Neonatal Seizures and management

Dhaka Sishu hospital Bangladesh

Objectives
Introduction Types/ Differential Diagnosis Investigations Management Areas of Uncertainty in Clinical Practice Prognosis

Introduction
Neonatal seizures are paroxysmal alterations in neurological function. This definition allows the inclusion of clinical seizures associated with EEG abnormalities as well as paroxysmal clinical activities (lip smacking, cycling etc.) that are not associated with EEG alterations.

 Relatively high incidence of seizures (13 per 1000 term infants and in preterm-10 to15/1000). Rarely idiopathic.

Aetiology of neonatal seizures: The main causes are: Hypoxic-ischaemic encephalopathy (HIE) Intracranial haemorrhage : subarachnoid (term > preterm), subdural (term infants with difficult deliveries) and peri/intraventricular (preterm infant) Cerebral infarction (stroke) : term infants Congenital CNS structural abnormalities / cortical dysplasia (neuronal migration disorders causing cerebral cortical dysgenesis). Intracranial infection : meningitis > encephalitis

Less common causes are: Inborn error of metabolism: amino and organic acidopathies, often seen after the infant starts feeding. Electrolyte disturbances: hypoglycaemia, hypocalcaemia, hypomagnesaemia, hyper- and hypo- natraemia, Pyridoxine deficiency Neonatal drug withdrawal Trauma: delivery and non accidental injury Benign familial neonatal seizure syndromes: AD, sz often start on day 2-3 and cease 6 months Benign idiopathic neonatal seizures at day 5 of life (ie, fifth day fits) Unknown aetiology / idiopathic : 2 - 5% Progressive epileptic syndromes in the first year of life with onset in the neonatal period

TYPES

Type

Clinical manifestation Eye signs: staring, deviation, blinking etc Buccal-oral-lingual: chewing, sucking, lip smacking Limbs: cycling, swimming rowing Systemic: apnoea, blood pressure alterations

Comments

Subtle 50-75%

It may be difficult to differentiate subtle seizures from extremes of normal behavior. Many subtle seizures are thought to arise from the basal ganglia as a result of diminished cortical inhibition. Further depression of the cortex with anticonvulsants may not alter these seizures
May be a clue to an underlying focal neuropathology e.g. hemorrhage or cerebral infarction Seen in drug withdrawal (especially opiates). If it occurs during sleep then it is probably "benign neonatal sleep myoclonus". Can also occur in a very severe form of encephalopathy.

Clonic 23-40%

Repetitive jerking, usually involve one limb or one side of the body at 1 4 times per second.

Myoclonic 8-18%

Rapid isolated jerking of muscles. Focal, multifocal or generalized D/D- benign sleep myoclonus.

Tonic 2-10%

Sustained posturing of the limbs or trunk or deviation of the head. It may mimic decerebrate or decorticate posturing. Only 30% have EEG correlates.

Often difficult to treat with anticonvulsants

Differential diagnosis
Movement Description Symmetrical rapid movements of the hands and feet Stimulus sensitive, and may be initiated by sudden movement or noise or spontaneous. Suppressed by holding the limb. No associated eye movements Bilateral or unilateral jerking during sleep Occurs during active sleep Not stimulus sensitive Often involve upper > lower trunk

Jitteriness

Benign neonatal sleep myoclonus

Management
Immediate management includesStabilization-evaluation of ventilation and perfusion. Identification of the cause and specific treatment. If needed, administration of an antiepileptic drug (AED) to prevent seizure recurrence.

Investigations:
All newborns with seizures : Blood glucose level Electrolytes: Na+, Ca2+, Mg2+ Full blood count Cranial ultrasound: to exclude gross CNS pathology, but is not effective at detecting subdural and epidural bleeds or identifying parenchymal injury.

Further investigations :
Acid base status Blood culture Lumbar puncture: for CSF study. Specimens for virology and congenital infections: TORCH (toxoplasmosis, rubella, CMV, herpes) Metabolic screen: urine for amino and organic acids Metabolic screen: blood for ammonia, lactate, pyruvate. Neurophysiology: formal 12 lead EEG, continuous EEG(BRAINZ monitor) Neuroimaging: CT, MRI

Anticonvulsant medication:
Indication for treatment of clinical seizures:
Prolonged > 3min Recurrent > 3 in 1hour Associated with cardiorespiratory compromise.

Therapy: Start with Phenobarbitone. If seizures are not controlled with maximum phenobarbitone, add Phenytoin. Drug levels should be monitored to determine maintenance dosages because of the variable pharmacokinetics in this age group.
If a combination of phenobarbitone and phenytoin is ineffective, then the options for achieving complete seizure control become limited. Clonazepam as a third line agent, .. In a recent report. Lignocaine appeared to be superior to clonazepam or midazolam. A trial of Pyridoxine should be performed in conjunction with EEG monitoring if pyridoxine deficiency is suspected in an infant with intractable seizures who does not have an underlying aetiology determined. Documenting cessation of seizures and normalisation of the EEG within minutes of IV pyridoxine often makes diagnosis.

Anticonvulsant

Indication for treatment

Loading dose

Maintenance

Other consideratio ns Therapeuticlev:4 0 130 mol/L Needs cardiorespira tory monitoring

Phenobarbitone Seizures duration: 3 minutes OR Seizure frequency: 3 per hour

20 mg/kg IV over 30 minutes. If initial dose is ineffective an additional 5 10 mg/kg can be administered every 5 minutes, up to a total of 40 mg/kg

4 mg/kg/dose IV/ oral every 12h Start 24 hours after the loading dose

Phenytoin

Inadequate response 20 mg/kg IV over 30 minutes to phenobarbitone

4 mg/kg/dose IV every 12 h Start 12 hours after the loading dose

0.025 mg/kg/dos e every 8 hours 50 100 mg daily oral

Therapeutic level: 40-80 mol/L Needs cardiorespira tory monitoring

Needs cardiorespira tory monitoring Pyridoxine trial (s) to be performed with EEG.

Clonazepam

Inadequate response 0.025 mg/kg/dose IV stat to phenobarbitone and phenytoin Intractable seizures with no underlying aetiology determined 100 mg IV or IM stat (test dose)

Pyridoxine

Areas of Uncertainty in Clinical Practice

Duration of therapy and decision to stop anticonvulsant medication is entirely empiric and should be judged on an individual basis taking into account the neurological exam, aetiology of seizures and interictal EEG. Withdraw anticonvulsants once seizures are controlled and neurological examination is normal. There is no indication that prolonged treatment of anticonvulsant therapy reduces the risk for the later development of epilepsy. The only recommendation for continuing anticonvulsant therapy (phenobarbitone 3-4 mg/kg/day) is in the setting of profound neonatal encephalopathy or severe brain injury and then only for 6-8 weeks.

Consequences
Short term: Prolonged seizures may cause
Hypoxia Lactic acidosis Hyperkalemia Myoglobinuria Arrhythmia Hypoglycemia Hyponatremia Hyperpyrexia

Long term: Prognosis depends on the:

Aetiology of the seizures. Neurological exam: Persistent neurological abnormalities are associated with poor outcome Gestational age: Adverse neurodevelopment outcome of cognitive changes, developmental delay , cerebral palsy . Seen in 20 40% of term and up to 75% of preterm infants. [9.3% in term & 33.3% in preterm babies with asphyxia (HIE-2,3), Mahbub et al DSHJ;2004;20:30-33] Seizure characteristics: Increased likelihood of adverse / poor outcome associated with Seizure type: Subtle, generalised or 2 or more seizure types. Prolonged or poorly controlled. EEG background: If there is persistent low voltage or burst suppression pattern this correlates with poor neurodevelopmental outcome in 65 to 90%.

Summary
Neonatal seizures are relatively common and rarely idiopathic

There are four different types of clinical seizures

Seizures must be differentiated from jitteriness and benign neonatal sleep myoclonus Treat with anticonvulsants if the seizure is prolonged (longer than 3 minutes), frequent or associated with cardiorespiratory disturbance 70% of seizures will abate with phenobarbitone only