Seizure Disorders - Epilepsy

Seizure Disorders - Epilepsy

 

Seizure disorders (epilepsy) can occur at any age and are associated with multiple etiologies.

Epidemiology

  • Prevalence – 0.5-1% in most countries
  • Gender – equal distribution

Classification

  • Partial onset seizures
    • Simple
    • Complex
  • Primary generalized seizures
    • Absence (petit mal)
    • Tonic-clonic (grand mal)
    • Tonic
    • Atonic
    • Myoclonic
  • Nonclassified
    • Neonatal
    • Infantile spasms

Etiology

  • Trauma
  • Hypoxia
  • Cerebrovascular disease
  • Fever (only in children)
  • Metabolic derangement
  • Drug withdrawal
  • Central nervous system infection
  • Tumor
  • Genetic disorders
  • Idiopathic

Clinical Presentation

  • Tonic-clonic seizure activity – contraction of all muscles with loss of consciousness
  • Partial seizures – motor, sensory, autonomic impairment with preserved consciousness
  • Absence seizures – loss of consciousness, but not postural control

Diagnosis

  • Clinical history of seizures
  • Electroencephalogram
    • May require continuous monitoring to identify seizure activity
  • Brain imaging

Differential Diagnosis

  • Central nervous system infection
  • Metabolic disorders
  • Migraine aura
  • Psychogenic seizures
  • Substance intoxication
  • Syncope
  • Transient ischemic attack or stroke

Treatment

  • Treat underlying cause, if present
  • Antiepileptic drugs are usually required in chronic disease

Monitoring

  • Serial serum drug levels are important for dose optimization of anti-seizure drugs because of variable pharmacokinetics, drug-drug interactions, non-compliance and a narrow therapeutic index of most drugs
  • Drug concentrations should be measured when signs of adverse effects or therapeutic failure are evident
  • Drug-drug interactions are very common; many anti-seizure medications affect the metabolism of and compete for protein binding with other drugs.  As such, drug concentrations should be measured after any changes to drug regime
  • Pharmacokinetics varies widely, particularly with co-medications and/or compromised renal function
  • Serum drug concentrations are best interpreted when pre-dose (trough) specimens are collected after steady-state is achieved
  • Serum drug concentrations change dramatically during pregnancy and may have important clinical and teratogenic consequences
  • Free drug concentrations are important to consider for patients with abnormal or unpredictable protein status, when drugs that exhibit >90% protein binding are employed
  • Recommended drug concentration monitoring (when steady state achieved)
    • Measurements: 
      • Baseline after starting drug therapy
      • After change in dosing
      • After adding a second antiepileptic drug or other new drug that may interfere with metabolism
      • After a change in patient’s liver, cardiac or gastrointestinal function
Indications for Seizure Drugs
Drug Indication (Type of Seizure) Therapeutic Ranges
Carbamazepine

(Tegretol)

Partial onset, generalized tonic-clonic 4-12 µg/mL (total)

Note: Ranges for carbamazepine 10,11-epoxide (active metabolite) and free carbamazepine may also be applicable

Ethosuximide

(Zarontin)

Absence seizures 40-100 µg/mL
Felbamate

(Felbatol)

Partial onset, generalized tonic-clonic, atonic Therapeutic range not well established.

The proposed therapeutic range for seizure control is 30-60 µg/mL. 

Gabapentin

(Neurontin)

Partial onset Therapeutic range not well established.

The proposed therapeutic range for seizure control is 2-10 µg/mL

Phenytoin

(Dilantin)

Generalized tonic-clonic, IV for status epilepticus

Not used in absence seizures

0-2 months: 6.0-14.0 µg/mL; 3 months and older: 10.0-20.0 µg/mL

Note: Ranges for free phenytoin may also be applicable

Lamotrigine

(Lamictal)

Partial onset, generalized tonic-clonic Therapeutic range not well established.

The proposed therapeutic range for seizure control is 3-14 µg/mL

Levetiracetam

(Keppra)

Absence, myoclonic, partial onset, generalized tonic-clonic Therapeutic range not well established.

The proposed therapeutic range for seizure control is 5-30 µg/mL

Oxcarbazepine

(Trileptal)

Partial onset, generalized tonic-clonic 15-35 µg/mL
Pregabalin

(Lyrica)

Partial onset

 

Primidone/Phenobarbital

(Mysoline)

Partial onset, myoclonic, generalized tonic-clonic, IV for status epilepticus

Primidone also used in essential tremor in the elderly

Primidone: 5-12 µg/mL

Phenobarbital (active metabolite): 0-2 months: 15-30 µg/mL

3 months and older: 15-40 µg/mL

Tiagabine

(Gabitril)

Partial onset

 

Topiramate

(Topamax)

Partial onset, generalized tonic-clonic, myoclonic Therapeutic range not well established.

The proposed therapeutic range for seizure control is 5-20 µg/mL

Valproate

(Depakote)

All seizure types

Also used in bipolar disorder

Valproic acid, total: 50-125 µg/mL

Valproic acid, free: 6-22 µg/mL

VPA-% free: 5-18%

Zonisamide

(Zonegran)

Partial onset, generalized tonic-clonic, myoclonic, absence Therapeutic range not well established.

The proposed therapeutic range for seizure control is 10-40 µg/mL


See Also