eMedicine Specialties > Neurology > Pediatric Neurology

Benign Neonatal Convulsions: Treatment & Medication

Author: Nancy Theresa Rodgers-Neame, MD, Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida; Director, Florida Comprehensive Epilepsy and Seizure Disorders Program
Contributor Information and Disclosures

Updated: Apr 8, 2009

Treatment

Medical Care

Although the seizures are benign, general agreement exists that they should be treated, particularly benign idiopathic neonatal convulsions.

  • Treatment with antiepileptic medications may prevent the occurrence or reduce the length of the period of status epilepticus. Continuing antiepileptic treatment for more than 10 days may not be necessary in benign idiopathic neonatal convulsions. One thing that should be kept in mind with treatment is that while seizures may abate the EEG may remain abnormal. In some cases, the EEG may change appearance but remain abnormal nevertheless.
  • The medications used most frequently are benzodiazepines, phenobarbital, and fosphenytoin, but no particular reason exists for the preferential use of these drugs rather than some of the newer drugs, except for their current availability in intravenous formulations and the long-term experience with their use in neonates.  GABA-A agonists (barbiturates and benzodiazepines) should be used with caution in the neonate.
  • When IV and liquid formulations become available, some of the newer drugs may prove to be of greater benefit in the future owing to their multiple mechanisms of action and their neuromodulatory/neuroprotective effects.
  • The disadvantages of phenobarbital and benzodiazepines are that they are overdosed easily in the neonate and can be very sedating. In addition, ample evidence shows that GABA-A agonists may not be a good choice in the immature brain. 
  • Fosphenytoin may be used acutely, but phenytoin is absorbed unpredictably in the neonate and should not be used as an oral preparation.
  • Use caution when treating status epilepticus with phenobarbital in neonates. Mistaking a normal deep anesthesia EEG in this age group with a burst suppression pattern of status epilepticus is easy.
  • Do not treat neonates in whom benign convulsions are suspected with valproate because of increased risk of liver failure with the drug and the benign nature of the syndrome.

Medication

No specific antiepileptic medication is preferred for the treatment of benign neonatal convulsions. In general, most epileptologists agree that status epilepticus should be treated when it occurs. Most neonates are best treated at this time with phenobarbital because of long experience with the drug, convenient monitoring, and adequate IV and PO absorption in the neonate. However, treatment has not been shown unequivocally to have an effect except possibly to decrease the duration or severity of the seizures. By definition, the seizures resolve in days (benign idiopathic neonatal convulsions) to weeks (benign familial neonatal convulsions).

Limit the choice of antiepileptic drug to those with no serious potential adverse effects. Most notably, avoid valproate in this age group if benign convulsions are suspected, since neonates are at the highest risk for liver failure due to valproate. Avoid phenytoin because of cardiac adverse effects, the high possibility of extravasation in neonates, and problems with reliable absorption if administered PO. A trial off the antiepileptic drug(s) should begin soon after the seizures stop and the EEG is normal.

An important factor to remember when treating neonates is that pharmacokinetics and pharmacodynamics are very different than in infants. Do not use infant loading dosages, since they may lead quickly to toxic levels that resolve slowly.

Neonatal pharmacology is complex. Maturation of general liver and renal function is in a period of transition from the fetal to infant state. Stresses or lack of stress on the systems in utero greatly affect the function and maturation of both systems.

Normal glomerular filtration rate (GFR) in the neonate varies in individuals from 1-4 mL/min and can increase rapidly as maturation of the renal cortex progresses. Adult values for GFR are not reached before the infant is aged 2.5-5 months.

Blood flow within the hepatic portal system changes at birth with closing of the ductus venosus. Maturation of the glucuronidation pathway often is slowed. Neonates whose mothers have been exposed to drugs (both prescribed and otherwise) may have active cytochrome P-450 enzymes, and unexposed neonates have initial low activities that usually increase rapidly with the introduction of drugs such as phenobarbital.

Anticonvulsants

These agents prevent seizure recurrence and terminate clinical and electrical seizure activity.


Phenobarbital (Barbita, Luminal, Solfoton)

DOC for treatment of neonatal seizures. Use care in dosing since toxicity can occur quickly and resolve slowly. Also doses that are initially adequate may need to be increased quickly as cytochrome P-450 becomes more active.

Adult

Pediatric

20 mg/kg loading dose IV and 5 mg/kg/day maintenance dosing; take care when administering to neonates whose drug biotransformation and excretion may be reduced at birth due to immaturity of glucuronidation pathway, cytochrome P-450 system, and reduced GFRs

May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects

Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema


Fosphenytoin (Cerebyx)

Initially may be used to control status epilepticus in patients with benign neonatal convulsions; however, unsuitable for long-term therapy.

Adult

Pediatric

Initial loading dose: 15-20 phenytoin equivalents per kg IV; maintenance should be guided by clinical response and free drug levels and may be as low as 1.5 mg/kg/d in divided doses; in older children, enteral dosing of phenytoin is typically 5 mg/kg/day, or in infants up to 10 mg/kg/day or higher

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), omeprazole, phenacemide, phenylbutazone, succinimides, fluconazole, isoniazid, metronidazole, miconazole, sulfonamides, trimethoprim, and valproic acid may increase toxicity
Barbiturates, carbamazepine, theophylline, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, methadone, metyrapone, mexiletine, oral contraceptives, quinidine, theophylline, valproic acid

Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; Adams-Stokes syndrome

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Death from cardiac arrest has occurred after too-rapid IV administration, preceded sometimes by marked QRS widening
Blood dyscrasias have occurred and thus blood counts and urinalyses should be performed when therapy is begun and at monthly intervals for several months thereafter; discontinue use if skin rash appears—if rash is exfoliative, bullous, or purpuric do not resume use; administer cautiously to patients with acute intermittent porphyria; exercise caution when administering to patients with diabetes—may raise blood glucose levels; discontinue drug if hepatic dysfunction occurs


Topiramate (Topamax)

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action, potentiates inhibitory activity of neurotransmitter GABA. May block glutamate activity.

Adult

Pediatric

Initial starting dose: 1 -3 mg/kg/d PO; increment of 1-3 mg/kg q3-4d
Maintenance dose: up to 9 mg/kg/day though 20 mg/kg/day is used for infantile spasms

Phenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants since may have an additive effect in CNS depression as well as other cognitive or neuropsychiatric adverse events

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Risk of developing a kidney stone formation is increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop can lead to glaucoma; primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia have been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures)
May cause hyperchloremic, nonanion gap metabolic acidosis acute or chronic metabolic acidosis resulting in hyperventilation and nonspecific symptoms, such as fatigue and anorexia, or more severe adverse effects including cardiac arrhythmias or stupor; chronic, untreated metabolic acidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate level

More on Benign Neonatal Convulsions

Overview: Benign Neonatal Convulsions
Differential Diagnoses & Workup: Benign Neonatal Convulsions
Treatment & Medication: Benign Neonatal Convulsions
Follow-up: Benign Neonatal Convulsions
References
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Further Reading

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Keywords

benign neonatal convulsions, second day seizures, benign neonatal seizures, benign familial neonatal convulsions, benign idiopathic neonatal convulsions, benign familial neonatal seizures, benign idiopathic neonatal seizures, fifth day disease, fifth day fits, seizure epilepsy treatment, symptoms, BFNC, BINC

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Contributor Information and Disclosures

Author

Nancy Theresa Rodgers-Neame, MD, Assistant Professor, Department of Molecular Pharmacology and Physiology, University of South Florida; Director, Florida Comprehensive Epilepsy and Seizure Disorders Program
Nancy Theresa Rodgers-Neame, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Medical Women's Association, Society for Neuroscience, Southern Clinical Neurological Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Robert Baumann, MD, Program Director, Professor, Departments of Neurology and Pediatrics, University of Kentucky
Robert Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American College of Epidemiology, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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