Margaret Jaynes, MD

Cerebral palsy (CP) refers to a group of nonprogressiveneurologic conditions defined byspecific motor deficits or movement disorders.It is often associated with other systemicsequelae. Because 65% to 90% of childrenwith CP survive into adulthood,1 it is importantfor clinicians-whether they have a pediatricoradult-based practice-to understand themultisystemic nature of CP.

 Prevalence in surviving neonates is about 0.2%, and CP has been reported to account for 2% to 8% of office visits to the pediatric neurologist.

 followed by the ataxic and athetoid types. Visits to the doctor are often precipitated by comorbidities involving organ systems other than the nervous system.

Historically, CP was thought to be associated with birth trauma. Although the percentage of CP cases attributable to birth asphyxia is debatable, Nelson and Ellenberg

 estimated that 6% to 7% of cases result from asphyxia at birth and that the cause of 80% of cases has to do with prenatal complications. Congenital, genetic, inflammatory, anoxic, traumatic, toxic, and metabolic causes all have been implicated as causes of CP. Prenatal risk factors include intrauterine infections; chorioamnionitis; fetal thrombophilia; exposure to teratogens; placental complications; multiple births; and maternal conditions such as mental retardation, history of seizures, and hyperthyroidism. New models that look at the inflammatory-mediated model of CP and its developmental sequelae are being developed.

Perinatal events such as preterm birth, low birth weight, intracranial hemorrhage, infection, seizure, hypoglycemia, and hyperbilirubinemia are well-known risks for neurologic sequelae. Careful developmental and neurologic screening is warranted in pediatric patients who have been affected by these conditions in the perinatal period. Furthermore, accurate determination of the cause of CP has specific implications for prevention in future pregnancies, treatment, prognosis, and medicolegal issues.

 Parents' and pediatrician's concerns about abnormal motor development provide the first clue to a possible diagnosis of CP and may initiate referral to a pediatric neurologist. The history may reveal risk factors; findings from the physical examination may identify the type of CP. For guidance on the diagnostic assessment of the child with CP see "Practice parameter: diagnostic assessment of the child with cerebral palsy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society," which was authored by Ashwal and colleagues and appeared in 

The traditional diagnostic approach consists of early assessment of impairments in muscle tone, strength, and control; assessment of involuntary movements; asymmetry; persistence of primitive reflexes; and late development of postural responses. Note that only about one quarter of children aged 7 years who have CP have a history of an abnormal neurologic examination at birth.

In reviewing the differential diagnosis, conditions such as metabolic disorders should not be overlooked. Be aware that genetic syndromes such as Lesch-Nyhan syndrome can mimic CP. Consider them in the differential diagnosis if the pregnancy and birth history are unremarkable.

CP also can be detected based on functional limitations.  Estimating functional limitations using the motor quotient (motor age divided by chronologic age multiplied by 100) is one diagnostic tool.  A motor quotient below 50 is predictive of gross motor delay.

 Neuroimaging is recommended in the evaluation of a child with CP if the cause has not been previously established by perinatal imaging. MRI is preferred to CT because this form of imaging is more likely to identify a cause.

 Cranial ultrasound is recommended for infants between 7 and 14 days old and near term-corrected age to identify intraventricular hemorrhage, periventricular leukomalacia, and low-pres- sure ventriculomegaly.

 When an asphyxial episode during gestation is suspected, cord and serum laboratory studies (ie, hemoglobin/hematocrit, platelet count, pH, liver, and renal function tests) are available to help make a determination of timing and severity of the insult. Metabolic and genetic studies should not be routinely ordered but should be considered when clinical history or findings and neuroimaging do not identify a specific structural abnormality.

 Coagulation studies should be obtained in hemiplegic CP.

 A genetics consultation may be useful to further evaluate specific conditions and dysmorphologies in which CP is one characteristic. An electroencephalogram should be obtained only when a child with CP has a history suggestive of epilepsy.

 CP is associated with motor and mental disabilities of variable severity in a growing child. The motor abnormalities include spasticity (spastic quadriplegia, hemiplegia, and diplegia) and movement disorders that may coexist in the same patient. Because bone growth exceeds muscle growth in the presence of spasticity in a growing child, contractures and bone deformities develop.

Dystonia, athetosis, or both are present in 10% to 20% of patients, and children with dystonia may have eye movement and oromotor abnormalities.

 The ataxic form of CP is uncommon and presents with gait abnormalities and fine motor dysfunction.

Although not a defining feature of CP, cognitive impairment occurs in many patients and ranges from learning disabilities to attention deficit disorders to severe mental retardation. Motor development is not a reliable predictor of cognitive development.

 For example, children with athetotic CP may have normal intelligence.

Hearing loss of the sensorineural or conductive type and visual impairment (refractory errors, visual field defects, cortical visual impairment, faulty accommodation, strabismus, nystagmus, and optic atrophy) are common.

 Other sensory defects may include impairment of touch and pain perception, proprioception, and ste- reoagnosis in spastic forms of CP.

Seizures--typically grand mal, which often are difficult to treat

--occur in many children with CP. They usually manifest in the first year of life, more so in children with spastic hemiplegia or quadriplegia.

 Dislocations and bony deformities are not uncommon in the CP population. Spinal deformities such as kyphoscoliosis and lordosis develop in children with CP, particularly those who cannot ambulate. Incidence is as high as 60%.

 The spinal deformities progress despite skeletal maturity and may interfere with good seating posture and cause pain, pelvic misalignment, and pressure sores. Cervical and lumbar spondylosis and myelopathy may occur in athetoid CP secondary to stresses incurred by repetitive complex trunk movements.

Nonambulators also are at high risk for osteopenia and fractures. Reduced bone mineral density is attributed mainly to immobility, poor nutrition, and use of anticonvulsant medication.

 Fractures usually occur at the metaphysis of the distal femur and proximal tibia and may be caused by contractures, falls, seizures, and overzealous physical therapy.

Contractures at the hip and knee in particular are a source of pain and disruption to daily activities such as sitting, standing, and perineal hygiene.

 Equinus deformity occurs in almost all patients with spastic CP secondary to gastronemius and soleus muscle spasticity, which results in toe walking.

Upper limb deformities are seen in patients with spastic hemiplegia and quadriplegia. The shoulders are internally rotated and flexion contractures occur at the elbow and wrist. Forearm pronations, fisted hand with thumb in palm, and swan finger deformities also are common.

 Oromotor muscle incoordination and spasticity may interfere with speech, suck, and swallow mechanisms and may cause temporomandibular joint contractures.

 Speech delay and dysarthria are potential sequelae. Also, dental hygiene can be difficult to maintain. Malocclusion, enamel dysplasia, and dental caries occur frequently.

 Gastroesophageal reflux disease (GERD) has been associated with dental erosion in CP, and degree of GERD severity has been correlated with degree of tooth erosion.

Drooling is one of the most troublesome oromotor problems for patients with CP. Poor head control and posture, impaired lip closure, abnormal tongue movements, and oral sensory impairment may contribute.

Swallowing difficulties, GERD, and constipation also contribute to feeding problems, which may occur very early in life. In a population survey of children with CP aged 12 to 72 months, more than 90% had clinically significant oromotor dysfunction. Severe feeding problems preceded the CP diagnosis in 60% of these children.

 The undernourishment that results from feeding problems leads to growth failure.

 In those children who do not have major feeding disturbances, however, excessive weight gain can occur because of the child's inability to participate in physical activities.

 Congential heart disease may be a component of genetically mediated CP. Pneumonia may occur frequently in the severely affected patient secondary to immobility, weak cough, contorted posture (scoliosis or chest wall deformities), GERD, and risk of aspiration.

 Over 90% of children with CP have associated GI symptoms, including constipation, swallowing problems, regurgitation and/or vomiting and abdominal pain.

 GERD, which is often difficult to control, has been found in up to 75% of patients

 and increases the risk of hematemesis, rumination, and dental erosion. Constipation has been associated with transit time delay in at least one segment of the colon and to ambulatory function.

 Bladder difficulties often occur concurrently with bowel difficulties in children with CP. Dysfunctional voiding symptoms, such as incontinence and urinary urgency, have been noted in more than half of all patients with CP.

Reproductive issues are often overlooked in the adolescent patient with CP. According to a recent cross-sectional survey, puberty tends to begin earlier in children with CP compared with the general population.

 However, menarche occurs later, with the median age being 14 years, as opposed to 12.8 years in the general population.

It is important to note that children with developmental disabilities are vulnerable to sexual abuse. Findings based on data from the National Center on Child Abuse and Neglect suggest that children with disabilities are twice as likely to be sexually abused as are children in the general population.

 Furthermore, the US Department of Justice reports that up to 83% of women with developmental disabilities are sexually abused at some point in their lives.

 Behavioral disorders, including attention-deficit/hyperactivity disorder, are more prevalent in children with CP.

 Frustration, aggression, and mood disturbances may be part of the picture. A change in behavior may signal that the child is in pain, especially in a child with communication difficulties. The degree of pain is difficult to assess and may also manifest as sleep disturbance, decreased appetite, or intolerance of movement. Several potential sources of pain include dental caries, GERD and esophagitis, constipation, infections, and musculoskeletal abnormalities.

 Management of the child with CP begins with a comprehensive medical evaluation by a multidisciplinary team that includes a pediatrician; a pediatric neurologist; physical, occupational, and speech therapists; an audiologist; an ophthalmologist; a social worker; and possibly a neurosurgeon and orthopedic surgeon. Family members are the most important part of the treatment team. Hearing tests and early referrals to audiologists and speech therapists are necessary to prevent delays in language and learning skills. Use of electronic communication devices may help alleviate frustration caused by communication difficulties. Screening for visual defects and ophthalmologic referrals should take place within the first year of life. Cognitive delays warrant careful assessment, initiation into early intervention programs, and the development of an individualized education plan in the face of severe motor and communication difficulties.

The goals of overall therapy should be aimed at maximizing the patient's level of function. Important areas of focus include ambulation, cognitive skills, activities of daily living, personal hygiene, and rehabilitation into society.

 The primary care physician will likely play the central role in coordinating care, but the pediatric neurologist will be called upon for expert guidance.

 Pharmacotherapeutic resources are available to manage symptoms such as spasticity and sleep disturbances and to manage seizures and movement disorders in general. Oral antispasticity medications include benzodiazepines, baclofen, a

-adrenergic agonists, and dantrolene sodium (Dantrium).

 Injectable medications include botulinum toxin A (Botox).

Invasive procedures include placement of an intrathecal infusion pump for continuous delivery of baclofen to the CNS for the treatment of severe spasticity. Several studies have shown that intrathecal baclofen therapy is safe and effective in children with CP.

Another neurosurgical procedure for spasticity is highly selective dorsal root rhizotomy. This procedure attempts to cut fewer than 50% of the sensory fascicles from each cauda equine nerve root, guided by intraoperative neuromuscular testing to identify the most abnormal nerve fascicles that should undergo ablation.

Few studies have directly compared the safety, efficacy, and long-term outcomes or relative costs of dorsal root rhizotomy and the baclofen pump. Therefore, the decision to use either of these interventions must be made on a case-by- case basis.

 Seizure control with antiepileptic drugs or use of a ketogenic diet or surgery also should be considered on a case-by-case basis, depending on patient presentation and seizure type.

Therapies for dystonia include anticholinergics and dopamine agonists. Sleep problems, which can be attributed to pain and motor dysfunction, can be managed with melatonin and other sleep aids and by simply establishing an appropriate bedtime routine.

 Management of the musculoskeletal sequelae of CP should include the participation of the pediatric orthopedic surgeon and physical therapist. Treatment should be tailor-made for the specific orthopedic abnormality present. Consultation with the specialists will determine optimum timing and type of treatment.

 Of various strategies studied to reduce plaque and gingivitis in patients with CP, an electric toothbrush was found most effective in optimizing oral hygiene.

 The use of cryotherapy to enhance mouth opening by providing a temporary reduction in masseter spasticity has been shown to improve oral access and thus facilitate preventative dental care and other dental procedures.

Occupational and behavioral therapy using oral stimulation techniques, such as stroking, tapping, and blowing exercises, has been shown to improve drooling.

 The centrally acting antispastic agent modafinil (Provigil)

 and anticholinergic medications such as scopolamine, glycopyrrolate (Robinul), and benzotropine improve drooling but are associat- ed with significant systemic adverse effects.

 Ultrasound-guided intraglandular injection of botulinum toxin A can successfully reduce drooling without major adverse effects.

 Surgical options include submandibular gland excision, parotid duct ligation, duct rerouting, and transtympanic neurectomy.

Placement of gastrostomy tubes (G-tubes) for non-oral feeding should be considered in patients at high risk for chronic undernourishment because of severe impairment of oromotor function. Oral feeding interventions for such patients have not been shown to be effective in promoting feeding efficiency or weight gain.

 Although concerns have been raised, no correlation between respiratory problems and G-tube placement has been found.

The placement of a G-tube has been shown to improve the caregiver's quality of life as measured by significantly reduced length of feeding times, increased ease of drug administration, and reduced parental concern regarding the child's nutritional status.

 Consultation with a nutritionist may be of benefit for the child with CP who experiences either poor weight gain or obesity.

 Any evidence of heart or lung disease should be aggressively evaluated. Pediatric cardiology consultation should be sought for definitive diagnosis and treatment of the cardiac abnormality. Effective pulmonary toileting and administration of antibiotics, including anaerobic coverage, are essential for the treatment of pneumonia in the patient with CP.

 In patients with GERD in whom medical management with proton pump inhibitors fails, Nissen fundoplication may be undertaken. A study

 of gastrojejunal tube placement suggested that the surgical procedure may be equally helpful in improving GERD. Administering baclofen orally or via a nasogastric tube to reduce symptoms of GERD also has been shown to reduce the frequency of emesis and the total number of events of acid reflux.

Treatment of chronic constipation demands a multifaceted approach that includes a regular toileting schedule, proper toilet positioning, dietary modifications, and medication. In patients with impacted stool, it is important to begin with a "clean-out" regimen using either oral osmotic agents or serial enemas. After the impacted stool is removed, a maintenance program using titrated agents such as polyethylene glycol to achieve daily soft stool should be continued on a long-term basis. Oral mineral oil should not be used because of risk of aspiration.

 Highly selective dorsal root rhizotomy may improve spasticity and bladder storage capacity in appropriate patients. Neurogenic detrusor overactivity--the most common finding in patients with lower urinary tract symptoms--can most often be controlled with a clean intermittent catheterization protocol and concomitant anticholinergic medication.

In regard to precocious puberty, a pediatric endocrinologist may be consulted. Gonadotropin-releasing hormone agonists remain the mainstay of treatment.

Older female patients in particular have unique medical needs, including contraceptive care and breast cancer screening. Mammography is underutilized by women with CP.

 Barriers to care include communication problems, transport, and physical limitations requiring adaptation of mammographic technique. Similar barriers also have been associated with access to contraceptive care in this patient population.

 Those patients who are taking antiepileptic agents for management of concomitant seizure disorders and who request contraceptive care should be counseled about the decreased effectiveness of oral contraceptives when used with certain antiepileptic drugs. The increased risk of thrombosis in women who have limited mobility also should be considered before initiating oral contraceptives.

 An integrative team approach, including monthly meetings between the rehabilitation therapist, child psychiatrist, developmental pediatrician, psychologist, and a preventative medicine specialist, has been shown to improve standardized measures of family stress associated with the parents' attitude toward the child with a disability. It also has shown significant improvements in the subscales of the Vineland Adaptive Behavior Scales assessment of the child.

Mood and behavioral disturbances are treated on a case-by-case basis, with behavior modifications and medication that depend upon the individual patient's circumstances. If pain is the possible trigger for the behavior change, for example, management should focus on uncovering and treating the underlying cause.   

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Articles

Cerebral Palsy: A Multisystem Review

A stroke is a devastating event, perhaps even more so in the pediatric population, since affected youngsters may require medical assistance for the rest of their lives. Adding insult to injury is the fact that many victims of pediatric stroke already suffer from a chronic disease. Since most parents are unaware that stroke can occur in children, several hours may elapse before medical attention is sought.

Once medical attention is obtained, it is not unusual for even more time to elapse before a proper diagnosis is made. One study

 puts the time from clinical onset of stroke in a child to first medical contact at an average of 28.5 hours and the time to definitive diagnosis at an average of 35.7 hours. Since delay in diagnosis is commonplace, children are rarely candidates for certain treatments (such as thrombolytic therapy) that may improve outcome if administered within a few hours of the event. In the hope of heightening professional awareness about the importance of a timely diagnosis, we present a review of pediatric stroke, with emphasis on the evaluation of children with acute onset of a neurologic deficit.

A 4-year-old white boy presented to an acute care facility complaining of a painful burning sensation in his right eye. His mother described him as quieter than usual, speaking with a "funny-sounding speech," and displaying a "funny smile." He had appeared well earlier that morning, with no other preceding symptoms. His past medical history was significant only for allergic rhinitis.

His physical examination revealed a well-appearing boy with normal vital signs. Findings were unremarkable, except for his cardiac and neurologic examinations, which revealed a grade 2/6 systolic heart murmur. His neurologic examination showed left facial weakness, with a left facial droop and prominence of the right labial fold. Other abnormalities included left ankle clonus and left upper extremity weakness, with generalized slower coordination of the left side of his body. Because of the significance of this child's presentation, he was transferred to tertiary care for pediatric and neurologic consultation.

After assurance of the ABCs of emergency care, a CT scan of the brain revealed an abnormal area of low attenuation in the right basal ganglia. An MRI scan of the brain showed an acute infarction in the putamen and caudate nucleus and adjacent internal capsule.

The results of intracranial magnetic resonance angiography (MRA) and extracranial (neck) MRA suggested intimal dissection of the right middle cerebral artery, with no abnormalities of the extracranial vasculature. Subsequent cerebral angiography found no dissection but did show a nonocclusive, adherent filling defect involving the right middle cerebral artery, which was determined to be a subocclusive, adherent thrombus.

An echocardiogram was significant for a patent foramen ovale (PFO) without intracardiac thrombi or vegetations. Results of an extensive laboratory investigation were normal except for an elevated cardiolipin antibody IgM level of greater than 150 IgM phospholipid (MPL) U/mL (greater than 80 MPL U/mL considered positive) and a cardiolipin antibody IgG level of 24 IgG phospholipid (GPL) U/mL (20 to 79 GPL U/mL considered moderately positive). A diagnosis of antiphospholipid syndrome was considered, but the criteria were not fulfilled. The exact cause of the stroke ultimately remained undetermined.

This case highlights 2 important points: the underlying cause of a significant proportion of pediatric strokes will remain unknown despite exhaustive evaluation, and the discovery of elevated anti- phospholipid antibody levels is of limited value. These antibody levels may be acutely elevated because of infection, and titers that remain elevated for 8 weeks are of greater significance.

The exact role of increased IgG titers in predicting recurrent stroke is controversial. A recent study by Lanthier and colleagues

 found that increased anticardiolipin antibody IgG titers do not predict future thromboembolism in children.

Atherosclerosis, a common underlying cause of adult stroke, is rare in children. Several other conditions (Table 1) put a child at risk for stroke. Congenital heart disease (particularly cyanotic lesions plus polycythemia) and sickle cell disease are at the top of the list. A review in the October 2005 issue of 

 describes the association of a PFO with cryptogenic stroke in patients younger than 55 years. Acquired heart diseases, collagen vascular diseases, CNS infections, hematologic and coagulation defects (hemophilias, thrombophilias), CNS vascular anomalies, inborn errors of metabolism (such as mitochondrial encephalopathies and homocystinuria), trauma (leading to vascular dissection), and other illnesses and their treatments (such as cancer and chemotherapy) are general classifications of the conditions that can increase a child's risk of stroke.

Several genetic disorders are associated with stroke

 or conditions that can lead to stroke, such as the association of trisomy 21 syndrome with moyamoya disease.

 A cerebrovascular accident may be the initial presentation of HIV infection in children.

 Varicella also has been described as a predisposing factor for pediatric stroke.

Arteriovenous malformations are the most common cause of hemorrhagic stroke in children.

Along with vascular malformations, malignancy, trauma, hemophilia, thrombocytopenia, liver failure, and warfarin administration also are associated with the development of hemorrhagic stroke.

Risk factors for sinus venous thrombosis include head and neck infections (such as orbital cellulitis and sinusitis), dehydration, cancer treatment (particularly with asparaginase), head trauma, surgery, and thrombophilias. Although several predisposing factors for pediatric stroke have been identified, a large proportion of cases will be classified as idiopathic.

Prothrombotic abnormalities deserve special mention because they are significant risk factors for ischemic stroke in children,

 even though their exact role is not fully understood. In one study

 of 59 children with arterial ischemic stroke or porencephaly, two thirds  had at least 1 prothrombotic risk factor--and many had several risk factors. Examples of prothrombotic conditions include protein C deficiency; protein S deficiency; antithrombin III deficiency; and the presence of factor V Leiden mutation, factor II G20219A variant, methylenetetrahydrofolate reductase variant, and antiphospholipid antibodies (specifically, lupus anticoagulant, anticardiolipin, anti- b2-glycoprotein).

Determining the mechanism of stroke is crucial because it will guide treatment and predict risk of recurrence. Recurrences are most likely in children with embolic stroke or an underlying systemic disease (such as sickle cell disease) and in children with a progressive arteriopathy (such as moyamoya disease).

 In the study that looked at the prevalence of prothrombotic risk factors,

stroke recurred in one fifth of the patients who had a prothrombotic abnormality.

The clinical presentation of stroke may be subtle in a young child, but in the first month of life, seizures, apnea, and persistent hypotonia are the predominant manifestations.

 Beyond the neonatal period, hemiplegia is the most common initial symptom. Other symptoms include headache, mental status changes, sudden collapse with loss of consciousness, speech disturbances, sensory complaints (numbness or tingling), and cranial nerve or cerebellar deficits.

 The acute neurologic changes that can occur may be confused with those that accompany other CNS disturbances such as hemorrhage, abscess, encephalitis, meningitis, drug ingestion, malignancy, sei- zures, and migraine. Along with these entities, stroke must be included in the differential diagnosis for any child in whom an acute neurologic change occurs.

 A detailed history of illness is necessary to support a diagnosis of stroke. What are the exact symptoms, and when did they begin? Inquiries into family history of predisposing factors such as sickle cell disease, prothrombotic conditions, and collagen vascular disease should be made. A thorough physical examination, focusing on the cardiac and nervous systems, will reveal any signs of underlying heart disease (such as a murmur or cyanosis) or neurologic deficits.

A more in-depth evaluation may include neurologic imaging and vascular, laboratory, and cardiac studies. Not all the studies listed may be necessary to diagnose stroke properly and treat each child. Physicians should choose their tests judiciously based on the patient's history and clinical presentation.

 Noncontrast CT is typically the initial diagnostic study because of its wide accessibility and its ability to detect nearly any lesion capable of producing an acute neurologic abnormality.

 Acute hemorrhage usually is detected by CT. Early ischemia is commonly not detected, but CT perfusion imaging may allow earlier identification of subtle indicators of infarction and clarify the amount of viable tissue.

Although an MRI scan of the brain is more sensitive than CT for detecting brain infarction, it is usually much more difficult to obtain quickly. Obtaining an MRI scan for a pediatric patient requires careful scheduling and finesse, because younger children will need more sedation than adults or may even require general anesthesia.

 Vascular studies used to evaluate children include CT angiography (CTA), MRA, and conventional angiography. CTA is helpful for identifying patients with occlusion of the major circle of Willis or extracranial cerebral arteries. Thanks to recent improvements in technique, CTA is superior to MRA in some instances.

 CTA is less prone to some of the artifacts that can limit MRA, and it can be used in patients with metallic implants.

MRA is an important study performed at many centers as part of a fast MRI protocol for acute ischemic stroke. Vascular stenosis or occlusion can be identified with this modality, as can aneurysms, arteriovenous malformations, arterial dissections, and arteriopathies. Conventional angiography, which is helpful in detecting vasculitis, is performed when the screening tests do not fully define the lesion and more characterization of the anatomy is warranted. CT or magnetic resonance venography is useful in the evaluation of sinus venous thrombosis.

 Potential laboratory studies are numerous and mostly geared toward trying to identify patients with a hypercoagulable state. Table 2 lists studies that can identify a child at risk for stroke. A pediatric hematologist should be involved in the management of a child with suspected or proven prothrombotic factors. Obtaining these studies is most important when the child has no evidence of cyanotic heart disease as a predisposing factor. If the child is of African descent, a screen for sickle cell disease is needed if the hemoglobin status of the child is unknown. A urine toxicology screen for illicit drugs may be necessary in certain situations, such as when an otherwise healthy adolescent experiences a stroke. In patients who have had a hemorrhagic stroke, evaluation for hemophilia and bleeding diathesis is essential.

 A transthoracic or transesophageal echocardiogram and ECG should be obtained in all pediatric patients to search for previously undiagnosed congenital heart disease, including the presence of a PFO. Although typically not needed in a young child, a bolus of agitated saline injected into the antecubital vein will help identify a PFO.

The echocardiogram is an important diagnostic tool. The ECG may identify patients with an arrhythmia as a possible source of emboli. Arrhythmia is more likely in a child with a history of heart disease or surgery.

Addressing the ABCs of life support is the initial treatment of the child after stroke. Securing the airway, monitoring cardiovascular parameters, and controlling seizures are paramount. Immediate transfer to a pediatric ICU is mandatory. Cerebral edema in the first several hours must be managed.

The exact role of thrombolytic therapy in children in the acute setting is unknown; large randomized controlled trials are not available. Some case reports and extrapolation from adult studies indicate that these medications may have a role in the care of pediatric patients.

Although not approved for use in children, recombinant tissue plasminogen activator has been reported to be successful in managing pediatric stroke.

 also have documented the successful use of urokinase in children with cerebral sinus venous thrombosis, but they note that the risk of symptomatic hemorrhage argues against thrombolysis as first-line therapy.

In 2002, the FDA approved a new formulation of urokinase, but only for the treatment of pulmo- nary embolism in adults.

 Since information is so limited, the routine use of antithrombolytics in a child is not recommended unless he or she is participating in a controlled clinical trial. However, the physician must use clinical judgment in each case, and weigh the risks and benefits with the family when deciding whether to administer thrombolytics in the setting of acute stroke. The delay that often accompanies the diagnosis of pediatric stroke usually precludes the use of antithrombolytic agents. More studies are needed to clarify the use of these agents in children.

A novel treatment alternative to antithrombolytic agents is the Merci Retrieval System (Concentric Medical). This device can restore vascular patency during acute ischemic stroke if used within 8 hours of symptom onset.

The usefulness of this intervention in children needs to be determined, but its success in treating adults has been reported.

In the long term, the decision to use an anticoagulant (antiplatelet agents, warfarin) should be made on a case-by-case basis with consideration of the underlying cause and risk of recurrence. Although large-scale clinical trials of anticoagulant use in children are also not available, aspirin is thought to be safe and effective for pediatric stroke; however, there is no universal agreement about when and how it should be used. The optimal dosage still needs to be determined. The risk of Reye syndrome in association with aspirin use is a special consideration in children.	

Warfarin is even more controversial and is used most frequently in children with congenital heart disease and hypercoagulable states. The use of any anticoagulant requires careful monitoring and titration so that bleeding complications may be avoided while a future CNS event is prevented.

Hemorrhagic stroke is a contraindication to anticoagulation therapy, and consultation with a pediatric hematologist and pediatric cardiologist (if heart disease is present) is recommended whenever long-term anticoagulation therapy is considered in a child after ischemic stroke. Treatment of hemorrhagic stroke depends on its cause; for instance, surgery and embolization are options for vascular malformations.

It is important for the neurologist to define the child's post-stroke disabilities and recommend ongoing adjuvant interventions such as speech, occupational, and physical therapies. Close monitoring for the development of sei- zures is necessary, along with educating the family about the risk of seizures post-stroke. The primary care provider coordinates and monitors the overall care, which may involve several subspecialists and other professionals.

Research concerning primary prevention strategies for pediatric stroke is lacking except in patients with sickle cell disease. A majority of children with sickle cell disease will have a recurrence. Regular blood transfusions to keep hemoglobin S to less than 30% have been shown to decrease the risk of recurrence

 but may cause serious complications (iron overload, transmission of infection, erythrocyte alloantibody and autoantibody production). An ongoing trial by the National Heart, Lung, and Blood Institute is focusing on the use of hydroxyurea plus phlebotomy as a preventive measure.

General preventive measures for all patients include counseling about the dangers of smoking and the use of illicit drugs and emphasizing the rewards of a good diet and an active lifestyle. Families with known thrombotic risk factors should be educated about the possibility of pediatric stroke and its presenting signs and symptoms. Raising awareness in families that stroke can occur in childhood and encouraging clinicians always to consider it as a possible cause in children with acute neurologic deficits may allow for a more timely diagnosis and treatment of this devastating event.	*

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6. Azarbal B, Tobis J. Interarterial communications, stroke, and migraine headache. 

7. Meschia JF, Brott TG, Brown RD Jr. Genetics of cerebrovascular disorders. 

8. Cramer SC, Robertson RL, Dooling EC, Scott RM. Moyamoya and Down syndrome. Clinical and radiological features. 

9. Visudtibhan A, Visudhiphan P, Chiemchanya S. Stroke and seizures as the presenting signs of pediatric HIV infection. 

10. Kenet G, Sadetzki S, Murad H, et al. Factor V Leiden and atiphospholipid antibodies are significant risk factors for ischemic stroke in children. 

11. Lynch JK, Han CJ, Nee LE, Nelson KB. Prothrombotic factors in children with stroke or porencephaly. 

12. Katsarou E, Attilakos A, Fessatou S, et al. Anti-beta2-glycoprotein I antibodies and isch- emic stroke in a 20-month-old boy. 

13. Chabrier S, Husson B, Lasjaunias P, et al. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients. 

14. Kurnik K, Kosch A, Strater R, et al. Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke: a prospective follow-up study. 

15. Halsted MJ, Jones BV. Pediatric neuroimaging for the pediatrician. 

16. Suzuki Y, Nakajima M, Ikeda H, Abe T. Evaluation of hyperacute stroke using perfusion computed tomography. 

17. Muir KW, Halbert HM, Baird TA, et al. Visual evaluation of perfusion CT imaging in acute stroke accurately estimates infarct volume and tissue viability. 

18. Thirumalai SS, Shubin RA. Successful treatment for stroke in a child using recombinant tissue plasminogen activator. 

19. Barnes C, Newall F, Furmedge J, et al. Cerebral sinus venous thrombosis in children. 

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21. Smith WS, Sung G, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. 

22. Pegelow CH, Adams RJ, McKie V, et al. Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. 

ABLE 1 Significant predisposing conditions of childhood stroke

Pediatric Stroke: Evaluation, Treatment, and Follow-up

The Workforce Task Force of the American Academy of Neurology projects that the number of pediatric neurologists will be 20% below demand, at least through the year 2020.

 Although it would be best for a child with epilepsy to see a pediatric neurologist, a general pediatrician, family practitioner, or adult neurologist may be required.

Traditional antiseizure medications--some of which have been in existence for almost a century--are still prescribed for children. The introduction of several new drugs over the past decade has expanded the armamentarium of possible treatments for childhood seizure disorders. When should these newer medications be administered to children? Practice parameters and reports have been put forth by expert panels on the use of these agents in children and adults.

 These parameters are based on available studies, which to date are somewhat limited for children.

The first crucial step in seizure management is proper diagnosis of the seizure disorder. Conditions such as breath-holding spells, gastroesophageal reflux, syncope, movement disorders, behavioral events, conversion disorders with nonepileptic seizures, and parasomnias that mimic seizures in children must first be excluded. This requires taking a careful history of the events leading up to the episode, getting a description of the event itself, and obtaining thorough knowledge about the child's development. The second step is to determine whether the seizure was unprovoked or provoked by an immediate precipitating factor, such as fever, CNS infection, or significant head trauma.

The third step is to accurately classify the seizure type in broad terms, such as focal, focal with secondary generalization, generalized convulsive (primary generalized tonic-clonic, myoclonic, clonic, tonic, or atonic seizures), and generalized nonconvulsive (typical or atypical absence seizures). Finally, the fourth step is to determine whether the seizure pattern fits a specific epilepsy syndrome.

Some examples of common epilepsy syndromes that have onset in childhood include benign rolandic, absence and juvenile myoclonic, and Lennox-Gastaut. Factors such as age at onset, developmental level, seizure type, and EEG data aid in determining pathology. Although it is not always possible to determine the specific epilepsy syndrome, it usually is possible to categorize the disorder as focal or generalized at onset.

After the diagnosis has been determined and the family has been educated about its implications (Table 1), the next step is deciding whether medication should be prescribed. Since treatment after an initial, afebrile generalized tonic-clonic or focal seizure has not been shown to improve long-term prognosis, it is prudent to delay initiation of anticonvulsant treatment until after a second seizure occurs.

 In some instances, such as when an EEG is abnormal, treatment with an antiepileptic drug (AED) should be initiated after a first seizure if the benefits  outweigh the risks.

Because infantile spasms and absence, myoclonic, and atonic seizures are recurrent, treatment typically is begun when the diagnosis is made because it is assumed that the child has experienced multiple events.

 Risk of recurrence is greatest in a child who has an abnormal EEG, underlying pathology, or evidence of an existing brain insult (such as cerebral palsy or mental retardation).

The Workforce Task Force of the American Academy of Neurology projects that the number of pediatric neurologists will be 20% below demand, at least through the year 2020

Author | Margaret Jaynes, MD

Articles

Cerebral Palsy: A Multisystem Review

Pediatric Stroke: Evaluation, Treatment, and Follow-up

A Guide to Interventions for Pediatric Seizure Disorders

Adverse Effects of Antiepileptic Medications in Children: A Case Report and Review