Intracranial complications of sinus and orbital infection are uncommon but can lead to significant morbidity and mortality. They include cavernous sinus thrombosis, epidural abscess, subdural empyema, cerebritis and brain abscess, and meningitis. These processes can occur in combination, at any stage of orbital cellulitis, and with rapid progression, so a high index of suspicion must be maintained when managing patients with orbital cellulitis.

The intimate association of the orbit with the anterior skull base allows intraorbital infectious processes to extend into the intracranial compartment. The roof of the orbit is formed by the orbital plate of the frontal bone, with variable interposition of the frontal sinus depending on its extent of pneumatization. Diploic channels and occasional areas of dehiscence form direct communications from the extracranial space to the dura. The cells of the ethmoid sinus, separated from the medial orbit only by the thin lamina papyracea, lead posteriorly to the sphenoid sinus, which abuts the sella turcica, optic canal, and cavernous sinus.

At the orbital apex, multiple neural and vascular structures enter and exit the orbit: the optic nerve and ophthalmic artery via the optic canal, and divisions of the oculomotor (CN III), trochlear (CN IV), ophthalmic (CN V1), and abducens (CN VI) nerves, the recurrent meningeal branch of the ophthalmic artery, and the superior ophthalmic vein via the superior orbital fissure (SOF). The optic nerve sheath is continuous with the intracranial dura and remains applied to the bone, so that the optic nerve freely traverses the subarachnoid space toward the optic chiasm. Posteriorly, the periorbita of the SOF is continuous with the connective tissue layer arising from the epineurium of the cranial nerves that forms the lateral wall of the cavernous sinus.

The paired cavernous sinuses are venous channels situated on either side of the sella, formed between the periosteal and meningeal layers of dura. They are connected by the anterior and posterior intercavernous sinuses and have venous communications with the cerebrum, cerebellum, face, orbit, nasopharynx, mastoid, and middle ear [1]. Anteriorly, the cavernous sinus is bounded by the medial end of the SOF and posteriorly by dura at the petrous apex and dorsum sellae. The roof is formed by a fold of dura attached to the anterior and posterior clinoid processes and petrous apex and the floor by the endosteum of the greater sphenoid wing. The oculomotor, trochlear, ophthalmic, and maxillary nerves run in the lateral wall and the cavernous segment of the internal carotid artery and abducens nerve within the sinus.

Tributaries of the anterior facial vein communicate with the superior ophthalmic vein, which drains to the cavernous sinus. In addition, the cavernous sinus receives blood from the inferior ophthalmic vein, the sphenoparietal sinus, the superficial middle cerebral vein, and variably the central retinal vein and middle meningeal vein tributaries. Emissary veins traverse the sphenoid emissary foramen, foramen ovale and foramen lacerum. The superior and inferior petrosal sinuses form a confluence with the basilar venous plexus and, respectively, drain the cavernous sinus to the transverse sinus and jugular bulb. These venous channels do not contain valves, so the direction of flow within the system is determined by relative pressure and can be altered by the presence of pathology.

Intracranial complications of sinusitis and orbital cellulitis arise through two major mechanisms: retrograde thrombophlebitis and direct extension [2]. The shared venous drainage of the face and paranasal sinuses and the intracranial structures facilitates the spread of infectious thrombophlebitis. As these veins are valveless, thrombophlebitis or septic emboli can progress in retrograde fashion into the cavernous sinus. Less commonly, direct extension of osteomyelitis of the sinus or orbital walls or suppurative penetration through natural or traumatic bony defects can admit infection to the epidural space. Purulence can then further penetrate through the dura to the subdural space, subarachnoid space, and brain parenchyma. The frontal bone is particularly vulnerable to infectious spread, likely due to its extensive network of diploic veins, and in adolescents, rapid growth of the frontal sinuses.

In the modern era, intracranial complications are seen in 1–2% of cases of orbital cellulitis [3]. Demographics parallel the incidence of orbital cellulitis, more commonly affecting older children and males. In the same way that orbital infection most commonly results from sinusitis, so does intracranial suppuration, although symptoms of sinusitis may be variable or absent. Clinical findings depend on the site or sites of involvement, although most patients have fever and headache. Altered mental status, focal neurological deficit, seizure, meningismus, and signs of increased intracranial pressure (ICP) may be present in intracranial infection, while proptosis, periorbital edema, and chemosis may reflect cavernous sinus pathology. The presentation of meningitis, subdural empyema, and cavernous sinus thrombosis may be acute and progress rapidly, while development of epidural abscess and focal encephalitis may be more insidious. It is important to note that patients may not have focal neurologic findings, and radiographic studies should be considered to identify intracranial complications prior to development of irreversible sequelae.

The initial medical management of orbital cellulitis includes broad-spectrum intravenous antibiotic coverage using agents with adequate central nervous system penetration, with consideration for local resistance patterns. In keeping with typical pathogens causing acute sinusitis in children, the most common agents include Streptococcus spp. and Staphylococcus spp., while introduction of the Haemophilus influenzae type B (HiB) vaccine has reduced the incidence of HiB-associated infection and complications. Polymicrobial infection, often on a background of chronic sinusitis, is more common in adults, and initial antibiotic selection should include coverage of anaerobic bacteria. Upon identification of the causative organisms and their sensitivity profile, a tailored choice of antibiotic should be made.

Contrast-enhanced CT scan provides distinct bony resolution and is readily available on an emergent basis, and has long been the imaging study of choice to evaluate patients with suspected orbital infection. However, MRI should be obtained when an intracranial abnormality is suggested on CT or when contrast-enhanced CT fails to provide adequate explanation for a patient’s clinical presentation. Contrast-enhanced MRI is highly sensitive for detection of inflammation and focal fluid collections, and diffusion-weighted imaging (DWI) can provide additional diagnostic certainty for identifying abscesses even without contrast administration. CT or MR venography can help define abnormalities of the dural sinuses and cortical veins. Findings of intracranial pathology necessitate close neurological monitoring and urgent consultation with neurological surgery. The presence of intracranial complications is generally an indication for functional sinus surgery to treat an underlying sinusitis, which can be performed at the same sitting as surgical management of intracranial and orbital infection.

The inclusion of cavernous sinus thrombosis (CST ) as group 5 in Chandler’s classification of orbital complications of sinusitis reflects its involvement in both orbital and intracranial processes [4]. CST is an infectious thrombosis of the cavernous sinus, due to retrograde propagation of thrombophlebitis and/or septic embolism along the superior or inferior ophthalmic vein or direct spread of infection from the sphenoid sinus or orbit. Signs of sepsis, including spiking pyrexia, tachycardia, hypotension, and rigors, may be present. Periorbital edema, chemosis, and proptosis reflect venous hypertension of the orbit and are seen in over 90% of cases. Retinal edema and retinal vein engorgement with hemorrhages may be evident on fundoscopy. An afferent pupillary defect and decreased visual acuity may result from increased intraocular pressure. Cranial neuropathy can result in internal and external ophthalmoplegia, ptosis, mydriasis, abnormal periorbital sensation, and corneal anesthesia. Many of these findings are present in the setting of orbital cellulitis alone, but CST should be suspected if clinical signs worsen rapidly. The cardinal sign of cavernous sinus involvement is the development of bilateral orbital findings.

CST is most commonly demonstrated as cavernous sinus filling defect(s) and outward lateral wall bowing on contrast-enhanced CT and MRI. Narrowing of the cavernous and petrous segments of the internal carotid artery and arterial wall enhancement is frequently seen. Associated findings include dilatation or filling defect of the superior ophthalmic vein, thrombosis of cavernous sinus tributaries, and thrombus in the sigmoid sinus and internal jugular vein, as well as suppurative intracranial collections [5]. Susceptibility weighted MR imaging is highly sensitive to blood breakdown product and can demonstrate venous thrombi, and restricted diffusion in thrombosed venous structures can be seen. Areas of high DWI signal intensity within the bran parenchyma may reveal infarction due to emboli or hypoperfusion.