What is the role of lactate and creatine kinase (CK) in diagnosing and managing a patient with suspected seizure and loss of consciousness?

Role of Lactate and Creatine Kinase in Diagnosing Suspected Seizures

Serum lactate is a valuable diagnostic tool to differentiate generalized tonic-clonic seizures from other causes of transient loss of consciousness, with significantly elevated levels (>2.4 mmol/L) providing high specificity and sensitivity when measured within 3 hours of the event. 1

Diagnostic Value of Serum Lactate

Lactate for Seizure Diagnosis

• Serum lactate levels are significantly higher in patients with generalized tonic-clonic seizures (GTCS) compared to other causes of transient loss of consciousness (TLOC)

  • Mean difference of 5.27 mmol/L higher in GTCS vs. other TLOC causes 1
  • Lactate levels increase approximately 8.7-fold shortly after GTCS 2
  • 90% of GTCS patients show lactate levels more than twice the upper limit of normal 2

• Optimal timing and cutoff values:

  • A lactate concentration of 2.4 mmol/L provides excellent discrimination between GTCS and non-GTCS events (AUROC 0.94-0.97) 1
  • Lactate levels return to baseline within approximately 2 hours after a seizure 2
  • Venous lactate threshold of 2.5 mmol/L has 97% specificity and 73% sensitivity for diagnosing generalized seizures 3

• Clinical correlation:

  • Postictal lactate levels correlate significantly with the duration of the tonic-clonic phase 2
  • Lactate elevations result from hypoxemia, increased catecholamines, and muscle metabolism during seizures 3

Diagnostic Value of Creatine Kinase (CK)

CK for Seizure Diagnosis

• CK elevations are less common and occur later than lactate elevations:

  • Only about 10% of GTCS patients show CK elevations above the upper limit of normal immediately after seizures 2
  • CK peaks approximately 48 hours after the seizure event 2

• Timing significantly affects CK diagnostic value:

  • Sensitivity improves when sampling at least 3 hours after the event (80% sensitivity, 94% specificity) 4
  • Sequential CK measurements (admission and 24 hours later) provide better diagnostic accuracy than single measurements 5

• Differentiating seizures from syncope:

  • An increase in CK of >15 mU/ml between first and second day measurements has 69% sensitivity and 94% specificity for GTCS vs. vasovagal syncope 5
  • CK levels >200 mU/ml are highly unlikely to result from vasovagal syncope 5

Clinical Application in Suspected Seizures

Recommended Diagnostic Approach

1. Obtain serum lactate as soon as possible (ideally within 3 hours of the event)

   • Levels >2.4-2.5 mmol/L strongly suggest GTCS 1, 3
   • Normal lactate levels do not rule out non-GTCS seizures

2. Consider sequential CK measurements

   • Initial measurement upon presentation
   • Follow-up measurement at 24 hours
   • An increase of >15 mU/ml between measurements strongly suggests GTCS 5

3. Interpret laboratory findings in clinical context

   • European Heart Journal guidelines emphasize that headache, muscle pain, and elevated CK and prolactin are more frequent after epilepsy than syncope 6
   • Clinical history remains essential for distinguishing seizures from syncope 6

Important Clinical Considerations

• Lactate has limited value in differentiating between:

  • Syncope and psychogenic non-epileptic seizures (PNES)
  • Syncope and non-GTCS seizures 1

• Other metabolic markers after GTCS:

  • Ammonia increases 2.6-fold in about 70% of cases
  • Prolactin increases 5.1-fold in about 70% of cases
  • Phosphate shows biphasic response (early increase, decrease after 2 hours) 2

• Avoid over-reliance on any single laboratory test:

  • Guidelines emphasize that laboratory tests should complement, not replace, careful clinical evaluation 6
  • Lactate levels should be interpreted alongside proper clinical context 1

Practical Implementation

When evaluating a patient with suspected seizure and loss of consciousness:

1. Measure serum lactate as early as possible (within 3 hours)
2. Consider initial and follow-up CK measurements (at presentation and 24 hours later)
3. Use these biomarkers to support clinical assessment, not as standalone diagnostic tools
4. Remember that lactate is particularly useful for identifying GTCS but less helpful for other types of seizures or TLOC

By incorporating these laboratory tests into the clinical evaluation, clinicians can more accurately distinguish seizures from other causes of transient loss of consciousness, potentially avoiding unnecessary treatments and ensuring appropriate management.