Intracranial aneurysms and dolichoectatic vessels

Intracranial aneurysms and dolichoectatic vessels account for up to 14% of CNIII palsies overall and a much higher proportion of isolated peripheral palsies. CNIV and CNVI are affected less frequently accounting for approximately 2% and 4% of cases, respectively. The vascular structures that potentially may give rise to ocular motor dysfunction are determined by the anatomic course of the cisternal segments of each nerve.

On route to the cavernous sinus, CNIII first passes between the PCA and SCA and then inferior to the PcomA. Although palsies related to aneurysms of the SCA are well recognized ( Fig. 2 ), aneurysms of the PcomA ( Fig. 3 ) are the most common culprit, with the incidence of a CNIII deficit at presentation ranging from 34% to 61%. In cases of ruptured aneurysm, neural injury occurs secondary to direct hemorrhagic dissection of the nerve or uncal herniation. In cases of unruptured aneuryms, localized extravasation leading to intraneural fibrosis or acute dilatation of the aneurysm sac leading to mechanical distortion and edema of the nerve are the proposed mechanisms.

SCA aneurysm. DSA of the left VA demonstrating an aneurysm of the right SCA ( black arrow ) in a patient presenting with a complete right CNIII palsy.

Posterior communicating artery aneurysms. Lateral projection DSA of the ICA of two separate patients ( A , B ) presenting with complete CNIII palsy. Aneurysms of the posterior communicating segment of the supraclinoid ICA are demonstrated pointing posteriorly and inferiorly ( black arrows ). ( Courtesy of Dr. F. Robertson, National Hospital for Neurology and Neurosurgery, London.)

Most series demonstrate that a high proportion of isolated CNIII palsies secondary to PcomA aneurysms are associated with disturbance of pupillomotor function. Anatomically, this is explained by the aneurysms tending to point posteriorly, inferiorly, and laterally, making the peripheral, dorsomedially sited parasympathetic pupillomotor fibers most vulnerable to impingement.

The discrimination between an acute onset of isolated CNIII palsy resulting from aneurysm and resulting from other causes, principally microvascular infarction, is critical. Microvascular infarction follows a benign self-limiting course with almost 100% recovery. In contrast, nerve dysfunction secondary to aneurysm may herald a more sinister outcome and it is shown that the rupture rate of aneurysms associated with CNIII palsy is 2.4 times that of aneurysms without. Most studies concur that the most important discriminatory feature clinically is the presence or absence of pupillary involvement. Between 68% and 80% of CNIII palsies resulting from microvascular infarction spare the pupil compared with 4% to 14% of those resulting from aneurysm. Another potentially useful discriminatory feature is the presence of aberrant CNIII innervation resulting from misdirected regrowth of fibers to an inappropriate target structure. This process takes at least 8 weeks and suggests a compressive lesion, such as an unruptured aneurysm or tumor, almost never occurring after microvascular infarction. Retro- or periorbital pain is associated with both causes and is not a useful discriminatory feature.

As CNIV passes anteriorly between the lateral midbrain and tentorial edge, it also passes between the PCA and SCA. In contrast to CNIII, CNIV nerve palsy secondary to aneurysms of these vessels is rare.

CNVI courses through the prepontine cistern in close proximity to the vertebral artery (VA) and BA. As a result, the most common vascular causes of cisternal segment dysfunction are dissecting aneurysms of the VAs or dolichoectatic vessels.

Although digital subtraction angiography (DSA) remains the gold standard investigation, CT angiography and magnetic resonance angiography (MRA) are demonstrated as having sensitivities approaching that of DSA for detecting aneurysms 5 mm or more in diameter. In the context of aneurysms presenting with CNIII palsy, it is estimated that MRA detects 98% of aneurysms and overlooks only 1.5% of those that subsequently rupture.

Neurovascular conflicts

Neurovascular conflicts are disorders believed to arise from vascular impingement and are characterized by hyperactive nerve dysfunction rather than nerve palsy. This group includes disorders, such as trigeminal neuralgia (CNV), hemifacial spasm (CNVII), and superior oblique myokymia (SOM) (CNIV). A proposed common mechanism for the neurovascular conflicts group is vascular compression at a specific portion of the cisternal segment of the nerve known as the root exit zone (RExZ). The cisternal portion of the ocular motor nerves can be divided into a central (glial) segment sheathed in myelin derived from oligodendrocytes and a peripheral segment sheathed in myelin derived from Schwann cells. The RExZ refers to this central portion and is less stable anatomically and electrophysiologically because it lacks perineurium and epineurium. It is proposed that the region of transition between oligodendrocyte and Schwann cell–derived myelin is particularly vulnerable to continued pulsatile pressure, which may result in focal demyelination and short-circuiting of impulses. The length of the RExZ differs for each nerve, measuring up to 4 mm for CNIII, 1 mm for CNIV, and 1 mm for the CNVI.

Neurovascular conflicts involving CNIII usually are the result of atherosclerotic, dolichoectatic, or abnormally positioned PCA or SCA. Neurovascular conflicts of CNIV occur because of the SCA or its branches lying in close contact with the nerve within the ambient cistern. Compression of the CNIV RExZ may lead to a rare recurring disorder of ocular motility, called SOM ( Fig. 4 ). SOM is characterized by unilateral paroxysmal oscillopsia and microtremor resulting from intermittent contractions of the superior oblique muscle.

A 54-year-old female patient who had right-sided SOM. High resolution 3-D–CISS MRI reveals a neurovascular contact between the RExZ of the right trochlear nerve ( arrowhead ) and a branch of the right SCA ( arrow ).

In microsurgical and radiologic studies the vessels that are identified as having a close relationship with CNVI are the AICA, posterior inferior cerebellar artery (PICA), BA, VA, SCA, and the petrosal vein. The VA, in particular, is reported as causing CNVI compression.

Neurovascular contacts within the central segment of the ocular motor nerves, however, commonly occur in asymptomatic individuals, and arteries may even penetrate the nerve without clinical consequences.

MRI is the most useful imaging tool for imaging neurovascular conflict syndromes. Although imaging of CNIII is relatively easy because of its larger diameter (2.5 to 3 mm), CNIV and CNVI are smaller (diameter 0.75 to 1 mm for CNIV and 0.43 to 1.85 for CNVI), and imaging the cisternal segments is more challenging. Furthermore, CNIV lies in close proximity to vessels of similar course and caliber in the ambient cistern, making depiction particularly difficult. The ocular motor nerves are identified best using high-resolution imaging techniques, such as the 3-D constructive interference in steady state (CISS) sequence, 3-D T2-weighted (T2-w) fast spin-echo, or 3-D fast imaging employing steady-state acquisition sequences. The 3-D datasets of these sequences allow reconstructions along each individual nerve course and very thin slices (down to 0.6 mm). The problem of misinterpretation of a vascular structure as a nerve can be overcome by adding a 3-D time-of-flight sequence, with and without administration of gadolinium-DTPA. Furthermore, this technique allows differentiation of arteries and veins.

Aneurysms

Aneurysms of the distal ICA may occur extradurally within the cavernous sinus ( Fig. 5 ). The most common symptom associated with such aneurysms is ocular motor dysfunction. Unlike intradural aneurysms, the nerve affected most commonly is CNVI, possibly related to its anatomic location within the central venous portion of the sinus tethered to the ICA. Frequently, there is evidence of a more extensive cavernous sinus syndrome with multiple ocular motor palsies, trigeminal pain, and Horner’s syndrome.

Cavernous ICA aneurysm. Axial T2-w images ( A ) and DSA ( B ) of the right ICA of a patient presenting with a right CNIII palsy demonstrating a large intracavernous aneurysm expanding the right cavernous sinus ( white and black arrows , respectively).

Carotid-cavernous fistulas

Carotid-cavernous fistulas represent abnormal shunting of arterial blood through the cavernous sinus and most commonly are secondary to rupture of extradural cavernous ICA aneurysms or trauma. They are categorized as direct or indirect depending on whether or not the arterial shunt is derived from the ICA itself or arteries supplying the dura of the cavernous sinus. Typically, patients who have the direct type present with chemosis, pulsatile exophthalmos, and ocular bruit, whereas those who have indirect type present with a more insidious onset of exophthalmos, glaucoma, and pain. Ophthalmoplegia is a common finding in both types and in one series examining indirect fistulae, isolated ocular motor dysfunction was found the presenting feature in one third of patients. Moreover, recovery rate of ocular motor function after treatment of the fistula was more than 50% at 1 year.

The sensitivity of CT in detecting carotid-cavernous fistulas is low, but dilatation of the cavernous sinus and superior ophthalmic vein, proptosis, and expansion of the extraocular muscles may be demonstrated. MRI is more sensitive and, in addition to the CT features, flow-related enhancement of the cavernous sinus with abnormal flow voids within the superior ophthalmic vein or petrosal veins may be visible. DSA is the most sensitive imaging modality and the diagnosis is made with visualization of arterial shunting to the cavernous sinus from the ICA or dural arteries ( Figs. 6 and 7 ).

Direct carotid cavernous fistula. A 30-year-old man presenting with proptosis, chemosis, and ophthalmoplegia after a head injury while snowboarding. Anteroposterior ( A ) and lateral ( B ) DSA projections of the right ICA demonstrate shunting of arterial contrast directly from the intracavernous ICA into the cavernous sinus ( white arrow , intracavernous ICA; black arrows , contrast within the cavernous sinus bilaterally; and white arrowhead , contrast within dilated superior ophthalmic vein). ( Courtesy of Dr. S. Brew, National Hospital for Neurology and Neurosurgery, London.)

Indirect carotid cavernous fistula. ( A ) Axial T2-w image showing expansion of the left cavernous sinus with multiple abnormal flow voids ( white arrowheads ) adjacent to the intracavernous ICA ( white arrow ). ( B ) Axial time-of-flight MRA image demonstrating increased signal within the cavernous sinus reflecting abnormally high flow ( open white arrow ). Lateral ( C ) and anteroposterior ( D ) projection DSA of a second patient who had an indirect fistula. ( C ) Demonstrates shunting of contrast into the cavernous sinus ( white arrow ) from dural branches of the ICA with drainage into the superior ophthalmic vein ( black arrow ). ( D ) Demonstrates shunting of contrast into the cavernous sinuses ( white arrows ) from dural branches of the external carotid artery ( arrowheads ). ( Courtesy of Dr. F. Robertson, National Hospital for Neurology and Neurosurgery, London.)

Primary injuries

The cisternal portions of the ocular motor nerves are particularly vulnerable at points of relative fixation.

CNIII has the shortest cisternal course of the ocular motor nerves. Traumatic injury to this segment occurs as a result of differential movement between the brainstem and supratentorial structures or skull base leading to rootlet avulsion or stretching over the tough posterior petroclinoid ligament.

CNIV has the longest cisternal course. In addition to avulsion injuries at the point of emergence from the dorsolateral midbrain, damage may be caused by compression of the nerve against the rigid tentorial edge as it passes anteriorly through the ambient cistern.

CNVI is tethered rostrally by Dorello’s canal, where most traumatic injuries occur.

The usefulness of CT and MRI is demonstrated in identifying blood within the ambient cistern in relation to avulsion injuries of CNIV. MRI also demonstrates hemorrhage at the point of emergence of CNIII in similar injuries. Fluid-attenuated inversion recovery (FLAIR) and gradient-echo sequences may be particularly sensitive in these scenarios.

Secondary injuries

In addition to primary injuries, the ocular motor nerves are susceptible to secondary injury as a result of raised intracranial pressure (ICP) leading to transcompartmental herniation. This is true of any etiology of raised ICP, including supra- and infratentorial space-occupying lesions, idiopathic intracranial hypertension, and venosinus thrombosis. CNVI reportedly is the nerve affected most commonly. In inferior transtentorial herniation, the proposed pathophysiology is descent of the brainstem resulting in necrosis of the nerve at Dorello’s canal or compression of the nerve against the clivus or BA. CNVI also is vulnerable to shifts in intracranial contents resulting from low ICP for similar reasons. In CNIII palsy, the mechanism is believed the result of impingement on the free edge of the tentorium or kinking over the clivus. The peripherally distributed parasympathetic pupilloconstrictor fibers are most vulnerable and mydriasis may be the earliest manifestation.