Botulinum toxin A in Clinical Neurology

BoNT-A, by acting at the neuromuscular junction to reversibly alter muscle tone and selectively functionally denervate muscle, is used extensively in disorders of muscle overactivity, such as facial movement disorders, limb and neck dystonias, and spasticity

Facial movement disorders

Overactivity of muscles involving eye and mouth closure were targeted . Blepahrospasm is a focal dystonia of eyelid closure, which can be quite disabling and, in more extreme cases, render the sufferer functionally blind (Patients may have a noticeable increased frequency in blink rate, endure spasms of eyelid closure, or have continuous lid closure with significantly impaired voluntary eyelid opening. Oromandibular dystonias involve the muscles of mastication, particularly masseter, temporalis, and pterygoid muscles, and can result in disabling jaw deviation, jaw clenching or protrusion. Tongue and pharyngeal muscles may also be involved, and the affected patient may be unable to speak, chew, or swallow effectively. Hemifacial spasms are non-dystonic paroxysms of muscle twitching on one side of the face, often due to vascular compression of the 7th cranial nerve.


Review of pooled case-controlled data of over 2500 patients demonstrated a 90% efficacy rate of BoNT-A injections in blepharospasm (Jost and Kohl 2001)..
Up to 20U per eye of are injected into the orbicularis oculi at 2.5–5.0U per site through a 27–30 gauge needle. Adverse effects of periocular BoNT-A injection include ptosis, dry eyes, and diplopia.

Oromandibular dystonia

Oromandibular dystonias have responded poorly to systemic medications (clonazepam, anticholinergics, and antispasmodics) (Greene et al 1988), but mostly small open-label trials of BoNT-A indicate significant improvement with neurotoxin injection). In a prospective uncontrolled study of 162 patients.followed an average of 4.4 years, Tan and Jankovic (Tan and Jancovic 1999) noted a mean duration of effect of 16.4 weeks and global improvement effect rated as a 3.1/4. Greatest improvement was seen in patients with primarily jaw-closure dystonias. Jaw opening dystonias proved more difficult to treat and had a 40% incidence of dysarthria and dysphagia (relative to only 19% with treated jaw closure dystonias.)
Jaw closure dystonia injections should include the masseters, and temporalis muscles, at starting doses of 40–50U BOTOX® or 100U Dysport® each; medial pterygoids may also be targeted with 20U BOTOX® or 30U Dysport® Jaw opening dystonias should focus primarily on the lateral pterygoids, with starting doses of 20U BOTOX or 60U Dysport® .

Hemifacial spasm

Hemifacial spasm (HFS) has been treated with oral anti-cholinergic, antispasmodic, and anticonvulsive medications with small degrees of success. Surgical microvascular decompression has been reported to offer long-term relief in up to 95% of treated patients but there may be significant morbidity and mortality from invasive intracranial procedures. BoNT-A offers the hope of symptom reduction or relief without the adverse effects of surgery.Therapeutic administration of BoNT-A for HFS is similar to strategies described for blepharospasm, with the addition of targeting very small doses to lower facial muscles as well. In addition to the 4 orbicularis oculi injections suggested for blepharospasm treatment, zygomaticus major, buccinator, and depressor anularis oris have been targeted . Adverse effects include dry eyes, ptosis, and facial or mouth drooping.

Focal neck and limb dystonias

Botulinum neurotoxins have been applied with particular success to the treatment of focal neck and appendicular dystonias. Cervical dystonias are involuntary movements or postures of the head, neck, and shoulders. There may be head rotation (torticollis), neck flexion (anterocollis) or extension (retrocollis), or lateral deviation (laterocollis). Movements may be spasmodic, rhythmic (tremoring), or fixed. Pain accompanies cervical dystonia in the majority of patients Focal dystonias can produce undesirable torsional, flexion or extension movements of the limbs or digits, limiting manual dexterity in the upper extremities, and impairing walking in the lowers. The most reported, and often most disabling, are the occupational dystonias, particularly writer’s cramp and musicians’ dystonia. Unwanted hand postures occur in relation to particular tasks, often writing or playing musical instruments

Cervical dystonia

Treatment of cervical dystonia (CD) has been the most studied of all the potential applications of BoNT-A. Early studies showed safety and efficacy in small cohorts (Tsui et al 1985; Tsui et al 1986) with a minority of patients reporting transient neck weakness or dysphagia
Although BoNT-A has statistically proven clinical improvement for treatment of neck dystonia, the disorder is quite heterogeneous in both presentation and therapy solutions and several questions remain unresolved. Like other dystonias, dosing strategies should be modified based on severity and muscle involvement. Experienced clinicians note a mean total of 200U of BOTOX® or 500U Dysport® as effective in cervical dystonias.
Primary non-response, duration of effect, and long-term results of BoNT-A treatment of CD have been studied. Although the majority of patients respond to their first dose of BoNT-A, approximately 15% fail to derive significant improvement of their cervical dystonia
Anterocollis with inaccessible prevertebral muscle involvement responds poorly to treatment (Comella and Thompson 2006). Inaccurate muscle targeting and insufficient dosing have also been cited as reasons for primary non-response. (Jancovic 2004a)

Limb dystonias

Focal dystonias of the upper and lower extremities are particularly well-suited to treatment with localized injections of BoNT-A.Clinical trials of BoNT-A have focused largely on occupational dystonias, especially writer’s cramp (WC). In one double-blinded, placebo-controlled trial (Tsui et al 1993), 12/20 WC sufferers experienced improved pen control after BoNT-A injections, but only 4/20 noted improved writing ability. Clinical experience suggests that most patients (75%–80%) have onset of benefit one week following BoNT-A injection, peaking at two weeks, and lasting 3 months .
Leg and foot dystonias are far less common and less well-studied. Case series of primary foot dystonia patients showed improvement to repeated BoNT-A injections in 6/8.


Central nervous system disorders with upper motor neuron dysfunction often produce spasticity, hypertonia of the limb that is distinguished from rigidity by being both velocity-dependent (Lance 1980) and dependent on range of motion. The muscles most prominently affected are those innervated by the pyramidal tracts. In the upper extremities, the shoulder adductors, elbow flexors, wrist pronators, finger and thumb flexors are most involved (Mayer et al 1997). In the lower extremities, hip adductors (often resulting in hygiene issues), knee extensors, and ankle plantar flexors and inverters may have increased spastic tone (Pathak et al 2006). The most common causes of spasticity in adults are trauma, stroke, and multiple sclerosis, while in children, cerebral palsy (CP) is the primary culprit (Jancovic 2004a). Treatment is aimed at prevention of contractures and improved functional outcome (Brin et al 1997).

Adult spasticity

BoNT-A has been studied as a spasticity treatment in adults. Upper limb tone has been shown in blinded, placebo-controlled studies to improve with 200–300U BOTOX® (Brashear et al 2002; Simpson et al 1996) and up to 1000U Dysport® (Hesse et al 1998); the effect is likely dose-dependent (Childers et al 2004). Lower extremity tone improved in spastic patients after BoNT-A injection, especially hip adductors (Hyman et al 2000) and calf spasticity (Mancini et al 2005).

Pediatric spasticity

BoNT-A as a treatment for the spasticity associated with cerebral palsy has also been studied. Rigorous reviews showed statistically significant improvement at two weeks and three months A larger and more recent trial of 125 children randomized to three doses of Dysport® (10, 20, 30U/kg) and placebo injections to the calves showed significant improvement in gastrocnemius shortening at 4 and 16 weeks (Baker et al 2002).
The clinician-injector is directed to the Neurotoxin Institute website ( which is an excellent clinical tool with dosing schemes, muscle localization charts, and education materials for limb spasticity.
The WEMOVE® website ( or is an excellent tool replete with anatomical diagrams and dosing recommendations for CD and other dystonias.