Does C‑reactive protein increase after seizures, and does the magnitude differ by seizure type (e.g., status epilepticus versus isolated tonic‑clonic seizures)?

Does CRP Elevate with Seizure Activity?

Yes, CRP consistently elevates after seizures, with the magnitude and pattern varying significantly by seizure type—secondarily generalized tonic-clonic seizures (SGTCS) produce the most robust CRP elevation, while focal seizures without generalization cause milder increases. 1, 2

Baseline CRP Elevation in Epilepsy Patients

• Patients with refractory focal epilepsy demonstrate significantly higher baseline CRP levels (3.5 mg/mL) compared to healthy controls (0.7 mg/mL, p < 0.001), even before acute seizure activity. 2
• Meta-analysis of 1,918 individuals across 16 studies confirms that epileptic patients have significantly elevated peripheral blood CRP compared to controls (SMD = 0.43; 95% CI: 0.19-0.67), with this effect more pronounced in adults (SMD = 0.47) than children (SMD = 0.26, not statistically significant). 3
• Among patients with elevated baseline CRP (>mean + 2 SD above controls), temporal lobe epilepsy accounts for all cases versus zero in extratemporal epilepsy (p = 0.018), suggesting regional differences in inflammatory burden. 2

Acute CRP Response by Seizure Type

Generalized tonic-clonic seizures produce the most significant CRP elevation:

• Secondarily generalized tonic-clonic seizures are the most important independent predictor of CRP increase from baseline to maximum post-seizure levels (p = 0.030). 2
• In patients presenting to emergency departments with seizures, 56.3% demonstrate inflammation-like responses (elevated temperature, WBC, or CRP), with CRP elevations occurring after any seizure type—not exclusively GTCS. 1
• Body temperature elevation occurs only with generalized tonic-clonic seizures, whereas leukocytosis and CRP elevation occur with any seizure type, providing a key distinguishing feature. 1

Temporal Pattern and Magnitude of CRP Elevation

• CRP levels correlate significantly with plasma IL-6 concentrations (r = 0.42, p = 0.009), reflecting the cytokine-mediated acute phase response triggered by seizure activity. 4
• In uncomplicated seizure cases without infection, CRP elevations remain below 6 mg/dL, providing a critical threshold for clinical decision-making. 1
• CRP levels above 6 mg/dL warrant close observation and consideration for concurrent infection rather than seizure-induced inflammation alone. 1

Clinical Implications for Status Epilepticus

• Higher initial CRP concentrations in status epilepticus independently predict in-hospital mortality and poor functional outcome at discharge, even after adjusting for SE severity, etiology severity, and treatment refractoriness. 5
• Initial CRP levels add prognostic value to status epilepticus outcome prediction, though the pathomechanisms linking CRP to SE prognosis remain incompletely understood. 5

Distinguishing Seizure-Induced Inflammation from Infection

Critical thresholds and timing help differentiate seizure-induced CRP elevation from infectious causes:

• CRP magnitude: Seizure-induced elevations typically remain <6 mg/dL, while concurrent infections produce CRP >6 mg/dL. 1
• Temperature pattern: Body temperature >39°C or fever persisting >8 hours after consciousness recovery suggests infection rather than seizure alone. 1
• Seizure type specificity: Elevated body temperature without generalized tonic-clonic seizures should raise suspicion for infection. 1
• Among emergency department visits with inflammation-like responses, 34.7% ultimately had confirmed infection, emphasizing that elevated CRP cannot definitively exclude infectious etiology. 1

Mechanistic Context

• Epileptic seizures provoke cytokine production (particularly IL-6) that activates the acute phase reaction, explaining both CSF pleocytosis and peripheral inflammatory marker elevation without infection. 4
• Peripheral blood leukocyte counts (7.9 × 10⁹ vs. 6.1 × 10⁹, p = 0.002) and CSF leukocyte counts (1.9 × 10⁶ vs. 1.1 × 10⁶, p = 0.032) are significantly elevated in seizure patients compared to controls, independent of infection. 4
• The association between inflammation and refractory epilepsy is bidirectional—chronic epilepsy elevates baseline inflammatory markers, while acute seizures trigger additional inflammatory responses. 2, 3

Common Pitfalls to Avoid

• Do not automatically attribute CRP elevation or CSF pleocytosis to infection in acute seizure patients—these are expected physiologic responses to seizure activity. 4
• Do not dismiss infection based solely on seizure history—use the 6 mg/dL CRP threshold, temperature pattern, and clinical context to guide further evaluation. 1
• Do not overlook the prognostic value of initial CRP in status epilepticus, as it independently predicts mortality and functional outcome beyond traditional severity measures. 5