Transcript Treatment of Spasticity and Dystonia in Children with Cerebral PalsY

Laura L. Deon, MD
Rush University Medical Center
La Rabida Children’s Hospital

Rett syndrome is a unique developmental disorder caused by a
MECP2 mutation that usually occurs in infant girls.

It is characterized by normal development up until between 6
and 18 months of age and then regression of developmental
milestones occurs.

The management of children with Rett syndrome ideally involves
a team of professionals

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Physical therapists
Occupational therapists
Speech therapists
Physiatrists
Pediatric neurologists
Orthotists
Primary Care
GI
Pediatric orthopedist

Care and comfort

Ease of care giving

Proper equipment makes care giving easier
 Hoyer lifts, wheelchair lifts/ramps, bath chairs,
adapted vans
Adaptive equipment for improved function
 Proper DME for home use to improve comfort and
safety




Hospital beds
Specialized chairs for feeding/bathing
Management of Spasticity

Therapy, bracing, oral medications, and intramuscular
medications
 May
help improve function in some cases by
temporarily decreasing stereotypic
movements.
 Help
promote neutral positioning of the
hands, limbs, and feet.
 Should
be used based on tolerance and
comfort of the patient.
 Can
control thumb and wrist muscles that
may be affected by increased tone.
 An
open hand and thumb may lead to
increased function through improved grasp.
A
neutral wrist may promote better hand
function.

May provide support to the arm to improve functional
activities such as eating.

May do a modest job of preventing hand wringing or
hand mouthing.

Can be used for brief periods during activities where
decreased wringing or hand mouthing may improve
function such as computer usage.

Should not be used for extended periods since
inhibiting hand wringing/mouthing over prolonged
periods can cause agitation or increased intensity of
the stereotypic movements.
 Can
assist with communicating basic needs
and more complex ideas.
 Communication
cards/boards can be used as
well as more advanced machinery such as an
ipad to tobi/dynavox.
 Can
be controlled with eye gaze or a switch
mechanism.

Spasticity is a common consequence of abnormal
brain development.

Spasticity is a velocity-dependent resistance of a
muscle to stretch.

It is defined as having one or both of the
following signs:


1) resistance to externally imposed movement
increases with increasing speed of stretch and varies
with the direction of joint movement
2) resistance to externally imposed movement rises
rapidly above a threshold speed or joint angle
 Spasticity
can vary depending on several
factors such as the patient’s level of activity,
level of alertness, emotional state, and
discomfort.
 On
exam, upper motor neuron signs such as
hyperreflexia, clonus, and Babinski response
are commonly present.
 There
are many ways to treat spasticity.
Carefully defining the goal of treatment is as
important as the treatment itself.

The goals should be explored and discussed
in the context of the child’s function with
the family and the medical team.
 Management
of spasticity or hypertonia is
divided into global or whole body
involvement and focal problems, which may
affect one joint level of one extremity.

Choosing a conservative therapy such as bracing
or medications to manage spasticity should
maximize function or improve the child’s general
care and comfort and minimize side effects or
complications.

The treatment should also suit the patient, the
family, and the available community resources
and capabilities.

Be sure to keep the goal in mind….



Comfort
Preventing orthopedic complications
Brace wear/shoe wear
 Hypertonia
and decreased selective motor
control contribute to decreased frequency
and variety of voluntary movements
 With
the decreased frequency and variety of
movements, patients are at risk for
contractures which can be treated and often
times prevented with proper care.
A
joint contracture develops when the
normal tissues are replaced by inelastic
fiber-like tissue in an area of the body that
isn’t moving.
 The
more you move and stretch, the less
likely you are to develop a contracture.
 ROM
exercises can help prevent
contractures.
 Sustained
stretch provided by bracing can be
very effective for improving ROM and
decreasing incidence of contracture.
 AFOs
are recommended to help prevent
ankle contractures along with night splints
that are worn while sleeping.
 Hand,
wrist, and elbow splints can help
reduce flexion contractures in the upper
extremities.
 If


a contracture develops…
Dynamic splinting, serial casting, or tendon
release may be recommended.
Intervention is only recommended if contracture
is inhibiting function, causing skin breakdown, or
inhibiting good hygiene.
 Stretching
 Oral
and bracing
medications
 Intramuscular
injections or nerve blocks
 Intrathecal
Baclofen Pumps
 Orthopedic
surgery
 Spasticity
can also be treated with the use of
oral medications.

Benzodiazepines, such as diazepam, have been
quite popular.

Baclofen

Dantrolene sodium

Tizanidine.

The benzodiazepines facilitate transmission at GABA-A receptors,
one of the principle types of inhibitory synapses in the central
nervous system. This results in increased inhibition and reduces
monosynaptic and polysynaptic reflexes

It is able to act supraspinally and at the spinal cord and has been
shown to reduce generalized spasticity, hyperreflexia, and
muscle spasms

Diazepam is one of the oldest pharmacologic treatments for
spasticity and it is still used today
It improves sleep and decreases anxiety.
 It is an excellent agent for patients who have poor sleep accompanied
by night time spasms


Since sedation is one of the most common side effects, dosing
usually starts with night time administration and tapers up to two
to three doses per day in those who can tolerate it.

Pediatric doses range from 0.12 to 0.8 mg/kg/day.

For adults, dosing is from 2-10 mg two to three times daily.

With the use of diazepam it is important to remember that
there is a risk for tolerance and/or dependence with the
use of this medication.

Diazepam should never be stopped abruptly in patients
who have been taking the medicine for an extended period
of time due to the risk of withdrawal.

Withdrawal symptoms may include agitation, irritability,
tremor, muscle fasciculation, nausea, hyperpyrexia, and
seizures

Baclofen is a structural analog of GABA. Baclofen binds to the
GABA B receptor which occur both pre- and post-synaptically. The
net effect is inhibition of monosynaptic and polysynaptic spinal
reflexes

Baclofen also reduces the release of excitatory neurotransmitters
and substance P when it binds to the GABA B receptors. It
primarily acts at the spinal cord level so it is an excellent
treatment for those with spasticity of spinal cord origin and it is
also used in children with abnormal brain development

Baclofen has been shown to reduce spasms, clonus, resistance to
stretch, and in some cases it has demonstrated an anxiolytic
effect

Baclofen can often cause sedation so dosing usually begins with
night time administration and usually tapers up to three to four
doses daily.

Pediatric dosing for Baclofen starts between 2.5 and
10mg per day and can taper up to 40 mg per day
divided into three or four doses.

For adults, dosing starts at 20mg per day and can
taper up to 80mg per day divided into three or four
doses.

Much like the benzodiazepines, care should be taken
when stopping this medication.

In patients who have been on baclofen for an
extended period of time, withdrawal syndromes can
sometimes occur.

Symptoms of withdrawal may include intensified
spasticity with increased spasms, hallucinations,
confusion, seizures, and hyperpyrexia

Dantrolene is unique in that it actually acts at the site of the skeletal muscle as
opposed to the neurotransmitter systems that most other oral agents act upon.

It inhibits release of calcium from the sarcoplasmic reticulum during muscle
contraction

Dantrolene is generally preferred in hemiplegia, traumatic brain injury, or cerebral
palsy, but it is also used as a secondary agent in some patients with spinal cord
injury.

It has been known to reduce clonus and muscle spasms resulting from innocuous
stimuli

Dantrolene is mildly sedating and may cause malaise, nausea, vomiting, dizziness,
diarrhea, and paresthesia

The most important side effect is hepatotoxicity. Although its occurrence is rare,
liver function tests should be performed before beginning a regimen of dantrolene
sodium and monitored periodically. The drug should be tapered or discontinued if
enzyme elevations are noted since most cases are reversible upon prompt
discontinuation
 The
goal for pediatric dosing of dantrolene is
6-8 mg/kg/day divided into two to four doses
per day.

The starting dose is usually 0.5 mg/kg/day for
seven days and then gradually increased week by
week.
 The
goal for adult dosing is 100mg divided
into two to four doses per day but dosing
usually begins at 25mg/day and then tapers
up every week thereafter.

Tizanidine is an alpha-2 adrenergic agonist that acts on
receptors in the brain and spinal cord

This causes a decrease in tone through the
hyperpolarization of motoneurons. Alpha-2 adrenergic
agonists may also have an antinociceptive effect which
may contribute to their ability to decrease tone.

Some common side effects include sedation, dizziness,
nausea, hypotension, and dry mouth. Hepatotoxicity is also
a concern when prescribing tizanidine because it is
extensively metabolized by the liver.

Liver function tests should be checked before initiation of
tizanidine and periodically during treatment
 Pediatric
dosing for tizanidine has not been
defined but most practitioners start at 2mg
at bedtime and taper up to 24-32mg divided
in three to four doses given throughout the
day.
 Adult
dosing starts at 4mg and may taper up
to 8mg three to four times daily.
Medication
Mechanism of Action
Side Effects
Pediatric Dosing
Diazepam
Facilitates transmission at
the GABA-A receptors,
one of the principle types
of inhibitory synapses in
the CNS.
Sedation, decreased
motor coordination,
impaired attention and
memory. Can cause
overdose or withdrawal.
0.12-0.8 mg/kg/day in
divided doses or once
daily at night.
Baclofen
Binds to GABA-B receptors
in the spinal cord to
inhibit reflexes that cause
spasticity.
Sedation, confusion,
nausea, dizziness,
hypotonia, muscle
weakness, and ataxia. Can
cause withdrawal.
Start at 2.5-10mg per day.
Can taper up to a
maximum of 40mg per day
divided TID or QID.
Dantrolene
Acts at the site of skeletal
muscle to inhibit calcium
release from the
sarcoplasmic reticulum.
Sedation, diarrhea, and
dizziness. Causes
hepatotoxicity in 2% so
LFTs must be monitored.
Start at 0.5mg/kg/day.
Can taper up to a
maximum of 3mg/kg QID.
Tizanidine
Alpha-2 agonist that acts
on the brain and spinal
cord to decrease tone
through hyperpolarization
of motoneurons.
Sedation, dizziness, dry
mouth, elevated LFTs,
insomnia, muscle
weakness.
Start at 2mg at bedtime.
Can taper up to a
maximum of 32mg/day
divided TID or QID.

Neuromuscular blockade/chemodenervation is another way that
hypertonia can be treated quite effectively.

Injections of phenol and ethyl alcohol have been used for several decades
and in the recent years the use of botulinum toxin has become very
popular.

Both phenol and alcohol have been used for the treatment of spasticity.

In order to localize the nerve that needs to be injected, electrical
stimulation is used. This can be painful so sedation or anesthesia is
usually necessary, especially in children.

The agent is injected perineurally, where it promotes denervation via
axonal degeneration. The effect is not permanent, with functional
reinnervation occurring over months to years.
 Adverse
effects of both agents include a
significant risk of dysesthesia when targeting
a mixed nerve, which may persist after the
procedure is complete.
 Other
complications may include muscle
necrosis or vascular complications.
 Phenol
and ethyl alcohol are excellent, cost
effective choices for patients with very
powerful muscles that are inadequately
treated by the recommended amounts of
botulinum toxin.
 Both
types of injections require a skilled
clinician.

The introduction of botulinum toxin for the relief
of focal muscle overactivity has resulted in a
major advancement in spasticity treatment

Botulinum toxin is an exotoxin produced by the
bacterium, Clostridium botulinum. The same
bacteria that is responsible for tetanus.

The site of action for botulinum toxin is at the
neuromuscular junction. A protease cleaves one
or more vesicle fusion proteins and prevents the
release of acetylcholine which causes muscle
weakness

Its effects on the neuromuscular junction are reversible so
reinjection is required every 3-4 months. However, in some
patients, the improvements outlast the direct effect on
the nerve terminal

Dosing is usually 10-12 units per kilogram but not to
exceed 400 units in any one procedure in most cases.

Two serotypes, A and B, are available in the United States.
Type A is marketed as BOTOX by Allergan, Inc. It is approved
for cervical dystonia, blepharospasm, hemifacial spasm,
primary axillary hyperhidrosis, and strabismus.
 Type B is marketed as MyoBloc by Solstice Neurosciences, Inc.
It is approved for cervical dystonia. Some other off label uses
include the treatment of spasticity in those with cerebral
palsy, traumatic brain injury, spinal cord injury, and other
diagnoses. It is also used to treat sialorrhea and myofascial
pain.

 The
most appropriate candidate for
botulinum toxin injections is the patient in
whom an appropriate weakening of a limited
number of muscles has the potential to
provide meaningful benefit in care, comfort,
or activity
 Those
with adequate selective motor control
stand to have the best results while those
with long standing contractures and
deformities have poorer outcomes
 Botulinum
toxin can also be used for focal
and regional management of spasticity in
conjunction with orthopedic surgery or in
combination with serial casting.
 Using
serial casting in conjunction with
botulinum toxin may decrease the amount of
time required to achieve the desired range of
motion goals
Medication
Mechanism
Site of Injection
Onset and
Duration
Disadvantages/R
isks
Cost
Phenol
Chemical
neurolysis
causes
denervation via
axonal
degeneration
Injected into the
motor points of
the involved
muscle.
Takes effect
immediately.
Can last 3-12
months.
Can be painful
and may require
anesthesia. Can
cause
dysesthesias,
numbness, or
hematoma.
Very low cost
Botulinum type
A
Presynaptic
block of
acetylcholine
release.
Intramuscular
Takes effect in
5-7 days. Can
last 3-6 months.
Lasts only 3-4
months and
cannot be
repeated in
shorter
intervals. Can
cause
swallowing and
respiratory
difficulties when
used in large
quantities in the
neck muscles.
Up to $600 per
100 unit vial

In cases where spasticity cannot be managed
with physical methods, oral medications, or
injectable medications, there are surgical
options such as selective dorsal rhizotomy and
intrathecal baclofen therapy that can be used.

Although these procedures are invasive, they can
be very effective in those who have spasticity
that is so severe that other methods of
treatment have been ineffective or in cases
where the side effects of other various antispasticity treatments could not be tolerated.

Always keep a goal of care and comfort in mind.
When planning for equipment needs and medications,
make sure the best interest of the child and family is
in the focus.

A pediatric physiatrist can typically provide expertise
in tone management and equipment/therapy needs.
Some pediatric neurologists and developmental
pediatricians may specialize in this as well.

First line medications such as Baclofen or Valium can
be initiated by the pediatrician or pediatric
neurologist however, children with Rett need close
monitoring for dose adjustments, side effect
monitoring, and evaluation of progress towards
rehabilitation goals.

Neurolytics such as botox and phenol can control
the focal tone that can be found in Rett
syndrome.

Despite aggressive treatment of hypertonia,
deformities and contractures can still occur.
Decisions regarding the timing of treatments
such as botulinum toxin, ITB, or orthopedic
surgery should be discussed with the family to
see what goals are in mind before proceeding.

Management of spasticity with a goal of
minimizing its effects and maximizing comfort
benefits the child and improves long term
functional outcomes.
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