Neonatal Seizures Clinical Guideline V1.0 September 2020

Neonatal Seizures Clinical Guideline

V1.0

September 2020

Neonatal Seizures Clinical Guideline V1.0 Page 2 of 15

Summary

Possible Seizures 1. Admit to NNU 2. ABC 3. Measure glucose

Initial Treatment 1. ABC 2. IV cannulation 3. First line investigations 4. Give antibiotics +/- Aciclovir 5. Initiate CFM monitoring

Evaluate History and Examination

Use section 2 to evaluate seizures

Treat seizures if they are Over 3 minutes

Greater than 3 seizures per hour

Associated dysautonomia

Consider treating electrical seizures As per treatment algorithm


Add Biotin (available as tablets that can be crushed. Order from pharmacy) and Calcium folinate (IV available from pharmacy or emergency cupboard) after

d/w neurology / metabolic team

Pyridoxine Trial Intravenous 100mg

2 doses – 2 hours apart

Phenobarbitone CD Intravenous: 20mg/kg

Loading dose over 20 minutes

Midazolam CD IV loading 150-200 microgram/kg

Then infusion 60 microgram/kg/hour adjusted according to response (Beware can make seizures worse)

Phenytoin Intravenous: 20mg/kg


Levetiracetam Intravenous: 40mg/kg


Phenobarbitone CD Intravenous: 10mg/kg

Aim to get Phenobarbitone level to ~40mcg/mL

If hypotensive/unstable/Concerns

about IV access

If seizure continues



Treat underlying Symptomatic cause Consider HIE, Hypoglycaemia, Metabolic, Sepsis, Drug withdrawal

Consider Lidocaine / Hypothermia / Phenobarbital coma

Valproate can be used if metabolic seizure disproven


Inform PNTS team


1. Aim/Purpose of this Guideline

Seizures are the commonest clinical manifestation of neurological dysfunction in neonates. The estimated incidence is 1.5 - 5.5 per 1000 births in term infants; however this is higher in preterm infants. ~85% of seizures in neonates are symptomatic in origin occurring secondary to an identifiable aetiology. Prompt diagnosis of the cause is important as this can help target the most appropriate approach to management

2. The Guidance

2.1. Aetiology

The commonest causes of ‘symptomatic’ seizures in neonates are; hypoxic ischaemic encephalopathy, infarctions, intracranial infection, hypoglycaemia, inborn errors of metabolism and structural malformations. The other 6-10% comprise of the neonatal epilepsy syndromes such as early myoclonic encephalopathy and self-limited neonatal seizures.

2.2. Recognition

Clinical diagnosis of neonatal seizures is difficult; paroxysmal events are misdiagnosed as epileptic in ~50% of cases. A seizure is defined as a transient occurrence of symptoms and / or signs due to abnormal excessive or synchronous neuronal activity within the brain. Several different seizure types can exist in neonates (See Table 1 on next page).

Data Protection Act 2018 (General Data Protection Regulation – GDPR) Legislation

The Trust has a duty under the DPA18 to ensure that there is a valid legal basis to process personal and sensitive data. The legal basis for processing must be identified and documented before the processing begins. In many cases we may need consent; this must be explicit, informed and documented. We cannot rely on opt out, it must be opt in.

DPA18 is applicable to all staff; this includes those working as contractors and providers of services.

For more information about your obligations under the DPA18 please see the Information Use Framework Policy or contact the Information Governance Team [email protected]

mailto:[email protected]


Table 1. The ILAE classification of neonatal seizures types. Type & frequency Clinical signs 12 lead EEG findings

Automatisms Coordinated motor activity mimicking a voluntary movement. Typically oral with other features. For example leg cycling.

Variable correlation. Can require more than one EEG. Easily mistaken for non-seizure activity.

Tonic Sustained stiffening & posturing of limbs/trunk. Can include deviation of head or eyes.

Variable correlation. Generalised tonic posturing is rarely epileptic in origin.

Clonic Rhythmic jerking at 1-4Hz. Can be unifocal or multifocal and symmetrical or asymmetrical.

Correlation high, especially if unifocal.

Myoclonic ‘Shock like’ jerking usually in the flexor muscle groups. Can be single or multiple.

Difficult to differentiate from non-epileptic myoclonus.

Epileptic Spasm Sudden flexion, extension or predominantly proximal and truncal muscle groups.

Can be difficult to differentiate between myoclonic seizures.

Autonomic A distinct alteration in autonomic nervous system function. Can involve pupils / cardiovascular / gastrointestinal / vasomotor and thermoregulation.

Can present at apnoea. Typically seen alongside other seizure types.

Behavioural arrest A sudden pause in activities. Freezing or immobilisation of movements.

May have other autonomic features.

Unclassified Unusual clinical features or inadequate description.

Poor EEG correlation.

2.3. Evaluation - (Resuscitation if needed should always be the priority)

2.3.1. History

Take a thorough birth history to include:

Gestational age

Pregnancy complications (Gestational diabetes / infection / Growth

restriction)

Maternal drug use including recreational.

Risk factors for infection (See infection guideline)

Labour + delivery (?Instrumentation / trauma)

Does baby meet criteria A for therapeutic cooling?

Is there a family history of seizures or metabolic conditions?

2.3.2. Seizure description

It is important that a description (semiology) of the paroxysmal event is documented in the notes by the witness. This should include: the type of movement seen and limbs involved, the onset and offset of movements, frequency + symmetry of movements, duration of movements, any eye or head deviation (versive) movements and association of movements with sleep.


An attempt to hold the limb and the response to this action should be documented. This is because seizures are highly unlikely to modify or stop with simple restraint.

2.3.3. Examination

Observations should be performed including: Temperature / BP / HR / Saturations / RR. A thorough examination should be completed of all systems but to include the following key areas:

Examination area Specific diagnostic signs and considerations

Head Circumference

Macrocephaly - Hydrocephalus / megalencephaly

Microcephaly - Congenital CNS infections / Cerebral malformations

Sutures and anterior fontanelle -Hydrocephalus and meningoencephalitis

Skin

Vesicular lesions - Consider HSV infection / Incontinentia pigmenti

Ash leaf macule - Tuberous sclerosis (Use Woods lamp)

Port wine stain - Consider Sturge-Weber syndrome

Blueberry Muffin skin - Consider congenital Rubella

Ophthalmology Absent red reflex - Retinoblastoma or Cataracts

Coloboma - Associated with absent Corpus Callosum

Dysmorphology Mid facial hypoplasia (Cleft palate, Hypotelorism) Cerebral dysgenesis

Multiple congenital abnormalities - Consider genetic diagnosis

Neurological status

Hypotonia / Jittery / Poor suck / reduced neonatal reflexes - HIE

Reduced response + other concerning features - Severe systemic disease

2.3.4. Investigations

A set of first line investigations are required to try to understand the underlying seizure aetiology. Supplementary investigations may be requested based on results from the first line investigations or at the discretion of the consultant neonatologist / paediatric neurologist.

Investigation type First line investigations Supplemental investigations.

Blood

U+E, Lab Glucose, Blood gas, Bone profile, Magnesium, Liver function tests, Lab lactate, FBC,

Coagulation screen, Blood culture, Blood Herpes PCR

Ammonia, TORCH screen, Acylcarnitines, Amino acids,

Biotinidase, Carbohydrate deficient transferrin, Carnitine profile.

Urine Consider a toxicology screen Organic acids, 5-Alpha aminoadipic

semialdehyde (5-AASA)

Cerebrospinal fluid (When safe to

undertake)

Glucose, Protein, Microscopy + Culture, Viral PCR

Lactate, Amino acids, Neurotransmitters.

Neuroimaging Cranial ultrasound Cranial MRI

Neurophysiology Cerebral function monitor + Consider departmental EEG

Departmental EEG


2.3.5. Monitoring of seizure

2.3.5.1. Clinical monitoring

Nursing staff and medical staff should document any abnormal movements or concerns about autonomic features on the neonatal seizure record sheet (See Appendix 3)

2.3.5.2. Cerebral function monitor (CFM; also known as Amplitude

integrated EEG (aEEG))

aEEG should be started if a seizure disorder is suspected; this is especially so in the paralysed infant as clinical seizures will be supressed.

Seizures normally present as an abrupt transient rise in the lower margin. Often accompanied by a smaller rise in the upper margin; hence narrowing of the bandwidth.

Due to limited electrode channels it is not possible to identify the locus of abnormal electrical activity as well as frequency and duration of seizures. Focal or brief seizures may also not be identified on CFM.

2.3.5.3. Departmental EEG

An EEG can be useful in confirming seizures and looking at the background cortical activity. Video EEG’s are useful when neurological signs are subtle and in neonates who are sedated. They can aid with locating the origin of the seizure. Their sensitivity is higher than aEEG but they may still miss seizures originating from deeper structures.

The neurophysiology scientists are an excellent resource if there are any questions about suitability for EEG.

2.4. Treatment

2.4.1. Inform the on-call consultant of the possibility of seizures.

2.4.2. It is important to firstly consider and treat underlying aetiologies which cause

symptomatic seizures.

1. Correct blood glucose (See hypoglycaemia guideline).

2. Give antibiotics and consider anti-virals if meningoencephalitis is likely.

3. Correct underlying metabolic / electrolyte abnormalities.

2.4.3. The infant should be nursed in an environment that minimises all sensory stimulation.


2.4.4. There is no consensus on when to initiate treatment for seizures. Consider treatment in the following scenarios.

1. A single seizure lasting > 3 mins or greater than 3 seizures per

hour. 2. Treat if signs of dysautonomia are present e.g cardiovascular

compromise. 3. Consider treating electrographic seizures only to reduce seizure

burden.

2.4.5. Be prepared to give respiratory support when initiating anticonvulsant therapy.

2.4.6. Treatment algorithm

See summary sheet for treatment algorithm

2.5. Antiepileptic choice + monitoring

Phenobarbitone (also known as phenobarbital):- Is the most studied anti-

epileptic in neonates. It has a more predictable metabolism and is more cardiovascularly stable than Phenytoin 7. Phenobarbitone can be sedating and therefore cause electroclinical dissociation (Clinical seizure reduces but continues electrographically). Measure levels after 12 hours and aim for a level of ~40mg/l.

Phenytoin:- Phenytoin is used as a second line and should be used if the child has a stable cardiovascular system. Due to its variable metabolism phenytoin should not be used for a prolonged period. Measure a level after 12 hours; levels should be 8-16mg/l. Levels are likely to be higher in therapeutically cooled infants and therefore maintenance doses are best avoided.

Levetiracetam:- Limited data but case series have not identified major adverse side effects. 7,8

Lidocaine:- In the only randomised controlled trial of Lidocaine in neonatal seizures it had a response rate of 70%. There is a narrow therapeutic window and in therapeutic hypothermia a dose modification is required. It should also not be used after Phenytoin to reduce chances of arrhythmias. The dosage schedule changes depending if the infant is preterm of term. The dosing schedule is found in the neonatal formulary.

Midazolam:- Benzodiazepines act on the GABA receptors. It is understood that the developing brain may have an excitatory response to benzodiazepines rather than the preferred inhibition. Because of this effect doctors should be aware of the potential of Midazolam making seizures worse and therefore preferential consideration of Lidocaine infusion should be thought about early. Some evidence suggests that midazolam can work synergistically with Lidocaine.

Sodium Valproate:- Sodium valproate has some restrictions to its use due to the potential to cause severe hepatotoxicity in unrecognised metabolic disorders e.g mitochondropathies. Other side effects can include pancreatitis /


thrombocytopenia / neutropenia. Therefore experience in the neonatal period is highly limited 5. However, it is useful in the term neonate with generalised refractory seizures where a metabolic cause is highly unlikely or disproven. Therefore, sodium valproate should be reserved for after a discussion with a paediatric neurologist.

2.6. Discontinuation of anti-epileptics

The majority of seizures in the neonatal population are symptomatic in origin. Seizure burden is highest around the time of insult and usually has a finite and short period of activity. In the context of acute symptomatic seizures discontinuing the anti-epileptics quickly when the seizures have stopped should be considered. If it is likely that there is an underlying neurometabolic syndrome precipitating the seizures then advice from the local Consultant with interest in epilepsy or Bristol Paediatric Neurology team should be sought.

2.7. Vitamin responsive seizures

Where a vitamin responsive seizure is suspected advice from the paediatric neurology team should be sought. They have a wide variability in the presentation but 40% of pyridoxine dependent seizures occur within the first 24 hours9. Nearly 40% of these infants present with evidence of hypoxic ischaemic encephalopathy, low Apgar scores and cord acidosis. They are irritable, often have low tone and have treatment refractory seizures with conventional anti-epileptics.

Investigations for vitamin responsive seizures and a therapeutic trial of vitamins should be given for refractory seizures.

A CFM or EEG should be in place before giving the vitamins as the electrographic seizures may quickly improve.

2.7.1. Pyridoxine:- 100mg Intravenous trial dose. Dose can be repeated after 2

hours 10. Can be given intravenously but be aware can cause apnoea and cerebral depression. Pyridoxine can also cause a transient drop in blood pressure so monitoring should be in place. Send a urine for 5- Alpha Amino Adipic Semialdehyde (5-AASA) which is commonly elevated in pyridoxine seizures.

2.7.2. Biotin:- Discuss with paediatric neurology team for dosage schedule.

2.7.3. Calcium Folinate (Follinic acid):- Discuss with paediatric neurology team for dosage schedule.


3. Monitoring compliance and effectiveness

Element to be monitored

Compliance with policy/Key changes to practice

Lead Dr Christopher Bell (Consultant Paediatrician and Neonatal Governance lead)

Tool Audit and review tool using WORD or Excel template

Frequency Annual

Reporting arrangements

Consultant led neonatal clinical guidelines group

Acting on recommendations and Lead(s)

Dr Chris Warren Consultant Paediatrician and Neonatologist

Change in practice and lessons to be shared

Required changes to practice will be identified and actioned within 3 months, immediately if required. A lead member of the team will be identified to take each change forward where appropriate. Lessons will be shared with all the relevant staff/stakeholders

4. Equality and Diversity

4.1. This document complies with the Royal Cornwall Hospitals NHS Trust

service Equality and Diversity statement which can be found in the 'Equality, Inclusion & Human Rights Policy' or the Equality and Diversity website.

4.2. Equality Impact Assessment The Initial Equality Impact Assessment Screening Form is at Appendix 2.

http://www.rcht.nhs.uk/GET/d10268876

http://intranet-rcht.cornwall.nhs.uk/shelf/equality-and-diversity/

http://intranet-rcht.cornwall.nhs.uk/shelf/equality-and-diversity/


Appendix 1. Governance Information

Document Title Neonatal Seizures Clinical Guideline V1.0

This document replaces (exact title of previous version):

New Document

Date Issued/Approved: July 2020

Date Valid From: September 2020

Date Valid To: September 2023

Directorate / Department responsible (author/owner):

Dr Christopher Butler (Consultant Paediatrician with Expertise in Epilepsy and Neurology Lead)

Contact details: 01872 252667

Brief summary of contents This guideline is designed to provide guidance to neonatal staff on the treatment of seizures in the neonatal period

Suggested Keywords: Neonatal, Epilepsy

Target Audience RCHT CFT KCCG

Executive Director responsible for Policy:

Medical Director

Approval route for consultation and ratification:

Neonatal Guidelines Group

General Manager confirming approval processes

Mary Baulch

Name of Governance Lead confirming approval by specialty and care group management meetings

Caroline Amukusana

Links to key external standards None required

Related Documents:

1. Management of seizures in neonates. Nottingham university Neonatal unit guideline.

2. ILAE classification of seizures and the epilepsies. Epilepsia; Pressler et al.

3. Shellhaas RA. Clinical features, evaluation, and diagnosis of neonatal seizures. Uptodate.

4. El-Dib M, Chang T, Tsuchida TN, et al. Amplitude-integrated electroencephalography in neonates. Pediatr Neurol 2009

5. Ainsworth SB. Neonatal Formulary: Drug Use in Pregnancy and the First Year of Life.

6. Slaughter LA, Patel AD, Slaughter JL. Pharmacological treatment of neonatal seizures: a systematic review. J Child Neurol 2013

7. Ramantani G, Ikonomidou C, Walter B, et al. Levetiracetam: safety and efficacy in neonatal


seizures. Eur J Paediatr Neurol 2011; 8. Fürwentsches A, Bussmann C, Ramantani G, et al.

Levetiracetam in the treatment of neonatal seizures: a pilot study. Seizure.

9. Baxter P. Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol 2001

10. Evalina London Paediatric Formulary, Online http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80#

11. Plymouth Neonatal Intensive Care neonatal seizure guideline.

Training Need Identified? Yes

Publication Location (refer to Policy on Policies – Approvals and Ratification):

Internet & Intranet Intranet Only

Document Library Folder/Sub Folder

Clinical / Neonatal

Version Control Table

Date Version

No Summary of Changes

Changes Made by (Name and Job Title)

July 2020 V1.0 Initial version

Dr Christopher Butler (Consultant Paediatrician with Expertise in Epilepsy and Neurology Lead)

All or part of this document can be released under the Freedom of Information Act 2000

This document is to be retained for 10 years from the date of expiry.

This document is only valid on the day of printing

Controlled Document This document has been created following the Royal Cornwall Hospitals NHS Trust Policy for the Development and Management of Knowledge, Procedural and Web

Documents (The Policy on Policies). It should not be altered in any way without the express permission of the author or their Line Manager.

http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80

http://cms.ubqo.com/public/d2595446-ce3c-47ff-9dcc-63167d9f4b80


Appendix 2. Initial Equality Impact Assessment

Section 1: Equality Impact Assessment Form

Name of the strategy / policy /proposal / service function to be assessed Neonatal Seizures Clinical Guideline V1.0

Directorate and service area: Child Health, Neonatal

Is this a new or existing Policy? New

Name of individual/group completing EIA Dr Christopher Butler

Contact details: 01872 252667

1. Policy Aim Who is the strategy / policy / proposal / service function aimed at?

The guideline is aimed at hospital staff responsible for the assessment and treatment of seizures on the neonatal unit.

2. Policy Objectives As above

3. Policy Intended Outcomes

To improve the well-being of patients by offering the appropriate management of epilepsy

4. How will you measure the outcome?

See section 3 above (Monitoring compliance and effectiveness)

5. Who is intended to benefit from the policy?

Patients, parents/carers and staff

6a). Who did you consult with?

b). Please list any groups who have been consulted about this procedure.

Workforce Patients Local groups

External organisations

Other

x

Neonatal Guidelines group

c). What was the outcome of the consultation?

Approved


7. The Impact Please complete the following table. If you are unsure/don’t know if there is a negative impact you need to repeat the consultation step. Are there concerns that the policy could have a positive/negative impact on:

Protected Characteristic

Yes No Unsure Rationale for Assessment / Existing Evidence

Age X

Sex (male, female non-binary, asexual etc.)

X

Gender reassignment X

Race/ethnic communities /groups

X Any information provided should be in an accessible format for the parent/carer’s needs – i.e. available in different languages if required/access to an interpreter if required

Disability (learning disability, physical disability, sensory impairment, mental health problems and some long term health conditions)

X

Those parent/carers with any identified additional needs will be referred for additional support as appropriate - i.e to the Liaison team or for specialised equipment. Written information will be provided in a format to meet the family’s needs e.g. easy read, audio etc

Religion/ other beliefs X

Marriage and civil partnership X

Pregnancy and maternity X

Sexual orientation (bisexual, gay,

heterosexual, lesbian) X

If all characteristics are ticked ‘no’, and this is not a major working or service change, you can end the assessment here as long as you have a robust rationale in place.

I am confident that section 2 of this EIA does not need completing as there are no highlighted risks of negative impact occurring because of this policy.

Name of person confirming result of initial impact assessment:

Neonatal Guidelines Group

If you have ticked ‘yes’ to any characteristic above OR this is a major working or service change, you will need to complete section 2 of the EIA form available here: Section 2. Full Equality Analysis For guidance please refer to the Equality Impact Assessments Policy (available from the document library) or contact the Human Rights, Equality and Inclusion Lead [email protected]

http://doclibrary-rcht-intranet.cornwall.nhs.uk/DocumentsLibrary/RoyalCornwallHospitalsTrust/ChiefExecutive/Templates/Section2FullEqualityAnalysis.docx

mailto:[email protected]


Appendix 3. Neonatal Seizure Chart (Pilot Form)