1. This is only for UAMS neurology internal use.
Pediatric Epilepsies
This is only for UAMS neurology internal use.

2. Questions taken from

3. At what age do human beings attain the predominant alpha frequency that is seen in adults?
A. 6-8 years
B years
C years
D years
E years

4. Basic EEG
Normal pediatric EEG activity has more variation than adult EEG
EEG varies greatly by age
Alpha rhythm
Not present at birth
5-6Hz by 12 months in 70% of children
8Hz by age 3 in 80% of children
Sleep
Sleep spindles by 2 months of age; synchronous by 2 years
Vertex waves by 5 months
Hyperventilation
Diffuse slowing but in young children can be maximum in posterior region
Done to provoke absence epilepsy
Photic stimulation
Photoconvulsive/photoparoxysmal response
Tends to outlast photic stimulation
Suggestive of primary generalized epilepsies

5. Syndrome with Onset in Infancy

6. Newborn with seizures characterized by apneic spells associated with unilateral or bilateral clonic movements that started on day 5 of life. Interictal EEG normal. Examine otherwise normal. Most likely diagnosis?
A. West Syndrome
B. Benign neonatal seizures
C. Aicardi syndrome
D. Ohtahara Syndrome
E. Benign Myoclonic Epilepsy of Infancy

7. Benign Neonatal Convulsions
Begins on days 2-7 of life (5th day fits)
2-7% of neonatal seizures
Frequent brief focal tonic or clonic seizures
usually resolve within 2 weeks
Diagnosis of exclusion
Normal neurological examination before seizure onset and during interictal periods
Etiology unknown
Some infants have de novo mutations in the KCNQ2 gene(voltage dependent potassium channel)

8. 2.5 year old started having seizures at 8mo described as brief generalized myoclonic seizures associated with fast (>3Hz) spike and polyspike and wave discharged. Interictal EEG is normal. Seizures are well controlled on treatment and development remains normal. Most likely diagnosis?
A. Dravet syndrome
B. Ohtahara syndrome
C. Benign myoclonic epilepsy of infancy
D. Generalized epilepsy with febrile seizures plus
E. Myoclonic astatic epilepsy

9. Benign myoclonic epilepsy of infancy
Starts between 4mo-3 years
Characterized by brief myoclonic seizures that are easily treatable
More prominent in drowsiness, photostimulation and external stimulation
Interictal EEG normal; ictal EEG shows generalized spike and polyspike wave discharges
Good prognosis with easy to treat seizures and most with spontaneous resolution of seizures in less than a year

10. You see a 15 day old neonate with severe hypotonia and frequent tonic spasms occurring in clusters of more than 100/day. EEG shows burst suppression present in wakefulness and sleep. Most likely diagnosis?
A. Dravet syndrome
B. Ohtahara syndrome
C. Benign myoclonic epilepsy of infancy
D. Generalized epilepsy with febrile seizures plus
E. Myoclonic astatic epilepsy

11. Early Infantile Epileptic Encephalopathy
Also known as Ohtahara Syndrome
Etiology typically associated with structural brain abnormalities
Inborn errors of metabolism are rare
Some genes identified including KCNQ2, SLC25A22, etc
Onset is within the first 3 months of life
Abnormal neurological examination at onset (dev delay, spasticity)
Predominant seizure type is tonic spasms
EEG shows burst suppression pattern seen across all sleep-wake cycles
Prognosis is poor with ~50% passing away in infancy

12. Early Myoclonic Encephalopathy
Most often associated with inborn errors of metabolism
nonketotic hyperglycemia, pyridoxine dependency, etc
Congenital brain anomalies are uncommon etiology for EME
Neurological examination is abnormal at onset with encephalopathic infant
Segmental erratic myoclonic seizures are earliest seizures typically seen but focal clonic seizures and repetitive tonic spasms can develop later on
EEG: burst suppression pattern mainly in sleep but can be present in all stages
Prognosis is poor with ~50% passing away in the first year of life

13. 6mo old brought in by parents for sudden episodes of tonic flexion of limbs and body occurring in clusters after wakening. EEG is as below. Diagnosis?
A. juvenile myoclonic epilepsy
B. Infantile spasms
C. myoclonic epilepsy
D. BECTS
E. Absence epilepsy

14. Which of the following is the most accepted treatment of this disorder?
A. lamotrigine
B. phenytoin
C. phenobarbital
D. ACTH
E. carbamazepine

15. Epileptic Spasms
Age on onset usually less than 1 year of age (range 1 day-4.5 years)
Seizures consist of usually symmetric and synchronous contractions of one or more muscle groups followed by a longer tonic phase
Can see flexor, extensor or mixed flexor-extensor spasms
Most often occur in clusters
Occur more frequently in waking state and arousal than during sleep
Developmental regression usually begins with onset of spasms
EEG: hypsarrhythmia (very high voltage chaotic slow wave and spikes diffusely)
Treatment: ACTH, Vigabatrin
Overall prognosis is poor
50-90% develop other seizure types
85% develop developmental retardation

16. E. Myoclonic-astatic epilepsy
A 9mo old girl has blindness, infantile spasms and abnormal retinal examination. Brain MRI shows agenesis of the corpus callosum. Which of the following is the most likely diagnosis?
A. West Syndrome
B. Ohtahara Syndrome
C. Dravet Syndrome
D. Aicardi Syndrome
E. Myoclonic-astatic epilepsy
X-linked pattern of inheritance. Mutation usually lethal in males. Presence of chorioretinal lacunae is pathognomonic for this syndrome.

17. Mutations in which gene is most commonly associated with generalized epilepsy with febrile seizures plus (GEFS+)?
A. SCN1A
B. SCN1C
C. SCN1B
D. SCN2A
E. GABRD

18. 2 year old with a history of developmental delays and a prolonged FS at the age of 1 is now admitted with frequent seizures of multiple types including myoclonic, absence, focal and generalized tonic clonic seizures. Most likely diagnosis?
A. Dravet Syndrome
B. Ohtahara syndrome
C. Benign myoclonic epilepsy of infancy
D. Landau-Kleffner Syndrome
E. Myoclonic-Astatic epilepsy

19. Dravet Sydrome
Early onset epileptic encephalopathy characterized by refractory epilepsy and neurodevelopmental declines
Patients typically present in 1st year of life with prolonged, often febrile, seizures with normal development prior to onset of seizures
Have multiple types of seizures that are often refractory with associated cognitive and behavioral impairment. Can have gait and posterior abnormalities
70-80% have mutation in SCN1A mutation
Avoid Na channel blocking medications such as phenytoin

20. Epilepsies in children and adolescents

21. 7 year old boy has recurrent nocturnal events where parents witness him shaking uncontrollably. Some events have only involved facial and arm twitching. EEG is most suggestive of what diagnosis?
A. Juvenile myoclonic epilepsy
B. Metabolic encephalopathy
C. Myoclonic epilepsy
D. BECTS
E. Periodic lateralized epileptiform discharges

22. A. phenytoin B. valproic acid
Given previous diagnosis, what is the antiepileptic of choice, given no contraindications?
A. phenytoin
B. valproic acid
C. topiramate
D. carbamazepine
E. ethosuximide
Temporal lobe is not generator; rolandic fissure is

23. BECTS Benign Epilepsy of Childhood with Centrotemporal spikes (BECTS)
Previously known as Benign Rolandic Epilepsy
25% of all childhood epilepsies
Onset between 4-10 years
Remission in midteens
Semiology initially consists of unilateral paresthesias of tongue, lips and cheek and/or unilateral clonic activity of facial muscles, at times with secondary generalization
70% only in sleep, 15% only awake, 15% both
EEG: independent bihemispheric centrotemporal spikes that increase with sleep; ~1/3 only have discharges during sleep
Prognosis: Very good; AEDs can generally be stopped after adolescence

24. Which of the following is true about oxcarbazepine in comparison to carbamazepine?
A. is not a hepatic enzyme inducer
B. no risk of hyponatremia
C. is not metabolized to an epoxide
D. indicated in both partial and generalized epilepsy
E. No risk of rash

25. 11 year old brought to EMU for possible pseudoseizures
11 year old brought to EMU for possible pseudoseizures. Spells mainly at ight with violent like movements. Awake EEG normal. Overnight, a seizure is captured during non-REM sleep. Diagnosis?
A. Electrical SE during slow wave sleep (ESES)
B. Lennox-Gastaut syndrome
C. Landau-Kleffner syndrome
D. AD nocturnal frontal lobe epilepsy
E. Panayiotopoulos syndrome

26. AD Nocturnal Frontal Lobe Epilepsy
Autosomal Dominant
Presents in childhood or adolescence (mean age: 14years) with clusters of usually brief nocturnal seizures arising in non-REM sleep
Interictal EEG often normal
Cognition and neurological examination usually normal
Most cases are non-lesional
Genetic forms: most related to neuronal nicotinic acetylcholine receptor
CHRNA4, CHRNA2, CHRNB2
Prognosis: spontaneous remission is rare and up to 1/3 will have drug resistant epilepsy

27. 4 year old wit episodes of visual phenomena, which he cannot describe, followed by eye deviation and vomiting. He has had 3 episodes total. EEG shows normal background with high-voltage occipital spikes which disappear with eye opening. Most likely diagnosis?
A. Ohtahara syndrome
B. Late onset or Gastaut type childhood occipital epilepsy
C. Early onset or Panayiotopoulos type childhood occipital epilepsy
D. Dravet Syndrome
E. Doose’s syndrome

28. Childhood Epilepsy with Occipital Paroxysms
Early Onset (Panayiotopoulos Syndrome)
Peak age of onset: 4-6 years
Semiology: variety of autonomic symptoms such as feeling sick, nausea, vomiting, tonic eye deviation lasting minutes
Partial or generalized tonic clonic seizures can occur during sleep
Nearly all patients become seizure free by age 12
Late Onset (Gastaut type)
Peak age of onset: 7-9 years
Semiology: visual symptoms lasting seconds; ½ of patients complain of severe headache with nausea and vomiting
Prognosis is variable but most patients have a benign course
EEG is the same in both with high amplitude occipital spikes which can be bilaterally independent; increases with sleep; disappears with eye opening and reappear with eye closure

29. Patient with inattentiveness at school has the following EEG which is characteristic of what type of epilepsy?
A. Juvenile Myoclonic Epilepsy
B. Absence Epilepsy
C. Myoclonic Epilepsy
D. BECTS
E. Lennox-Gastaut Epilepsy

30. Absence Epilepsy Childhood Absence Epilepsy Juvenile Absence Epilepsy
Onset of seizures between 3-12 years
Juvenile Absence Epilepsy
Onset between years
More likely to develop GTC and myoclonic seizures
Less likely to remit
EEG: Generalized 3cps spike and wave discharges
Initial complex may have polyspike pattern
Hyperventilation precipitates bursts in 50-80% of patients
20-40% will show OIRDA
Pathophysiology: generated through thalamus with the low threshold (T-type Ca channels of thalamic neurons playing a central role in thalamocortical interactions
Mutations: Ca channel, Chloride channel (CLCN2), GABAa receptor (GABRG2, GABRA1)
Treatment: Ethosuximide (acts via T-type calcium channel inhibition), VPA, Lamotrigine

31. A. Lamotrigine significantly incrases the half life of valproic acid.
Which of the following best describes the interaction between valproic acid and lamotrigine?
A. Lamotrigine significantly incrases the half life of valproic acid.
B. Valproic acid significantly decreases the half life of lamotrigine
C. Valproic acid significantly increases the half life of lamotrigine
D. Lamotrigine significantly decreases the half life of valproic acid
E. Lamotrigine and valproic acid do not have any significant interactions
Vpa can increase the half life of lamotrigine by hours

32. In a patient with absence epilepsy, which of the following AEDs is least likely to precipitate absence status epilepticus?
A. Phenytoin
B. Topiramate
C. Carbamazepine
D. Lamotrigine
E. Gabapentin

33. 12 year old boy with complaints of early morning falls, clumsiness and dropping objects presents with GTC seizure. EEG is most consistent with which diagnosis?
A. Juvenile myoclonic epilepsy
B. Absence epilepsy
C. Myoclonic epilepsy
D. BECTS
E. Lennox-Gastaut epilepsy

34. A. phenytoin B. valproic acid
When necessary, what is the antiepiletic of choice for this condition, given no contraindications?
A. phenytoin
B. valproic acid
C. topiramate
D. carbamazepine
E. phenobarbital
Remember carbamazepine and phenytoin can worsen absence and myoclonic seizures

35. JME Juvenile Myoclonic Epilepsy Onset between 12-18 years
Both myoclonic and GTC convulsions tend to occur within 1-2 hours of awakening
History of absence seizures coexists with or preceded myoclonic seizures in ~1/2 patients
Seizure triggers include sleep deprivation and alcohol consumption
EEG:
4-6Hz spike and polyspike and wave discharges; photosensitivity in 20-40%
Mutations: GABAa, Ca channel, Cl channel
Tx: Levetiracetam, VPA
Initially thought to be life long epilepsy but recent studies suggest some patients might outgrow this.

36. 4 year old boy with normal cognitive development is brought in after a GTC seizure. Recently he has been having increased falls. Mother reports he loses tone, causing him to fall. He can also have episodes of jerk-like movements that cause him to fall. EEG shows bilateral synchronous irregular 2-3Hz spike and wave complexes as well as parietal rhythmic theta activity. Most likely diagnosis?
A. Dravet Syndrome
B. Ohtahara syndrome
C. Benign myoclonic epilepsy of infancy
D. Generalized epilepsy with febrile seizures +
E. Myoclonic-astatic epilepsy (Doose’s syndrome)

37. Epilepsy of Doose (Myoclonic-Astatic Epilepsy)
Typical onset between 1-5 years
Children are normal prior to onset of seizures and many continue to have normal development; however, some have severe developmental delay and intractable seizures
Main seizures are myoclonic or astatic
Can have other types of generalized seizures
EEG can show interictal bilateral synchronous irregular 2-3Hz spike and wave complexes as well as rhythmic parietal theta activity

38. 3 year old with cognitive and developmental delay
3 year old with cognitive and developmental delay. He began having seizures involving drop attacks one year ago but progressively developed multiple seizure types. Multiple AEDs tried with mild improvement but he still has multiple seizures per day. EEG shows 2cps spike- wave discharges. Diagnosis?
A. Panayiotopoulos syndrome
B. West syndrome
C. Landau-Kleffner Syndrome
D. Lennox-Gastaut Syndrome
E. seizures associated with mesial temporal sclerosis

39. Lennox-Gastaut Syndrome
Most commonly present between 3-5 years of age
Often evolve from other syndromes such as infantile spasms
Characterized by:
Multiple seizure types
Slow <2.5cps spike wave pattern
Mental retardation (90%)
Prognosis is poor with low likelihood of seizure control

40. Parents of 5 year old report he has been more withdrawn over the past several months. One year ago he began having seizures, initially myoclonic and recently GTC. About 9 months ago he was having problems understanding verbal communication and now appears aphasic. EEG shows multifocal spikes. Diagnosis?
/a. Panayiotopoulos syndrome
B. West syndrome
C. Landau-Kleffner syndrome
D. Lennox-Gastaut syndrome
E. Seizures associated with mesial temporal sclerosis

41. Landau Kleffner Syndrome
Patients develop normally until approximately 3-6 years of age
Begins with auditory verbal agnosia (children behave as if they were deaf) and ultimately develop expressive language difficulties
75% will have clinical seizures of various types
EEG: bilateral independent temporal or temporoparietal spikes; eventually near continuous spike and wave during non-REM sleep
Epileptiform process appears to originate in the language cortex of the dominant temporal lobe and secondarily spreads
Prognosis: many have persistent seizures and residual language dysfunction

42. Epileptic Encephalopathy with Continuous Spikes and Waves during Sleep (CSWS)
Epileptic encephalopathy characterized by:
Seizures
Developmental regressions in at least two domains
EEG pattern of ESES
Etiology unknown in many cases but often structural causes or mutations such as in the GRIN2A gene have been found
Typically normal or only mild cognitive difficulties until seizures start around 2-4 years of age
Unlike LKS, regression is seen across many domains
EEG: during wakefulness shows focal or multifocal spikes with continuous bilateral slow spike and waves during at least 85% of nonREM sleep.
Prognosis usually poor with severe neurocognitive regression and outcomes

43. 13 year old is being evaluated for epilesia partialis continua
13 year old is being evaluated for epilesia partialis continua. Rasmussen’s syndrome is suspected. What would be the most common finding on brain MRI in Rasmussen’s syndrome?
A. Lissencephaly
B. Schizencephaly
C. Cortical atrophy
D. Pachygyria
E. Porencephaly

44. Rasmussen’s Syndrome
Rasmussen’s syndrome is characterized by progressive unilateral hemispheric atrophy, associated progressive neurologic dysfunction and intractable focal seizures
Uncertain pathogenesis but thought to be immune-mediated
Usually presents between 14mo-14 years
Best treatment for those with intractable seizures is hemispherectomy

45. 14 year old with progressive cognitive decline and ataxia has a history of myoclonic epilepsy ad multiple seizure types. EEG shows spikes and waves with predominance in the occipital region. Skin biopsy shows periodic-acid-Schiff- positive intracellular inclusions. Most likely diagnosis?
A. Lafora body disease
B. Unverricht-Lundborg Syndrome
C. Sialidosis
D. Juvenile myoclonic epilepsy
E. Neuronal Ceroid Lipofuscinosis

46. Progressive Myoclonic Epilepsies
Lafora body disease: AR; mutations in EPM2A encoding Laforin; presents between years; various seizures, dysarthria, ataxia, dementia; most patients die within 10 years of onset and treatment is palliative
Unverricht-Lundborg Syndrome:AR; presents between 6-15 years with stimulus sensitive myoclonus but eventually develops multiple seizure types; patients may worsen progressively but in some cases the disease stabilizes over time
Sialidosis: AR; Type 1 is caused by deficiency of alpha-neuroaminidase and presents in adolescents with action myoclonus and slowly progressive ataxia, tonic-clonic seizures and vision loss. Cherry red spot. Do not have cognitive deterioration
NCL: AR; progressive psychomotor retardation, seizures and blindness; mutations in several genes have been described (CLN1-CLN10); can present in infantile, late infantile, juvenile and adult forms
Photoparoxysmal responses are common in patients with Lafora disease, Unverricht-Lundborg disease, and Batten disease. In Batten disease, single or low-frequency intermittent photic stimulation characteristically produces prominent spike discharges at occipital electrodes with a one-to-one relationship with the light flash

47. The other stuff….

48. In a patient who has suffered a febrile seizure, which of the following choices is least likely predictor of developing subsequent epilepsy?
A. Family history of febrile seizures
B. Complex febrile seizure
C. Developmental delay
D. Family history of epilepsy
E. Neurologic Abnormality

49. Febrile Seizures 6 months-6 years of age
90% of seizures occur in first 3 years of life
Up to 5% of children have at least one febrile convulsions
Occurs in the setting of a fever
Simple
Only one in 24 hours
Less than 15 minutes in duration
Generalized
Complex
More than one in 24 hours
Greater than 15 minutes
Focal semiology or deficit

50. Febrile Seizures
For simple febrile seizure, EEG and MRI are not indicated
Recurrence risk after a single febrile seizure
Simple: 30% (1/3 will have another febrile seizure)
Complex: 50%
Risk of Epilepsy in children after febrile seizures
<5% risk of epilepsy after simple febrile seizure
Increased risk of epilepsy if: developmental delay, abnormal neurologic examination, complex febrile seizures and family history of epilepsy
Treatment: supportive (AAP does not recommend continuous or intermittent anticonvulsant therapy in children with simple febrile seizures)

51. Non-Epileptic Paroxysmal Events in Pediatrics
Infants
Benign neonatal myoclonus
Repetitive myoclonic jerks of extremities during sleep
Tends to have migratory myoclonus
Goes away when infant wakes up
Tends to resolve around 3 months of age
Reflux/Sandifer Syndrome
Intermittent spells of stiffening and posturing
Associated with feedings
Benign myoclonus of early infancy
Brief contractions involving axial muscles
Can occur in clusters
Resolves by age 2

52. Non-Epileptic Paroxysmal Events in Pediatrics
Infants
Spasmus Nutans
Head nodding, head tilt, nystagmus
4-12 months of age
MRI to rule out mass lesion of optic chiasm or 3rd ventricle based on examination
Shuddering Attacks
Precipitated by emotions (fear, frustration)
Can see family history of essential tremor
Self gratification
Rocking pelvis, rubbing of thighs together
Sweating, flushing of face
distractible

53. Non-Epileptic Paroxysmal Events in Pediatrics
Older Children
Breath Holding Spells
6mo-6 years with peak around 2-3 years
Cyanotic
Provocation—cries—holds breath in expiration—cyanosis
Pallid
Induced by mild trauma—stops breathing, pale—loss of consciousness
Can do iron deficiency screening
Movement disorders
Paroxysmal kinesiogenic dyskinesia
Repetitive attacks of dystonia or choreoathetosis precipitated by movement
Chromosome 16p11.2

54. Non-Epileptic Paroxysmal Events in Pediatrics
Parasomnias
Night terrors (typical onset age 4), Narcolepsy
Migraine Headaches
Confusional migraines
Alice in Wonderland
Distortions of perception, change in size and shape of surroundings
Syncope
Nonepileptic events

55. Non-Epileptic Paroxysmal Events in Pediatrics
Nonepileptic Events
5-10% but higher rate in those admitted to EMUs
Up to 10% of those with PNES have comorbid epileptic seizures
Men: Woman= 1:3
Risk factors
Younger age
Poor social economic status
Female
Psychosocial stressors
Psychiatric comorbidity

56. Non-Epileptic Paroxysmal Events in Pediatrics
Nonepileptic events
PNES symptoms in history:
Not responding to AEDs
Unusual presentation
Signs on exam:
Eye flutter
Closed eyes
Fluctuating course
Pelvic thrusting
Ictal weeping
Flapping hand movements
Asynchronous movements
Recall of apparent unconsciousness

57. Questions?