Pathophysiology of Cavernous Sinus Thrombosis with Streptococcus pneumoniae Meningitis
Cavernous sinus thrombosis (CST) with S. pneumoniae meningitis develops through direct extension of infection from adjacent paranasal sinuses (primarily sphenoid and ethmoid) or via hematogenous spread during bacteremic meningitis, resulting in septic thrombophlebitis of the cavernous sinus with subsequent venous obstruction and cranial nerve compression.
Primary Infection Source and Spread Mechanisms
The pathophysiologic cascade begins with S. pneumoniae infection establishing itself in the paranasal sinuses or meninges, with two distinct mechanisms of cavernous sinus involvement 1, 2:
- Direct anatomic extension: Sphenoid sinusitis spreads directly to the adjacent cavernous sinus through the thin bony walls separating these structures 2
- Hematogenous seeding: During pneumococcal bacteremia and meningitis, bacteria seed the cavernous sinus via bloodstream dissemination 3
- Retrograde venous spread: Infection propagates through valveless facial venous plexus connecting facial structures to the cavernous sinus 2
Thrombosis Formation
The septic process triggers endothelial damage and activation of the coagulation cascade within the cavernous sinus 1, 4:
- Bacterial invasion causes direct endothelial injury and inflammatory cytokine release
- Inflammatory mediators activate tissue factor and platelet aggregation
- Progressive thrombosis obstructs venous drainage from orbital structures 4
- Thrombus propagation can extend to contralateral cavernous sinus through intercavernous connections 2
Cranial Nerve Involvement
Cranial nerves III, IV, V (ophthalmic and maxillary divisions), and VI traverse the cavernous sinus and become compressed or directly infected 4:
- CN VI is most vulnerable due to its location freely within the sinus (not protected by dural sheath), causing lateral rectus palsy as the earliest sign 4
- CNs III and IV run in the lateral wall and are affected as thrombosis progresses 4
- CN V involvement produces facial pain and sensory deficits 4
Venous Obstruction Consequences
Impaired venous drainage produces characteristic orbital manifestations 1, 4:
- Chemosis and periorbital edema from venous congestion
- Proptosis from increased orbital venous pressure
- Retinal venous engorgement and potential vision loss
- Elevated intraocular pressure
Meningeal Extension
In cases with concurrent S. pneumoniae meningitis, the pathophysiology involves 5, 6:
- Direct spread through dural venous sinuses to subarachnoid space
- Hematogenous seeding during bacteremia
- Inflammatory CSF findings with elevated protein, decreased glucose, and pleocytosis 6
- Potential for increased intracranial pressure from combined venous obstruction and meningeal inflammation 5
Systemic Complications
The septic thrombophlebitic process can extend beyond the cavernous sinus 4:
- Septic emboli to pulmonary circulation
- Extension to other dural venous sinuses (superior sagittal, transverse)
- Cerebral venous infarction from progressive thrombosis 5
- Subdural empyema or brain abscess formation 5
Critical Pathophysiologic Distinction
A crucial caveat: While S. aureus is the most common pathogen in CST overall 1, 4, 3, S. pneumoniae CST typically occurs in the context of pneumococcal meningitis or severe sinusitis 5, 6. The viridans streptococci group (including S. constellatus) has been documented in CST from sinus sources 6, but S. pneumoniae specifically represents hematogenous spread during invasive pneumococcal disease rather than primary sinus infection 5.