SEIZURE DISORDERS

Of neonatal seizures approximately 85% begin in the first 15 days of life with about 65% occurring between the second and fifth days of life.

Etiology/Pathogenesis

  1. HIE (most frequent cause in the full term infant.)
  2. Intraventricular hemorrhage (most frequent cause in the preterm infant.)
  3. Subdural hemorrhage
  4. Infectious causes such as generalized sepsis, meningitis, TORCH agent infections, and viral encephalitis
  5. Hypoglycemia in the asphyxiated infant, infant of a diabetic mother, or infants with identifiable hyperinsulinism disorders.
  6. Hypocalcemia as in the asphyxiated infant, infant of a mother with hyperparathyroidism, infant with DiGeorge phenotype, or infant with chronic idiopathic hypoparathyroidism
  7. Hyponatremia
  8. Neonatal abstinence syndrome
  9. Disorders of amino acid and ketoacid metabolism.
  10. Pyridoxine deficiency
  11. Congenital cerebral malformations.
  12. Neurocutaneous disorders (Sturge-Weber, Neurofibromatosis, Incontentia pigmenti, Tuberous sclerosis)
  13. Familial history of neonatal seizures.

Seizure onset and etiology

0 to 3 Days

Hypoxic-ischemic encephalopathy

Hypoglycemia

Hypocalcemia

Intracranial hemorrhage

Drug toxicity

Drug withdrawal

Cerebral malformation

Cerebral infarction

Pyridoxine dependency

 

3 to 7 Days

Intracranial infection

Cerebral malformation

Hereditary metabolic disorders

Hypocalcemia

 

>7 Days

Cerebral malformation

Hereditary metabolic disorders

Viral meningoencephalitis

Clinical Presentations

Only rarely will newborns have well-organized symmetric generalized tonic-clonic seizures.

Neonatal seizures may be clinically expressed in various manners.  These include:

  1. Abnormal movements or alterations of tone in trunk and extremities (fragmentary clonic, focal clonic, tonic, myoclonic, bicycling, tonic-clonic, loss of tone).               
  2. Facial, oral, lingual movements (sucking, grimacing, chewing, yawning).
  3. Ocular movements (staring, blinking, horizontal eye blinking)
  4. Autonomic manifestations (apnea, alterations in heart rate and blood pressure,hyperpneic breathing)

Any alteration in the state of the infant that is "on-off" in character and is repetitive or paroxysmal may be a seizure.   Clinically, nonepileptic activity can be differentiated by (1) sensitivity to stimulation with spatial and temporal summation, (2) suppression with restraint of movement, and (3) absence of autonomic changes. 

Evaluation

Regardless of previous history, each child must be treated as having a potentially treatable disorder. The time of onset may be helpful to determine the etiology. Evaluation of an infant with seizures should include:

1. Laboratory

a. Blood glucose, calcium, magnesium and electrolytes including BUN.

b. Screening for systemic and intracranial infections. (CBC, Blood culture, CSF cultures, analysis of spinal fluid for protein, glucose, cell count and gram stai

c. Urine drug screen if the history suggests prenatal or perinatal drug use.

     d. Urine metabolic screen and ammonia level in suspected metabolic disorders.

2. Examination:

a. Complete neurologic examination

b. Complete physical examination making note of any pigmented cutaneous lesions.

3. Neuroimaging and Examination

a. Head ultrasonography is best for IVH while a head CT scan is best for subarachnoid/subdural hemorrhage, intracranial calcifications or lesions.

b. Electroencephalographic study should be obtained whether the patient has been treated for seizures or not. An abnormal EEG can confirm the diagnosis of seizures and provide a means to monitor improvement with anticonvulsant treatment.

Acute Management

A quick determination of the blood glucose level by bedside testing can rule out hypoglycemia.  

Treat while awaiting the results.

 1. Drugs of choice to treat seizures, in order of administration:

a. Phenobarbital. Loading dose: 20 mg/kg IV over 15-20 minutes (alternative routes IM, PO).

b. Lorazepam. Loading dose: 0.1 mg/kg/dose every 8 hours.

c. Phenytoin

May administer up to a total dose of 40 mg/kg in 10 mg/kg/dose increments.

Maintenance dose: 3-5 mg/kg/day begun no earlier than 12 to 24 hours after the loading dose.

Serum level: 20-40 mcg/ml. Obtain the level on days 3-5 of maintenance.

Used for acute management and desired cessation of seizures refractory to conventional management

When Loading dose: 15-20 mg/kg IV over 20-30 minutes (IV only at a rate of 0.5 -1.0 mg/kg/min)

To be used in seizures refractory to phenobarbital.

Maintenance dose: 4-8 mg/kg/day at rate indicated with loading dose. Serum level: 6-15 mcg/ml. Obtain trough level 48 hours after loading dose.

When these approaches fail in treating refractory neonatal status epilepticus, administration of IV anesthetic agents such as thiopental or pentobarbital may be necessary.              

2. Duration of Treatment

Causation of the seizures influences the length of therapy. Discontinuation of drugs may be considered before discharge if the infant shows no demonstrable brain lesions on cranial imaging, demonstrates age-appropriate neurologic examination, and has a normal interictal EEG background. However, most anticonvulsant therapy is continued for the first 3 months. 

 


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