Currículum vitae Javier Angulo Frutos TITULACION ACADEMICA Licenciado en CC. Biológicas Especialidad de Bioquímica y Biología Molecular Universidad Autónoma de Madrid (1986 - 1991) Doctor en CC. Biológicas por el Dpto. de Bioquímica de la Universidad Autónoma de Madrid (Octubre, 1996) ACTIVIDAD INVESTIGADORA Becario predoctoral en el Departamento de Farma
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Wdairy.kau.edu.saCerebral Palsy: Comprehensive Review and Update
Mohammed M. S. Jan
From the Department of Pediatrics, Cerebral palsy (CP) is a common pediatric disorder occurring in about 2 to 2.5 per 1000 live births. It is a chronic motor disorder resulting from a non-progressive (static) insult to the developing brain. CP is the clini- cal presentation of a wide variety of cerebral cortical or sub-cortical Specialist Hospital & Research insults occurring during the first year of life. The commonest cause of CP remains unknown in 50% of the cases; prematurity remains the com- monest risk factor. Children with CP suffer from multiple problems and potential disabilities such as mental retardation, epilepsy, feeding dif- ficulties, and ophthalmologic and hearing impairments. Screening for these conditions should be part of the initial assessment. The child with CP is best cared for with an individualized treatment plan that provides a combination of interventions. This requires the provision of a number Professor of Pediatric Neurology, of family-centered services that make a difference in the lives of these children and their families. Management of spasticity can be challeng- King Faisal Specialist Hospital & ing with a wide variety of possible therapeutic interventions. The treat- ment must be goal oriented, such as to assist with mobility, reduce or prevent contractures, improve positioning and hygiene, and provide comfort. Each member of the child’s multidisciplinary team, including the child and both parents, should participate in the serial evaluations and Cerebral palsy (CP) was first described in 1862 by an orthopedic surgeon named william James Little. A motor disorder result- ing from a non-progressive (static) insult to the developing brain,1 CP is, in fact, a clinical presentation of a wide variety of cerebral cortical or sub-cortical insults occurring during the first year of life. Preterm infants are at the highest risk for developing CP. The vulner- able brain is harmed during a critical period of development primarily by known CNS complications of prematurity such as intraventricular hemorrhage (ivH) and periventricular leukomalacia (PvL). Children with CP suffer from multiple problems and potential disabilities that require the provision of family-centered services that make a difference in the lives of these children and their families.2 The aim of this article is to provide an updated overview of CP and review the most recent advances in clinical and therapeutic interventions.
The worldwide incidence of CP is approximately 2 to 2.5/1000 live births. The incidence is strongly associated with gestational age, occur- ring in 1 of 20 surviving preterm infants. it is important to note that although prematurity is the commonest risk factor for developing CP, the majority of affected children are full-term. This can be explained by the fact that there are many more full-term than preterm infants Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals born at a given time.3 Despite the reduction in the A smaller percentage of children with CP demon- rate of birth asphyxia from 40/100 000 in 1979 to strate extrapyramidal (dyskinetic) features, including 11/100 000 in 1996, no associated reduction in the combinations of athetosis, chorea, and dystonia. The prevalence or incidence of CP was seen.4 in fact, abnormal movements usually develop in the second the prevalence of CP in the USA increased by 20% year of life and become most apparent during vo- (from 1.9 to 2.3/1000 live births) between 1960 and litional motor activities with associated speech im- 1986.5 This increase is likely related to the survival pairments.8 Most children with extrapyramidal CP of very low birth weight premature infants.5 There is have normal intelligence, but their abilities can be also evidence of an associated increase in the severity underestimated due to the severity of their motor of the disability.6 This emphasizes the need for more and communication deficits. Kernicterus (bilirubin efforts to decrease the rate of prematurity in addi- encephalopathy) is a leading cause of extrapyrami- tion to decreasing the associated neurological injury dal CP. The affected neonate appears weak, listless, and hypotonic, with poor feeding. Over a period of months, hypertonia, opisthotonus, choreoathetosis, Clinical manifestations and classification
and sensorineural hearing loss develops.8 Hypotonic schemes
cerebral palsy occurs rarely; however, most children progress to other CP subtypes. Mixed CP occurs Children with CP usually present with developmen- when the child displays a combination of features, tal delay and motor deficits. The distinction between such as spasticity and choreoathetosis.
a static (non-progressive) and progressive clinical course is very important. Classically, loss of previous- Etiologic Classification
ly acquired milestones (regression) marks the onset Up to 50% of CP cases have no identifiable underly- of most metabolic and neurodegenerative disorders ing etiology.3 The etiologies can be classified accord- (NDD). However, some NDD or metabolic disor- ing the timing of the insult as prenatal (commonest), ders have a slow rate of progression and can be mis- natal, or postnatal. Another etiologic classification diagnosed as CP.7 Therefore, clear developmental re- system depends on the actual cause such as congeni- gression may not be evident, particularly in the early tal (developmental, malformations, syndromic) or stages of the disease or at a younger age of onset. in acquired (traumatic, infectious, hypoxic, ischemic, addition, the neurological consequences of CP may TOrCH infections, and others). Perinatal asphyxia is be delayed for several months because of the imma- a cause in only 8% to 15% of all cases.9 Most of these turity of the nervous system.7 Motor deficits of CP children have clinical features of neonatal hypoxic include negative phenomena such as weakness, fa- ischemic encephalopathy (Hie) such as a disturbed tigue, incoordination and positive phenomena such level of consciousness, seizures, and other end organ as spasticity, clonus, rigidity, and spasms. Spasticity dysfunction. Although a normal cord pH excludes is a velocity dependent increased muscle tone with Hie, a pH of <7.0 is associated with encephalopa- hyperreflexia resulting from hyperexcitability of the thy in only 15% of infants.10 Similarly, apgar scores stretch reflex. it can lead to muscle stiffness, func- are predictive of mortality but not sensitive in pre- tional impairment, and atrophy. if not treated, it can dicting the neurological outcome. Chorioamnionitis progress to muscle fibrosis, contractures, and subse- and maternal infections have been shown to be risk quent musculoskeletal deformities. CP can be clas- factors for Hie and CP.11 PvL is the strongest and sified according to the severity of motor deficits as most independent risk factor for the development mild, moderate, or severe. Several other classification of CP. Ultrasonographic abnormalities of persistent systems exist based on the pathophysiology, etiology, ventricular enlargement or persistent parenchymal and distribution of motor deficits as follows. echodensities carry a 50% risk for CP, and large bi- lateral periventricular cysts carry a risk of 85%.12 in Pathophysiologic classification
another study, CP occurred in 56% of infants with insults resulting in neuronal loss can be 1) cortical PvL and ivH.13 (pyramidal), resulting in spasticity, 2) basal ganglial (extrapyramidal), resulting in abnormal movements Classification of Motor Dysfunction
such as choreoathetosis, 3) cerebellar, resulting CP can be classified according to the topographic in hypotonia, or 4) mixed. Spastic CP is the most distribution of motor involvement. Motor deficits common type, accounting for up to 75% of cases.8 include monoplegia, diplegia, hemiplegia, triplegia, Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals quadriplegia, and double hemiplegia. Diplegia is increased cognitive impairment include epilepsy and present when the lower extremities are primarily af- cortical abnormalities on neuroimaging.
fected, although the upper extremities are not com- pletely spared. Spastic diplegia is the most common Epilepsy
type of CP and is associated with prematurity. The Up to 36% of children with CP have epilepsy, with periventricular germinal matrix, which is a region of onset in the first year of life in 70%.15 Focal seizures active neuronal proliferation, is particularly suscep- with or without secondary generalization are most tible to bleeding and hypoxic ischemic injury. The common with frequently focal eeG abnormalities.16 surrounding periventricular white matter contains every effort should be made to avoid sedation prior pyramidal fibers that descend through the internal to eeG as this may affect the result of the test.17 capsule to supply the lower limbs. More peripheral epilepsy can be an indicator of the severity of neu- in the periventricular white matter are the pyramidal rological injury (quadriplegic CP) or cortical insult tracts of the upper limbs. Therefore, periventricular (hemiplegic CP).18 Children with spastic diplegic insult in preterm infants affects the lower limbs more CP are at a lower risk for epilepsy mainly because than the upper limbs, resulting in spastic diplegia. their pathology predominantly involves the periven- Note that the term paraplegia should not be used in tricular white matter. Several new antiepileptic drugs this context as it implies a spinal cord insult result- have improved our ability to control the seizures in ing in lower motor neuron lesion involving the lower these children.19,20 limbs only, i.e. not cerebral in origin with completely normal arm function. Hemiplegia is characterized by Feeding, Nutrition, and Growth
involvement of one side of the body, with the arm These are the most common issues encountered in typically more affected than the leg. This is because children with severe CP. About 30% are undernour- of larger cortical representation (motor homunculus) ished, and many show reduced linear growth below of the hand and arm compared to a smaller leg area. the third percentile.21 Although growth delays ap- Monoplegia refers to single limb involvement. This pear to be multifactorial in origin, the leading cause is usually the result of very mild hemiplegia with appears to be poor nutrition secondary to pseudo- arm deficits only. when all four limbs are involved, bulbar palsy. This is an upper motor neuron disorder quadriplegia is the appropriate descriptive term. This resulting in poor coordination of sucking, chewing, is the most disabling, with 25% of the affected chil- and swallowing. in addition, gastroesophageal (Ge) dren requiring total care.1 Double hemiplegia refers reflux results in regurgitation, vomiting, and possible to the child with quadriplegia involving the arms aspiration. Ge reflux can be a source of pain and more than the legs with side asymmetry. Triplegia is food refusals in the difficult-to-feed child. Dystonic rare and usually results from milder and very asym- dyspepsia (Sandifer’s syndrome) in children with se- metric double hemiplegia (sparing one leg) or milder vere Ge reflux can be confused with tonic seizures. asymmetric diplegia (sparing one arm). These sub- early nasogastric (NG) or gastrostomy tube (GT) types can be difficult to delineate clinically in some feedings can be solutions to these problems with im- children, particularly since the degrees of disability proved growth and greater family satisfaction (22). NG tube feeding can be used for short-term nutri- tional support. However, on a long-term basis, NG Associate Manifestations and
feeding is not socially acceptable and can be associ- Complications
ated with nasal discomfort, sinusitis, irritation of the larynx, and recurrent tube blockage or displacement. Mental Retardation
Surgically or endoscopically placed GT provides a Not all children with CP are cognitively impaired. long-term solution to the feeding disorder in con- in fact, the commonest type (spastic diplegic CP) is junction with treating the associated Ge reflux (21). characterized by normal cognition because the lesion Fundoplication may be indicated at the time of GT is in the periventricular white matter, i.e. sparing the placement if medical treatment for Ge reflux fails. cortical grey matter. However, there is a relationship between the severity of CP and mental retardation.14 Bladder Dysfunction
Children with spastic quadriplegic CP have greater Children with CP are at increased risk for urinary in- degrees of mental retardation than children with continence, urgency, and infections.23 Spastic CP can spastic hemiplegia.14 Other factors associated with be associated with spasticity of the detrusor muscles Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals resulting in small frequent voids and a low capacity ing, and early arousals.25 The drug has minimal side irritable bladder. Primary incontinence has been re- effects and no tolerance or dependence.
ported in up to 23% of these children and correlates with lower cognition and severe motor deficits.24 The Drooling
communication skills and physical ability to go to Drooling occurs in up to 30% of children with CP.27 the bathroom promptly and manage clothing influ- it is not usually related to increased production of ences the attainment of continence. Adapted toilet saliva unless an irritating lesion is present, such as seats, handrails, and clothing modifications can in- dental caries or throat infection. Drooling is usually secondary to mouth opening and/or swallowing dif- ficulties due to pseudobulbar palsy. it is not socially Bowel Dysfunction
acceptable and can lead to aspiration, skin irritation, Constipation is common in children with CP and and articulation difficulties.27 Management for this results from multiple factors including poor feeding, difficult problem is not very effective. Anticholinergic reduced water intake and immobility. The long-term medications, such as glycopyrrolate, decrease saliva- solution involves increased consumption of water, tion by blocking parasympathetic innervation. Side juices, fruits, and vegetables. initiating bowl evacu- effects include irritability, sedation, blurred vision, ation is recommended and requires a combination and constipation.28 Scopolamine is another anti- of laxatives (upper intestinal tract) and enemas or cholinergic agent that is available as a skin patch. suppositories (lower tract). Afterward, a schedule Surgical re-routing of salivary ducts is an option, but of softening agents such as artificial powdered fi- may lead to increased aspiration.28 recent studies ber or docusate sodium with dietary modifications suggest that botulinum toxin injection into the pa- can result in more regular and softer bowel move- rotid and submandibular glands may be an effective ments. Sitting on the toilet daily after the main meal in reducing excessive drooling.29 takes advantage of the gastro-colic reflex and may be further stimulated occasionally with glycerin sup- Hearing Loss
positories.23 with effective bowel management pro- Certain etiologies, such as kernicterus, post-men- grams, many children can attain reasonably regular ingitis, and congenital rubella, increase the risk for hearing loss. if not diagnosed and treated early, hear- ing loss can interfere with developmental progress Sleep Disturbances
and rehabilitation, thereby contributing further to Sleep disorders are common in children with CP, developmental delays. Screening is recommended, particularly those with visual impairment, occur- including behavioral audiometry, auditory-evoked ring in up to 50% of cases.25 These children often brainstem responses (ABr), or transient evoked oto- have disturbed sleep patterns with fragmented sleep acoustic emissions. ABr should be performed before and frequent nocturnal awakenings, which is highly or shortly after discharge from the neonatal inten- disruptive to parents. Medications that improve the sive care unit for every preterm. Hearing assessment sleep-wake cycle may also decrease spasticity and is recommended routinely for any child with global improve daytime behavior.25,26 Hypnotics are gener- developmental delay, particularly if language delay is ally effective for short periods but lose their effect in a present. The yield may reach 91% if hearing loss was few days due to tolerance. Melatonin is a recently de- suspected clinically.30 veloped natural compound with a phase setting effect on sleep. it is the hormone of darkness as the detection Visual Abnormalities
of darkness by visual receptors drives the hypothalamus Children with CP, particularly preterm infants, are to stimulate the pineal gland via sympathetic pathways also at increased risk for visual impairment, includ- to increase melatonin secretion.25 visual impairment ing retinopathy of prematurity, myopia, strabismus, diminishes the ability of the child to perceive and glaucoma, and amblyopia.31 if not diagnosed and interpret the multitude of cues for synchronizing managed early, visual deficits can interfere with de- their sleep with the environment. This makes these velopmental progress and rehabilitation. Strabismus children susceptible to circadian sleep-wake cycle can lead to permanent monocular vision loss (am- disturbances. Up to 80% of children had a dramatic blyopia). visual impairments can be cortical due to response to a 3-mg melatonin dose at bedtime with a damage to the visual cortex of the occipital lobes. reduction in delayed sleep onset, nocturnal awaken- Screening is recommended including acuity, eye Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals movements, and fundoscopy. visually evoked poten- diagnosis of dopa-responsive dystonia is the diurnal tials assess the integrity of the visual pathway from fluctuation with worsening of symptoms towards the the optic nerve to the visual cortex. Serial ophthal- end of the day, and lower limb onset. it is impor- mologic assessments are recommended routinely on tant to recognize this disorder because it responds any child with global developmental delay, particu- dramatically to small dose L-dopa.35 early warning larly if vision loss is suspected. The yield is 13% to signs of CP include developmental delay, toe walk- 25% for refractive errors and strabismus, and 20% to ing, persistent fisting, microcephaly, epilepsy, irrita- bility, poor sucking, handedness before 2 years of age (indicating hemiparesis), and scissoring of the lower Orthopedic Abnormalities
limbs.33 in addition, persistence of primitive reflexes The developing bones grow in the direction of the can be an early indicator. A multidisciplinary evalua- forces placed upon them. Spasticity can lead to pro- tion is recommended and may necessitate input from gressive joint contractures, shortened muscles, and physiotherapy, occupational therapy, ophthalmology, hip or foot deformities. Other orthopedic complica- audiology, orthopedics, radiology, neurology, genet- tions that need to be watched for include scoliosis ics, developmental pediatrics, and social services. and fractures due to osteomalacia or osteoporosis. Metabolic and chromosomal analyses are not rec- These manifestations are more common with severe ommended routinely, but are indicated if the child motor disability and immobility, such as quadriple- has dysmorphic features, a family history of delay, or consanguinity. Brain CT may be abnormal in 63% to 73% of CP cases.30 Brain Mri is more sensitive than Diagnosis
CT, particularly in delineating the extent of white matter changes. if available, it should be obtained in Diagnostic labels should not be taken for granted as preference to CT.30 Once the diagnosis of CP is es- misdiagnoses are not uncommon. Many times the tablished, communicating such news to the parents term CP is loosely applied to children with vari- is often both difficult and emotionally unwelcome.36 ous chronic neurological disorders.7 A comprehen- in addition, most physicians do not feel comfortable sive history for risk factors and genetic background, dealing with children with neurological disorders complete physical and neurological examinations such as CP.37 At the same time, it is important that are mandatory for accurate diagnosis. Serial de- the transfer of such information is done well as the velopmental evaluations may be necessary in the manner in which neurological bad news is conveyed young child for proper diagnosis and follow up.32,33 to parents can significantly influence their emotions, Perinatal complications such as prematurity, head beliefs, and attitudes towards the child, the medical injury, kernicterus, and meningitis are important risk staff, and the future.36 Most families find the attitude factors for CP. On the other hand, a family history of the newsgiver, combined with the clarity of the of neurological disorders and early or unexplained message and the newsgiver’s knowledge to answer deaths indicates an undiagnosed inherited neurode- questions as the most important aspects of giving generative disorder. Familial CP is a misdiagnosis the news. that should not be made. Occasionally CP recur- rence occurs due to similar perinatal risk factors; Management
however, a family history of CP should always raise the suspicion of an undiagnosed NDD or meta- The primary care physician should provide antici- bolic disorder. An example is glutaric aciduria type patory guidance, immunizations, and developmen- 1, which is an autosomal recessive disorder that re- tal surveillance. Additionally, the child’s respiratory sults in a clinical picture similar to dyskinetic CP. status should be carefully assessed, as bronchopul- Another rare disorder that can be confused with CP monary dysplasia, reactive airway disease, aspiration, is dopa-responsive dystonia (Segawa disease). in one and recurrent chest infections are not uncommon.23 series, up to 24% of patients with dopa-responsive All routine immunizations should be provided, in- dystonia had been misdiagnosed as CP.34 Dystonic cluding pertussis vaccine, even if the child has epi- movements do not usually cause the wasting, con- lepsy. Progressive uncontrolled epilepsy indicates tractures, and deformities that develop in spasticity.35 DT rather than DPT vaccine. Annual influenza vac- Patients usually have a good muscle bulk because of cination should be provided for those with recurrent the repeated dystonic contractions. The clue to the or chronic respiratory illnesses. Pneumococcal im- Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals munization is recommended for those with chronic subspecialists, social workers, nutritionists, and edu- or recurrent pulmonary illnesses, and for those at cators, as indicated by the individual needs of the risk for infection with antibiotic resistant organisms, children and their families. This team setting allows such as children in long-term care facilities and resi- for the most effective care delivery system.38 There are a number of therapeutic interventions that have Specific treatment options for children with CP no scientific literature supporting their use in CP include physical and occupational therapy, drug treat- including patterning, conductive education, and hy- ments for spasticity (local, intrathecal, systemic), and perbaric oxygen therapy.45 it is important to empha- orthopedic and neurosurgical interventions. Most size that each child with CP should have the right patients require combinations of these therapies, to comprehensive management, medical education, but physical therapy is always essential. early insti- and environmental modifications that would im- tution of physical, occupational, and speech thera- prove their quality of life. Several internet resources pies are essential for proper developmental prog- for physicians and parents dealing with children ress.38 Therapeutic challenges include formulating with CP are summarized in Table 1.
an individualized treatment plan that is functional, goal-oriented, time-limited, and cost-effective. This Management of Spasticity
treatment plan should be team delivered and hos- pital-home-rehabilitation center-based according to Spasticity often generates widespread and debilitat- the needs of each child. The basic treatment goals in- ing consequences for many children with CP includ- clude parent education, facilitation of normal motor ing pain, spasm and subsequent contractures. while development and function, prevention of secondary spasticity need not be treated in every case, physi- complications such as deformities and disabilities cians today have a wide variety of treatment options. and improvement of functional acquisition, commu- However, tone reduction is indicated only if spastici- nity integration, and family adjustment.39 Thus, em- ty interferes with some level of function, positioning, phasis has shifted from a strict focus on impairments care or comfort. Familiarity with the strengths and to a broader focus on the function of the child.40 The weaknesses of each treatment option is an impor- key participants on any multidisciplinary treatment tant aspect of clinical decision-making. The impact team are the child and family as well as physical and of spasticity on function must be assessed as children occupational therapists.41 Physical therapists focus may rely on lower limb extensor tone for stance and on gross motor skills, including sitting, standing, ambulation. Spasticity management therefore must walking, wheelchair mobility, transfers, and commu- be goal-specific, such as to assist with mobility, re- nity mobility. wheelchairs can allow the children to duce or prevent contractures, improve positioning keep up with peers in social, educational, and rec- and hygiene, and provide comfort. each member of reational activities and to develop independence.23 the child’s multidisciplinary team, including the par- Power wheelchairs are appropriate for children who ents, should participate in treatment planning and lack the strength or coordination to operate a manual serial evaluations.46 in some centers, spasticity clin- chair, but demonstrate the cognitive skills necessary ics exist where a pediatric neurologist, clinical neu- for safe navigation.42 Occupational therapists ad- rophysiologist, orthopedic surgeon, physiotherapist, dress the visual and fine motor skills that enable co- and occupational therapist assess each child. Team ordinated functions of activities of daily living such assessment identifies each child’s strengths and defi- as dressing, toileting, eating, bathing, and writing.43 cits, sets the goals with the family, and develops a Forced use or constraint-induced movement therapy comprehensive problem list. Objective spasticity can be an effective technique to increase the use of measures (rating scales) help in documenting base- the affected arm in hemiplegic CP. restraining the line deficits, progress, and response to various thera- stronger arm forces the weaker arm to become more peutic modalities.47 These rating scales are summa- functional. Orthotic interventions are aimed at the rized in Table 2. prevention and/or correction of deformities, provi- Systemic treatments for spasticity include ba- sion of support, facilitation of skill development, and clofen, diazepam, dantrolene, and tizanidine, alone improvement of gait.44 The most common ortho- or in combinations. Baclofen is the most commonly ses used is ankle-foot orthoses (AFO), designed to used oral medication in children with generalized hold the heel and forefoot in optimal biomechanical spasticity. Spasticity results from an inadequate re- position. The multidisciplinary team also includes lease of gamma-aminobutyric acid (GABA), an Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals Table 1. Internet resources for professionals and parents dealing with cerebral palsy.
inhibitory neurotransmitter in the central nervous system. Baclofen is a structural GABA analog en- Organization
hancing presynaptic inhibition.48 it crosses the National library Service for the blind and blood-brain barrier poorly. Therefore, high doses Physically Handicapped may be necessary to achieve clinical response. Side Children’s Hemiplegia and Stroke Association www.chasa.org effects include fatigue, irritability, hypotension, United Cerebral Palsy Associations drooling, impaired memory and attention, and a lowered seizure threshold. Slow drug titration may CP Parent Home Page minimize these side effects. Abrupt withdrawal of The Cerebral Palsy Network baclofen results in rebound spasticity, irritability, and National Parent Network on Disabilities subsequently fever, hallucinations, and seizures.49 Benzodiazepines, including diazepam, clonazepam, Special Needs Advocate for Parents and clobazam, are also useful for generalized spas- ticity. They increase presynaptic neuronal inhibition Disabled Sports through GABA pathways.50 Sedation and tolerance are the most common adverse effects. Dantrolene Special Olympics International exerts its action directly at the muscular level by in- hibiting calcium release from sarcoplasmic reticulum Disability and rehabilitation research and thereby uncoupling excitation and contraction.51 Muscle weakness, hepatotoxicity, and fatigue are the National Information Center for Children and main side effects, making it a less favorable option. youth with Disabilities Tizanidine is an alpha-2 adrenergic agonist that hy- perpolarizes motoneurons and decreases the release National Association of Developmental of excitatory amino acids. Side effects include nau- sea, vomiting, hypotension, sedation, and hepatotox- Disability rights Education and Defense Fund icity.49 Children with spasticity that are refractory or intolerant to oral medications may be candidates for intrathecal baclofen therapy. After a favorable re- sponse to an initial intrathecal test dose, baclofen is drug is not useful if fixed contractures are present. provided via a programmable, refillable pump, sur- Orthopedic procedures are best left as a last resort gically implanted into a subcutaneous abdominal for children with severe spasticity and/or fixed con- pocket. The pump is connected to a catheter system tractures or deformities. Tendon lengthening proce- that delivers a continuous infusion of baclofen into dures are used to reduce abnormal muscle activity. the spinal canal with significant reduction in limb The timing of these procedures is critical and best tone.48 Complications are related to the medica- planned after the development of a mature gait tion or mechanical pump failure. Overdose typically pattern (5-8 years of age). rapid growth, postural caused by programming errors, leads to somnolence, maturation, and physiologic ligamentous tighten- hypotonia, and respiratory depression and may prog- ing during the first few years of life contraindicate ress to loss of consciousness and respiratory failure.52 these procedures in the younger child. A lengthened withdrawal can be life threatening, with severe hy- muscle is also weakened, and postoperative reha- pertonicity progressing to seizures, hyperthermia, bilitation is essential. Selective dorsal rhizotomy is rhabdomyolysis, and multiorgan failure.53 a neurosurgical procedure that reduces lower limb Spasticity can be focal, or unequally distributed spasticity.55 it involves intraoperative electromyo- in the extremities. in such instances, botulinum graphic monitoring to identify the sensory rootlets toxin injections can be used before any surgical con- from L2 to S2, which, when stimulated, result in siderations.54 Botulinum toxin blocks the release of abnormal motor responses. Approximately 50% of acetylcholine at the neuromuscular junction with the stimulated rootlets are cut.55 The ideal candidate an onset of action of 3 to 10 days and an average for this procedure is the cooperative, motivated child therapeutic duration of 3 to 6 months.54 with on- with spastic diplegic CP who demonstrates good going active physiotherapy, longer benefits from the strength, balance, and range of motion in the lower injections can occur. Side effects are rare and include limbs. The procedure reduces lower limb spasticity transient local pain, fever, and muscle weakness. The and improves joint range of motion, and gait. Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals Table 2. Objective spasticity measures (rating scales).
1- Percent of Function Scale
Estimate the amount of function you had at your best. rate as if 0% represents fully disabled with no functional ability and 100% represents normal functional ability 0%—5—10—15—20—25—30—35—40—45—50—55—60—65—70—75—80—85—90—95—100% 2- Disability Scale
Use 0.5 increments to describe the patient’s disability (e.g., 0.5, 1.5 etc) Mild, barely noticeable spasm, tremor, pain without functional impairment Mild to moderate, spasm, tremor, pain with minimal functional impairment Moderate spasm, tremor, pain with moderate functional impairment 3- Spasm Frequency Scale
Number of spasms in the last 24 hours in affected muscles or extremity? 4- Global Pain Scale
rate the total amount of pain you have had in the last 24 hours 0%—5—10—15—20—25—30—35—40—45—50—55—60—65—70—75—80—85—90—95—100% 5- Modified Ashworth Scale
Slight increase in muscle tone (a catch and release or minimal resistance) A catch followed by resistance throughout the movement Marked increase in muscle tone through most rOM, but the part is easily moved Considerable increase in muscle tone, passive movement is difficult Affected part is rigid in flexion, extension, abduction or adduction 6- Adductor Tone Rating Scale
Increased tone, hips easily abducted to 45˚ by one person Hips abducted to 45˚ by one person with mild effort Hips abducted to 45˚ by one person with moderate effort Two people required to abduct the hips to 45˚ Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals Prognosis
tic advances and the degree of parental care have a strong influence on the length of survival of these in general, children have an enhanced capacity for children. brain plasticity, resulting in a capacity to recover and improve from brain insults.56 There are many pos- Conclusions
sible theories and mechanisms for this brain plas- ticity. in simple terms, it implies that normal and CP is a chronic motor disorder that various efforts less damaged areas of the brain have the ability to failed to prevent its occurrence. in most cases, the develop and maturate with time to result in devel- cause is unknown and prematurity remains the opmental progression and motor improvements. A commonest risk factor. Children with CP suffer common question asked by parents is whether the from multiple problems and potential disabilities child wil be able to walk independently. The ability such as mental retardation, epilepsy, feeding diffi- to sit independently at 2 years of age is predictive culties, vision, and hearing impairments. Screening of future ambulation. Most children with hemiple- for these conditions should be part of the initial gic CP wil be able to ambulate independently. assessment. The child with CP is best cared for regarding life expectancy and mortality rates in with an individualized treatment plan that provides children with CP, the type and severity of disability a combination of interventions. This requires the and feeding skil s are major determinants.23 Those provision of a number of family centered services. who require NG feeding during the first year of life Management is not curative; however, if provided have a 5-times greater mortality rate than children optimal y it can improve the quality of life of these with oral feeding. Overal , the probability of reach- children and their families. Physicians, in coopera- ing the age of 20 years in a child with severe CP is tion with the child, family, and members of a mul- 50%.57 respiratory infections, aspiration, and epi- tidisciplinary team, can coordinate a complex care lepsy are leading causes of death. Newer therapeu- system to the maximal benefit of each child. References
1. Shevel MI, bodensteiner Jb. Cerebral palsy:
13. Papile lA, Munsick.bruno G, Schaefer A. rela-
24. roijen lEG, Postema K, limbeek J, Kuppevelt
defining the problem. Semin Pediatr Neurol tionship of cerebral intraventricular hemorrhage HJM. Development of bladder control in children and early childhood neurologic handicaps. J Pe- and adolescents with cerebral palsy. Dev Med 2. King S, Teplicky r, King G, rosenbaum P. Family-
centered service for children with cerebral palsy 14. russman bS, Ashwal S. Evaluation of the
25. Jan MMS: Melatonin for the Treatment of
and the families: a review of the literature. Semin child with cerebral palsy. Semin Pediatr Neurol Handicapped Children with Severe Sleep Disor- Pediatr Neurol 2004;11(1):78-86.
der. Ped Neurol 2000;23(3):229.232.
3. Taft l. Cerebral palsy. Pediatr rev 1995;16:411-
15. Zafeiriou D, Kontopoulos E, Tsikoulas I. Char-
26. Tanaka H, Araki A, Ito J, Tasaki T, Miyamoto
acteristics and prognosis of epilepsy in children A, Cho K. Improvement of hypertonus after treat- 4. Nelson K, Grether J. Causes of cerebral palsy.
with cerebral palsy. Epilepsy Cerebral Palsy ment for sleep disturbances in three patients with Curr Opin Pediatr 1999;11:487-96. severe brain damage. Brain Dev 1997;19:240.244. 5. bhushan V, Paneth N, Kiely J. Impact of im-
16. Jan MMS: Assessment of the Util-
27. Siegel l, Klingbeil M. Control of drooling with
proved survival of very low birth weight infants on ity of Pediatric Electroencephalography. Seizure transdermal scopolamine in a child with cerebral recent secular trends in the prevalence of cere- palsy. Dev Med Child Neurol 1991;33:1010.1014. bral palsy. Pediatrics 1993;91:1094-1100. 17. Jan MMS, Aquino MF: The Use of Chloral Hy-
28. Toder D. respiratory problems in the adoles-
6. Pharoah P, Platt MJ, Cooke T. The changing
drate In Pediatric Electroencephalography. Neu- cent with developmental delay. Adolesc Med epidemiology of cerebral palsy. Arch Dis Child 18. Fennel Eb, Dikel TN. Cognitive and neuropsy-
29. bothwel JE, Clarke K, Dooley JM, Gordon KE,
7. Jan MMS: Approach to Children with Suspect-
chological functioning in children with cerebral Anderson r, Wood EP. botulinum toxin as a treat- ed Neurodegenerative Disorders. Neurosciences palsy. J Child Neurol 2001;16:58.63. ment for excessive drooling in children. Pediatr 19. Hassan A, Jan MMS, Shaabat AO: Topiramate
8. Matthews D, Wilson P. Cerebral Palsy. In: Mol-
for The Treatment of Intractable Childhood Epi- 30. Practice parameters. American Academy of
nar G, Alexander M (eds). Pediatric rehabilitation lepsy. Neurosciences 2003;8(4):233.236.
Neurology & Child Neurology Society practice 3rd edition. Philadelphia: Hanley & belfus, Inc; 20. Jan MMS, Shaabat AO: Clobazam For The
committee. Neurology 2003;60:367.380.
Treatment of Intractable Childhood Epilepsy. 31. Menaker S, batshaw M. In: batshaw M.
9. Pschirrer r, yeomans E. Does asphyxia cause
Saudi Med J 2000;21(7):622.624.
Our window to the world. baltimore: brooks; cerebral palsy?. Semin Perinatol 2000;24:215.220. 21. Eltumi M, Sul ivan Pb. Nutritional management
10. blumenthal I. Cerebral palsy: medicolegal as-
of the disabled child: the role of percutaneous 32. blair E, Stanley F. Issues in the classification
pects. J Royal Soc Med 2001;94:624.627.
endoscopic gastrostomy. Dev Med Child Neurol and epidemiology of cerebral palsy. Ment Retard 11. Stelmach T, Kal as E, Pisarev H, Talvik T. An-
Dev Disabil Res Rev 1997;3:184.193. tenatal risk factors associated with unfavorable 22. Stevenson r, roberts C, Vogtle l. The effects
33. McMurray J, Wilson.Jones M, Khan J. Cere-
neurologic status in newborns and at 2 years of of non.nutritional factors on growth in cerebral bral palsy and the NICU graduate. Neonatal Net- age. J Child Neurol 2004;19(2):116.22.
palsy. Dev Med Child Neurol 1995;37:124.130. 12. Hoon A. Neuroimaging in the high risk in-
23. Dormans J, Pel egrino l. In Caring for children
34. Nygraad TG, Marsden CD, Fahn S. Dopa.re-
fant: relationship to outcome. J Perinatol with cerebral palsy, Paul H. brookes Publishing sponsive dystonia: long.term treatment response and prognosis. Neurology 1991;41:174.181.
Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals 35. Jan MMS. Misdiagnoses in Children
50. Albright Al. Spastic cerebral palsy. CNS Drugs
with Dopa.responsive Dystonia. Ped Neurol 43. Children With Disabilities Committee. The role
of the pediatrician in prescribing therapy services 51. Davidoff r. Antispasticity drugs: mechanisms
36. Jan MMS, Girvin JP. The Communication of
for children with motor disabilities. Pediatrics of action. Ann Neurol 1985;17:107.116. Neurological bad News to Parents. Can J Neurol 52. yeh rN, Nypaver MM, Deegan TJ, Ayyangar r.
44. Condie DN. Conclusions and recommenda-
baclofen toxicity in an 8.year.old with an intrathe- 37. Jan MMS. Perception of Pediatric Neurol-
tions. In: Condie DN, Meadows Cb (eds). report cal baclofen pump. J Emerg Med 2004;26(2):163.7.
ogy Among Non.neurologists. J Child Neurol of a consensus conference on the lower limb 53. Coffey r, Edgar T, Francisco G, Graziani V,
orthotic management of cerebral palsy. Copenha- Meythaler J, ridgely P. Abrupt withdrawal from 38. Delucca P. The musculoskeletal management
gen, Denmark: International Society for Prosthet- intrathecal baclofen: recognition and manage- of children with cerebral palsy. Common Orthope- ment of a potential y life threatening syndrome. 45. Children With Disabilities Committee. The
Arch Phys Med Rehabil 2002;83:735.739. 39. Horn E. Achieving meaningful motor skil s: con-
treatment of neurological y impaired children us- 54. Edgar T. Clinical utility of botulinum toxin in
ceptual and empirical bases of a neurobehavioral. ing patterning. Pediatrics 1999;104(5):1149-51. the treatment of cerebral palsy: comprehensive Ment Retard Dev Disabil 1997;3:138.144. 46. brunstrom J. Clinical considerations in cerebral
review. J Child Neurol 2001;16:37.46. 40. Palmer F. Evaluation of developmental thera-
palsy and spasticity. J Child Neurol 2001;16:10.15. 55. Wright V, Sheil E, Drake J, Wedge J, Naumann
pies in cerebral palsy. Ment Retard Dev Disabil 47. Pierson SH. Outcome measures in spasticity
S. Evaluation of selective dorsal rhizotomy for the management. Muscle Nerve 1997;20(6):S36.S60. reduction of spasticity in cerebral palsy: a ran- 41. Palisano rJ, Snider lM, Orlin MN. recent ad-
48. butler C, Campbel S. Evidence of the ef-
domized control ed trial. Dev Med Child Neurol vances in physical and occupational therapy for fects of intrathecal baclofen for spastic and children with cerebral palsy. Semin Pediatr Neurol dystonic cerebral palsy. Dev Med Child Neurol 56. Johnston MV. Clinical disorders of brain plas-
ticity. Brain Dev 2004;26(2):73.80.
42. Furumasu J, Guerette P, Tefft D. relevance of
49. Krach l. Pharmacotherapy of spasticity: oral
57. Hutton J, Cooke T, Pharoah P. life expec-
the pediatric powered wheelchair screening test medications and intrathecal baclofen. J Child tancy in children with cerebral palsy. BMJ in children with cerebral palsy. Dev Med Child Ann Saudi Med 26(2) March-April 2006 www.kfshrc.edu.sa/annals
22/02/2012 Avisos DGA Ref. Preajustes de valor (Villa Regina) - Rezagos (Ezeiza) - Procedimientos Legales Aduaneros (BO 22/02/2012) ADUANA DE VILLA REGINA LISTADO DE PREAJUSTES DE VALOR APLICABLES DE CONFORMIDAD CON EL ART. 748 (C.A.), Inciso a) - R.G. AFIP Nº 620/1999 Dentro de los quince (15) días posteriores a la publicación en el B.O. deberá aportar la documentación que respalde los prec