HOW DO I MANAGE REFRACTORY NEONATAL SEIZURES?
Rhishikesh Thakre*
DM (Neo.), MD, DNB, DCH, FCPS, Neo Clinic, 27, Samarth Nagar, Aurangabad. *
Neonatal seizures may be both over and under-diagnosed. Important steps in the management are provisions of basic life support, identification of conditions which mimic seizures, identification of its etiology and its treatment and finally recognition of a truly refractory seizure.
Management
Step I:Ensure patency of airway, breathing, circulation.

Step II: Conditions mimicking seizures to be ruled out.


Seizure-like conditions

Clinical features

Jitteriness

Stimulus sensitive, stops on restrain, normal neurology, no involvement of face or eyes.

Benign neonatal sleep
myoclonus

Bilateral / unilateral, synchronous / asynchronous myoclonus, during active sleep, not stimulus-sensitive.

Stimulus-evoked
Myoclonus

Associated with severe central nervous system dysfunction, focal or generalized myoclonus.

Hyperekplexia (Still-man syndrome 1)

Hyperactive startle, generalized myoclonus, severe hypertonia, may have apnea and bradycardia, responds to benzodiazepine.


Step III: Do not miss treatable causes. Cause specific therapy to be instituted.


 

Acute Therapy

Maintenance Therapy

Glucose (10%)

2 ml/kg IV

Up to 8 mg / kg / minutes, IV

Calcium gluconate (10%) 2 ml/kg IV over 10 minutes 8 ml / kg d IV
Magnesium sulfate (50%) 0.25 ml / kg IM 0.25 ml / kg IM repeat 12 hrly
Pyridoxine 100 mg, IV until normal sr. Mg level

Step IV: A seizure is considered refractory when it fails to respond to 2 or more AED regimens and in addition to some adverse effects of the drug. In this situation, one must check the right drug, right dose, duration, compliance, drug vehicle and IV patency and also rule out a pseudo-seizure once again. In this situation, the possibilities of metabolic diseases, epilepsy or structural anomaly should be considered.
  • Fifth day fit (Benign idiopathic neonatal convulsions by PLOUIN'S Diagnostic Criteria): Normal pregnancy and delivery, full term, AGA, Apgar > 7 at 1 minute, seizure onset on 4th - 6th day, normal neurology pre and inter-ictally, normal laboratory findings (including, but not limited to, metabolic studies, neuroimaging and lumbar puncture), and no family history of either neonatal seizures or post-neonatal epilepsy./li>
  • Benign neonatal familial convulsions: Contributory family history
  • Devastating epileptic syndromes: Evolve over a period of time and can differentiated as follows:

Neonatal Epileptic Syndromes:
  • Fifth day fit (Benign idiopathic neonatal convulsions by PLOUIN'S Diagnostic Criteria): Normal pregnancy and delivery, full term, AGA, Apgar > 7 at 1 minute, seizure onset on 4th - 6th day, normal neurology pre and inter-ictally, normal laboratory findings (including, but not limited to, metabolic studies, neuroimaging and lumbar puncture), and no family history of either neonatal seizures or post-neonatal epilepsy.
  • Benign neonatal familial convulsions: Contributory family history
  • Devastating epileptic syndromes: Evolve over a period of time and can differentiated as follows:


Comparison

Early Myoclonic
Encephalopathy

Early Infantile Epileptic Encephalopathy

Age of onset

Neonatal period

Within first 3 months

Neurologic status of onset

Abnormal at birth or at seizure

onset

Always abnormal, even prior to seizure onset; tonic spasm

Characteristic seizure type

Erratic or fragmentary myoclonus

 
Additional seizure types Massive myoclonus; simple partial seizures; infantile spasms (tonic)

Focal motor seizures;

hemiconvulsions; generalized

seizures

Background EEG

Suppression-burst

Suppression-burst

Etiology

Inborn errors of metabolism;

familial; cryptogenic

Cerebral dysgenesis; anoxia;

cryptogenic

Natural course

Progressive impairment

Static impairment

Incidence of death High, occurring in infancy

High, occurring in infancy

childhood, or adolescence

Status of survivors Vegetative state

Severe mental retardation

quadriplegia and bedridden

Longterm seizure

evolution

Infantile spasms

West's syndrome; Lennox-

Gastaut syndrome


  • B 6-dependent seizures: B6 should be administered when neonatal seizures are refractory, or in any infant < 18 months of age. EEG normalizes rapidly in B6 dependent seizures.
  • Glucose transporter defect: Autosomal dominant; presents above 2 weeks of age and should be considered when other causes of hypoglycorrhachia are excluded. Ketogenic diet is the specific treatment. If left untreated, microcephaly and mental retardation may occur.
  • Folinic Acid responsive seizures: This rare disorder is suspected if seizures are refractory to B6. CSF neurotransmitter studies are obtained and folinic acid is started at 2.5 mg BID (up to 4 mg/kg per day initially) until the CSF study results are available. Seizures may stop within 24 hours of folinic acid initiation.
  • Structural cerebral defects can be picked up on CT or MRI.
  • Biotinidase deficiency usually have skin rash, total or partial alopecia and persistent conjunctivitis. Treatment consists of biotin, 5 to 20 mg orally each day.
  • Brain tumors usually are supratentorial. Progressive hydrocephalus is the hallmark. Seizures occur in about 14% to 20% of newborns with brain tumors.
  • Antibiotic-induced seizures:
    Pre-existing CNS disease, renal and or hepatic insufficiency are the risk factors. High dose intravenous co-administered drugs with theophylline increase the risk.

Clinical pearls:
  1. Response to the first AED is the most powerful predictor of longterm prognosis.
  2. The commonest cause of refractory seizures in newborn is hypoxia. Do not chase seizures in asphyxia as majority burn themselves out. Asphyxial seizures are best treated if they occur for more than 3 per hour or last for more than 3 minutes or are associated with hemodynamic instability.
  3. Infants with metabolic disorders usually are lethargic and feed poorly even prior to seizures. Alteration in mental status far outweighs other signs early on and a child is more likely to present comatose but with a preserved blood pressure.
  4. Abnormal odor can be very helpful when present but is an infrequent occurrence.
  5. Ammonia and lactate must be collected as free flowing blood without prolonged tourniquet time and immediately placed on ice and run within 90 minutes by the laboratory.
  6. Neonates who present in the first 6 hours of life and have dilated and fixed pupils and absence of extraocular movements suspect local anesthetic toxicity. The usual offenders are mepivacaine and lidocaine.
  7. The possibility of an inborn error of metabolism is very unlikely if there is no ketonuria (excludes propionic and methylmalonic acidemias) and the following laboratory values are in the normal range: (1) blood glucose (excludes carbohydrate and fatty acid abnormalities); (2) ammonia level (excludes a urea cycle defect); (3) lactic acid (excludes pyruvate, citric acid, and mitochondrial respiratory chain abnormalities); and (4) sulfite in blood and urine (excludes sulfite oxidase deficiency and molybdenum cofactor deficiency)
Conclusions
The single most important factor in determining treatment of neonatal seizures is recognition of the underlying etiology for the seizures.


Parenteral

Oral

High-dose Phenobarbital: > 30 mg/kg

Pentobarbital: 10 mg/kg, then 1 mg/kg/hr

Midazolam: Bolus 0.2 mg/kg, then 0.1 to 0.4 mg/kg per hour

Thiopental: 10 mg/kg, then 2 to 4 mg/kg/hr

Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses

Lidocaine: 2 mg/kg, then 6 mg/kg per hour



Clonazepam: 0.1 mg/kg

Paraldehyde: 200 mg/kg, then 16 mg/kg/hr

Chlormethiazole: Initial infusion rate of 0.08 mg/kg per minute

Dexamethasone: 0.6 to 2.8 mg/kg

Pyridoxine (B6): 50 to 100 mg, then 100 mg every 10 minutes (up to 500 mg)

Primidone: 15 to 25 mg/kg/day in 3 doses

Clonazepam: 0.1 mg/kg, in 2 to 3 doses

Carbamazepine: 10 mg/kg, then 15 to 20

mg/kg per day in 2 doses

Oxcarbamazepine: No data

Valproic acid: 10 to 25 mg/kg, then 20 mg/kg

per day in 3 doses



Vigabatrin: 50 mg/kg/day 2 div (max 200mg/kg/day)

Lamotrigine: 12.5 mg in 2 doses

Topiramate: 3 mg/kg per day

Zonisamide: 2.5 mg/kg per day

Levetiracetam: 10 mg/kg per day in 2 div

Folinic acid: 2.5 mg BID, up to 4 mg/kg per day.
How to Cite URL :
Thakre R.. Available From : http://www.pediatriconcall.com/fordoctor/ Conference_abstracts/report.aspx?reportid=302
Disclaimer: The information given by www.pediatriconcall.com is provided by medical and paramedical & Health providers voluntarily for display & is meant only for informational purpose. The site does not guarantee the accuracy or authenticity of the information. Use of any information is solely at the user's own risk. The appearance of advertisement or product information in the various section in the website does not constitute an endorsement or approval by Pediatric Oncall of the quality or value of the said product or of claims made by its manufacturer.
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.