What cerebrospinal fluid (CSF) studies should be ordered in a patient with new onset seizures and encephalopathy?

CSF Studies for New-Onset Seizures with Encephalopathy

Lumbar puncture with CSF analysis should be performed after head CT in patients with new-onset seizures and encephalopathy, particularly when there is concern for meningitis, encephalitis, or autoimmune encephalitis, or in immunocompromised patients. 1

When to Perform Lumbar Puncture

The primary indication for CSF analysis in seizure patients is to evaluate for infectious or immune-mediated causes 1:

• Fever with meningeal signs - This is the most critical indication for immediate lumbar puncture 1
• Immunocompromised status - These patients require lumbar puncture after head CT due to higher rates of CNS infections presenting with seizures 2, 3
• Persistent altered mental status or encephalopathy - When patients have not returned to baseline, CSF analysis helps differentiate seizure etiology 1
• Signs of meningeal irritation - Any clinical suspicion of CNS infection warrants CSF evaluation 3

Essential CSF Studies to Order

Core CSF Parameters

• Cell count with differential - Pleocytosis (>4 cells/µL) is uncommon after seizures alone (only 3-6% of cases) and should prompt investigation for intrathecal infection or autoimmune CNS disease 4, 5
• Glucose and protein - Elevated CSF protein occurs in 34% of seizure patients but is nonspecific; glucose helps identify infectious causes 5
• Gram stain and bacterial culture - Essential for ruling out bacterial meningitis 1
• Lactate - Elevated in 14-28% after seizures, but levels should normalize within 6 hours; persistent elevation beyond 6 hours may indicate ongoing epileptic activity or alternative pathology 4, 5

Autoimmune Encephalitis Workup

When autoimmune encephalitis is suspected (which commonly presents with new-onset seizures and encephalopathy), additional CSF studies are critical 1:

• CSF oligoclonal bands - Rare after seizures alone; presence suggests immune-mediated disease 6
• Neural antibody panel in CSF - Should be sent alongside serum antibodies 1
• CSF neopterin and quinolinic acid - These neuroinflammatory markers can discriminate infection-triggered encephalopathy syndromes (ITES) from other causes of seizures with 99.3% sensitivity, significantly better than pleocytosis alone (87.3%) 7

Additional Studies Based on Clinical Context

• Viral PCR panel (HSV, VZV, enterovirus) - When viral encephalitis is suspected 1
• Albumin quotient (QAlb = CSF albumin/serum albumin) - Detects blood-CSF barrier dysfunction, present in 34-47% after seizures but does not correlate with time from seizure onset 4, 5

Critical Interpretation Pitfalls

CSF pleocytosis should NOT be attributed to the seizure itself - Only 3-6% of patients have elevated cell counts after seizures, so pleocytosis demands thorough investigation for infection or autoimmune disease 4, 5. This is the most important clinical pearl.

Timing matters for lactate interpretation - CSF lactate is most frequently elevated within the first 6 hours after a single seizure and should normalize thereafter; persistent elevation suggests ongoing seizure activity or alternative diagnosis 4

Blood-CSF barrier dysfunction is common but nonspecific - Present in 34-47% of seizure patients regardless of timing, so this finding alone does not distinguish seizure-related changes from pathology 4, 5

Algorithm for CSF Analysis Decision

1. Perform head CT first - Always obtain neuroimaging before lumbar puncture to rule out mass effect 1

2. Proceed with LP if any of the following:

   • Fever or meningeal signs 1
   • Immunocompromised status 2, 1
   • Persistent encephalopathy/altered mental status 1
   • Clinical suspicion for autoimmune encephalitis 1

3. Order comprehensive CSF panel including:

   • Cell count, glucose, protein, Gram stain, culture 1
   • Lactate 4
   • Oligoclonal bands if autoimmune disease suspected 6
   • Neural antibody panel (CSF and serum) for autoimmune encephalitis 1
   • Consider neopterin/quinolinic acid if available for ITES evaluation 7

Do not perform routine lumbar puncture in patients with uncomplicated first-time seizures who have returned to baseline with normal neurologic examination 1.