It is capable of identifying both gait deviations and the response to BoNT-A therapy [ 19 , 48 ]. However, 3DGA has limited availability and is not easy to use in children under the age of 3—4 years or below one meter in height. However, we found the PRS to have poor reliability, necessitating modifications in clinical trials [ 50 ]. Observational scales are best conducted using good quality 2-dimensional video recording with the option for archiving data and video replay with slow-motion capability [ 51 — 53 ].
The EVGS is currently the best available observational tool for gait assessment when 3-dimensional gait analysis is not available [ 53 ]. All observational gait scales are limited in sensitivity to detect small changes following injection of BoNT-A and have limitations in both reliability and validity.
Three-dimensional gait analysis provides objective, valid and reliable documentation of gait in children with CP [ 19 , 45 ]. Earlier studies utilised isolated kinematic measures at the ankle and knee and were able to detect improvements following injection of BoNT-A [ 54 ].
More recently, dynamic electromyography, kinetics and summary statistics of gait such as the Gait Profile Score GPS have also been reported [ 55 , 56 ]. A combination of kinematic parameters and a summary statistic of overall gait pattern GPS are recommended as the highest level for objective documentation of changes in gait in children with CP [ 55 , 56 ].
The gold standard for the measurement of Gross Motor Function is the Gross Motor Function Measure GMFM , which has been shown to be valid, reliable and responsive to clinically meaningful change [ 57 ]. The GMFM requires approximately 1 h to perform and is conducted by experienced, trained physiotherapists. In children who can walk, dimensions D and E are most relevant. It was not intended to be used as an outcome measure and it does not have the psychometric properties to be used as such [ 19 ].
Children at GMFCS Level IV and V generally have a mixed movement disorder with generalised hypertonia, which is often severe and affects all four limbs as well as the trunk [ 19 , 22 ]. Many non-ambulant children have complex medical comorbidities [ 19 , 22 ]. Injecting multiple muscle groups on a recurrent basis poses a risk of serious adverse events including severe respiratory events and mortality [ 61 ].
For the majority of non-ambulant children, generalised tone management may require oral medications or a neurosurgical procedure such as insertion of an intrathecal baclofen pump ITB [ 62 ]. In children at GMFCS IV and V, the musculoskeletal pathology becomes fixed with a very high prevalence of muscle tendon contractures, joint contractures, hip dislocation and spinal deformity [ 19 , 24 ]. BoNT-A is not ideal as standard therapy for hypertonia in the non-ambulant child because only a few of the many hypertonic muscles can be treated due to limitations in total BoNT-A dose [ 1 — 6 ].
Upper-limb function is more complex than gait function and is impacted to a greater degree by impairments of sensation, proprioception and selective motor control [ 22 ].
More complex classification systems that can also be used as outcome measures include the House classification [ 65 ]. The COPM and GAS are also applicable as they can be individualised to the child and family goals and are not specific to lower-limb function [ 44 , 48 ]. Upper-limb outcome measures have been reviewed in detail elsewhere [ 66 , 67 ]. The choice of interventions for the management of the movement disorders associated with CP in children is extensive [ 19 ].
It can be difficult at first sight to determine on what criteria the choice should be made between the many options. Oral medications are increasingly used as first-line management for spasticity and dystonia in children with CP.
Medications include baclofen, diazepam, tizanidine and less commonly dantrolene [ 69 , 70 ]. Artane and l -dopa are being trialled in dystonia [ 70 ]. Most oral medications are limited by a combination of limited benefit and a high prevalence of side effects [ 19 , 69 , 71 ]. Medications for both spasticity and dystonia management have been reviewed extensively elsewhere and will not be considered further here [ 69 — 72 ].
Some studies have examined the benefits of using a background of oral spasticity management using either tizanidine or baclofen, combined with focal neurolytic injections of hypertonic muscles with BoNT-A [ 73 , 74 ].
Others have investigated combining injections of BoNT-A and phenol [ 75 ]. Neurosurgical procedures for hypertonia include selective dorsal rhizotomy SDR for spasticity, the insertion of an ITB or insertion of electrodes for deep brain stimulation DBS for various forms of hypertonia [ 19 , 76 , 77 ].
Chemo-denervation by the injection of neurolytic agents has a long history in the management of focal and regional spasticity. Neurolysis by injection of phenol and alcohol was widely used before the introduction of BoNT-A [ 75 , 78 , 79 ]. Botulinum neurotoxins BoNT are large proteins of approximately kilodaltons kDa that are produced by bacteria from the Clostridia Botulinum family.
The heavy chain consists of two principal domains, the N terminal portion, which is the translocation domain that is involved in the release of the light chain into the cytosol of the motor neuron, and the C-terminal part that is the receptor binding domain, critical for the binding and endocytosis of BoNT-A into the presynaptic neuron [ 18 ]. BoNT primarily acts to inhibit the release of acetylcholine from the presynaptic terminal.
BoNT interferes with normal vesicle-membrane fusion by a multi-step process, illustrated in Fig. The overall effect can be described as a neuro-paralysis or chemical denervation of muscle [ 80 — 82 ].
BoNT does not cross the blood—brain barrier and although retrograde transfer to the CNS from peripheral injection sites occurs to a limited degree, there is little evidence for direct central effects. The explanation for central effects is that peripheral chemo-denervation may lead to central reorganisation as a result of neuroplasticity [ 18 ].
The BoNT-A heavy chain is shown in green and the light chain in yellow, linked by a disulphide bond. Acetylcholine Ach , the neurotransmitter which is blocked by BoNT-A, is shown as red dots within a circular vesicle in the nerve terminal. The effects of chemodenervation by injection of BoNT-A are summarised at macroscopic, microscopic and molecular levels. Injection of BoNT-A produces a dose-dependent, partially reversible chemo-denervation of injected muscle by blocking pre-synaptic release of acetylcholine at the neuromuscular junction [ 18 , 80 , 81 ].
Because of rapid and high-affinity binding to receptors at the neuromuscular junction of the target muscle, little systemic spread of toxin occurs. However, it is important to note that some systemic spread occurs following every injection and this can be detected at remote sites by specialised techniques [ 18 ].
The diffusion of BoNT-A may be altered by alterations in muscle morphology such as reduced muscle volume and increased connective tissue [ 7 , 25 , 26 ]. Neurotransmission is restored initially by the sprouting of new nerve endings, but these are eliminated after about 3 months when the original nerve endings regain their ability to release acetylcholine [ 83 ].
Muscle strength is reduced because of acute muscle atrophy with the secondary effect of a reduction in muscle spasticity [ 7 ]. The clinical effects last from 3 to 6 months. The duration of action therefore should be considered not just in clinical terms but also in terms of muscle biomechanics and the effects on skeletal muscle at the macroscopic, microscopic and molecular levels [ 7 ]. It is particularly concerning that the adverse effects such as muscle atrophy last longer than the clinical effects, such as muscular relaxation [ 7 , 84 ].
The predictable movement patterns and postures that are characteristic of spasticity enable a systematic rationale to be developed to identify the role of BoNT-A to manage muscle overactivity [ 1 — 6 ]. The management of dystonia with BoNT-A is more complex and spasticity and dystonia frequently occur in combination as in mixed movement disorders [ 19 , 22 , 30 ].
Although the principle of BoNT-A therapy in children with CP is remarkably simple, the application is challenging in the presence of complex changing movement disorders and the insidious development of fixed contractures [ 22 ] Fig. Algorithm as to the timing of the use of botulinum toxin type A BoNT-A and orthopaedic surgery for ambulant children with cerebral palsy CP. The peak age for the use of BoNT-A is between 2 and 6 years. The peak age for the use of orthopaedic surgery is between 6 and 12 years.
Injection of the gastrocnemius or the gastrosoleus is the most common indication for BoNT-A therapy in children with CP [ 1 — 6 ]. This is for two main reasons. Injection of the gastrosoleus is moderately effective in the younger child with dynamic equinus and the alternative, muscle—tendon lengthening surgery, is unpredictable and frequently harmful [ 86 ].
However, the reverse is true as the child becomes older. The response to BoNT-A is barely detectable and surgical lengthening of the gastrocsoleus is effective and reliable [ 87 , 88 ].
To assess the evidence for the use of BoNT-A in equinus, we reviewed numerous publications, which were mainly cohort studies, in combination with the higher quality studies previously reviewed in systematic reviews and evidence statements [ 6 , 82 ].
The majority of studies were cohort studies, and more were described as prospective then retrospective. However, the majority were uncontrolled, which has little impact on the evidence for change in scales in the domain of body structure such as MAS or MTS. The lack of controls undermine many claims for improvements or changes in gross motor function.
The majority of studies reported had a single injection cycle and the mean follow-up was usually about 6 months. Observational gait scales PRS, OGS, EVGS were used with or without video in about a third of studies and some form of instrumented gait analysis was used in almost half of the studies, but the equipment used and the reliability were poorly described.
When MAS or MTS was the primary outcome measure, the majority reported a statistically significant improvement, that is, a reduction in spasticity. The majority of studies utilising observational gait scales reported an improvement, as did those utilising instrumented gait analysis [ 6 , 82 ]. The majority of studies that reported GMFM reported improved gross motor function, but the majority of these studies were uncontrolled, making gains in GMFM as the result of natural history difficult to disentangle from gains as a result of injection of BoNT-A [ 22 ].
There was a trend for better study designs to report smaller or no improvements in GMFM [ 58 ]. Of concern was the observation that change in GMFCS was reported as an outcome measure in a number of studies. Study designs were variable, the numbers of participants were generally small and mean follow up was short. Outcome measures were often poorly described and reliability was not reported.
Some measures were used incorrectly e. The majority of studies reported outcomes in the ICF domain of body structure, fewer reported valid measures of function and very few reported outcomes in the domains of activities and participation [ 34 ]. It was concluded that there is strong evidence for a reduction in spasticity in the plantar flexors of the ankle after injection of BoNT-A; there was moderate evidence for small improvements in gait with the caveat that observational gait scales have limitations [ 51 , 52 , 89 ].
There was weak evidence for improvements in gross motor function, related to lack of controls and incorrect use of GMFCS [ 6 , 82 ]. These studies have been reviewed and graded by Simpson et al. It is important to note that the higher the quality of the study design and the more objective the outcome measure in terms of validity and reliability, the smaller and less predictable the response to BoNT-A therapy is reported. Even with 3-DGA, earlier studies focused on outcome measures of interest such as the range of equinus in stance and swing phases of gait [ 50 , 54 ].
When newer, more global measures of gait function such as the GPS have been utilised, improvements in overall gait function have been noted to be much smaller, or absent [ 56 ]. One of the reasons for the paradox is that injection of BoNT-A to the gastrosoleus in children with spastic diplegia bilateral CP is in the context of generalised spasticity affecting proximal muscle groups including the hamstrings and iliopsoas [ 19 ].
Improvements in ankle dorsiflexion may be offset by deterioration in knee extension or hip extension, resulting in the paradox of improvement at the ankle level with deterioration at proximal levels [ 56 ]. Most clinicians are aware that in the long term, crouch gait increased hip and knee flexion is a more insidious and intractable gait disorder than equinus, which is easy to correct surgically, when a child is older, as a definitive procedure with a low rate of recurrence [ 87 ].
Most studies have shown that the improvements following BoNT-A therapy in children for spastic equinus are small and short-lived. In addition, children become unresponsive to injection of BoNT-A at a younger age than previously thought [ 52 , 56 ]. Most clinically significant improvements are seen under the age of 4 years for equinus in spastic hemiplegia [ 6 ].
The response reduces between the ages of 4 and 6 years, and after the age of 6 years recent studies including both EVGS and 3DGA confirm little or no benefit from continued use of BoNT-A therapy [ 52 , 56 ]. Doses and dilutions of BoNT-A for the management of equinus depend on the preparation used and have been published and discussed extensively elsewhere [ 1 — 6 ]. There is one comprehensive dose ranging study for spastic equinus which clearly shows a dose response curve [ 90 ].
There are two RCTs that investigated and reported frequency of injection for spastic equinus. Both studies compare an injection schedule of three times per year every 4 months to once per year.
Both studies reported that the once-per-year injection schedule was as effective with fewer adverse events than three times per year [ 91 , 92 ]. Despite this Level I evidence, many clinicians inject at more frequent intervals. The once-per-year schedule is also aligned to experimental work in small mammal models, in which more frequent injections were reported to cause cumulative harm in terms of muscle atrophy, weakness and loss of contractile elements and fibrosis [ 7 , 93 , 94 ].
Identification of the target muscle has traditionally been based on anatomical landmarks and palpation [ 1 , 2 ]. The accuracy of injection based on palpation is poor except for the gastrocsoleus [ 95 ]. Electromyography, electrical stimulation and real-time ultrasound have improved the accuracy of injection of target muscles in children with CP [ 13 , 95 ]. It has been more difficult to determine if improved accuracy of injection has improved clinical outcomes.
Extensive literature and atlases now exist to enhance the understanding of 3-dimensional topographical anatomy based on real-time, high-quality ultrasound. The use of ultrasound is strongly recommended and requires specific training and equipment [ 13 ]. In younger children with no fixed contracture, injection of BoNT-A for equinus increases the dynamic length of the gastrocsoleus and results in improvements in selected gait parameters [ 96 ].
There is also evidence that appropriate use of BoNT-A in younger children may delay the onset of fixed equinus to a small but important degree, permitting later utilisation of orthopaedic surgery at optimum age [ 19 , 56 ]. In general, this means a more predictable outcome for surgical treatment for equinus and less need for repeat surgery [ 87 , 88 ].
The optimism regarding prevention of contractures generated by the spastic mouse study has never been translated to the clinical situation [ 33 ]. In fact, there is mounting evidence that injection of BoNT-A might cause loss of contractile elements and increased fibrosis, which might lead to increases in contracture [ 7 , 93 , 94 ]; hence the need for constant dialogue between clinicians in the multidisciplinary team who practice both non-operative and operative management for children with CP [ 6 ].
Hence the urgent need for long-term studies, over multiple injection cycles Fig. The benefits decreased spasticity, increased range of motion and improvements in gait may outweigh the harms weakness, muscle atrophy and fibrosis. The understanding of risk to benefit may change with further studies, both clinical and in animal models. The endpoint is orthopaedic surgery for gait improvement. The indications, techniques and outcomes for injecting the hamstrings and adductor muscles were first described by Cosgrove et al.
Muscle hyper-activity in the hamstring and adductor muscles is more prevalent in the more severely involved child with bilateral involvement. This may result in scissoring postures and flexed, stiff-knee gait. Injection of the hamstrings can be combined with injection of the gastrocnemius in high-functioning children with diplegia [ 96 , 97 ].
Most experienced clinicians consider that injection of up to four large muscle groups at a single session may be appropriate and is generally safe, if dose limitations and appropriate techniques are used [ 3 — 6 ].
Injection of more than four large muscle groups increases the risk of systemic spread, and local and systemic adverse events [ 19 , 61 ]. Molenaers et al. Gait deviations are identified using 3DGA, muscle overactivity is identified using a combination of 3DGA, electromyography and instrumented measures for spasticity.
A tailored programme is then developed for each child consisting of targeted injections to the spastic muscles, serial casting, orthoses for daytime use, night splinting and intensive post-injection physiotherapy. The Leuven Group has reported improvements in gait and function in several studies, of a degree and level that have rarely been matched in other centres [ 45 , 56 , 99 ].
Perhaps the integration of all of the components of their approach is required for optimum outcome [ 45 ]. However, the combination of so many medical, physical and therapy components to the programme makes it very difficult to isolate the contribution of each of the components to the overall outcome [ 45 ].
In contrast to the Leuven philosophy, Bakheit argues that BoNT-A injections can be effective as a stand-alone intervention when ancillary management is not available [ ]. The evidence base for or against ancillary interventions is weak because it is very difficult to isolate component parts of the multimodal intervention strategy and subject them to adequately powered RCTs.
In the past, spastic adduction was considered to be the primary cause of hip displacement and the management of adductor spasticity and contracture received much attention [ 19 ].
It is now known that hip displacement in the non-ambulant child is much more related to limited function in hip abductors than spasticity in the hip adductors. Graham et al. The outcomes of this study were negative.
Gross motor function as determined by GMFM did not improve in the treatment group compared with the control group [ ]. Hip displacement was not prevented and children in both groups required the same number of orthopaedic operations for hip displacement with the same outcomes in terms of hip morphology and pain at year follow-up [ , ]. Although smaller studies with short-term follow-up have suggested more optimistic outcomes, the weight of evidence suggests that gross motor function is not improved, and hip displacement and the need for orthopaedic surgery is not avoided by injection of the hip adductors in non-ambulant children with CP [ — ].
Copeland et al. They described the use of sham injections as controls and reported significant benefits in the COPM as the primary outcome measure. The combination of imperfect blinding and subjective outcome measures undermines the validity of the conclusions. Although there was no increase in serious adverse events in the treatment group compared with the control group, this may not be the case when BoNT-A is used in non-ambulant children in non-RCT conditions, when serious adverse events and deaths have been reported [ 61 , ].
In the ambulant child, the logical endpoint of BoNT-A therapy, for the majority of children, is orthopaedic surgery for fixed contracture [ 87 , 88 ]. In the non-ambulant child, the endpoint is not clear and each injection cycle exposes the child to a greater risk of serious adverse events than is the case in the ambulant child [ 19 , , ] Fig. Hip adductor spasticity is more effectively treated by phenolisation of the obturator nerve than by injection of BoNT-A, especially when combined with adductor release surgery [ 78 ].
There may not be a defined endpoint and intermittent, life-long injections are not an ideal proposition. There is a small role for focal management of spastic-dystonia in the non-ambulant child for specific functional goals [ 11 , 22 ]. In the upper limb, these include improvement of reach and grasp to facilitate control of a powered wheelchair. In the lower limb, a very useful indication is palliation of painful hip dislocation in a child who is too fragile to consider orthopaedic surgery [ ].
However, prevention of hip displacement by hip surveillance and early surgery is clearly a better option. In non-ambulant children, global spasticity management using oral medications and when appropriate an intrathecal baclofen pump are both more effective and safer than injecting multiple muscles on a recurring basis with large doses of BoNT-A [ 76 ].
Despite the limited benefits and poor evidence base, BoNT-A therapy continues to be widely used in non-ambulant children. In Australia, there have been four deaths in recent years attributed to the use of BoNT-A therapy in non-ambulant children with CP and the risk-to-benefit profile is poor [ , ]. One exception may be the use of BoNT-A for pain relief, which is so prevalent in this population [ , ].
Upper-limb dysfunction is a common functional and cosmetic consequence of CP, particularly in children with hemiplegia [ 22 ]. A wide variety of management strategies have been adopted and the evidence base has been reviewed by Boyd et al. Conventional therapeutic management of upper-limb hyperactivity in children with CP has involved the use of splinting and casting, and passive stretching, the facilitation of posture and movement, medication and sometimes orthopaedic or plastic surgery [ ].
In a recent high-quality meta-analysis, Sakzewski et al. Constraint-induced movement therapy achieved modest to strong treatment effects on improving movement quality and efficiency of the impaired upper limb compared with usual care [ ]. Impairment of upper-limb function can impact on self-care abilities, activities of daily living, education, leisure activities and vocational outcomes participation [ 22 ].
Children may not be able to reach for objects, manipulate toys, feed themselves efficiently or use assistive communication devices [ 22 , , ]. A modest improvement in reaching function can be beneficial. Different muscles develop fixed contracture at different speeds. The pronator teres is invariably the first muscle in the hemiplegic upper limb to develop a contracture [ 22 ].
The principal goal of treatment using BoNT-A in the upper limb of children with CP is to enhance function by allowing children to employ their treated arm and conduct daily activities more efficiently and effectively [ 9 , 10 , 22 ].
Additional aims are to decrease tone and increase ROM to prevent contracture and delay the need for surgery [ 9 , 10 , 22 , , ]. It is invariably the non-dominant arm that requires treatment, except in children with quadriplegia, when the dominant arm may benefit from intervention to improve grasp and release in activities such as steering a power wheelchair [ ].
In the upper limb, it is even more important that BoNT-A therapy be goal-directed in the context of a multidisciplinary programme including splinting and occupational therapy [ 22 , ]. Additional problems in the upper limb will relate to a higher prevalence of dystonia, weakness, sensory impairment and impairment of selective motor control [ 19 , 22 ].
These negative features may overshadow any benefit gained from BoNT-A injection and lead to more limited results of shorter duration [ 9 ].
The suitable candidate for BoNT-A therapy in the upper limb should be able to initiate active finger movements and activate and strengthen antagonist muscles to take advantage of temporary BoNT-A paresis of the agonists [ 10 ]. Children should have good grip strength because good grip strength may be reduced by BoNT-A injection [ 9 , 10 , ]. Family-identified limitations, problems and goals should be analysed in great detail [ , ].
In typical hemiplegic posturing, the most common target muscles are the biceps, brachialis, pronator teres, flexor carpi ulnaris, flexor carpi radialis and the adductor pollicis [ 22 , ]. Injection of the long finger flexors should be minimised to avoid weakening of grip strength [ 9 , 10 ]. However, in non-ambulant children with severe spastic dystonia, and in some children with hemiplegia, if the aim is to improve palmar hygiene, injection of the long finger flexors is required in combination with serial casting [ ].
The larger muscles are injected in one or two sites with the smaller muscles injected in a single site. Small-volume, high-concentration injections are advised, using ultrasound control, to avoid injection of unwanted muscles and diffusion into other muscle groups [ , ]. Corry et al. As with many studies, a reduction in measures of spasticity were demonstrated but improvements in function were much more difficult to achieve [ 9 ].
Fehlings et al. Wallen et al. Olesch et al. In , Speth et al. As in the first upper-limb RCT by Corry et al. Objective evaluation of upper-limb function using a standardised, validated instrument is strongly recommended to document baseline function and also to assess changes following treatment. In studies utilising these valid, reliable and objective measures, sustained improvements in function have been difficult to identify [ ].
As in the lower limb, the use of adjunctive interventions makes interpretation of treatment effects problematic [ ]. As in the lower limb, children with upper-limb involvement should be considered for definitive orthopaedic surgery, when the response to injections of BoNT-A plateau, especially when fixed contractures progress and impair function [ ]. In the first RCT in which injections of BoNT-A, tendon transfer surgery and usual therapy were compared, the surgical group had superior outcomes [ ].
Nurs Stand. PMID: pubmed. Updated by: Linda J. Editorial team. Giving an IM intramuscular injection. You will need: One alcohol wipe One sterile 2 x 2 gauze pad A new needle and syringe -- the needle needs to be long enough to get deep into the muscle A cotton ball. Where to Give the Injection. Thigh: The thigh is a good place to give an injection to yourself or a child less than 3 years old. Look at the thigh, and imagine it in 3 equal parts.
Put the injection in the middle of the thigh. Hip: The hip is a good place to give an injection to adults and children older than 7 months. Have the person lie on the side. Put the heel of your hand where the thigh meets the buttocks. Your thumb should point to the person's groin and your fingers point to the person's head. Pull your first index finger away from the other fingers, forming a V. You may feel the edge of a bone at the tips of your first finger. Put the injection in the middle of the V between your first and middle finger.
Upper arm: You can use the upper arm muscle if you can feel the muscle there. If the person is very thin or the muscle is very small, do not use this site. Uncover the upper arm. This muscle forms an upside down triangle that starts at the bone going across the upper arm. The point of the triangle is at the level of the armpit. Put the injection in the center of the triangle of the muscle. This should be 1 to 2 inches 2. Permissions info. Installation Get this app while signed in to your Microsoft account and install on up to ten Windows 10 devices.
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