What pupil changes occur during generalized versus focal seizures and how should abnormal unilateral or bilateral pupil findings be managed?

Pupil Reactions During Seizures

Unilateral pupillary dilatation during focal seizures represents a contralateral frontal epileptic focus and should be recognized as a focal seizure feature requiring urgent neuroimaging, while bilateral pupillary abnormalities in the setting of declining consciousness suggest raised intracranial pressure and constitute a medical emergency. 1, 2

Pupillary Changes in Focal Versus Generalized Seizures

Focal Seizures

• Unilateral mydriasis (pupillary dilatation) occurs with contralateral frontal epileptic foci, likely through inhibition of homolateral pupil dilatation, permitting only contralateral pupil dilatation 2
• This unilateral pupillary abnormality may represent a pupillary "Todd's paralysis" caused by the contralateral frontal focus 2
• Unilateral sluggish or absent pupillary responses are reliable signs of focal pathology and should prompt immediate investigation 1
• The presence of any focal feature including asymmetric pupillary findings is independently associated with clinically relevant abnormalities on neuroimaging, with detection rates of 50% on CT when neurologic findings are focal 3

Generalized Seizures

• Generalized seizures typically do not produce isolated unilateral pupillary changes, as they involve both cerebral hemispheres from onset 3, 4
• Bilateral pupillary abnormalities (dilated, poorly responsive, or unequal pupils) in the context of declining consciousness suggest raised intracranial pressure rather than simple seizure activity 1
• Pupillary signs during the peri-ictal state (immediately surrounding the seizure) may be misleading and should be interpreted with caution, as they do not reliably indicate raised intracranial pressure in this specific timeframe 1

Critical Diagnostic Pitfalls

Distinguishing Seizure-Related from Structural Causes

• Unequal, dilated, or poorly responsive pupils combined with declining conscious level, focal neurology, or abnormal posturing indicate raised intracranial pressure—a medical emergency 1
• Papilloedema and the combination of hypertension with relative bradycardia are late findings in acute raised intracranial pressure and should not be awaited before intervention 1
• Pupillary abnormalities in the immediate peri-ictal period may reflect transient seizure effects rather than structural pathology, requiring careful temporal correlation with seizure timing 1

Misdiagnosis Risks

• Generalized-onset seizures can acquire focal features during evolution, including focal ictal rhythm, which may be misinterpreted as complex partial seizures 5
• Idiopathic generalized epilepsies may present with focal features that suggest focal epilepsy to the unwary clinician, including versive seizures accompanied by generalized EEG discharges 6
• Focal seizures with impaired awareness have a 94% recurrence rate compared to 72% for generalized seizures, making accurate classification critical for management 3, 7

Management Algorithm for Abnormal Pupillary Findings

Unilateral Pupillary Abnormality

• Immediately obtain urgent neuroimaging with MRI brain using dedicated epilepsy protocol as the primary modality, which detects 55% of abnormalities in focal seizures compared to only 18% with CT 7
• If MRI is unavailable or the patient is unstable, perform non-contrast CT head first to rapidly identify acute hemorrhage, mass effect, or surgically treatable lesions 7
• Even if CT is negative, proceed with MRI, as 29% of abnormal intracranial findings in focal seizures are not seen on initial CT 7
• Check glucose immediately, as hypoglycemia can present with focal neurologic deficits including pupillary abnormalities 3
• Initiate antiseizure medication with levetiracetam as first-line therapy given the high recurrence rate of focal seizures 7

Bilateral Pupillary Abnormalities with Declining Consciousness

• Treat as raised intracranial pressure emergency with rapid induction of anesthesia, tracheal intubation, mechanical ventilation, and close monitoring of blood gases 1
• Maintain PCO2 within normal range to stabilize cerebral blood flow; if initial PCO2 is low from hyperventilation, allow gradual rise to normal range 1
• Administer mannitol 0.5 mg/kg infused rapidly over 5-10 minutes to lower intracranial pressure, with repeated doses often necessary due to short-term effect 1
• Do not use steroids, as their effect on raised intracranial pressure remains unclear and may adversely affect outcome 1

Peri-Ictal Pupillary Changes

• Document timing relative to seizure onset and offset, as pupillary signs immediately surrounding seizures may not reliably indicate structural pathology 1
• Ensure high-flow oxygen and appropriate airway management, as these are as important as anticonvulsant administration 1
• Reassess pupillary responses after the peri-ictal period (at least 24 hours after focal aware seizures, 48 hours after focal impaired awareness or focal-to-bilateral tonic-clonic seizures) to determine if abnormalities persist 1

Key Clinical Pearls

• Unilateral sluggish or absent pupillary responses are the only reliable focal signs in the acute setting and should never be dismissed 1
• Approximately 4% of children with first-time afebrile focal seizures have urgent intracranial pathology, most commonly infarction, hemorrhage, and thrombosis 3, 7
• MRI detected abnormalities not identified by CT in 47% of children with focal seizures, making MRI essential even after negative CT 3
• Seizure prophylaxis is not recommended, as prophylactic phenobarbital increased mortality in children with cerebral malaria, particularly when combined with diazepam 1