about seizures in children, epilepsy, various classifications and management

1. SEIZURES IN CHILDREN
Presentor- Dr. Anusha Kattula, DNB pediatrics
St.philomenas hospital,Bangalore
Moderators- Dr.Rajeev
Dr. Pankaj
18-5-2015

2. Definition
• A seizure is a transient occurrence of signs and/or symptoms resulting
from abnormal excessive or synchronous neuronal activity in brain
• 2 large categories
1. Focal/ partial
2. Generalized
febrile seizures is a special category

3. • Acute symptomatic seizures- acute problem affecting brain excitability
• Unprovoked seizures
• Remote symptomatic seizures- distant brain injury

5. • Most common- febrile seizures
• Infections
• Metabolic disorders
• Drugs

10. EPILEPSY
• Disorder of brain characterized by an enduring predisposition to
generate seizures and by the neurobiologic, cognitive, psychological
and social consequences of this condition
• 1 unprovoked epileptic seizure+ 2nd such seizure
OR
enough EEG or clinical predisposition
• More than 2 unprovoked seizures in >24 hrs

11. • Seizure disorder- any one of the several disorders including
 epilepsy
 Febrile seizure
 single seizures
 secondary to metabolic, infectious , or other etiologies

12. • Epileptic syndrome- manifests one or more seizure types
specific age of onset and specific prognosis
• Epileptic encephalopathy- severe EEG abnormality to result in
cognitive impairment
• Idiopathic epilepsy- genetic
• Symptomatic epilepsy- by an underlying brain disorder
• Cryptogenic epilepsy(presumed symptomatic epilepsy)- underlying
brain disorder which is not known

16. EVALUATION OF FIRST SEIZURE
• HISTORY
• 1st step- focal/ generalized
• Motor seizures may be focal/generalized and tonic-clonic, tonic,
clonic, myoclonic or atonic
• Duration
• State of consciousness
• Aura and behavior preceding convulsion
• Posture, cyanosis, vocalization, sphincter control, post ictal state

17. • Look for causes of seizures
meningitis
systemic sepsis
hypoglycemia/hypocalcemia
unintentional and intentional head trauma
ingestion of drugs of abuse and other toxins
• Family history

18. • Seizure mimics
Benign paroxysmal vertigo
Night terrors
Breath-holding spells
Syncope
Prolonged QT syndrome
Paroxysmal kinesigenic choreoathetosis
Shuddering attacks
Benign paroxysmal torticollis of infancy
Narcolepsy and cataplexy
 masturbation
Pseudo seizures
Hereditary chin trembling
Rage attacks or episodal dyscontrol
syndrome

19. • Cardiorespiratory and metabolic status
• General and neurologic examination
• Eyegrounds
• Facial features,skin lesions, hepatospleenomegaly

20. • EEG
• Brain imaging- CT and MRI
• Spinal tap- in suspected meningitis/ encephalitis
without brain swelling/papilloedema
suspected intracranial bleed
for xanthochromia
glucose transporter deficiency/ cerebral folate deficiency
pyridoxine deficiency, NKH, neurotransmitter deficiency

21. • Recurrent seizures- 2 seizures spaced >24hrs needs further workup
a full metabolic workup
vitamin B6(100 mg i.v)- to rule out pyridoxine responsive seizures
• Pyridoxal phosphate orally upto 50mg/kg
• Folinic acid(upto 3mg/kg)

22. PARTIAL SEIZURES
• 40% of seizures in children
• Simple partial
• Complex partial
• Can progress to secondary generalized seizures

23. • SIMPLE PARTIAL SEIZURES
• Sensory seizures(auras)
• Brief motor seizures
• Motor march(Jacksonian ), adversive head and eye movements
• Postictal paralysis(todds)
• Not under partial voluntary control, often stereotyped

24. • COMPLEX PARTIAL SEIZURES
• Last 1-2 min
• Preceeded by aura- micropsia and macropsia(temporal lobe)
- generalized difficult to characterise(frontal lobe)
- focal sensations(parietal lobe)
- simple visual experiences( occipital lobe)
• Automatisms
• Frontal lobe seizures- often occur at night, numerous and brief

25. • SECONDARY GENERALISED SEIZURES
• Start with generalized clinical phenomena
• Or generalization from partial seizures
• Last 1-2min
• Adversive head deviation suggest frontal origin
• Fencing, hemi or full figure of four arm

26. • EEG- focal spikes or sharp waves
• 15%- normal EEG
• 24 hour video EEG monitoring
• MRI> CT ( can show pathologies)

27. • BENIGN EPILEPSY SYNDROMES WITH PARTIAL SEIZURES
Benign childhood epilepsy with centrotemporal spikes( BECTS)
• Wakes up at night- simple partial seizure of one side of face
• EEG – broad based centrotemporal spikes
• MRI- normal
• Respond well to AEDs

28. • Benign epilepsy with occipital spikes
Early childhood(panayiotopoulos)- complex partial, ictal vomiting
Later childhood(gastaut)- complex partial, visual auras, migraine
• Benign infantile familial convulsion syndromes
• Benign infantile nonfamilial syndromes
• Nocturnal autosomal dominant frontal lobe epilepsy

29. SEVERE EPILEPSY SYNDROMES WITH PARTIAL SEIZURES
• Multifocal severe partial seizures MIGRATING PARTIAL
• progressive mental regression EPILEPSY OF
• Cerebral atrophy INFANCY
• Absence seizures and drop attacks- pseudo lennox gastaut syndrome

30. • Temporal lobe epilepsy- mesial temporal sclerosis
• Activation of temporal discharges in sleep- Landau-Kleffner epileptic
aphasia syndrome
• Activation of frontal and secondary generalized discharges in sleep-
Syndrome of continuous spike waves in slow wave sleep
• Rasmussen’s encephalitis- u/l intractable partial seizures, epilepsia
partialis continua, progressive hemiparesis of affected side,
progressive atrophy of contralateral hemisphere

31. Mesial temporal sclerosis
gliosis and atrophy of left hippocampus

32. Rasmussens encephalitis
Atrophy of left cerebral hemisphere

33. GENERALISED SEIZURES AND RELATED
SYNDROMES
• ABSENCE SEIZURES
• Start at 5-8 yrs of age
• No aura, last for few seconds, flutter or upward rolling of eyes
• No post ictal period
• Hyperventilation can precipitate
• Atypical absence- associated myoclonic component
tone changes are difficult to treat
precipitated by drowsiness
1-2 hz spike and slow wave discharges

34. • Juvenile absence- at later age
- 4-6 hz spike and slow wave, polyspike and slow
wave discharges
a/w juvenile myoclonic epilepsy

36. • GENERALISED MOTOR SEIZURE
• Most common- GTCS
• Starts with loss of consciousness, sudden cry, upward rolling of eyes
and generalized tonic contraction
• Tonic phase----clonic phase
• Incontinence and post ictal period( 30 min to hours)
• Single idiopathic GTCS- a/w intercurrent illness or cause that cant be
ascertained

37. • BENIGN GENERALISED EPILEPSIES
• Petit mal epilepsy- starts in midchildhood
• Benign myoclonic epilepsy of infancy- onset of myoclonic and other
during 1st yr with 3 hz spike and slow wave
• Febrile seizure plus syndrome- febrile seizures and multiple types of
generalized seizures in multiple family members

38. • Juvenile myoclonic epilepsy( janz syndrome)- m.c generalized epilepsy
in young adults(5%)
Myoclonic jerks in morning
Generalised tonic clonic or clonic-tonic-clonic upon awakening
Juvenile absences
EEG- 4-5 hz polyspike and slow wave

39. • Photoparoxysmal epilepsy-
Occipital, GTCS, absence or myoclonic generalized seizures are
precipitated by photic stimuli

40. • SEVERE GENERALISED EPILEPSIES
• Intractable seizures and developmental delay
• Early myoclonic infantile encephalopathy( EMIE)- starts during 1st 2
months, severe myoclonic jerks and burst suppression pattern
• Early epileptic infantile encephalopathy(EIEE, Ohtahara syndrome)-
tonic seizures, brain malformations or syntaxin binding protein1
mutations)

41. • Severe myoclonic epilepsy of infancy( dravet syndrome)- focal febrile
status epilepticus--- to myoclonic and others
• West syndrome- starts between ages 2 and 12 months
triad of infantile spasms, developmental regression,
hypsarrythmia

42. • Lennox-gastaut syndrome- 2 and 10 yrs
- triad of developmental delay, multiple
seizure types, 1-2 hz spike and slow waves, polyspike bursts in sleep
Myoclonic astatic epilepsy- milder

43. Progressive myoclonic epilepsies- progressive dementia, worsening
myoclonic and other seizures
• Type 1 or Unvericht Lundborg disease- slowly progressive, starts in
adolescence
• Type 2 or Lafora body disease- early childhood onset, quickly
progressive, fatal
-photosensitivity, manifests PAS positive lafora inclusions in
muscle or skin biopsy

44. • Myoclonic encephalopathy in non progressive disorders- epileptic
encephalopathy in angleman syndrome
• Landau-Kleffner syndrome- m.c in boys
-mean onset 5 ½ yrs
- loss of language skills
- aphasia, auditory agnosia, normal hearing
- high amplitude spike and wave( bitemporal)
- CT and MRI- normal results
- PET- u/l or b/l hypo/hypermetabolism

45. • Valproic acid is DOC
• leviteracetam/ or nocturnal diazepam therapy(0.2-0.5mg/kg PO)
• If seizures persist- prednisone- 2mg/kg /day for 1 month
tapered to 1mg/kg/day- 1month
• Speech therapy
• subpial transection
• methylphenidate

46. MECHANISMS OF SEIZURES
• Underlying etiology- brain tumors, strokes, scarring or mutations
• Mutations can involve voltage gated channels,ligand gated channels
and Ɣ-amino butyric acid A receptors [ GABA A]
• Kindling- animal model for temporal lobe epilepsy
- repeated stimulation- activation of metabotropic and
ionotropic glutamate receptors as well as TrkB receptor , BDNF and
neurotrophin 4

47. • Increase in intraneuronal Ca
• Activates CaMK2 and calcineurin
• Ca dependant epileptogenic gene expression
• Sprouting of mossy fibres
• Increased excitability and epilepsy

49. • Epileptic state of increased excitability present in all patients
• In a seizure focus each neuron has stereotypic synchronized response
called paroxysmal depolarization shift

50. • Sudden depolarization( glutamate and Ca channel activation)
• Afterhyperpolarisation(K channels and GABA receptors)

53. • T-type Ca channels on thalamic relay neurons are activated resulting
in spike wave pattern
• 4th process
• Seizure related neuronal injury
• In MRI after prolonged febrile and afebrile status epilepticus
• Acute swelling in hippocampus and long term hippocampal atrophy
with sclerosis
• Apoptosis and necrosis of neurons

55. NEUROCUTANEOUS DISORDERS
• Tuberous sclerosis
• Type 1 neurofibromatosis
• Sturge weber syndrome
• Epidermal nevus syndrome
• Hypomelanosis of ito
• Incontinentia pigmenti

56. Neurocutaneous syndrome?

59. • Brain malformations and maldevelopments
• Abnormalities of cortical development-
Metabolic disorders-peroxisomal disorders, menkes disease
Chromosomal disorders
Neuromuscular diseases
• Heterotopias
• Agyria-pachygyrias
• lissencephaly

60. • Schizencephaly
• Hemimegalencephaly
• Agenesis of corpus callosum
• Aicardi syndrome
• Cortical microdysgenesis

61. BRAIN TUMORS
• Low grade astrocytomas
• Oligodendrogliomas
• Gangliogliomas
• Gangliocytomas
-mostly focal
-gelastic seizures

62. • Dysembryoplastic neuroepithelial tumors(DNET)- benign
supratentorial
• Angiocentric neuroepithelial tumors(ANET)
• MRI is imaging of choice

63. CAVERNOUS ANGIOMAS
• Thin walled clusters of dilated blood vessels
• CT- areas of calcification
• MRI
• Can enlarge- space occupying lesions
• Treatment- surgical

64. GENETIC DISORDERS
• Angelman syndrome- epilepsy in 90%
Happy puppet syndrome
Cortical myoclonus- responds to piracetam
May present as west/ lennox gastaut syndrome
Early to mid childhood
EEG- high amplitude posterior slow waves with or without spikes

65. • RETT SYNDROME
• X-linked dominant
• Seizures in 3rd or pseudostationary period(2-10 yrs)
• Atypical absences
• Hyperventilation

66. • FRAGILE X SYNDROME
• PEHO(progressive encephalopathy with edema, hypsarrythmia and
optic atrophy)

67. • METABOLIC DISORDERS
• Nonketotic hyperglycinemia- early myoclonic and ohtahara syndrome
• Vitamin responsive seizures- pyridoxine dependant
-40-300 mg pyridoxine
• Biotidinase deficiency- a/w skin rashes, alopecia,ataxia
• Glucose transporter deficiency

68. • CEREBRAL PALSY
• Not a disease
• Abnormalities of movement and posture
• Epilepsy in 10-40%
• More common in spastic hemiplegia and quadriplegia

69. INVESTIGATIONS
• EEG
• Single most useful investigation in children
• Visual representation of differences in electric potential between
different areas of brain
Recorded from scalp using 20 electrodes
Interictal EEG
Ictal EEG

70. • NEUROIMAGING
• MRI- only method of importance
• CT- skull fractures, fresh bleed, ready availability
• Cranial ultrasound in neonates
• MRI detects
Malformations/maldevelopments
Vascular disorders
Sclerosis and gliosis in old infarcts
tumors

71. • Malformations- T1 weighted images
• Tumors and gliotic tissue- T2 images
• FDG(fluoro deoxy glucose) PET- interictal focal areas of
hypometabolism
• SPECT(single photon emission tomography)

72. TREATMENT
• After 1st seizure if risk of recurrence is low, normal
neurodevelopment, EEG and MRI- no treatment
• COUNSELLING
• Educating family and child about disease, its management and
limitations
• Restrictions on driving and swimming
• Educational and psychological evaluation- learning disabilities or
abnormal behavior patterns

73. • Long term AED after 2nd seizure
• Aim of treatment is complete seizure control without side effects
• AED based on predominant seizure type
• Started in low doses and gradually increased to maximum doses

74. DOC
• Focal seizures and epilepsies- oxcarbazepine, carbamazepine
• Absence seizures- ethosuximide
• Juvenile myoclonic epilepsy- valproate and lamotrigine
• Lennox gastaut- valproate , topiramate, lamotrigine
• Infantile spasms- ACTH

77. • ADDITIONAL TREATMENT
• Patients with drug resistance- careful diagnostic evaluation for
degenerative, metabolic or inflammatory
• Steroids- ACTH or prednisone 2mg/kg/day in epileptic
encephalopathies
• IVIG- in non immune deficient patients
- 2g/kg over 4 days
-1g/kg once a month- 6 months

78. • KETOGENIC DIET
• Effective in GLUT 1,PDH deficiency,myoclonic astatic epilepsy,tuberous
sclerosis, rett and dravet syndrome
• Initial period of fasting followed by 3:1or 4:1 fat: non fat ratio
• GI disturbances and acidosis, weight loss
• Considered failure if no benefit in 3-6 months
• In responders for 2-3 years

79. • APPROACH TO EPILEPSY SURGERY
• When patients fail 2/3 AEDs
• Within 2yrs of onset of epilepsy
• Properly defined epileptogenic zone- by EEG or MRI
• WADA test- intracarotid infusion of amobarbital
• Focal resection- m.c
• Hemispherectomy
• Multiple subpial transection

80. • Corpus callostomy in lennox-gastaut syndrome
• Vagal nerve stimulation

81. • REFRACTORY EPILEPSY
• epilepsy which is uncontrolled despite adequate trials of three first
line AEDs and when it disrupts developmental progress or normal
childhood activity
• Try and confirm the diagnosis
• inadequate dose, irrational polytherapy or wrong choice of AED
• Refer to tertiary centre
• Newer AEDs, steroids, ketogenic diet

82. • EPILEPSIES AND COGNITION
• Cognitive deterioration, academic underachievement and behavioral
problems
• Screened with child behavior checklist
• early referral for psycho-educational evaluation and special education
• monotherapy
• Identification of rare syndromes

84. References
• Nelsons textbook of pediatrics
• Fenichel textbook of neurology
• Forfar and Arneil’s textbook
• IAP article for management of childhood seizures

93. THANK YOU
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