Infantile Spasms

Infantile Spasms: Excerpt from The 5-Minute Pediatric Consult

Amy R. Brooks-Kayal, MDEric Marsh, MD, PhD

Infantile Spasms - BASICS

Infantile Spasms - description

• Myoclonic seizures, usually occurring in clusters, associated with a typical electroencephalographic pattern: High-voltage slowing, asynchrony, disorganization, and multifocal spikes (hypsarrhythmia)
• Flexor, extensor, mixed flexor/extensor, and arrest/akinetic seizures occur.
• The combination of infantile spasms, hypsarrhythmia, and mental retardation is known as West syndrome.
• Infantile spasms are symptomatic if a specific etiology can be identified and cryptogenic if no underlying cause is found.

Infantile Spasms - epidemiology

• Boys more often affected than girls
• Peak age of onset is 4–9 months; onset usually before 1 year of age

Infantile Spasms - incidence

Incidence is 0.25–0.42 per 1,000 live births.

Infantile Spasms - risk factors

Infantile Spasms - genetics

• Families of probands have a higher incidence of epilepsy, suggesting multifactorial inheritance.
• Tuberous sclerosis may be sporadic or autosomal dominant.
• X-linked infantile spasms syndrome shows variable penetrance.

Infantile Spasms - etiology

• Syndromes:
  • Tuberous sclerosis
  • Down syndrome
  • Aicardi syndrome
  • X-linked infantile spasms syndrome (a mutation in the ARX gene)
• Metabolic disorders:
  • Congenital lactic acidoses
  • Phenylketonuria
• Malformations of cortical development
• Almost any cause of pre- or perinatal brain injury may lead to infantile spasms, including meningitis, hypoxic-ischemic injury, uremia, and congenital infection.
• 40% of infantile spasms are cryptogenic.

Infantile Spasms - associated conditions

• Intrauterine infection, CNS infections
• Cerebral malformations: Malformation of cortical development
• Perinatal asphyxia, prenatal/perinatal stroke
• Lennox-Gastaut syndrome
• Traumatic brain injury
• Intraventricular hemorrhage
• Kernicterus
• Genetic conditions noted above

Infantile Spasms - DIAGNOSIS

Infantile Spasms - signs & symptoms

Infantile Spasms - history

• Prenatal and perinatal history, including maternal age, pregnancy complications, perinatal difficulties
• Elicit family history of tuberous sclerosis, seizure, or previous children with infantile spasms
• Developmental history to establish any pre-existing developmental delay
• Description of spells to differentiate spasms from nonepileptic seizures

Infantile Spasms - physical exam

• Check general growth parameters, especially head circumference.
• Microcephaly suggests pre-existing brain abnormality, poorer prognosis.
• Dysmorphism (Down stigmata).
• Retinal defects as in Aicardi syndrome, suggesting syndromic or genetic basis
• Hepatomegaly, suggesting inborn errors of metabolism or congenital infection
• Careful skin examination, including Wood lamp examination, should be performed for evidence of neurocutaneous disorders, especially the hypopigmented macules associated with tuberous sclerosis.
• Neurologic examination: Particular attention should be paid to level of alertness (visual attentiveness often impaired at presentation), developmental milestones, and motor tone.

Infantile Spasms - tests

• EEG: High-voltage, disorganized, multifocal spikes; asynchronous, hypsarrhythmic
• Infants with cutaneous signs of tuberous sclerosis should undergo cardiologic and ophthalmologic evaluation and renal ultrasound; genetic counseling for family; other family members should be evaluated
• Pyridoxine or folinic acid challenge: Infantile spasms are rarely an atypical presentation of pyridoxine or folinic acid–dependent seizures.

Infantile Spasms - lab

• Routine blood studies:
  • Electrolytes
  • Calcium
  • Glucose (although generally unrevealing)
• Chromosomal analysis (should include testing for ARX mutations if family history of lissencephaly, mental retardation, ataxia, or dystonia)
• Consider DNA test for tuberous sclerosis if any clinical or radiologic evidence to support diagnosis
• Metabolic screening, including blood lactate and pyruvate, serum amino acids, urine organic acids
• TORCH titers, depending on level of suspicion for congenital infection or microcephaly

Infantile Spasms - imaging

• MRI is the single most useful laboratory test; intracranial calcifications associated with intrauterine infections and tuberous sclerosis are more apparent on CT.

Infantile Spasms - diag proced-surgery

If no cause is found using other diagnostic modalities, consider lumbar puncture to look for evidence of hypoglycorrhachia, hyperglycinemia, lactic acidosis, or abnormalities of neurotransmitter levels.

Infantile Spasms - pathological findings

Depends on etiology: May include gliosis, atrophy, remote stroke, malformation of cortical development, tubers, etc.

Infantile Spasms - differencial diagnosis

• Nonepileptic disorders:
  • Benign myoclonus
  • Benign sleep myoclonus
  • Paroxysmal torticollis
  • Posturing related to gastroesophageal reflux (Sandifer syndrome)
  • Shuddering spells
  • Exaggerated startle in children with cerebral palsy
• Myoclonic epilepsies of infancy:
  • Benign myoclonic epilepsy of infancy
  • Severe myoclonic epilepsy (early infantile epileptic encephalopathy)

Infantile Spasms - TREATMENT

Infantile Spasms - initial stabilization

If patient appears ill (possible with metabolic disorders) tend to (ABCs) before treatment of spasms. (Infantile spasms themselves rarely threaten vital functions.)

Infantile Spasms - medication

Infantile Spasms - first line

Adrenocorticotropic hormone (ACTH) is generally considered the most effective therapy for infantile spasms:

• Treatment is often initiated at 150 U/m²/d IM) (high dose) or 20–30 U/d (low dose) for 1–2 weeks, and gradually tapered over 1–6 months. No consistent differences have been established between the high- and low-dose groups, and the decision on which treatment to use is based on the physician’s experience
• Side effects: Weight gain, irritability, sleep disturbance, hyperglycemia, hypertension, electrolyte abnormalities, cardiomyopathy, immunosuppression, gastritis/GI bleeding, osteoporosis, growth failure
• ACTH therapy has not been proven to affect outcome in infants whose spasms are caused by prenatal or perinatal brain abnormalities (symptomatic infantile spasms)
• Many practitioners use vigabatrin as the 1st-line agent for infantile spasms in the setting of tuberous sclerosis.

Infantile Spasms - second line

• A trial of pyridoxine (100 mg IV) should be considered to rule out pyridoxine deficiency or dependency. Reports (primarily from Japan) exist of successful treatment of infantile spasms with daily high-dose pyridoxine (200–300 mg/d).
• Vigabatrin (100–150 mg/kg/d) is considered the initial treatment of choice in Europe; not currently available in the US because of concern of visual-field constriction
• Topiramate (at dosages up to 20–60 mg/kg/d)
• Zonisamide (5–15 mg/kg/d)
• Clonazepam (0.1–0.15 mg/kg/d) or nitrazepam (0.5–3.5 mg/kg/d)
• Tiagabine (0.3–1.3 mg/kg/d)
• Valproate (at dosages up to 100 mg/kg/d) used cautiously because of the increased rate of fatal hepatotoxicity in this age group
• Phenobarbital (3–6 mg/kg/d)
• Prednisone (2 mg/kg/d)

Infantile Spasms - surgery

May be indicated in malformations of cortical development, particularly hemimegalencephaly

Infantile Spasms - FOLLOW UP

Infantile Spasms - disposition

Infantile Spasms - admission criteria

Initiation of ACTH therapy or for differential diagnosis of events

Infantile Spasms - discharge criteria

Stable on medications. Parents are taught to administer ACTH and check for signs of toxicity.

Infantile Spasms - issues for referral

Follow-up in 2 weeks with EEG to child neurologist

Infantile Spasms - prognosis

• Poor developmental prognosis, attributable to the underlying etiology
• ~65–90% of patients are developmentally delayed at diagnosis.
• 10% of cases achieve normal cognitive, physical, and educational development.
• ~60% of children go on to develop other seizure types, and 23–50% develop Lennox-Gastaut syndrome.
• Prognosis is better in the cryptogenic group, with up to 40% of children having normal cognitive development and freedom from seizures on long-term follow-up.

Infantile Spasms - patient monitoring

ACTH therapy necessitates weekly follow-up to monitor BP, glucose, electrolytes, BUN/creatinine, stool guaiac, and signs of infection. Stopping ACTH resolves its side effects.

• Hypertension and hemorrhagic gastritis may occur during ACTH therapy and must be anticipated by weekly follow-up visits.
• Other seizure disorders may supervene after infantile spasms have remitted and may require alternative anticonvulsant therapy.

Infantile Spasms - bibliography

1. Baram TZ, Mitchell WG, Tournay A, et al. High-dose corticotrophin (ACTH) versus prednisone or infantile spasms: A prospective, randomized, blinded study. Pediatrics. 1996;97:375–379.
2. Sherr E. The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): One gene leads to many phenotypes. Curr Opin Pediatr. 2003;15:567–571.
3. Shinnar E, et al. Practice parameter: Medical treatment of infantile spasms. Neurology. 2004;62;1668–1681.
4. Wong M, Tevathan E. Infantile spasms. Pediatr Neurol. 2001;24:89–98.

Infantile Spasms - ADDITIONAL READING

• Epilepsy Foundation. Patient information. Available at: http://www.epilepsyfoundation.org
• The National Institute of Neurological Disorders and Stroke NINDS Web site: http://www.ninds.nih.gov/disorders/infantilespasms/infantilespasms.htm

Infantile Spasms - CODES

Infantile Spasms - icd9

345.6 Infantile spasms

Infantile Spasms - FAQ

• Q: Do infantile spasms ever remit spontaneously?
• A: Spontaneous remission of infantile spasms has been reported but appears to be rare.
• Q: What is the developmental prognosis in idiopathic infantile spasms?
• A: Guarded; periodic evaluation by a child neurologist or developmental pediatrician helps to detect delays in motor or cognitive development; neither EEG nor any laboratory test contributes prognostic information in cryptogenic infantile spasms.

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Aicardi syndrome

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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

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