Medication Summary
The goal of pharmacotherapy in patients with cerebral palsy is to reduce symptoms (eg, spasticity) and prevent complications (eg, contractures). Most of the medications used for this disorder in children are off label for age and indication and should be used only by physicians experienced in their use and familiar with their adverse effects.
Note that the indications and doses listed in this section are from a general formulary. A wide range of dosing can be encountered in clinical practice, because information in the literature regarding medication for cerebral palsy in children is scant.
Neuromuscular Blockers, Botulinum Toxins
Class Summary
Botulinum toxins cause presynaptic paralysis of myoneural junctions and reduces abnormal contractions by preventing acetylcholine release from the presynaptic membrane. The therapeutic effects may last 3-6 months.
AbobotulinumtoxinA (Dysport)
First botulinum toxin to gain FDA approval for the treatment of lower limb spasticity in children aged 2-17 years. The dose is selected based on affected muscle, spasticity severity, and treatment history with botulinum toxins. Total dose per treatment session should not exceed 10-15 units/kg for unilateral lower limb injections or 20-30 units/kg for bilateral lower limb injections or 1000 units, whichever is less. Divide the total dose between the affected spastic muscles of the lower limb(s).
OnabotulinumtoxinA (BOTOX)
OnabotulinumtoxinA treats excessive, abnormal contractions associated with blepharospasm, hemifacial spasm, and cervical dystonia. This drug binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which, in turn, inhibits transmission of impulses in neuromuscular tissue. This indication is off-label use in children.
Reexamine patients 7-14 days after the initial dose to assess for a treatment response. Increase the doses 2-fold over the previous doses for patients experiencing incomplete paralysis of the target muscle. The procedure needs to be repeated every 3-6 months depending on the response.
Muscle relaxants
Class Summary
The muscle-relaxing effects of muscle-relaxant agents may come from inhibition of the transmission of monosynaptic and polysynaptic reflexes at the spinal cord level. These are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.
Baclofen (Lioresal, Gablofen)
Baclofen is a gamma-aminobutyric acid (GABA) analogue that inhibits calcium influx into presynaptic terminals and suppresses the release of excitatory neurotransmitters.
Baclofen may induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level. This agent undergoes rapid gastrointestinal absorption, which peaks in 1-2 hours. It is primarily excreted renally and is partially metabolized by the liver. Baclofen works better in the treatment of spinal spasticity than it does against cerebral spasticity, but the drug should be tried in both conditions.
This drug's use is often limited by central nervous system (CNS) adverse effects, and thus, an effective dose is usually not obtainable with oral dosing. Intrathecal baclofen is available for use with a surgically implanted pump, which may improve the effectiveness of dosing.
Dantrolene (Dantrium, Revonto)
Dantrolene inhibits the release of calcium into the sarcoplasmic reticulum. This agent may weaken even nonspastic muscles and is generally used only in patients with severe hypertonicity.
Benzodiazepines
Class Summary
Benzodiazepines are used in the acute management of seizures that may accompany cerebral palsy. By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate neurotransmission of GABA and other inhibitory transmitters. Benzodiazepines may act in the spinal cord to induce muscle relaxation.
Diazepam (Valium, Diastat)
Diazepam is effective in treating seizures by depressing all levels of the central nervous system (CNS) (eg, limbic and reticular formation), possibly by increasing the activity of GABA at the spinal and supraspinal sites. Individualize the dosage, and increase cautiously to avoid adverse effects. Diazepam undergoes rapid gastrointestinal absorption; renal excretion and hepatic metabolism occur.
Sedation is common. Diazepam may worsen swallowing problems. This drug is generally used only in patients in whom severe hypertonicity is compromising care.
Anticholinergic Agents
Class Summary
Anticholinergic agents provide benefit for tremor in approximately 50% of Parkinson's disease patients, but they do not improve bradykinesia or rigidity. If 1 anticholinergic does not work, try another. Adverse effects include dry mouth and dry eyes, memory difficulty, confusion, and rare urinary retention.
Trihexyphenidyl
Trihexyphenidyl is a synthetic tertiary amine anticholinergic agent that reduces the incidence and severity (by 20%) of akinesia, rigidity, tremor, and secondary symptoms such as drooling. Besides suppressing central cholinergic activity, these agents may inhibit reuptake and storage of dopamine at central dopamine receptors, thereby prolonging the action of dopamine.
Dopamine Prodrugs
Class Summary
Dopamine does not the cross blood-brain barrier, but levodopa (L-dopa) (the metabolic precursor of dopamine) does. L-dopa is decarboxylated to dopamine in the brain and in the periphery. The formation of dopamine in the blood causes many of the adverse effects associated with L-dopa. When administered alone, levodopa induces a high incidence of nausea and vomiting.
A peripheral decarboxylase inhibitor such as carbidopa is combined with levodopa to reduce the incidence of nausea and vomiting by inhibiting the peripheral conversion of levodopa to dopamine. Levodopa/peripheral decarboxylase inhibitor is the criterion standard of symptomatic treatment for Parkinson disease; it provides the greatest antiparkinsonian efficacy in moderate to advanced disease with the fewest acute adverse effects.
Because dopaminergic drugs block cholinergic nerve impulses that affect the muscles in the arms, legs, and other parts of the body, these agents may help patients with cerebral palsy. These medications help regulate muscle movement and motor function.
Levodopa/carbidopa (Sinemet, Sinemet CR, Parcopa)
Levodopa/carbidopa is a large, neutral amino acid absorbed in the proximal small intestine by a saturable carrier-mediated transport system. Absorption of this drug is decreased by meals that include other large, neutral amino acids. Only patients with meaningful motor fluctuations need to consider a low-protein or protein-redistributed diet.
Anticonvulsant Agents
Class Summary
Anticonvulsant drugs are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.
Levetiracetam (Keppra)
Levetiracetam is used as adjunct therapy for partial seizures and myoclonic seizures. This agent is also indicated for primary generalized tonic-clonic seizures. The mechanism of action of levetiracetam is unknown.
Oxcarbazepine (Trileptal)
The pharmacologic activity of oxcarbazepine is primarily by the 10-monohydroxy metabolite (MHD) of oxcarbazepine. This agent may block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. The anticonvulsant effect of oxcarbazepine may also occur by affecting potassium conductance and high-voltage activated calcium channels.
The drug pharmacokinetics of oxcarbazepine are similar in older children (>8 y) and adults. Young children (< 8 y) have a 30-40% increased clearance compared with older children and adults. Children younger than 2 years have not been studied in controlled clinical trials.
Valproic acid (Depakote, Depakene, Depacon)
Valproic acid is chemically unrelated to other drugs used to treat seizure disorders. Although its mechanism of action is not established, the activity of valproic acid may be related to increased brain levels of gamma-aminobutyric acid (GABA) or enhanced GABA action; it may also potentiate postsynaptic GABA responses, affect potassium channels, or have a direct membrane-stabilizing effect.
Phenobarbital
Phenobarbital exhibits anticonvulsant activity in anesthetic doses and can be administered orally; in status epilepticus, it is important to achieve therapeutic levels as quickly as possible. The intravenous (IV) dose may require approximately 15 minutes to attain peak levels in the brain. If injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed that which is required to control seizures. It is important to use the minimal amount required and to wait for an anticonvulsant effect to develop before giving a second dose.
Restrict IV use to conditions in which other routes are not possible, either because the patient is unconscious or because prompt action is required.
If an intramuscular (IM) route is chosen, administer phenobarbital into areas with little risk of encountering a nerve trunk or major artery, such as a large muscle (eg, gluteus maximus, vastus lateralis). A permanent neurologic deficit may result from injecting into or near peripheral nerves.
Alpha2 Adrenergic Agonist Agents
Class Summary
These agents are used for their antispasticity effects.
Tizanidine (Zanaflex)
Tizanidine is an imidazoline derivative and a central alpha2 noradrenergic agonist. The antispasticity effects are the probable result H-reflex inhibition. The drug may facilitate the inhibitory actions of glycine, reduce the release of excitatory amino acids and substance P, and produce analgesic effects. Tizanidine is a centrally acting muscle relaxant that is metabolized in the liver and excreted in the urine and feces.
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Magnetic resonance image (MRI) of a 1-year-old boy who was born at gestational week 27. The clinical examination was consistent with spastic diplegic cerebral palsy. Pseudocolpocephaly and decreased volume of the white matter posteriorly were consistent with periventricular leukomalacia. Evidence of diffuse polymicrogyria and thinning of the corpus callosum is noted in this image.
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Magnetic resonance image (MRI) of a 16-month-old boy who was born at term but had an anoxic event at delivery. Examination findings were consistent with a spastic quadriplegic cerebral palsy with asymmetry (more prominent right-sided deficits). Cystic encephalomalacia in the left temporal and parietal regions, delayed myelination, decreased white matter volume, and enlarged ventricles can be seen in this image. These findings are most likely the sequelae of a neonatal insult (eg, periventricular leukomalacia with a superimposed left-sided cerebral infarct).
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Magnetic resonance image (MRI) of a 9-day-old girl who was born at full term and had a perinatal hypoxic-ischemic event. Examination of the patient at 1 year revealed findings consistent with a mixed quadriparetic cerebral palsy notable for dystonia and spasticity. Severe hypoxic-ischemic injury to the medial aspect of the cerebellar hemispheres, medial temporal lobes, bilateral thalami, and bilateral corona radiata is observed in this image.
