Cerebral palsy, treatment

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

There are reports of the benefits of botulinum toxin in the treatment of cerebral palsy in children. The toxin, produced by Clostridium botulinum, is a powerful and deadly poison, but is also an effective muscle relaxant. It is not licensed for use as such in the UK but is undergoing clinical trials. Current evidence suggests that repeat injections are necessary some 4-6 months after the first. 

Dystonia due to identifiable structural or biochemical abnormalities ( secondary dystonia) often occurs weeks or months after strokes or other focal lesions, which commonly involve the basal ganglia, but may also involve the thalamus or cerebellum. Dystonia is also seen in children with cerebral palsy and in patients with abnormalities of dopaminergic transmission. For instance, dystonia may develop in the context of Parkinson s disease, either as an early parkinsonian sign, or in response to dopaminergic drugs. A particularly interesting inherited disease results in a combination of dystonia and parkinsonian features at a young age, which responds dramatically to treatment with low-dose levodopa ( dopamine-responsive dystonia ). 

Spasticity Cyclobenzaprine is not effective in the treatment of spasticity associated with cerebral or spinal cord disease, or in children with cerebral palsy. 

The therapeutic use of botulinum toxin for ophthalmic purposes and for local muscle spasm was mentioned in Chapter 6. Local facial injections of botulinum toxin are widely used for the short-term treatment (1-3 months per treatment) of wrinkles associated with aging around the eyes and mouth. Local injection of botulinum toxin has also become a useful treatment for generalized spastic disorders (eg, cerebral palsy). Most clinical studies to date have involved administration in one or two limbs, and the benefits appear to persist for weeks to several months after a single treatment. Most studies have used type A botulinum toxin, but type is also available. 

Ronan S, Gold JT Nonoperative management of spasticity in children. Childs Nerv Syst 2007 23 943 [PMID 17646995] Verrotti A et al Pharmacotherapy of spasticity in children with cerebral palsy. Pediatr Neurol 2006 34 1. [PMID 16376270] Ward AB Spasticity treatment with botulinum toxins. J Neural Transm 2008 115 607. [PMID 18389166]... 

Arbel E, Goldberg M, Gur I, Naor N, Sirota L, 59. Mogilner S, Zaritsky A, Barak M, Gottfried E. Early postnatal dexamethasone treatment and increased incidence of 60. cerebral palsy. Arch Dis Child Fetal Neonatal Ed 2000 83(3) F177-81. 

Pidcock FS. The emerging role of therapeutic botu-linum toxin in the treatment of cerebral palsy. J Pediatr. 2004 145(suppl 2) S33—S35. 

Wasiak J, Hoare B, Wallen M. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst Rev. 2004 CD003469. 

Botulinum toxin A complexed with haemagglutinin is currently employed medicinally to counter involuntary facial muscle spasms, e.g. around the eye. Very small (nanogram) amounts are injected locally and result in the destruction of the acetylcholine release mechanism at the neuromuscular junction. Since new nerve junctions will gradually be formed over two months or so, the result is not permanent, and the treatment will need to be repeated. It has also been found useful in easing muscle spasticity in children with cerebral palsy. 

Benzodiazepines are used to treat insomnia and for the acute treatment of epileptic seizures, convulsive disorders, and spastic disorders such as cerebral palsy,... 

Muscular disorders Diazepam is useful in the treatment of skeletal muscle spasms such as occur in muscle strain, and in treating spasticity from degenerative disorders, such as multiple sclerosis and cerebral palsy. 

Economic costs for adverse reproductive and developmental outcomes are noteworthy and expected to grow. Annual costs for infertility treatment in the United States exceed one billion dollars (U.S. Congress 1988). According to the Centers for Disease Control and Prevention (CDC), the cost to society for developmental defects is massive (i.e., the lifetime costs for children bom annually with 17 of the most common birth defects and cerebral palsy is over 8 billion (CDC 1995)). However, these abnormalities affect only 22% of children with birth defects, and the cost estimate does not consider costs associated with many other developmental disorders. A recent study estimated the total lifetime costs for persons bom in 1996 with mental retardation, autism, or cerebral palsy to be 47 billion, 4.9 billion, and 12 billion, respectively (Honeycutt et al. 1999). 

A 2-year old girl with epilepsy and dyskinetic cerebral palsy due to kemicterus, who was taking carbamaze-pine and valproate, was also given clonazepam 0.05 mg/day and 3 days later developed urinary retention, which did not improve with antibiotic treatment (10). A urine sample obtained by catheterization was sterile. Urinary retention persisted for 10 days, requiring repeated catheterization, but resolved after clonazepam was withdrawn. She was symptom free for the next 6 months. 

Dexamethasone is widely used for the prevention and treatment of chronic lung disease in premature infants, in whom follow-up studies have raised the possibility of an association with alterations in neuromotor function and somatic growth. In 159 survivors (mean age 53 months) of a previous placebo-controlled study, the children who had received dexamethasone had a significantly higher incidence of cerebral palsy (39/80 versus 12/79 OR = 4.62 95% Cl = 2.38, 8.98) (36). The most common form of cerebral palsy was spastic diplegia. Developmental delay was more frequent in the dexamethasone group (44/80 versus 23/79 OR = 2.9 Cl = 1.5, 5.4). 

Exacerbation or precipitation of seizures has been reported in children with cerebral palsy taking long-term treatment with high doses of dantrolene (4—12 mg/kg) (7). 

Denhoff E, Feldman S, Smith MG, Litchman H, Holden W. Treatment of spastic cerebral-palsied children with sodium dantrolene. Dev Med Child Neurol 1975 17(6) 736-42. 

Helweg-Larsen J, Jacobsen E. Treatment of spasticity in cerebral palsy by means of phenol nerve block of peripheral nerves. Dan Med Bull 1969 16(l) 20-5. 

B. Drugs Used for Acute Muscle Spasm Many drugs are promoted for the treatment of acute spasm due to muscle injury. Most of these drugs are sedatives or act in the brain stem or spinal cord. Cyclobenzaprine, a typical member of this group, is believed to act in the brain stem, possibly by interfering with polysynaptic reflexes that maintain skeletal muscle tone. The drug is active by the oral route and has marked sedative and antimuscarinic actions. Cyclobenzaprine may cause confusion and visual hallucinations in some patients. It is not effective in muscle spasm due to cerebral palsy or spinal cord injury. 

Muscle relaxant blocks Ca " release from sarcoplasmic reticulum of skeletal muscle. Used in muscle spasm (cerebral palsy, multiple sclerosis, cord injury) and in emergency treatment of malignant hyperthermia. 

It is also used in the treatment of parkinsonism, cerebrovascular mishaps and cerebral palsy. 

Examples of teratogens include thalidomide, ethyl alcohol, and o-benzoic sulfim-ide (the artificial sweetener saccharin). Thalidomide is a drug that was used in the 1960s as a treatment for morning sickness in pregnant mothers. However, the toxic effects were discovered too late for 10,000 babies who were bom with various malformations. In Japan, where fish is a staple food, mothers ate fish contaminated with mercury compounds, causing children to be bom with cerebral palsy. 

Dietary chemoprevention represents an attractive approach to this problem, especially given the yonng age of the patient popnlation. Dietary supplements could be taken orally, which is certaiidy advantageous compared with the daily injections required with interferon therapy or direct injections of the lesions with steroids. Presumably, the side-effect profile would be minimal and certainly much more favorable than the fevers, irritabihty, growth disturbance, immunosuppression, and spastic diplegia (a form of cerebral palsy) associated with the other treatment options discussed in the previous section. Indeed, the EOMA model has proven efficacy to demonstrate the antiangiogenic properties of edible beny extracts and to explore the feasibility of dietary chemoprevention for endothehal cell neoplasms." ... 

Rodda, J.M. et al, Sagittal gait patterns in spastic diplegia, / Bone Joint Surg. Br., 86,251,2004. Schwartz, M.H. et al, Comprehensive treatment of ambulatory children with cerebral palsy an outcome assessment, / Pediatr. Orthop., 24,45,2004. 

Ounpuu, S., Davis, R.B., and DeLuca, P.A., Joint kinetics methods, interpretation and treatment decision-making in children with cerebral palsy and myelomeningocele. Gait Posture, 4,62,1996. 

Gage, J.R., Ed., The Treatment of Gait Problems in Cerebral Palsy, Mac Keith Press, London, 2004. Perry, J., Gait Analysis Normal and Pathological Function, Slack, Thorofare, NJ, 1992. 

Documentation repotting on the use of dynamic Lycra garments in fee treatment and management of cerebral palsy and/or other neurological disorders has been increasing over fee past twelve years. However, there is still a lot that is not known about these garments. It is not yet known how, if at all, the physiology of a child wife cerebral palsy... 

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