2. Definition: Refractory Seizures
• Seizures that are not completely controlled by
medical therapy, seizures continue to occur despite :
• treatment with a maximally tolerated dose of a first-line anti-
epilepsy drug (AED) as monotherapy or in at least one
combination with an adjuvant medication.
• Primarily generalized seizures are the most common type of
intractable seizures in children

3. Definition: Epilepsy
• A seizure is defined clinically as a paroxysmal alteration in
neurologic function, i.e. motor, behavior and/or autonomic
function. This definition includes:
1. Epileptic seizures: phenomena associated with corresponding
EEG seizure activity e.g. clonic seizures
2. Non-epileptic seizures: clinical seizures without corresponding
EEG correlate e.g. subtle and generalized tonic seizures
3. EEG seizures: Abnormal EEG activity with no clinical correlation.

4. Prevalance
• USA: 0.6% persons are suffering from epilepsy
• India

5. Definition: Status Epilepticus (SE)
• The International League Against Epilepsy
(ILAE) and the World Health Organization
currently define SE as
– “a condition characterized by an epileptic seizure
that is so frequently repeated or so prolonged as
to create a fixed and lasting condition”
• functionally as
– A seizure lasting more than 30 minutes or
recurrent seizures lasting more than 30 minutes
from which the patient does not regain
consciousness

6. Revised Definition
• Generalized, convulsive status epilepticus in
older children (> 5 years) refers to > 5 minutes
of continuous seizure or >2 discrete seizures
with incomplete recovery of consciousness
• Patients with generalized seizure activity at
arrival in the ER are treated promptly
regardless of prior duration
Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status
epilepticus. Epilepsia 1999;40(1):120-2.

7. Refractory Seizures
Trial of AED
Failure to respond to 2 or more regimens
Side effects seen at the cost of Seizure control
Check-
Right drug+ Dose + Duration + Compliance+
Drug Vehicle + IV patency
Is it pseudo-seizure?
Search for
Metabolic Epileptic Structural Anomaly

8. Algorithm for acute therapy of
neonatal seizures
Ensure Assess Collect blood
thermoneutral respiration, for
environment & heart rate, Check glucose investigations
Start Oxygen Secure iv line
patecy of blood pressure, by glucometer depending on
airway colour, O2 clinical
(suction) saturation suspicion

9. Cause Specific Therapy
 Identify the underlying cause:
hypocalcemia - Calcium gluconate
hypomagnesemia- Magnesium sulfate
Inj. Lorazepam : 0.05 – 0.1 mg/kg
pyridoxine deficiency- Pyridoxine 50-100mgIV
Inj. Medazolam : 0.05 – 0.2 mg/kg
meningitis/sepsis- initiation of antibiotics
Correction of electrolyte imbalance

12. Prolonged seizures
Life
Temporary
threatening Death
systemic
systemic
changes
changes
Duration of seizure

13. What are Prediction Factors?
Seizure type
Etiologies
Frequency of seizures
Response to first AED
Genetic?

14. Poor Prognostic Factors
• Symptomatic/lesional epilepsy (MTS)
• Poor response to the first antiepileptic drug
• High pre-treatment seizure number/frequency
• Others:
– Poor response to AED at 6 – 12 months
– Generalised epileptiform activity on EEG
– Generalised tonic-clonic seizures
• Genetic predisposition?

15. MDR1 and Epilepsy
• P-glycoprotein encoded by MDR1 (or ABCB1)
• Pumps drugs out of cells
• Expressed in cerebral capillary endothelium (BBB)
• Over-expressed in patients with refractory
epilepsy
• Induced by experimental seizures
• Certain AEDs are substrates of P-gp
Hypothesis: Over-expression of MDR1 causes drug resistance
by reducing AED access to the epileptogenic lesion

16. Summary Of Differential Considerations
• Errors in Diagnosis failure to identify a seizure syndrome or
causative condition
– incorrect seizure classification (partial or generalized)
– non-epileptic seizures (syncope, pseudo-seizures, etc.)
• Errors in drug choice or management
– wrong drug for the seizure type or seizure syndrome
– inadequate dose of medication
– inappropriately treating the "levels"
• Poor medication compliance
– inadequate patient instructions or education
– too frequent or complex of dosing schedule
– intolerable adverse effects of the medication
• True pharmacological intractability

17. Etiological types of Refractory seizures
– unknown or as yet unidentified etiologies (termed
cryptogenic) 50% of new-onset pediatric epilepsy
cases
– suspected or confirmed genetic etiologies
(termed idiopathic; e.g., absence seizures, rolandic
epilepsy) 30 % of new onset cases
– Seizures due to structural brain lesions (termed
symptomatic; e.g., stroke, cortical dysplasia) in
around 20% of children

18. Causes of Refractory seizures in new born
• Inborn error of metabolism (4%)
• Consider in patient with:
– Family history
– Change in diet (milk intro)
– Persistent acidosis
– Strange odor
– Refractory seizures
• Aminoacidurias
• Urea cycle defects
• Pyridoxine deficiency
• Peroxisomal disorders
• Organic acidopathies

19. More Rare Causes:
• CNS structural abnormalities:
– AVM
– Lissencephaly
– Polymicrogyria
– Pachygyria
– Migrational Defects
• Severe, recurrent seizures with burst-
suppression pattern on EEG
• Poor prognosis

20. Syndromes associated with refractory seizures
• Werdnig-Hoffman/Spinal Muscular Atrophy
type I.
– Loss of anterior horn cells (motor nuclei) 2/2 deletion on chromosome
7
– Results in myoclonic jerks and mucle fasiculations
• Infantile spasms (West Syndrome)

21. Inborn Errors of Metabolism Associated
With Neonatal Seizures
Conditions That Have a Specific Treatment
Pyridoxine (B6) dependency
Folinic acid-responsive seizures
Glucose transporter defect
Creatine deficiency
Other Conditions with no specific treatment
Nonketotic hyperglycinemia
Sulfite oxidase deficiency
Molybdenum cofactor deficiency (combined deficiency)
Carbohydrate-deficient glycoprotein disorder
Lactic acid disorders
Mitochondrial disorders
Maple syrup urine disease
Isovaleric acidemia (sweaty feet, cheesy odor)

22. Inborn Errors of Metabolism
Associated With Neonatal Seizures
Other conditions
• Isovaleric acidemia (sweaty feet, cheesy odor)
• 3-methylcrotonyl-CoA carbosylase deficiency
• Propionic acidemia
• Mevalonic aciduria
• Urea cycle defects
• Hyperornithemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome
• Neonatal glutaric aciduria type ll
• Biotin deficiencies, holocarboxylase synthetase deficiency
• Fructose 1,6-diphosphatase deficiency
• Hereditary Fructose intolerance
• Menkes disease (trichopoliodystrophy
• Peroxisomal disorders

23. Laboratory Studies to Evaluate Neonatal
Seizures
Clinical Suspicion of Specific Disease
Serum immunoglobulins, TORCH antibody titers, and
viral cultures
Blood and urine metabolic studies (bilirubin,ammonia,
lactate, reducing substance.)
Blood and urine toxic screen
Blood and urine amino and organic acid screen
CT or ultrasound scan

24. Metabolic Evaluation for Refractory
Neonatal Seizures
Consider individually by case specifics
Serum
Glucose
Electrolytes (sodium, potassium, chloride, carbon dioxide), blood urea nitrogen, chromium,
calcium, phosphorus, magnesium
Uric acid
Creative kinase
Serum ammonia
Lactic and pyruvic acids
Biotinidase
Amino acids
Serum carnitine, acylcarnitines
Serum transferrin
Copper and ceruloplasmin
Cholesterol
Fatty acids (short-chain, medium-chain, long-chain)
Pipecolic acid
NeoReviews vol.5 no.6 June 2004

25. Metabolic Evaluation for Refractory
Neonatal Seizures
Urine
• Organic acids
• Acylglycines
• Uric acid
• Sulfites
• Xanthine, hypoxanthine
• Guanidinoacetate
• Pipecolic acid
Cerebrospinal Fluid
• Cell count, glucose,protein
• Lactic and pyruvic acids
• Amino acids
• Organic acids
• Neurotransmitters
Other Studies
• Skin biopsy
• Muscle biopsy
• Magnetic resonance imaging with magnetic resonance spectroscopy (especially for
creatine)
NeoReviews vol.5 no.6 June 2004

26. Features Of Medically Intractable
Seizures
Etiologies:
• mesial temporal sclerosis, tuberous sclerosis, Sturge-Weber
syndrome, cerebral tumors, hamartoma, Vascular Malformations,
developmental malformations, and sequela of cerebral infections,
infarcts or trauma
Catastrophic epilepsies:
• West syndrome, Lennox-Gastaut syndrome, progressive myoclonic
epilepsy, and cerebral metabolic disorders
Common seizure types:
• complex partial, tonic, atonic, and atypical absence
Common clinical features:
• mental retardation, focal neurologic deficits, and concurrent
psychiatric illness

27. Some Intractable seizure causes

28. Mesial temporal sclerosis. Coronal inversion recovery T1W and high
resolution T2W images of left hippocampal sclerosis. The black arrows
localize a small, T2-hyperintense left hippocampus. The internal
architecture of the left hippocampus is indistinct as well.

29. Mesial Temporal Sclerosis
• hippocampal atrophy, with or without damage
to surrounding structures in the mesial
(amygdala, fornix, and mammillary body)
temporal lobe
• synonymous with temporal lobe epilepsy (TLE)
or epilepsy with partial complex seizures
• may be associated with other developmental
abnormalities of the brain, especially
porencephaly

30. Mesial Temporal Sclerosis
• causal link between very prolonged febrile
seizures, or febrile status epilepticus, and
subsequent hippocampal injury, mesial
temporal sclerosis, and temporal lobe epilepsy
• Antiepileptogenic drugs usually suppress
secondary generalized seizures successfully,
but 50% of patients or more will continue to
have partial seizures.
• anterior temporal lobectomy is the treatment
of choice

31. Tuberous Sclerosis (Bourneville’s Disease)
• Autosomal dominant inheritance with variable
expressivity
• Mutations TSC1(9q34.3)
and TSC2 (16p13.3)
• Seizure types:
– Generalized, infantile spasms (common)
– Tonic, atonic and atypical absences
• Neurologic Exam.
– Hydrocephalus, movement disorders, visual disturbances,
mental retardadtion, and rare focal motor deficit
• Treatment
– Seizures refractory to treatment
– Infantile Spasms - ACTH, Valproate, vigabatrin, zonisamide, or
topiramate
– Focal Abn./ Tubers - Surgery

32. Sturge-Weber.
Horizontal post contrast
T1W image
demonstrates diffuse,
bilateral leptomeningeal
enhancement and
atrophy of the right
hemisphere typical of
encephalotrigeminal
angiomatosis. The
surface of the cortical
gyri are enhancing.
Bilateral involvement is
present in this example,
but unilateral
involvement is the more
typical presentation

33. Sturge Weber Syndrome
• Encephalotrigeminal angiomatosis
• Characterized by Portwine stain
unilaterally over the upper face,
superior eyelid, or supra orbital region
(sensory component of the
ophthalmic branch of the V nerve)
• Buphthalmos / Glaucoma
• Intracranial calcification
• Presenting symptom seizure
(partial or sec. generalized seizure)
• EEG: Dec. amplitude and frequency over the affected hemisphere
with diffuse multiple and independent spikes
• Treatment:
– Surgical removal of the affected lobe / hemisphere

34. Cerebral Tumors
• Dysembryoplastic neuroepithelial tumors (DNET or
DNT) are benign glioneuronal neoplasms of the cortex
associated with partial complex epilepsy, usually
without neurologic deficit, 60% of these tumors are
located in the temporal lobe with 30% in the frontal
lobe
• Mixed glioneuronal tumors (gangliogliomas and
gangliocytomas): long histories of partial seizures,
occasionally with focal neurologic deficits
• Oligodendrogliomas commonly cause seizures when
they are present

35. Hypothalamic hamartomas
• rare congenital malformations
• located in the region of the tuber cinereum of
the hypothalamus
• associated with precocious puberty, epilepsy,
developmental delay, and gelastic seizures as
well as other types of partial and generalized
seizures, including atypical absence and drop
attacks

36. Vascular Malformations
• Cavernous angioma (or cavernoma):
characterized by sinusoidal vascular spaces with
dilated capillary beds filled with blood and
breakdown products of varying age
• Arteriovenous malformations (AVM): abnormal,
often friable connections between cerebral
arteries and veins without intervening capillaries;
can cause seizures, neurologic deficits, headache,
hydrocephalus, or hemorrhage

37. West Syndrome (Infantile Spasms)
• Severe Encephalopathic Epilepsy in Infants
• some degree of mental and developmental
retardation
• 0.05 to 0.60 per 1,000 live births
• Spasm onset is usually within the first 4 to 8
months of life with a peak at 6 months. Most
cases occur before 3 years of age.

38. West Syndrome
• The motor spasm typically consists of a brief,
bilaterally symmetrical contraction of the muscles of
the neck, trunk, and extremities.
• Three main types of motor spasm have been
identified:
– flexor, extensor, and mixed flexor-extensor.
• The interictal electroencephalogram (EEG) pattern,
hypsarrhythmia:
– random high voltage slow waves and spikes. These spikes
vary from moment to moment, both in duration and in
location. At times they appear to be focal, and a few
seconds later they seem to originate from multiple foci.

39. West Syndrome (EEG)

40. West Syndrome
• Diagnostic Evaluation and Treatment
– Good clinical history, thorough general physical and
neurological examinations
– careful ophthalmic evaluation and close examination of
the skin using a Wood’s lamp to rule out such conditions
as tuberous sclerosis
– EEG / MRI
• apparent association between DPT immunization
and infantile spasms is coincidental and that no
causal relationship exists

41. West Syndrome

42. West Syndrome

43. Lennox-Gastaut Syndrome
• Childhood epileptic encephalopathy with diffuse slow spike-and-
waves
• The current definition of LGS by the International League Against
Epilepsy (ILAE) classification is as follows (13):
– LGS manifests itself in children aged 1–8 years, but appears mainly in
preschool-age children.
– Tonic-axial, atonic, and absence seizures are the most common seizure
types, but other types such as myoclonic, generalized tonic-clonic
seizures (GTCS), or partial seizures are frequently associated with this
syndrome. Seizure frequency is high, and status epilepticus is frequent
(stuporous states with myoclonias, tonic and atonic seizures). The EEG
usually has abnormal background activity, slow spike-and-waves 3Hz
and, often, multifocal abnormalities. During sleep, bursts of fast rhythms
(10 Hz) appear. In general, there is mental retardation. Seizures are
difficult to control, and the development is unfavorable.

44. Lennox-Gastaut Syndrome
• 1% to 4% of all cases of childhood epilepsy, but 10% of cases
that start in the first 5 years of life
• Males are affected more often than females
• Two types: idiopathic or symptomatic
• In young children-
– Psychiatric symptoms :
• mood instability and personality disturbances,
– Neuropsychological symptoms.
• slowing or arrest of psychomotor development and educational progress
• Older children-
– Character problems predominate and acute psychotic episodes or
chronic forms of psychosis with aggressiveness, irritability, or
social isolation may occur .
– Prolonged reaction time and information processing are the most
impaired of the cognitive functions.

45. Lennox-Gastaut Syndrome (T/t)
• First-line treatments based on clinical experience or conventional wisdom
– Valproic acid
– Benzodiazepines
– Pyridoxine
• Suspected effective treatments based on open-label uncontrolled studies
– Adrenocorticotropic hormone–corticosteroids
– Intravenous immunoglobulin
– Vigabatrin
– Zonisamide
– Ketogenic diet
– Corpus callosotomy
– Vagus nerve stimulation
• Effective treatments based on double-blind, placebo- controlled studies
– Felbamate
– Lamotrigine
– Topiramate
– Rufinamide

46. Treatment

47. Supportive Management
A – Maintain Airway
B – Keep Oxygenation
C – Maintain Circulation
Prevent Injury

48. Choosing Antiepileptic Drugs
Classify the seizure disorder correctly
Treat the patient's symptoms, not the EEG findings or the serum levels
Pharmacokinetic profile
Interactions/other medical conditions
Balance the maximal effective dose with minimal side effects
Choose dosing to maximize compliance
Cost
Goal: Complete seizure control without side effects

49. Classification of AEDs
Classical Newer
Phenytoin Lamotrigine
Phenobarbital Felbamate
Topiramate
Primidone
Gabapentin/Pregabalin
Carbamazepine
Tiagabine
Ethosuximide
Vigabatrin
Valproate (valproic acid)
Oxycarbazepine
Trimethadione (not currently in use)
Levetiracetam
Fosphenytoin

50. Lancet Neurol 2006; 5: 252

51. The Steps of Status Epilepticus
Emergency Management
1. Ensure adequate brain oxygenation and cardiorespiratory function
2. Terminate clinical and electrical seizure activity as rapidly as possible
3. Prevent seizure recurrence
4. Identify precipitating factors such as hypoglycemia, electrolyte imbalance, lowered
drug levels, infection, and fever
5. Correct metabolic imbalance
6. Prevent systemic complications
7. Further evaluate and treat the etiology of SE

52. Step wise treatment of seizure control in
Status Epilepsy (Excluding Neonates)
Step I: Benzodiazepine - Lorazepam: 0.1 mg/kg IVI at 2 mg/min
NB: Lorazepam, if available, is the drug of choice
because the anticonvulsant effect last up to 24 hours
OR
- Valium: 0.25-0.5 mg/kg IVI
Followed by

Step II: Phenytoin 20 mg/kg IVI slowly not faster than 25-50 mg/min
Seizures continuing

Step III: Phenytoin Additional 5 mg/kg
Seizures continuing


53. Step wise treatment of seizure control in
Status Epilepsy (Excluding Neonates)
Step IV: Has to be done in ICU as ventilatory support is usually
necessary
1. Thiopentone Starting infusion dose is 1-3 mg/kg/hour and one
may need to go as high as 5-7 mg/kg/hour
OR
2. Midazolam Start with a loading dose of 0.2 mg/kg IVI bolus,
then at a dose of 0.75 – 10 microgram/kg/min
OR
3. Propofol 1-2 mg/kg IVI, followed by 2-10 mg/kg/hour.
Its use in children is limited and should be used
with caution.

54. Felbamate (FBM)
• Antagonizes the glycine site on the NMDA receptor and
blocks Na+ channels*
• Dose
– 15-45 mg/kg/day
• Very potent AED lacking sedative effect (unlike nearly
all other AEDs)
• Effective against partial seizures, restricted for use only
in extreme refractory epilepsy
• Toxicity:
• Aplastic anemia
• Severe hepatitis

55. Topiramate (TPM)
• Acts on AMPA receptors, blocking the glutamate binding
site, but also blocks kainate receptors and Na+ channels, and
enhances GABA currents (highly pleiotropic*)
• Dose
– As monotherapy 3 mg/kg/day
– As adjunctive therapy 6 to 9 mg/kg/day
• Indication
– ages 2–16 years with partial-onset seizures or primary GTC
seizures
– patients ages 2 years and older with seizures associated with
Lennox-Gastaut syndrome.

56. Topiramate (TPM)
• Common side effects
– Nausea, abdominal pain, anorexia, cog. Impairment,
Somnolence, Fatigue, Dizziness, Paresthesias, Nervousness,
Confusion, Urolithiasis
• Comments
– Watch for weight loss and depressive psychosis
– Ensure adequate hydration; increased risk of kidney stones.
Avoid carbonic anhydrase inhibitors e.g. Acetazolamide
– Half life 18 to 30 hours reduced where given with enzyme
inducing drugs

57. The Use of Benzodiazepines in Status Epilepticus

58. Benzodiazepine Dosages for
Prevention of Seizures

59. Clonazepam (Klonopin)
• Most specific AED among benzodiazepines, appearing
to be selective for GABAA activation in the reticular
formation leading to inactivation of T-type Ca++
channels, hence its useful for absence seizures
• One of the most potent antiepileptic agents known.
• Indicated for
– Refractory absence and myoclonic seizures
• Therapeutic plasma concentration : 0.63 to 2.2
mmol/litre

60. Clonazepam (Klonopin)
• Common side effects
– Sedation, ataxia, behaviour problems,
hyperactivity
• Comments
– Used for partial seizures
– Half life 18 to 50 hours
– Tolerance develops in 30%

61. Clobazam
• Indicated for
– Refractory partial seizures
– Cluster seizures
– Seizures connected with periods
• Common side effects
– Same as clonazepam
• Comments
– Same as clonazepam
61

62. Tiagabine (Gabatril)
• Derivative of nipecotic acid.
• GABA uptake inhibitor GAT-1.
• Dose
– 0.5-1.5 mg/kg/day in three divided doses
• Indicated for
– Effective against partial and generalized tonic-clonic
seizures.
– Adjunctive treatment for refractory partial seizures

63. Tiagabine (Gabatril)
• Common side effects
– Diarrhoea, dizziness, tiredness, concentration difficulties,
speech impairment, Nervousness, Tremor, Depression,
Asthenia, Emotional lability, Psychosis, Skin rash
• Comments
– Short half life (4 to 10 hours)
– Used when add on therapy is required
– Efficacy reduced by enzyme inducing AEDs
– Reduces plasma concentration of sodium valproate
63

64. Vigabatrin (Sabril)
• not currently available
• elevates GABA levels by irreversibly inhibiting its
main catabolic enzyme,
GABA- transaminase
• Dose
– 30-100 mg/kg/day in one to two divided doses
• T 1/2 6-8 hrs
• Indicated for
– Adjunctive treatment for refractory generalised tonic
clonic, partial seizures and Infantile spasms

65. Vigabatrin
• Common side effects
– Drowsiness, Dizziness, confusion, irritability, fatigue,
Weight gain, psychosis
– Visual field defects
– Psychotic experiences
• Contraindicated if preexisting mental illness is
present.
• Comments
– Irreversible inhibitor of GABA transaminase
– Short half life irrelevant to dosing regime
65

66. Zonisamide 1
• Dose –
– 1 mg/kg/day increased every 2 weeks to max of 8
mg/kg/day
– higher doses in presence of enzyme inducers
– T1/2 = 1 - 3 days
– Peak plasma – after 2-6hours
– delayed by food but total absorbed not affected.
– Steady state 14days
– Low plasma protein binding but bound to erythrocytes
• Indicated for partial seizures
66

67. Zonisamide 2
• Contra indications : sulfonamide hypersensitvity
• Cautions:
– Renal impairment - excreted in urine
– Tendancy to kidney stones - advise plenty of fluids
– Co-administration with enzyme inducers
• Very Common Side effects
- Agitation, confusion, dizziness, somnolence, double
vision
• Common side effects
- Diarrhoea, nausea, anorexia, rash
67

68. Zonisamide 3
• Serious but rare effects:
– Blood dyscrasias, panreatitis
– Hallucinations, psychosis
– High incidence of renal stones (?).
• Comment:
- New drug - monitor
68

69. Lamotrigine 1
69

70. Lamotrigine 2
• Common side effects
– Dizziness, ataxia, double vision, nausea, somnolence
– Rash (worse in children) less if slow escalation
• Comments
– Complex interaction with valproate very slow escalation
needed
– Indicated for partial seizures and secondarily generalised
tonic clonic seizures
– Half life 25 hours shorter with enzyme inducers
– Excreted in breast milk
– Reasonably safe in overdose (10x)
70

71. Gabapentin 1
• Dose
– Children 20-50mg/kg/day (needs tds dose)
– Adolescent 900-3600 mg/day
• Therapeutic plasma concentration
– Not established
• Indicated for
– Adjunctive treatment for refractory partial
seizures
71

72. Gabapentin 2
• Common side effects
– Drowsiness, dizziness, fatigue, ataxia, tremor, diplopia,
nausea and vomiting
• Comments
– Excreted unchanged; 95% in urine
– Only 60% of dose absorbed
– Unaffected by food
– Seizure frequency may increase
– No common drug interactions
– Comparatively safe in overdose
72

73. Levetiracetam
• Dose
– 20 to 40 mg/kg/day
• Therapeutic plasma concentration
– Not relevant
• Indicated for
– Partial seizures, Generalised absences
• Common side effects
– Nausea, drowsiness, anorexia, headache, rash,
– Very rarely leucopenia
• Comments
– No drug interactions described
73

74. Antiepileptic drugs
withdrawal
• Can cause increased seizure frequency and severity.
• In general, barbiturates and benzodiazepines
are the most difficult to discontinue. Weeks or months may be
required, with very gradual dosage decrements, to accomplish
their complete removal.
• Complete discontinuance is an especially difficult problem. If a
patient is seizure-free for 3-4 years, gradual discontinuance
might be considered.

75. Side effect issues
• Sedation - especially with barbiturates
• Cosmetic – phenytoin
• Weight gain – valproic acid, gabapentin
• Weight loss – topiramate
• Reproductive function – valproic acid
• Cognitive – topiramate
• Behavioral – felbamate, leviteracetam
• Allergic - many

76. Adverse Effects of AEDs

77. The Ketogenic Diet
• Ketosis and acidosis exert anticonvulsant effects.
• The efficacy of a daily regimen of 1g/kg of protein, enough
fat to make up the desired caloric requirements and a very
small amount of carbohydrates for establishing
anticonvulsant levels of ketosis has been well established.
• Most successful in children with medically refractory
seizures, especially handicapped children less than 10 years
old.
• 38% of medically intractable children had a seizure
reduction of almost 50%, and 29% of patients became
seizure free.
• The primary drawback to the diet :poor compliance

78. Types of Surgery in Pediatric Epilepsy
In children undergoing epilepsy neurosurgery, 70% of cases involve
extratemporal resection, which is a much higher proportion than
typically observed in adult epilepsy surgery cohorts

79. Vagal Nerve Stimulator
• first nonpharmacologic therapy approved by the FDA for the
treatment of seizures
• Only approved for the treatment of medically refractory partial
epilepsies in those >12 years of age who are not surgical
candidates.
– Approximately 1/3 of those treated greater than 50% reduction in
their seizure frequency.
– Another one-third less than a 50% reduction in seizure frequency,
– The remaining one-third have no improvement.
• Equally efficacious as the addition of a second or third AED to a
patient's regimen, but does not have the added systemic toxic
effects.
• Generally well tolerated, although minor side effects of neck pain,
hoarseness, and a brief cough can be associated with the activation
of the stimulator.
• Drawbacks are the need for surgical implantation and the high cost.

80. 1. Which has the best evidence as
most effective drug for primary
generalized epilepsy?
1. Lamotrigine
2. Carbamazepine
3. Valproate
4. Keppra
5. Phenytoin

81. 2. Which is the most effective drug for
partial epilepsy?
1. Phenytoin
2. Keppra
3. Lamotrigine
4. Valproate
5. Carbamazepine

82. 3. Drug levels are routinely useful for:
1. Valproate
2. Lamotrigine
3. Phenytoin
4. Carbamazepine

83. 4. The most useful investigation for
partial onset seizures is
1. EEG
2. MRI
3. CT
4. USG

84. Thank You