Treatment of cervical dystonia hand spasms and laryngeal dystonia with botulinum toxin

Summary One hundred and twenty-six patients with different forms of focal dystonia (89 with cervical dystonia, 12 with hand cramps and 25 with laryngeal dystonia) were treated with localised injections of botulinum toxin. Mean doses per muscle were 200 mouse units (m.u.) for treating cervical dystonia, 40–120 m.u. for forearm muscles in writers' cramp and 3.7 m. u. for the thyroarytenoid muscle in laryngeal dystonia. Responder rates have been above 80% in all patient groups and beneficial effects could be reproduced over follow-up periods of up to 4 years. The commonest side-effects were dysphagia after treatment of spasmodic torticollis, weakness of neighbouring muscles after injections for hand cramps and breathiness and hypophonia following laryngeal injections. All these were transient and generally well tolerated. It is concluded that botulinum toxin injections are a safe and effective treatment in all three types of focal dystonia.     

Treatment of chronic limb spasticity with botulinum toxin A.

The purpose of this open study was to find out whether botulinum toxin A (BTX-A) relieves the signs and symptoms of chronic limb spasticity. The study comprised 40 patients, aged 12-82 years, with moderate to severe spasticity of the upper (13) or lower limbs (27) refractory to conventional physical and medical treatments. Outcome measures were clinical and blinded videotape assessments of spasticity and motor function. Electromyography guided BTX-A injections were given in one or two sessions at total doses averaging 175 U in the upper limb (range 70-270 U) and 221 U in the lower limb (range 100-500 U). Thirty four patients (85%) derived worthwhile benefit, with improved limb posture and increased range of passive motion in 31, pain reduction in 28 of 31 with pain, and improved function in 16. Side effects were limited to local and usually mild discomfort from the injections (19), symptomatic local weakness (one), and local infection (one). Preliminary experience indicates that BTX-A is a promising adjunctive treatment for selected patients with spasticity.     

Intrafusal effects of botulinum toxin in post-stroke upper limb spasticity

A previous study in subjects with focal dystonia suggested that the greater and longer-lasting effect induced by botulinum toxin type A (BoNT-A) on the tonic vibration reflex (TVR) than on the maximal M-wave (M-max) might be the physiological marker of the toxin's action at the level of intrafusal muscle fibres. With this approach, we investigated the possible effect of BoNT-A on fusimotor synapses in eight patients with post-stroke spasticity (four with no residual motor capacity before treatment and four with partially spared muscle strength and residual motor capacity). TVR and M-max were recorded from the wrist and finger flexor muscles before treatment and at 1, 4 and 7 months afterwards. The TVR reduction was greater than the M-max reduction and remained fairly constant over time only in the subjects with a residual motor capacity before the treatment. This pilot study suggests that some degree of strength and active movement is necessary for the action of BoNT-A on intrafusal fibres.     

Use of botulinum toxin in stroke patients with severe upper limb spasticity.

OBJECTIVES--Spasticity can contribute to poor recovery of upper limb function after stroke. This is a preliminary evaluation of the impact of botulinum toxin treatment on disability caused by upper limb spasticity after stroke. METHODS--Seventeen patients with severe spasticity and a non-functioning arm were treated with intramuscular botulinum A neurotoxin (median age at treatment 54.5 years; median time between onset of stroke and treatment 1.5 years). Baseline and assessments two weeks after treatment were compared to assess efficacy. The duration of improvement in disability was documented. Outcome measures used were; passive range of movement at the shoulder, elbow, wrist, and fingers; modified Ashworth scale to assess spasticity of biceps and forearm finger flexors; an eight point scale to assess the degree of difficulty experienced by the patient or carer for each functional problem defined before treatment; the presence of upper limb pain. The biceps, forearm finger flexors, and flexor carpiulnaris were treated with intramuscular botulinum toxin. Up to a total dose of 400-1000 mouse units (MU) of Dysport (Speywood) or 100-200 MU of BOTOX (Allergan) was used in each patient. RESULTS--Functional problems reported by the patients before treatment were difficulty with cleaning the palm, cutting fingernails, putting the arm through a sleeve, standing and walking balance, putting on gloves, and rolling over in bed. Hand hygiene improved in 14 of 17 patients; difficulty with sleeves improved in four of 16; standing and walking balance improved in one of four; shoulder pain improved in six of nine; wrist pain improved in five of six. Passive range of movement at shoulder, elbow, and wrist improved after treatment. Benefit was noted within two weeks and lasted one to 11 months. No adverse effects occurred. CONCLUSION--This preliminary study suggests that intramuscular botulinum toxin is a safe and effective treatment for reducing disability in patients with severe upper limb spasticity.     

Efficacy of botulinum toxin A in upper limb function of hemiplegic patients

Botulinum toxin A has been reported to reduce spasticity and increase the comfort of hemiplegic patients. The aim of this study was to assess the efficacy of the treatment on disability, especially in manual activities, and to attempt to identify predictive factors of improvement. Twenty patients (mean age: 54.4 years; M: 14; right hemiplegia: 12) were included, with a delay of at least three months after unilateral hemispheric stroke. Botulinum toxin A (BOTOX) was injected into the arm adductors (8 cases), forearm flexors (17 cases), pronators, wrist and finger flexors (20 cases),with a total dose of 200 to 300 U. Examination (day 1 and 15, month 2 and 5) consisted of spasticity assessment (modified Ashworth scale), muscle strength, passive range of motion (goniometry), and pain, followed by functional tests, especially the Rivermead Motor Assessment (RMA) and Nine-hole Peg Test (NHPT). Performance in daily living was assessed with the Functional Independence Measure (FIM), and an original analysis of hand grasp, grip and pinches used in domestic activities (9 items), and of comfort of patients and caregivers. Significant reduction in spasticity was observed on the elbow flexors, pronators, wrist and fingers flexors, especially at day 15 (mean 0.90 to 1 point), with wide variations in effect. Muscle strength was increased in wrist and fingers extensors, with concomitant increase in the opening of the thumb to index finger space. There was no effect on the NHPT requiring distal manipulation, but the RMA, which especially concerned picking up and releasing a tennis ball, showed significant improvement. Furthermore, use of the upper limb in daily living increased, particularly for internal grasping of objects, and for grasping by the top, transporting and releasing of objects. Patients and caregivers re ported facilitation in dressing, and in proximal and distal care of the upper limb. The global flexor position of the limb improved. Ad verse reactions were rare and mostly consisted of transitory pain during injection. The improvement in the RMA was better explained by the quality of the initial motor command on distal prehension (positive correlation with motor strength), and that in hand using in domestic activities by a lower level of spasticity on pronators and wrist flexors (negative correlations with spasticity). Conversely, the severity of the motor deficit (negative correlations with motor strength) and a high level of spasticity before injection (positive correlations with spasticity) mostly explained the improvement in comfort. In conclusion, botulinum toxin A is efficient in improving hand use in patients with relatively preserved distal motricity, and in increasing comfort in patients with severe global disorders.     

Open-label study of botulinum toxin for upper limb spasticity in cerebral palsy

The objective of this study was to assess the efficacy of botulinum toxin for upper limb spasticity in cerebral palsy. An open-label study was conducted in 11 children with cerebral palsy. Post-botulinum toxin assessment was conducted in weeks 1, 4, and 16, with averaged scores being analyzed. The Clinical Global Impression Scale of the mothers showed marked, moderate, and mild improvement in five, four, and two cases, respectively. The Modified Ashworth Spasticity Scale score showed a statistically significant decrease in the mean spasticity score (P < .003). Other tests were performed depending on the cognition of the child. Increase in joint motion occurred in all five children assessed using web space (P = .043). For the Jebson Hand Function Test, improvement occurred in all five cases assessed (P < .03). Four of five (80%) children could perform tasks that they failed before they were given botulinum toxin. Botulinum toxin is useful in decreasing spasticity and improving the upper limb function of young children with cerebral palsy with normal cognition. Motivated families should be selected with a specific target of using botulinum toxin as an adjunct in a habilitation program.     

Treatment recommendations and practical applications of botulinum toxin treatment of cervical dystonia

CD is a complex disorder that can have significant impact on a patient's quality of life and physical well-being. BoNTs are a very effective and well-tolerated first-line therapy in relieving CD symptoms over long-term treatment. BoNT treatment should be administered at the lowest effective dose with a minimum of 3 months between treatments. As the incidence of immunoresistance is low, a reassessment of muscle selection, dosing, and diagnosis should take place in the event of suboptimal patient response. Optimal treatment may involve a combination of oral pharmacologic treatment with BoNTs to maintain the use of lowest possible dosing and to extend effectiveness to the recommended 3-month dosing interval. Physical therapy in conjunction with BoNT treatment can also extend treatment efficacy as well. Comorbidities such as insomnia, depression, and anxiety can interfere with successful CD treatment and should be actively managed along with the symptoms of CD. Although our understanding of CD is incomplete, it is ever expanding. As a deeper understanding of disease pathophysiology and disease progression is gained, treatment efforts will be refined for optimal outcome and patient satisfaction.     

Treatment of cervical dystonia with botulinum toxins

Botulinum toxin (BoNT) treatment has been used extensively for the treatment of cervical dystonia. In most studies, there is significant improvement following treatment for head posture and pain. The common side effects following treatment include dysphagia, dry mouth, and neck weakness. There are five brands and two serotypes of BoNT available. The dosing of each serotype and brand differs. Perhaps more importantly, each brand and serotype may differ in immunogenic potential and occurrence of secondary unresponsiveness, an issue that is currently under active investigation. Although many aspects of the technique of injection have not been adequately studied, general guidelines are available.     

Focal dystonia: The role of botulinum toxin

Botulinum toxin (BTX) has been found to be effective in a wide range of focal dystonias. Debate surrounds the selection of injection sites. In general, localization is satisfactory by clinical examination, but poor response, requiring localization of deep muscles, may necessitate use of electromyography for localization. Delineation of optimal doses of BTX is a work in progress; as studies have tended to show efficacy at lower doses than used in the past, the trend is to use lower doses. This is important, because development of antibodies to BTX, the main reason for secondary resistance to this treatment, is more frequent with larger doses and shorter inter-injection intervals. Although the mechanism of denervation of the neuromuscular injunction by BTX is relatively well understood, secondary changes at the level of the basal ganglia, thalamus, and cortex, and their role in response to BTX, need further exploration.     

Sustained attention in cranial dystonia patients treated with botulinum toxin

BACKGROUND: Primary cranial dystonia (PCD) is related to a functional disorder in basal ganglia usually accompanied by impaired executive function. AIM: To investigate symptom relief and neurocognitive change in response to treatment with botulinum toxin (BTX) in a group of patients with PCD. METHODS: We assessed nine patients with PCD and nine age- and educationally matched healthy individuals using tests of memory, sustained attention, span of auditory attention, and perceptual flexibility. RESULTS: Despite well-preserved intellectual skills relative to controls, we identified a sustained attention deficit in patients with PCD. After BTX treatment, there was an increase in the scores of the concentration endurance test (sustained attention) and the values did not differ significantly from control group patients' scores. CONCLUSION: The results support the view that executive dysfunction in PCD is secondary to the disrupting effects of the symptoms. Treatment with BTX alleviates the symptoms and, consequently, improves sustained attention.     

Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke

The authors evaluated the long-term efficacy and safety of botulinum toxin type A (BTX-A) in poststroke spasticity patients who completed a 12-week placebo-controlled study and received multiple open-label treatments with 200 to 240 U BTX-A for 42 weeks. Significant and sustained improvements were observed for Disability Assessment and Ashworth scores. Adverse events were generally mild. This extension of a double-blind study demonstrates that repeated treatments of BTX-A significantly improve function and tone in spasticity.     

Polyradiculoneuritis after botulinum toxin therapy for cervical dystonia

A 40-year-old man with cervical dystonia developed an acute inflammatory demyelinating polyradiculoneuritis after botulinum toxin type A treatment. Some cases of idiopathic brachial plexopathy and polyradiculoneuritis have been reported to date. Although a causal relationship is not firmly established, the clinical temporal profile suggests a pathogenic relationship. In patients with cervical dystonia, further use of type A botulinum toxin should be considered contraindicated, and the use of another type of botulinum toxin should be taken into consideration.     

Treatment of headaches with botulinum toxin

Primary headache disorders, such as migraine, chronic daily headache (CDH), and chronic tension-type headache (CTTH), are some of the most frequent disorders encountered by physicians in the outpatient setting. Chronic headache disorders cause significant morbidity and functional impairment. Despite important advances in both pharmacological and behavioral management of headache disorders, a number of patients remain treatment resistant. Botulinum toxin (BT) is emerging as a new therapeutic alternative in the preventative treatment of headaches. BT has several advantages over current prophylactic strategies, such as reduced side-effect profile and improved patient compliance. Furthermore, there have been several studies supporting the safety and tolerability of BT in the treatment of headache disorders. Although additional large-scale studies are needed to clarify clinical predictors of response as well as optimal dosing, injection sites and mechanism of action, BT has demonstrated efficacy in the treatment of migraines and CDH. The evidence for the treatment for CTTH is less compelling.