Neonatal seizures (NSz)

Definition And Types

Definition Of Neonatal Seizures

• A neonatal seizure is a paroxysmal alteration in neurological function.
• This paroxysmal alteration involves motor, behavior, and autonomic function.
• It represents an abnormal electrical discharge in the central nervous system.

Types Of Seizures

• The presentation can be strictly an electrographic seizure.
• The presentation can also be an electroclinical seizure.

Classification Of Neonatal Seizures

Subtle Seizures

• Subtle seizures present as mild motor, behavioral, or autonomic paroxysms.
• This is the most common type of seizure in neonates.
• Ocular manifestations in term infants include tonic horizontal fixation of eyes.
• Preterm infants may exhibit sustained eye opening.
• Cycled fluttering is another ocular manifestation.
• Oral-facial-lingual movements include chewing and tongue thrusting.
• Lip smacking is also a common oral movement.
• Limb movements mimic complex activities like cycling and paddling.
• Boxing jabs and hooking movements of the limbs are also observed.
• Autonomic phenomena manifest as either tachycardia or bradycardia.
• Apnea is a frequent manifestation of subtle seizures.

Clonic Seizures

• Clonic seizures involve the rhythmic movement of muscle groups.
• They feature a rapid phase followed by a slow return.
• The frequency of movements is usually 1 to 3 jerks per second.
• These seizures are commonly associated with electroencephalogram changes.
• Clonic seizures can present as either focal or generalized.
• Focal clonic seizure has the best prognosis among seizure types.

Tonic Seizures

• Tonic seizures feature sustained flexion or extension of muscle groups.
• This sustained posture affects axial or appendicular muscles.
• The posturing can resemble decerebrate or decorticate positioning.
• These are not associated with electroencephalogram changes in 85 percent of cases.
• They represent a brainstem release phenomenon.
• This phenomenon occurs secondary to severe brain injury.

Myoclonic Seizures

• Myoclonic seizures involve single or multiple lightning-fast jerks.
• These jerks affect the upper or lower limbs.
• There is a specific predilection for the flexor muscle groups.
• This seizure type carries the worst prognosis.

Pathophysiology

Mechanisms Of Seizure Generation

• There is reduced connectivity in the developing neonatal brain.
• Therefore, neonatal seizures are mostly focal and rarely generalized.
• Excitatory circuits develop earlier in the newborn brain.
• Inhibitory circuits develop later.
• Gamma-aminobutyric acid sometimes acts as an excitatory neurotransmitter.
• This paradoxical action is due to an alteration in the chloride channel.
• A clinical seizure can occur without any electrographic change.
• This phenomenon is known as paroxysms.
• An electrographic change can occur without a clinical seizure.
• This mismatch is termed uncoupling.

Etiology Of Neonatal Seizures

Hypoxic Ischemic Encephalopathy

• This is the most common cause of neonatal seizures in low and middle income countries.
• Onset occurs within 12 to 24 hours of life in 50 to 65 percent of cases.
• The remaining cases manifest in 24 to 48 hours.
• Additional clinical problems can co-exist with this etiology.
• Subtle seizures are the most common type of seizure seen in this condition.

Metabolic Causes

• Hypoglycemia is a highly common metabolic cause.
• Hypocalcemia and hypomagnesemia frequently trigger seizures.
• Both hyponatremia and hypernatremia can present with seizures.
• Inborn errors of metabolism must be considered.
• Pyridoxine dependent seizures are a specific metabolic etiology.
• Folic acid responsive seizures are also encountered.

Infection

• Bacterial meningitis typically causes seizures in the latter part of the first week of life.
• Meningoencephalitis can occur secondary to intrauterine infection.

Intracranial Hemorrhage And Vascular Causes

• Intraventricular hemorrhage is a major cause in preterm infants.
• Subarachnoid hemorrhage causes seizures in term infants.
• Intraparenchymal hemorrhage and subdural hemorrhage also occur in term neonates.
• A seizure in a well baby on day 2 or 3 of life suggests vascular causes.

Developmental Defects And Miscellaneous Causes

• Cerebral dysgenesis is a structural cause of seizures.
• Neuronal migration disorders fall into this category.
• Polycythemia and maternal narcotic withdrawal are miscellaneous triggers.
• Drug toxicity can induce neonatal seizures.
• Phacomatosis syndromes like tuberous sclerosis cause seizures.
• Incontinentia pigmentii is another phacomatosis to consider.

Clinical Approach To A Neonate With Seizures

History Taking

Seizure History

• Elicit a history of abnormal eye movements.
• Check if the episode could be restrained by passive flexion.
• Note any changes in skin color during the event.
• Document any accompanying autonomic phenomenon.
• Seizures presenting on day 1 to 3 are typically associated with perinatal asphyxia.
• Intracranial hemorrhage also presents in this early timeframe.
• Seizures on day 4 to 7 are associated with sepsis or meningitis.
• Developmental defects also manifest later in the first week.

Antenatal And Perinatal History

• Evaluate for a history of intrauterine infection.
• Check for maternal diabetes and maternal narcotic addiction.
• Perinatal asphyxia remains the most common cause of neonatal seizure.
• A detailed history regarding fetal distress is essential.
• Document any reports of decreased fetal movements.
• Note the use of instrument delivery during birth.
• Document the need for resuscitation in the labor room.
• Record the APGAR score at birth.
• Check for an abnormal cord blood pH less than 7.
• Check for a base deficit greater than 12 mEq/L.

Feeding And Family History

• Late-onset hypocalcemia is seen in children fed on cow's milk.
• Inborn errors of metabolism present immediately following feeding.
• Symptoms include lethargy, poor activity, drowsiness, and vomiting.
• Note any consanguinity in the parents.
• Document a positive family history of seizures.

Physical Examination

• Carefully record the vital signs.
• Perform a general examination assessing gestation and birth weight.
• Screen for the presence of congenital malformations.
• A seizure in a well baby might indicate a subarachnoid hemorrhage.
• Perform a central nervous system examination assessing for a bulging fontanelle.
• Perform a systemic examination to look for hepatosplenomegaly.
• Assess for an abnormal urine odor which suggests an inborn error of metabolism.
• Specifically check for the presence of neurocutaneous markers.

Diagnosis And Investigations

Electroencephalogram Criteria

• Continued video electroencephalogram is the gold standard for diagnosis.
• The tracing shows stereotyped repeated waveforms.
• This presents as rhythmic activity with a distinct beginning and end.
• The abnormal electrical activity is focal in origin.
• The morphology and frequency of the waveforms evolve over time.
• The required minimum peak to peak voltage is 2 microvolts.
• The minimum required duration is 10 seconds or more.
• There is no requirement for clinical evidence of a seizure to meet these criteria.

Investigations Protocol

Management Protocol

Initial Management

• Initial management must be completed within 2 to 5 minutes.
• Maintain appropriate body temperature.
• Secure the airway and ensure adequate breathing.
• Support the circulation and administer oxygen.
• Secure intravenous access rapidly.
• Check the blood glucose level immediately.
• Obtain a quick and relevant clinical history.

Hypoglycemia And Hypocalcemia Correction

• Correct hypoglycemia with 2 ml/kg of 10 percent dextrose.
• Follow this with a continuous glucose infusion of 6 to 8 mg/kg/min.
• Correct suspected hypocalcemia if hypoglycemia is ruled out.
• Give 2 ml/kg of 10 percent calcium gluconate intravenously over 10 minutes.
• If hypocalcemia is proven, continue 8 ml/kg/day of calcium gluconate for 3 days.
• Add magnesium if seizures continue despite calcium therapy.
• Give 0.25 ml/kg of 50 percent magnesium sulphate via intramuscular route.

Antiseizure Medications

Phenobarbitone

• Phenobarbitone is the drug of choice in neonatal seizures.
• Close respiratory monitoring is required during administration.
• Administer a 20 mg/kg loading dose.
• Give an additional 10 mg/kg dose if seizures persist.
• Give another 10 mg/kg dose if necessary.
• These doses can be given every 20 to 30 minutes.
• The maximum dose is 40 mg/kg/day.
• A maintenance dose of 3 to 5 mg/kg/day is generally not necessary.

Phenytoin And Fosphenytoin

• Phenytoin is used after phenobarbitone fails.
• Adverse effects include respiratory depression, hypotension, and bradycardia.
• The dose is 20 mg/kg given slowly intravenously.
• The infusion must take at least 20 minutes.
• Avoid oral suspension in neonates because absorption is highly erratic.
• Fosphenytoin has fewer adverse effects than phenytoin.
• A dose of 1.5 mg/kg of fosphenytoin is equivalent to 1 mg/kg of phenytoin.

Benzodiazepines

• These agents are required in 15 to 20 percent of neonatal seizures.
• Lorazepam is given as a 0.05 mg/kg intravenous bolus over 2 to 5 minutes.
• Midazolam is given as a 0.15 mg/kg intravenous bolus.
• This is followed by an infusion of 0.1 to 0.4 mg/kg/hour.

Levetiracetam

• The dose range is 20 to 50 mg/kg/day.
• It can be used as a first-line agent.
• This is due to its low adverse effect profile.

Refractory Seizures

Lidocaine

• Administer a 4 mg/kg intravenous loading dose.
• Follow this with a continuous infusion of 2 mg/kg/hr.
• Adverse effects include arrhythmia, hypotension, and paradoxical seizures.

Paraldehyde

• Administer 0.1 to 0.2 ml/kg/dose via intramuscular route.
• Alternatively, use 0.3 ml/kg/dose mixed with coconut oil in a 3 to 1 ratio.
• This mixture may be used via the rectal route.
• Additional doses can be used after 30 minutes.
• Dosing can be repeated every 4 to 6 hours.
• Adverse effects include pulmonary edema and pulmonary hemorrhage.
• Hypotension and liver injury are also significant risks.

Sodium Valproate

• Administer a loading dose of 20 to 25 mg/kg.
• Follow with a maintenance dose of 5 to 10 mg/kg every 12 hours.
• There is a high risk of hepatotoxicity in children less than 2 years of age.
• This medication must be used very cautiously.

Vigabatrin And Topiramate

• Vigabatrin is specifically used in infantile spasms.
• The standard dosage is 50 mg/kg/day.
• Topiramate has neuroprotective properties in seizures.
• It has a higher volume of distribution compared to other drugs.
• This requires high initial and maintenance doses of approximately 3 mg/kg.

Other Specific Therapies

• Pyridoxine is utilized as a last resort.
• The intravenous route is preferred but is not always readily available.
• It can cause adverse effects like hypotension and apnea.
• Administer 1 ml of Neurobion in each gluteal region.
• Each milliliter contains 50 mg of pyridoxine.
• Exchange transfusion is indicated in life-threatening metabolic disorders.
• It is also used for bilirubin encephalopathy.
• Transplacental transfer of maternal drugs is another indication for exchange transfusion.

Principles Of Therapy And Discontinuation

• Monotherapy is the ultimate goal of treatment.
• Maintain the neonate preferably on 3 to 5 mg/kg/day of phenobarbitone.
• Add a second-line drug only if the seizures are completely uncontrolled.
• Stop the antiseizure medication as early as possible.
• Discontinuation is preferably done at the time of discharge.
• If the baby is discharged on medication, review the clinical status in 1 month.
• At 1 month, if the neurological examination is abnormal, plan an electroencephalogram.
• Stop the medication when the electroencephalogram is not overly paroxysmal.
• Reassess the patient at 3 months.
• Continue follow-up every 3 months until 1 year of age.