Use of serum prolactin in diagnosing epileptic seizures.

Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

A recent AAN Practice Parameter concluded that postictal prolactin (PRL) elevation is useful in differentiating generalized tonic-clonic and complex partial seizures from psychogenic nonepileptic seizure. This observation was previously suggested by Trimble. An interesting finding is that serum PRL does not increase during status epilepticus (SE). As stated in the parameter, “on the basis of inconsistent studies, no conclusion can be established regarding serum PRL changes following termination of SE.” The purpose of this monograph is to shed light on this paradox and to suggest clues to the pathophysiology and treatment of SE.

Normally, seizures spontaneously stop as the cortical inhibitory mechanisms extinguish the abnormal neuronal electric activity. The postictal EEG slowing, Todd's paralysis, and postictal psychological depression are examples of manifestations of the cortical inhibition. Various mechanisms have been proposed to contribute to the postictal state. One hypothesis is that the cortical activity in SE does not reach the threshold to initiate the shut-off mechanism. Thus the inhibitory process may not be fully activated in SE leading to failure of seizure termination. Because SE often is the first clinical seizure of an epileptic patient it has been proposed that the naïve brain must be trained to harness its built-in antiseizure mechanism.

GABA(A) receptors undergo functional changes during prolonged SE perhaps further compounding the deficiency in cortical inhibition. The longer SE continues the more refractory to treatment it becomes. It is rare that a prolonged seizure is induced during electroconvulsive therapy (ECT), and typically another electric shock at higher or maximum energy levels will terminate the seizure. Can it be that SE really is “status hypoepilepticus?” This hypothesis may change our view regarding the treatment algorithm for SE that conventionally aims at inhibition of the seizure activity. This is generally achieved by administration of serial anticonvulsants or induction of pharmacologic coma or generalized anesthesia that carry a considerable morbidity. Instead, a full generalized seizure using ECT may be able to reach the threshold required for effective cortical depression in refractory SE.

The spread of ictal activity from the hippocampus or amygdala to the hypothalamus can elicit pituitary PRL release. Complex partial seizures involving the temporal lobes and high-frequency simple partial seizures involving limbic structures increase PRL release. A study of PRL response to ECT demonstrated that suprathreshold and bilateral stimulations yielded more robust PRL rise than threshold and unilateral stimulations, respectively. According to one study, the shorter the interictal period the smaller the PRL release.

In repetitive or continuous seizures, the postictal PRL release may decrease, and in SE it does not increase. PRL stores may be exhausted and not sufficiently replenished during SE. However, this hypothesis has been refuted by at least two experiments that were able to induce a PRL surge during SE using metoclopramide or TRH as a PRL-releasing factor.

Another possible explanation for the decremental PRL release in SE is that the intensity of ictal discharges gradually diminishes during the course of SE. This is supported by the common clinical observation that motor phenomena usually decrease during SE.