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[ ] neonatal seizures.rtf.doc Document Transcript

  • 1. Approach to Neonatal Seizures One of the strongest risk factors for adverse outcomes (mortality and neurologic morbidity) in perinatal period and a symptom that heralds an underlying systemic or CNS disorder - seen in almost all brain disorders in this period - incidence of 4.4 per 1000 live births - more frequent with decreasing gestational age - seizures in immature brain may be detrimental, with changes in perfusion / BP / ICP and can trigger epileptogenesis (eg. changes in hippocampus after status epilepticus) Characterized by stereotyped, repetitive activity often with abnormal eye movements - Four main types: 1. Tonic: extension of arms & legs, stiffening of body - usually with upward deviation of eyes and apnea (if both of these absent then likely not a seizure) - may result from lack of cerebral inhibition and not represent cortical electrical discharges - seen more often in premature infants (with intraventricular hemorrhage) and common with structural damage rather than metabolic disturbance - distinguish esp from opisthotonos (see below) 2. Clonic: focal if one limb, multifocal if random migration of movements esp facial involvement (these are neonatal equivalent of generalized tonic clonic seizures) - repeated irregular jerking movements rarely sustained for long - don’t see typical "march" as doesn’t spread smoothly along motor cortex - especially if associated with eye deviation in term infants, best associated with cortical discharges - multifocal clonic seizures are an indicator of severe generalized cerebral disturbance such as HIE 3. Subtle: sucking, rowing, pedaling, swimming movements - esp hard to distinguish from normal activity or sleep movements (see below) - tonic deviation of eyes is good sign of a true seizure 4. Myoclonic: single or multiple rapid flexion or extension movements of extremities - relatively uncommon but suggestive of severe diffuse brain damage - need to distinguish from jitteriness (see below) NB: in general, seizure activity is more fragmented than that in older children (intracortical pathways not well established, so spread is not smooth); - bilaterally synchronous epileptic discharges rare (so don’t see typical 'grand mal' seizure) - may not be detected on scalp EEG discharges (? emanate from subcortical grey matter) - most seizures arise focally in immature brain; tend to last longer in term vs preterm infants Differential Diagnosis of Epileptic Seizures: Not every abnormal movement in neonates is a seizure, must must be distinguished from normal neonatal movements. 1. Sleep activity (+/- myoclonus) - rapid transition from wakefulness to REM sleep with ++ sucking & stretching activity - also as wake from REM to quiet sleep may see sleep myoclonus (even multifocal) - may be confused with seizure activity but end with arousal 2. Neonatal clonus or "jitteriness" - distinguished since stimulus provoked, ablated with change in posture or restraint and no abnormal eye movements (also see low threshold for Moro reflex)
  • 2. - seen commonly in drug withdrawal states as well as perinatal asphyxia and metabolic disorders (may need EEG to fully distinguish from seizures) 3. Recurrent apnea may be manifestation of a seizure, esp if associated with tonic posturing - convulsive apnea usually in REM sleep and see parosysmal alpha-like activity on EEG - usually not associated with profound changes in heart rate (reassuring if bradycardia !) - but much more often due to pulmonary, cardiovascular, or GI disturbances, or due to immaturity of brainstem respiratory centres (periodic breathing); associated with bradycardia and should resolve with maturation (by 52 weeks conceptional age) 4. Opisthotonos: prolonged arching of back without abnormal eye movements - usually due to meningeal irritation - seen in kernicterus, infantile Gaucher disease, some aminoacidurias Etiology of Neonatal Seizures: Time of onset may be useful as certain etiologies more likely to occur early (first 24 hours) while others typically occur later in neonatal period First 24 hours: 1. Hypoxic-ischemic encephalopathy (perinatal asphyxia); HIE - w/ need for positive-pressure ventilation > 1 minute before start to breath - 1-minute Apgars very unreliable predictors of poor outcome from HIE as only 1% of those with scores 0-3 do poorly as long as 10-minute score is 4 or more - usually get seizures only 4-6 hours after birth, almost always subside by 72 hours - deterioration as edema progresses by 1-3 days manifested by coma, bulging fontanelles, loss of brainstem reflexes and respiratory arrest (+/- frequent refractory seizures) - accounts for over 50% of neonatal seizures 2. CNS & Intrauterine Infections + sepsis - bacterial meningitis, viral meningoencephalitis (CMV, HSV-2, coxsackie), abscess 3. Drug withdrawal: (taken by mother) esp hypnotic, analgesics, barbiturates (esp short-acting), heroin, methadone, propoxyphene; usually see autonomic instability, jitteriness and myoclonic jerking; may occur up to few days after birth (if long half-life) 4. Vascular: - intraventricular hemorrhage in term neonates (usually tonic, possibly from lack of brainstem inhibition rather than cortical seizure?) - cerebral venous thrombosis due to coagulopathies, polycythemia, sepsis, asphyxia 5. Birth trauma - esp in large infants of primiparous mothers; labor usually prolonged with difficult extraction - laceration of tentorium or falx w/ subdural hematoma can result with pressure on head - presents 12 hours or more after delivery as blood collects with lethargy, irregular respirations, hypotonia, seizures, and tense fontanelle - also primary subarachnoid hemorrhage from shearing of veins during difficult delivery 6. Pyridoxine dependency - AR trait with intractable multifocal clonic seizures shortly after birth, may have meconium staining, flaccidity and be misdiagnosed as HIE; give 100 mg pyridoxine IV with EEG monitoring and seizures respond in minutes with EEG reverting to normal in 10 minutes or so from polyspikes, burst-suppression or generalized spike patterns ! 7. Inadvertent local anesthetic toxicity: may be injected into the neonate inadvertently intended for mother, eg. saddle block; - neonatae look like has asphyxia with apnea, meconium, flaccidity ... but self-limiting 24 to 72 hours: 1. Cerebral dysgenesis 2. Vascular - cerebral infarct - intracerebral hemorrhage - cortical vein / sinus thrombosis
  • 3. - IVH in premature infants present at this stage (not immediate as in terms) - SAH with cerebral contusion from birth trauma 3. Metabolic: - Hypocalcemia (eg infants of mothers with hyperparathyroidism or diabetes, phosphate load, hypomagnesemia, hypoparathyroidism incl. DiGeorge syndrome - look for prolonged QT) - Hypoglycemia (with asphyxia, sepsis, infant of diabetic mother, after complicated labor and delivery, IUGR / prematurity; more persistent and present slightly later in aminoacidurias, disorders of carbohydrate metabolism - Hypo- or hypernatremia - Glycine encephalopathy (nonketotic hyperglycinemia); autosomal recessive with hiccuping, failure to feed though normal at birth, then progressive lethargy, hypotonia, apneas and myoclonic seizures; EEG shows burst suppression, Dx with high CSF glycine - Urea cycle disorders (high ammonia with progressive lethargy, vomiting, and hypotonia, seizures occur when NH3 very high) incl. carbamyl phosphate synthetase (CPS) deficiency, ornithine transcarbamylase (OTC) deficiency, citrullinemia, argininemia - Aminoacidurias and organic acidurias (latter with high ketones or lactic acid buildup) NB: infants with metabolic disorders usually lethargic and feed poorly even prior to seizures 4. Drug withdrawal 5. Pyridoxine dependency 6. Incontinentia pigmenti - rare genetic disorder with X-linked dominant segregation - almost always seen in females with abnormalities of skin, hair, nails, teeth, eyes & CNS - erythematous vesicular rash on flexor surfaces of limbs and lateral aspect of trunk soon after birth with seizures usually at 1-2 days of age 7. Tuberous sclerosis 72 hours to 1 week: 1. Familial neonatal seizures - incl. benign familial neonatal convulsions (see below) - Smith-Lemli-Opitz syndrome 2. Cerebral malformations 3. Cerebral infarction 4. Hypoparathyroidism (hypocalcemia) 5. Vascular events (venous thrombosis, hemorrhage) 6. Kernicterus (bilirubin encephalopathy) - very high levels of bilirubin deposited in brain, now mainly seen in sick premature infants with RDS & sepsis where lower levels are toxic than in term infants - hypotonia, lethargy and poor sucking noticed first (within 24 hrs) then increased tone and opisthotonic posturing +/- febrile, may have seizures; ultimately extrapyramidal dysfunction 7. Acidurias (methylmalonic acidemia, propionic acidemia) 8. Urea cycle disorders 9. Tuberous sclerosis 1 to 4 weeks: - Peroxisomal disorders incl. neonatal adrenoleukodystrophy, Zellweger syndrome - Cerebral dysgenesis - Fructose dysmetabolism - Gaucher disease type 2 - GM1 gangliosidosis type 1 - HSV-2 encephalitis (rash on scalp, conjunctivitis, jaundice, bleeding then irritability & seizures, often refractory; progressive deterioration with over 50% mortality) - Ketotic hyperglycinemia - Maple syrup urine disease - Tuberous sclerosis - Urea cycle disorders
  • 4. NB: focal clonic seizures in responsive and alert newborn suggests cerebral infarction or hemorrhage while if decresed LOC then suspect infarction with encephalopathy Benign Familial Neonatal Convulsions: - multifocal and focal clonic seizures in first 2 weeks of life +/- associated with apnea - autosomal dominant inheritance - peak onset at 3 days - usually few seizures every day but no status epilepticus - 70% remit within one week - interictal EEG normal and otherwise healthy infant - usually normal cognitive outcome but 16% risk of subsequent epilepsy incl febrile seizures - recently found to harbor mutations in sodium channel (SCN2A) as well as potassium channel gene (KCNQ2 and KCNQ3) Smith-Lemli-Opitz syndrome: - autosomal recessive - severe developmental disorder with multiple congenital anomalies and mental retardation - defect in cholesterol biosynthesis - diagnosed with low cholesterol with elevated 7-dehydrocholesterol levels - mutations in DHCR7 gene with deficiency of 7-dehydrocholesterol reductase (final enzyme in cholesterol biosynthetic pathway); chr 11q History: Birth history: - gestational age at birth - any complications during pregnancy , maternal diabetes, IUGR - maternal drug use (incl. illicit drugs like heroin, cocaine) - labor & delivery complications incl. birth trauma, forceps use, fetal heart rate, meconium - any evidence of fetal asphyxia (need for resuscitation, Apgars, cord pH & base excess) - any use of local anesthetics for the mother and did they not take effect? (suggesting perhaps not injected into her but into baby !) Account of spells: - are they stereotyped with clear onset and offset? - any provoking factors - relationship to feeding and sleep patterns (eg just sleep behaviours) - can they be stopped or modified with posture or restraint (unlikely seizures) - type of activity (eg. clonic, tonic, myoclonic, focal vs generalized) - abnormal eye movements during? Age at onset: - right from birth, few hours later, or after days Number of spells, duration of each, and frequency per day Family History of seizures: - with similar presentation and transient nature in siblings or parent suggests benign familial neonatal convulsions (ask grandparents as parents often not know!) - neurocutaneous disorders may also be inherited Examination: Vitals esp fever (suggesting CNS infection) - in neonates paralysed for ventilation, unable to see convulsive movements but rhythmic increases in blood pressure, heart rate, and oxygenation may be clues
  • 5. Dysmorphisms as seen in Zellweger syndrome or Smith-Lemli-Opitz Cutaneous exam for vesicular rash (of herpes simplex or incontinentia pigmenti); latter heals leaving whorled lesion - examine scalp for needle marks, suggesting inadvertent local anesthetic administration Neurological: - mental status (eye opening, tracking) - fontanelle (? bulging) - evidence of chorioretinitis - is the baby floppy? NB: neonatal encephalopathy associated with frequent seizures can occur with burst-suppression pattern on EEG (Ohtahara syndrome) or with myoclonic seizures - may occur from structural brain damage, hyperglycinemia, or other genetic / metabolic syndromes Can an event be provoked with startle (implying "jitteriness") or putting to sleep Evaluation: 1. EEG - try to capture a spell ideally - may also show abnormality of background, in severe encephalopathies (eg HIE) incl. suppression / burst pattern (charactersitic of Ohtahara syndrome +/- hyperglycinemia) 2. Laboratory investigations: - Glucose, Calcium, Sodium, Urea, Bilirubin, Ammonia, Blood gases +/- serum amino acids - Urine for amino acids, organic acids and 2-4-DNP (leads to precipitation if MSUD present) 3. Trial of pyridixone if refractory seizures (while monitoring EEG for changes) 4. Consider LP for CSF testing of glycine as well as to rule out CNS infection (esp bacterial meningitis) Management: Unless believe transient due to metabolic derangement that is corrected or other non-persistent abnormality, likely treat neonatal seizures (esp if recurrent) - phenobarbital may be first-line (loaded 20 mg/kg IV then low maintenance dose of 2-4 mg/kg/day; may need to track levels aiming for 40 ug/mL or higher if refractory ~ 70) - phenytoin can also be used, often as second-line (loaded as phenobarb then 4-6 mg/kg/d) - both have equivalent first-line effectiveness of roughly 40% (with additional 20% controlled on two drugs together) - benzodiazepines (clonazepam, lorazepam) have also been tried, usually as adjunctive - severity of seizures best predictor of response to therapy - consider pyridoxine trial (see above) May stop AED therapy after two seizure-free weeks in most patient groups Outcomes: Neonatal seizures are adverse predictors of neurological morbidity - but also largely depends on underlying cause of seizures - 50% or more have some neurological sequellae
  • 6. - often go on to develop epilepsy, developmental delay, and cerebral palsy - esp bad if asphyxia as cause (70% bad outcomes; 30-40% risk of epilepsy) - if EEG shows poor background or > 2 seizures on EEG per hour - worse outcomes - abnormal neurological status on discharge is also predictor of poor outcome References: Fenichel GM. Clinical pediatric neurology. 3rd ed. Morgan JD, Painter MJ. Neonatal seizures. In Swaiman KF, Ashwal S. eds. Pediatric neurology: principles and practice. 3rd ed. Last update: June 2004 Reviewed by: pending Neurological Medicine Pocketbook © 2003-2004 UWO Neurology Residents http://www.uwo.ca/cns/resident All Rights Reserved Disclaimer