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
