Note: Descriptions are shown in the official language in which they were submitted.
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BOTULINUM TOXIN IN TREATMENT OF CLUBFOOT RELAPSE
BACKGROUND OF THE INVENTION
1. Field of Invention
The present invention relates to the field of clubfoot therapy. More
specifically,
the invention relates to methods of therapy for clubfoot when a relapse has
occurred.
2. Description of Related Art
Clubfoot, though predominantly a condition that occurs in isolation
(idiopathic
clubfoot), is also well-recognized in a variety of pre-existing conditions.
Throughout most of the 20th century the mainstay of treatment of clubfoot has
been surgical correction involving a variety of techniques (9,10,13,31,48).
"Good" to "excellent" initial results have been reported in the range of 52%
to
91 % for these surgical methods (21,45). However, surgical interventions have
associated reported complications in 11% to 50% of cases (2,4,14,33,46).
Often, complications are related to the Achilles tendon that may result in
calcaneal deformity, from over-lengthening of the tendon or equinus from
insufficient posterior release with or without under-lengthening of the
Achilles
tendon (14). Postoperative gait analysis has shown abnormalities in ankle
rocker formation and timing (1,3,20,24,25,28,37,49) and kinetic studies have
revealed a significant decrease in power generation, with an average
gastrosoleus muscle complex strength reduction of 27% after one Achilles
tendon lengthening (24,25,28,49).
Ponseti published a protocol of serial manipulations and castings in 1980,
reporting, at that time, that traditional surgery could be avoided in 89% of
cases (29) and, more recently, excellent functional and clinical outcomes in
78% of patients at 30-year follow-up (12). Unresolved hindfoot equinus,
occurring in 70% to 90% of cases, was treated with percutaneous Achilles
tenotomy. Other investigators have reported their experiences using the
method described by Ponseti, quoting similarly favorable outcomes, albeit
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over a shorter follow-up (<3 years). Similarly, the physical therapy method
also requires a significant rate of Achilles tenotomy (7). Bensahel et al
reported a 26% surgical rate, which includes Achilles tenotomy (7) and
Richards and Wilson (44) reported a 47% overall tenotomy rate.
Once correction of the clubfoot is achieved by the chosen method,
maintenance is required. Maintenance involves 'boots and bars' or various
orthoses, and has the prerequisite of correction, regardless of the methods
and therapy involved in correction (surgical, non-surgical, pharmaceutical or
a
combination of these). A clubfoot that was corrected and goes on to
redevelop features of a clubfoot is considered a relapse or recurrence of
clubfoot. Recurrence is observed in about 30% of cases, with the highest
incidence between the ages of 2 and 5.
A method of therapy for recurring or relapsing clubfoot that permits
restoration
of the normal foot position without requiring surgical intervention is
desirable
and needed. Novel pharmaceutical compositions comprising botulinum toxin
or toxins are derived from the bacterium Clostridium botulinum and cause
reversible muscle denervation by blocking the release of acetylcholine at the
neuromuscular junction, leading to muscle relaxation. Botulinum toxin,
specifically botulinum toxin A, is currently used in the treatment of cerebral
palsy, poststroke spasticity, and other instances of inappropriate muscle
contraction.
Reiter (52) teaches use of BTX-A in combination with taping methods for
treatment of spasticity following stroke. This treatment was administered to
adult patients with previously normal foot function and was not directed to
clubfoot treatment.
Delgado (51 ) reported application of a nonsurgical intervention for clubfoot
therapy with the initial management involving physical therapy. A group of
infant patients under the age of 1 year with clubfoot deformity were treated
with BTX-A to resolve the abnormal foot posture. Several of these patients'
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conditions were dystonic in nature due to underlying disorders, and could not
be considered 'idiopathic' in nature. Delgado's methods involved injection
into
both the gastrocnemius and the posterior tibial muscles, and dosages varied
from 6-11 IU/kg. Delgado's methods used multiple muscle sites at multiple
irregular intervals (on average three separate injection events) for all
patients.
In addition, 50% of the patients required additional surgery after 1 year of
age. No discussion of relapse or therapeutic approaches to relapse was
addressed.
Cummings (53) presented a study suggesting that use of BotoxT"" in
combination with the Ponseti methods was not a successful treatment for
clubfoot.
There are a wide variety of approaches to therapy of spastic muscle
disorders, particularly clubfoot in infants. Given the range of casting and
manipulation methods, and the range in patient classification, dosages and
compositions of botulinum toxin used, the method may have promise,
however very specific diagnoses and treatment methodologies may be
required. The conclusions of Cummings (53) suggest that the details of the
methods used, including the injected sites, matter significantly. Merely
'mashing together' various treatment regimens as may be suggested by some
studies will not be successful in both primary treatment of idiopathic
clubfoot
and prevention of relapse.
In situations where the clubfoot deformity relapses, surgical correction is
currently the standard of care in almost every case. Surgical correction
carries with it additional complications and, if surgical methods can be
avoided, scarring, tissue weakness and overcorrection are also avoided, and
in severe cases, multiple correction attempts may be made. Surgical
correction of clubfoot is limited - tenotomy is strongly recommended to not be
performed more than twice as it causes causing structural weakness in the
tendon having adverse effects on recovery and gait. Non-invasive methods
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are better accepted by parents and caregivers, and are less distressing on the
patient.
SUMMARY OF THE INVENTION
In accordance with one aspect of the invention, there is provided a method of
reducing supination in a relapsed clubfoot-affected foot of a patient, the
method comprising injecting a medicament comprising a neuromuscular
paralytic agent into at least two sites of a tibialis posterior muscle
adjoining
the clubfoot-affected foot.
In accordance with another aspect of the invention, there is provided a
method of reducing equinus in a relapsed clubfoot-affected foot of a patient,
the method comprising, injecting a medicament comprising a neuromuscular
paralytic agent into at least four sites of a gastrosoleus muscle complex
adjoining the clubfoot-affected foot.
In accordance with another aspect of the invention, there is provided a
method of reducing adductus in a relapsed clubfoot-affected foot of a patient,
the method comprising, injecting a medicament comprising a neuromuscular
paralytic agent into at least 1 site of an abductor hallucis muscle adjoining
the
clubfoot-affected foot.
The tibialis posterior or the abductor hallucis may be first identified by use
of a
muscle stimulator.
The neuromuscular paralytic agent may be an acetylcholine antagonist, such
as a botulinum toxin, more specifically botulinum toxin A. A medicament
comprising such a toxin may include BotoxT"" and MyobIocT""
Following administration of the neuromuscular paralytic agent, the clubfoot-
affected foot is casted.
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Other aspects and features of the present invention will become apparent to
those ordinarily skilled in the art upon review of the following description
of
specific embodiments of the invention in conjunction with the accompanying
figures.
DETAILED DESCRIPTION
Any terms not directly defined herein shall be understood to have the
meanings commonly associated with them as understood within the art of the
invention. As employed throughout the specification, the following terms,
unless otherwise indicated, shall be understood to have the following
meanings.
"Clubfoot" or "clubfoot deformity" as used herein refers to the presence of a
foot of a human that cannot be corrected with manipulation to a normal
flexible forefoot, midfoot, and hindfoot position. Clubfoot may occur in one
or
both feet of an individual. Clubfoot may occur as a single isolated defect
with
no underlying cause, or may occur in conjunction with one or more coexisting
disorders.
"Idiopathic clubfoot" or "idiopathic clubfoot deformity" as used herein refers
to
clubfoot with no coexisting disorders.
"Non-idiopathic clubfoot" or "non-idiopathic clubfoot deformity" as used
herein
refers to clubfoot in the presence of a coexisting disorder. Such coexisting
disorders may include myelomenginocoele, arthrgryposis, migration
abnormalities of the brain, cerebral palsy, positional deformitie,
neurological
disorders, spins bifida, trichorhinophalangeal syndrome or other unspecificed
genetic syndromes resulting in the presence of clubfoot in a patient.
"Normal foot posture" or "normal posture of the foot" as used herein refers to
a
hindfoot that is in neutral to valgus and plantigrade, a midfoot which is
neutral
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with mild limits of supination and pronation, and a forefoot that is neutral
with
the heel bisector at the 2/3 space plus or minus 1 heel bisector.
"Triceps surge complex", as used herein, refers collectively to the
gastrocnemius and soleus muscles of the lower leg. An alternative term may
be gastrosoleus or gastrocsoleus, also referring collectively to the
gastrocnemius and soleus muscles of the lower leg.
"Percutaneous Achilles tenotomy", as used herein, refers to a surgical
procedure to lengthen the Achilles tendon, where under sterile conditions, a
surgical blade is inserted deep into the Achilles tendon near the insertion
into
the calcaneus and the tendon incompletely transected. A full tenotomy
transects the tendon and releases it, while an Achilles lengthening procedure
actually gives length to tendon but reattaches the two ends together, thereby
allowing control in the desired extent of lengthening.
A "Pirani score" as used herein refers to a scoring system for assessment of
clubfoot (38, 50). The Pirani score used comprised three measures for the
midfoot and three for the hindfoot (each scored as 0, 0.5, or 1.0, for a total
score
ranging from 0 to 6, the higher score reflecting the more severe deformity).
An
alternate classification schema for clubfoot is that of Dimeglio and Bensahel
("Dimeglio system") (54). The Dimeglio system characterizes the severity of
clubfoot deformity into four grades, based on varus and equinus in the
sagittal
plane, derotation of the calcaneopedal block, and position of the forefoot
relative
to the hindfoot in the horizontal plane. A Grade 1 foot is mild (soft-soft); a
Grade
2 foot is moderate (soft to stiff); a Grade 3 foot is severe (stiff to soft)
and a
Grade 4 foot is very severe, pseudoarthrogrypotic feet (stiff stiff. The
efficacy of
correction of clubfoot may be assessed by the degree of ankle dorsiflexsion,
as
assessed with the knee in both extension and flexion.
Clubfoot correction resulting from treatment refers to a response to this
treatment. An alternate term is 'clubfoot management'. The corrected clubfoot
deformity is measured by the amount of motion achieved by a patient. This is
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based on clubfoot treatment decisions, specifically, if the patient is able to
fit
into corrective bracing (achieve ankle dorsiflexion of 10 degrees or greater)
which is an indicator of correction of the clubfoot.
A patient relapse, as used herein refers a loss of dorsiflexion (with knee in
flexion <5 degrees and/or with knee in extension <0 degrees), in a patient
currently receiving or having previously received therapeutic intervention for
clubfoot.
"Equinus", or "talipes equinus", as used herein, refers to a deformity of the
foot in which the sole is flexed below neutral or in the plantarflexed range
(specifically ankle dorsiflexion is less than 0 degrees). Walking is done on
the
toes without touching the heel to the ground. 'Toe walking' is an alternate
term to describe this altered foot position's resulting gait.
"Hindfoot stall", as used herein, refers to a state wherein the forefoot may
be
abducted to 60 degrees with persistent hindfoot equinus present, or if the
lateral radiograph of the foot demonstrates a downgoing calcaneus and/or
talocalcaneal parallelism.
An 'antagonist', as used herein, refers to a chemical entity that acts to
reduce
the physiological activity of another chemical entity, for example by
combining
with and blocking the receptor of the endogenous chemical entity.
A "chemical entity", as used herein refers to small organic or inorganic
molecules with distinct molecular composition made synthetically, found in
nature, or of partial synthetic origin. Included in this group are
nucleotides,
nucleic acids, amino acids, peptides, proteins, or complexes comprising at
least one of these entities, such as a chromosome.
A "medicament", as used herein, refers to a chemical entity capable of
producing an effect that may be administered to a patient or test subject. The
effect may be chemical, biological or physical, and the patient or test
subject
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_$_
may be human, or a non-human animal, such as a rodent or transgenic
mouse. The medicament may be comprised of the effective chemical entity
alone or in combination with a pharmaceutically acceptable excipient.
A pharmaceutically acceptable excipient includes any and all solvents,
dispersion media, coatings, antibacterial, antimicrobial or antifungal agents,
isotonic and absorption delaying agents, and the like that are physiologically
compatable. The excipient may be suitable for intravenous, intraperitoneal,
intramuscular, intrathecal or oral administration. The excipient may include
sterile aqueous solutions or dispersions for extemporaneous preparation of
sterile injectable solutions or dispersion. Use of such media for preparation
of
medicaments is known in the art.
A pharmacologically effective amount of a medicament as used herein refers
to using an amount of a medicament present in such a concentration to result
in a therapeutic level of drug delivered over the term that the drug is used.
This may be dependent on mode of delivery, time period of the dosage, age,
weight, general health, sex and diet of the subject receiving the medicament.
The medicaments of the present invention may be formulated for
administration by any of various routes. The medicaments may include an
excipient in combination with the effective chemical entity, and may be in the
form of, for example, tablets, capsules, powders, granules, lozenges, pill,
suppositories, liquid or gel preparations, or an injectable formulation,
suitable
for subcutaneous, intramuscular, intravenous, intraperitoneal, intra-arterial
or
other modes of injectable delivery. Medicaments may be formulated for
parenteral administration in a sterile medium. The medicament may be
dissolved or suspended in the medium. Medicaments may be formulated for
a subdermal implant in the form of a pellet, rod or granule. The implant or
implants may be inserted subcutaneously by open surgery or by use of a
trochar and cannula under local anaesthesia. The implant may be periodically
replaced or removed altogether. Medicaments may also be formulated for
transdermal administration using a patch. The patch is applied to a shaven
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_g_
area of the skin of the patient while the medicament is desired for
administration, and removed when no longer needed.
A "neuromuscular paralytic agent", as used herein, refers to an acetylcholine
antagonist, an acetylcholine release inhibitor or a cholinergic release
inhibitor.
Neuromuscular paralytic agents generally exert their effect by blocking
acetylcholine release from a presynaptic terminal of a nerve ending at a
neuromuscular junction. Administration of a neuromuscular paralytic agent in
a medicament may result in a degree of paralysis of the muscle at the site of
administration. The paralysis may be reversible or irreversible.
"Botulinum toxin", as used herein, refers to a neuromuscular paralytic agent
normally produced by the Clostridium botulinum bacteria. Botulinum toxin A,
botulinum type A toxin or botulinum toxin type A may be abbreviated as BTX-
A. Botulinum toxin B, botulinum type B toxin or botulinum toxin type B may be
abbreviated as BTX-B. BotoxT"" (Allergan), also referenced as OculinumT"" or
DysportT"", is a commercially produced medicament comprising BTX-A.
MyobIocT"" or NeuroblocT"" (Solstice Neurosciences) is a commercially
produced medicament comprising BTX-B. Other botulinum toxins include
botulinum toxin C, botulinum toxin D, botulinum toxin E, botulinum toxin F and
botulinum toxin G - these may be administered in the form of a medicament
comprising such toxins.
Physical therapy approaches for the treatment of clubfoot in infants vary. The
most commonly used and peer-reviewed method is that of Bensahel and
Dimeglio (55, 56, 57). The Ponseti method involves a set methodology of
manipulations and casting of the foot and is an intensive and involved
method, requiring significant caregiver compliance and participation. The
Ponseti method generally requires that all components of the clubfoot be
corrected simultaneously, except for equinus, which is corrected last. The
cavus is corrected together with the adduction by supinating and abducting
the forefoot in proper alignment with the hindfoot. With the arch well moulded
and the foot in slight supiation, the entire foot can be gently and gradually
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abducted under the talus, which is secured against toration in the ankle
mortise by applying counterpressure (with the thumb of the therapist) against
the lateral part of the talus head. Heel varus is corrected when the entire
foot
is fully abducted. Finally, equinus is corrected by performing an Achilles
tenotomy in 80% of cases. Percutaneous Achilles tenotomy is the current
approach in the art, and while simple to perform technically, may lead to
immediate complications causing neurovascular injury. Further, it may lead to
future complications of such as skin scarring and deep tissue fibrosis
resulting
in reduced ankle joint range of motion and power push off, affecting the gait.
Additional complications are introduced if the clubfoot deformity relapses,
especially if an initial tenotomy has been performed.
Relapse occurs in about 30% of cases, and usually after the patient has
become an active child and in some cases ready to enter school. The most
common deformities in relapse are supination, equinus and adductus.
The deforming force causing the supination is in part attributed to the
tibialis
posterior muscle. In the untreated club foot one of the major deforming forces
is the tibialis posterior and its lengthening is one of the principal steps
performed in a clubfoot release (10, 13, 31, 48). During stance, tibialis
posterior contracts as part of the intrinsic foot muscle control. The tibialis
posterior contracts specifically at initial contact with the ground causing a
supination torque. The peak action of the tibialis posterior is related to
subtalar deceleration and stability. It therefore presents as supination of
the
midfoot in stance and can contribute to an associated hindfoot varus. In swing
phase, the tibialis posterior does not normally contract, however if
overactive
it will act alongside the anterior tibial muscles, having the net effect of
both
supination and equinus during leg swing.
The equinus deformity in the recurrences is mostly attributed to the Achilles
tendon and its associated gastrosoleus. muscle complex. Here too, if the
complex is overactive, equinus will be seen both in the stance and swing
phases of gait as it normally fires in both.
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Recurrence of the forefoot adductus is also common in relapse. The abductor
hallucis muscle is the primary deforming force causing adduction of the
forefoot. In the swing phase of the affected patient's gait, exaggeration of
forefoot internal progression is the result in part of abductor hallucis, and
its
overactivity can persist in stance causing an increase in the heel bisector.
The heel bisector score described by Bleck refers to the reference line
passing through the longitudinal axis of the heel along the plantar surface of
the foot (58). A normal foot is characterized by the line passing through the
2"d toe (a heel bisector score of 2), mild forefoot adductus by a heel
bisector
of 3, moderate by a heel bisector of 4, and severe by a heel bisector of 5.
For relapse of clubfoot with supination, the standard of treatment is a
tibialis
anterior transfer. In this surgical procedure, the tibialis anterior muscle is
transferred from its original insertion in the 1 St metatarsal into the 3~d
(lateral)
cuneiform (63, 64). This transfer addresses the supination deformity of the
foot by balancing out the action on the foot imposed by tibialis posterior. By
moving the tibialis anterior onto the lateral dorsum of the foot, the activity
of
the tibialis posterior is counteracted during the swing phase of the patient's
gait, allowing the foot to swing through in a neutral position. The tibialis
anterior has no deforming force in a clubfoot however, and by transferring it
surgically, it does not directly address the problem - the pathologic forces
incurred by tibialis posterior on the relapsed foot. The tibialis posterior is
predominantly a stance phase muscle and cannot be balanced out is stance
as tibialis anterior is silent in stance. The tibialis posterior, therefore
needs to
be treated directly to effect the appropriate changes, rather than surgically
treating a 'surrogate' muscle - the tibialis anterior.
For treating relapse of clubfoot with an equinus contracture, additional
Achilles lengthening is required and an Achilles tenotomy or formal open
lengthening is the standard of care. Depending on the progress of the initial
clubfoot management, this may be at least the second Achilles tenotomy or
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lengthening procedure performed on the patient. The deformation induced by
the muscle is directly addressed by tenotomy, but the surgery is accompanied
by the risks inherent with the procedure, including general anaesthesia.
Furthermore, each time the Achilles tendon is sectioned, weakness is
introduced resulting in decreased power of push-off when ambulating, and
diminished range of ankle motion (59, 60, 61, 62).
The standard of care for relapse of clubfoot with forefoot adductus is a
double
tarsal osteotomy or "flip flop" osteotomy, usually performed once the child is
over 4 years of age and ideally 6 years or older (65). This procedure involves
dividing the medial cuneiform in half and taking a laterally based wedge out
of
the cuboid and inserting this wedge into the divided medial cuneiform thereby
forcing the foot from adductus to abductus, based on the size of the wedge.
Metatarsus adductus, independent of clubfoot, may also treated initially with
manipulation and casting, but may require surgical intervention such as tarsal
osteotomy if unsuccessful, or if a relapse occurs.
Each of these relapse or recurrence events do not necessarily occur in
isolation, and frequently are concurrent, however each deformity must be
addressed individually. Injection of a neuromuscular paralytic agent, for
example a botulinum toxin, into the effector muscle in each case will
circumvent the need for surgical intervention. Supination may be addressed
by specifically treating the tibialis posterior. Equinus may be addressed by
specifically treating the gastrosoleus complex, while forefoot adductus may be
addressed by specifically treating the abductor hallucis muscle, weakening it
sufficiently to address the adductus. Manipulations and casting methods
accompany all of these interventions to obtain correction after relapse, and
further bracing methods used for maintenance of the corrected foot posture.
Neuromuscular paralytic agents, for example botulinum toxin type A (BTX-A,
BotoxT"") cause partial reversible muscle paralysis (8,16,22). BTX-A acts by
blocking acetylcholine release from the presynaptic terminal of peripheral
nerve endings at the neuromuscular junction. Intramuscular injection of BTX-A
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has been shown to lead to partial paralysis of the respective muscle and has
been shown to be effective in a number of disorders (6,8,16,22,26,47) and
safe across all ages studied (2 days old to adults) (8,17,32). Side effects
are
rare and transient (5,22,26) and repeated doses may be given if necessary
without concern of inducing any long-term complications (8,34).
Methods
Identification of relapse
A clubfoot relapse is identified by assessment of equinus, supination and
adductus in a patient previously or currently treated for clubfoot. A relapse
of
equinus is determined based on the dorsiflexion scores, a relapse of
supination is based on heel and midfoot varus and supination respectively,
and a relapse of adductus is determined on the basis of heel bisector. A
general indication of relapse is the ability to place the affected foot or
feet of
the patient into boots and bars or orthoses. If any of these 3 relapses exist
bracing becomes intolerable and therefore correction is, or has been, lost.
Treatment of clubfoot relapse with supination
The tibialis posterior of the clubfoot-affected limb is injected with BotoxT""
while the patient is sedated or under a general anaesthetic. A muscle
stimulator is used to identify the tibialis posterior in advance of injection.
A
minimum of two sites of the tibialis posterior are injected and the muscle is
massaged for about 20 seconds following injection. Above-knee
manipulation in the maximally abducted and externally rotated position
tolerated by the patient is performed, followed by above knee casting. The
patient is permitted to fully weight bear on the cast ad libidum. The cast is
changed 2-3 weeks later and a below knee manipulation and casting
performed with maximum tolerable correction. 2-3 weeks following the
second casting, the patient enters a maintenance bracing program full time for
3 months and then only at night (about 12 hours per day) until the brace is
outgrown. Daytime shoe wear is then prescribed.
Treatment of clubfoot relapse with e4uinus
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The gastrosoleus muscle complex of the clubfoot-affected limb is injected with
BotoxT"" while the patient is sedated or under a general anaesthetic, if the
tibialis posterior and/or abductor hallucis are treated simultaneously. If the
gastrosoleus muscle complex is treated in isolation, the procedure may be
performed in an outpatient setting. Injection of the gastrosoleus muscle
complex is performed in a stellate pattern at a minimum of 4 sites, including
the distal soleus of the affected leg. The muscle is massaged for about 20
seconds following injection and a below-knee cast (if the gastrosoleus muscle
complex is treated in isolation, otherwise an above-knee cast is used) is
applied to the clubfoot-affected leg in the maximum tolerated dorsiflexion
posture. The patient is permitted to fully weight bear on the cast ad libidum.
The cast is changed 2-3 weeks later and a second cast applied to the affected
leg in maximal dorsiflexion. 2-3 weeks following the second casting, the
patient enters a maintenance bracing program full time for 3 months and then
only at night until the brace is outgrown. Daytime shoe wear is then
prescribed.
Treatment of clubfoot relapse with adductus
The abductor hallucis of the clubfoot-affected limb is injected with BotoxT""
while the patient is sedated or under a general anaesthetic. A muscle
stimulator is used to identify the abductor hallucis muscle in advance of
injection. Up to 3 sites are injected and the muscle is massaged for 20
seconds following each injection and a below -knee cast (if the abductor
hallucis is treated alone or in conjunction with the gastrosoleus muscle
complex, otherwise an above-knee cast is used) is applied to the clubfoot-
affected leg in the maximum tolerable corrected foot posture. The patient is
permitted to fully weight bear on the cast ad libidum. The cast is changed 2-3
weeks later and a second cast applied to the affected leg in maximum
tolerated corrected foot posture. 2-3 weeks following the second casting, the
patient enters a maintenance bracing program full time for 3 months and then
only at night until the brace is outgrown. Daytime shoe wear is then
prescribed.
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Treatment of metatarsus adductus relapse
A relapse of metatarsus adductus, independent of clubfoot may also be
treated in a similar manner to that of adductus relapse in clubfoot.
For all treatments, a dosage range from about 10 IU/kg to about 20 IU/kg may
be used, divided between the required injection sites. Minimal dosing at an
individual site may comprise:
Gastrocnemius 3-6 IU/kg; soleus 2-3 IU/kg
Tibialis posterior 1-2 IU/kg
Abductor hallucis 1-2 IU/kg
Bracing Protocol
As required, Denis Browne bar and corrective shoes (boots and bars) were
fitted to the patient as described in the art. Alternatively, custom-fitted
knee-
ankle-foot orthoses (KAFO) were required in a few patients due to intolerance
of the boots and bars.
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Examples
Table 1: Results of treating Gastrosoleus only
Number of Patients7
Patient OutcomesAnkle Range
of Motion:
DFF (ankle
dorsiflexion
with knee
in flexion)
DFE (ankle
dorsiflexion
with knee
in extension)
Pilot Results Pre-Injection Post-Injection
8 weeks post
Right Foot Left Foot Right Foot Left Foot
Mean DFF: Mean DFF: Mean DFF: Mean DFF:
3 5 18 22
Mean DFE: Mean DFE: Mean DFE: Mean DFE:
1 2 11 17
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Table 2: Results of treating gastrosoleus and tibialis posterior
simultaneously
Number of Patients13
Patient Outcomes1. Ankle
Range of
Motion:
DFF (ankle
dorsiflexion
with knee
in flexion)
DFE (ankle
dorsiflexion
with knee
in extension)
2. Clinical
observation
of hindfoot
position
3. Pedobarography
Pilot Results
1. Ankle Range Pre-Injection Post-Injection
of
Motion 8 weeks
post
Right Foot Left Foot Right Foot Left Foot
Mean DFF: Mean DFF: Mean DFF: Mean DFF: 19
9 7 9
Mean DFE: Mean DFE: Mean DFE: Mean DFE: 17
5 5 5
2. Clinical The influence
of the tibialis
posterior
muscle is
seen in
the hindfoot
and the
observation midfoot during
of standing
(static
phase) and
walking
(dynamic
phase).
The
hindfoot positioncharacteristics
of the foot
that are
observed
clinically
are as follows:
Static Phase:
Hindfoot
in varus?
Midfoot in
supination?
Dynamic Phase:
Hindfoot
(heel) striking
at initial
contact?
Midfoot in
supination
at initial
contact?
Hindfoot
in varus
during swing?
Midfoot in
supination
during swing?
Clinical
observation
of the hindfoot
and midfoot
was synthesized
as dichotomous
data (yes/no)
for each
patient.
Pre-injection,
patients
showed hindfoot
varus and
midfoot supination
during the
static phase.
There was
no hindfoot
strike and
the
midfoot was
in supination
at hindfoot
strike during
initial
contact
of the dynamic
phase. During
swing in
the dynamic
phase, the
hindfoot
was in varus
and midfoot
in supination
for patients.
Such clinical
features
were indications
for Botox
injection
in the tibialis-posterior
muscle.
Post-injection,
1 of 13
patients
(1 of 22
injected
clubfeet)
converted
and showed
response
to the Botox.
3. PedobarographyPedobarography
data were
not synthesized
for purposes
of this
patent
application.
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Table 3 Results of treating abducutor hallucis only
Number of 4
Patients
Patient Heel
Bisector
Scores
Outcomes
Pilot Results Pre-Injection Post-Injection
8 weeks
post
Right Right Avg Left Avg
Left Foot
Foot
Foot Foot Change Change
Pt 1: Pt 1: Pt 1: 1/2 Pt 1: 0
3/4 3/4 3 3/4
Pt 2: Pt 2: Pt 2: 1 1/2 Pt 2: 1 1/2
4/5 4/5 3 3
Pt 3: Pt 3: Pt 3: 1 1/2 Pt 3: 1 1
3/4 3/4 2 2 /2
Pt 4: Pt 4: Pt 4: 0 Pt 4: 2 1/2
3/4 3/4 3/4 1
Six out howed
of 8 an average
patients improvement
s of 1.125
heel
bisectors.
While specific embodiments of the invention have been described and
illustrated, such embodiments should be considered illustrative of the
invention only and not as limiting the invention as construed in accordance
with the accompanying claims.
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Based on the foregoing, it will be appreciated that the present invention
provides the following advances over the art:
A method of reducing supination in a relapsed clubfoot-affected foot of a
patient, the method comprising;
injecting a medicament comprising a neuromuscular paralytic agent into at
least two sites of a tibialis posterior muscle adjoining said clubfoot-
affected
foot.
A method of reducing equinus in a relapsed clubfoot-affected foot of a
patient,
the method comprising;
injecting a medicament comprising a neuromuscular paralytic agent into at
least four sites of a gastrosoleus muscle complex adjoining said clubfoot-
affected foot.
A method of reducing adductus in a relapsed clubfoot-affected foot of a
patient, the method comprising;
injecting a medicament comprising a neuromuscular paralytic agent into at
least 1 site of an abductor hallucis muscle adjoining said clubfoot-affected
foot.
The method of any of the above, wherein said tibialis posterior or said
abductor hallucis is first identified by use of a muscle stimulator.
The method of any of the above, wherein said neuromuscular paralytic agent
is an acetylcholine antagonist.
The method of any of the above, wherein said acetylcholine antagonist is a
botulinum toxin.
The method of any of the above, wherein said botulinum toxin is botulinum
toxin type A.
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The method of any of the above, wherein said medicament is selected from
the group of BotoxT"" and MyobIocT""
The method of any of the above, wherein said injection is followed by casting
of said clubfoot affected foot.
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