Pathophysiology & Diagnostics

Pathophysiology

Status epilepticus occurs when mechanisms that normally terminate seizure activity fail, leading to abnormally prolonged neuronal excitation. The exact pathophysiology is not fully elucidated but is thought to involve:

• Imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission
• Changes in synaptic receptor trafficking – internalization of GABAA receptors, increased NMDA receptors
• Sustained depolarization from glutamate acting on NMDA and AMPA receptors
• Systemic effects from prolonged ictal activity like metabolic acidosis, rhabdomyolysis, hyperthermia

With increasing duration of seizures, pharmacoresistance develops due to changes in receptor dynamics. Prolonged status epilepticus also leads to neuronal injury, likely through excitotoxicity, oxidative stress, and inflammation.

Diagnostic Approach

Status epilepticus represents a clinical diagnosis based on observation of prolonged seizure activity, with neurodiagnostic and laboratory testing aimed at identifying etiology, complications, and prognosis.

• Detailed history and physical examination focusing on:
  • Seizure duration, type, and timing
  • Presence of aura or triggers
  • Mental status before, during, and after seizures
  • Medication history, drug/alcohol use
  • Evidence of trauma, infections
• Diagnostic criteria:
  • Clinical diagnosis – seizure lasting >5 minutes or recurrent seizures without full recovery between events
  • EEG – epileptiform discharges persisting for >30 minutes
• Laboratory tests:
  • Complete blood count, electrolytes, renal function tests, liver function tests, calcium, magnesium
  • Toxicology screen, antiseizure drug levels
  • Blood cultures, plasma lactate
  • Urinalysis for myoglobin, infectious studies as needed
• Neuroimaging:
  • Non-contrast CT to assess for acute brain injury
  • MRI brain with contrast to evaluate for underlying structural lesions
  • CT or MR angiography if vascular cause suspected
• EEG:
  • Mandatory to confirm seizures and monitor treatment response
  • Helps distinguish clinical versus electrographic seizures
  • Identifies seizure focus and classifies subtype of status epilepticus
• Lumbar puncture if CNS infection suspected
• Additional testing guided by suspected etiology: autoimmune panels, metabolic studies, genetic testing

The combination of clinical evaluation, EEG, neuroimaging, and laboratory assessment facilitate rapid diagnosis of status epilepticus, allowing initiation of targeted treatment to improve outcomes.