Neonatal Seizures Sanjay Wazir Pandita

Neonatal Seizures Identification and Treatment : 

Neonatal Seizures Identification and Treatment Sanjay Wazir Pandita NICU, Medway Martime Hospital, Gillingham,Kent February, 2010

Slide 2: 

D3 jerky movements of left arm and leg for 30 sec noted by parents.3 episodes in 24 hrs.Midwife noted jerky movements for 2 min.Transferred to NICU. CLD,Ventricular dilatation,rec episodes of stifness of body and desaturation and bradycardia Pierre Robin Sequence - episodes of stiffness of body HIE recurrent clinical and electrical fits within 4h GBS sepsis and meningitis with refractory seizures

Slide 3: 

Stereotypic paroxysmal alteration in neurological function- motor behaviour autonomic

Slide 4: 

Seizure type Occurs in Clinical signs Subtle Preterm and Term Ocular Oral-facial-lingual Limb movements Autonomic/Apnoea Tonic Primarily Preterm Focal or generalized Tonic extension or flexion of limbs Clonic Primarily term Focal or multifocal Fast and slow component Myoclonic Rare Focal, Multifocal, or Generalized Lightning-like jerks of extremities Upper> Lower

Slide 5: 

Normal Neonatal Motor Activity AWAKE OR DROWSY Roving eye movements, with occasional nonsustained nystagmus at the extremes of horizontal movement (contrast with fixed, tonic horizontal deviation of eyes with or without jerking -subtle seizure) Sucking movements not accompanied by ocular fixation or deviation Benign Neonatal Sleep Myoclonus NREM Abolished on arousal, EEG normal

Slide 6: 

Jitteriness Versus Seizure CLINICAL FEATURE JITTERINESS SEIZURE Abnormality of gaze or eye Nil + movement Movements exquisitely stimulus + Nil sensitive Predominant movement Tremor Clonic jerking Movements cease with passive + Nil flexion Autonomic changes Nil + ------------------------------------------------------------------------------------------------------------------

Classification of Neonatal Seizures : 

Classification of Neonatal Seizures Epileptic seizures Non-epileptic seizures Electrographic seizures

Why do neonatal seizures have such unusual presentations? : 

Why do neonatal seizures have such unusual presentations? Dendritic and axonal ramifications—in process Synaptogenesis not complete Deficient myelination in cortical efferent systems

Neonatal Brain Physiology : 

Neonatal Brain Physiology High NMDA and AMPA receptor levels Altered composition of NMDA and AMPA to favour excitation Excitatory action of GABA Prolonged action potential due to low level of Na K ATPase Excitatory synapses develop before inhibitory Delayed dev of substantia nigra for inhibition of seizures Delayed maturation of post synaptic inhibition

SEIZURE RECOGNITION CLINICALLY : 

SEIZURE RECOGNITION CLINICALLY Normal sleep awake pattern Benign sleep myoclonus Environmental restriction Medication Motor and autonomic behaviour normal

Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures D M Murra, G B Boylan, I Ali, C A Ryan, B P Murphy Arch Dis Child Fetal Neonatal Ed 2008;93 : 

Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures D M Murra, G B Boylan, I Ali, C A Ryan, B P Murphy Arch Dis Child Fetal Neonatal Ed 2008;93 Background: Neonatal seizures are often subclinical, making accurate diagnosis difficult. Objective: To describe the clinical manifestations of electrographic seizures recorded on continuous video-EEG, and to compare this description with the recognition of clinical seizures by experienced neonatal staff. Methods: 51 Term infants, at risk of seizures,video-EEG from <6 hrs -72hr All clinical seizures were recorded by experienced neonatal staff. Video-EEG recordings were subsequently analysed and compared with the seizures clinically suspected by the neonatal staff.

Slide 12: 

Results: N= 51 9 had electrographic seizures. A further three had clinically suspected seizures, without associated electrographic abnormality. 526 episodes of electrographic seizures. 179 (34%) fits on video Staff documented 177 fits. Out of 177 seizures 48 had corresponding electrical seizures. Thus, only 9% (48/526) of electrographic seizures were accompanied by clinical manif, which were identified by staff Two-thirds of electrical fits picked on video are unrecognized, or misinterpreted by experienced neonatal staff.

Non-expert use of the cerebral function monitor for neonatal seizure detectionJ Rennie, G Chorley, G Boylan, R Pressler : 

Non-expert use of the cerebral function monitor for neonatal seizure detectionJ Rennie, G Chorley, G Boylan, R Pressler Arch Dis Child Fetal Neonatal Ed. 2004 Jan; 89(1): N:19 infants with seizures and 21 without. Sensitivity for individual seizure detection to be 38%–55% Approximately half of all neonatal seizures may be missed using CFM alone. The CFM may then be useful for long term monitoring.

Sensitivity of Amplitude-Integrated Electroencephalography for Neonatal Seizure Detection : 

Sensitivity of Amplitude-Integrated Electroencephalography for Neonatal Seizure Detection PEDIATRICS Vol. 120 No. 4 Oct 2007, pp. 770-777 Neonatologists with the most aEEG experience identified 38% of all of the individual seizures. Neonatologists, with 1 year of aEEG experience, detected as few as 12% of individual seizures Many neonatal seizures are difficult to detect on an aEEG, especially when they are infrequent, brief, or of low amplitude.

Treatment : 

Treatment ? Resuscitation ? Primary cause  Glucose /Ca/Mg Anticonvulsants ( no randomised trails ) When to start - > 3 mins / > 3/hr, early in HIE, Phenobarbitone has cerebral protection effect Reassess before maintenance dose Continue for 48 hrs after last fits, also depends on the cause, neurological state & risk of recurrence 1. Phenobarbitone – Upto 40 mg/kg IV & 3.0 mg/kg/dose bd 2. Clonazepam – 100mcg/kg IV over 30 sec & 50 - 100 mcg/kg 12-24 hrly 3. Phenytoin - 20 mg/kg over 20 mins 4. Valproate – 20 mg/kg & 10mg/kg/dose b.d 5. Paraldehyde – 0.2 ml/kg PR (100 mg/kg/hr IV 5%solution – pneumonitis, hepatic necrosis) 6. Pyridoxine – 100mg IV slow bolus (C*) 7. Lignocaine – 2 mg/kg & 6mg/kg/hr infusion (useful in HIE, can cause arrhythmia) (C*) Use in above order and Consultant should be informed if step 3 & onwards is indicate

Slide 16: 

Antiseizure drug–enhanced Na+ channel inactivation. Phenytoin/Topiramate/ Prolong the inactivation of the Na+ channels, thereby reducing the ability of neurons to fire at high frequencies.

Slide 17: 

Enhanced GABA synaptic transmission.In the presence of GABA, the GABAA receptor is opened, allowing an influx of Cl–, which in turn increases membrane polarization Some antiseizure drugs act by reducing the metabolism of GABA. Others act at the GABAA receptor, enhancing Cl– influx in response to GABA.

Slide 18: 

Seizures AEDs Etiology Neurodev

Do neonatal seizures cause brain injury? : 

Do neonatal seizures cause brain injury? NORMAL BRAIN: Most animal studies suggest immature healthy brain is resistant to seizure induced neuronal injury. Morphological changes in hippocampal neurons METABOLICALLY COMPROMISED BRAIN: In asphyxia and hypoglycaemia seizure induced brain damage is increased Increased hippocampal injury with HIE Learning and cognitive impairment More vulnerable to status epilepticus in later life.

Do AEDs cause brain damage? : 

Do AEDs cause brain damage? Phenobarbitone : Inhibition of brain growth and neuronal toxicity. Behavioural and Cognitive effects in adult life Phenytoin: Neuronal death due to apoptosis.

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.Painter MJ, Scher MS, Stein AD, Armatti S et al : 

Phenobarbital compared with phenytoin for the treatment of neonatal seizures.Painter MJ, Scher MS, Stein AD, Armatti S et al N Engl J Med. 1999 Aug 12;341(7):485-9 1990-1995 , total of 59 neonates electroclinical seizures Phenobarbitone:13/30 neonates(43%) Phenytoin:13/29 neonates(45%) Phenobarb+Phenytoin:17(57%) Phenytoin+Phenobarb:18(62%)

Anticonvulsants for Neonates with Seizures Cochrane Database of Systematic Reviews, Issue 4, 2004 : 

Anticonvulsants for Neonates with Seizures Cochrane Database of Systematic Reviews, Issue 4, 2004 Background Most neonates with seizures are treated with anticonvulsants. There is wide variation in clinical practice in both diagnosis and treatment of such seizures.The routine use of anticonvulsants to treat seizures in neonates needs to be evaluated.Objectives To assess and compare (with respect to benefits and harm) different anticonvulsants administered to neonates for the treatment of established seizures.

Slide 23: 

Main results Only two randomised controlled trials Painter 1999 showed phenobarbital and phenytoin were similarly effective controlling seizures in less than fifty percent of infants. Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004 randomised infants who failed to respond to phenobarbital to receive either lidocaine or midazolam as second-line agents. There was a trend for lidocaine to be more effective in reducing seizure burden but both groups had similarly poor long term outcomes assessed at one year.

Slide 24: 

CONCLUSION There is little evidence from RCT to support the use of any of the anticonvulsants currently used in the neonatal period. Whether seizures should be treated because of the concern that seizures in themselves may be harmful, is only supported by relatively low grade evidence

Comparison of continuous drip of midazolam or lidocaine in the treatment of intractable neonatalseizures Shany E, Benzaqen O, Watemberg N( Israel) Child Neurol. 2007 M : 

Comparison of continuous drip of midazolam or lidocaine in the treatment of intractable neonatalseizures Shany E, Benzaqen O, Watemberg N( Israel) Child Neurol. 2007 M 30 infants 22 8 Lignocaine Miazolam 17/22( 77%) 4/8(50%) 20 HIE 2: 18/20( 90%) 10 HIE 3: 3/10 (30%)

Approach to seizures in the neonatal period: a European perspective.Vento M, de Vries LS, Alberola A et al Acta Paediatr.Jan,2010 : 

Approach to seizures in the neonatal period: a European perspective.Vento M, de Vries LS, Alberola A et al Acta Paediatr.Jan,2010

Slide 27: 

Questionnaire Phenobarbital is still considered the initial drug of choice,followed by benzodiazepines. In refractory seizures, the use of continuous lidocaine infusion is most common. Amplitude-integrated electroencephalography is a valuable tool for diagnosis and evaluation of treatment response.  Newer drugs (topiramate, levetiracetam, and bumetanide) are currently being evaluated.

Prognosis : 

Prognosis Two most useful approaches in utilizing outcome EEG Recognition of the underlying neurological disease

Prognosis : 

Prognosis EEG BACKGROUND NEURO SEQ Normal 10 Severe abnormalities 90 Moderate abnormalities ~50 Electroencephalogy Clin Neurophysiol 60:183-196, 1985; Lombroso CT

Summary : 

Summary Any repetitive stereotyped movement can be seizure EEG is important in defining seizures Conventional anticonvulsants are ineffective in >50% Exposure neonatal brain to multiple anticonvulsants causes neuronal death Future research is needed to evaluate more effective anticonvulsants

Slide 31: 

Thank You