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Neonatal seizure: what is the cause?

BMJ 2012; 345 doi: https://doi.org/10.1136/bmj.e6003 (Published 12 September 2012) Cite this as: BMJ 2012;345:e6003
  1. Manish Prasad, paediatric neurology grid registrar,
  2. Gabriel Chow, consultant paediatric neurologist
  1. 1Queens Medical Centre, Nottingham University Children’s Hospital, Nottingham NG7 2UH, UK
  1. Correspondence to: M Prasad m.prasad{at}nhs.net

A 7 day old girl presented with a one day history of decreased feeding, lethargy, and shaking of her extremities. She was born at term by normal vaginal delivery. She did not have a fever and there were no maternal risk factors for sepsis. She was hypotonic and minimally responsive on examination, with no signs of focal neurology.

Urea, electrolytes, calcium, and glucose values were normal. She was started empirically on intravenous antibiotics and aciclovir after full septic screen. She was ventilated and given an infusion of midazolam because her generalised clonic seizures with apnoea failed to respond to intravenous phenobarbital. Her seizures finally responded and she was extubated after 24 hours; she was maintained on regular phenobarbital with good effect.

Urgent neuroimaging (figs 1 and 2) was arranged because of her acute presentation with seizures and a history of deep vein thrombosis and pulmonary embolism in her mother and maternal uncle.

Figure1

Fig 1 Sagittal T1 weighted magnetic resonance image of the brain

Figure2

Fig 2 Axial T1 weighted magnetic resonance image of the brain

Questions

  • 1 What are the causes of seizures in a neonate?

  • 2 What is the differential diagnosis of seizures in neonates?

  • 3 What are the findings on neuroimaging?

  • 4 What is the most likely diagnosis?

  • 5 How would you manage this condition in neonates?

Answers

1 What are the causes of seizures in a neonate?

Short answer

Common causes of neonatal seizures include hypoxic ischaemic encephalopathy, intracranial haemorrhage, intracranial infections, congenital cerebral malformations, metabolic disorders, and focal ischaemic stroke.

Long answer

Seizures are more common in the neonatal period than in any other time of life, with 80% occurring in the first week of life. This is because the immature brain seems to be more prone to seizures then the more mature brain. The incidence of seizures is much higher in preterm infants (10-130/1000 live births) than in term infants (1-3/1000 live births).1

Neonatal seizures are mostly symptomatic, and it is crucial to determine the underlying causes, which will determine the prognosis and outcome and direct the treatment.2

In term babies, hypoxic ischaemic encephalopathy is the most common cause of neonatal seizures, with onset typically within the first 24-48 hours of life. In preterm babies, intracranial haemorrhage is the most common cause.

Table 1 summarises the causes of neonatal seizures along with their frequency.

Table 1

 Causes of neonatal seizures1 3 4

View this table:

2 What is the differential diagnosis of seizures in neonates?

Short answer

Jitteriness and benign neonatal sleep myoclonus are the two most common conditions that mimic seizure in neonates.

Long answer

Clinicians should be aware of the non-epileptiform movements presenting in the neonatal age group. As a general rule, non-epileptiform movements can be stopped by gentle restraint and can be reproduced by sensory stimuli.

True seizures are not usually reproducible by sensory stimuli; cannot be suppressed; are often associated with eye movements and cardiorespiratory changes; and neurological examination, electroencephalography, and neuroimaging results may be abnormal.

Benign neonatal sleep myoclonus is an important differential diagnosis in neonates. It is characterised by bilateral or localised myoclonic jerks only in sleep, consistent cessation with arousal, absence of epileptiform discharges on electroencephalography, normal neurological examination, and good outcome.5

Jitteriness is probably the most common differential diagnosis. Table 2 lists the differences between jitteriness and true seizure.

Table 2

 Differences between seizure and jitteriness

View this table:

Other more rare but important conditions to be considered in the differential diagnosis are Sandifer syndrome and hyperekplexia or “startle disease.”

Sandifer syndrome is characterised by the association of symptomatic gastro-oesophageal reflux with spastic torticollis and dystonic body movements, including opisthotonic posturing, which mainly affects the neck, back, and upper extremities.6

Hyperekplexia is characterised by excessive startle reflex to unexpected stimuli, generalised stiffness soon after birth, and short periods of generalised tonic spasms after the startle response. Electroencephalography and neuroimaging results are normal and clonazepam is the most effective treatment.

3 What are the findings on neuroimaging?

Short answer

The MRI of the brain shows extensive venous thrombosis.

Long answer

The sagittal section shows complete thrombosis of the superior sagittal sinus and straight sinus (fig 3) and the axial section (fig 4) shows bilateral thalamic hyperintensity suggestive of haemorrhage.

Figure3

Fig 3 Sagittal T1 weighted magnetic resonance image of the brain showing thrombosis of the superior sagittal sinus (arrow) and straight sinus (arrowhead)

Figure4

Fig 4 Axial T1 weighted magnetic resonance image of the brain showing bilateral thalamic hyperintensity (arrowheads) suggestive of haemorrhage; superior sagittal venous thrombosis is also clearly visible (arrow)

4 What is the most likely diagnosis?

Short answer

Neonatal cerebral sinovenous thrombosis.

Long answer

Cerebral sinovenous thrombosis is a rare disorder in children. The annual incidence is 0.67 per 100 000 children, and 43% are neonates.7 Seventy one per cent of neonates present with seizures,7 with the other common presentation being lethargy.8 Older children usually present with seizures, decreased level of consciousness, headache with papilloedema, intracranial hypertension, or focal neurological deficits.8

Occlusion of the venous sinuses may cause cerebral infarction and haemorrhage. In our patient, the thrombosis of the straight sinus and internal cerebral veins probably resulted in bilateral thalamic haemorrhages. MRI and magnetic resonance venography are the investigations of choice because computed tomography can be falsely negative in a fifth of patients.7

Genetic prothrombotic risk factors are present in 39-54% of children with this condition.7 9 These prothrombotic risk factors include deficiency of protein C, protein S, and antithrombin III; presence of the methylenetetrahydrofolate reductase (MTHFR) C677 T mutation, the factor V G1691A (Leiden) mutation, the prothrombin G20210A mutation, and antiphospholipid antibodies; and raised lipoprotein (a) concentrations. Acquired causes of neonatal cerebral sinovenous thrombosis include head and neck infections, meningitis, dehydration secondary to feeding difficulties or gastroenteritis, and congenital heart disease.10

Cerebral sinovenous thrombosis is associated with adverse outcomes in neonates, older infants, and children, with 2-10% of neonates dying,11 and 38% of children exhibiting long term neurological deficits.7 Outcomes are worse in neonates.7 12

5 How would you manage this condition in neonates?

Short answer

Management involves anticoagulation with low molecular weight heparin, ultrafractionated heparin, or warfarin and management of seizures and any identified acquired causes of cerebral sinovenous thrombosis.

Long answer

No randomised clinical trials have been conducted in neonatal cerebral sinovenous thrombosis, so treatment practices have been extrapolated mainly from adult studies.7

If identified, acquired causes such as meningitis, head and neck infection, sepsis, or dehydration should be promptly treated.

In children and neonates, the mainstay of treatment is anticoagulation, including low molecular weight heparin, ultrafractionated heparin, and warfarin for six weeks to three months. Recently published guidelines recommend that anticoagulation should be considered and continued for six weeks to three months in neonates with acute cerebral sinovenous thrombosis.8

Follow-up imaging should be performed six weeks after starting anticoagulation to assess recanalisation. If complete, treatment should be stopped, otherwise anticoagulation should be continued for a total of three months.13 14

Anticonvulsant treatment is considered reasonable even after a single seizure because recurrent seizures increase the risk of anoxic damage to the brain.15

Although early seizures are present in most patients, only about 10% of patients have epilepsy after cerebral sinovenous thrombosis.16

Along with early symptomatic seizures, a haemorrhagic lesion on admission brain scan and paresis are considered to be risk factors for the development of epilepsy after cerebral sinovenous thrombosis.17

Although there is no clear consensus on the length of anticonvulsant treatment, European Federation of Neurological Societies guidelines recommend prolonged treatment with anticonvulsants for one year when risk factors for post-ictal epilepsy are present. In patients without these risk factors, treatment may be tapered off gradually after the acute stage.18

Patient outcome

Subcutaneous low molecular weight heparin was started after diagnosis. Her neurology improved over the course of a week and has remained normal at one month; we plan to repeat her neuroimaging after six to eight weeks. The results of investigations into a possible prothrombotic tendency in the family are so far normal.

Notes

Cite this as: BMJ 2012;345:e6003

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.

References

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