Approach
The general approach to any cranial neuropathy is to establish whether it is an isolated finding or if there are other neurological symptoms or signs. The patient may not be aware of these, and a thorough neurological exam is needed.
If several cranial nerve defects are identified, the possible diagnosis can be varied, and intracranial imaging is usually required. Clinical history and associated examination findings are crucial in narrowing down the possible causes of a cranial nerve neuropathy and directing further imaging. Urgent considerations should always be excluded first.
Olfactory (I)
Patients with olfactory nerve dysfunction are often unaware of their deficit and infrequently present to a clinician.[2] Those who do present may have anosmia (complete loss of smell), hyposmia (partial lack of smell), dysosmia (normal smells inaccurately detected as unpleasant odours), phantosmia (olfactory hallucinations), or a loss of taste sensation.[4]
Establishing the cause of olfactory loss relies heavily on history.[117] Olfactory dysfunction is often due to causes other than olfactory nerve damage, such as an age-related decline in olfactory function, viral infections or chronic sinus disease, exposure to possible toxins such as pesticides, solvents, heavy metals, or hydrogen sulfide, septal surgery, or radiation. A feeling of unilateral nasal blockage or pressure may suggest an intranasal neoplasm, but this is also rare.
Given the relationship with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, early signs of cognitive or motor dysfunction should be sought.[38]
Patients with congenital abnormalities such as Kallmann's syndrome either do not go through puberty or have incomplete puberty if untreated. Male patients with Kallmann's may experience decreased libido and erectile dysfunction, while women may have dyspareunia. Both will usually be infertile if left untreated.
There may be evidence of previous head trauma, and a temporal relationship to olfactory dysfunction would support this aetiology. Occipital and side impacts are most likely to affect olfactory function.[36] If anosmia is ipsilateral, fundoscopy is indicated to assess for optic atrophy or papilloedema, which may indicate an intracranial mass lesion or Foster Kennedy syndrome.
Most patients will have a non-neurological cause for their olfactory loss and do not require imaging. Clinicians should not necessarily obtain magnetic resonance imaging (MRI) in adult patients with olfactory dysfunction who have no identifiable cause after a thorough history and physical examination (including nasal endoscopy), together with negative findings for preceding viral illness or head trauma.[118]
If imaging is required, MRI scan of the orbits, face, and neck (without and with contrast) is usually appropriate for examining the olfactory nerve and its pathway, although computed tomography (CT) is useful in cases of trauma, paranasal sinus disease, and bony anatomy that impacts olfaction.[119]
Optic (II)
Clinicians should determine whether visual loss is sudden or progressive, monocular or binocular, and whether it is associated with pain. Optic nerve lesions typically produce monocular visual loss. Pain is variable, but when present suggests optic nerve disease such as multiple sclerosis (MS).
Trauma to the outer brow or temporal bone may cause optic nerve trauma.[55] If a fracture is suspected, orbital CT is advised, with brain imaging if indicated (depending on the presence of any other features such as alteration in consciousness level).[120]
In patients with sudden visual loss and a positive family history, Leber's hereditary optic neuropathy (LHON) or dominant optic atrophy (DOA) may be considered. The contralateral eye is usually affected within days to months. In addition, a multiple sclerosis-like illness also sometimes occurs in patients with LHON, especially in women. Diagnosis is confirmed by molecular genetic testing. NCBI: Leber hereditary optic neuropathy Opens in new window
Use of certain drugs such as ethambutol, infliximab, sildenafil, and amiodarone may damage the optic nerve, and a trial discontinuation or substitution with an alternative drug is recommended.[61] If there is an epidemic of optic neuropathy (usually in the developing world), nutritional deficiency of B-group vitamins (B1, B2, B9, and/or B12) may be responsible.[62] Formal visual field testing is recommended, and bilateral central scotoma is the most common finding.
Children with disc swelling on fundoscopy are likely to have optic neuritis. A history of preceding viral infection or immunisation may be elicited. If disc swelling is absent, further evaluation is recommended with a lumbar puncture (LP), cerebrospinal fluid (CSF) evaluation, and/or brain MRI to look for an intracranial or intraorbital mass lesion or idiopathic intracranial hypertension.
In young adults, optic neuritis is often the first presentation of MS. It affects women more frequently. Most cases are retrobulbar, so most patients have a normal fundus, but one third have papillitis.[62] Loss of colour vision and a central scotoma are common findings. There may be associated symptoms of tingling, numbness, or weakness in the limbs. If symptoms are bilateral, are associated with fever, or are atypical for optic neuritis, then a brain MRI is essential to exclude inflammatory or compressive optic neuropathies such as sarcoid tumour, optic nerve meningioma or glioma, or pituitary tumour. MRI may show white matter hyperintensities consistent with MS. Severe or bilateral optic neuritis should raise the possibility of neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein-associated disorder (MOGAD), which are antibody-mediated demyelinating diseases with predilection for the optic nerves and spinal cord.[121] Pattern reversal visual evoked potentials (VEPs) may be performed to assess for abnormalities related to past or ongoing optic nerve demyelination, even among patients without any abnormal physical examination findings.[8]
Meningioma is most common in women of middle age. Proptosis may be a feature of a glioma. Brain MRI and/or head CT should be arranged for patients with proptosis.[120] With compressive lesions, venous drainage can become obstructed, resulting in a diagnostic triad of progressive visual loss, optic pallor, and optociliary shunts. An optociliary shunt is recognised on fundoscopy by large, tortuous vascular loops on the optic disc.[122] Severe headache, worse on coughing, and bilateral papilloedema in a young woman, especially if obese, suggest idiopathic intracranial hypertension. An LP can be both diagnostic and therapeutic. The most effective treatment is weight loss.
In older adults with sudden and painless onset, ischaemic optic neuropathy is the most frequent cause. Patients often have risk factors for microvascular disease, such as hypertension, diabetes mellitus, hypercholesterolaemia, and tobacco use. Screening with erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) is warranted when arteritis involvement is suspected (i.e., patient 50 years or older, presenting with temporal headache, visual disturbances, jaw or tongue claudication, fatigue, weight loss, malaise, or fever).[111] If ESR or CRP is elevated, high-dose corticosteroids should be started and a temporal artery biopsy arranged to confirm the diagnosis.[112] If tests for arteritis are negative and the history is not consistent with arteritic ischaemic optic neuropathy, then a brain MRI should be considered to evaluate for unusual causes such as inflammatory disorders and mass lesions.[120]
In a patient with known systemic lupus erythematosus (SLE), Sjogren's syndrome, granulomatosis with polyangiitis, or Behcet's disease, ischaemic optic neuropathy, or optic neuritis may develop, although these are rare causes and other eye conditions such as uveitis are more commonly associated. Symptoms may include red or dry eyes, itchy eyes, eye pain, or visual impairment. Patients may also have systemic symptoms of underlying disorders, such as fever, malaise, arthralgia, myalgia, butterfly rash, anaemia, or haematuria. If an underlying disorder is suspected, serology for ANA (SLE) or antineutrophil cytoplasmic antibody (granulomatosis with polyangiitis) should be performed. The Schirmer test can diagnose Sjogren's syndrome, and pathergy testing is required for suspected Behcet's disease. Optic nerve neuropathy should improve with treatment of the underlying condition.
Oculomotor (III), trochlear (IV), and abducens (VI)
Patients with third nerve palsy often present with paralysis of adduction, elevation, and depression of the eye. They usually have sudden-onset binocular horizontal, vertical, or oblique diplopia and a droopy eyelid. If a pupil is enlarged, the patient is frequently unaware. Isolated mydriasis is rarely caused by a third nerve palsy.
Acquired third nerve palsy can be further subdivided according to pupillary involvement and degree of extraocular muscle dysfunction into 3 types.[64]
Normal pupillary function with complete ophthalmoplegia: cerebral angiography (to exclude an intracranial aneurysm) and brain MRI are not initially required, as the yield for a compressive lesion is very low.[123][124] Observation is an appropriate diagnostic choice in older patients with vascular risk factors such as diabetes mellitus, hypertension, and smoking, as an ischaemic nerve palsy is most likely. Patients who are over 50 years of age with third nerve palsy and intact pupillary function, and who have atherosclerotic risk factors, do not require brain imaging.[118] Patients may be followed up without further investigation for 6-8 weeks unless they have signs and symptoms suggesting arteritic ischaemic neuropathy.[9] If symptoms resolve, then no further work-up is required. Any progression of symptoms or failure to resolve warrants neuroimaging with a brain MRI, and angiogram if MRI is negative.[9] Head CT and magnetic resonance angiography (MRA) are commonly used for screening purposes. Older patients with signs and symptoms suggesting arteritic involvement (headache, visual disturbances, jaw or tongue claudication, fatigue, weight loss, malaise, or fever) should have their ESR and/or CRP tested, and if these are abnormal a temporal artery biopsy is advised with presumptive treatment with high-dose corticosteroids.[9] Ocular myasthenia gravis may rarely mimic pupil-sparing third cranial nerve palsy; features include fluctuating fatigable ptosis or ophthalmoplegia.[125][126] Recent use of sildenafil or cocaine may also account for ophthalmoplegia with normal pupillary function.[65][66]
Normal pupillary function with incomplete ophthalmoplegia: an MRI of the brain is needed to rule out a mass lesion. Cerebral angiography may be considered to rule out an intracranial aneurysm or vascular malformation such as a cavernous-carotid fistula.[9]
Pupillary dysfunction with partial or complete ophthalmoplegia: the most worrying presentation and should be urgently evaluated.[127] Head CT and/or brain MRI is usually required.[118][120] Any signs of neurological deterioration warrant urgent head CT to rule out an intracranial mass lesion causing uncal herniation. Signs of meningismus, sudden severe headache, nausea and vomiting, and altered level of consciousness suggest subarachnoid haemorrhage.[9][123] Migraines can also be consistent with headache, photophobia, and nausea, but consciousness is unimpaired and pupil function is not typically affected.[128] If abnormal pupillary function and partial or complete ophthalmoplegia is associated with fever, an LP should be performed to exclude meningitis. Signs suggesting a cavernous sinus thrombosis or mass include eye pain and headache, proptosis, chemosis, and ophthalmoplegia. There may also be sensory loss in the first 2 branches of the trigeminal nerve. Evaluation with gadolinium-enhanced brain MRI is advised. If head CT or brain MRI does not reveal a compressive lesion, a cerebral angiogram is needed to exclude a compressive intracranial aneurysm.[9][123]
Trochlear (IV) nerve palsy is the most common cause of vertical diplopia. Patients often have a characteristic head tilt, away from the affected side, to reduce their diplopia. Abducens (VI) nerve palsy usually presents with horizontal diplopia and esotropia in primary gaze. Diagnosis of sixth nerve palsy involves excluding deficits in other cranial nerves, as truly isolated sixth nerve palsies are rare.[129]
In children <3 months old, congenital third nerve palsy is likely. All have some degree of ptosis and ophthalmoplegia, and most have pupillary involvement. A brain MRI is recommended to detect any associated brain anomalies.[130] Congenital lesions of the fourth and sixth nerves are very rare.
A history of head trauma may be elicited, but the mechanism is usually severe. The possibility of an underlying structural abnormality must be considered if a third, fourth, or sixth nerve palsy results from minor trauma, and neuroimaging is recommended.[77][78] The fourth nerve is very susceptible to trauma due to its long intracranial course.
In younger patients, a thorough evaluation is warranted, including assessment of vascular risk factors and neuroimaging to rule out myriad structural causes, including base-of-brain tumours and aneurysm.[131] Brain MRI is the choice for imaging in cases without a definitive diagnosis.
Trigeminal (V)
This is the sensory nerve to the face and motor supply to the muscles of mastication. Any of its 3 main branches, ophthalmic (V1), maxillary (V2), or mandibular (V3), may be affected by a wide variety of aetiologies. Urgent considerations to exclude are meningitis, skull-base osteomyelitis, herpes zoster infection, and cerebellopontine angle masses.
Intra-axial nerve pathology is suggested by the presence of other neurological deficits, which may include arm weakness, speech difficulties, or facial droop (due to seventh cranial nerve involvement). A sensory deficit on the opposite side of the body with ipsilateral facial anaesthesia and loss of the corneal reflex may indicate lateral medullary (Wallenberg's) syndrome. Isolated, sudden-onset sensory loss in the trigeminal distribution may represent pontine haemorrhage, and contrast-enhanced brain MRI is the best investigation. A trigeminal neuropathy may occur in the context of known MS, but it is rarely the presenting feature. Ipsilateral facial pain and temperature loss may be a feature of a high cervical spinal cord lesion at the C1/C2 level.
Fever, headache, photophobia, non-blanching rash, stiff neck, or an altered level of consciousness may indicate meningitis. This requires urgent head CT imaging to exclude other serious pathology, such as subarachnoid haemorrhage, and an LP for CSF evaluation. Broad-spectrum antibiotics should be given presumptively, ideally after blood cultures have been taken.
Otalgia, otorrhoea, hearing loss, and headaches, with or without fever and trigeminal neuropathy, may indicate a diagnosis of skull-base osteomyelitis. Patients with these symptoms should undergo head CT or brain MRI to assess for bone destruction and soft-tissue changes.
The presence of a herpetic rash in the V1 distribution needs a prompt ophthalmological consult, as herpes ophthalmicus can lead to keratitis, corneal scarring, and visual loss. A recent history of herpes zoster may suggest a diagnosis of postherpetic neuralgia.
A history of trauma and acute onset of trigeminal neuropathy may indicate the presence of orbital, mid-face, mandibular, or skull-base fractures. Therefore, non-contrast thin section head CT is the best diagnostic tool. Electrodiagnostic (EDX) examination, including blink reflexes and needle electromyography (EMG) of the muscles of mastication, may be informative.[8] Additionally, symptoms in the V3 distribution and a history of oral surgery may suggest iatrogenic injury to the inferior alveolar nerve.
Slowly progressive symptoms of trigeminal neuralgia may result from compression of the trigeminal nerve by a mass at the cerebellopontine angle.[81] Characteristic features of trigeminal neuralgia are paroxysmal, lancinating pain in the distribution of the trigeminal nerve, lasting a few seconds and often precipitated by specific triggers (e.g., touch, chewing).[132] The V2 and V3 divisions are the most commonly involved. These symptoms should be evaluated with high-resolution MRI (head, orbits, face, neck) without or with contrast.[119] Atypical facial pain is characterised by constant, deep pain of the face, but it may also localise to areas outside the trigeminal distribution; it is not caused by a trigeminal neuropathy. The cause is not known and it is considered a diagnosis of exclusion.[81]
Symptoms of numbness with or without associated dysaesthesia or paraesthesia in the distribution of the trigeminal nerve may suggest an autoimmune cause.[87][133] The neuropathy is usually purely sensory and eventually bilateral. Preservation of the jaw-jerk reflex with impairment of the other trigeminal reflexes is characteristic.[87][133] Additionally, patients often have stigmata of the specific autoimmune disease. Appropriate diagnostic serology is recommended.
Numb chin syndrome may occur due to metastasis to the mandible involving the mental nerve (a branch of the inferior alveolar nerve).
Rarely, trigeminal dysfunction may be present from birth due to Chiari malformations or nerve aplasia. Chiari malformations may present with severe headaches (worse in the morning) or symptoms of syringomyelia such as pain and stiffness in the back and shoulders.
Painful ophthalmoplegia of acute onset and boring in nature may be accompanied by paraesthesias across the forehead (corresponding to the V1 division of nerve V), suggesting the rare Tolosa-Hunt syndrome (inflammation of the superior orbital fissure).
Facial (VII)
Presenting symptoms depend on the location of the lesion along the path of the facial nerve, but the most common is unilateral facial muscle weakness (1% to 2% may be bilateral), with or without associated facial and retroauricular pain, dysgeusia (distortion or loss of sense of taste), xerostomia (dry mouth), impaired salivation and lacrimation, and hyperacusis. It is important to determine whether a lesion is peripheral or central (a supranuclear or nuclear facial palsy). Central lesions generally spare the upper facial muscles and are often associated with additional neurological findings, including contralateral limb weakness or altered mental status. Additionally, central facial palsies may spare emotional facial expression.[13]
Central lesions are most frequently caused by contralateral cortical or ipsilateral pontine lesions, such as ischaemic stroke or neoplasm. The presence of any of these additional signs should prompt immediate head CT or brain MRI.[134]
A nuclear facial palsy may also result from a cerebral infarct or neoplasm involving the facial nucleus. Involvement of adjacent structures often results in additional neurological findings, such as ipsilateral sixth cranial nerve (abducens) palsy or contralateral limb weakness.
A history of trauma and the subsequent acute development of unilateral facial weakness and dysgeusia, without hyperacusis or reduced tearing, should be evaluated with a non-contrast thin section head CT of the skull base to assess for possible skull-base fracture just proximal to the origin of the chorda tympani.
Temporal bone fractures can also result in a seventh nerve palsy. EDX examination including facial motor nerve conduction studies (NCS) and EMG of the facial-innervated muscles in each branch of the facial nerve may be helpful but may be limited in the first 5 days of injury.[8][32] Nerve ultrasonography of the facial nerve at the site of trauma can be beneficial, if the nerve is able to be visualised.
Fever, headache, photophobia, non-blanching rash, stiff neck, or an altered level of consciousness may indicate meningitis. In the context of a coexistent seventh nerve palsy, this requires urgent head CT followed by an LP for CSF evaluation. Broad-spectrum antibiotics should be given presumptively, ideally after blood cultures have been taken.
Sudden-onset headache associated with a cranial nerve palsy requires a head CT and LP to look for evidence of subarachnoid haemorrhage.
Otalgia, otorrhoea, retroauricular pain, and fever with seventh nerve neuropathy suggest middle ear or mastoid infection. There is frequently no fever, and white blood cell (WBC) count is generally normal, while ESR is markedly elevated. Suspicion for skull-base osteomyelitis should prompt radiological evaluation with head CT and brain MRI.
Acute progressive bifacial weakness may be seen in the setting of Guillain-Barré syndrome or its variants, either in conjunction with limb weakness, other cranial neuropathy, or in isolation. CSF evaluation and EDX studies should be strongly considered when Guillain-Barré syndrome is suspected, possibly with addition of neuroimaging and/or antibody testing.[114] Peripheral nerve ultrasonography can be helpful.
Slowly progressive facial weakness with or without associated hearing loss or tinnitus generally points to a neoplastic aetiology (such as schwannoma in the cerebellopontine angle, meningioma, or metastasis to the temporal bone). Brain MRI without and with contrast is recommended.[119] Surgical resection of such tumours can carry a risk of iatrogenic postoperative facial palsy, although intraoperative neuromonitoring can partially mitigate this risk.[135][136]
Patients with a history of tick exposure should be investigated for Lyme disease, especially in endemic regions. Unilateral or bilateral facial nerve palsy is a very early symptom in Lyme disease, and serological testing is abnormal in 90% of patients with this infection.[90]
A mass in the parotid region may be visible externally or palpable intra-orally, and it may be increasing in size. This can put pressure on one or more branches of the facial nerve. Surgery to remove a parotid tumour also risks injury to the facial nerve. Referral to an otolaryngologist for evaluation and biopsy of any mass is recommended.
In the absence of other neurological findings, the most common causes of isolated facial nerve palsy are Bell's palsy and Ramsay Hunt syndrome. A viral prodrome of symptoms of upper respiratory tract infection, myalgias, nausea and vomiting, diarrhoea, and hypaesthesia/dysaesthesia in the region of the fifth cranial nerve may be present. Involvement of the facial nerve often progresses in a distal to proximal fashion, initially resulting in facial weakness (motor branch involvement), dysgeusia and reduced salivation (chorda tympani involvement), hyperacusis (stapedial branch involvement), and decreased tear production (geniculate ganglion involvement). Brain MRI is not usually indicated with isolated unilateral Bell’s palsy, although a high percentage of patients with Bell's palsy show enhancement of the abnormal facial nerve after receiving gadolinium.[118][119][137] EDX studies, including direct facial motor NCS or EMG, may be performed at an early stage in the disease to aid in prognosis, but the usefulness of NCS in the first 5 days is limited.[138] Ramsay Hunt syndrome can be differentiated from Bell's palsy by the concomitant presence of an erythematous herpetic rash of the ear or mouth, or by elevated serum varicella zoster virus (VZV) antibody titres or presence of VZV DNA.
Vestibulocochlear (VIII)
Rapidly progressive vertigo (over several hours) with horizontal-torsional nystagmus is characteristic of vestibular neuritis. It is a self-limiting condition that lasts for days and then slowly remits over several weeks.
Head thrusts and head heaves can be used to demonstrate 'catch-up saccades', which tests for semicircular canal or utricle dysfunction. The head shake test involves tipping the head back by about 30˚ and shaking it from side to side quickly for 30 seconds. A unilateral vestibular defect causes slow nystagmus toward the side of the lesion. It is specific but not very sensitive. The Unterberger stepping test involves asking the patient to walk with his or her eyes shut and arms out in front. Rotation of >45° is abnormal, and usually this is towards the side of the lesion. Most patients recover completely. Associated symptoms may include nausea, vomiting, sweating, imbalance, disequilibrium, and unilateral hearing loss. Pure-tone audiogram is used to confirm and characterise hearing loss.
A reduction in speech discrimination out of proportion to abnormalities on pure-tone audiogram suggests neural presbycusis.
High-frequency sensorineural hearing loss and tinnitus that is bilateral and symmetrical is consistent with damage from excessive noise or ototoxic drug. This includes aminoglycosides, platinum-based antineoplastic agents, salicylates, quinine, and loop diuretics.[102] Onset may be after only one dose of the offending drug or several months after exposure.
Hearing loss in combination with tinnitus, vertigo, and disequilibrium may suggest a cerebellopontine angle mass. Tinnitus is often high pitched and ipsilateral to the side of the mass. Concomitant facial nerve palsy may also be present. Suspicion for a cerebellopontine angle mass should prompt brain MRI with gadolinium.[139] Surgical resection of such tumors can carry a risk of iatrogenic postoperative hearing loss, although intraoperative neuromonitoring can partially mitigate this risk.[135][140]
The presence of other neurological deficits such as ipsilateral facial or contralateral limb weakness, contralateral temperature and pain loss, trigeminal sensory loss, or Horner's syndrome should raise suspicion for a central cause.
Glossopharyngeal (IX) and vagus (X)
Isolated ninth cranial nerve neuropathy is rare, as lesions often result in tenth (vagus), eleventh (spinal accessory), or twelfth (hypoglossal) cranial nerve palsies due to the anatomical proximity to these nerves. Factors that help to differentiate between specific aetiologies include the duration since onset and a history of recent head or neck surgery.
Iatrogenic injury to the recurrent laryngeal nerve is the most common single vagal nerve lesion, and should be suspected when there is acute onset of vagal dysfunction after surgery (particularly thyroid, anterior cervical spine, and carotid endarterectomy). The left recurrent laryngeal nerve is more frequently injured than the right due to its longer course through the mediastinum.
Fever, headache, photophobia, non-blanching rash, stiff neck, or an altered level of consciousness may indicate meningitis. In the context of a coexistent cranial nerve palsy, this requires urgent head CT followed by an LP for CSF evaluation. Broad-spectrum antibiotics should be given presumptively, ideally after blood cultures have been taken.
Sudden-onset headache associated with a cranial nerve palsy requires a head CT and LP to look for evidence of subarachnoid haemorrhage.
A history of slowly progressive symptoms should raise suspicion of a compressive mass in the cerebellopontine angle (e.g., schwannoma), jugular foramen (e.g., glomus tumour), or parapharyngeal space (e.g., carotid body tumour). A glossopharyngeal neuroma located in the cerebellopontine angle may present with hearing loss (due to involvement of nerve VIII), while a neuroma located at the jugular foramen is likely to produce deficits in nerves IX to XI.[141] In this instance, head and/or neck CT or brain MRI with contrast should be obtained. Angiography may be considered for further evaluation of enhancing masses.
Glossopharyngeal neuralgia is characterised by paroxysmal episodes of unilateral pain in the base of the tongue and deep neck, usually elicited by chewing or swallowing.[20] Potential causes include vessel loop or neoplastic compression, inflammatory or demyelinating disease, or rarely compression via an elongated styloid process (i.e., Eagle’s syndrome). Neuroimaging of the brainstem should be pursued for further evaluation.
Trauma to the skull base may result in a ninth or tenth nerve palsy, but it is unlikely to be an isolated finding. If trauma is evident, then a prompt thin section head CT of the skull base is recommended.
Otalgia, otorrhoea, hearing loss, and headaches may indicate skull-base osteomyelitis, but this rarely results in isolated ninth or tenth nerve palsy. There is frequently no fever, and WBC count is generally normal, while ESR is markedly elevated. These symptoms should prompt radiological evaluation with head CT and brain MRI. Neck pain and fever might be due to a parapharyngeal space infection, and cervical spine CT with contrast should be obtained, with routine blood chemistries, FBC, and cultures.
Vagus nerve enlargement can be seen in patients with Guillain-Barre syndrome, particularly in the most common form of acute demyelinating inflammatory polyradiculoneuropathy, with nerve ultrasonography at the carotid sheath. The nerve will lie adjacent to the carotid artery and jugular vein.[19][142]
A new onset of hoarseness with a long history of smoking is suspicious of an apical lung tumour impinging on the recurrent laryngeal branch of the tenth nerve. Chest radiograph or CT aids diagnosis. CT-guided or thoracoscopic biopsy may be required to establish the diagnosis. A history of cardiovascular disease, particularly left atrial enlargement or mitral stenosis, can cause impingement of the left recurrent laryngeal nerve in cardiovocal syndrome. Plain chest radiographs and chest CT can be helpful in making this diagnosis.
Spinal accessory (XI)
Injury to the spinal accessory nerve is rare and is most commonly a result of iatrogenic injury. A history of operative intervention, including neck dissection, cervical lymph node biopsy, carotid endarterectomy, jugular vein cannulation, and cosmetic rhytidectomy (face lift) is often elicited.[106] Blunt or penetrating trauma may also result in an isolated palsy.
The involvement of other lower cranial nerves may suggest an intracranial mass lesion. When lesions of the skull base are suspected, brain MRI with gadolinium enhancement is recommended.[27]
Typically, tumours of the jugular foramen and cerebellopontine angle extending into the foramen magnum or spinal cord also affect other cranial nerves. Three syndromes are recognised depending on the combination of cranial nerves involved:[108][18]
Vernet's syndrome (neuropathy of IX, X, and XI)
Collet-Sicard syndrome (neuropathy of IX, X, and XI, plus cerebellar disturbance)
Villaret's syndrome (neuropathy of IX, X, XI, and XII).
Neuralgic amyotrophy may be mistaken for a spinal accessory mononeuropathy in view of restricted arm movements, including weak shoulder shrug and lateral scapular winging.[143] This is due to painful idiopathic inflammation of proximal branches of the brachial plexus, with resulting arm weakness or paralysis, and resolves slowly over time. EDX examination including spinal accessory motor NCS and EMG of the sternocleidomastoid (SCM) and/or trapezius muscles may be of benefit.[32]
Ultrasonography of the spinal accessory nerve in the posterior triangle of the neck can show focal nerve changes, such as nerve or isolated fascicular enlargement. Muscle ultrasonography of the SCM and/or trapezius muscles, including the upper, middle, and lower portions, may show atrophy and muscular changes with restricted dynamic motion of the muscles on activation.[144]
Hypoglossal (XII)
Causes can be nuclear or infranuclear. Additionally, motor neurone disease and progressive bulbar palsy (a bulbar form of motor neurone disease) can result in dysfunction. EMG of the tongue is the most sensitive diagnostic test to detect denervation; however, muscle ultrasonography is the most sensitive diagnostic test to detect fasciculations.
Fever, headache, photophobia, non-blanching rash, stiff neck, or an altered level of consciousness may indicate meningitis. In the context of a co-existent cranial nerve palsy, this requires urgent head CT followed by an LP for CSF evaluation. Broad-spectrum antibiotics should be given presumptively, ideally after blood cultures have been taken.
Sudden-onset headache associated with a cranial nerve palsy requires a head CT and LP to look for evidence of subarachnoid haemorrhage.
A history of slowly progressive symptoms raises suspicion for compression by a mass or tumour, and further evaluation with CT or MRI with contrast of the brain and/or neck is warranted. Dural arteriovenous fistulas and internal carotid artery aneurysms or dissections can present in the same way. Fistulas may present with headaches, pulsatile tinnitus, or stroke-like symptoms. If fistula is suspected, CT or conventional angiography is suggested.
Patients with otalgia, otorrhoea, hearing loss, and headaches with hypoglossal nerve dysfunction may have skull-base osteomyelitis. ESR is markedly elevated, and patients should be promptly evaluated with head CT and brain MRI.
Fever and neck pain may indicate a neck abscess, and CT of the neck with contrast should be obtained.
In a patient with a history of trauma and acute onset of nerve palsy, head CT (with fine cuts through the skull base to assess for skull-base fracture) or neck CT (if penetrating neck injury) should be obtained.
Onset of hypoglossal palsy after neck irradiation or dissection should raise suspicion of iatrogenic injury.
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