Treatment of First Unprovoked (Nonfebrile) Seizure

 

Epilepsy:  Disorder of the brain characterized by an enduring predisposition to generate seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition. (1)

 

Unprovoked Seizure- Seizure as a transient occurrence of signs and or symptoms as a result of abnormal excessive or enhanced synchronous neuronal activity in the brain that cannot be associated with a precipitating factor.  (1)

 

Types of Seizures:

·      Partial, Tonic-Clonic, Clonic, Status Epileptics-seizures lasting longer than 30 minutes

·      Seizures that were excluded were one’s associated with epilepsy which could not be diagnosed after one seizure, neonatal seizures, and seizures that were caused by an obvious cause such as CNS trauma, CNS insult, or infection

 

Incidence of Seizures: 

·      10% of the population will have had at least one seizure in their lifetime.

·      25,000-40,000 children in the US will experience an unprovoked seizure a year

 

Risk of recurrences:

·      Current research is highly variable and is dependent on age of occurrence

·      The younger the appearance of the first seizure, the higher the risk

·      All studies performed have level 3 evidence and range from 15%-46%

·      Recurrence of multiple seizures are also highly variable

o   Incidence is higher in children with prior insult such as Cerebral Palsy or Mental Retardation

o   Incidence also higher with patients who had abnormal EEG pattern

 

 

Is treatment after first seizure effective for short-term prognosis?

·      Current research does not have strong evidence in the pediatrics population

·      Only one class 2 study which is RCT shows reduced risk after 1-yr follow up of recurrence after treatment with Carbamazepine 14% vs. 53%

·      One class one study used Valproic Acid and used RCT with both adults and pediatric patients which showed 4% risk of recurrence vs. 46%, however another study with similar design showed no difference

 

Is treatment after first seizure effective for long-term prognosis?

·      Currently 2 level 2 studies show that there is no long term benefit of starting treatment after first seizure vs. after second seizure in achieving a 1-2 year remission of seizure activity

 

Current Drugs and Side Effects?  There is level 2 evidence that use of AED’s have serious side effects including serious cognitive, behavioral, and system side effects. The worst of these is Phenobarbital where rates of systemic side-effects range anywhere from 4%-58%!!!!!

 

 

·      Phenobarbital- behavioral changes, drowsy feeling, disturbed auditory info processing, declining cognitive performance, hyperactivity which is very common

·      Carbamazepine- Nausea/Vomiting, ataxia, headache, rash, gingival hyperplasia, impaired recent recall, severe behavior changes

·      Valproic acid- Somnolence, ataxia, rash, wt. gain, alopecia, hyperactivity

·      Phenytoin (the most side effects)- gingival hyperplasia, ataxia, rash, blood dyscrasia, impaired information processing early in infancy, mood problems

 

Conclusion: Overall there is some weak evidence that treatment with AED after a first unprovoked seizure reduces seizure activity short term. There is stronger evidence that treatment after first seizure does not improve long term prognosis and remission rates of seizure activity compared to treatment after 2nd unprovoked seizure.

 

Current recommendation: The decision to treat a patient with AED after first unprovoked seizure is case dependent but should not be performed routinely. One must weigh the benefits vs. the harmful side effects of the AED in deciding whether to begin treatment.

 


Drug Systemic S/E Behavioral & cognitive S/E
Phenobarbital Drowsy, behavioral -disturbed auditory info processing

-dec. cognitive performance

-hyperactivity(22%)

Carbamazepine N/v, ataxia, somnolence, h/a, rash, gingival hyperplasia, blood dyscrasia(rare) -impaired recent recall

-mod/severe behavior problems

Valproic acid Somnolence, ataxia, rash, wt gain, alopecia -hyperactivity(13%)
Phenytoin Gingival hyperplasia(58%), ataxia(25%), rash, blood dyscrasia -impaired info processing at 1 mo

-mod/severe behavior problems

***Overall rate of S/E is about 24%

Conclusions:

  1. First unprovoked seizure should NOT be treated with AED routinely; instead risks of recurrent seizures and their sequelae should be weighed against possible side effects of chronic AED use.
  2. AED use does NOT prevent epilepsy, as shown by no difference in long-term outcomes in treatment and no treatment groups.
Reference:
1-Beghi E. Management of a first seizure. General conclusions and recommendations.
Epilepsia 2008; 49 (Suppl. 1):

 2- Berg AT. Risk of recurrence after a first unprovoked seizure. Epi- lepsia 2008; 49 (Suppl. 1): 13–8.

3- Fisher RS, van Emde Boas W, Blume W et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005; 46: 470–2.

 4- Hirtz, D. et al. Practice parameter: Treatment of the child with a first unprovoked seizure. Neurology 60, January(2), 2003: 166-175.

5  Hout,SR.et al.  Considerations in the Treatment of a First Unprovoked Seizure.  Seminars in Neurology 28(3), 2008:289-296