Imaging of cranial nerves: a pictorial overview

The olfactory nerve is a sensitive nerve that conveys olfactory stimuli from the nasal cavity to the brain [7]. It consists of white matter tracts not surrounded by Schwann cells. Olfactory receptors are located in the mucosa of nasal cavity and olfactory filiae represent their axons. They enter the anterior cranial fossa through the cribriform plate and terminate in the olfactory bulb [6]. Successively, the nerve courses between the gyrus rectus and the medial orbital gyrus. The secondary axons terminate in the inferomedial temporal lobe, uncus, and entorhinal cortex [3] (Fig. 4).

Optic nerve represents an extension of central nervous system and is myelinated by oligodendrocytes [8]. Optic nerve emerges from the posterior pole of the ocular globe. It is approximately 50 mm in length, divided in four segments: intraocular (1 mm), intraorbital (25 mm), intracanalicular (9 mm), and prechiasmatic (16 mm) [8]. The nerve joins the contralateral to form the optic chiasma, where the nasal fibers from each nerve decussate, while the temporal fibers not. From the optic chiasm, optic tract courses posteriorly along the cerebral peduncles and synapses at the lateral geniculate nuclei. From the lateral geniculate body, optic radiation reaches the primary visual cortex in the occipital lobe (Brodmann area 17) [6] (Fig. 5).

The oculomotor nerve has a somatic motor function of most ocular estrinsic muscles (inferior, superior, middle rectus, inferior oblique, and levator palpebrae superior muscles) and a parasympathetic function (ciliaris and sphincter pupillae muscles) [6]. Somatic motor fibers of oculomotor originate from the nuclear complex located in the midbrain at the level of the superior colliculi, ventral to the cerebral aqueduct and the periaqueductal gray matter. The parasympathetic fibers arise in the Edinger-Westphal nucleus, situated dorsally to the oculomotor nuclear complex. The nerve emerges from the interpeduncular cistern running through the perimesencephalic cistern, superiorly to the posterior cerebral artery (PCA) and inferiorly to the superior cerebellar artery (SCA) [6]. Successively, the nerve enters in the cavernous sinus where is the most superior nerve, to reach the orbit through the superior orbital fissure [3] (Fig. 5).

The trochlear nerve innervates only the superior oblique muscle. It is the unique nerve with a root zone arising from the posterior brainstem where its nucleus lies [3]. After exiting the pons, the nerve curves over the superior cerebellar peduncle and then runs between the SCA and the PCA. Successively, it runs along the free margin of the tentorium and then enters the cavernous sinus, inferior to the III nerve and superior to the ophthalmic division of the V nerve [6]. Passing the cavernous sinus, the trochlear nerve enters the orbit through the superior orbital fissure [3] (Fig. 5).

The trigeminal nerve is the largest cranial nerve, composed of sensory and motor roots [3]. Four trigeminal nuclei (spinal nucleus of V, principal sensory nucleus of V, motor nucleus of V, and mesencephalic nucleus) extend from the midbrain down to the upper cervical medulla [6]. The nerve emerges straight forward from the lateral pons and pass in the Meckel’s cave, where is located the trigeminal ganglion (Gasserian ganglion), from which the nerve splits into three subdivisions. The ophthalmic (V1) and the maxillary (V2) divisions pass in the lateral wall of cavernous sinus, inferior to the VI cranial nerve. The ophthalmic division exits the skull via the superior orbital fissure (with the III, IV, VI cranial nerves and the superior ophthalmic vein). The maxillary division exits the skull through the foramen rotundum and crosses the pterygopalatine fossa. Successively, it enters the orbits via the inferior orbital fissure, passes within the infraorbital groove, and reaches the face through the infraorbital foramen. The mandibular division (V3) exits the skull via the foramen ovale and passes in the infratemporal fossa, where it divides into some branches (meningeal branch, medial and lateral pterygoid nerves, masseteric nerve, deep temporal nerve, buccal nerve, auriculotemporal nerve, lingual nerve, and inferior alveolar nerve) [3, 6] (Fig. 6).

The abducens nerve is a motor nerve that emerges from the abducens nucleus, located just beneath the floor of the IV ventricle in the dorsal pons [3]. The nerve courses anteriorly to exit the brainstem at the pontomedullary junction and crosses prepontine cistern in a dorsal-to-ventral direction. Successively, it descends near to the posterior aspect of the clivus, passing through the Dorello’s canal, and enters in the cavernous sinus [9]. It is the unique cranial nerve that courses through the central venous portion of the sinus. Finally, it enters the orbit via the superior orbital fissure to innervate the lateral rectus muscle [3, 6] (Fig. 5).

The facial nerve is a mixed nerve and consists of two portions: the proper VII nerve (whit motor function) and the intermediate nerve (with sensory and parasympathetic motor fibers) [6]. The motor nucleus is located in the lower portion of the pons and motor fibers exit from the lateral portion of the pontomedullary sulcus. Successively, the nerve traverses the cerebellopontine cistern and enters the temporal bone through the internal acoustic meatus. In the petrous bone, it passes through the facial canal, giving three segments (labyrinthine, tympanic, and mastoid). The nerve exits the skull base at the stylomastoid foramen and reaches the parotid gland [6]. From the mastoid portion, the nerve of the stapedius muscle and corda tympani emerge [6]. The afferent sensory fibers that originate from receptors of the first two-thirds of the tongue arrive at the geniculate ganglion, via the chorda tympani. They run with the intermediate nerve in the internal acoustic meatus and the cerebellopontine cistern to terminate in the nucleus of tractus solitarius. The parasympathetic fibers of the intermediate nerve arise from the superior salivatory nucleus. At the geniculate ganglion, the great petrosal nerve provides parasympathetic fibers for the lacrimal gland and the mucosa of mouth, nose, and pharynx [6] (Fig. 7).

The vestibulocochlear nerve is formed by two nerves: the cochlear nerve that transmits sound and originates in the cochlear membrane, and the vestibular nerve (divided in superior and inferior) that controls balance and originates from the ciliary sensory cells in the membranous labyrinth [10]. Both nerves traverse the internal acoustic meatus, together with the facial nerve, and pass in the cerebellopontine cistern. In the internal acoustic meatus, the nerve is so placed: the facial nerve is anterosuperior, the vestibular superior nerve is posterosuperior, the cochlear nerve is anteroinferior, and the inferior vestibular nerve is posteroinferior (for this, remember the acronym “Seven Up Coke Down”). Successively, vestibulocochlear nerve enters the brainstem and reaches the dorsal and ventral cochlear nucleus and the four vestibular nuclei that are located in the dorsolateral pons [6] (Fig. 8).

The glossopharyngeal nerve is a mixed sensory, motor, and secretory nerve. It emerges from the lateral medulla into the lateral cerebellomedullary cistern, where it is closely associated with the flocculus of cerebellum [3]. Successively, the nerve exits the skull through the jugular foramen (pars nervosa), and it enters in the carotid space; successively, it turns lateral to the carotid artery and the stylopharyngeal muscle and continues lateral to the palatine tonsil area. Its lingual branch ends in the posterior sublingual space, to innervate the posterior third of the tongue (taste and sensory). Other nervous branches of the extracranial segment of IX nerve are pharyngeal (sensation from posterior oropharynx and soft palate), sinus nerve (parasympathetic supply to carotid body and sinus), stylopharyngeus (motor innervation to the stylopharyngeus muscle), and tympanic branch or Jacobson nerve (sensory information from the middle ear) [6] (Fig. 9).

The vagus nerve emerges from the lateral medulla, from the base of the nucleus ambiguus and the dorsal nucleus of the vagus [6]. The nerve enters the lateral cerebellomedullary cistern and exits the skull through the jugular foramen (pars vascularis) between the glossopharyngeal nerve and the accessory nerve. Into and below the jugular foramen, the nerve forms the superior ganglion, and just below the jugular foramen, the nerve forms the inferior vagal ganglion. Successively, it descends vertically in the retrostyloid space together with the carotid artery, to join the upper mediastinum where it gives off the recurrent laryngeal nerve. Successively, the vagus nerve enters the abdominal cavity through the esophageal hiatus [6] (Fig. 9).

The accessory nerve has both cranial and spinal roots [3]. Cranial roots emerge into the lateral cerebellomedullary cistern, while spinal roots emerge from upper cervical segment of the spinal cord (from C0 to C5) and pass superiorly through the foramen magnum into the cisterna magna. Successively, conjoined cranial and spinal roots enter the jugular foramen, posterior to the glossopharyngeal and vagus nerve. Within the jugular foramen, cranial roots mix with vagus nerve at the level of the superior vagal ganglion, while spinal roots descend laterally to the internal carotid artery and internal jugular vein, and achieve the sternocleidomastoid and trapezius muscle [3, 6] (Fig. 10).

The hypoglossal nerve emerges from the medulla oblongata as a series of rootlets extending from the ventrolateral sulcus of the medulla into the lateral cerebellomedullary cistern, near to the vertebral artery and the posterior inferior cerebellar artery (PICA). The nerve exits the skull trough the hypoglossal canal and then runs medial to the glossopharyngeal, vagus, and accessory nerves, deeply to the digastric muscle, to innervate a large part of extrinsic and intrinsic tongue muscles [3] (Fig. 10).

Schwannoma is a benign nerve sheath tumor that originates from Schwann cells. Approximately 90% of intracranial schwannomas arise from the VIII cranial nerve with trigeminal involvement as the second most common (0.8–5%) [11, 12]. Intracranial schwannomas can be associated with neurofibromatosis 2 (NF2), a genetic condition characterized by the presence of multiple schwannomas, meningiomas, and ependymomas. Patient with NF2 may have bilateral vestibular schwannomas or non-vestibular schwannomas [13]. Imaging shows the slow growth of the tumor, with bone remodeling of neural foramen and deformation of the adjacent brain tissue. Features of end-organ compromise can be present. On CT, schwannomas have low-intermediate attenuation with variable enhancement. MR imaging findings include iso-hypointensity on T1-weighted sequences, high signal on T2-weighted sequences, and marked enhancement on post-contrast images, eventually with unenhanced cystic spaces [13] (Figs. 11, 12, 13, and 14).

Neurofibromas rarely involve cranial nerves, and are more commonly found extracranially. They are typically associated with neurofibromatosis 1 (NF1) and can show malignant transformation. NF1 is a genetic condition characterized by the presence of café au lait spots, neurofibromas, optic nerve glioma, osseous lesions, iris hamartomas, and axillary or inguinal freckling (Figs. 15 and 16).

Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant tumor of neural crest origin, arising from the olfactory epithelium of the nasal vault. It presents typically in the second and sixth decades of life, without gender predilection [14]. Clinical presentation may include, in a various combination, epistaxis, nasal obstruction, decreased olfactory function, diplopia, and proptosis. ENB may invade paranasal sinuses, orbits, and anterior cranial fossa, and, if metastatic, involve local lymph nodes, with distant metastasis to lungs, liver, and bone. At CT, ENB does not have specific features appearing as a homogeneous soft tissue mass in the nasal cavity. However, CT is useful to evaluate bone involvement. On MRI, ENB usually appears hypointense on T1-weighted sequences and intermediate to hyperintense on T2-weighted sequences. Contrast enhancement is avid and homogeneous, except for areas of necrosis or hemorrhage. MRI may be useful to detect dural involvement [14] (Fig. 17).

Optic nerve glioma is a relatively rare tumor that typically occurs in children. If associated with NF1, glioma can be multifocal and bilateral. In NF1 patient, optic nerve is the most common site of the tumor, whereas in non-NF1 patients, chiasma involvement is the most frequent. On MRI, the tumor typically appears isointense on T1-weighted images and iso-hyperintense on T2-weighted images, with variable contrast enhancement; in non-NF1 patients, cystic components may be detected (Fig. 18). If present, perineural arachnoidal gliomatosis shows hyperintense signal on T2-weighted sequences and may have contrast enhancement [8].

Two types of perineural growth of tumor are described: perineural invasion (PNI), a microscopical process that affect small nerves, and perineural spread of tumor (PNS) that extends along the sheaths covering larger central nerves [15]. The incidence of perineural spread is about 2.5–5% and may occur with any head and neck malignancy [16, 17]. It is typically associated with carcinoma arising from minor or major salivary glands (e.g., adenoid cystic carcinoma), mucosal or cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, lymphoma, and sarcoma. In most cases, the peripheral branches of second (V2) and third (V3) divisions of the trigeminal nerve, and the descending branch of the facial nerve serve as conduit for perineural spread. Also, the ophthalmic nerve and the hypoglossal nerve may be interested [17]. Clinical findings include neural dysfunction symptoms, as pain, dysesthesias, or muscle denervation atrophy [5]. For radiologist, the knowledge of the anatomy of cranial nerves is crucial to evaluate the perineural spread. On MRI, it can be visualized as segmental nerve thickening and enhancement on post-gadolinium sequences. Typically, imaging techniques with fat suppression are used to better increase the conspicuity of the enhancement [17]. Skull base invasion may result as replacement of normal fatty marrow signal [5] (Figs. 19, 20, and 21). Tumoral growth may cause enlargement of foramina or canals through which nerves exit the skull.

Primary (medulloblastoma, ependymoma, oligodendroglioma, and glioblastoma) and secondary (leukemia/lymphoma, breast cancer, lung cancer, and melanoma) tumors may spread through subarachnoid spaces with extension along the cranial nerves. VII and VIII cranial seem to be the most affected nerves [18]. Clinically, symptoms of irritation and neural compression are present with multiple cranial neuropathies and mental status changes, secondary to meningeal irritation and hydrocephalus. The nerve may enhance on post-gadolinium sequences and appear enlarged (Fig. 22). Neural enhancement can be very subtle and better demonstrated on post-Gadolinium fluid-attenuated inversion recovery (FLAIR) sequences [5, 19‐21].

Meningioma is the commonest extra-axial tumor of central nervous system and arises from the meningothelial cells of arachnoid layer. Typical locations include parasagittal and lateral aspect of the cerebral convexity, sphenoid wing, middle cranial fossa, and olfactory groove. The tumor may show transforaminal extension, for example into the orbit or following the trigeminal course. After the acoustic schwannoma, it represents the second most common mass in the cerebellopontine angle. On imaging, meningioma appears as a lobular, extra-axial mass with well-circumscribed margins and a broad-based dural attachment. On MRI, it is isointense/hypointense relative to gray matter on the T1-weighted sequences and isointense/hyperintense relative to gray matter on the T2-weighted sequences. A rim of high T2 signal that separates the mass from the adjacent brain is often visible (“cleft signs”). Post-contrast sequences show marked and homogeneous enhancement with rare central nonehancing areas, corresponding to necrosis or calcification phenomena. In up to 72% of cases, a “dural tail” is evident, as enhancement of the neighboring dura mater. Possibly associated bony changes can be osteolysis, hyperostosis, and enlargement of the adjacent foramina [21] (Fig. 23). Meningioma may also affect the optic nerve, appearing as homogeneous enhancing lesion around the optic nerve, with intermediate T1 and T2 signal [22].

The term optic neuritis (ON) usually refers to inflammatory process that involve optic nerve. Clinically, it presents with painful eye movements and visual loss. On MRI, the nerve appears swollen and hyperintense on T2-weighted sequences, with contrast enhancement best seen on fat-suppressed T1-weighted sequences [8] (Fig. 24). ON may be observed in autoimmune (for example multiple sclerosis and neuromyelitis optica spectrum disorders) and systemic diseases (sarcoidosis, lupus erythematosus, Wegener disease, Sicca syndrome,  Behcet disease) [23]. Particularly, in neuromyelitis optica spectrum disorder (NMOSD), nerve involvement may be bilateral and more severe than in multiple sclerosis (MS). NMOSD is also characterized by involvement of spinal cord, with brain MRI features not suggestive for MS [8].

Tolosa-Hunt is an uncommon disease related to a retro-orbital pseudotumor extending in the cavernous sinus [24, 25]. It is an idiopathic disorder that can manifest with a unilateral painful ophthalmoplegia, diplopia, and deficit of the V1 branch of trigeminal nerve. Bilateral pseudotumor is described in 5% of cases [24]. Tolosa-Hunt consists in a granulomatous inflammation of the lateral wall of the cavernous sinus or superior orbital fissure. Imaging techniques can show an infiltrative soft tissue mass within the cavernous sinus that appears enlarged. The tissue is hypo-isointense on T2-weighted sequences, with avid contrast enhancement on post-gadolinium images (Fig. 25). Differential diagnosis may include lymphoma, sarcoidosis, metastatic disease, meningioma, infection, granulomatous pachimeningitis, Meckel’s cave schwannoma, aneurysm, and pituitary macroadenoma [25]. Clinical findings may overestimate this condition and MRI is critical to exclude other similar conditions, allowing for precise management and therapeutic planning. After diagnosis, a good response to steroid therapy can be achieved.

Bell’s palsy (idiopathic facial palsy) is the most common cause of unilateral peripheral nerve neuropathy. Clinical presentation is variable, with dysgeusia, mastoid pain, impaired salivation, and lacrimation. A Herpes-Simplex-Virus reactivation seems to be the most probable etiology [5]. Prognosis is often good and the treatment is based on corticosteroid therapy, often with the addition of acyclovir. Typical Bell’s palsy does not require imaging studies. However, MRI may be useful to exclude other lesions responsible of atypical Bell’s palsy (gradual-onset palsy, failure to improve with time) or recurrent palsy [26]. On MRI, the facial nerve shows increased enhancement on post-contrast sequences that may involve one or more segments, without nodularity (Fig. 26). Enhancement of distal intrameatal and labyrinthine segments is typical [26]. On T2-weighted sequences, the nerve may be hyperintense. In case of irregular or nodular enhancement, other causes of pathology (such as perineural spread of tumor) should be evaluated. Bilateral Bell’s palsy is unusual, often associated with HIV or other systemic pathologies like sarcoidosis, Lyme, and syphilis [5, 26‐28].

Vestibular neuritis presents as unilateral acute vertigo without hearing loss. Nausea and vomiting are also associated. It affects young and mid-adults with no sexual preponderance. The etiology is various. Viral, bacterial, and protozoan infections have been reported, but also allergic and autoimmune causes are described. Inflammation of the vestibular nerve may be complicated by demyelination, with loss of function, not always reversible [29]. MRI shows hyperintensity of the cisternal tract of the vestibular nerve on T2-weighted and FLAIR sequences [30] with enhancement on post-gadolinium images [31] (Fig. 27). Acute labyrinthitis is similar to vestibular neuritis with associated hearing loss and tinnitus [5].

Neurovascular compression syndromes are caused by vascular structures (usually arteries) that directly contact the cisternal segment of a cranial nerve (Fig. 30). Typically, the transition zone between the central and the peripheral myelin is the most vulnerable region of the nerve [35]. Clinical presentation is variable and includes trigeminal and glossopharyngeal neuralgia, vestibular paroxysm, and hemifacial spasm. However, neurovascular compression should be evaluated only in the presence of specific clinical features [6]. Also, nonhemorrhagic aneurysms may be associated to nerve dysfunction, for example in the case of vision loss due to compression of II nerve or optic chiasm by proximal internal carotid artery, and III, IV, or VI cranial nerves’ palsy secondary to intracavernous aneurysm. Imaging may be useful to detect the displacement and the compression of a nerve by redundant arteries. Steady-state sequences and corresponding Time-of-Flight (TOF) or 3D T1-weighted gadolinium-enhanced images are very useful for diagnosis and preoperative evaluation [35].

Superficial siderosis is a rare pathological condition that results from chronic deposition of hemosiderin in the subpial layers of the brain and spinal cord. Classically, it is bilateral and it may present with the typical triad: ataxia, sensorineural hearing loss, and myelopathy. Other clinical presentations include dysarthria, nystagmus, myelopathy, bladder dysfunction, sensory and pyramidal signs. Hemosiderin deposition has predilection for the superior cerebellar vermis, cerebellar folia, frontal lobe, temporal cortex, brainstem, spinal cord, nerve roots and cranial nerve, mainly the VIII. Rarely, extraocular nerve palsies, optic and trigeminal neuropathy have been reported in literature. MRI is useful to identify hemosiderin deposition, based on magnetic susceptibility, better demonstrated as hypointensity on T2*-weighted sequences (blooming effect) (Fig. 33) [36].