Can status epilepticus cause elevated proteins in cerebrospinal fluid (CSF)?

Can Status Epilepticus Cause Elevated CSF Proteins?

Yes, status epilepticus can cause elevated proteins in cerebrospinal fluid, with the degree of elevation correlating directly with seizure duration and severity.

Mechanism and Pathophysiology

Status epilepticus triggers blood-CSF barrier disruption and neuronal damage, leading to measurable protein elevations in the cerebrospinal fluid 1. The inflammatory response during seizures is typically short-lived but results in increased expression of inflammatory cytokines (IL-1β, IL-6, and TNF) in brain regions where epileptogenesis occurs 2.

Specific Protein Elevations

Albumin Quotient (Blood-CSF Barrier Disruption)

• Elevated in 34% of patients with epileptic seizures 1
• The albumin quotient increases proportionally with seizure duration, indicating blood-CSF barrier breakdown 1
• Status epilepticus produces the highest values compared to other seizure types 1

Tau Protein (Neuronal Damage Marker)

• Elevated in 36% of CSF samples from patients with epileptic seizures 1
• CSF t-tau levels are significantly higher in refractory status epilepticus compared to seizures controlled by antiepileptic drugs 3
• T-tau values correlate positively with status epilepticus duration 3
• Patients with higher CSF t-tau have 32.5 times higher risk of developing disability and 12 times higher risk of chronic epilepsy 3

Neuron-Specific Enolase (NSE)

• NSE is one of the first described markers of neuronal death and is elevated in status epilepticus 4
• Serum NSE levels are higher in status epilepticus patients compared to control patients or those with pharmacoresistant epilepsy 5
• However, NSE has lower diagnostic accuracy (AUC 0.624) compared to other biomarkers 5

S100-Beta Protein (Glial Injury)

• Serum S100B levels above 0.09 ng/mL indicate status epilepticus with 84% specificity 5
• S100B demonstrates good diagnostic accuracy (AUC 0.748) for detecting status epilepticus 5
• Reflects gliosis resulting from inflammatory responses after status epilepticus 4

Progranulin (Neuroprotective Response)

• Plasma progranulin levels are elevated in status epilepticus with good diagnostic accuracy (AUC 0.756) 5
• Both NSE and progranulin levels are higher in CSF from status epilepticus patients compared to controls 5
• Progranulin reflects neuroprotective mechanisms resulting from brain adaptation to excitotoxicity 4, 6

Clinical Correlations

Seizure Type and Duration Matter

• Status epilepticus produces the highest protein elevations, while simple partial seizures produce the lowest 1
• All CSF parameters (except cell count) are influenced by seizure type 1
• Duration of epileptic seizures correlates positively with albumin quotient, lactate, and tau-protein levels 1

Etiology Influences Protein Levels

• Symptomatic partial and generalized epileptic seizures have significantly higher tau-protein levels than cryptogenic partial seizures 1
• Patients with repetitive and occasional epileptic seizures show higher tau-protein levels than those with psychogenic seizures 1

Important Clinical Caveats

Cell Count Remains Normal

• Cell counts are only slightly elevated in 6% of patients with epileptic seizures 1
• Elevated cell counts should NOT be uncritically interpreted as a postictal phenomenon and warrant investigation for other causes such as infection 1
• This contrasts with systemic lupus erythematosus with CNS involvement, where abnormal CSF findings (elevated proteins, lymphocytic pleocytosis, oligoclonal bands) are associated with poor prognosis 2

Lactate Elevation

• Lactate concentration is elevated in 14% of patients, reflecting increased glucose metabolism during seizures 1

High Variability Limits Diagnostic Certainty

• High variability of CSF parameters within each subgroup makes clear separation between epileptic and psychogenic seizures impossible based on CSF alone 1
• Clinical context, EEG findings, and seizure semiology must guide interpretation 7, 8

Prognostic Implications

CSF t-tau levels serve as both a severity marker and prognostic indicator 3. Patients with elevated t-tau face substantially higher risks of disability and chronic epilepsy development, making this measurement clinically valuable beyond simple diagnosis 3.