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content:neonatal_seizures [2020/02/23 12:53] – [Duration] icnacontent:neonatal_seizures [2022/04/30 11:32] (current) – changed pubmed syntax administrator@icnapedia.org
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   * Neonatal epileptic seizures occur from birth to the end of the neonatal period.   * Neonatal epileptic seizures occur from birth to the end of the neonatal period.
   * The neonatal period is defined as the first 28 days of life of a full-term infant.   * The neonatal period is defined as the first 28 days of life of a full-term infant.
-  * Most neonatal seizures are acute (pro-voked, occasional, reactive) symptomatic seizures caused by an acute illness such as hypoxic–ischaemic encephalopathy, stroke or infection.+  * Most neonatal seizures are acute symptomatic seizures caused by an acute illness such as hypoxic–ischaemic encephalopathy, stroke or infection.
   * seizures are the most common and important sign of acute neonatal encephalopathy   * seizures are the most common and important sign of acute neonatal encephalopathy
   * neonatal seizures are a major risk for death or subsequent neurological disability and, by themselves, may contribute to an adverse neuro-developmental outcome.   * neonatal seizures are a major risk for death or subsequent neurological disability and, by themselves, may contribute to an adverse neuro-developmental outcome.
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 ===== Classification ===== ===== Classification =====
  
-  * The ILAE Commission (1989)[(:cite:2502382>{{pubmed>2502382}})] broadly classifies the neonatal seizures among ‘epilepsies and syndromes undetermined as to whether they are focal or generalised’ under the subheading ‘with both generalised and focal seizures’ +  * The ILAE Commission (1989)[(:cite:2502382>{{pmid>2502382}})] broadly classifies the neonatal seizures among ‘epilepsies and syndromes undetermined as to whether they are focal or generalised’ under the subheading ‘with both generalised and focal seizures’ 
-  * In the ILAE (2010)[(:cite:20196795>{{pubmed>20196795}})] revised classification neonatal seizures are no longer regarded as a separate entity.+  * In the ILAE (2010)[(:cite:20196795>{{pmid>20196795}})] revised classification neonatal seizures are no longer regarded as a separate entity.
  
 ===== Clinical features ===== ===== Clinical features =====
  
-Five main types of seizures are recognised[(:cite:2671912>{{pubmed>2671912}})]+Five main types of seizures are recognised[(:cite:2671912>{{pmid>2671912}})]
     * subtle seizures (50%)     * subtle seizures (50%)
     * tonic seizures (5%)     * tonic seizures (5%)
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 **Myoclonic seizures** **Myoclonic seizures**
   * rapid, single or arrhythmic repetitive jerks. They may affect a finger, a limb or the whole body. They may mimic Moro reflex and startling responses   * rapid, single or arrhythmic repetitive jerks. They may affect a finger, a limb or the whole body. They may mimic Moro reflex and startling responses
-  * more frequently in pre-term than in full-term infants indicating, if massive, major brain injury and poor prognosis[(:cite:7124705>{{pubmed>7124705}})].+  * more frequently in pre-term than in full-term infants indicating, if massive, major brain injury and poor prognosis[(:cite:7124705>{{pmid>7124705}})].
   * healthy pre-term and, although rarely, full-term neonates may have abundant myoclonic movements during sleep   * healthy pre-term and, although rarely, full-term neonates may have abundant myoclonic movements during sleep
   * Neonates have cortical, reticular and segmental types of myoclonus, similar to adult forms (Scher, 1985).   * Neonates have cortical, reticular and segmental types of myoclonus, similar to adult forms (Scher, 1985).
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   * autonomic ictal manifestations commonly occur with motor manifestations in 37% of subtle seizures   * autonomic ictal manifestations commonly occur with motor manifestations in 37% of subtle seizures
   * paroxysmal changes of heart rate, respiration and systemic blood pressure, salivation, pupillary changes   * paroxysmal changes of heart rate, respiration and systemic blood pressure, salivation, pupillary changes
-  * Apnoea, as an isolated seizure phenomenon unaccompanied by other clinical epileptic features, is rare[(:cite:7124705>{{pubmed>7124705}})]+  * Apnoea, as an isolated seizure phenomenon unaccompanied by other clinical epileptic features, is rare[(:cite:7124705>{{pmid>7124705}})]
    
  
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   * suppression–burst pattern in neonatal epileptic encephalopathies[{{ :content:ch5f4.jpg?direct&100|suppression-burst pattern}}]   * suppression–burst pattern in neonatal epileptic encephalopathies[{{ :content:ch5f4.jpg?direct&100|suppression-burst pattern}}]
     * relatively common in neonatal period     * relatively common in neonatal period
-    * can be induced by drugs[(:cite:11727229>{{pubmed>11727229}})]+    * can be induced by drugs[(:cite:11727229>{{pmid>11727229}})]
     * usually transient in ischemic encephalopathy     * usually transient in ischemic encephalopathy
     * stable lasting for more than 2 weeks in [[content:ohtahara_syndrome|Ohtahara syndrome]] and [[early myoclonic encephalopathy]]     * stable lasting for more than 2 weeks in [[content:ohtahara_syndrome|Ohtahara syndrome]] and [[early myoclonic encephalopathy]]
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 **Stimulus-evoked electrographic patterns** **Stimulus-evoked electrographic patterns**
   * electrographic seizures are elicited by tactile or painful stimulation (with or without concomitant clinical ictal manifestations)   * electrographic seizures are elicited by tactile or painful stimulation (with or without concomitant clinical ictal manifestations)
-  * represent an abnormal form of cortical reactivity to sensory stimuli in the developing brain[(:cite:9546495>{{pubmed>long:9546495}})]+  * represent an abnormal form of cortical reactivity to sensory stimuli in the developing brain[(:cite:9546495>{{pmid>long:9546495}})]
   * most neonates with these patterns have significant diffuse or multifocal damage to the neocortex   * most neonates with these patterns have significant diffuse or multifocal damage to the neocortex
  
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   * clinical component of a seizure occurs at times with or without an electrical correlate   * clinical component of a seizure occurs at times with or without an electrical correlate
   * ‘decoupling response’ - commonly seen after starting AEDs where AEDs may suppress the clinical manifestations of seizures but not the EEG ictal discharge   * ‘decoupling response’ - commonly seen after starting AEDs where AEDs may suppress the clinical manifestations of seizures but not the EEG ictal discharge
-  * may arise from foci not consistently echoed by surface electrodes[(:cite:1764139>{{pubmed>1764139}})] +  * may arise from foci not consistently echoed by surface electrodes[(:cite:1764139>{{pmid>1764139}})] 
 +==== Differential diagnosis ==== 
 +  * [[hyperekplexia]] 
 +  * [[benign neonatal sleep myoclonus]] 
 +  * [[Benign Non-Epileptic Myoclonus of Early Infancy]] ([[benign non-epileptic infantile spasms]]) 
 +    * paroxysmal, non-epileptic movement disorder of otherwise healthy infants who have normal EEG and development[(:cite:889296>{{pmid>889296}})][(:cite:889296>{{pmid>889296}})][(:cite:10937134>{{pmid>10937134}})][(:cite:11292215>{{pmid>11292215}})] 
 +    * ‘benign non-epileptic infantile spasms’ is descriptively more accurate than myoclonus[(:cite:3960282>{{pmid>3960282}})]  
 +    * thought to be the same condition as ‘shuddering attacks’[(:cite:11118798>{{pmid>11118798}})].
 ==== Prognosis ==== ==== Prognosis ====
   * depends on the underlying cause[(:cite:panayitopoulos2005>Panayiotopoulos CP. (2005). **The Epilepsies: Seizures, Syndromes and Management**. Oxfordshire (UK): Bladon Medical Publishing)]   * depends on the underlying cause[(:cite:panayitopoulos2005>Panayiotopoulos CP. (2005). **The Epilepsies: Seizures, Syndromes and Management**. Oxfordshire (UK): Bladon Medical Publishing)]
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     * EEG persistence of immature patterns     * EEG persistence of immature patterns
     * Frequent or prolonged clonic seizures and clonic status epilepticus     * Frequent or prolonged clonic seizures and clonic status epilepticus
 +
 +==== Management ====
 +=== Investigations ===
 +  * Neuroimaging
 +    * CT, MRI, Cranial USS
 +  * EEG
 +  * Blood tests
 +  * CSF studies
 +
 +=== Treatment ===
 +{{page>template:sectionupdate}}
 +There is limited evidence regarding the best pharmacologic treatment for neonatal seizures. World Health Organisation recommends electrographic seizures should be treated in the same way as clinical seizures[(:cite:who2011>World Health Organisation . Guidelines on neonatal seizures. Geneva: World Health Organisation; 2011)].
 +
 +  * **phenobarbital**
 +    * often recommended as first-line treatment[(:cite:16777818>{{pmid>16777818}})]
 +    * recommended as first line treatment in the UK[(:cite:25824891>{{pmid>25824891}})] 
 +    * included in RCTs of first-line treatment of neonatal seizure
 +    * most studied anti-epileptic medication in animals
 +    * historical precedence as the first-line antiepileptic drug for neonates
 +    * extremely limited evidence on the effect of phenobarbital on long-term neonatal neurodevelopment
 +    * U.S. Food and Drug Administration (FDA) has never approved phenobarbital for use in any patient population[(:cite:17342837>{{pmid>17342837}})]
 +    * animal studies have raised concerns that neonatal phenobarbital exposure induces neuronal apoptosis, disruption of synaptic development in the striatum, and other behavioral deficits[(:cite:29315524>{{pmid>29315524}})]
 +  * **Levetiracetam**
 +    * effective as second-line treatments for neonatal seizures that are unresponsive to phenobarbital
 +    * FDA-approved for children as young as one-month of age[(:cite:fda>U.S. Dept. of Health and Human Services. [cited 2012 Oct 5];Food and Drug Administration Center for Drug Evaluation and Research. Application Number NDA 21505/S-026 [Internet] Available from: http://www.accessdata.fda.gov)]
 +    *  efficacy and safety profile has not been adequately studied in term or preterm neonates within the first month of life
 +    * current literature suggests loading doses of 10 to 20 mg/kg are appropriate and effective in neonates, with a maintenance dose range of 10 to 80 mg/kg/day divided twice daily[(:cite:25964725>{{pmid>25964725}})]
 +    * dosing of 40–50mg/kg bolus has also been suggested [(:cite:21397167>{{pmid>21397167}})]
 +    * a recent open labelled RCT (Level III neonatal unit; 100 neonates) used Levetiracetam (20 mg/kg) or Phenobarbitone (20 mg/kg) intravenously and concluded that Levetiracetam achieves better control than Phenobarbitone for neonatal clinical seizures when used as first-line antiepileptic drug, and is not associated with adverse drug reactions[(:cite:31477643>{{pmid>31477643}})]
 +  * phenytoin/fosphenytoin
 +    * effective as second-line treatments for neonatal seizures that are unresponsive to phenobarbital
 +    * requires frequent blood-level monitoring
 +    * erratic oral absorption & needs 6-8hrly oral dosing
 +  * **lidocaine**
 +    * effective as second-line treatments for neonatal seizures that are unresponsive to phenobarbital.
 +    * narrow therapeutic window and the potential to cause cardiac arrhythmias or hypotension
 +    * can induce seizures at high doses
 +    * may be considered in status epilepticus if phenytoin was no previously given
 +  * Benzodiazepines (midazolam)
 +    * sedation is a serious side effect
 +    * may be considered as a second- or third-line therapy choice, especially in already intubated neonates
 +
 +Other considerations
 +  * consider pyridoxine challenge when other antiepileptics provide no response
 +  * minimal data for many antiepileptics including topiramate, which is being increasingly used in neonates
 +  * steroids and / or [[vigabatrin]] are considered in epileptic spasms
 +  * Low-dose carbamazepine (CBZ) should be considered as first-line treatment for benign familial neonatal epilepsy (BNFE), even in cases of status epilepticus[(:cite:27888506>{{pmid>27888506}})]
 +  * there is equipoise on levetiracetam vs phenobarbitone as first line treatment[(:cite:31992265>{{pmid>31992265}})]
 +  * The 2011 World Health Organization (WHO) guidelines for neonatal seizures[(:cite:who2011)] and the 2010 Queensland Maternity and Neonatal Clinical Guidelines for neonatal seizures[(:cite:queensland2013>Queensland Department of Health. Queensland Clinical guidelines. Translating evidence into best clinical practice: maternity clinical guidelines. http://www.health.qld.gov.au/qcg/html/publications.asp#Neonatal. Accessed March 10, 2013)] recommend phenobarbital as the first-line agent for treatment of neonatal seizures, followed by phenytoin, and then benzodiazepines
 +
 +
 +
 +
 ===== References ===== ===== References =====
 ~~REFNOTES cite~~ ~~REFNOTES cite~~
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