Practice Assessment: The Use of Serum Prolactin in Diagnosing Epileptic Seizures

1. Practice Assessment: The Use of Serum Prolactin in Diagnosing Epileptic Seizures Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology David K. Chen, MD; Yuen T. So, MD, PhD; and Robert S. Fisher, MD, PhD Published in Neurology 2005;65:668-675

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3. Introduction • Prolactin (PRL) released from the pituitary is under the control of the hypothalamus via the prolactin inhibitory factor, now believed to be dopamine • May alter the hypothalamic regulation of PRL release • Trimble first demonstrated that generalized tonic-clonic seizures could raise serum prolactin • The sensitivity and specificity of serum PRL assay for diagnosis of epileptic seizures remain uncertain

4. Objective To review the use of serum prolactin assay in epileptic seizure diagnosis, and present evidence-based practice recommendations.

5. Description of Process • Searched MEDLINE, Science Citation Index, and the Cochrane Database • A total of 381 articles met the keywords search, as of October, 2003 • Reviewed the abstracts of these articles, looking for controlled studies that reported on PRL changes following seizures or seizure-like events

6. Description of Process • Reviews without original data, letters, meeting abstracts, and case reports/series were excluded • Examined 39 articles in their entirety, along with 5 additional articles identified upon reviewing bibliographies of the retrieved articles

7. AAN Strength of Evidence

8. AAN Strength of Evidence

9. Translation of Evidence to Recommendation Level

10. Translation of Evidence to Recommendation Level

11. Guideline’s Clinical Questions Question #1 Is serum PRL assay useful in differentiating epileptic seizures from psychogenic non-epileptic seizure ?

12. Analysis of the Evidence Table: Prospective controlled studies investigating PRL changes following either ES or psychogenic NES

13. Analysis of the Evidence

14. Analysis of the Evidence

15. Analysis of the Evidence Table: Validity measures of serum prolactin assay in differentiating ES and NES

16. Analysis of the Evidence

17. Analysis of the Evidence

18. Analysis of the Evidence

19. Conclusion • On the basis of one class I and conflicting class II studies, an elevated PRL level when measured within 20 minutes of a suspected event is probably a useful adjunct to differentiate GTC or CPS from psychogenic NES among adults and older children. • On the basis of consistent class I and II studies, the low sensitivity and low negative predictive value of a normal serum PRL assay does not permit the diagnosis of psychogenic NES nor exclude the possibility of GTC or CPS.

20. Guideline’s Clinical Questions Question #2 Does serum PRL measure change following other neurological conditions?

21. Analysis of the Evidence Table: Methodologic characteristics of studies evaluating serum prolactin changes following tilt-induced syncope

22. Analysis of the Evidence

23. Analysis of the Evidence Table: Methodologic characteristics of studies evaluating serum prolactin changes following status epilepticus, or repetitive seizures (not SE).

24. Analysis of the Evidence

25. Conclusion • On the basis of limited class II studies, serum PRL probably increases at least two-fold from baseline level when measured within 10 minutes after syncope in adults. • On the basis of one negative class II study that did not show a significant change in PRL level, no conclusion can be established regarding serum PRL changes following termination of status epilepticus.

26. Conclusion • On the basis of conflicting class II studies, no conclusion can be established regarding serum PRL changes following repetitive seizures (not SE). • On the basis of conflicting class II studies, no conclusion can be established regarding serum PRL changes following epileptic seizures in neonates

27. Evidence-based Recommendations

28. Evidence-based Recommendations

29. Recommendations for future research • Standardization of “abnormal” PRL elevation: A large sample size, gender-matched study of baseline PRL values in healthy and epileptic subjects, allowing for uninterrupted sleep, may provide more accurate standardization of gender-specific PRL threshold values. • Capillary PRL assays: Future studies investigating the utility of an outpatient PRL kit kept at home to document capillary PRL changes shortly post-event may circumvent current practical limitations.

30. Recommendations for future research • PRL in other types of physiologic non-epileptic events: Future studies are necessary to define the specificity of PRL assay in the setting of these events • Pediatric population: Future prospective studies of postictal PRL measures in neonates and young children are needed • PRL in other epileptic disorders: Further data are needed in order to interpret PRL value following status epilepticus and repetitive seizures.

31. Acknowledgement Therapeutics and Technology Assessment Subcommittee Members: Douglas S. Goodin, MD (Chair); Yuen T. So, MD, PhD (Vice-Chair); Carmel Armon, MD; Richard M. Dubinsky, MD: Mark Hallett, MD; David Hammond, MD; Cynthia Harden, MD; Chung Hsu, MD, PhD (ex-officio); Andres M. Kanner, MD (ex-officio); David S. Lefkowitz, MD ;Janis Miyasaki, MD; Michael A. Sloan, MD; James C. Stevens, MD

32. To view the entire guideline and additional AAN guidelines visit: AAN.com/Guidelines Published in Neurology 2005;65:668-675

33. Disclaimer • This assessment focused on the use of serum prolactin assay in epilepsy diagnosis. The utility of serum PRL assay in other indications is beyond the scope of this review. This statement is provided as an educational service of the American Academy of Neurology. It is based on an assessment of current scientific and clinical information. It is not intended to include all possible proper methods of care for a particular neurological problem or all legitimate criteria for choosing to use a specific procedure. Neither is it intended to exclude any reasonable alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient, based on all of the circumstances involved.