What are the traumatic and non-traumatic causes of non-reactive pupils?

Causes of Non-Reactive Pupils

Non-reactive pupils result from either traumatic brain injury with elevated intracranial pressure causing brainstem ischemia, or non-traumatic causes including cranial nerve III compression from aneurysm, botulism, pharmacologic agents, and structural brainstem lesions.

Traumatic Causes

Primary Mechanism: Brainstem Ischemia

• Decreased brainstem blood flow (BBF) below 40 ml/100 g/min is the primary mechanism causing pupillary non-reactivity in severe head injury, rather than direct mechanical compression of the third cranial nerve 1
• Patients with bilaterally non-reactive pupils demonstrate significantly lower BBF (30.5 ± 16.8 ml/100 g/min) compared to those with reactive pupils (43.8 ± 18.7 ml/100 g/min) 1
• Pupillary dilation serves as an early indicator of brainstem ischemia and may precede peak intracranial pressure elevation by an average of 15.9 hours 2

Specific Traumatic Scenarios

• Bifrontal contusions with progressive edema can cause fixed, dilated pupils even while consciousness is preserved, representing acutely rising ICP 3
• Traumatic subdural and epidural hematomas may produce pupillary changes before deterioration of consciousness 3
• Orbital trauma with direct globe injury, optic nerve damage, or intraorbital foreign bodies can affect pupillary responses 4

Critical Pitfall: False Localization

• Unilateral fixed dilated pupils may be contralateral to the hemispheric mass lesion in up to 25% of cases with intracranial hemorrhage, representing a false-localizing sign 5
• The pupil ipsilateral to the lesion may initially remain reactive while the contralateral pupil becomes fixed and dilated 5

Prognostic Implications

• Bilateral fixed dilated pupils in severe head injury (GCS ≤8) carry a 74.69% poor outcome rate, though 25.30% achieve functional recovery with aggressive management 6
• Factors worsening prognosis include: age, polytrauma with shock, initial GCS of 3-4, and basal cistern compression on CT 6

Non-Traumatic Causes

Cranial Nerve III Pathology

• Pupil-involving third nerve palsies suggest vascular compression from adjacent aneurysm, requiring urgent CTA or MRA evaluation 4
• Pupil-sparing third nerve palsies indicate vasculopathic etiologies (typically microvascular ischemia) 4
• Lesions at the cavernous sinus or orbital apex affecting cranial nerves III, IV, and VI together produce multiple ipsilateral cranial nerve palsies 4

Botulism

• Abnormally reactive pupils (including sluggish, poorly reactive, and non-reactive or fixed pupils) occur in 24% of confirmed botulism cases 4
• Dilated pupils specifically occur in 37% of botulism patients 4
• Fixed pupils are a recognized clinical criterion for triggering suspicion of botulism 4
• Descending paralysis (93% of cases) and multiple cranial nerve findings accompany pupillary abnormalities 4

Structural Brainstem Lesions

• Demyelinating plaques (multiple sclerosis in younger patients, stroke in older patients) affecting the brainstem can produce pupillary abnormalities 4
• Tumors, hemorrhage, and infections involving the brainstem may cause non-reactive pupils 4
• Posterior circulation stroke presenting with acute diplopia may involve pupillary changes 4, 7

Infectious and Inflammatory Causes

• Infectious meningitis (tuberculosis, fungal, Lyme disease) affecting the basilar subarachnoid space can involve cranial nerves and produce pupillary abnormalities 4
• Non-infectious causes including sarcoidosis, neoplasm, or leptomeningeal tumor spread may affect pupillary function 4

Pharmacologic and Metabolic

• While not explicitly detailed in the provided guidelines, pharmacologic mydriasis from anticholinergic agents, sympathomimetics, or topical medications must be considered in the differential diagnosis

Diagnostic Approach

Imaging Strategy

• CT head without contrast is the initial study for acute traumatic presentations to assess for hemorrhage, mass effect, and basal cistern compression 4
• MRI brain with and without contrast is preferred for non-traumatic, subacute presentations to evaluate structural lesions, demyelination, or neoplasm 4, 7, 8
• CTA or MRA should be obtained when pupil-involving third nerve palsy suggests aneurysmal compression 4

Clinical Examination Priorities

• Document pupil size, reactivity, and symmetry using quantitative measurement (Neurological Pupil index) when available 2
• Assess for associated findings: level of consciousness, motor deficits, other cranial nerve palsies, and signs of increased ICP 1, 3
• Evaluate for descending paralysis, dysphagia, diplopia, and facial weakness when botulism is considered 4

Temporal Considerations

• Pupillary abnormalities precede peak ICP elevation, making serial examinations critical for early intervention 2
• Rapid restoration of cerebral perfusion pressure in traumatic cases with dilated pupils may improve prognosis despite initially grave presentation 1