Some patients may experience a paradoxical worsening of a seizure disorder following therapy with valproic acid. This may serve as a clue to the patient's underlying diagnosis.

Causes of worsening of a seizure disorder with valproic acid therapy:

(1) hyperammonemic encephalopathy:

(1a) carnitine deficiency

(1b) urea cycle disorder

(1c) valproate-induced hyperammonemic encephalopathy

(1d) valproic acid overdose (from an excessive dose)

(2) nonketotic hyperglycinemia


Other conditions contributing to a seizure disorder need to be excluded.


A patient may also experience other findings which makes early recognition important:

(1) impaired consciousness

(2) focal neurological symptoms

(3) worsening of hepatic function


Testing might include:

(1) serum ammonia concentration

(2) valproic acid serum concentration

(3) serum glycine concentration

(4) response to L-carnitine administration

(5) testing for urea cycle disorders

To read more or access our algorithms and calculators, please log in or register.