You are the registrar on call, and the midwife asks you to review a baby on the postnatal ward due to concerns about abnormal movements. She is worried that these could be seizures.
What you know so far: The baby is 6 hours old and was born at 36+2 weeks, needing some resuscitation at birth. Their weight is 1.7 kg.
Neonates are at a higher risk of developing acute symptomatic seizures than older age groups. This is due to their immature brain excitability and multifactorial causes such as hypoxic ischaemic encephalopathy (HIE), stroke, intracranial haemorrhage, infection, metabolic disturbance and malformation.
Only 50% of seizures are detected clinically.
Incidence
Incidence is 1-5 per 1000 live births in term babies and much higher in preterm and low birth weight (< 1500 g) neonates, ranging from 57.5 – 132 per 1000 live births.
However, given the poor clinical detection and high number of electrographic seizures that do not have a clinical correlation, the real incidence is difficult to estimate.
What causes neonatal convulsions?
The underlying cause of neonatal convulsions is identifiable in most cases.
For term babies, HIE is by far the most common cause (35-45% of cases), whereas in preterm babies intraventricular haemorrhage is the leading cause. Infections and metabolic disturbances (hypoglycaemia, hypocalcaemia, hypomagnesaemia, hypo- and hypernatraemia) are second, followed by brain malformations and genetic conditions.
Other causes could be subdural and subarachnoid haemorrhage, stroke, neonatal abstinence syndrome (NAS), maternal non-narcotic drug use (SSRIs), vitamin-responsive seizures, and inborn errors of metabolism.
What are other differential diagnoses to consider?
Newborns may exhibit normal movements that could be mistaken for seizures such as:
- Jitteriness – this is a common finding in up to two-thirds of babies in the first few days of life. It is characterised by rapid, tremulous movement in one or more limbs, usually in response to minor stimulation. These movements stop when held, unlike during a seizure, where they would continue despite restraint. However, they could be associated with hypoglycaemia, hypocalcaemia, sepsis, HIE and drug withdrawal.
- Benign neonatal sleep myoclonus – usually seen in the upper limbs and only during sleep and settles on arousal.
- Reflux/ Sandifer Syndrome
- Hyperekplexia (Exaggerated Startle Reflex)
How could neonatal convulsions look like?
There are four main types of neonatal convulsions that could be seen:
- Subtle – these are by far the most common.
- Clonic
- Myoclonic
- Tonic
Subtle seizures can present with eye movements (eye deviation, eyes rolling up, eyelid flickering, blinking, staring), oral–buccal–lingual movements (sucking, lips smacking, tongue protruding, chewing), progression movements (rowing, swimming, bicycling, thrashing in upper or lower limbs), sudden arousal with crying.
These may mimic normal behaviour and are often overlooked. Some subtle seizures are associated with autonomic ictal manifestations such as apnoea, changes in heart rate and blood pressure, salivation, and pupillary changes. Â
Generalised tonic-clonic seizures are rare.
The duration of neonatal seizures is often brief (few seconds up to 2 minutes), and they are usually repetitive.
You go and review the baby.
A closer look at the history reveals oligohydramnios and PROM.
The baby needed stimulation and two sets of inflation breaths at birth, after which they began breathing spontaneously. Their tone normalised within 5 minutes.
On examination, the baby is slightly lethargic and has frequent myoclonic jerks in one arm and eye staring lasting 2-3 seconds.
You are worried these could be seizures and admit the baby to NICU.
What investigations should you perform first?
These would be guided by the most likely aetiology, based on the history and examination. However, first-line investigations should include:
– Septic screen (including blood culture and lumbar puncture)
– Plasma (FBC, LFTs, U&Es, calcium, magnesium, blood glucose, CRP, Blood gas).
– Consider TORCH and drug abuse screening
– Cranial Ultrasound
– CFM/ EEG
CFM confirms the presence of seizures, and you initiate antibiotic therapy according to local guidelines. But what antiseizure treatment should you start?
Antiseizure medication
Neonatal seizures are particularly difficult to treat.
The immature brain may be resistant to GABA-A receptor agonists due to lower receptor expression and an immature subunit composition that makes it less sensitive to benzodiazepines than in the adult brain.
Phenobarbitone remains the drug of choice in the treatment of neonates. The initial dose is 20 mg/kg in unventilated babies and 30 mg/kg in ventilator-dependent babies, aiming to achieve a serum level of 90-180 μmol/L.
Phenytoin and clonazepam are used as second-line anti-epileptic drugs. Phenytoin can cause significant myocardial depression and should be avoided in babies requiring inotropic support.
Midazolam has a shorter half-life than clonazepam, does not accumulate, and it avoids the side effect of increased oropharyngeal secretions.
Recent studies show up to 50% of neonatal seizures are refractory to first-line medications and an additional 30% fail second-line therapy.
The baby’s seizures are difficult to control despite two medications.
An MRI is organised urgently, which shows perinatal stroke.
Difficult-to-control seizures warrant further investigations such as neuroimaging (MRI) and metabolic and genetic testing.
What is the prognosis?
The prognosis depends on the aetiology. Seizures secondary to stroke, subarachnoid haemorrhages, transient metabolic disturbances, familial cases and ‘fifth day fits’ are all associated with a more favourable outcome. In cases of HIE, it depends on the severity of the brain insult. Brain malformations and inborn errors of metabolism have poor outcomes.
Neonatal seizures have an adverse effect on neurodevelopmental outcome, and predispose to cognitive, behavioural, or epileptic complications in later life. Even a single seizure in the neonatal period may lead to long-term neurodevelopmental consequences.
More recently, a clear association between the number of electrographic seizures and subsequent mortality and morbidity has been shown, illustrating the need for EEG monitoring in neonatal seizures.
However, phenobarbital, the preferred first-choice medication internationally, is effective in only 50% of cases and may be harmful, especially when used in high doses or for prolonged periods.
There is an urgent need for research to develop safe, accurate, and widely available methods for identifying and treating electrographic seizures.
Summary
Neonatal convulsions are among the most common neurological emergencies in the neonatal period and are most likely caused by HIE and intracranial haemorrhage
They need prompt investigation and treatment due to potential long term consequences
Most neonatal seizures are subtle and are easily overlooked as normal behaviour
Phenobarbitone is the first-line medication, but most seizures require multiple drugs to control them.
References
A manual of Neonatal Intensive Care, Fifth Edition, by Janet M Rennie and Giles S Kendall
The Epilepsies: Seizures, Syndromes and Management, by Panayiotopoulos CP., Bladon Medical Publishing; 2005
Neonatal seizures RONIT M. PRESSLER Department of Clinical Neurophysiology, Great Ormond Street Hospital, London, www.epilepsysociety.org.uk
Duygu Besnili Acar, Current Overview of Neonatal Convulsions, Sisli Etfal Hastan Tip Bul. 2019 Mar 22;53(1):1–6. doi: 10.14744/SEMB.2018.22844
Neonatal Seizures Advances in Mechanisms and Management by Hannah C. Glass,
www.bpna.org.uk
