para>Certain common anticonvulsants may exacerbate absence including carbamazepine, oxcarbazepine, phenytoin, phenobarbital, tiagabine, vigabatrin, pregabalin, and gabapentin. ‚
First Line
- Ethosuximide blocks T-type calcium channels:
- First-line, except in absence patients with tonic " “clonic seizures (lacks efficacy)
- High efficacy (4)[A], fastest onset of efficacy (5)[B], and fewer adverse attentional effects compared to valproic acid (4)[A]
- Side effects: vomiting, diarrhea, abdominal discomfort, hiccups, headache, sedation
- Adverse effects: rare blood dyscrasias (monitor CBC)
- Valproic acid has multiple mechanisms:
- First choice in absence patients with tonic " “clonic, myoclonic, mixed seizure types
- Very effective, but has highest rate of adverse events leading to treatment discontinuation, including negative attentional effects (4)[A]
- Side effects: tremor, drowsiness, dizziness, weight gain, alopecia, sedation, vomiting
- Adverse effects: teratogenicity, pancreatitis, thrombocytopenia, rare fulminant hepatic failure (especially in children <2 years)
Second Line
- Lamotrigine affects sodium channels:
- Controls seizures but may be less efficacious than ethosuximide or valproic acid (4)[A]
- May be equally as efficacious for new-onset CAE (5)[B]
- Side effects: rash, diplopia, headache, insomnia, dizziness, nausea, vomiting, diarrhea
- Adverse effects: rare Stevens-Johnson rash, more often when coadministered with valproic acid
- Topiramate affects GABA and excitatory neurotransmission:
- FDA approved for Lennox-Gastaut syndrome
- Side effects: psychomotor slowing
- Adverse effects: weight loss, renal stones, myopia, glaucoma (rare), anhidrosis
- Levetiracetam is used off-label:
- Has been used as both monotherapy and adjunct therapy for absence seizures
- A small multicenter randomized controlled trial (RCT) showed modest efficacy but not statistically significant versus placebo (6)[C].
- Zonisamide is also used off-label.
- Clonazepam, nitrazepam and clobazam may be effective in the short-term but are not recommended for long-term management due to development of tolerance (few months to a year) and side effects.
Pregnancy Considerations
Anticonvulsants, especially valproic acid, are associated with an increase in fetal malformations. Use of valproic acid in women who are or are likely to become pregnant generally is contraindicated. Obtain specialty consultation.
‚
ADDITIONAL THERAPIES
- Most absence seizure patients respond to a single medication.
- Male sex and an early age at diagnosis are associated with the need for two medications to control the disease (7)[B].
- Vagal nerve stimulator (VNS) may be considered as an option for medically refractory absence epilepsy (8)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Absence epilepsy rarely requires admission.
- Status epilepticus requires inpatient management.
Discharge Criteria
Resolution of status epilepticus ‚
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Patients with associated tonic " “clonic seizures should avoid high places and swimming alone.
- Absence rarely persists into adulthood, but affected adults may be restricted from driving, working over open flames, and so forth, as with other generalized and partial epilepsy subtypes.
- Patients should be monitored periodically by a neurologist for evolution of absence epilepsy into tonic " “clonic or other seizure types.
PROGNOSIS
- Patients whose shortest pretreatment EEG seizures are >20 seconds in duration are more likely to achieve seizure freedom, regardless of treatment (9)[A].
- Of those with CAE without tonic " “clonic seizures, 90% remit by adulthood.
- 35% of patients with tonic " “clonic seizures experience complete remission of absence seizures.
- 15% of patients develop juvenile myoclonic epilepsy.
COMPLICATIONS
Reported frequencies of typical absence status epilepticus range from 5.8% to 9.4% of patients with CAE. ‚
REFERENCES
11 Berg ‚ AT, Berkovic ‚ SF, Brodie ‚ MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005 " “2009. Epilepsia. 2010;51(4):676 " “685.22 Betting ‚ LE, Mory ‚ SB, Lopes-Cendes ‚ I, et al. MRI reveals structural abnormalities in patients with idiopathic generalized epilepsy. Neurology. 2006;67(5):848 " “852.33 Kesselheim ‚ AS, Stedman ‚ MR, Bubrick ‚ EJ, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: a systematic review and meta-analysis. Drugs. 2010;70(5):605 " “621.44 Glauser ‚ TA, Cnaan ‚ A, Shinnar ‚ S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013;54(1):141 " “155.55 Hwang ‚ H, Kim ‚ H, Kim ‚ SH, et al. Long-term effectiveness of ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. Brain Dev. 2012;34(5):344 " “348.66 Fattore ‚ C, Boniver ‚ C, Capovilla ‚ G, et al. A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy. Epilepsia. 2011;52(4):802 " “809.77 Nadler ‚ B, Shevell ‚ MI. Childhood absence epilepsy requiring more than one medication for seizure control. Can J Neurol Sci. 2008;35(3):297 " “300.88 Arya ‚ R, Greiner ‚ HM, Lewis ‚ A, et al. Vagus nerve stimulation for medically refractory absence epilepsy. Seizure. 2013;22(4):267 " “270.99 Dlugos ‚ D, Shinnar ‚ S, Cnaan ‚ A, et al. Pretreatment EEG in childhood absence epilepsy: associations with attention and treatment outcome. Neurology. 2013;81(2):150 " “156.
ADDITIONAL READING
- Matricardi ‚ S, Verrotti ‚ A, Chiarelli ‚ F, et al. Current advances in childhood absence epilepsy. Pediatr Neurol. 2014;50(3):205 " “212.
- Vrielynck ‚ P. Current and emerging treatments for absence seizures in young patients. Neuropsychiatr Dis Treat. 2013;9:963 " “975.
CODES
ICD10
- G40.409 Other generalized epilepsy and epileptic syndromes, not intractable, without status epilepticus
- G40.419 Oth generalized epilepsy, intractable, w/o stat epi
- G40.401 Oth generalized epilepsy, not intractable, w stat epi
- G40.411 Oth generalized epilepsy, intractable, w status epilepticus
- G40.A19 Absence epileptic syndrome, intractable, w/o stat epi
- G40.A09 Absence epileptic syndrome, not intractable, w/o stat epi
ICD9
- 345.00 Generalized nonconvulsive epilepsy, without mention of intractable epilepsy
- 345.01 Generalized nonconvulsive epilepsy, with intractable epilepsy
SNOMED
- 79631006 Absence seizure (disorder)
- 23374007 Atypical absence seizure (disorder)
CLINICAL PEARLS
- If parents are unable to determine the cause of a staring spell, try suggesting that parents mention something exciting or unexpected like "ice cream " ť during a spell to get the child 's attention rather than calling his or her name.
- To help aid with diagnosis during an exam, try having the child blow repetitively on a pinwheel (causing hyperventilation) to attempt to trigger absence seizure.
- Ethosuximide and valproic acid are first line agents in treatment of absence seizures. Valproic acid and lamotrigine are recommended for absence patients with tonic-clonic and mixed seizure types.