NEONATAL SEIZURES INTRODUCTION Neonates with illnesses affecting the CNS present with convulsions.

The incidence rate for neonatal seizures has been started as 2.6/1000 live births as per Western statistics, with 2/1000 live births for term neonates, and 11.1/1000 live births for preterm neonates. Seizures are often the first sign of neurological dysfunction, and they are powerful predictors of long-term cognitive and developmental impairment. Most (80%) neonatal seizures occur in the first 12 days to the first week of life. DEFINITION A seizure is a paroxysmal behaviour caused by hypersynchronous discharge of a group of neurons. Neonatal seizures are the most common overt manifestation of neurological dysfunction in the newborn. Seizures episode of paroxysmal and transient brain dysfunction Convulsion motor manifestation of seizures Epilepsy recurrent chronic seizures Status epilepticus any seizure that lasts for more than 30 min or occurrence of serial convulsion between which there is no return of consciousness. Most (80%) neonatal seizures occur in the first 12 days to the first week of life. The duration of neonatal seizures is usually brief (10 s to 12 min) and repetitive with a median of 8 min in between each seizure. Longer seizures and status epilepticus develop more readily at this age, but convulsive neonatal status epilepticus is not as severe as that of older infants and children. PATHOPHYSIOLOGY Seizures occur when a large group of neurons undergo excessive, synchronized depolarization. Depolarization can result from excessive excitatory amino acid release (eg, glutamate) or deficient inhibitory neurotransmitter [GABA]. Another potential cause is disruption of ATP-dependent resting membrane potentials, which causes a flow of sodium into the neuron and potassium out of the neuron. According to neurotransmitter theory:Seizures occur due to imbalance of neurotransmitter that enhance excitation and diminish inhibition. Increase in excitatory neurotransmitter (Ach) Decrease in inhibitory neurotransmitter (GABA)

Imbalance favouring excitation

Epileptic attack

Low GABA levels lead to decrease in inhibitionGlucose Protein

Glutamine Cofactor Pyridoxine (B6) GABA In children (especially in newborns) with B6 deficiency, seizures can occur. According to Na+ - K+ ATPase theory:Hypoxic-ischemic encephalopathy disrupts the ATP-dependent sodium-potassium pump and appears to cause excessive depolarization. It is an important cause of neonatal seizures. In epileptic corticesLevels of Na+ - K+ ATPase are low

Na+ leaks into the neuronal cell and K+ remains outside the cell

Resting Membrane Potential (RMP) altered

Depolarization

Electrical discharges (as long as depolarization continues) K+ present outside causes excitation of neuron allowing synchronization of firing of neurons. Duration of accumulation of K+ is correlated with excitability of neurons. ETIOLOGY Hypoxic-ischemic encephalopathy Metabolic Hypoglycemia Hypocalcemia Hypomagnesemia (often with Hypocalcemia) Hyper/Hyponatremia Drug Withdrawal

Local Anesthetic Toxicity Pyridoxine (Vitamin B6) Dependency Disorders of Small Molecules (Amino Acid, Organic Acid &Urea Cycle Disorders) Disorders of Subcellular Organelles (Mitochondrial & Peroxisomal Disorders)

Intracranial infection Bacterial meningitis (E. coli, Group B Strep, Listeria) Viral Encephalitis (Herpes Simplex, Enterovirus) Intrauterine Infection (CMV, Toxoplasm., HIV, Rubella, Syphilis Cerebral Vascular Intraventricular hemorrhage Primary subarachnoid bleed Subdural/epidural hematoma Focal Ischemic Necrosis (Stroke) Sinus Thrombosis Developmental defects Neurocutaneous Disorders (Tuberous Sclerosis Complex) Epilepsy Syndromes Epileptic Encephalopathies (Early Myoclonic Encephalopathy) Benign Familial Neonatal Convulsions autosomal dominant trait CAUSES DEPENDING ON DAYS OF LIFE First day birth asphyxia intraventricular hemorrhage cerebral agenesis/dysgenesis inborn errors of metabolism infections narcotic withdrawal metabolic causes accidental injection of local anaesthetic into foetal scalp

Second and third day prolonged obstructed labour difficult forceps or vacuum extraction hypoglycaemia infections

Fourth to seventh day tetany kernicterus developmental malformations microcephaly, agenesis of corpus callosum meningitis intrauterine infections toxoplasmosis, CMV tetanus neonatorum

TYPES AND SYMPTOMS OF SEIZURES Seizure type Subtle (>50%) Most common type. Occurs Clinical signs in Preterm Eye deviation and term Blinking/fixed stare Repetitive mouth and tongue movements Apnoea Pedaling Tonic posturing of limbs Sucking and yawning Nystagmus Lip smacking, hiccoughs Preterm Decerebrate or decorticate posturing Eye movements and apnoea Asymmetric position of trunk/neck Term Clonic jerking of one limb with no loss of consciousness Good prognosis Term Random clonic movements of limbs (non-jacksonian migration) Many muscle groups are involved simultaneously Synchronous single or multiple jerks of upper or lower limbs EEG changes Usually no

Tonic seizures (CNS disease) Focal clonic Seizures (Metabolic problems) Multifocal clonic seizures (Metabolic problems) Myoclonic seizures (CNS pathology)

Usually no

Abnormal

Abnormal

Rare

Electroencephalographic classification 1. Clinical seizure with a consistent EEG event: clinical seizure occurs in relationship to seizure activity recorded on EEG. These seizures are clearly epileptic. They respond to anticonvulsants. Eg:clonic seizures

2. Clinical seizures with inconsistent EEG events: clinical seizures without corresponding seizure discharge on EEG. Neonates are neurologically depressed or comatosed. They are non-epileptic origin. Not respond to anticonvulsants. e.g.subtle and generalized tonic seizure 3. Electrical seizures with absent clinical seizures: Abnormal EEG activity with no clinical correlation. Seen in comatose neonates or in a patient with low levels of anticonvulsant in the blood. NON-EPILEPTIC BEHAVIOURS OF NEWBORN Jitteriness spontaneous or stimulus sensitive flexion and extension of equal amplitude diminished by repositioning/flexion of extremity no associated abnormal events

Benign neonatal sleep myoclonus bilateral/unilateral or synchronus/asynchronus myoclonus occurs during active sleep not stimulus reactive Stimulus evoked myoclonus occurs with severe CNS dysfunction focal or generalized myoclonus may have cortical spike-wave discharge on EEG Hyper-reflexia (stiff man syndrome) rare familial disorder hyperactive startle, generalized myoclonus severe hypertonia may have apnoea and bradycardia responds to benzodiazepines Difference between jitteriness and seizures Symptoms Abnormal gaze/eye movement Movements Movements cease Predominant movement EEG Rate or jerks BP/HR Jitteriness Nil Stimulus sensitive Passive flexion/gentle restraint Tremor Normal 5-6/sec Normal Present Spontaneous On their own Colonic jerking Abnormal 2-3/sec Increased Seizures

DIAGNOSIS Seizure history: History of associated eye movements Restraint of episode by passive flexion of the affected limb Change in colour of skin (mottling or cyanosis) Whether the infant was conscious/ sleeping at the time of seizure should be elicited. The day of life on which the seizure occurred may provide an important clue to its diagnosis.

Antenatal history: History suggestive of intrauterine infection, maternal diabetes and narcotic addiction should be elicited in the antenatal history. A history of sudden increase in fetal movements may be suggestive of intrauterine convulsions. Perinatal history: Perinatal asphyxia is the commonest cause of neonatal seizures and a detailed history including history of fetal distress, decreased fetal movements, instrumental delivery, need for resuscitation in the labor room, low Apgar scores (<3 at 1 and/ or 5 minutes) and abnormal cord pH (<7) and base deficit (> 10 mEq/L) should be obtained. Use of a pudendal block for mid-cavity forceps may be associated with accidental injection of the local anesthetic into the fetal scalp. Feeding history: Appearance of clinical features including lethargy, poor activity, drowsiness, and vomiting after initiation of breast-feeding may be suggestive of inborn errors of metabolism. Late onset hypocalcemia should be considered in the presence of top feeding with cows milk. Family history: History of consanguinity in parents, family history of seizures or mental retardation and early fetal/neonatal deaths would be suggestive of inborn errors of metabolism. History of seizures in either parent or siblings in the neonatal period may suggest benign familial neonatal convulsions Examination Vital signs: Heart rate, respiration, blood pressure, capillary refill time and temperature should be recorded. General examination: Gestation, birth-weight and weight for age should be recorded as it may provide important clues to the etiology of the seizure. Seizures in a term well baby may be suggestive of sub-arachnoid hemorrhage. Seizures in a large for date baby may be due to hypoglycaemia. The neonate should be examined for the presence of any obvious malformation or dysmorphic features. CNS examination

Presence of a bulging anterior fontanelle may be suggestive of meningitis or intracranial hemorrhage. A detailed neurological examination should include assessment of consciousness (alert/drowsy/comatose), tone (hypotonia or hypertonia) and fundus examination for chorioretinitis. Systemic examination Presence of hepatosplenomegaly or an abnormal urine odor may be suggestive of IEM. The skin should be examined for the presence of any neuro-cutaneous markers. Presence of hypopigmented macules / ash-leaf spot would be suggestive of tuberous sclerosis. Investigations Mandatory investigations: Blood sugar, hematocrit, bilirubin (if jaundice is present clinically), serum electrolytes (Na, Ca, Mg), arterial blood gas Cerebrospinal fluid (CSF) examination, cranial ultrasound (US) and electroencephalography (EEG). 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 pH, seizure onset within 12-24 hrs). An arterial blood gas (ABG) may have to be performed if IEM is strongly suspected. Specific investigations: These may be considered in neonates who do not respond to a combination of phenobarbitone and phenytoin or earlier in neonates with specific features. These include neuroimaging (CT, MRI), screen for congenital infections (TORCH) and for inborn errors of metabolism. Imaging Neurosonography is an excellent tool for detection of intraventricular and parenchymal hemorrhage but is unable to detect SAH and sub-dural hemorrhage. 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 has both diagnostic and prognostic role in seizures. It should be done in all neonates who need anticonvulsant therapy. 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. 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 electrocerebral inactivity. TREATMENT Immediate management of airway, breathing and circulation. This can be done by suctioning the neonate, providing oxygen and starting IV fluids if circulation is compromised. If baby develops respiratory arrest during or post convulsion, resuscitation with bag and mask ventilation or endotracheal intubation should be done immediately. After stabilizing the neonate, a heel stick glucometer blood sugar (GRBS) is done. If GRBS is 40 mg/dl, 2ml/kg of 10% dextrose is given, followed by 6mg/kg/min of dextrose infusion. If seizure persist blood samples are collected for calcium, electrolytes etc. And 1-2 ml/kg of 10% calcium gluconate is given under IV slowly under continous heart rate monitoring. If seizure persists, anticonvulsant medications have to be used.

Seizures Glucometer blood sugar > 40 mg/dl Blood for calcium estimation Give 2ml/kg 10% calcium gluconate iv Seizure control No yes

<40 mg/dl

Give 2ml/kg IV Infuse glucose 6-8 mg/kg/min

Treat for hypocalcemia

Phenobarbitone 20 mg/kg/kg iv Seizure persistent Seizure persists Phenobarbitone 10 mg/kg iv maximum of 40 mg/kg

Phenytoin iv 20 mg/ kg slow infusion Pyridoxine magnesium Second line anticonvulsants (benzodiazepines) Thiopental Initial medical management: The first step in successful management of seizures is to nurse the baby in thermoneutral environment and ensure airway, breathing and circulation (TABC). O2 should be started, IV access should be secured, and blood should be collected for sugar and other investigations. All this should not require more than 2-5 minutes. Hypoglycemia: If glucostix shows 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. Hypocalcemia: If hypoglycemia has been treated or excluded as a cause of convulsions, the neonate should receive 2ml/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).

Pharmacotherapy for neonatal seizures 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 after the loading dose. Phenytoin 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 ensure with phenobarbitone. The dose is 20 mg/kg IV at a rate of not more than 1 mg/kg/min under cardiac monitoring. 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. Benzodiazepines This group of drugs may be required in up to 15% of neonatal seizures. The commonly used benzodiazepines are diazepam, lorazepam, midazolam, and clonazepam. Diazepam is generally avoided due to its short duration of action, narrow therapeutic index, and because of the presence of sodium benzoate as a preservative. 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. It requires strict monitoring for respiratory depression, apnea and bradycardia. The doses of these drugs are given below: 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: 0.10.2 mg/kg IV bolus followed by infusion 10-30 mg/kg/hr. Other therapies 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). It should ideally be done in the NICU as hypotension and apnea can occur. Exchange transfusion: It is indicated in life-threatening metabolic disorders, accidental injection of local anaesthetic, transplacental transfer of maternal drugs (e.g. chlorpropamide) and bilirubin encephalopathy.

NURSING MANAGEMENT Detailed history collection and physical examination Prevent the newborn from sustaining any harm during seizure Keep the baby on floor Place the newborn on side lying position, it facilitates drainage and help to maintain a patent airway If newborn become cyanotic, administer oxygen Raise the side rails when newborn is sleeping. Side rails and other hard objects padded

Identify and avoid triggering factors like sudden loud noises, sudden movements, dehydration, fatigue, hypoglycaemia, hyperventilation, etc Educate them about the importance of drug therapy and follow up. Advice them not to stop medicines abruptly. Provide psychological support to parents NURSING DIAGNOSIS Nursing Diagnosis 1. Ineffective breathing pattern related to dysfunctional neuro muscular function Place nothing into childs mouth during convulsion Position the child in recovery position Monitor for adequate oxygenation Administer o2 2. Ineffective airway clearance related to inability to control secretions during seizure Place nothing into childs mouth during convulsion Position the child in recovery position Monitor for adequate oxygenation Administer o2 3. Risk for trauma related to uncontrolled movement of seizure activity Protect the baby from injury Keep the padded side rails up Dont try to make the hands straight while convulsion 4. Anxiety related to unpredictable nature of the disease condition 5. Ineffective therapeutic regimen management related to poor adherence with medication 6. Potential for aspiration related to inability to control the secretions Give recovery position Put an airway Do suctioning Dont give water or anything to drink or eat CONCLUSION The prognosis depends on gestational maturity, underlying etiology, EEG, neurologic examination and presence or absence of abnormalities on imaging studies. It is important to impress on the family the need to continue the medication regularly without interruption for as long as required. Nurse should help parents in dealing with psychological and sociologic problems BIBLIOGRAPHY 1. 2. 3. 4. Meherban Singh. Care of the newborn. 6th edition: Sagar publications; New Delhi: 2004 Dipak K Guha. Guhas neonatology principles and practice. 3rd edition: Jaypee publications; 2005 Hockenberry .M. Wongs. Essentials of paediatric nursing,8th edition:Noida,2009 Marlow D R, Redding B.A. Textbook of paediatric nursing,6th edition: Noida,2008