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Epilepsy Management and Epilepsy Surgery. Melissa A. Carran, M.D. Assistant Professor, Division of Neurology Cooper University Hospital/UMDNJ. Introduction. Current state of drug therapies Alternative therapies Epilepsy Surgery cases. The Ketogenic Diet.

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epilepsy management and epilepsy surgery

Epilepsy Management and Epilepsy Surgery

Melissa A. Carran, M.D.

Assistant Professor, Division of Neurology

Cooper University Hospital/UMDNJ

introduction
Introduction
  • Current state of drug therapies
  • Alternative therapies
  • Epilepsy Surgery cases
the ketogenic diet
The Ketogenic Diet
  • The ketogenic diet was first used as a treatment in 1921
  • .Mimics the effects of fasting, using fat as major energy source leading to the production of ketone bodies. It is effective for myoclonic, focal and temporal lobe epilepsy.
  • The exact mode of action still unknown
slide10
Monitoring
  • Regular testing of urinary ketone levels: ketone level = 3.9- 7.8mmol/1. 3-4x/d
  • If an initial starvation period is not instigated prior to the commencement of the diet then testing for ketones should not be carried out until the diet has been followed for at least 10 days.
  • Dehydration 1L/ day
slide11
4g fat to each 1g protein and carbohydrate combined; in children under the age of 18 months a ratio of 3:1
  • Calculation of daily amounts. If the patient's weight is Wkg then:
  • Energy content (kcal) = 75 x W
  • 4:1 ratio:
  • Fat content (g) = 7.5 x W
  • Protein content (g) = W
  • Carbohydrate content (g) = 0.875 x W
johns hopkins study kinsman et al 1992
Johns Hopkins Study (Kinsman et. Al 1992)
  • 58 children <10y/o
  • most Lennox Gastaut
  • Improvement usually in 1st 2 weeks
  • over 2 years: 38% had 1/2 seizure freq.; 29% seizure free
  • diet tappered after 2 years
side effects
Side effects
  • hyperlipidemia
  • hyperuricemia
  • hypercalciuria
  • hypoglycemia
  • growth retardation
epilepsy surgery in children
Epilepsy Surgery in Children
  • Predicting medical intractability
  • 125,000 new cases/yr
  • 30% < 18y/o; most birth - 2y/o
slide24
Berg et. Al, Neurology 2001
  • 613 Children (5.3y/o median)
  • intractable= failed 2 or more drugs. One sz/month over 18 mos.
  • Symptomatic Generalized epilepsy, high initial sz frequency, focal EEG
  • remissions 14% after 1.5-3 years
temporal lobe epilepsy
Temporal lobe epilepsy
  • (Mohamed et al. Neurology 6/01)
  • 17 children/ 17 adolescents (12y/o)
  • MRI hipp. Sclerosis on side of Sz onset
  • 78% seizure free after ATL
phenytoin dilantin
Loading dose 15-20mg/kg

Maintenance: 200-300 mg/d (qd or bid)

T 1/2 7-42 hrs

Saturation Kinetics

Level 10-20 mcg/ml

Unbound 10%

Side effects: nystagmus, ataxia, dizziness, hirsutism, gingival hyperplasia, peripheral neuropathy, oseomalacia, folate deficiency, cerebellar atrophy, hepatitis, hypersensitvity syndrome, local rxn.

Phenytoin (Dilantin)
carbamazepine tegretol
Initiate: 100-200mg qhs x 5-7 days; add 200mg/day

Maintenance: 400-2400mg/d

T1/2= 25-60h (initial),12-17h (chronic)

Hepatic autoinduction

Side effects: drowsiness, dizziness, diplopa, ataxia, visual blurring, osteoporosis, peripheral neuropathy, water retention, hyponatremia

Carbamazepine (Tegretol)
oxcarbazepine trileptal
Partial seizures

1200-2400 mg/day

Rapid hepatic reduction

Metabolites renal elim.

No drug interactions

Side effects:

Oral contraceptive reduction? Bone loss?

Hyponatremia

Oxcarbazepine (Trileptal)
phenobarbitol

Phenobarbitol

Side effects: sedation,

dizziness mood change,

insomnia, hyperkinesis,

cognitive dysfunction,

osteoporosis,

Dupuytren’s contracture,

frozen shoulder, reduced

libido, rash,

hepatotoxicity

10-20 mg/kg

loading

60-240 mg/day

25%

renal/65%hepatic

T 1/2= 50-140 hr

Primidone

(mysoline)

gabapentin neurontin

Gabapentin (Neurontin)

Side effects:

somnolence,

dizziness,

ataxia, edema

Initiate 300mg/day,

bid, then tid

Maintenance 900-

4,800 mg/d

98%renal

excretion

Not protein bound

lyrica
Lyrica
  • Pregabalin is a 3-substituted analogue of gamma-amino butyric acid (GABA) and a compound related to Pfizer's hugely successful antiepileptic drug gabapentin. (Source: ABPI)
valproic acid
Partial and Generalized Sz and Absence

5-10 mg/kg/day (250-750mg)

Depakote ER; 250mg more up to 2000mg (500)

Depacon 60 min IV or <20mg/min

Side effects: Hair loss, tremor, weight gain, thrombocytopenia, hepatiotoxicity, pancreatitis,

Valproic Acid
levetiracetam keppra

Levetiracetam (Keppra)

Side effects:

irritability, rare

psychosis,

somnolence,

personality

change

Start 250mg bid,

500mg bid

renal excretion

Not protein bound

topiramate topamax
Initial: 50mg increase/wk bid

Maintenance: 200-600mg/day (bid)

70% renal excretion; dosage 1/2 in renal impairment

Side effects: kidney stones (1.5%), somnolence, fatigue, psychomotor slowing, difficulty with concentration, confusion, paresthesias

Topiramate (Topamax)
zonisamide zonegran
Partial and Gen.Sz. Myoclonic Jerks; ?absences

Renal elimination

400-800mg/day

Saturation kinetics

Side Effects: weight loss, oligohydrosis, CBC/LFT monitoring

Zonisamide (Zonegran)
status epilepticus
Status Epilepticus
  • Consecutive seizures without return to consciousness
  • Seizure for 30 min.
  • High mortality
  • Subtle convulsive status
treatment of status
Treatment of Status
  • R/O hypoglycemia
  • Lorazepam IV 0.1 mg/kg; 1-2mg/min.
  • Phenytoin 20mg/kg IV (50-150mg/min)
  • Addt’l 10 mg/kg phenytoin
  • Intubate: Phenobarbitol 20mg/kg IV
  • EEG monitoring: sodium pentobarbital 5-15mg/kg; 5mg/kg/hr; midazolam or propofol