What is more accurate for differentiating between true seizures and pseudo-seizures, lactate (lactic acid) levels or prolactin levels in bloodwork?

Prolactin vs. Lactate for Differentiating True Seizures from Pseudoseizures

Prolactin measurement is more accurate than lactate for differentiating between true seizures and pseudoseizures, with elevated prolactin levels showing high specificity for true seizures when measured 10-20 minutes post-event.

Prolactin as a Diagnostic Marker

• Serum prolactin levels rise significantly after generalized tonic-clonic seizures and complex partial seizures, but remain normal after pseudoseizures, making prolactin measurement a valuable diagnostic tool 1, 2, 3
• Prolactin levels should be measured within 10-20 minutes after the seizure-like event for optimal diagnostic accuracy 1
• In patients with generalized tonic-clonic seizures, prolactin measurement has shown 100% accuracy in differentiating from pseudoseizures when using any elevation above laboratory upper limit of normal as the criterion 1
• For complex partial seizures, prolactin measurement has approximately 71% accuracy in distinguishing from pseudoseizures 1
• The neurophysiological basis for post-ictal prolactin elevation is a decrease in GABAergic and dopaminergic systems associated with true seizures 4

Diagnostic Performance of Prolactin

• Studies show that post-ictal prolactin levels in patients with generalized seizures average around 28.6 ± 2.3 ng/ml, compared to 10.4 ± 3.8 ng/ml in pseudoseizures and 9.8 ± 2.6 ng/ml in controls 3
• When measured within 60 minutes of the event, elevated prolactin has a positive predictive value of 89% for true seizures 5
• The negative predictive value of prolactin (ability to rule out true seizures when normal) is approximately 61% 5
• Prolactin levels typically increase 2-3 fold over baseline after generalized tonic-clonic and complex partial seizures 4

Lactate as a Diagnostic Marker

• While serum lactate is a sensitive marker for tissue hypoperfusion and shock, it is not specific for seizures 6
• Lactate can be elevated due to multiple factors unrelated to seizures, including cerebral hypoxia/ischemia, anaerobic glycolysis, vascular compromise, and alcohol consumption 6
• The non-specificity of lactate elevation limits its usefulness in differentiating true seizures from pseudoseizures 6

Clinical Application and Considerations

• Capillary blood collection (finger-stick method) for prolactin measurement correlates well with venous sampling (Pearson coefficient of 0.90), making it more practical for outpatient settings 1
• Prolactin samples on filter paper remain stable at room temperature for up to one week, enhancing clinical utility 1
• When interpreting prolactin results, consider other causes of hyperprolactinemia, including medications (especially dopamine antagonists), hypothyroidism, renal or hepatic disease, and stress 7
• Stress can elevate prolactin levels up to five times the upper limit of normal, which may confound interpretation in the acute setting 7

Practical Recommendations

• Obtain blood sample for prolactin measurement 10-20 minutes after a seizure-like event 1, 5
• Consider prolactin measurement particularly useful for differentiating generalized tonic-clonic seizures from pseudoseizures 2, 3, 4
• Be aware that prolactin may not rise after simple partial seizures or absence seizures, limiting its diagnostic utility in these cases 4
• When using prolactin as a diagnostic tool, rule out other causes of hyperprolactinemia including medications, hypothyroidism, and stress 7
• For improved diagnostic accuracy, compare post-ictal prolactin levels to the patient's baseline or to samples taken 1-2 days after the event 5