LES CONVULSIONS NONATALES Professeur Oreste Battisti Facult de

LES CONVULSIONS NÉONATALES Professeur Oreste Battisti Faculté de Médecine Université de Liège Battisti: Convulsions néonatales 1

Summary Seizures in the newborn period constitute a medical emergency. Subtle seizures are the commonest type of seizures occurring in the neonatal period. Other types include clonic, tonic, and myoclonic seizures. Myoclonic seizures carry the worst prognosis in terms of long term neurodevelopmental outcome. Hypoxic ischemic encephalopathy is the most common cause of neonatal seizures. Multiple etiologies often co exist in neonates and hence it is essential to rule out common causes such as hypoglycemia , hypocalcemia , meningitis before initiating specific therapy. A comprehensive approach for management of neonatal seizures is the best way for management. Battisti: Convulsions néonatales 2

Structure of presentation Introduction and epidemiology Definitions and patterns of convulsions or neonatal seizures Classification: clinical and EEG Etiology Physiopathology Treatment and follow up Battisti: Convulsions néonatales 3

Epidémiologie prévalence: 80 120 /100, 000 naissances § Incidence: 1 5/1000 § La période néonatale est particulièrement ciblée § Battisti: Convulsions néonatales 4

Causes of Neonatal Seizures and Outcomes Percent of Patients Who Have Normal Development Cause Hypoxic ischemic encephalopathy Intraventricular hemorrhage Subarachnoid hemorrhage Hypocalcemia Early onset Later onset Hypoglycemia Bacterial meningitis Developmental malformations Benign familial neonatal convulsions Fifth day fits 50 10 90 50 100 50 50 0 ~100 Battisti: Convulsions néonatales 5

Prognosis of Neonatal Seizures: Relation to Neurological Diseases Neurological Disease Normal Development Hypoxic ischemic encephalopathy 50% Intraventricular hemorrhage 10% Primary subarachnoid hemorrhage 90% Hypocalcemia Early onset 50% Later onset 100% Hypoglycemia 50% Bacterial meningitis 50% Developmental defect 0% Battisti: Convulsions néonatales 6

Prognosis in general Myoclonic seizures carry the worst prognosis in terms of neuro-developmental outcome and seizure recurrence. Focal clonic seizures have the best prognosis. Seizures due to Subarachnoid Hemorrhage and late onset hypocalcemia carry a good prognosis for long term neurodevelopmental outcome while seizures related to hypoglycemia, cerebral malformations and meningitis have a high risk for adverse outcome. A background abnormality in both term and preterm neonates indicates a high risk for neurological sequelae. These changes include burst suppression pattern, low voltage invariant pattern and electro cerebral inactivity Battisti: Convulsions néonatales 7

1. Definition, classification and patterns of neonatal: seizures convulsions epilepsy Battisti: Convulsions néonatales 8

The Definition of a Seizure “paroxysmal discharge of cerebral neurons sufficient to cause clinically detectable events that are apparent either to the subject or to an observer” Battisti: Convulsions néonatales 9

clinical patterns of seizures in newborns (Fenichel) Apnea with tonic stiffening of body Focal clonic movements of one limb or both limbs on one side Multifocal clonic limb movements Myoclonic jerking Paroxysmal laughing Tonic deviation of the eyes upward or to one side Tonic stiffening of the body Battisti: Convulsions néonatales 10

§ Why do neonatal seizures have such unusual presentations? Immature CNS cannot sustain a synchronized, well orchestrated generalized seizure

Normal Neonatal Motor Activity Commonly Mistaken for Seizure Activity AWAKE OR DROWSY Roving, sometimes dysconjugate eye movements, with occasional nonsustained nystagmoid jerks at the extremes of horizontal movement (contrast with fixed, tonic horizontal deviation of eyes with or without jerking —characteristic of subtle seizure Sucking, puckering movements not accompanied by ocular fixation or deviation SLEEP Fragmentary myoclonic jerks—may be multiple Isolated, generalized myoclonic jerk as infant wakes from sleep Volpe Neurology of the Newborn. . Battisti: Convulsions néonatales 12

Classification of Neonatal Seizures § Clinical § Electroencephalographic Battisti: Convulsions néonatales 13

Classification I. Clinical Seizure § Subtle § Tonic § Clonic § Myoclonic

Classification II. Electroencephalographic seizure § Epileptic § Non epileptic

Classification of Neonatal Seizures ELECTROENCEPHALOGRAPHIC SEIZURE CLINICAL SEIZURE COMMON UNCOMMON Subtle +* Clonic Focal + Multifocal + Tonic Focal + Generalized + Myoclonic Focal, multifocal + Generalized + -------------------------------------------------------*Only specific varieties of subtle seizures are commonly associate with simultaneous Electroencephalographic seizure activity. Volpe JJ. Neonatal Seizures: Neurology of the Newborn. 4 th ed. Battisti: Convulsions néonatales 16

Classification of neonatal seizures Seizure type Occurs in Clinical signs EEG changes Subtle Preterm and Term Eye deviation (Term) Blinking, fixed stare (Preterm) Repetitive mouth & tongue movements Apnea Pedaling, tonic posturing of limbs Usually No Tonic Primarily preterm May be focal or generalized Tonic extension or flexion of limbs (often signals severe IVH in preterm infants) Usually No Clonic Primarily term May be focal or multifocal Clonic limb movements (synchronous or asynchronous, localized or often with no anatomic order to progression) Consciousness may be preserved Often signals focal cerebral injury. Yes Myoclonic Rare Focal, multifocal, or generalized Lightning-like jerks of extremities (upper>lower) + Battisti: Convulsions néonatales 17

Classification of Neonatal Seizures § Clinical § Electroencephalographic Battisti: Convulsions néonatales 18

Neonatal Seizures Tonic Seizures focal or generalized, may mimic decorticate or decerebrate posturing, primarilyseen in preterms with intracranial hemorrhage & generally have poor prognosis Subtle seizures Consist of chewing motion, excessive salivation and alteration in respiratory rate including apnea, blinking, nystagmus, bicycling and pedaling movements, changes in color Battisti: Convulsions néonatales 19

Clonic- focal (repetitive movements localized to a single limb) or multifocal (random migration of movements from limb to limb), consciousness may be preserved, primarily seen in term infants • Myoclonic sudden flexor movements (lightning like jerks), may be focal, multifocal or generalized, may occuring singly or in clusters, if due to early myoclonic encephalopathy it carries a poor prognosis. Brief focal or generalized jerks of the extremities or body that tend to involve distal muscle groups Battisti: Convulsions néonatales 20

Clinical Classification Focal/Multifocal Clonic Not generalized Migratory Focal Tonic Generalized Myoclonic Battisti: Convulsions néonatales 21

Neonatal seizures The most common presentation is focal clonic or multifocal clonic movments. The rhythmic jerking is well localized to a limb, may migrate to other limbs, not necessarily in a contiguous fashion with the infant usually not conscious. Neonatal seizures do not manifest with generalized clonic activity. Neonatal seizures may present with focal tonic, so persistently increased tone in a limb. Generalized tonic activity, of the whole body, usually is not associated with seizure activity on EEG, but may be posturing. Then there are myoclonic seizures; myoclonus being more rapid, more erratic and non rhythmic than clonic movements. Focal or multifocal myoclonus is usually not associated with sz activity, but bilateral synchronous generalized myoclonic more likely to be seizures with the kids more likely to be sicker, and we can talk about the difference in mechanism there later as well. Other than descriptive terminology, there’s this funny classification that’s used, called “subtle” seizures, because they are. Some also classify these as “hypomotor” seizures, which may present with activity arrest, apnea, or eye deviation. The art in diagnosing these as true seizures, and not just diagnosing every bowel movement as a seizure is in looking for any associated signs, such as autonomic changes like BP or HR increase. Autonomic sx may be an isolated finding in preemies, but usually accompanies sz’s in term. The most common subtle manifestation is tonic horizontal eye deviation. Battisti: Convulsions néonatales 22

Clinical Classification Subtile (“Hypomotor”) Motor activity arrest Apnea Eye deviation Autonomic changes Motor automatisms Oral buccal lingual movements Swimming Bicycling Battisti: Convulsions néonatales 23

Subtle seizures More in preterm than in term § Eye deviation (term) § Blinking, fixed stare (preterm) § Repetitive mouth and tongue movements § Apnea § Pedaling and tonic posturing of limbs § “Tonic deviation of the eyes Repetitive fluttering of eyelids Drooling, sucking, chewing Swimming movements of the arms Pedaling movements of the legs Paroxysmal laughing » Battisti: Convulsions néonatales 24

Subtle seizures (ct) Ocular Tonic horizontal deviation of eyes or sustained eye opening with ocular fixation or cycled flutering Oral–facial–lingual movements Chewing, tongue thrusting, lip smacking, etc. Limb movements Cycling, paddling, boxing jabs, etc. Autonomic phenomena Tachycardia or bradycardia Apnea may be a rare manifestation of seizures. Apnea due to seizure activity has an accelerated or a normal heart rate when evaluated 20 seconds after onset. Bradycardia is thus not an early manifestation in convulsive apnea but may occur later due to prolonged hypoxemia. Battisti: Convulsions néonatales 25

Tonic seizures Primarily in Preterm § May be focal or generalized Sustained extension of the upper and lower limbs (mimics decerebrate posturing) § Sustained flexion of upper with extension of lower limbs (mimics decorticate posturing) § Signals severe ICH in preterm infants This type refers to a sustained flexion (mainly in premature) or extension (mainly in term) of axial or appendicular muscle groups. Resemble decerebrate (tonic extension of all limbs) or decorticate posturing (flexion of upper limbs and extension of lower limbs). Usually there are no EEG changes in generalized tonic seizures. § Battisti: Convulsions néonatales 26

Clonic Primarily in term § Focal or multifocal § Clonic limb movements(synchronous or asynchronous, localized or often with no anatomic order of progression) § Consciousness may be preserved § Signals focal cerebral injury They are rhythmic movements of muscle groups. They have both fast and slow components, occur with a frequency of 1 3 jerks per second, and are commonly associated with EEG changes. Multifocal clonic seizures on the 5 th day may be related to low zinc levels in the CSF fluid (benign idiopathic neonatal convulsions). Battisti: Convulsions néonatales 27

Myoclonic Rare § Focal, multifocal or generalized § Lightning like jerks of extremities (upper > lower) These manifest as single or multiple lightning fast jerks of the upper or lower limbs and are usually distinguished from clonic movements because of more rapid speed of myoclonic jerks, absence of slow return and predilection for flexor muscle groups. Common changes seen on the EEG include burst suppression pattern, focal sharp waves and hypsarrhythmia Battisti: Convulsions néonatales 28

Benign familial neonatal seizures Begins on the 2 nd – 3 rd day of life Seizure frequency : 10 – 20 /day Patients are normal between seizures Seizure stops in 1 – 6 months Battisti: Convulsions néonatales 29

5 th day Seizures 5 th day of life ○ normal appearing neonates with mulifocal seizures ○ Present for less than 24 hours ○ Good prognosis Battisti: Convulsions néonatales 30

Jitteriness Versus Seizure CLINICAL FEATURE JITTERINESS SEIZURE Abnormality of gaze or eye O + movement Movements exquisitely stimulus + O sensitive Predominant movement Tremor Clonic jerking Movements cease with passive flexion Autonomic changes + O + Battisti: Convulsions néonatales 31

Weird Baby Movements Jitteriness ○ Stimulus sensitive ○ “Tremor” ○ Suppressable Benign neonatal sleep myoclonus Spinal myoclonus Apnea of non neurologic etiology ○ bradycardia Battisti: Convulsions néonatales 32

Non-epileptic movements commonly confused with seizures Jitteriness or tremors Normal movements seen more commonly in preterm infants Benign neonatal sleep myoclonus: Occurs during NREM sleep in preterm infants in the first week of life. Restraint and benzodiazepines may increase the frequency of jerks, while on arousal they are usually abolished. EEG will be normal in this condition. Fragmentary myoclonic jerks Eye movements: Roving or dys conjugate eye movements with occasional non sustained nystagmoid jerks. Battisti: Convulsions néonatales 33

Classification of Neonatal Seizures § Clinical § Electroencephalographic Battisti: Convulsions néonatales 34

Electroencephalographic seizure I. Epileptic Consistently associated with electro cortical seizure activity on the EEG § Cannot be provoked by tactile stimulation § Cannot be suppressed by restraint of involved limb or repositioning of the infant § Related to hyper synchronous discharges of a critical mass of neuron §

Electroencephalographic seizures II. Non epileptic § No electro cortical signature § Provoked by stimulation § Suppressed by restraint or repositioning § Brainstem release phenomena (reflex)

Neonatal Seizures EEG Classification Clinical seizure with consistent EEG event Clinical seizure occurs in relationship to seizure activity Includes focal clonic, focal tonic and myoclonic Responds to antiepileptic drugs Clinical seizure with inconsistent EEG event Clinical seizures with no EEG abnormality Seen in all generalized tonic and subtle seizures Seen in patients who are comatose, HIE Battisti: Convulsions néonatales 37

Neonatal Seizures EEG Classification Electrical seizures with absent clinical seizures Electrical seizures associated with markedly abnormal background EEG Seen in comatose patients Battisti: Convulsions néonatales 38

Epileptic vs Non epileptic Neonatal Phenomena Clinical Characteristics Epileptic Non-epileptic Increases with Sensory stimulation Rare Common Suppresses with restraint + Autonomic Accompaniments + Battisti: Convulsions néonatales 39

Does absence of EEG seizure activity indicate that a clinical seizure is non epileptic? § Certain clinical seizures in the human newborn originate from electrical seizures in deep cerebral structures (limbic regions), or in diencephalic, or brain stem structures and thereby are either not detected by surface recorded EEG or inconsistently propagated to the surface

EEG tracing Battisti: Convulsions néonatales 42

Battisti: Convulsions néonatales 43

Exercices on movies Battisti: Convulsions néonatales 44

In addiction Battisti: Convulsions néonatales 45

Focal crisis Battisti: Convulsions néonatales 46

3. Etiology of neonatal convulsions or seizures Battisti: Convulsions néonatales 47

Etiology § It is critical to recognize neonatal seizures, to determine their etiology, and to treat them for three major reasons: 1. Seizures are usually related to significant illness, sometimes requiring specific therapy Battisti: Convulsions néonatales 48

Etiology 2. Neonatal seizures may interfere with important supportive measures, such as alimentation and assisted respirations for associated disorders. 3. Experimental data give some reason for concern that under certain circumstances the seizure per se may be a cause of brain injury. Battisti: Convulsions néonatales 49

Major Etiologies of Neonatal Seizures in Relation to Time of Seizure Onset and Relative Frequency FREQUENCY† TIME OF ONSET* RELATIVE 0 3 DAYS >3 DAYS PREMATURE FULL TERM Hypoxic ischemic + +++ +++ encephalopathy Intracranial + ++ + hemorrhage‡ Intracranial infection + ++ Developmental + ++ defects Hypoglycemia + Hypocalcaemia + + + Other metabolic + Epileptic syndromes + Battisti: Convulsions néonatales 50

Comparison of prominent etiologic diagnoses of seizures in the newborn period. (Data modified from Mizrahi and Kellaway, 1987; Rose and Lombroso, 1970) Fanaroff A, Martin R. Neonatal seizures. In: Neonatal and Perinatal Medicine, Diseases of the Fetus and Infant, 6 th ed. Battisti: Convulsions néonatales 51

Etiology Pregnancy history is important § Search for history that supports TORCH infections § History of fetal distress, preeclampsia or maternal infections § Battisti: Convulsions néonatales 52

Major Causes of Neonatal Seizures In Relation to Time of Seizure Onset and Relative Frequency TIME OF ONSET* FREQUENCY Cause Full Term 0 -3 Days Hypoxic-Ischemic encephalopathy Intracranial hemorrhage Intracranial infection Developmental defects Hypoglycemia Hypocalcemia Other metabolic Epileptic syndromes + + + + Battisti: Convulsions néonatales RELATIVE >3 Days + + + Premature +++ ++ ++ + 53

Neonatal Seizures Etiologic diagnosis Hypoxic –ischemic encephalopathy Metabolic Infections Trauma Structural abnormalities Hemorrhagic and embolic strokes Maternal disturbances Battisti: Convulsions néonatales 54

Differential diagnosis of neonatal seizures by peak time of onset 24 hours Bacterial meningitis and sepsis Direct drug effect Hypoxic ischemic encephalopathy Intrauterine infection Intraventricular hemorrhage at term Laceration of tentorium or falx Pyridoxine dependency Subarachnoid hemorrhage 24 to 72 hours Bacterial meningitis and sepsis Cerebral contusion with subdural hemorrhage Cerebral dysgenesis Cerebral infarction Drug withdrawal Glycine encephalopathy Glycogen synthase deficiency Hypoparathyroidism–hypocalcemia Idiopathic cerebral venous thrombosis Incontinentia pigmenti Intracerebral hemorrhage Intraventricular hemorrhage in premature newborns Pyridoxine dependency Subarachnoid hemorrhage Tuberous sclerosis Urea cycle disturbances Battisti: Convulsions néonatales 55

Causes of neonatal seizures Ages 1 – 4 days HIE Drug withdrawal Dug toxicity Lidocaine, penicillin Intraventricular hemorrhage Acute metabolic disorder Hypocalcemia Hypoglycemia Inborn errors of metabolism Battisti: Convulsions néonatales 56

Causes of neonatal seizures Ages 4 – 14 days Infection Metabolic disorders Hypocalcemia Diet Hypoglycemia Inherited disorder of metabolism such as galactosemia, fructosemia Hyperinsulinemic hypoglycemia Becwith syndrome Anterior pituitary hypoplasia Drug withdrawal Benign neonatal convulsion Kernicterus, hyperbilirubenemia Battisti: Convulsions néonatales 57

Causes of neonatal seizures Ages 2 – 8 weeks Infection Head injury Malformations of cortical development Subdural henatoma Lissencephaly Inherited disorder of metabolism Focal cortical dysplasia Aminoacidurias Tuberous sclerosis Sturge weber syndrome Urea cycle defects Organic acidurias Neonatal ALD Battisti: Convulsions néonatales 58

Neonatal Seizures Etiologic diagnosis Blood Glucose, calcium, magnesium, electrolytes, BUN In hypomagnesemia Mg. SO 4 0. 2 ml/kg Lumbar puncture Indicated in all neonates with seizures unless related to a metabolic disorder Inborn errors of metabolism Inherited as autosomal recessive or X linked recessive Battisti: Convulsions néonatales 59

Neonatal Seizures Etiologic diagnosis Inborn errors of metabolism Serum ammonia urea cycle abnormalities Acidosis + anion gap + hyperammonemia urine organic acids should be determined Unintentional injection of local anesthetic Supportive measures Promotion of urine output with IV fluids Battisti: Convulsions néonatales 60

Idiopathic Syndromes of Clinical Seizures in the Newborn Epileptic Syndromes Benign familial Neonatal Seizures Benign idiopathic neonatal seizures (fifth day fits) Early myoclonic encephalopathy Early infantile epileptic encephalopathy (Ohtahara syndrome) Malignant migrating partial seizures Nonepileptic Syndromes Benign neonatal sleep myoclonus Hyperekplexia Battisti: Convulsions néonatales 61

Neonatal Seizures (Epileptic Syndromes) Benign familial neonatal seizures Begins on the 2 nd – 3 rd day of life Seizure frequency : 10 – 20 /day Patients are normal between seizures Seizure stops in 1 – 6 months Battisti: Convulsions néonatales 62

Neonatal Seizures Fifth day fits – ○ 5 th day of life ○ normal appearing neonates mulifocal seizures ○ Present for less than 24 hours ○ Good prognosis Battisti: Convulsions néonatales with 63

Neonatal Seizures Etiologic diagnosis Pyridoxine dependency resistant to conventional AED’s Inherited as autosomal recessive Tx: Pyridoxine 100 – 200 mg IV May not have a dramatic effect with IV pyridoxine thus maintain on oral pyridoxine 10 20 mg/day x 6 weeks Lifelong supplementation : 10 mg/day Battisti: Convulsions néonatales 64

Neonatal Seizures Etiologic diagnosis Drug withdrawal seizures Barbiturates, benzodiazepenes, heroin and methadone Jittery, irritable, lethargic, may show myoclonus or frank seizures Serum or urine analysis may identify the responsible agent Battisti: Convulsions néonatales 65

Causes of Neonatal Seizures Within first 24 hours of life Hypoxic ischemic encephalopathy Meningitis/sepsis Subdural/Subarachnoid/Interventricular hemorrhage Intrauterine infection Trauma Pyridoxine dependency Drug effect/withdrawal Battisti: Convulsions néonatales 66

Causes…. 24 72 hours Meningitis/sepsis In premature infants: IVH In full term infants: infarction, venous thrombosis Cerebral dysgenesis Battisti: Convulsions néonatales 67

Causes…. 72 hours to 1 week Above causes Inborn errors of metabolism Hypocalcemia Familial neonatal seizures 1 week to 4 weeks Above causes HSV Battisti: Convulsions néonatales 68

Other Syndromes Benign idiopathic neonatal convulsions (BINC or Fifth day fits) Benign familial neonatal convulsions (BFNC) Early myoclonic encephalopathy (EME) Early infantile epileptic encephalopathy (EIEE) Glucose transporter type I Battisti: Convulsions néonatales 70

Inborn Errors of Metabolism Associated With Neonatal Seizures Conditions That Have a Specific Treatment Pyridoxine (B 6) dependency Folinic acid responsive seizures Glucose transporter defect Creatine deficiency Other Conditions Nonketotic hyperglycinemia Sulfite oxidase deficiency Molybdenum cofactor deficiency (combined deficiency) Carbohydrate deficient glycoprotein disorder Lactic acid disorders Mitochondrial disorders Maple syrup urine disease Isovaleric acidemia (sweaty feet, cheesy odor) Battisti: Convulsions néonatales 71

The patho physiology of neonatal convulsions or seizures Battisti: Convulsions néonatales 72

Why are seizure patterns in neonates more fragmentary than in older children? The cellular organization of the mature and immature brain is different. The neonatal brain has incomplete glial proliferation, w/ continuing migration of neurons, establishing complex axonal & dendritic contacts and myelin deposition. The electrical discharges therefore spread incompletely and may remain localized to one hemisphere. The electrical discharges are slow to diffuse and bilateral synchronous discharges are rare. Battisti: Convulsions néonatales 73

Perinatal Anatomical and Physiological Features of Importance in Determining Neonatal Seizure Phenomena ANATOMICAL Neurite outgrowth—dendritic and axonal ramifications— in process Synaptogenesis not complete Deficient myelination in cortical efferent systems Volpe JJ. Neonatal Seizures : Neurology of the Newborn. Battisti: Convulsions néonatales 74

Perinatal Anatomical and Physiological Features of Importance in Determining Neonatal Seizure Phenomena PHYSIOLOGICAL In limbic and neocortical regions, excitatory synapses develop before inhibitory synapses ( N-methyl-D-aspartate receptor activity, gamma-aminobutyric acid excitatory) Immature hippocampal and cortical neurons more susceptible to seizure activity than mature neurons Deficient development of substantia nigra system for inhibition of seizures Impaired propagation of electrical seizures, and synchronous discharges recorded from surface electroencephalogram may not correlate with behavioral seizure phenomena Volpe JJ. Neonatal Seizures. In: Neurology of the Newborn. 4 th ed. Battisti: Convulsions néonatales 75

Probable Mechanisms of Some Neonatal Seizures PROBABLE MECHANISM DISORDER Failure of Na + -K + pump secondary to adenosine triphosphate Excess of excitatory neurotransmitter (eg. glutamic acid—excessive excitation) Hypoxemia, ischemia, and hypoglycemia Hypoxemia, ischemia and hypoglycemia Pyridoxine dependency Deficit of inhibitory neurotransmitter (i. e. , relative excess of excitatory neurotransmitter) Membrane alteration— Na + Hypocalcemia and Permeability hypomagnesemia _______________________________ Volpe JJ. Neonatal Seizures: Neurology of the Newborn. ed. Battisti: Convulsions néonatales 76

Particularity of a Seizure in a Neonate Glutamate receptors predominate, and in addition, GABA, which later in life acts as an inhibitory neurotransmitter, actually acts at at least one receptor in an excitatory fashion. some true seizures do not demonstrate a paroxysmal discharge on EEG. Axons, dendrites, synapses are still in the process of forming and organizing, so may not be capable of propagating widely enough for electrodes to see. . The electrical activity is originating from deeper brain regions, such as the midbrain. in a few studies looking at human infants with subtle events and EEG correlation, sometimes the events were associated with discharges and sometimes not within the same child; in those infants, the clinical onset was more likely to begin seconds before discharge seen, suggesting that perhaps the discharges were originating from deep and travelling up to the cortex. Another possibility for not seeing discharges on EEG is that the event really is not a seizure, but could be a brain stem release brain stem and spinal motor patterns released from inhibition that normally is imposed by a healthy forebrain and cortex. Battisti: Convulsions néonatales 77

Particularity of a Seizure in a Neonate Excitatory activity predominates: No paroxysmal discharge on EEG? True seizure ○ The cortex is undeveloped ○ Deeper origin “Brainstem release phenomena” Battisti: Convulsions néonatales 78

Causes of neonatal seizures Ages 4 – 14 days Infection Metabolic disorders Hypocalcemia Diet Hypoglycemia Inherited disorder of metabolism such as galactosemia, fructosemi a Hyperinsulinemic hypoglycemia Becwith syndrome Anterior pituitary hypoplasia Drug withdrawal Benign neonatal convulsion Kernicterus, hyperbilirubenemia Battisti: Convulsions néonatales 79

Causes of neonatal seizures Ages 2 – 8 weeks Infection Head injury Malformations of cortical development Subdural henatoma Lissencephaly Inherited disorder of metabolism Focal cortical Aminoacidurias Urea cycle defects Organic acidurias dysplasia Tuberous sclerosis Sturge weber syndrome Neonatal ALD Battisti: Convulsions néonatales 80

Causes of neonatal seizures 50 -65% of all seizures < Hypoxic-ischemic encephalopathy (HIE) Intracranial hemorrhage Metabolic causes Common metabolic causes of seizures include hypoglycemia, hypocalcemia, hypomagnesemia. Rare causes include pyridoxine deficiency and inborn errors of metabolism (IEM). Infections Developmental defects Cerebral dysgenesis and neuronal migration disorders are rare causes of seizures in the neonatal period. Miscellaneous Polycythemia maternal narcotic withdrawal drug toxicity (e. g. theophylline, doxapram) local anesthetic injection into scalp (Accidental injection of local anesthetic into scalp may be suspected in the presence of unilateral fixed and dilated pupils) phacomatosis (e. g. tuberous sclerosis, incontinentia pigmentii). Multifocal clonic seizures on the 5 th day may be related to low zinc levels in the CSF fluid (benign idiopathic neonatal convulsions). Battisti: Convulsions néonatales 81

Les entités cliniques et électrophysiologiques des paroxysmes du nouveau-né Syndrome post-hypoxique ou post-asphyxique : « pointes ondes en bouffées, entrecoupées par des activités normales » ; Etat de mal convulsif focal ( occlusive vascular disorder ) : « pointes lentes rythmiques unilatérales » ; Etat de mal généralisé : « pointes ondes en bouffées » ; Convulsions néonatales bénignes ( à j 4 5 ) : « théta pointu alternant » , avec (myo)clonies ; Convulsions néonatales bénignes familiales précoces : souvent j 2 3, mais parfois plus tard, avec prédominance chez le garçon ( anamnèse ! ) : « pas de tracé spécifique » ; Encéphalopathie myoclonique précoce : « pointes ondes en bouffées, jamais synschrones sur les deux hémisphères, séparées par des tracés plats = suppression bursts » : penser à une maladie métabolique ( surtout une hyperglycinémie ou une acidémie D glycérique ) ou annonce d’une encéphalopathie épileptique infantile précoce comme une hypsarythmie. Convulsions généralisées relatées à un dysfonctionnement de la vitamine B 6 ( dosage de l’acide pipécolique sanguin ) [ R/ 100 mg IV pyridoxine ] ; ou de l’acide folinique ( dosage acide pipécolique, AA sanguins , HVA et 5 HIAA dans les urines ; [ R/ 100 mg vit B 6 et 2. 5 mg acide folique ]; anomalie du transporteur 1 du glucose vers le SNC ( GLUT 1 deficiency ) : anomalie à distance des repas. Battisti: Convulsions néonatales 82

AG ou APC Faits marquants 24 -27 semaines Ondes polymorphes, discontinues, amples Possibilités de courtes périodes (1 -2 min) d’activités continues Eveil/sommeil indissociable 28 -32 semaines Bouffées theta (donc tracé discontinu) NB 28 -29 semaines : ces bouffées sont synchrones (dans les 2 hémisphères) Après 30 semaines, il y a des bouffées delta Eveil / sommeil indissociables 32 – 36 semaines Disparition des bouffées theta Pointes multifocales Eveil / sommeil dissociables > 36 semaines Eveil / sommeil structuré Eveil : bas voltage, diffus REM : ondes lentes avec épisodes d’ondes rapides, activité continue NREM : activité discontinue > 44 semaines Tracé continu en sommeil calme > 46 semaines Fuseau de sommeil dans les régions centrales > 48 semaines Activité rythmique occipitale qui disparaît à l’ouverture des yeux 4 à 5 mois Bouffées d’ondes pointes frontales ( encoches ) 6 à 8 mois Rythme theta pendant l’endormissement Battisti: Convulsions néonatales 83

The evaluation neonatal convulsions or seizures Battisti: Convulsions néonatales 84

Maladies métaboliques et p. H Une acidose métabolique avec cétonurie et avec acidose lactique : penser à une maladie mitochondriale ; Une acidose métabolique avec cétonurie et sans acidose lactique : penser à une acidurie organique ; Une acidose métabolique avec cétonurie, avec ou sans acidose lactique : penser à une leucinose ; Une acidose métabolique sans cétonurie, avec acidose lactique et avec hypoglycémie : penser à une glycogénose ou défaut de la gluconéogenèse ou défaut d’oxydation des acides gras ; Une acidose métabolique avec cétonurie, sans hypoglycémie et sans acidose lactique : penser à un défaut de la chaîne respiratoire ; Une acidose métabolique avec cétonurie sans acidose lactique et sans hypoglycémie : penser aussi à une acidurie organique et à une acidurie pyroglutamique ; Pas d’acidose métabolique sans acétonurie avec hyperammoniémie et hypoglycémie : penser à un défaut d’oxydation des acides gras, à un défaut en glutamate déshydrogénase ; Pas d’acidose métabolique sans acétonurie avec hyperammoniémie et sans hypoglycémie : penser à un défaut du cycle de l’urée. Pas d’acidose métabolique sans acétonurie sans hyperammoniémie et sans hypoglycémie : penser à hyprglycinémie ( sans cétose ), ou un déficit en sulfite oxydase. Pas d’acidose métabolique avec acétonurie : penser à une leucinose. Battisti: Convulsions néonatales 85

Mandatory investigations blood sugar Hematocrit bilirubin (if jaundice is present clinically) serum electrolytes (Na, Ca, Mg) arterial blood gas, anion gap cerebrospinal fluid (CSF) examination: CSF examination should be done in all cases as seizures may be the first sign of meningitis. It should not be omitted even if another etiology such as hypoglycemia is present, because meningitis can often coexist. CSF study may be withheld temporarily if severe cardio respiratory compromise is present or in cases with severe birth asphyxia (documented poor cord p. H, seizure onset within 12 24 hrs). An arterial blood gas (ABG) may have to be performed if IEM is strongly suspected. cranial ultrasound (US) electroencephalography (EEG). Battisti: Convulsions néonatales 86

Specific investigations Imaging Neurosonography CT scan should be done in all infants where an etiology is not available after the first line of investigations. It can be diagnostic in sub arachnoid hemorrhage and developmental malformations. MRI scan is indicated only if investigations do not reveal any etiology and seizures are resistant to usual anti epileptic therapy. It can be diagnostic in cerebral dysgenesis, lissencephaly and other neuronal migration disorders. Screen for congenital infections A TORCH screen and VDRL should be considered in the presence of hepato splenomegaly, thrombocytopenia, growth retardation, small for gestational age and presence of chorioretinitis. Metabolic screen A metabolic screen includes blood and urine ketones, urine reducing substances, blood ammonia, anion gap, urine and plasma aminoacidogram, serum and CSF lactate/ pyruvate ratio Electro-encephalogram (EEG) EEG Ictal EEG may be useful for the diagnosis of suspected seizures and also for diagnosis of seizures in muscle relaxed infants. It should be done as soon as the neonate is stable enough to be transported for EEG, preferably within first week. EEG should be performed for at least 1 hour Inter ictal EEG is useful for long term prognosis of neonates with seizures. A background abnormality in both term and preterm neonates indicates a high risk for neurological sequelae. These changes include burst suppression pattern, low voltage invariant pattern and electro cerebral inactivity Battisti: Convulsions néonatales 87

Evaluation of Neonatal Seizures Serum lytes (gluc, Ca, Mg, Na) CSF Head ultrasound EEG (B 6? ) Tox screen CT or MRI of brain ? metabolic w/u, congenital infection w/u Battisti: Convulsions néonatales 88

Grading IVH Battisti: Convulsions néonatales 89

1. Where is the hemorrhage? 2. Name the Anatomy 3. Grade the Hemorrhage Grade II Hemorrhage Extension into lateral ventricle without dilation Normal Anatomy Germinal Matrix Extension into Lateral Ventricle (no dilation) Battisti: Convulsions néonatales Choroid Plexus 90

Electroencephalographic seizures II. Non epileptic § No electro cortical signature § Provoked by stimulation § Suppressed by restraint or repositioning § Brainstem release phenomena (reflex) Battisti: Convulsions néonatales 92

Surface EEG Silent Seizure Can “ surface EEG silent ” seizure in the newborn result to brain injury? § Can this be eliminated by conventional anticonvulsant therapy? § Further investigation needed § Battisti: Convulsions néonatales 94

Laboratory Studies to Evaluate Neonatal Seizures Indicated Complete blood count, differential, platelet count; urinalysis Blood glucose (Dextrostix), BUN, Ca, P, Mg, electrolytes Blood oxygen and acid base analysis Blood, CSF and other bacterial cultures CSF analysis EEG Battisti: Convulsions néonatales 95

Laboratory Studies to Evaluate Neonatal Seizures Clinical Suspicion of Specific Disease Serum immunoglobulins, TORCH antibody titers, and viral cultures Blood and urine metabolic studies (bilirubin, ammonia, lactate, FECl³, reducing substance. ) Blood and urine toxic screen Blood and urine amino and organic acid screen CT or ultrasound scan Battisti: Convulsions néonatales 96

$Metabolic Evaluation for Refractory Neonatal Seizures Consider individually by case specifics Serum Glucose Electrolytes$

Metabolic Evaluation for Refractory Neonatal Seizures Consider individually by case specifics Serum Glucose Electrolytes (sodium, potassium, chloride, carbon dioxide), blood urea nitrogen, chromium, calcium, phosphorus, magnesium Uric acid Creative kinase Serum ammonia Lactic and pyruvic acids Biotinidase Amino acids Serum carnitine, acylcarnitines Serum transferrin Copper and ceruloplasmin Cholesterol Fatty acids (short chain, medium chain, long chain) Pipecolic acid Neo. Reviews vol. 5 no. 6 June 2004 Battisti: Convulsions néonatales 97

$Metabolic Evaluation for Refractory Neonatal Seizures Urine Organic acids Acylglycines Uric acid Sulfites Xanthine,$

Metabolic Evaluation for Refractory Neonatal Seizures Urine Organic acids Acylglycines Uric acid Sulfites Xanthine, hypoxanthine Guanidinoacetate Pipecolic acid Cerebrospinal Fluid Cell count, glucose, protein Lactic and pyruvic acids Amino acids Organic acids Neurotransmitters Other Studies Skin biopsy Muscle biopsy Magnetic resonance imaging with magnetic resonance spectroscopy (especially for creatine) Neo. Reviews vol. 5 no. 6 June 2004 Battisti: Convulsions néonatales 98

The treatment of neonatal convulsions or seizures Battisti: Convulsions néonatales 99

Treatment Identify the underlying cause: hypoglycemia D 10 solution hypocalcemia Calcium gluconate hypomagnesemia Magnesium sulfate pyridoxine deficiency Pyridoxine meningitis initiation of antibiotics § Battisti: Convulsions néonatales 100

Treatment To minimize brain damage § Some controversy when to start anticonvulsants § If seizure is prolonged (longer than 3 minutes), frequent or associated with cardiorespiratory disturbance § Battisti: Convulsions néonatales 101

Acute therapy of neonatal seizures If with hypoglycemia Glucose 10%: 2 ml/k IV § If no hypoglycemia Phenobarbital: 20 mg/k IV loading dose If necessary : additional phenobarbital: 5 mg/kg IV to a max of 20 mg/kg (consider omission of this additional Phenobarbital if with baby is asphyxiated) Phenytoin: 20 mg/kg, IV (1 mg/kg/min) § Lorazepam: 0. 05 0. 10 mg/kg, IV Battisti: Convulsions néonatales 102

Treatment of neonatal convulsions Within 5 minutes: baby in thermoneutral environment and ensure airway, breathing and circulation. O 2 should be started, IV access should be secured, and blood should be collected for sugar and other investigations. A brief relevant history should be obtained and quick clinical examination should be performed. All this should not require more than 2 5 minutes. If hypoglycemia or if there is no facility to test blood sugar immediately, 2 ml/kg of 10% dextrose should be given as a bolus injection followed by a continuous infusion of 6 8 mg/kg/min. If hypoglycemia has been treated or excluded as a cause of convulsions, the neonate should receive 2 ml/kg of 10% calcium gluconate IV over 10 minutes under strict cardiac monitoring. If ionized calcium levels are suggestive of hypocalcemia, the newborn should receive calcium gluconate at 8 ml/kg/d for 3 days. If seizures continue despite correction of hypocalcemia, 0. 25 ml/kg of 50% magnesium sulfate should be given intramuscularly (IM). Anti-epileptic drug therapy (AED) Battisti: Convulsions néonatales 103

Acute Therapy of Neonatal Seizures With Hypoglycemia -Glucose, 10% solution: 2 m. L/kg, IV No Hypoglycemia Phenobarbital: 20 mg/kg, IV (1 -2 mg/kg/min) If necessary: Additional phenobarbital: 5 mg/kg IV to a max. of 40 mg/kg (consider omission of this additional phenobarbital if infant is severely “asphyxiated”) Phenytoin*: 20 mg/kg, IV (0. 5 -1. 0 mg/kg/min) (Lorazepam: 0. 05 -0. 10 mg/kg, IV) if available Midazolam: 0. 2 mg/kg, IV; then, 0. 1 -0. 4 mg/kg/hr, IV Battisti: Convulsions néonatales 104

Acute Therapy of Neonatal Seizures Other (as Indicated) Calcium gluconate, 5% solution: 4 m. L/kg, IV Magnesium sulfate, 50% solution: 0. 2 m. L/kg, IM Pyridoxine: 50 100 mg, IV; repeat to maximum of 500 mg if needed Pyridoxal 5 phosphate, 30 mg/kg/day, PO Folinic Acid, 4 mg/kg/day, PO Battisti: Convulsions néonatales 105

Drug Therapy For Neonatal Seizures Standard Therapy AED Initial Dose Maintenance Dose Route Phenobarbital 20 mg/kg 3 to 4 mg/kg per day l. V, l. M, PO Phenytoin 20 mg/kg 3 to 4 mg/kg per day l. V, POª Fosphenytoin 20 mg/kg phenytoin 3 to 4 mg/kg per day l. V, l. M equivalents Lorazepam² 0. 05 to 0. 1 mg/kg Every 8 to 12 hours l. V Diazepam²´ 0. 25 mg/kg Every 6 to 8 hours l. V AED= andtiepileptic drug; l. V= intravenous; l. M= intramuscular; PO= oral ªOral phenytoin is not well absorbed. ²Benzodiazepines typically not used for maintenance therapy. ³Lorazepam preferred over diazepam. Battisti: Convulsions néonatales 106

Battisti: Convulsions néonatales 107

Pharmacological properties of Phenobarbital § § § Enters the CSF/brain rapidly with high efficiency The blood level is largely predictable from the dose administered It can be given IM or IV(more preferred) Maintenance therapy accomplished easily with oral therapy Protein binding lower in newborn—free levels of drug are higher Entrance to the brain increased by local acidosis associated with seizures Battisti: Convulsions néonatales 108

Anti-epileptic drug therapy (AED) Equipment for resuscitation and assisted ventilation should be available at the bedside of all neonates given multiple doses Phenobarbitone - It is the drug of choice in neonatal seizures. The dose is 20 mg/kg/IV slowly over 20 minutes (not faster than 1 mg/kg/min). If seizures persist after completion of this loading dose, repeat dose of phenobarbitone 10 mg/kg may be used every 20 -30 minutes till a total dose of 40 mg/kg has been given. The maintenance dose is 3 -5 mg/kg/day in 1 -2 divided doses, started 12 hours afterthe loading dose. Recommendation for use of prophylactic phenobarbitone still awaits further studies. Phenytoin and Fosphenytoin - - Phenytoin is indicated if the maximal dose of phenobarbitone (40 mg/kg) fails to resolve seizures or earlier, if adverse effects like respiratory depression, hypotension or bradycardia ensue with phenobarbitone. The dose is 20 mg/kg IV at a rate of not more than 1 mg/kg/min under cardiac monitoring. Phenytoin should be diluted in normal saline as it is incompatible with dextrose solution. A repeat dose of 10 mg/kg may be tried in refractory seizures. The maintenance dose is 3 -5 mg/kg/d (maximum of 8 mg/kg/d) in 2 -4 divided doses. Oral suspension has very erratic absorption from gut in neonates, so it should be avoided. Thus only IV route is preferred in neonates and it should preferably be discontinued before discharge. Fosphenytoin, the prodrug of phenytoin, does not cause the same degree of hypotension or cardiac abnormalities, has high water solubility (therefore can be given IM), and is less likely to lead to soft-tissue injury compared with phenytoin. It is dosed in phenytoin equivalents (1. 5 mg/kg of fosphenytoin is equivalent to 1 mg/kg of phenytoin). Benzodiazepines Lorazepam is preferred over diazepam as it has a longer duration of action and results in less adverse effects (sedation and cardiovascular effects). Midazolam is faster acting than lorazepam and may be administered as an infusion. Diazepam: 0. 25 mg/kg IV bolus (0. 5 mg/kg rectal); may be repeated 1 2 times. Lorazepam: 0. 05 mg/kg IV bolus over 2 5 minutes; may be repeated Midazolam: 0. 15 mg/kg IV bolus followed by infusion of 0. 1 to 0. 4 mg/kg/hour. Clonazepam: 0. 1– 0. 2 mg/kg IV bolus followed by infusion 10 30 ìg/kg/hr. Battisti: Convulsions néonatales 109

$Antiepileptic drugs for refractory seizures The expected response to anticonvulsants is 40% to the$

Antiepileptic drugs for refractory seizures The expected response to anticonvulsants is 40% to the initial 20 - mg/kg loading dose of phenobarbitone, 70% to a total of 40 mg/kg of PB, 85% to a 20 - mg/kg LD of PHT, and 95% to 100% to 0. 05 to 0. 10 mg/kg lorazepam 4. In exceptional circumstances when the seizures are refractory to these first-line drugs, the following second-line drugs might be tried. Lidocaine: Start with 4 mg/kg/hr IV on first day, reduce by 1 mg/kg/hr on each subsequent day or load with 2 mg/kg IV and maintain on 6 mg/kg/hr. Adverse effects include arrythmias, hypotension and seizures. It should not be administered with phenytoin. Paraldehyde: It may be used in seizures refractory to the first line drugs. A dose of 0. 10. 2 ml/kg/dose may be given IM or 0. 3 ml/kg/dose mixed with coconut oil in 3: 1 may be used by per rectal route. Additional doses may be used after 30 minutes and q 4 -6 hourly. Adverse effects include pulmonary hemorrhage, pulmonary edema, hypotension, and liver injury. Pyridoxine: Therapeutic trial of pyridoxine is reserved as a last resort. IV administration is the preferred method; however, suitable IV preparations are not available at present in India. Hence intramuscular (IM) route may have to be used instead (1 ml of neurobion has 50 -mg pyridoxine and 1 ml each may be administered in either the gluteal region or anterolateral aspect of thigh). Sodium valproate: It can be used for maintenance therapy in neonates. Per rectal route may be used in acute condition. IV preparation is now available. Dose is 20 -25 mg/kg/d followed by 5 -10 mg/kg every 12 hours. Vigabatrin: It has been used in neonates for refractory seizures, primarily for infantile spasms. The dose is 50 mg/kg/day. Topiramate: It shows promise in neonatal seizures because of its potential neuroprotective but has also secondary effects Battisti: Convulsions néonatales 110

Alternative Antiepileptic Drugs (AED) for Neonatal Seizures Intravenous AEDs High dose phenobarbital: >30 mg/kg Pentobarbital: 10 mg/kg, then 1 mg/kg per hour Thiopental: 10 mg/kg, then 2 to 4 mg/kg per hour Midazolam: 0. 2 mg/kg, then 0. 1 to 0. 4 mg/kg per hour Clonazepam: 0. 1 mg/kg Lidocaine: 2 mg/kg, then 6 mg/kg per hour Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses Paraldehyde: 200 mg/kg, then 16 mg/kg per hour Chlormethiazole: Initial infusion rate of 0. 08 mg/kg per minute Dexamethasone: 0. 6 to 2. 8 mg/kg Pyridoxine (B 6): 50 to 100 mg, then 100 mg every 10 minutes (up to 500 mg) Battisti: Convulsions néonatales 111

Alternative AEDs for Neonatal Seizures Oral AEDs Primidone: 15 to 25 mg/kg per day in 3 doses Clonazepam: 0. 1 mg/kg in 2 to 3 doses Carbamazepine: 10 mg/kg, then 15 to 20 mg/kg per day in 2 doses Oxcarbamazepine: no data on neonates, young infants Valproic acid: 10 to 25 mg/kg, then 20 mg/kg per day in 3 doses Vigabatrin: 50 mg/kg per day in 2 doses, up to 200 mg/kg per day Lamotrigine: 12. 5 mg in 2 doses Topiramate: 3 mg/kg per day Zonisamide: 2. 5 mg/kg per day Levetiracetam: 10 mg/kg per day in 2 doses Folinic acid: 2. 5 mg BID, up to 4 mg/kg per day Neo. Reviews vol. 5 no. 6 June 2004 Battisti: Convulsions néonatales 112

Maintenance Therapy of Neonatal Seizures Glucose: < 8 mg/kg/, IV Phenobarbital: 3 4 mg/kg/24 hr, IV, IM, or PO Phenytoin (as fosphenytoin): 3 4 mg/kg/24 hr, IV Calcium gluconate: 500 mg/kg/24 hr, PO Magnesium sulfate (50%): 0. 2 m. L/kg/24 hr, IM Volpe, Neurology of the Newborn, 5 th ed. 2008 Battisti: Convulsions néonatales 113

Treatment of Electroclinical Seizures Phenobarbital 20 mg/kg 10 mg/kg boluses until 40 50 microgm/ml Phenytoin 20 mg/kg Lorazepam 0. 1 mg/kg Pyridoxine 50 100 mg IV with EEG Battisti: Convulsions néonatales 114

Maintenance anti-epileptic therapy Monotherapy is the most appropriate strategy to control seizures. Attempts should be made to stop all anti epileptic drugs and wean the baby to only phenobarbitone at 3 5 mg/kg/day. If seizures are uncontrolled or if clinical toxicity appears, a second AED may be added. The choice may vary from phenytoin, carbamezepine, and valproic acid. Battisti: Convulsions néonatales 115

Why should the infant with epileptic seizures be treated with AED Potential adverse effects of seizure on: Ventilatory function Circulation Cerebral Metabolism Brain Development disturbance in cerebral blood flow energy metabolism homeostasis of excitotoxic amino acids neurogenesis and synaptic reorganization Battisti: Convulsions néonatales 116

Determinants of Duration of anticonvulsant therapy for neonatal seizures § Neonatal neurological examination § Cause of neonatal seizure § Electroencephalogram Battisti: Convulsions néonatales 117

Duration of anticonvulsant therapy Guidelines Neonatal period § If neonatal neurological examination becomes normal discontinue therapy § If neonatal neurological examination is persistently abnormal, consider etiology and obtain EEG § In most such cases Continue phenobarbital Discontinue phenytoin Reevaluate in 1 month Battisti: Convulsions néonatales 118

Duration of anticonvulsant therapy Guidelines One month after discharge § If neurological examination has become normal, discontinue phenobarbital § If neurological examination is persistently abnormal, obtain EEG § If no seizure activity on EEG, discontinue phenobarbital Battisti: Convulsions néonatales 119

When to discontinue AED This is highly individualized Volpe: try to discontinue all medication at discharge if clinical examination is normal, irrespective of etiology and EEG. If neurological examination is persistently abnormal at discharge, AED is continued and the baby is reassessed at 1 month. If the baby is normal on examination and seizure free at 1 month, phenobarbitone is discontinued over 2 weeks. If neurological assessment is not normal, an EEG is obtained. If EEG is not overtly paroxysmal, AED are tapered and stopped. If EEG is overtly abnormal, the infant is reassessed in the same manner at 3 months and then 3 monthly till 1 year of age. Ellison Battisti: Convulsions néonatales 120

Battisti: Convulsions néonatales 121

Score de Patricia Ellison: Stopper le traitement si ∑ < 5 « à terme » ou < 6 à 3 mois du terme Poids de naissance : < 1500 g 2 > 1500 g 1 type de paroxysme : subtil ou atypique 0 clonique 1 tonique ou myoclonique 2 facteur déclenchant : inconnu 0 hypocalcémie, hypoglycémie 1 hémorragie sous arachnoïdienne ou stades 1 Sarnat stade 2 Méningite 2 Hémorragie stade 3, 4 2 Malformation cérébrale 2 Sarnat stade 3 2 EEG : Normal 0 Anomalies mineures 1 Anomalies marquées 2 Examen neurologique : Normal 0 hypotonie modérée, hyperexcitabilité 1 Hémi syndrome, hyper- hypo – tonie majeure 2 Battisti: Convulsions néonatales 122

Duration of Anticonvulsant Therapy Guidelines Neonatal Period If neonatal neurological examination becomes normal, discontinue therapy If neonatal neurological examination is persistently abnormal, consider the cause and obtain an EEG. In most such cases: Continue phenobarbital Discontinue phenytoin Reevaluate in 1 month At 1 Month After Discharge If neurological examination has become normal, discontinue phenobarbital If neurological examination is persistently abnormal, obtain an EEG. If no seizure activity is noted on the EEG, discontinue phenobarbita Volpe, Neurology of the Newborn, 5 th ed. 2008 Battisti: Convulsions néonatales 123

The following and prognosis of neonatal convulsions or seizures Battisti: Convulsions néonatales 124

Outcome 45 % controlled after either phenobarb or phosphenytoin 60 % controlled with both 30% of survivors develop epilepsy WORSE: HIE, meningitis, dysplasia WORSE: electrographic seizures BETTER: hypo. Ca, BINC, BIFC, stroke Battisti: Convulsions néonatales 125

Prognosis Two most useful approaches in utilizing outcome § EEG § Recognition of the underlying neurological disease Battisti: Convulsions néonatales 126

Prognosis of Neonatal seizures in relation to EEG BACKGROUND NEUROLOGICAL SEQUELAE(%) Normal Severe abnormalities† Moderate abnormalities‡ 10 90 ~50 Based primarily on data reported by Rowe JC, Holmes GL, Hafford J, et al: Electroencephalogr Clin Neurophysiol 60: 183 196, 1985; Lombroso CT: In Wasterlain CG, Treeman DM, Porter R, editors: Advances in neurology, New York, 1983, Raven Press; and includes both full term and premature infants. †Burst suppression pattern, marked voltage suppression, and electrocerebral Silence. ‡Voltage asymmetries and “immaturity. ” Battisti: Convulsions néonatales 127

Complications § § § Cerebral palsy Hydrocephalus Epilepsy Spasticity Feeding difficulties Battisti: Convulsions néonatales 128

Consultations Neurology consult needed for evaluation of seizures evaluation of EEG and video EEG monitoring management of anticonvulsant medications § Battisti: Convulsions néonatales 129

Further Outpatient Care Neurology outpatient evaluation § Developmental evaluation for early identification of physical or cognitive deficits § Orthopedic evaluations if with joint deformities § Consider physical medicine/physical therapy referral if indicated § Battisti: Convulsions néonatales 130