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

2. 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

3. 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

4. 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

5. 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

6. 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.

7. 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

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

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

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

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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

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

20. 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 mg/day x 6 weeks
Lifelong supplementation : 10 mg/day

21. 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

22. Prognosis of Neonatal Seizures: Relation to Neurological Diseases
Neurological Disease* Normal Development
Hypoxic-ischemic encephalopathy %
Intraventricular hemorrhage %
Primary subarachnoid hemorrhage %
Hypocalcemia
Early-onset %
Later-onset %
Hypoglycemia %
Bacterial meningitis %
Developmental defect %

23. 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

24. 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 ( mg/kg/min)
(Lorazepam: mg/kg, IV) if available
Midazolam: 0.2 mg/kg, IV;then, mg/kg/hr, IV

25. 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: 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

26. 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

27. Clinical Scenario 1
F.M. a 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 ( ) 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.

28. 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.

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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 : years old, females

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

37. 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

38. 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

39. 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

40. 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

41. 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

42. 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

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

44. 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

45. 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

46. 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)

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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)

53. 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.

54. 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

55. 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

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

57. 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

58. 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

59. 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

60. 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

61. 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.

62. 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