II. Conditions That Mimic Seizures I. Neonatal Seizures II. Conditions That Mimic Seizures

Seizure transient and reversible alteration of behavior caused by a paroxysmal, abnormal and excessive neuronal discharge attack of cerebral origin sudden and transitory abnormal phenomena motor, sensory, autonomic, or psychic transient dysfunction of part or all of the brain

Epilepsy A paroxysmal brain disorder of various etiologies characterized by recurrent seizures due to excessive electrical discharge of cerebral neurons associated with a variety of clinical and laboratory manifestations two or more seizures not directly provoked by intracranial infection, drug withdrawal, acute metabolic changes or fever

Neonatal Seizures Tonic Seizures—focal or generalized, may mimic decorticate or decerebrate posturing, primarily seen 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

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

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.

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

Neonatal Seizures EEG Classification Electrical seizures with absent clinical seizures Electrical seizures associated with markedly abnormal background EEG Seen in comatose patients

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

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

Neonatal Seizures Etiologic diagnosis Hypoxic –ischemic encephalopathy Metabolic Infections Trauma Structural abnormalities Hemorrhagic and embolic strokes Maternal disturbances

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

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

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

Neonatal Seizures Etiologic diagnosis Blood Glucose, calcium, magnesium, electrolytes, BUN In hypomagnesemia  MgSO4 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

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

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

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

Neonatal Seizures Fifth-day fits – 5th day of life normal appearing neonates with mulifocal seizures Present for less than 24 hours Good prognosis

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

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

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%

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

Acute Therapy of Neonatal Seizures With Hypoglycemia -- Glucose, 10% solution: 2 mL/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

Acute Therapy of Neonatal Seizures Other (as Indicated) Calcium gluconate, 5% solution: 4 mL/kg, IV Magnesium sulfate, 50% solution: 0.2 mL/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

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 mL/kg/24 hr, IM Volpe, Neurology of the Newborn, 5th ed. 2008

Clinical Scenario 1 F.M. a 36-37 month old baby boy is noted to have blinking of the eyelids with sucking movements of the mouth at 30 hours of life. The extremities are jittery when tactile stimuli is applied. Maternal history is unremarkable, NSD, G1P1 (1-0-0-1) no hypertension, no infection. Birth weight is 2.5kg. Apgar 8 and 10 at 1 and 5min. The blinking of the eyes and jittery movements of the extremities recur within the next hour.

Clinical Scenario 1 What is your impression? What work-ups will you request? Hgt, CBC, Serum Calcium, Electrolytes What will be your management? Na Luminal 20mg/g IV at 1mg/Kg/min infusion, maintain at 3.5 mg/g/day.

Management of Neonatal Seizures Na Luminal 20 mg/kg/day IV bolus Rate of infusion—1 mg/kg/min Example: Wt is 3 kg, 3 x 20 = 60 mg Give 60 mg for 20 mins. IV push Maintenance dose of Na luminal—5mg/kg/day Example: 3 x 5 = 15 mg Give 7.5 mg IV q12 hrs

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, 5th ed. 2008

Conditions that Mimic Seizures Night terrors Common in boys 5 – 7 years of age Sudden onset between midnight and 2:00 am during stage 3 or 4 of sleep or slow-wave sleep Child screams and appears frightened, dilated pupils, tachycardia and hyperventilation Child thrash violently can not be consoled , unaware of parents or surroundings

Conditions that Mimic Seizures Night terrors 1/3 will have somnambulism Emotional disorder should be explored in patient with prolonged and persistent night terrors Short course diazepam maybe considered while the family dynamics is investigated

Conditions that Mimic Seizures Breath holding spells Cyanotic spells Provoked by upsetting or scolding an infant Brief shrill cry followed by forced expiration and apnea Rapid onset of generalized cyanosis or loss of consciousness may be associated with repeated generalized tonic jerks, opisthotonos, bradycardia EEG: normal Rare before 6 months, peak about 2 years & abate by 5 years old TX: parent counseling

Conditions that Mimic Seizures Breath holding spells Pallid spells Initiated by painful experience Child stops breathing  loss of consciousness  pale and hypotonic  tonic seizures Bradycardia with asystole for 2 seconds may be recorded EEG: normal TX supportive but may give atrophine sulfate at 0.01 mg/kg/24 hr in divided doses with a maximum dose of 0.4 mg

Conditions that Mimic Seizures Syncope Simple syncope Decreased blood flow  loss of consciousness  ischemia influences the higher cortical centers to release inhibiting influence on reticular formation within the brainstem  brief tonic contractions of muscles Results from vasovagal stimulation precipitated by pain, fear, excitement , prolonged standing particularly in a warm environment Age : 10 -12 years old, females

Conditions that Mimic Seizures Syncope Simple syncope Tilt test – effective in producing symptoms including hypotension Tx: oral B adrenergic blocking agents

Conditions that Mimic Seizures Syncope Cough syncope Most common in asthmatic children Occurs shortly after sleep and coughing paroxysm awakens the child Patients face become plethoric, perspires, agitated, frightened Loss of consciousness with generalized muscle flaccidity, vertical upward gaze and clonic muscle contraction lasting for several minutes Urinary incontinence is frequent

Conditions that Mimic Seizures Syncope Cough syncope Cough causes an increased intrapleural pressure  decreased venous return to the right side of the heart  decreased right ventricular output  reduction of left ventricular filling  rapidly diminished cerebral blood flow  cerebral hypoxia  loss of consciousness Tx: Prevention of bronchoconstriction

Conditions that Mimic Seizures Syncope Prolonged QT syndrome Sudden loss of consciousness during exercise or emotional and stressful experience Onset late childhood or adolescence With cardiac arrhythmias such as ventricular fibrillation ECG: abnormal lengthening of the QT interval (corrected QT of 0.46 or more) May be associated with acquired heart disease (myocarditis, mitral valve prolapse, electrolyte abnormalities, drug induced) or congenital forms

Conditions that Mimic Seizures Syncope Prolonged QT syndrome Autosomal recessive trait (Jervell and Lange-Nielsen syndrome) associated with deafness Autosomal dominant (Romano-Ward syndrome)  mutations in cardiac potassium channel gene linked to chromosome 11p15.5 LQT1 LQT2 results from mutation to second potassium channel gene linked to chromosome 7q35-36

Conditions that Mimic Seizures Syncope Prolonged QT syndrome LQT3 result in mutation in cardiac sodium channel linked to 3p21-24 LQT4 linked to chromosome 4q25-27 Testing include supervised exercise test or Holter monitoring Tx: B adrenergic antagonist drugs Permanent implantable cardiac pacing or left thoracic sympathectomy may be considered if drug is not effective Parents shoudls be taught CPR

Conditions that Mimic Seizures Paroxysmal Kinesigenic Choeoathetosis Sudden onset of unilateral or occasional bilateral choreoathetosis or dystonic posturing of a leg, arm and facial grimacing and dysarthia Precipitated by sudden movements, excitement or stress Rare last for more than 1 minute Onset between 8 – 14 years Attacks may be daily or intermittent

Conditions that Mimic Seizures Paroxysmal Kinesigenic Choeoathetosis NE, MRI and EEG – normal Autosomal recessive inheritance is suggested Tx: Phenytoin

Conditions that Mimic Seizures Shuddering attacks Onset at 4 – 6 months of age Sudden flexion of the head and trunk and shuddering or shivering movements May be a precursor to benign essential tremors

Conditions that Mimic Seizures Benign Paroxysmal torticollis of infancy Recurrent attacks of head tilt with pallor, agitation and vomiting Onset : 2 – 8 months Spontaneous remission at 2 – 3 years of age Abnormalities in vestibular function Some patients develop migraine in childhood

Conditions that Mimic Seizures Hereditary Chin trembling Repeated episodes of rapid 3/sec chin trembling movements Precipitated by stress, anger, frustration Autosomal dominant NE and EEG - normal Narcolepsy and cataplexy Narcolepsy begins before adolescence Attacks of irrepressible daytime sleep with transient loss of muscle tone (cataplexy)

Conditions that Mimic Seizures Narcolepsy and cataplexy EEG shows recurrent sleep attacks consist of REM sleep Patients are easily aroused Tx for narcolepsy Modafinil acetamide 200 mg/day

Conditions that Mimic Seizures Cataplexy sudden loss of muscle tone and fall to the floor precipitated by laughter, stress or frightening experience Tx: scheduled naps, amphetamines, methyphenidate, tricyclic antidepressant and counselling regarding occupational safety

Conditions that Mimic Seizures Rage attacks or episodic dyscontrol syndrome Sudden and recurrent episodes of violent behavior with minimal provocation Seem to be psychotic at the time of the attack EEG: normal

Conditions that Mimic Seizures Pseudoseizures Occurs typically between 10 – 18 years old Lack of cyanosis, normal reaction of pupils to light, no loss of sphincter tone Normal plantar response Absence of tongue biting Can be persuade to have an attack by the physician EEG-excessive muscle artifact

Febrile Seizures 3 mo – 6 yrs (peak age of onset 14 – 18 mo) Normal Neurological Exam & development Occurs with fever (not due to CNS Infection) Most commonly due to viral URTI, otitis media, Roseola, UTI Normal EEG Mapped to Chromosomes 19p and 8q13-21 in some families- Autosomal Dominant pattern Incidence Rate: 3-4% of young children

Simple Febrile Seizures Seizures are Generalized Lasts a few seconds, not more than 15 min Occurs only once in 24 hours Complex Febrile Seizures Seizures are focal Lasts more than 15 min More than 2 seizures on the first day, (recurrent)

Factors associated with increased risk of recurrence Age less than 12 mo A positive family history of febrile seizures Complex features Lower temperature before seizure onset Febrile seizures are not associated with decreased intellectual performance.

Factors associated with an increased risk of developing Epilepsy In Children with FS Complex type of FS focal seizures / post ictal neurological sx Positive family history of Epilepsy Onset of FS below 12 years Delayed milestones / Pre Existing Neurologic Disorder

Management Of Febrile Seizures In an actively convulsing patient: Do not put anything in the mouth Time the event Don’t restrain the patient Don’t give anything to drink to the patient Turn the patient to the side to prevent choking Put something under the patient’s head to prevent injury

Management of Febrile Seizures In a convulsing patient with seizures lasting more than 5 min or with recurrent seizures Diazepam 0.2- 0.4mg per kg IV In a patient with just a history of febrile seizure No maintenance anticonvulsant is recommended

Management of Febrile Seizures Careful evaluation of the patient to look for the cause of the fever Antipyretics to lessen discomfort (Have not been shown to lessen the recurrence of febrile seizures) Reassurance and Education of the Parents Advise the parents regarding the use of oral diazepam at the onset of febrile illness Oral Diazepam 0.3 mg/kg every 8 hours on the first day of illness

Use of Maintenance Anticonvulsants 2 AEDs can prevent the recurrence of febrile seizures: Phenobarbital and Valproate However routine use as maintenance anticonvulsants are not recommended for Simple Febrile Seizures Phenobarbital-decreases cognitive function in treated children Valproate – May cause hepatotoxicity in children <2yrs old

Use Of AED’S as prophylaxis in Preventing Recurrence of Febrile Seizures The potential side effects and risks using Phenobarbital and Valproate do not justify its use in a disorder with an excellent prognosis regardless of treatment (SIMPLE FEBRILE SEIZURES) Carbamazepine and Phenytoin do not prevent febrile seizures

Clinical Practice Guidelines on the First Simple Febrile Seizure Lumbar Puncture should be performed in all children below 18 months for a first simple febrile seizure Neuroimaging studies should not be routinely performed In children for a Simple First FS Antipyretic Drugs are used to lower fever and should not be relied upon to prevent the occurrence of FS

Summary of Recommendations First FS 4. The use of continuous anticonvulsants are not recommended in children after a FIRST SIMPLE FEBRILE SEIZURE .Although anticonvulsants can reduce the recurrence of febrile seizures, the adverse side effects of these do not warrant their use in this disorder. 5. The use of intermittent anticonvulsants are not recommended for the prevention of febrile seizures.

Clinical Practice Guidelines (Con,t) 6. Electroencephalogram should not be routinely requested in children with a first simple febrile seizure. Child Neurology Society Philippines and Philippine Pediatric Society, 2000