What is the role of prolactin levels in differentiating between true and pseudo-seizures?

Role of Prolactin Levels in Differentiating True Seizures from Pseudoseizures

Serum prolactin measurement is a useful diagnostic tool for differentiating true epileptic seizures from pseudoseizures, with significant elevations occurring after generalized tonic-clonic and complex partial seizures but not after pseudoseizures.

Diagnostic Value of Prolactin

• Prolactin levels rise significantly in the postictal period (10-20 minutes after the event) in patients with generalized tonic-clonic seizures and complex partial seizures, but not in patients with pseudoseizures 1, 2
• The sensitivity of elevated serum prolactin is higher for generalized tonic-clonic seizures (60.0%) than for complex partial seizures (46.1%), while specificity is approximately 96% for both types 2
• A serum prolactin level of at least twice the baseline value is generally considered abnormal and indicative of a true seizure 2
• Prolactin levels do not rise significantly after simple partial seizures or pseudoseizures, making this test valuable for differential diagnosis 1, 3

Timing and Collection Methods

• Blood samples for prolactin measurement should be collected 10-20 minutes after the suspected event for optimal diagnostic value 2
• Both venous and capillary blood collection methods are valid, with strong correlation (Pearson coefficient of 0.90) between the two methods 4
• Capillary blood collection via finger-stick method applied to filter paper can be particularly useful for outpatient diagnosis, as samples remain stable at room temperature for up to one week 4

Clinical Application

• In pediatric populations, prolactin levels are significantly elevated following generalized seizures (mean 28.6 ± 2.3 ng/ml) compared to pseudoseizures (mean 10.4 ± 3.8 ng/ml) and controls (mean 9.8 ± 2.6 ng/ml) 5
• The American Academy of Neurology rates serum prolactin assay as a Level B recommendation (moderately strong evidence) for differentiating generalized tonic-clonic or complex partial seizures from psychogenic nonepileptic seizures in adults and older children 2
• The test correctly identified seizure versus pseudoseizure in 100% of patients with generalized tonic-clonic seizures, 71% of patients with complex partial seizures, and 100% of patients with pseudoseizures in clinical studies 4

Important Limitations

• Serum prolactin assay cannot distinguish epileptic seizures from syncope, as prolactin levels also rise after tilt-test-induced syncope 2
• The test has not been established for evaluation of status epilepticus, repetitive seizures, or neonatal seizures 2
• Prolactin levels can be affected by various factors including stress, medications, hypothyroidism, renal or hepatic disease, and pituitary disorders, which must be considered when interpreting results 6

Potential Confounding Factors

• Stress can elevate prolactin levels up to five times the upper limit of normal 6
• Medications that antagonize dopamine are among the most common causes of hyperprolactinemia 6
• Primary hypothyroidism can cause hyperprolactinemia in 43% of women and 40% of men 6
• Chronic kidney disease is associated with hyperprolactinemia in 30-65% of adult patients 6
• Severe liver disease can also cause elevated prolactin levels 6

Clinical Implementation

• When evaluating a patient with suspected pseudoseizures, collect blood 10-20 minutes after the event 2
• Compare the prolactin level to the patient's baseline or to laboratory reference ranges, looking for at least a two-fold increase 2, 3
• Consider using capillary blood collection kits for outpatient diagnosis when venous sampling is not feasible 4
• Always interpret results in conjunction with clinical presentation, as false negatives can occur, particularly with complex partial seizures 2