Abstract

Cranial nerve palsy is characterized by a decreased or complete loss of function of one or more cranial nerves. The etiology may be congenital or acquired. Multiple cranial neuropathies are common, particularly in lesions arising from tumors, trauma, impaired blood flow, and infections. While a diagnosis can usually be made based on clinical features, further investigation is often warranted to determine the specific etiology, which should determine the course of treatment.

Cranial nerve types and functions

Cranial nerve		Nerve Type	Nerve Function
I	Olfactory nerve	Sensory	Smell
II	Optic nerve	Sensory	Vision Afferent arm of the pupillary light reflex
III	Oculomotor nerve	Motor (somatic)	Eye movement: superior rectus, inferior rectus, medial rectus, and inferior oblique muscles Eyelid opening: levator palpebrae superioris
III	Oculomotor nerve	Motor (parasympathetic)	Pupillary constriction: sphincter pupillae (Edinger-Westphal nucleus and muscarinic receptors) Accommodation: ciliary muscle
IV	Trochlear nerve	Motor	Eye movement (abduction and internal rotation): superior oblique muscle
V	Trigeminal nerve	Sensory	Facial sensation: ophthalmic (V₁), maxillary (V₂), mandibular nerve (V₃) Mucous membranes of the oral and nasal cavity; soft and hard palate Teeth; temporomandibular joint Meninges Anterior wall of the external auditory canal Somatosensation of anterior ⅔ of the tongue Afferent arm of the corneal reflex
V	Trigeminal nerve	Motor	Muscles of mastication: masseter, temporalis, medial pterygoid, lateral pterygoid muscles Tensor tympani muscle Tensor veli palatini muscle Anterior belly of the digastric muscle Mylohyoid muscle
VI	Abducens nerve	Motor	Eye movement (abduction): lateral rectus
VII	Facial nerve	Sensory	Taste perception: anterior ⅔ of the tongue (chorda tympani) Skin behind the ear (posterior auricular branch) Tympanic membrane (chorda tympani)
		Motor (parasympathetic)	Salivation: submandibular and sublingual glands Lacrimation: lacrimal gland
		Motor (somatic)	Muscles of facial expression Eyelid closing: orbicularis oculi muscle Jaw opening: posterior belly of the digastric muscle Hyoid elevation: stylohyoid muscle Efferent arm of the acoustic reflex (stapedius muscle)
VIII	Vestibulocochlear nerve	Sensory	Balance and equilibrium: vestibular nerve Hearing: cochlear nerve
IX	Glossopharyngeal nerve	Sensory	Taste perception: posterior ⅓ of the tongue (lingual branch) Somatosensation: posterior ⅓ of the tongue; middle ear and eustachian tube (tympanic nerve) Afferent arm of the gag reflex Visceral sensation: carotid sinus (baroreceptors detect blood pressure) Chemoreception: carotid body (chemoreceptors detect partial pressure of O₂ and CO₂, and pH)
		Motor (somatic)	Swallowing: pharyngeal muscles Stylopharyngeus
		Motor (parasympathetic)	Salivation: parotid gland
X	Vagus nerve	Sensory (somatic)	Posterior wall of the external auditory canal Supraglottic region; larynx; trachea
		Sensory (visceral)	Taste perception: supraglottic region Visceral sensation: aortic body (baroreceptors detect blood pressure), lung, stomach, liver, kidneys, intestines up to Cannon point Chemoreception: aortic body (chemoreceptors detect partial pressure of O₂ and CO₂)
		Motor (parasympathetic)	↓ Heart rate Blood vessel vasodilation Visceral function: promotes the motility of the esophagus, stomach, intestines (up to the splenic flexure), and other abdominal organs
		Motor (somatic)	Swallowing Middle and inferior pharyngeal constrictor muscles (passage of bolus) Palatoglossus muscle (elevates posterior tongue upon swallowing) Speech: laryngeal muscles
XI	Accessory spinal nerve	Motor	Head turn: sternocleidomastoid muscle Shoulder elevation: trapezius
XII	Hypoglossal nerve	Motor	Tongue protrusion: intrinsic and extrinsic muscles of the tongue

References:^[1]^[2]

Origin and pathways of the cranial nerves

Cranial Nerve	Nerve Origin	Pathway of the cranial nerve
I	Left and right olfactory bulbs Olfactory epithelium of the nasal mucosa Exits through the cribriform plate of the ethmoid bone	Olfactory receptor cells (first order neurons) → cribriform plate → olfactory bulb → olfactory tract (second order neurons) → (split into two) lateral portion connects directly with the telencephalon (prepyriform area), medial portion connects with the amygdala
II	Optic disc Retinal ganglion cells of the retina	Ganglion cells (in the retina) → optic nerve → optic canal (sphenoid bone) → left and right side of of the optic chiasm (middle cranial fossa) → optic tracts → lateral geniculate nuclei → superior colliculus → calcarine sulcus– lingual and cuneus gyrus (visual cortex on the occipital lobe) Fibers from nasal retina: cross at the optic chiasm Fibers from temporal retina: continue ipsilaterally at the optic chiasm
III	Midbrain	Somatic: oculomotor nucleus Visceral: Edinger-Westphal nucleus → cavernous sinus (lateral wall) → superior orbital fissure (sphenoid bone) → ciliary ganglion (in the orbit) → sphincter muscle (iris) and ciliary muscle
IV	Midbrain	Contralateral trochlear nucleus → decussates in the midbrain → exits dorsally and caudally to the inferior colliculus → encircles the midbrain anteriorly → cavernous sinus (lateral wall, inferior to CN III) → superior orbital fissure (sphenoid bone)
V	Pons	Trigeminal ganglion → foramen ovale Principal nucleus/chief sensory nucleus, spinal trigeminal, mesencephalic nucleus, trigeminal motor nucleus V1 ophthalmic branch Cavernous sinus (lateral wall) Superior orbital fissure (sphenoid bone) V2 maxillary branch: foramen rotundum (sphenoid bone) V3 mandibular branch: foramen ovale (sphenoid bone)
VI		Abducens nucleus (caudal pons) → inferior pontine sulcus → cavernous sinus (middle wall) → superior orbital fissure (sphenoid bone)
VII		Exits the brainstem in the cerebellopontine angle → internal acoustic meatus and the facial canal Geniculate ganglion (temporal bone) Facial canal → stylomastoid foramen → exits the skull → muscles of facial expression Lacrimal pathway: superior salivatory nucleus → intermediate nerve, greater petrosal nerve → pterygopalatine ganglion → zygomatic nerve (branch of V2) → lacrimal nerve (branch of V1) → lacrimal gland Submandibular pathway: superior salivatory nucleus → chorda tympani and intermediate nerve → submandibular ganglion → submandibular and sublingual glands
VIII		Enters through the internal acoustic meatus → cerebellopontine angle → brain stem Cochlear: outer and inner hair cells (from the organ of Corti) → bipolar neurons of the spiral (cochlear) ganglion → ventral and dorsal nuclei (in the medullopontine junction); see auditory pathway for more info. → superior olivary nucleus (from the ventral nucleus to the trapezoid body) → bilaterally to the lateral lemniscus → inferior colliculus → medial geniculate body → auditory radiations → primary auditory cortex (transverse temporal gyri) and amygdala → auditory association cortex Vestibular pathway: hair cells of the semicircular canals, macule, and saccule (otolith organs) → bipolar neurons of the vestibular ganglion → vestibular nerve → vestibular nuclei: inferior, medial, superior, and lateral (in the pons and medulla) → to cerebellum (flocculonodular lobe), nuclei of CN III, IV, VI (for the vestibulo-ocular reflex), reticular formation (aids in body positioning), spinal cord, and the thalamus
IX	Medulla	Postolivary sulcus (along with CN X and XI) → superior ganglion → jugular foramen (formed by temporal and occipital bones) Innervates part of the external ear: passes through the external auditory meatus Innervates the carotid body: via the inferior petrosal ganglion Innervates taste buds: via the inferior petrosal ganglion Stylopharyngeus muscle: from the nucleus ambiguus (in the lateral medulla) Parotid glands: inferior salivary nucleus → otic ganglion → auriculotemporal nerve → parotid glands
X	Medulla	Postolivary sulcus → jugular foramen (formed by temporal and occipital bones) Synapses Superior (jugular) ganglion Inferior (nodose) ganglion Intramural ganglia of visceral organs (e.g., esophagus, stomach)
XI	Medulla	Postolivary sulcus → jugular foramen (formed by temporal and occipital bones) Ventral horn of cervical segments C1–C6 → foramen magnum → jugular foramen → trapezius and sternocleidomastoid muscles
XII	Medulla	Hypoglossal nucleus → preolivary sulcus → hypoglossal canal (occipital bone) → intrinsic and extrinsic muscles of the tongue

Cranial mononeuropathies

A cranial nerve mononeuropathy is a condition in which only a single cranial nerve or nerve group is damaged. The clinical presentation of cranial nerve mononeuropathies depends on the underlying cause as well as the region that is affected along its pathway.

Olfactory nerve palsy

Etiology
- Trauma: especially impact to the lateral and occipital regions (e.g., ethmoid bone fracture)
- Neurodegenerative diseases (e.g., Alzheimer disease)
- Congenital (e.g., Kallmann syndrome)
- Intracranial space-occupying lesion
Clinical features: anosmia

Optic nerve palsy

Etiology
- Ischemic optic neuropathy (i.e., caused by microvascular disease)
- Inflammation: multiple sclerosis, sarcoidosis, viral infections (e.g., measles, mumps)
- Trauma
- Tumors (e.g., optic nerve glioma)
- Impaired nutrition: vitamin B deficiency
- Drugs: sildenafil; , amiodarone; , ethambutol
Clinical features: impaired vision
- Complete transection → ipsilateral blindness + loss of direct pupillary light reflex
- Increased intracranial pressure → papilledema
- Compression (e.g., tumor) → optic atrophy

Oculomotor nerve lesion (III)

Neuroanatomy

Structure	Anatomy	Typical lesions	Localizing clinical features
Oculomotor nuclei	A pair of oculomotor nuclei are located at the level of the midbrain, ventral to the aqueduct of Sylvius Fascicles (efferent fibers) from each oculomotor nucleus pass through the red nuclei and the emerge anteriorly through the medial aspect of the cerebral peduncle as the oculomotor nerve	Ischemic stroke involving branches of the posterior cerebral artery	Benedikt syndrome Weber syndrome
Basilar segment	The oculomotor nerve emerges anteriorly from the midbrain into the interpeduncular fossa and passes between the posterior cerebellar artery and the superior cerebellar artery. The oculomotor nerve then courses in the subarachnoid space over the base of the skull alongside the posterior communicating artery. The parasympathetic pupillomotor fibers from the Edinger-Westphal nucleus join the oculomotor nerve in the basilar segment and lie superficially on the nerve.	Aneurysm of the posterior communicating artery Base of skull fractures Basal meningitis	Recent history of headache Isolated oculomotor nerve palsy with a fixed, dilated pupil
Basilar segment		Tentorial (uncal) herniation	Features of elevated intracranial pressure Abducens nerve palsy Hutchinson pupil
Intracavernous segment	The oculomotor nerve pierces the dura mater, enters the cavernous sinus, and runs along the lateral wall. In the anterior part of the cavernous sinus, the oculomotor nerve divides into a superior division and an inferior division, which enter the orbital cavity via the superior orbital fissure.	Cavernous sinus thrombosis Tolosa-Hunt syndrome Internal carotid artery aneurysms Large parasellar tumors (e.g., meningioma)	Associated palsies of the trochlear (IV), trigeminal (V₁, V₂ nerve), and/or abducens (VI) nerve
Intraorbital segment	The superior division innervates the levator palpebrae superioris and the superior rectus muscle. The inferior division inferior innervates the inferior rectus, the medial rectus, the inferior oblique muscle.	Tumors within the orbital cavity Trauma Orbital cellulitis	Loss of vision Pain Proptosis Associated palsies of the trochlear (IV) and/or abducens nerve (VI) Non-reactive pupil
Ischemic microangiopathy can affect any part of the oculomotor nerve from the basilar segment and typically results in an oculomotor nerve palsy with pupillary sparing.

Isolated oculomotor nerve palsy

Etiology
- Ischemic microangiopathy (more common in patients above the age of 60)
  - Diabetic cranial mononeuropathy
  - Hypertension
- Compression or transection
  - Posterior communicating artery aneurysm
  - Base of skull fractures
Clinical features
- Paralytic squint
  - Adduction weakness
  - The affected eye looks outwards (exotropia) and downwards (hypotropia)
- Ptosis
- Horizontal diplopia that is worse when the head is turned away from the side of the nerve palsy
- Pupillary involvement
  - Compressive lesions: a non-reactive, dilated pupil
  - Ischemic microangiopathy; or demyelinating cranial neuropathies: typically sparing of the pupil
Diagnostics
- A dilated pupil → often a compressive lesion (e.g., posterior communicating artery aneurysm)
  - Best initial test: urgent MRI with MR angiography
  - If MRI is normal: perform a lumbar puncture
- Pupillary sparing → often due to ischemic microangiopathy
  - Assess risk factors for atherosclerosis or arteritis (e.g., blood pressure, glucose, ESR, lipid profile)
  - If no recovery at 3 months: perform an MRI
Treatment
- Compressive lesions: surgery
  - Posterior communicating artery aneurysm: urgent neurosurgical clipping or endovascular coiling
- Ischemic microangiopathy or demyelinating lesions: medical management with adequate control of the underlying disease

Prognosis

Compressive lesions: Partial recovery may occur within 6–7 months.
Ischemic microangiopathy or demyelinating lesion: usually resolves spontaneously within 3–4 months.

For more details about oculomotor nerve lesions and drugs affecting pupillary size, see the learning card pupillary abnormalities.

With an isolated ocuLOVEmotor nerve palsy, nobody loves you when you are down and out (the pupil points outwards and downwards)!

Compression of the oculomotor nerve can cause isolated pupillary dilation due to injury of the parasympathetic fibers. Microangiopathy (e.g., due to diabetes mellitus) typically affects the deeper somatic fibers first, causing ophthalmoplegia without pupillary dilation.

The rule of pupillary involvement is not infallible since approx. 20% of patients with ischemic microangiopathy may have pupillary involvement.

Trochlear nerve lesion (IV)

In acquired lesions of fourth nerve, patients report vertical, torsional, or oblique diplopia. Diplopia is usually worse on downgaze and gaze away from side of affected muscle.

Etiology
- Microvascular damage (diabetes, hypertension, arteriosclerosis)
- Trauma
- Cavernous sinus thrombosis
Clinical features
- Extorsion of the eye: inability to depress and adduct the eyeball simultaneously (the pupil shoots upward during attempted adduction of the eyeball)
- Diplopia (double vision)
  - Vertical or oblique diplopia , which is exacerbated on downgaze (e.g., reading)
  - Diplopia worsens when the patient turns their head towards the paralyzed muscle; → The patient compensates by turning his head to the opposite side of the lesion.
- Mild esotropia

Trigeminal nerve lesion (V)

Etiology
- Tumor
- Vascular compression of the nerve
- Oral surgery
- Inflammation of the nerve
- Cavernous sinus thrombosis
Clinical features
- Peripheral trigeminal nerve lesions
  - Ophthalmic nerve (V₁) is affected → absent corneal reflex (afferent limb), anesthesia of the forehead
  - Maxillary nerve (V₂) is affected; → anesthesia of the midface
  - Mandibular nerve (V₃) is affected → anesthesia of the chin, lower lip, and anterior two-thirds of the tongue; muscles of mastication are paralyzed
    - The jaw deviates towards the side of the lesion because of unopposed action from the opposite pterygoid muscle.
  - Involvement of any of the three branches can cause trigeminal neuralgia.
- Lesion of the tensor tympani branch → hearing impairment (particularly difficulty hearing low-pitched sounds)
- Lesions of the trigeminal nerve nuclei: Depending on which nuclei are affected; , the patient may present with ipsilateral weakness of muscles of mastication and/or ipsilateral loss of sensation.
- Complete trigeminal nerve lesions are rare.

References:^[3]

Abducens nerve lesion (VI)

Most common ocular cranial nerve palsy
Etiology
- Tumor
- Trauma (e.g., at the superior orbital fissure of the sphenoid bone)
- Pseudotumor cerebri
- Cavernous sinus thrombosis
- Duane syndrome: rare, congenital palsy of the abducens nerve
Clinical features
- Horizontal diplopia, which is worse when looking at distant objects
- Esotropia: medial deviation of one or both eyes at primary gaze

References:^[4]^[5]

Facial nerve lesion (VII)

See facial nerve palsy.

Vestibulocochlear nerve lesion (VIII)

Etiology
- Bacterial meningitis (most common cranial nerve palsy)
- Lyme disease
- Tumor (e.g., acoustic neuroma, neurofibromatosis type 2)
Clinical features
- Sensorineural hearing loss
- Vertigo
- Horizontal nystagmus: Movement of the head induces saccadic movement of the eye toward the opposite side the side of the lesion.
- Motion sickness

References:^[6]

Glossopharyngeal nerve lesion (IX)

Etiology: often unknown; may be associated with compression by a blood vessel
Clinical features
- Loss of the gag reflex (afferent limb)
- Loss of the carotid sinus reflex
- Flaccid paralysis of the soft palate → deviation of the uvula away from the lesion (similar to vagus nerve lesions)
- Sensory loss over the soft palate, upper pharynx, and posterior third of the tongue (including loss of taste sensation)
- Mild dysphagia
- Glossopharyngeal neuralgia: throat and ear pain

Lesions that affect the glossopharyngeal nerve typically also affect the vagus nerve because the glossopharyngeal nerve exits the medulla above the vagus nerve.

Vagus nerve lesion (X)

Etiology
- Trauma
- Diabetes
- Inflammation
- Aortic aneurysms
- Tumors
Clinical features
- Loss of the gag reflex (efferent limb)
- Flaccid paralysis of the soft palate → nasal speech and deviation of the uvula away from the lesion
- Epiglottic paralysis → aspiration
- Dysphagia
- Features of vocal cord paralysis
  - Dysphonia (hoarseness)
  - The vocal cord assumes a paramedian position.
- Dysfunction of vagal nerve in the stomach → features of gastroparesis (poor gastric emptying)

Accessory nerve lesion (XI)

Etiology: surgeries of the lateral cervical region, especially the posterior border of the sternocleidomastoid (e.g., resection of cervical lymph nodes)
Clinical features
- Paresis of the sternocleidomastoid muscle → weakness turning the head towards the contralateral side (the left SCM turns the head to the right)
- Paresis of the trapezius muscle → weakness during elevation of the ipsilateral shoulder (→ shoulder drooping) and lateral winging of the scapula

Hypoglossal nerve lesion (XII)

Etiology
- Tumors
- Trauma
Clinical features
- Atrophy and fasciculation of the tongue on the side of the lesion
- The tongue deviates to the side of the lesion when protruded.

Multiple cranial neuropathies

	Lesion	Etiology	Clinical features
Chronic meningitis	Any cranial nerve	Infection (Lyme disease, tuberculosis, cryptococcus neoformans) Inflammation	Insidious or subacute headache, fever, and neck stiffness Additional symptoms depend on which cranial nerves are involved.
Jugular foramen syndrome	CN IX, X, and XI	Glomus tumors Schwannoma Meningiomas Metastatic tumors Cholesteatomas	Loss of taste from the posterior half of the tongue (CN IX) Impaired speech and swallowing: paralysis of vocal cords and palate (CN X) Impaired head turning and shoulder elevation: weakness of the trapezius muscle and sternocleidomastoid (CN XI)
Cavernous sinus syndrome	CN III, IV, V₁,V_2, VI	Neoplasm or inflammation affecting the cavernous sinus (e.g., Tolosa-Hunt syndrome) Intracavernous aneurysms Cavernous sinus thrombosis	Impaired movement of the eye: paralysis of muscle of the eye (CN III, IV, VI) Horner syndrome: Decreased sensation of the upper face (CN V₁_,CN V₂) See skull base syndromes.
Cerebellopontine angle syndrome	CN V, VI, VII, VIII, IX, X	Neoplasms of the cerebellopontine angle Vestibular schwannomas Meningiomas Metastases Cholesteatomas	Progressive sensorineural hearing loss Gait disequilibrium Vertigo is uncommon. See skull base syndromes.
Guillain-Barré syndrome	Any cranial nerve; most commonly III, VII, IX, X	Autoimmune inflammation of peripheral cranial nerves	Facial droop (CN VII) Dysarthria and dysphagia (CN IX and X) Ophthalmoplegia and diplopia (CN III)
Multiple sclerosis	CN II Connection between III, IV, and VI	Autoimmune inflammation of the cranial nerves	Vision loss (CN II) Internuclear ophthalmoplegia (INO)

References:^[7]^[8]^[9]^[10]