areas. Head tremor and neck spasms are cardinal features of CD, and the majority of affected patients complain of pain. Approximately half of patients are able to identify a sensory trick, or geste antagoniste, to help control their abnormal neck spasms. ¹⁵ Typically, this trick constitutes placing the hand on the side of the face or neck, and this contact reduces the muscle spasm without actually mechanically opposing the spasm. Some patients can even imagine the sensory trick to diminish symptomatic spasms. ¹⁶ The pathophysiology of the sensory trick is unknown. Although early in the course of disease these tricks are helpful in most patients, they tend to lose effectiveness as the disease progresses.

Additional palliative factors include relaxation, alcoholic beverages, and “morning benefit,” in which symptoms are less intense just after waking. CD is exacerbated by activity, stress, and fatigue.

On physical examination, muscles should be palpated for hypertrophy, activity, and contracture/fibrosis, although it may be difficult to differentiate these conditions. Areas of pain should be noted. By convention, the direction of the rotation is defined by the chin, so right-turning torticollis means that the chin deviates to the patient’s right. Abnormal head and neck postures can occur in multiple planes. Rotational torticollis occurs around the longitudinal axis, laterocollis rotates the head in the coronal plane tilting the ear to the shoulder, and anterocollis and retrocollis rotate the head in the sagittal plane. In addition, there may be sagittal or lateral deviation of the base of the neck from the midline. Deviations in only one plane are seen in less than one-third of patients. ⁵

It is important to remember that an abnormal head and neck posture with cervical musculature spasm can be a manifestation of other disease processes, both acute and chronic. Thus, a full history and diagnostic workup should be performed. Wilson disease should be excluded in all patients younger than 50 years through evaluation of serum ceruloplasmin and slit lamp examination. Lesions and abnormalities of the brain, posterior fossa, and spinal cord can be excluded through imaging studies. A full neurologic examination should be performed. The presence of fasciculations, cerebellar signs, cranial nerve weakness, or cortical dysfunction should alert the clinician that there may be additional pathology present. The differential diagnoses of torticollis are as follows:

Cervical spine fracture or disease.
Peritonsillar or retropharyngeal abscess.
Drug reaction (tardive dystonia).
- Neuroleptics: droperidol, haloperidol, pimozide, Thorazine, Compazine.
- Dopamine receptor antagonists: metoclopramide.
Wilson disease.
Klippel-Feil syndrome.
Sandifer syndrome.
Bobble-head doll syndrome (with third ventricle cyst).
Progressive supranuclear palsy.
Posterior fossa tumor.
Spinal cord tumor or syrinx.
Multiple sclerosis.
Systemic lupus erythematosus.
Huntington disease.
Psychogenic dystonia.

7.5 Management

7.5.1 Medical Therapy

Although the efficacy of oral drug therapy is limited, there are medications that can ameliorate the severity of CD, or serve as adjuncts in the treatment of CD (Table 7‑2). Anticholinergic medications such as trihexyphenidyl or benztropine have been shown to have some effect in about a third of patients, but may be poorly tolerated due to anticholinergic side effects of dry mouth, constipation, confusion, and blurred vision. Benzodiazepines, particularly clonazepam, may also show some effect. ¹⁷

**Table 7.2** Medications used for dystonia
Names	Mechanism	Beneficial effects	Adverse effects
Trihexyphenidyl Ethopropazine Benztropine	Anticholinergic	In a double-blind placebo-controlled trial using trihexyphenidyl, 71% had a clinically significant response, with 42% maintaining long-term benefit ¹⁸ In a prospective, randomized, double-blind controlled trial, botulinum neurotoxin type A (BoNT-A) was shown to be more effective in treatment of abnormal movements and pain as compared with trihexyphenidyl ¹⁹ Anticholinergics are considered the most beneficial oral pharmacologic agent ²⁰	Dry mouth, blurred vision, imbalance, forgetfulness, fatigue, depression, micturition disturbance Can use pyridostigmine to overcome peripheral effects ²¹ Can use pilocarpine eyedrops for blurred vision ²¹ Dose usually limited by side effects Need to discontinue slowly to prevent rare occurrence of neuroleptic malignant syndrome
Benzodiazepines	GABA agonist	Muscle relaxation, works at spinal cord level A review of over 500 patients treated over 15 y showed marked improvement in 63% of patients with idiopathic dystonia ²²	Sedation
Baclofen	GABA-B agonist		Sedation
Tetrabenazine	Presynaptic catecholamine depleting agent		Akathisia, depression, sedation, fatigue, insomnia, anxiety, Parkinsonism