What are neonatal convulsions, and why is it important to distinguish between epileptic and non-epileptic seizures, including types such as partial (focal) and generalized, simple and complex seizures?

Neonatal Convulsions: Definition, Classification, and Diagnostic Approach

What Are Neonatal Convulsions?

Neonatal convulsions are uncontrolled electrical discharges of neurons in the brain manifesting as violent muscle contractions, typically with generalized movements and unresponsiveness, representing excessive synchronous cortical electrical activity in infants from birth to 28 days of age. 1

• Seizures are defined as transient occurrences of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain 1
• The incidence is approximately 1.5-5.5 per 1000 live births, with 80% occurring during the first week of life 2, 3
• Neonates have a lower seizure threshold due to immature neurons and differences in neurotransmitters 2
• Mortality remains very high at 20-45% 3

Why Distinguishing Epileptic from Non-Epileptic Seizures Is Critical

Accurate differentiation between epileptic and non-epileptic paroxysmal events is essential to avoid inappropriate treatment with anticonvulsants that carry significant risks in neonates, while ensuring true epileptic seizures receive prompt intervention to prevent brain damage and reduce mortality. 4

Key Clinical Implications:

• Treatment consequences: Non-epileptic movements do not require anticonvulsant therapy, which can cause unnecessary side effects and complications 4
• Prognostic differences: Epileptic seizures may indicate serious underlying brain injury requiring urgent intervention, while many non-epileptic movements are benign 4
• Diagnostic challenge: The majority of neonatal seizures are subclinical (not visible clinically), and conversely, not all abnormal movements identified clinically are accompanied by EEG seizure discharges 5

Common Non-Epileptic Paroxysmal Movements:

• Jitteriness: Distinguished by stimulus sensitivity, cessation with passive flexion, and absence of eye deviation 2, 4
• Benign neonatal sleep myoclonus: Occurs only during sleep, stops with arousal, and has normal interictal EEG 2, 4
• Hyperekplexia: Excessive startle response to unexpected stimuli 2, 4
• Key distinguishing feature: Myoclonic movements in syncope are brief and few, whereas epileptic seizures show synchrony, rhythmicity, and many movements 1

Classification of Neonatal Seizures

Clinical Seizure Types:

Neonatal seizures are classified into four main clinical types based on semiology: 2, 3

1. Subtle seizures (most common):

   • Include autonomic signs (apnea, tachycardia, blood pressure changes) 3
   • Automatisms (eye deviation, repetitive movements, cycling movements) 3
   • Often difficult to recognize clinically 2

2. Clonic seizures:

   • Rhythmic jerking movements 2, 3
   • Can be focal or multifocal 3

3. Tonic seizures:

   • Sustained muscle contraction 2, 3
   • May be focal or generalized 3

4. Myoclonic seizures:

   • Brief, shock-like jerks 2, 3
   • Can be axial, focal, or erratic 3

Partial (Focal) vs. Generalized Seizures:

• Focal seizures: Originate from one hemisphere or localized brain region, may present as clonic movements of one limb or body side 3
• Generalized seizures: Affect both hemispheres simultaneously, presenting with bilateral motor manifestations 3
• Note: The terms "simple" and "complex" (referring to consciousness preservation) are not typically applied to neonatal seizures due to difficulty assessing consciousness in this age group 5, 3

Diagnostic Workup

Immediate Stabilization and Assessment:

The diagnostic approach must prioritize immediate stabilization, rapid exclusion of treatable metabolic causes, and systematic evaluation to identify the underlying etiology. 1

1. Airway, Breathing, Circulation:

   • Ensure patent airway and adequate oxygenation 1
   • Continuous monitoring of heart rate, blood pressure, temperature, oxygen saturation 1
   • Establish IV/IO access immediately 1

2. Point-of-Care Glucose Testing (mandatory):

   • Exclude hypoglycemia immediately 1
   • If hypoglycemic, correct with D10%-containing isotonic IV solution at maintenance rate 1

Essential Laboratory Investigations:

Immediate labs include: 1

• Electrolytes: sodium, calcium, magnesium (correct hypocalcemia and hypomagnesemia BEFORE initiating anticonvulsants) 1
• Blood gas analysis 1
• Complete blood count 1
• Blood culture if infection suspected 1

Lumbar Puncture Indications:

Perform lumbar puncture if: 6

• Clinical signs of meningism present 6
• After a complex convulsion 6
• Child is unduly drowsy, irritable, or systemically ill 6
• Age less than 12-18 months (especially <12 months) 6
• Critical caveat: Avoid lumbar puncture in comatose infants due to risk of herniation; brain imaging may be necessary first 6, 1

Neuroimaging Algorithm:

Based on clinical stability: 1

1. Head Ultrasound (initial bedside imaging):

   • Use if infant is unstable or MRI unavailable 1
   • Identifies intraventricular hemorrhage, hydrocephalus, white matter changes, cystic periventricular leukomalacia 6
   • Limitations: Low sensitivity for hypoxic-ischemic injury, small infarctions, developmental anomalies, and encephalitis 6
   • Identifies etiology in only approximately 38% of cases 6

2. MRI with Diffusion-Weighted Imaging (gold standard):

   • Most sensitive for hypoxic-ischemic encephalopathy (the most common cause) when performed at appropriate time interval 6
   • Greatest sensitivity for detecting malformations of cortical development 6
   • Shows findings in 11.9% of patients not apparent on ultrasound 6
   • Contributes to diagnosis in 39.8% of patients by providing additional information beyond ultrasound 6
   • Prognostic value: Absence of major cerebral lesions on MRI is highly predictive of normal neurological outcome 6
   • Risks: Transportation, positioning, and sedation in physiologically unstable neonates 6

3. CT Head (limited but specific role):

   • Perform noncontrast CT to detect hemorrhagic lesions in encephalopathic infant with history of birth trauma, low hematocrit, or coagulopathy 6
   • Useful for quantifying and characterizing extra-axial collections 6
   • Less sensitive than MRI for most pathology 6

Electroencephalography:

Continuous video-EEG monitoring is essential: 2, 5

• Necessary to recognize seizures, as majority are subclinical 5, 3
• Interictal tracing helps assess prognosis 3
• Not all clinical movements have EEG correlate, and not all EEG seizures have clinical manifestations 5
• Important: EEG is not indicated for simple febrile seizures but is essential for neonatal seizures 6, 2

Common Etiologies to Identify:

Hypoxic-ischemic encephalopathy (HIE) is the dominant cause, accounting for 46-65% of cases, with 90% occurring within first 2 days of life 7, 1, 2

Other causes include: 7, 1

• Intracranial hemorrhage and perinatal ischemic stroke (10-12% combined) 7, 1
• Metabolic derangements: hypoglycemia, hypocalcemia, hypomagnesemia, hyponatremia 7, 1
• Infections (encephalitis, meningitis) - more likely beyond seventh day of life 7, 1
• Genetic disorders and malformations of cortical development 7, 1
• Inborn errors of metabolism, vitamin B6 dependency 3

Critical Pitfalls to Avoid:

• Never delay metabolic correction: Hypocalcemia and hypomagnesemia must be corrected BEFORE anticonvulsants 1
• Do not assume all movements are seizures: Requires EEG confirmation when possible 5
• Do not perform lumbar puncture in comatose infants without imaging first 1
• Do not delay empirical antibiotics when infection is suspected 1