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Boyer Children’s Clinic
Evidence-Based Practice Flyer
The Use of Botox* as Adjunct Treatment in
Children with Cerebral Palsy Who Toe-Walk
Elizabeth B. McCarthy, MS, PT
December 2006
Why do some children with cerebral palsy walk on their toes?
Pes Equinus is the condition of the ankle joint lacking at least 5-10 degrees of
dorsiflexion when maintained in a biomechanically neutral position (Cusick,
1990). It is commonly seen in children with cerebral palsy who have hypertonus
(aka, increased muscle tone, or spasticity) in one or both lower extremities, and
often results in “toe-walking”. In this situation, hypertonus causes persistent
contraction of the calf muscles, especially in standing. The tightness of the calf
muscles moves the ankle joint into relative plantarflexion (a “pointed foot”
position), and prevents the child from standing with their heels on the floor. The
more severe the hypertonus, the higher the heel is off the floor in standing. Over
time, permanent shortening or contracture of the calf muscles can develop,
resulting in permanent loss of mobility in the ankle joint, as well as compensatory
changes in the neuromuscular structure of the upper leg, hip and back (Gage,
1991). According to Gage, a child who persistently walks on his or her toes,
whether on one side only or bilaterally, has compromised stability in standing and
decreased dynamic balance when moving over the affected leg. This results in
walking being slower, more difficult, more dangerous, and more tiring for the
child.
How is pes equinus due to hypertonus traditionally treated?
Traditional management of pes equinus due to hypertonus in children with
cerebral palsy has included physical therapy techniques (including strengthening,
motor training, stretching and other techniques to minimize soft tissue and joint
restrictions, use of orthotic devices, etc.) and orthopedic surgery, (Nolan, Cole,
and Liptak, 2006; Bower, 2000; Cosgrove, 2000; Gage, 1991). Physical therapy
and orthopedic interventions aim to maximize function, and minimize or delay
development of deformity, but do not result in any physiological change to the
amount of hypertonus.
What is Botox*, how does it work, and what are the clinical indications for
use?
Botox* is one of eight toxins produced by the bacterium Clostridium botulinum
(Eames and Cosgrove, 2000). It is administered by local injection into specifically
targeted muscles. It has been used medically to treat muscular hypertonus in
varying disorders for more than 20 years (Nolan et al., 2006). Botox* acts by
preventing release of the neurotransmitter acetylcholine at the neuromuscular
junction; thus, nerve signals intended for the muscles are blocked (Kita and
Goodkin, 2000). This produces muscle weakness or paralysis, depending on the
dose administered and the number of synapses between nerve and muscle that
are shut down (Kessler and Benecke, 1997). The effects of Botox* are
temporary, with clinical reduction of hypertonus becoming apparent within 12-72
hours of injection, and lasting for 3-6 months (Koman, Mooney, Smith, Goodman,
and Mulvaney, 1993).
Infrequent side effects have been reported in studies of Botox* use on children,
and they are generally described as mild and transient (Nolan et al., 2006). It
should be noted that the toxin binds strongly to its target receptors in the nerve
terminal, and does not cross the blood-brain barrier; however, it can cross soft
tissue fascial planes easily in the local area of injection, so that urinary
incontinence is a side effect seen with injection into hip muscles (Eames and
Cosgrove, 2000). Other infrequent side effects include generalized muscle
weakness, falls, pain and fatigue.
There is currently no established clinical consensus regarding optimal dosages of
Botox*; however, one multi-center retrospective review done in Europe
concluded that the best therapeutic responses with the fewest side effects were
achieved with total doses of less than 1,000 IU (Bakheit, et al., 2001). Over time,
the per kilogram bodyweight doses used in clinical trials have increased from
eight units to 24 units per kilogram maximum dose (Bell and Williams, 2003).
Who are good candidates for treatment with Botox*?
A consensus statement on guidelines for candidate selection has been published
by an international group of clinicians and researchers (Graham et al., 2000).
Important factors they identified included patient or family goals for specific
functional gains, the presence of hypertonus without other dystonias, and full
passive joint range of motion prior to Botox* injection. However, one study did
show Botox* to be as effective as serial casting for children with ankle
dorsiflexion deficits, and with longer-lasting effects (Corry et al., 1998). There
should also be close collaboration between patient, family, community care
providers, and the hypertonus management team in designing the
comprehensive and individualized therapy program that must follow treatment
with Botox* in order to maximize beneficial outcomes (Mulligan and Wilmshurst,
2006). Strength training, functional training, and possible revision of orthotic
devices are all important parts of the post-injection program (Leach, 1997;
Ketelaar, Vermeer, Hart, van Petegem-van Beek, and Helders, 2001; Damiano,
Dodd, and Taylor, 2002). In addition, some researchers suggest that Botox* has
its optimal effect in candidates age seven years or younger with only moderate
involvement, who have yet to develop fixed soft tissue deformities (Preiss,
Condie, Rowley, and Graham, 2003; Bakheit et al., 2001; Eames and Cosgrove,
2000; Wissel et al., 1999).
Is there research evidence for the use of Botox for pes equinus due to
hypertonus in children with cerebral palsy?
In 1993, Koman et al. published the first paper examining the possible use of
Botox* in the management of hypertonus in children with cerebral palsy. They
determined that Botox* did produce a temporary reduction in focal hypertonus in
the targeted muscles. Other researchers have examined the use of Botox* in
studies designed to assess whether this temporary localized reduction in
hypertonus can contribute to functional gains in motor skills (Cosgrove, Corry,
and Graham, 1994; Wong, 1998; Sutherland, Kaufman, Wyatt, Chambers, and
Mubarak, 1999; Boyd, Pliatsios, Starr, Wolfe, and Graham, 2000; Koman,
Mooney, Smith, Walker, and Leon, 2000).
Because long term hypertonus can cause muscle shortening, soft tissue
contractures, joint dislocations and bony deformities, all of which can interfere
with motor function, reducing hypertonus would be expected to improve the
acquisition and maintenance of functional motor skills. Several researchers found
that Botox* treatment reduced hypertonus in the lower extremity muscles
specifically responsible for the loss of mobility characteristic of pes equinus
(Heinen et al., 1997; Corry et al., 1998). This temporary reduction can contribute
to clinical therapy programs aimed at motor skill acquisition (Nolan et al., 2006).
However, it should be noted that researchers of surgical approaches to
hypertonus reduction (e.g., selective dorsal rhizotomy) have noted that even with
surgical elimination of hypertonus, residual functional disability can still be quite
significant. According to McLaughlin (2000), “This suggests that spasticity is not
as important a determinant of disability as neurological impairments of balance,
postural maintenance and selective motor control” (p.116).
These and other researchers also found Botox* injections resulted in improved
mobility at the ankle joint in children with pes equinus (Calderon-Gonzalez,
Calderon-Sepulveda, Rincon-Reyes, Garcia-Ramirez, and Mino-Arango, 1994;
Heinen et al., 1997; Zelnik et al., 1997; Corry et al., 1998; Wong, 1998). Such
improvement may decrease the risk or severity of long term soft tissue
contracture. The period of improved mobility again presents a temporary window
of opportunity for the patient to work on acquiring or refining functional motor
skills without the obstacle of limited joint mobility and the biomechanical
compensations such limitations produce.
Improvement in the gait of children with pes equinus was seen by several
researchers, some of whom also documented concomitant changes in
hypertonus and/or range of motion (Cosgrove et al., 1994; Wong, 1998;
Sutherland et al., 1999; Boyd et al., 2000; Koman et al., 2000). Because a variety
of measurements were used to assess both changes in gait efficiency as well as
quality, studies are difficult to compare directly with each other. However, positive
changes were noted in clinical parameters such as walking speed, stride length,
joint alignment and movement, and power production, as well as qualitative
changes noted in video-taped gait evaluations. In addition, Wissel et al. (1999)
found that higher doses were associated with greater improvements across
experimental groups.
Conclusion
Botox* injection, which temporarily reduces focal hypertonus, can be a clinically
useful adjunct to the management of hypertonus induced pes equinus in children
with cerebral palsy. Data from research suggests that families, patients and
caregivers should have clear functional goals in mind before deciding to pursue
this treatment. Researchers have found Botox* to be potentially most useful in
younger children who have moderate involvement and minimal fixed loss of joint
mobility. In addition, careful communication and collaboration between the family,
patient, community therapist and hypertonus management team, both before and
after treatment, is required for optimal outcomes.
*Allergan In., 2525 Dupont Dr, PO Box 19534, Irvine, CA 92623-9534.
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