First Unprovoked Seizure

by Michael Wong, MD, PhD

EPIDEMIOLOGY

Cumulative (Lifetime) Incidence: ~5% of people have at least one unprovoked seizure in their lifetime (Hauser et al. 1993, Forsgren et al. 1996). This contrasts with the ~3-4% cumulative incidence of epilepsy (at least two unprovoked seizures) and ~4% incidence of acute symptomatic seizures. Thus, the incidence of a first unprovoked seizure is ~33% greater than the incidence of epilepsy, reflecting the proportion of first seizures that do not recur.

The age-dependent incidence of a first unprovoked seizure is similar to the incidence of epilepsy (See III.A.2), with peak incidences at the extremes of life (Hauser et al. 1993).

In comparison to epilepsy (See IIIA.4-5), the distribution of seizure types (~50% partial, 50% generalized) and etiology (~30% remote symptomatic, ~70% idiopathic/cryptogenic) of first unprovoked seizures differs with higher proportions of generalized and idiopathic seizures (Hauser et al. 1993), reflecting the increased risk of partial and remote symptomatic seizures for recurrence (See IID.1).

DIAGNOSTIC EVALUATION

American Academy of Neurology Practice Parameter (2000) on evaluation of a first non-febrile seizure in children recommends that an EEG be obtained in all children, but the use of MRI, LP, or other laboratory tests (e.g. electrolytes, tox screen) depends on the specific clinical circumstances (Quality Standards Subcomittee of the AAN 2000). However, at least one study has argued that a EEG should not be routinely obtained after a first unprovoked seizure (Gilbert and Buncher 2000).

EEG

  1. Overall: ~30-40% of first EEGs show epileptiform abnormalities (King et al. 1998, Shinnar et al. 1994).
  2. Early vs Late EEG: Early EEGs may have a higher yield of epileptiform abnormalities with 51% 24 hrs of seizure (King et al. 1998).
  3. Repeated EEG: Repeating an EEG up to 4 times may significantly increase yield of epileptiform abnormalities with ~30% on 1st, ~40% on 2nd, ~50% on 3rd, and ~55% on 4th. Minimal additional yield obtained from more than 4 EEGs (Salinsky et al. 1987).
  4. Age: Children have more EEG abnormalities (30-60%) than adults (10-40%) (Hopkins et al. 1988, Shinnar et al. 1994). Children >3 yrs had more EEG abnormalities (53%) than children
  5. Seizure Type: Abnormal EEGs were more common in patients with partial seizures (56%) than generalized seizures (35%) (Shinnar et al. 1994).
  6. Etiology: Abnormal EEGs were more common in patients with remote symptomatic etiologies (60%) than idiopathic (38%) (Shinnar et
    al. 1994).

Neuroimaging

  1. Diagnostic Yield: MRI detected abnormalities in ~10-20% in a combined pediatric-adult study (King et al. 1998) and purely pediatric studies (Berg et al. 2000, Shinnar et al. 2001). However, the percentage of cases where diagnosing the lesion changed patient management was much less (Shinnar et al. 2001).
  2. Partial vs Generalized: Patients with clinically-diagnosed partial seizures had epileptogenic lesions on MRI detected in 17% of cases. 1 of 50 patients with a clinical diagnosis of generalized seizures had a focal lesion on MRI; 0 of 49 patients with generalized epileptiform EEG abnormalities had a focal lesion (King et al. 1998).

TREATMENT

Treatment with AEDs after a first seizure significantly reduces the risk of seizure recurrence (Camfield et al. 1989, First Seizure Trial Group 1993, Gilad et al. 1996).
Treatment with AEDs after a first seizure does not alter the chance of remission after starting AEDs compared to patients treated after 2 seizures (First Seizure Trial Group 1997). Combined with the significant probability of no recurrence, this supports the approach of withholding AED treatment until after a second seizure.

PROGNOSIS

Overall Recurrence Rate and Risk Factors

  1. Meta-analysis: Meta-analysis of 16 studies (Berg and Shinnar 1991) found an overall risk of recurrence of 51% (range 23 to 71%).
    1. Variability in results was attributed to study design, inclusion criteria, interval between seizure and enrollment, and follow-up period. Retrospective studies, community-based studies, and studies that enrolled patients within 24 hours of the seizure have higher recurrence rates than prospective studies, hospital-based studies, and studies with longer intervals to enrollment, respectively.
    2. Remote symptomatic etiology and abnormal EEG were the strongest and most consistently-identified risk factors for recurrence.
  2. Pediatric Study: Prospective study of 407 children, 1 mo to 19 yrs old, with mean follow-up of 6.3 years (Shinnar et al. 1990, 1996). Overall recurrence risk = 42% at 5 years. 5 risk factors for recurrence were identified:
    1. Etiology: remote symptomatic (66%) vs. idiopathic (37%).
    2. EEG: abnormal EEG (59%) vs normal EEG (32%).
    3. Sleep state: seizure in sleep (53%) vs awake (36%).
    4. Hx of febrile seizure: positive history (54%) vs negative (39%).
    5. Todd’s paresis: present (61%).
    6. Status epilepticus did not increase recurrence risk, but did increase risk of second episode of status (21% of recurrences vs 1% of recurrences in patients with first non-status seizure).
    7. Multiple seizures within 24 hours did not increase recurrence risk.
  3. Minnesota Study: 208 primarily adult patients with mean follow-up of 4 years (Hauser et al. 1982, 1990). Overall recurrence risk = 34% at 5 years. Risk factors:
    1. Etiology: remote symptomatic (48%) vs idiopathic (29%).
    2. Among idiopathic cases, increased recurrence was associated with positive FHx of epilepsy (46% vs 27%), GSW on EEG (58% vs 26%), and Hx of febrile/acute symptomatic seizure (39% vs 27%).
    3. Among remote symptomatic cases, increased recurrence was associated with Todd’s paresis (75% vs 39%), Hx of febrile/acute symptomatic seizure (80% vs 41%), status epilepticus (56% vs 43%).
  4. Other Studies (Annegers et al. 1986, Camfield et al. 1985, Hart et al. 1990) have found partial seizures and an abnormal neurological
    examination to have increased recurrence risk.

Timing of Recurrence: risk decreases rapidly with time after first seizure.

  1. Patients initially enrolled in study within 4 weeks of seizure had 50% recurrence rate compared to patients enrolled at least 8 weeks after the seizure who had only 15% recurrence rate, likely secondary to exclusion of patients from the study that had already recurred prior to 8 weeks (Hopkins et al. 1988).
  2. >50% of recurrences occur within first 3 (Hart et al. 1990) to 6 months (Annegers et al. 1986, Shinnar et al. 1996).
  3. Only 2% of recurrences occurred after 5 years (Shinnar et al. 1996).

First Two Seizures in Same Day (Camfield and Camfield 2000). Patients with the first two seizures on the same day had a similar prognosis for epilepsy (~80% progressed to 3rd seizure) than patients with first two seizures on different days, suggesting that a diagnosis of epilepsy is appropriate for patients with the first two seizures on the same day.

Risk of 3rd Seizure (Hauser et al. 1998, Shinnar et al. 2000): Risk of 2nd seizure = 33% at 5 years. Risk of 3rd seizure after 2nd seizure = ~75% at 4 years.

REFERENCES

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