Seizure Disorder, Absence – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

  • Committee on Classification and Terminology of the International League Against Epilepsy divides epilepsy syndromes into 4 groups (1):
    • Localization-related: Focal or multifocal seizures
    • Generalized: Generalized seizures
    • Undetermined epilepsies: Both focal and generalized seizures where objective studies (e.g., EEG) do not indicate etiology or localization
    • Special syndromes: Now called “conditions with epileptic seizures that do not require a diagnosis of epilepsy” (e.g., febrile seizures)
  • Epilepsy syndromes further classified by etiology:
    • Idiopathic: Presumed genetic etiology without structural brain lesion or other neurologic deficits
    • Symptomatic: Clearly identified cause (e.g., Mesial temporal lobe epilepsy with hippocampal sclerosis)
    • Cryptogenic: Etiology suspected but exact cause cannot be identified
  • Absence seizures are a generalized epileptic seizure type, characterized by brief lapses of awareness.
  • Typical absence:
    • Associated with pediatric idiopathic generalized epilepsy syndromes, namely, childhood absence epilepsy
    • Formerly called petit mal seizures
    • Abrupt-onset behavioral arrest, loss of awareness, and blank staring, sometimes with mild upward eye deviation, repetitive blinking
    • May include automatisms, tonic or atonic features, eyelid or facial clonus, autonomic features
    • Last 5–30 s
    • Immediate return to normal consciousness
  • Atypical absence:
    • Associated with symptomatic generalized epilepsy syndromes such as Lennox-Gastaut
    • Onset and offset less abrupt than typical absence seizures
    • Last 10–45 seconds
    • Impairment of consciousness often incomplete with continued purposeful activity
    • Postictal confusion sometimes occurs.
    • Associated clinical features more pronounced and frequent than typical absence; atonia most common
  • Myoclonic absence:
    • Additional proposed seizure type by the International League Against Epilepsy (2)
    • Seizure type in epilepsy with myoclonic absences, a cryptogenic generalized epilepsy syndrome
    • Rhythmic clonic jerking at 2–4 Hz
    • Last 5–10 s
    • Unlike myoclonic seizures with no impairment of consciousness, brief lapses of awareness characteristic of myoclonic absence
  • Rest of chapter details idiopathic generalized epilepsy syndromes characterized by typical absence seizures, specifically childhood absence epilepsy (CAE)
  • Juvenile absence epilepsy is mentioned briefly here.
  • Childhood absence epilepsy (CAE):
    • Also known as pyknolepsy
    • Typical absence seizures are the only seizure type in 90% of children.
    • 10% develop additional generalized tonic–clonic seizures.
    • Seizures last about 10 seconds and often occur hundreds of times per day.
    • Onset ages 4–10 years, with peak at ages 5–7 years (3)
    • Normal neurologic state and development
    • Spontaneous remission occurs in 65–70% of patients during adolescence (4).
  • Juvenile absence epilepsy (JAE):
    • Typical absence seizures are the main seizure type.
    • Seizures last longer than in CAE and occur usually less than once a day (5).
    • Onset ages 9–16 years, with peak at ages 10–13 years
    • Generalized tonic–clonic seizures occur in most patients, often in the first 1–2 h after awakening.
    • Seizures often persist into adulthood.

Epidemiology

Incidence

6–8/100,000

Prevalence

5–50/100,000

Risk Factors

Genetics

  • 70–85% concordance occurs in monozygotic twins; 82% share EEG features.
  • 33% concordance among 1st-degree relatives
  • 15–45% have a family history of epilepsy.
  • Girls are more often affected by a 3:2–2:1 ratio.
  • Complex multifactorial inheritance
  • For childhood absence, genes/loci implicated include 6q, 8q24, and 5q14 (5).
  • Mutations of GABAA receptor and voltage-gated Ca2+ channel are implicated.

Pathophysiology

  • Corticoreticular theory implicates abnormal activity in thalamocortical circuits (6).
  • Thalamic reticular nucleus is responsible for both normal sleep spindles and pathologic slow-wave discharges; contains inhibitory GABAergic neurons.
  • These neurons affect low-threshold calcium currents.
  • These circuits can fire in oscillatory/rhythmic fashion:
    • Normally, activation of GABAA receptors causes 10-Hz oscillations in sleep spindle frequency.
    • If GABAB receptors strongly activated, oscillation frequency will be 3–4 Hz, similar to spike-and-wave typical absence seizure frequency.

Commonly Associated Conditions

  • 3–8% of CAE cases evolve into juvenile myoclonic epilepsy.
  • Associated with cognitive/learning problems (7)

Diagnosis

Seizures are often so brief that untrained observers are not aware of the diagnosis.

History

  • Frequently diagnosed in children being evaluated for poor school performance
  • Teachers report that child seems to daydream or zone out frequently.
  • Child will forget portions of conversations.
  • Child with normal IQ underperforms in school.

Physical Exam

  • Unless child has other genetic or acquired abnormality, neurologic exam is usually normal.
  • Seizures may be frequent enough to be observed during physical exam:
    • Manifest by behavior arrest: Child will stop speaking in midsentence, stare blankly, etc.
    • Automatisms (repetitive stereotyped behaviors) may be present.
    • Child resumes previous activity.
  • Seizures may be induced by hyperventilation:
    • Have child blow on pinwheel or similar exercise to provoke seizure.
    • Alternatively, ask patient to perform hyperventilation with eyes closed and count. Patient will open eyes at onset of seizure and stop counting (5).
  • Patient manifests unresponsiveness but retains postural tone in a typical absence seizure.

Diagnostic Tests & Interpretation

Lab

  • No specific hematologic workup
  • Follow blood chemistry, hepatic function, and blood counts specific to drug regimen.
  • Drug levels are useful in evaluating symptoms of toxicity or for breakthrough seizures.

Initial lab tests

  • EEG is standard for diagnosis:
    • Typical absence features: 3.0-Hz spike-and-wave activity on normal EEG background
    • Seizures feature bursts of 3- to 4-Hz spike-and-wave activity, which may slow to 2.5–3 Hz during seizure.
    • Seizure is usually evident clinically if bursts last >3 seconds; subtle changes of transient cognitive impairment may be evident with briefer seizures.
  • Hyperventilation and occasionally photic stimulation may induce seizure, thus confirming diagnosis of typical absence epilepsy.

Imaging

  • Not routinely indicated in children with typical absence and normal neurologic exam and IQ
  • Brain MRI is indicated in atypical absence and in children with mixed seizure types when combined with abnormal neurologic exam or low IQ (7).

Differential Diagnosis

  • Typical absence seizures frequently are misdiagnosed as complex partial seizures.
  • Nonepileptic staring spells: Suggestive features include:
    • Events do not interrupt play.
    • Events are first noticed by professional such as school teacher, speech therapist, occupational therapist, or physician (rather than parent).
    • During staring spell, child is responsive to touch or other external stimuli.

Treatment

Medication

Certain common anticonvulsants may exacerbate absence: Carbamazepine, tiagabine, vigabatrin, and gabapentin.

First Line

  • Ethosuximide blocks T-type calcium channels:
    • 1st-line, except in absence patients with tonic–clonic seizures (lacks efficacy) (4)[A]
    • Side effects: Headache, hiccups, behavior changes, tremor
    • Adverse effects: Rare blood dyscrasias (monitor CBC)
  • Lamotrigine affects sodium channels (4)[B]:
    • Side effects: Headache, insomnia, dizziness
    • Adverse effects: Rare Stevens-Johnson rash, more often when coadministered with valproic acid
  • Valproic acid has multiple mechanisms:
    • 1st choice in absence patients with tonic–clonic, myoclonic, mixed seizure types (4)[A]
    • Side effects: Weight gain, alopecia, sedation
    • Adverse effects: Thrombocytopenia, rare fulminant hepatic failure (especially in children <2 years of age)

Second Line

  • Topiramate affects GABA and excitatory neurotransmission:
    • Food and Drug Administration (FDA) approved for Lennox-Gastaut syndrome
    • Side effects: Psychomotor slowing
    • Adverse effects: Weight loss, renal stones, myopia, glaucoma (rare), anhidrosis
  • Zonisamide and levetiracetam are also used off-label.

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 Treatment

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  • Most absence seizure patients respond to a single medication.
  • Male gender and an early age at diagnosis are associated with the need for 2 medications to control the disease (8)[A].

In-Patient Considerations

Admission Criteria

  • 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, etc., 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

  • In childhood absence epilepsy without tonic–clonic seizures, 90% remit by adulthood (3).
  • 35% of patients with tonic–clonic seizures experience complete remission of absence seizures.
  • 15% of patients develop juvenile myoclonic epilepsy (JME) (9).

Complications

Reported frequencies of typical absence status epilepticus range from 5.8–9.4% of patients with CAE (10).

References

1. Commission on Classification and Terminology of the International League Against Epilepsy Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30(4):389–399.

2. Engel J. Report of the ILAE classification core group. Epilepsia. 2006;47:1558–68.

3. Valentin A, Hindocha N, Osei-Lah A, et al. Idiopathic generalized epilepsy with absences: syndrome classification. Epilepsia. 2007;48:2187–90.

4. Crunelli V, et al. Childhood absence epilepsy: Genes, channels, neurons, and networks. Nat Rev Neurol. 2002;3:371–82.

5. Nordli DR. Idiopathic generalized epilepsies recognized by the International League Against Epilepsy. Epilepsia. 2005;46(Suppl 9):48–56.

6. Blumenfeld H. From molecules to networks: cortical/subcortical interactions in the pathophysiology of idiopathic generalized epilepsy. Epilepsia.2003;44(Suppl 2):7–15.

7. Camfield P, Camfield C. Epileptic syndromes in childhood: clinical features, outcomes, and treatment. Epilepsia. 2002;43(Suppl 3):27–32.

8. Nadler B, Shevell MI. Childhood absence epilepsy requiring more than one medication for seizure control. Can J Neurol Sci. 2008;35:297–300.

9. Grosso S, Galimberti D, Vezzosi P, et al. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia. 2005;46:1796–801.

10. Shorvon S, Walker M. Status epilepticus in idiopathic generalized epilepsy. Epilepsia. 2005;46(Suppl 9):73–9.

11. 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;70:605–21.

Codes

ICD9

345.00 Generalized nonconvulsive epilepsy, without mention of intractable epilepsy

Snomed

79631006 absence seizure (disorder)

Clinical Pearls

  • To help aid with diagnosis during exam, try having child blow repetitively on pinwheel (causing hyperventilation) to attempt to trigger absence seizure.
  • Alternatively, ask patient to perform hyperventilation with eyes closed and count. Patient will open eyes at onset of seizure and stop counting (5).
  • Concern regarding generic medications allowing more breakthrough seizures has not been supported in evidence-based studies (11)[A].

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