Mark Gormley

Recommendations for the use of botulinum toxin type A in the management of cerebral palsy

Botulinum toxin type A (BTX-A) is increasingly being used for the treatment of childhood spasticity, particularly cerebral palsy. However, until very recently, all such use in this indication has been unapproved with no generally accepted treatment protocols, resulting in considerable uncertainty and variation in its use as a therapeutic agent. In view of the increasing awareness of, and interest in, this approach to the treatment of spasticity, and also the recent licensing in a number of countries of a BTX-A preparation for treating equinus deformity in children, it would seem timely to establish a framework of guidelines for the safe and efficacious use of BTX-A for treating spasticity in children. This paper represents an attempt, by a group of 15 experienced clinicians and scientists from a variety of disciplines, to arrive at a consensus and produce detailed recommendations as to appropriate patient selection and assessment, dosage, injection technique and outcome measurement. The importance of adjunctive physiotherapy, orthoses and casting is also stressed.

DEFINITION AND CLASSIFICATION OF HYPERKINETIC MOVEMENTS IN CHILDHOOD

Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random‐appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock‐like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back‐and‐forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials.

Definition and Classification of Negative Motor Signs in Childhood

In this report we describe the outcome of a consensus meeting that occurred at the National Institutes of Health in Bethesda, Maryland, March 12 through 14, 2005. The meeting brought together 39 specialists from multiple clinical and research disciplines including developmental pediatrics, neurology, neurosurgery, orthopedic surgery, physical therapy, occupational therapy, physical medicine and rehabilitation, neurophysiology, muscle physiology, motor control, and biomechanics. The purpose of the meeting was to establish terminology and definitions for 4 aspects of motor disorders that occur in children: weakness, reduced selective motor control, ataxia, and deficits of praxis. The purpose of the definitions is to assist communication between clinicians, select homogeneous groups of children for clinical research trials, facilitate the development of rating scales to assess improvement or deterioration with time, and eventually to better match individual children with specific therapies. “Weakness” is defined as the inability to generate normal voluntary force in a muscle or normal voluntary torque about a joint. “Reduced selective motor control” is defined as the impaired ability to isolate the activation of muscles in a selected pattern in response to demands of a voluntary posture or movement. “Ataxia” is defined as an inability to generate a normal or expected voluntary movement trajectory that cannot be attributed to weakness or involuntary muscle activity about the affected joints. “Apraxia” is defined as an impairment in the ability to accomplish previously learned and performed complex motor actions that is not explained by ataxia, reduced selective motor control, weakness, or involuntary motor activity. “Developmental dyspraxia” is defined as a failure to have ever acquired the ability to perform age-appropriate complex motor actions that is not explained by the presence of inadequate demonstration or practice, ataxia, reduced selective motor control, weakness, or involuntary motor activity.

Cerebral palsy: A rational approach to a treatment protocol, and the role of botulinum toxin in treatment

Cerebral palsy (CP) is characterized by aberrant control of movement or posture and appears early in life secondary to central nervous system damage. The symptoms of CP fallinto four groups: Symptoms due to loss of selective motor control; symptoms due to abnormal muscle tone; symptoms due to imbalance between muscle agonists and antagonists; and symptoms due to impaired balance. The goals of treatment are to maximize function and minimize the development of hoint conrtacture and other secondary porblems. Development of a tratment plan begins with hte deginition of obhectiones and consideration of the effects of gtrowth and development on the patients abilities. The role of botulinum toxin in CP treatment has grown in recent years. The patient who could benefit most from botulin toxin treatment is one who is hypertonic and whose abnormal muscle tone is interfering with function, or who is expected to develop joint contracture with growth because of this abnormal tone. By altering this muscle tone, function can be enhanced or additional therapeutic modalities can be employed. Assessing treatment outcomes for BTX injection involves the same set of questions and measurements as for other types of treatments and depends on the careful definition of treatment objectives beforehand. ©1997 John Wiley & Sons, Inc. Spasticity: Etiology, Evaluation, Management, and the Role of Botulinum Toxin Type A, MF Brin, editor. Muscle Nerve 1997;20(suppl):S181‐S193.

A clinical overview of treatment decisions in the management of spasticity

Spasticity from an upper motor neuron syndrome may cause a variety of symptoms that interfere with function. Decisions regarding spasticity treatment are influenced by the chronicity, severity, and distribution of the spasticity; the locus of injury; the presence and severity of co‐morbidities; the availability of support; and the goals of treatment. Not all spasticity can or even should be treated; tone reduction is indicated only if spasticity interferes with some level of function, positioning, care, or comfort. Treatment goals should be well outlined before treatment begins. Botulinum toxin may be used to treat focal spasticity as part of an overall treatment plan.

Use of botulinum toxin type A in pediatric patients with cerebral palsy: a three-center retrospective chart review.

Over the last several years, botulinum toxin type A has gained widespread use for the management of focal spasticity in children with cerebral palsy. To assess the current patterns of botulinum toxin type A use in the clinical setting, the dose, muscles injected, age at injection, and interval between injections of botulinum toxin type A treatments were examined in a retrospective chart review of children with cerebral palsy (N = 270) over a 2-year period at three major treatment centers. The average dose of botulinum toxin type A across the three centers ranged from 7.7 to 10.8 U/kg body weight, and the average total amount of botulinum toxin type A injected at a single visit ranged from 154 to 205 U. The majority of botulinum toxin type A injections were to the muscles to the lower limbs. The average age at first injection was 6.2 years, and the average interval between injections ranged from 134 to 199 days. (J Child Neurol 2001;16:113-118).

AbobotulinumtoxinA for Equinus Foot Deformity in Cerebral Palsy: A Randomized Controlled Trial.

BACKGROUND: Although botulinum toxin is a well-established treatment of focal spasticity in cerebral palsy, most trials have been small, and few have simultaneously assessed measures of muscle tone and clinical benefit. METHODS: Global, randomized, controlled study to assess the efficacy and safety of abobotulinumtoxinA versus placebo in cerebral palsy children with dynamic equinus foot deformity. Patients were randomized (1:1:1) to abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injections into the gastrocnemius-soleus complex (1 or both legs injected). In the primary hierarchical analysis, demonstration of benefit for each dose required superiority to placebo on the primary (change in Modified Ashworth Scale from baseline to week 4) and first key secondary (Physician’s Global Assessment at week 4) end points. RESULTS: Two hundred and forty-one patients were randomized, and 226 completed the study; the intention to treat population included 235 patients (98%). At week 4, Modified Ashworth Scale scores significantly improved with abobotulinumtoxinA; mean (95% confidence interval) treatment differences versus placebo were –0.49 (–0.75 to –0.23; P = .0002) for 15 U/kg/leg and –0.38 (–0.64 to –0.13; P = .003) for 10 U/kg/leg. The Physician’s Global Assessment treatment differences versus placebo of 0.77 (0.45 to 1.10) for 15 U/kg/leg and 0.82 (0.50 to 1.14) for 10 U/kg/leg were also significant (both Ps < .0001). The most common treatment-related adverse event was muscular weakness (10 U/Kg/leg = 2; placebo = 1). CONCLUSIONS: AbobotulinumtoxinA improves muscle tone in children with dynamic equinus resulting in an improved overall clinical impression and is well tolerated.

Management of hypertonia in cerebral palsy

Purpose of review The review provides an update on the treatment of hypertonia in cerebral palsy, including physical management, pharmacotherapy, neurosurgical, and orthopedic procedures. Recent findings Serial casting potentiates the effect of Botulinum neurotoxin A injections for spasticity. Deep brain stimulation, intraventricular baclofen, and ventral and dorsal rhizotomy are emerging tools for the treatment of dystonia and/or mixed tone. The long-term results of selective dorsal rhizotomy and the timing of orthopedic surgery represent recent advances in the surgical management of hypertonia. Summary Management of hypertonia in cerebral palsy targets the functional goals of the patient and caregiver. Treatment options are conceptualized as surgical or nonsurgical, focal or generalized, and reversible or irreversible. The role of pharmacologic therapies is to improve function and mitigate adverse effects. Further investigation, including clinical trials, is required to determine the role of deep brain stimulation, intraventricular baclofen, orthopedic procedures for dystonia, and rhizotomy.

Poster 485 Safety and Tolerability of AbobotulinumtoxinA (Dysport) in Children (2-17 Years) with Lower Limb Spasticity Due to Cerebral Palsy: A Pooled Analysis of 8 Clinical Trials

vertebral fusion and a shortened neck. The frequency of finger abnormalities is reported to be 12 percent. When applying hand orthotics, it is important to leave certain sensory portions open in order to enhance hand locomotion. Orthotics without open portions to the sensory nerve can lead to poor compliance among patients. Conclusions: 3D printing is a good utility to provide those afflicted with Klippel-Feil Syndrome with orthoses that accommodate various finger abnormalities. Level of Evidence: Level V

Use of Rimabotulinum Toxin for Focal Hypertonicity Management in Children with Cerebral Palsy with Nonresponse to Onabotulinum Toxin

ObjectiveThe aim of this study was to review the effect of rimabotulinum toxin (BoNT-B) for focal hypertonicity management in children with cerebral palsy and secondary nonresponse to onabotulinum toxin treated at the authors’ tertiary care academic medical center. DesignA retrospective review of the medical treatment of children was conducted at the authors’ institution (March 16, 2001, to August 2, 2002) using the key words botulinum toxin B and Myobloc (Solstice Neurosciences Inc, South San Francisco, CA). Demographic information was analyzed using descriptive statistics (number [percentage] and mean [range]). The Pearson &khgr;2 test was used to evaluate differences in incidence of adverse events. ResultsEighty-two children had BoNT-B injections (116 treatments). Overall, 26.8% (19/71) of the children or their parents/guardians reported no or minimal response to the injections, with 89.5% (17/19) of these children having secondary nonresponse to onabotulinum toxin. Adverse events were frequent but did not require hospitalization of any patient. No significant differences were found in incidence of adverse events related to BoNT-B dosing, medical fragility, or Gross Motor Function Classification System level. ConclusionsMore than one-fourth of the children receiving BoNT-B injections had nonresponse, with most having previous nonresponse to onabotulinum toxin. Adverse events related to BoNT-B injections were frequent and unpredictable but not severe.