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THE TREATMENT OF CEREBRAL PALSY: WHAT WE KNOW,
WHAT WE DON’T KNOW
MURRAY GOLDSTEIN, DO, MPH
The treatment of cerebral palsy is directed at repair of the injured brain and at the management of the impairments and
disabilities resulting from developmental brain injury. Currently, there are no clinically meaningful interventions that can
successfully repair existing damage to the brain areas that control muscle coordination and movement. However, several
interventions are available todiminish thedegreeof impairment (eg,muscle spasticity) and to increaseparticipation in activities of
daily living. Data on treatment compatiblewith evidence-basedmedicine are nowbeing collected. (J Pediatr 2004;145:S42-S46)
The management of cerebral palsy involves two issues: (1) treatment of the injured areas of the developing brain that controlmuscle coordination and movement, and (2) management of the impairments of muscle coordination and of the resultingdisabilities that are the consequences of cerebral palsy. The latter include (1) impairments such as muscle spasticity, muscle
weakness, and uncontrolled muscle movements, and (2) disabilities such as impaired mobility, inability to feed oneself, anddifficulty with speech and communication. It must also be remembered that the muscle control dysfunctions that characterizecerebral palsy are often accompanied by one or more other nervous system dysfunctions (comorbidities) such as visual difficulties,hearing loss, convulsive disorders, bone fragility, learning disabilities, cognitive deficits, behavioral problems, and the effect ofaging.1
REPAIR OF THE INJURED BRAINAt this time, there are no clinically meaningful interventions that are able successfully to repair existing damage to the areas
of the brain that control muscle coordination and movement. There are three major directions of research to repair the injuredbrain: (1) replacing the several types of brain cells that have been injured, have died, or arefunctioning poorly; (2) repairing injured neuronal processes such as dendrites and axons;and (3) stimulating the development and use of alternative brain pathways to controlmuscle coordination and movement better.
Experimental procedures have been used in animals and in human beings to replaceinjured brain cells. When embryonic neural cells were injected into the basal ganglia ofpatients with Parkinson disease to see whether they would produce dopamine ina controlled fashion, the resulting modest return of function for a limited period did notsupport this treatment. More recently, stem cells have been injected into degenerating basalganglia.2 Stem cells have the advantage of being able to multiply and differentiate in thebrain.3,4 Again, the clinical results did not support the use of this treatment methodology.Similarly, stem cell injections after ischemic stroke were of limited benefit.5
The use of embryonic neural cells or stem cells in either animal models of cerebralpalsy or human beings with cerebral palsy has not been reported. However, the conceptremains a scientifically intriguing hypothesis. Because the immature brain may be moreamenable than the mature brain to their functional incorporation, studies of their potentialare needed. At this time, the repair of the injured brain by replacing injured or dead cellswith embryonic or stem cells must be considered highly speculative, with guardedexpectation for its efficacy. Preliminary evidence does indicate that stem cells can producethe neurotrophic factors that support brain cell and neuronal process repair.
From UCP Research and EducationalFoundation, Washington, DC.Submitted for publication March 2,2004; accepted May 11, 2004.Reprint requests: Murray Goldstein,DO, MPH, UCP Research and Educa-tional Foundation, 1660 L Street NW,Ste 700, Washington, DC 20036.E-mail: [email protected]/$ - see front matter
Copyright� 2004 Elsevier Inc. All rightsreserved.
10.1016/j.jpeds.2004.05.022CAM Complimentary and alternative medicine
S42
Periventricular leukomalacia is a result of a lack ofmyelination of brain nerve cell processes (eg, axons) and theresulting poor transmission of nerve impulses. Theoligodendrocytes responsible for myelination fail to matureand become functional. The introduction of cell growthfactors into the brain cell environment6 to learn whether theirdevelopment can be stimulated and their myelination functionrestored is being investigated.
Another potential treatment approach involves brainplasticity or developing the use of other brain pathways toassume the function of the damaged areas of brain. Thefunctional anatomy of brain synapses is constantly changing inresponse to alterations in the cell’s environment such asstimulation from the sensory systems (eg, touch). Thesechanges are one biological basis of learning during de-velopment and maturity. As a result, the brain is able toacquire new or improved skills in controlling motor co-ordination. Studies using specific sensory inputs (eg, pro-prioception) to target specific brain functions to correct themuscle coordination impairments and functional loss associ-ated with cerebral palsy are in progress.
Programmed repetition such as is used in physiotherapy,occupational therapy, speech and language therapy, andspecial education is one means of teaching the brain toimprove motor performance skills.5 There are several schoolsin each of these disciplines that claim to be more effective thanthe others (eg, neurodevelopmental therapy, conductiveeducation).7-12 Meaningful evidence that these differences inapproach are significant is lacking. In trials comparingtherapies, patient motivation and the intensity and theduration of therapy appear to be more important than thedetails of the specific therapy per se. Sensory input linked tomotor performance is now recognized as a critical factor inbringing about the desired motor improvement. One exampleof this is the recent application of intermittent partialconstraint therapy as a component of physiotherapy. Otherexamples include the controlled use of training devices (eg,stationary bicycles and treadmills linked to sensory stimula-tion) to provide brain input, and the use of an Adeli suit tostrengthen muscles by increasing resistance at joints andheighten proprioception.13 The resulting improvements inmotor control are usually of relatively short duration initially,but with repetition, they often become long-lasting. Thatcertain neurostimulatory drugs can improve motor perfor-mance in animal models is currently under study in humanbeings.
Persons with disabilities and their caregivers sometimesturn to unconventional approaches to repair the injured brainbecause of their dissatisfaction with the results of conventionaltherapies and their impatience with the time it often requiresto develop and to evaluate carefully newmethods of treatment.These unconventional approaches are referred to as comple-mentary and alternative medicine (CAM). Examples of CAMinclude dietary supplements, herbal extracts, electrical andmagnetic brain stimulation, acupuncture, patterning, cranio-sacral manipulation, spiritual energy, and hyperbaric oxygentherapy.14 Reports of successful CAM interventions are
The Treatment of Cerebral Palsy: What We Know, What WeDon’t Know
almost always anecdotal (personal experience andtestimonials) and lack the rigorous data that are collected inorganized clinical trials. Also, the biologic rationale for CAM(proof of principle) is typically highly speculative, if notcontrary to accepted science. To date, there are no CAMtherapies that have been demonstrated scientifically toimprove brain function for the control of muscle spasticityor improvement in motor coordination.1
Despite all the exciting possibilities under study, there isa fundamental problem with the concept of any singleintervention being able to repair the injured brain of allpersons with cerebral palsy. Cerebral palsy is not a singledisorder with a single cause. It includes several different typesof injury to a variety of areas of the developing brain. Theseinjuries include (1) failure of cells to migrate during braindevelopment from their site of origin to appropriate functionallocations; (2) failure of oligodendrocytes to deposit myelin oncell fibers, resulting in the poor transmission of nerve impulses;(3) the death of grey matter cells; and (4) poor function atbrain cell synapses, resulting in faulty or no transmission ofnerve impulses between cells. An effective treatment willprobably need to be specific to one of these pathologies. Ata functional level, however, the recruitment of other nervetract pathways may be useful in addressing several of thepathological situations, depending on the magnitude and sitesof brain injury.
The repair of specific injuries in the motor control areasof the developing brain is an exciting area of active researchthat has captured the attention of clinical and basicneuroscientists. Research answers will provide the basis bothfor clinical experiments that address the repair of specific braininjuries and for the development of methods to improvefunction in persons with disabilities caused by cerebral palsy.13
STUDIES OF THE MANAGEMENT OFIMPAIRMENT AND FUNCTIONAL LOSSIN THE NEUROMUSCULAR SYSTEMIncreased or decreased muscle tone, spasticity, muscle
weakness, involuntary movement, and loss of control of musclecoordination are the hallmarks of damage to the developingbrain’s motor system. Although muscles and peripheral nervesare not damaged initially (with time, there are morphologicand biochemical changes), the brain is unable to provide thedelicate control that is necessary to permit the multitude ofcoordinated small and large muscle movements necessary forthe common activities of daily living (eg, using a fork, walking,swallowing, articulation). In technical terms, the damage tothe brain is an upper motor neuron lesion characterized bypoor muscle tone, spasticity, increased reflexes, and in-voluntary movements. Several treatments are available todiminish the degree of impairment (eg, muscle spasticity) and,in some instances, improve participation in activities of dailyliving (eg, independent mobility).
The specific characteristics of the impairments associ-ated with upper motor neuron lesions can provide clues as towhich focal areas of the brain have been damaged. Therapeutic
S43
interventions to lessen impairments of the neuromuscularsystem do not necessarily lead to improved function. Thus,although limb spasticity may have been decreased (a lesseningof the impairment), more efficient limb use may not result. Animprovement in function often requires additional steps toimprove strength and coordination. The research and clinicalapproaches to diminish both impairment and the associateddisability can be considered according to the neuromuscularsites that are being approached.
Brain and Spinal Cord
A variety of oral medications have been used to diminishthe sensitivity of local nerves and muscles to control theirreactions to environmental stimuli that result in musclespasticity or involuntary movements. These medications areoften of only modest benefit because of undesirable sideeffects. The negative effects on brain function (eg, awareness,alertness, personality) and on muscle strength at therapeuticlevels are usually unacceptable. Preliminary reports do supportthe use of L Dopa to treat muscle incoordination andinvoluntary movements associated with what is calleddopamine-deficient cerebral palsy.
Several neurosurgical ablative procedures have beenattempted. Their therapeutic effect on spasticity has beenminimal, with undesirable side effects. Neurosurgical pro-cedures are still under evaluation for the treatment ofathetosis. Areas of brain are sometimes ablated or electronicstimulators implanted to help control these involuntarymovements. Case series reports of success by using brainelectronic stimulation devices to treat patients with abnormalmovements can be striking. However, there are no systematicstudies that evaluate the indications for such interventions.
Dorsal rhizotomy or the transection of selected sensorynerves entering the lower spinal cord has been evaluated incontrolled clinical trials.15 The procedure clearly decreasesspasticity in the muscles associated with the severed nerves. Insome cases, there are undesirable side effects on bowel andbladder function. To have a beneficial functional effect onlower limb function, however, the patient must also participatein an intense program of physiotherapy. It remains contro-versial for whom the beneficial effects of dorsal rhizotomy areworth its side effects, whereas other, less intrusive therapiesmay still be of benefit. The expert consensus is that dorsalrhizotomy should be considered as one of several possibleinterventions but used only for persons with severe musclespasticity in the lower extremities for whom other therapieshave been unsuccessful.
Intrathecal Baclofen has been evaluated as a treatmentfor lower limb muscle spasticity16 and for general dystonia.17
Baclofen (a gamma aminobutyric acid agonist) is a drug thatdiminishes nerve cell sensitivity. When its concentration isincreased in the cerebrospinal fluid, muscle spasticitydecreases. The drug can be administered by means of a smallpump implanted under the skin of the abdomen with a tubeleading to the spinal canal. The pump’s reservoir stores thechemical, and the rate of release is electronically programmed.
S44 Goldstein
In experienced hands, there are relatively few side effects orassociated risks. Although Baclofen clearly diminishes musclespasticity, it decreases tone in all of the muscles whose nervecells it bathes. When addressing the impairment, it has nodirect effect on improving function apart from setting thestage for other interventions (eg, physiotherapy). Initialreports also suggest a potential role in the control ofinvoluntary limb movements.
Bone and Muscle
Medical and surgical orthopedic procedures can be usedto repair injured bones, strengthen weakened bone, alignpoorly positioned bones, lengthen shortened muscles, andmove tendons. Such procedures are aimed at providingstability to a poorly aligned skeletal structure and to redirectforces at joints to allow improved function. Until recently,innovations and variations in such orthopedic procedures werebased almost exclusively on the skill of the individual surgeonwith a subjective analysis of case series. The recent availabilityof both structured evaluations and of electronic gait analysisbefore and after a procedure has brought quantitativeobjectivity to outcome studies of such orthopedic inter-ventions.11,18-22 In addition, attention is now being given tothe long-term effect of these interventions on patient qualityof life. Nevertheless, controlled clinical trials continue toremain a rarity in the evaluation of both established andinnovative surgical procedures.
When botulinum toxin is injected into the neuromus-cular junction of a hypertonic or spastic muscle, that musclewill relax for a period of 4 to 6 months. The use of limitedamounts of the drug at one time restricts the number ofmuscles that can be injected. Several clinical trials havedemonstrated its effectiveness in the treatment of spasticity23
associated with cerebral palsy.24 During the extended period ofmuscle relaxation, other interventions (eg, physiotherapy)should be used to improve muscle strength and coordination.The timing for the physiotherapy (eg, both before and thenafter injection, or only after injection) to maximize results isunder investigation. Several courses of botulinum therapy areusually needed. Other medical nerve block techniques toproduce muscle relaxation include alcohol or phenol injectioninto the spastic muscle’s nerve supply. These injections haverelatively long-lasting effects but often cause sensory loss andpermanent damage. At this time, nerve block injections arereserved for use only in very special circumstances.
Physical therapy, occupational therapy, and speechtherapy use several physical and behavioral approaches todiminish disability, improve function, and maintain perfor-mance.1,25 These approaches are often incorporated withinother intervention strategies (eg, postsurgical, after botulinumtoxin injection) and aim at lengthening contracted muscles,improving the strength of weakened muscles, increasing therange of motion at restricted joints, improving movementcoordination, and developing compensatory strategies toaccomplish tasks. Clinical trials relate the success of a particularapproach more to the motivation of the patient, the type and
The Journal of Pediatrics � August 2004
degree of impairment, the effect of the therapist–patientinteraction, the intensity of therapy, the duration of therapy,and sometimes the environment in which the therapy isconducted than to the specifics of the particular intervention.These therapies can be either primary treatments or adjunctsto other interventions. However, a number of controlledclinical triaH They can serve both to improve function and tomaintain existing function. However, important questionsabout their use remain: for whom, when, how much, and forhow long?
Other devices and approaches have been developed toadd to the techniques used by physicians and therapists todecrease impairment and improve function. These includebiofeedback and therapeutic electrical stimulation.8,11 Therehave been limited evaluations of these technologies, and theirrole in the treatment of cerebral palsy remains questionable.On the other hand, orthotic devices and casting9 are regularlyused by clinicians for the appropriate alignment of bone andadjustment of the range of motion at joints. These often havenot been objectively evaluated as independent modalitiesbut usually have been included as part of a treatment protocolevaluating other interventions. Although their value is rarelyquestioned, the actual clinical evidence supporting theirusefulness remains limited. In addition, there are nowavailable many technological devices to assist persons inactivities of daily living. This continuously evolving fieldranges from simple mechanical devices to assist in eating, topowered wheel chairs, to highly sophisticated electroniccommunication devices. In recent years, adapting computerprograms to the tasks important to education and toemployment has broadened the opportunities for personswith disabilities to participate in family and communityactivities. However, as these devices have become moresophisticated, their availability has become problematicbecause of increasing cost the special training needed.
The exercise and sport-related regimens currently beingused to strengthen weak muscles and improve coordinationinclude aquatic exercises, martial arts training, T’ai Chi, andhippotherapy (therapeutic horsemanship). These are bothpleasurable and motivating for the participants to build musclestrength and coordination as well as to maintain generalhealth. Only observational reports about their usefulness areavailable.
CONCLUSIONSConventional methods of intervention and newer
methodologies are being evaluated to treat the injured brainand to ameliorate the impairments and disabilities associatedwith cerebral palsy. Controlled clinical trials are steadilyreplacing case observations and clinical case series. Thischange in assessment methodology is having an importanteffect on the quality and significance of studies to evaluate theefficacy of interventions: data are replacing clinical observationas the basis for decision making for treatment.24
The Treatment of Cerebral Palsy: What We Know, What WeDon’t Know
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The Journal of Pediatrics � August 2004
