Table of Contents

Pain Sensitive Cranial Structures

Overview

The major pain sensitive structures of the head are:

1.The skin, subcutaneous tissues, muscles, extracranial arteries and external periosteum of the skull;

2.Eye, ear, nasal cavities and paranasal sinuses;

3.Intracranial venous sinus system;

4.The dura within the cranial fossae and primarily the proximal anterior, middle and intracranial segment of the carotid arteries;

5.Cervical nerves 1-3 and the cranial nerves as they traverse the dura

The pia-arachnoid, brain parenchyma, ependyma, and choroid plexus are insensitive to pain.

An understanding of pain radiations is critical for differential diagnosis of craniofacial pain. Middle meningeal artery pathology radiates retro-orbitally and to the temporal region. Pain that originates from the intracranial carotid, proximal middle and anterior cerebral arteries radiates to the eye and orbito-temporal areas. The first and second divisions of the trigeminal nerve transmit pain from the forehead, orbit, anterior and medial skull fossae and the upper surface of the tentorium. Sphenopalatine branches of the facial nerve subserve the nasoorbital areas. The ninth and tenth cranial nerves and the first three cervical nerves subserve the posterior fossa and the undersurface of the tentorium. Cranial nerves IX and X transmit pain to the soft palate and fauces of the tonsils. Cervical nerve one has no external pain radiation and innervates the odontoid process. Cervical nerves C2-C4 form the lesser occipital, pre and postauricular nerves and the third occipital nerve that innervate the posterior cranium and the external ear. Pressure on the tentorium may radiate pain into the inner ear. C2 irritation may be felt above the eyebrow. Diaphragma sellae distortion may be perceived as infrabrow pain. The tentorium delineates the trigeminal from the cervical-vagal-glossopharyngeal innervation territories. The trigeminal nerve carries sympathetic fibers from the first three cervical ganglia and parasympathetic fibers from the sphenopalatine and otic ganglia.

General rules of pain referral:

1)Supratentorial pathology refers pain to the anterior 2/3 of the head in the distribution of V1 and V2 of the trigeminal nerve

2)Infratentorial pathology refers pain to the vertex, brow, and neck primarily by the C2 root.

There is convergence of trigeminal and cervical afferents on dorsal horn pain projecting neurons at the C2 segmental level which is the anatomical basis for pain from the neck and occipital areas to project to the forehead (extremely common with C2 involvement in elderly patients with cervical spondylosis and during cough with Chiari malformations). The seventh nerve refers pain to the mastoid region, nine and 10 cranial nerves to the soft palate, fauces of the tonsils and eardrum (X) and larynx. The vertebral artery may refer pain to the lateral eyebrow. Dental and temporomandibular pain is carried by V2 and V3 (alveolar and buccal nerves). Cervical carotid arterial pain may also refer rarely to the eyebrow. Angina characteristically may radiate to the jaw and rarely to the cranial vertex.

Mechanisms of Cranial Pain

Intracranial lesions cause pain by distorting blood vessels and the dura at the base of the brain that may occur before there is increased intracranial pressure. Patients with increased intracranial pressure have bioccipital and bifrontal headache.

The Trigeminal Innervation of Blood Vessels

The proximal portions of large intracerebral blood vessels, nervous sinuses and the pial vessels are innervated by unmyelinated C-fibers. The unmyelinated C-fibers’ origin is the ophthalmic division (V1) of the trigeminal nerve and the upper cervical roots (posterior fossa structures). These C-fibers co-release the vasoactive neuropeptides substance P and calcitonin gene related peptide in addition to glutamate when the trigeminal ganglia are stimulated. Some form of sensitization of these thinly myelinated and unmyelinated blood vessels occurs during migraine and other forms of vasodilatory headache.

Specific headaches are thought to occur from dilatation of intracranial and extracranial blood vessels that may also have sensitized nociceptive C and A-delta fibers in their walls. These include seizures, alcohol intoxication, nitrate ingestion, and monosodium glutamate (MSG). Compression of the carotid or superficial temporal artery may partially relieve this form of headache by decreasing arterial pulsation. Rapid arterial pressure increases that occur with pheochromocytoma, malignant hypertension, Valsalva maneuvers (intercourse) and with monoamine oxidase inhibitors may also be caused by arterial dilatation.

Vasodilation of Vessels Innervated by the Sensitized Trigeminal System

Inflammation of the extracranial temporal and occipital arteries (from giant cell arteritis) frequently causes burning persistent scalp pain early in its course and then becomes diffuse (activation of C-fibers for burning pain). Ischemic vascular disease in and of itself does not cause pain. Dissection of the carotid artery projects pain to the ipsilateral face, eye, brow, and forehead. Dissection of a vertebral artery projects pain postauricularly, to the upper neck and rarely to the outer 1/3 of the ipsilateral eyebrow. Basilar artery thrombosis causes a pain radiation to the basi-occiput and rarely to the forehead. Posterior communicating or distal internal carotid artery pain causes retroorbital pain.

Paranasal sinus pain or blockage accrues from infection of the maxillary or frontal sinuses. There is usually mechanical hyperalgesia over the sinuses. The ethmoid sinus causes pain deep in the midline behind the root of the nose. The sphenoid sinus may project pain to the vertex of the cranium (controversial lower face pain). The putative mechanism for these pains is activation of nociceptors in the sinus walls. The pain of frontal and ethmoidal sinusitis is at its maximum upon awakening and lessens with upright posture. The reverse is true for maxillary and sphenoid sinusitis. These symptoms are dependent on intrasinus pressure (activation of sensitized ASIC receptors; these are upregulated in nociceptive afferents when hydrogen ion is generated by the infection).

Ocular induced headaches are primarily localized to the orbit, forehead, temple, or the eye itself. In general, it follows a prolonged use requiring adduction and is steady and aching. It is usually caused by astigmatism, hypermetropia, and rarely myopia. Refractive error may also cause headache. Diplopia and eye patching are associated with frontal headache. Acute angle glaucoma causes raised intraocular pressure and steady, aching eye pain that radiates to the forehead. It is accompanied by an erythematous conjunctiva and may be precipitated by anything that dilates the pupil.

Meningeal irritation from blood or infection is most often acute (in the case of subarachnoid hemorrhage) and may be insidious with fungal or tuberculous infection. SAH causes severe generalized headaches that reach maximum intensity almost immediately and is associated with nausea, vomiting, and neck stiffness. A major component of meningeal irritation is pro-inflammatory cytokines released from immune cells, prostaglandins (PGE2), kinins, serotonin, and blood components. Sensitized blood vessel and meningeal nociceptors may also be activated by increased intracranial pressure. Sudden severe headaches (“thunderclap”) are also caused by posterior reversible encephalopathy syndrome, eclampsia, migraine, dissection of major arteries but most importantly subarachnoid hemorrhage from any source.

Low CSF pressure headaches are most frequently caused by lumbar puncture. They may occur spontaneously from leakage of CSF from perineural cysts or dural tears. They are associated with a steady occipital nuchal and frontal headache that occurs with erect posture and are relieved rapidly with recumbency. The headache may be exacerbated by jugular vein pressure. It is often associated with mild nausea and is purported to be caused by traction of dural structures by caudal brain displacement.

Postural headaches, particularly those with recumbency occur with subdural hematoma (may also be exacerbated by the upright posture) and with posterior fossa mass lesions. The headache of idiopathic intracranial hypertension (pseudotumor cerebri) may also be worse in the morning.

Tension Headache

General Characteristics

1.Tension type headache is classified as:

a.Infrequent episodic

i.Fewer than one headache per month

b.Frequent episodic TTH

i.Two to 14 headaches per month

c.Chronic TTH

i.15 or more headache days a month

d.Tension headache has been estimated to affect more than 4% of the population and is more prevalent in women

Clinical Manifestations

1.The onset is usually in middle age rather than childhood or adolescence

2.It is typically bilaterally located in occipital nuchal, temporal or frontal areas

3.The pain is usually dull, aching or tightness and pressure from a band surrounding the cranium; in some instances, they may have a throbbing quality.

4.There are no migraine type auras and the headaches usually do not interfere with activities of daily living

5.The onset is often gradual and once established may be very long-lasting; from 30 minutes to 7 days

6.They are more variable in duration, more quality specific and less severe than migraine

7.Migraine and traumatic headaches may be complicated by tension headache.

Neuropathology

1.Pressure pain thresholds over the temporalis, masseter and frontalis muscles are lower in TTH than age-matched controls

2.Increased presence and tenderness of myofascial trigger points may sensitize central pain projecting neurons

Neuroimaging

1.MRI to delineate a structural cause of headache

2.Sedimentation rate to rule out giant cell arteritis

Brain Tumor Headache

General Characteristics

1.Headache occurs in approximately 1/3 to 50% of patients with brain tumors. It is rare to be the initial symptom that brings the patient for an examination

Clinical Manifestations

1.There are no specific features that delineate brain tumor headaches

2.In general, it is felt as deep seated, usually steady (rarely throbbing), and may be described as aching.

3.Physical activity may be provoking and rest may be a relieving factor

4.Nocturnal awakening due to pain is unusual and is caused by cluster headache, hypnic headaches or caffeine withdrawal

5.Projectile vomiting without nausea may occur in late stages in adults or in posterior fossa tumors that irritate the vomit center in the floor of the IVth ventricle. It is more common in children with posterior fossa tumors

6.If the headache is unilateral it is on the same side as the tumor

7.Bifrontal and bioccipital headache after a period of unilateral headache suggests hydrocephalus

8.Colloid cysts of the IIIrd ventricle or those that obstruct the foramina of Monroe as well as giant subependymal astrocytomas at this site frequently are associated with headache

9.Paroxysmal headaches have been described with both intra and peri-ventricular brain tumors. Their characteristics are:

a.Severity

b.Reach maximum intensity in a few seconds

c.Last for minutes to an hour and then rapidly subside

10. Brain tumors with greatly elevated intracranial pressure cause:

a.Vomiting

b.Transient obscuration of vision (suprachiasmatic cistern pressure that renders the chiasm ischemic)

c.Leg weakness with “drop attacks”

d.Loss of consciousness

e.These paroxysmal attacks have been described with colloid cysts of the IIIrd ventricle, craniopharyngiomas, pinealomas and cerebellar tumors

Neuropathology

1.Headaches of brain tumors are caused by displacement of major cerebral blood vessels or hydrocephalus from blockage of CSF flow at different levels. Unilateral ventricular enlargement from a choroid plexus papilloma may cause headache on the ipsilesional side

Laboratory Evaluation

1.Sed rate to rule out inflammatory conditions

Neuroimaging

1.MRI:

a.To delineate the mass lesion and consequent cerebral edema

b.To rule out multiple intraparenchymal lesions

c.To rule out brain tumor mimics that include subdural hematoma and abscess as well as hemorrhage or unusual pathologies associated with mass lesions

2.Electroencephalogram:

a.To evaluate seizure potential

Post-Traumatic Headache

General Characteristics

1.Impact-related mild traumatic brain injury is primarily caused by contact sports, motor vehicle accidents, falls and assaults

2.It is estimated that approximately 1.6-3.8 million mild TBI occur each year in the USA

Clinical Manifestations

1.Longitudinal studies demonstrate an incidence of 71% of headache after moderate (mTBI) or severe TBI and a cumulative incidence of 91% after mild mTBI; prevalence remains at 44% over one year with moderate TBI and 54% after mTBI

2.A prior history of headache is associated with a higher risk of PTH

3.Five symptom clusters are identified in patients with mTBI:

a.Post-traumatic headache / migraine

b.Nausea

c.Emotional / affective

d.Fatigue / malaise

e.Dizziness / mild cognitive impairment

4.The most common headache phenotypes utilizing ICHD-3 criteria with mTBI are:

a.Migraine / probable migraine in 50% of patients with headache

b.Tension type headache

Neuropathology

1.Concussion is associated with diffuse axonal injury that may not be detectable with conventional MRI

2.In mTBI:

a.Biomechanical forces cause linear and rotational acceleration-deceleration of the brain that creates diffuse shear strains on parenchymal tissue

b.Axonal injury in mTBI develops over days to weeks after the injury

c.Present theories support a post-traumatic metabolic cascade that involves glutamate release, ion fluxes and free radicals that cause mitochondrial dysfunction and calcium sequestration

d.Energy crisis with lack of ATP leads to cytoskeletal damage as excess intracellular calcium damages myelin and oligodendrocytes

e.Impaired axonal transport may cause secondary axonal disconnection and Wallerian degeneration

f.Global and regional decreased blood flow also occur with concussion and with cerebral hypoperfusion there is oxidative stress

g.Histopathology:

i.Axonal bulbs, irregular tortuous axonal varicosities and small globoids of degraded myelin sheath are described

ii.Mechanical strains that are diffuse along the length of an axon cause an elongated pattern of axonal swelling

Laboratory Evaluation

1.Relationship between the apolipoprotein E gene and headache following concussion

a.Patients with the APOe4 allele may be more likely to sustain a post-concussion headache

b.Headache may be more severe after the concussion’

Neuroimaging

1.Myelin water imaging:

a.Evaluates changes in myelin water fraction derived from the T2 decay signal

b.After 2 weeks post-injury (concussion) decreased myelin water fraction in:

i.The splenium of the corpus callosum

ii.Posterior thalamic radiations

iii.Superior corona radiata

iv.Superior longitudinal fasciculus

v.Posterior limb of the internal capsule

vi.Myelin water fraction recovers to pre-injury values by 2 months post-injury

Laboratory Evaluation

1.Relationship between the apolipoprotein E gene and headache following concussion:

a.Patients with the APOe4 allele may be more likely to sustain a post-concussion headache

b.Headache may be more severe after the concussion

Subdural Hematoma (SDH)

General Characteristics

1.Definition:

a.A subdural hematoma is loculation of blood below the inner layer of the dura but external to the brain parenchyma

b.Acute SDH are less than 72 hours old. The subacute phase is thought to begin 3 to 7 days following acute injury

c.Chronic SDH develop over weeks

Clinical Manifestations

1.Lucid intervals (following concussions) occur in approximately 40% of patients with acute SDH

2.Acute subdural hematomas are more likely than chronic ones to be associated with primary brain injury

3.More than 50% of comatose patients with acute SDH suffer parenchymal contusions

4.Headache of chronic subdural hematoma:

a.Deep seated and dull

b.Steady and is unilateral (the scalp may be tender to mechanical stimuli)

c.May be associated with lethargy, confusion and fluctuating hemiparesis

d.In acute SDH:

i.Positional exacerbation of pain after recumbency or leaning the head to one side

ii.The headache increases in frequency and severity over weeks

e.Tentorial hematomas may cause pain in the eye

Neuropathology

1.Acute SDHs are caused by high-impact trauma to the skull with consequent acceleration-deceleration brain tissue movement relative to fixed blood vessel and dural structures

2.The usual ruptured vessels are those that connect the cortical surface to a dural sinus, the bridging veins

3.Bridging veins are stretched with brain parenchymal atrophy; less frequently, a cortical vein or small artery may be torn by direct trauma. One study has demonstrated that ruptured cortical arteries are located around the Sylvian fissure.

4.Associated with the head trauma are:

a.Parenchymal hematomas

b.Contusions

c.Subarachnoid hemorrhage

d.Diffuse axonal injury

5.Low pressure venous bleeding from ruptured cortical veins dissects the arachnoid from the dura and then layers out over the convexity

6.In the subacute phase the clotted blood liquefies (a hematocrit-like effect)

7.The chronic phase demonstrates that cellular elements disintegrate leaving serous fluid in the subdural space which rarely calcifies

8.The rate of acceleration-deceleration of the head determines bridging vein failure

9.Risk factors for chronic SDH include:

a.Chronic alcoholism

b.Seizures

c.Coagulopathy

d.Arachnoid cysts

e.Anticoagulant therapy

f.Hypertension

g.Arteriosclerosis

h.Thrombocytopenia

i.Diabetes mellitus

Laboratory Evaluation

1.Initial blood tests:

a.Complete blood count

b.Coagulation profile

c.Metabolic panel:

i.Serum sodium is of particular importance as hyponatremia is seen in 5-12% of patients with head injury and exacerbates cerebral edema and lowers seizure threshold

Neuroimaging

1.CT scan:

a.Images can be obtained within 5 minutes

b.Highly sensitive to acute blood

2.MRI:

a.Sensitive to the size of the hematoma and to soft tissue pathology

Mimics of Subdural Hematoma

1.Metastasis

2.Lymphoma

3.Sarcoma

4.Infections

5.Autoimmune disorders

Headache of Temporal Arteritis (GCA)

General Characteristics

1.A very important headache in older patients; almost all patients are older than 65 years of age

2.Giant cell arteritis primarily involves the major branches of the aorta with typical involvement of the extra-cranial branches of the carotid artery

Clinical Manifestations

1.Constitutional symptoms are present in a significant number of patients that consist of a low-grade fever, weight loss and associated mild anemia

2.The headache:

a.Insidious throbbing or non-throbbing headache with superimposed lancinating pain

b.Rarely the headache has an explosive onset

c.The pain is usually unilateral, less frequently bilateral and often localized to the affected arteries

d.Approximately 50% of patients have aching in the proximal limb girdle muscles that is associated with polymyalgia rheumatica

e.The headache pain is persistent throughout the day and is often exacerbated at night

f.If untreated, the headache may last for months

g.Associated symptoms include:

i.Jaw claudication

ii.A burning scalp

iii.Episodes of amaurosis fugax:

1.Transient monocular blindness or looking through a haze with loss of visual acuity

2.Rare ophthalmoplegia

h.Ischemic nodules in the scalp, a perforated nasal septum and tongue lesions that resemble squamous cell carcinoma have been described

i.The superficial temporal and other scalp arteries may be thickened and tender

Neuropathology

1.Temporal artery biopsy demonstrates:

a.An intense granulomatous or “giant cell” arteritis

2.Recent experimental work supports the role of cytokine pathways that include:

a.Pro-inflammatory interleukins

b.IL-6-IL-17 axis

c.IL-12 interferon-gamma-axis

Laboratory Evaluation

1.The sedimentation rate is usually >50mm/h and often >75mm/h

2.The C-reactive protein is more sensitive than the sedimentation rate and is particularly helpful if the sed rate is only mildly elevated

3.A subgroup of patients have leukocytosis

4.Ultrasonography:

a.May demonstrate a halo and irregularly thickened vessel walls

5.Temporal artery biopsy is the gold standard for diagnosis; occasionally extracranial external arteriography is utilized for selection of the biopsy site

Headache of Idiopathic Intracranial Hypertension (IIH)

General Characteristics

1.Definition – IIH is characterized by increased intracranial pressure without radiological and laboratory evidence of intracranial pathology except for an empty sellae, optic nerve sheaths distended with cerebrospinal fluid and smooth-walled non-flow-related venous sinus stenosis or compression

2.The most commonly affected patients are obese women of child-bearing age but it is described in patients of any age or sex

3.The incidence of IIH varies from 0.03 to 2.36/100,000/year of the total population

Clinical Manifestations

1.Headache is the most common symptom and is present in 80-90% of patients

2.Headache characteristics:

a.Typically frontal or retro-orbital pressure-like or less frequently throbbing

b.May be associated with nausea, vomiting and transient visual obscurations

c.Some patients note exacerbation with recumbency

d.There is no relationship between the severity or frequency of the headache and the intracranial pressure

e.Approximately 40% of IIH patients have a migraine headache history

f.Headache may resemble a tension-type pattern

3.Visual deficits:

a.Transient visual obscurations

i.Loss or graying out of vision (looking through “gauze”) for less than 30 seconds (usually a few seconds) is seen in 68% of patients and is due to ischemia of the optic chiasm from pressure on the suprachiasmatic cistern); other mechanisms proposed are ischemia of the optic nerve head and herniation of the parahippocampal gyrus into the tentorial notch

ii.Tunnel vision

iii.Decreased visual acuity

iv.Papilledema

v.Pulsatile tinnitus is reported in 52% of patients; rarely low-frequency hearing loss and vertigo are reported

vi.Diplopia from VIth nerve palsy

Neuropathology

1.The cause of IIH is being evaluated. The link between obstructive segments in the distal transverse sinus and increased arterial inflow is a possible mechanism

2.It is seen in association with:

a.Metabolic disorders

b.Drugs and their withdrawal

c.Disruption of venous outflow from the brain

d.Systemic diseases

Laboratory Evaluation

1.Complete blood count

2.Pro-coagulant profile

3.Serum iron and iron-binding capacity

4.Antinuclear antigen

5.Lyme screen

6.Lumbar puncture:

a.CSF is under pressure but otherwise negative; rarely the protein is low

Neuroimaging

1.MRI:

a.Imaging of the head and orbit with contrast and magnetic resonance venography (MRV)

b.MRI features:

i.Empty sellae

ii.Narrowing of the trigeminal cave

iii.Enlargement of the foramen ovale; less frequent enlargement of the jugular foramen and hypoglossal canal

iv.Slit ventricles

v.Stenosis of the transverse sinus

vi.Enlarged optic nerve sheaths

vii.Flattening of the posterior globe

Low CSF Pressure Headache

General Characteristics

1.Spontaneous intracranial hypotension most often occurs from cerebrospinal leaks at the spinal level and rarely from the skull base

2.The leaks cause loss of CSF volume that may be associated with subdural fluid collections

Clinical Manifestations

1.The headaches’ most distinguishing feature is exacerbation with the upright posture and relief with recumbency

2.If untreated the headache may last for days or weeks

3.The headache may be at the brow the back of the skull and radiates to the upper back of the neck and thoracic spine and shoulders

4.The headache is often associated with nausea, neck stiffness and vomiting

5.Tinnitus, vertigo and VIth nerve palsy are not uncommon

6.Self-audible bruit

Neuropathology

1.The syndrome is posited to be caused by downward displacement of the upper brainstem and posterior fossa with the upright posture; the VI nerve may be trapped under the petroclinoid ligament

2.The CSF pressure may be extremely low (60mm H2O) or not measurable

3.Rupture of a perineurial spinal nerve sleeve may be causitive

4.Connective tissue diseases that include Marfan’s syndrome, Ehlers-Danlos syndrome and autosomal dominant polycystic kidney disease may be associated

Laboratory Evaluation

1.CSF:

a.A subgroup of patients may demonstrate a mild lymphocytic pleocytosis; slight to moderate elevated protein and normal glucose concentration

Neuroimaging

1.MRI:

a.Subdural fluid collections, pachymeningeal enhancement, engorgement of venous structures, pituitary hyperemia and sagging of the brain

b.Radioisotope cisternography and CT myelography are utilized to delineate the site of CSF leakage

Cough Headache

General Characteristics

1.A headache that is precipitated by coughing or straining in the absence of intracranial disorder lasting up to 30 minutes

Clinical Manifestations

1.Cough headache is usually bilateral but can be unilateral

2.Most often is localized to the fronto-temporal areas of the cranium

3.Usually affects individuals over 40 years of age

4.Usually lasts for 1 second to 30 minutes but longer duration headaches have been described (a few patients with headaches lasting 2 hours)

5.Cough headache can be triggered by other Valsalva maneuvers but not by exercise

6.Nausea, vomiting photo- and phonophobia are distinctly rare

7.The pain may have a bursting quality

8.May be so severe as to simulate headache of subarachnoid hemorrhage

Symptomatic Cough Headache

General Characteristics

1.Underlying etiologies are present in approximately 40% of patients with cough headache and are primarily caused by Chiari type I malformation

Clinical Manifestations

1.Patients with an underlying etiology for cough headache:

a.Have more associated symptoms that depend on the etiology

b.Have additional headache triggers

c.More severe pain

d.More diverse headache durations

2.Etiologies of symptomatic cough headache include:

a.Chiari I malformation

b.Posterior fossa lesions (vascular malformations)

c.Low cerebrospinal pressure

d.Obstructive hydrocephalus

e.Arachnoid cysts (posterior fossa)

f.Dermoid tumor (posterior fossa)

g.Meningioma (posterior fossa)

h.Os odontoideum

3.Headache characteristics of cough headache from an underlying etiology:

a.Occipital or suboccipital location

b.Explosive, lancinating, pressure or mixed in quality

c.Duration is typically seconds or more than 1 minute

d.Triggers include postural movements, laughing and defecation

e.A proportion of patients have:

i.Dizziness, unsteadiness, facial and upper extremity numbness, vertigo and syncope

ii.Unusual triggers for symptomatic cough headache:

1.Carotid artery disease

2.Non-ruptured cerebral aneurysm

Neuropathology (Primary Cough Headache)

1.Increased intracranial pressure caused by coughing due to increased intra-thoracic and intra-abdominal pressure that causes increased central venous pressure that leads to ICP in primary cough headache

2.Putative mechanisms for primary cough headache include:

a.Transverse or jugular vein stenosis that leads to increased venous cerebral pressure

b.Hypersensitive pressure receptors on venous vessel walls

c.CSF hypervolemia

d.Crowded posterior fossa

3.Increased intracranial pressure is posited to be the mechanism for symptomatic cough headache:

a.Chiari I malformation:

i.Descent of the cerebellar tonsils below the foramen magnum

ii.A craniospinal pressure dissociation with greater pressure in the ventricles than the lumbar subarachnoid space such that coughing would displace the tonsils further into the foramen magnum

Laboratory Evaluation

1.MRI:

a.To delineate structural lesions of the posterior fossa or craniovertebral junction

Other Headache Disorders Triggered or Aggravated by Coughing Include

1.Idiopathic increased intracranial pressure

2.Post-ictal headache

3.High-altitude headache

4.Migraine

5.Tension-type headache

6.Cluster headache

Exertional Headache

General Characteristics

1.Athletes and runners as well as weight lifters are primarily involved

Clinical Manifestations (Weight-Lifters Headache)

1.May occur as a single event or repeatedly over months

2.Each episode may last for hours or days

3.The pain begins immediately or within minutes of heavy lifting

4.Indomethacin is generally effective in treatment of exertional headache

Neuropathology

1.Need to rule out subarachnoid hemorrhage

2.Increased ICP

Laboratory Evaluation

1.CT to evaluate for blood

2.MRI to delineate any structural lesion

3.LP to rule out subarachnoid hemorrhage if there is neck stiffness

Sexual Headache

General Characteristics

1.Sexual activity may cause a tension-type headache or a severe sudden headache with orgasm

Clinical Manifestations (Orgasmic Headache)

1.The headache occurs with orgasm and may last for minutes to hours

2.The headache may occur several times and then abate

Neuropathology

1.Need to rule out hypertensive and aneurysmal bleeds, vascular malformation with bleeding and carotid artery dissection

2.Probable cause is increased intracranial pressure

3.Indomethacin is often effective therapy

Laboratory Evaluation

1.Lumbar puncture to rule out SAH on the first occasion

2.CT

3.MRI

Thunderclap Headache

General Characteristics

1.Definition:

a.Thunderclap headache is an acute and severe headache that has its maximum intensity at onset; it can be primary or secondary

Clinical Manifestations

1.Primary thunderclap headache is diagnosed when no underlying cause can be found

2.The headache is severe, may be diffuse or frontal and reaches maximum intensity immediately

3.It may be accompanied by nausea and vomiting and infrequently by hypertension

Neuropathology

1.Most thunderclap headaches are benign

2.Secondary forms include:

a.Migraine

b.Aneurysmal SAH

c.Perimesencephalic hemorrhage

d.Arteriovenous malformation

e.Dural arteriovenous fistula

f.Reversible vasoconstriction syndrome

g.Conditions that may present with or without thunderclap headache include:

i.Pituitary apoplexy

ii.Cervical artery dissection

iii.Cerebral venous thrombosis

iv.Posterior reversible leukoencephalopathy

v.Cocaine and / or adrenergic agents

3.Non-vascular causes of TCH include:

a.Colloid cyst of the IIIrd ventricle

b.Spontaneous intracranial hypotension

Laboratory Evaluation

1.CT to evaluate for blood

2.MRI to delineate a structural lesion

3.Judicious use of LP if there is any neck stiffness or neurologic sign

Headaches from Secreting Endocrine Tumors

General Characteristics

1.This type of headache most often occurs with tumors that either secrete vasoactive substances or cause accelerated hypertension

Clinical Manifestations

1.The headache is intense and throbbing

2.It is associated with flushing of the hands and face and on occasion with numbness and paresthesias of the fingers

3.Episodes occur upon awakening

Neuropathology

1.The endocrine tumors in which this type of headache has been reported are:

a.Mastocytosis:

i.Tissue is infiltrated by mast cells that secrete histamine, heparin and serotonin

b.Carcinoid tumors

c.Serotonin secreting tumors

d.Pancreatic islet tumors

e.Pheochromocytoma

Laboratory Evaluation

1.Serum analysis to delineate the secreted endocrine or neurotransmitter

Neuroimaging

1.MRI:

a.To rule out a structural lesion

b.MRA to evaluate for vasospasm

Migraine Headache

Overview

At present, both clinical and experimental evidence supports the hypothesis that the pathophysiology of migraine headache involves:

  1. Inherited alteration of brain excitability
  2. Intracranial arterial dilatation
  3. Recurrent activation and sensitization of the trigeminovascular system
  4. Structural and functional alterations in a subset of patients

Altered brain excitability has been derived from the study of sensory auras, ictal, and interictal hyper-responsiveness to visual, auditory, and olfactory stimuli in conjunction with decreased descending inhibition of pain by the conditioned pain system. There is activation and sensitization of the trigeminovascular system that is demonstrated by pain in specific radiations of the Vth nerve and central sensitization of the pain matrix that causes progressive cephalic and whole body dynamic and static mechanoallodynia during a migraine attack. Structural changes include subcortical white matter hyperintensities (consistent with small vessel vascular disease) and thickening of cortical areas involved in sensory processing. Cortical spreading depression has been proffered as the mechanism for migraine aura.

Migraine

General Characteristics

1.Migraine is frequently divided as to patients with aura and those without aura. The first has been termed classic migraine and the latter common migraine

2.The ratio of classic to common migraine is 1:5

Clinical Manifestations

1.Both types may have preceding changes in mood, appetite and fatigue

Migraine with Aura

1.The auras effect vision, motor and sensory function that are followed in a few minutes to hours by a hemicranial headache

2.Approximately 1/3 of patients suffer bilateral headache that is frequently associated with nausea, vomiting, photophobia and phonophobia

3.The headache usually lasts for hours or a day or two

4.Migraine without aura has an insidious onset over minutes to an hour of a hemicranial or generalized headache that may or may not be associated with nausea and vomiting

5.Both types have sensitivity to light, sounds and smells

6.Head movement exacerbates the headache in both types

7.A distinguishing feature of the headache is its throbbing quality. Most often one side of the head is affected more often than the other but the headache shifts sides in some attacks

8.In 60 to 80% of patients an inherited pattern is discerned although it is not as evident with common migraine

9.Onset is in adolescence to middle aged adults; children are involved; it is more common in women

10. The headache is often premenstrual in younger women; in approximately 15% of women they may be solely premenstrual (catamenial)

11. In 75-80% of pregnant patients, migraine decreases or ceases during the last two trimesters; rarely migraine may start in the first trimester

12. Migraine may exacerbate in post-menopausal women and has a variable response to estrogen

13. In many migraineurs, birth control pills are associated with both an increased frequency and severity of headaches

14. Triggers for migraine include specific foods, alcohol, a low barometric pressure, glare (particularly from computer screens), cervical nerve root irritation, caffeine withdrawal and strong sensory stimuli

15. Frequently has its onset with awakening but may occur at any time during the day

16. In the preceding day, patients may note a change of mood which may be either euphoria or depression without an obvious trigger

17. Hunger, drowsiness and yawning may be precedents

18. The onset of the aura may be abrupt if visual:

a.Unformed flashes of light, rarely multicolored (photopsia) that are followed by an enlarging blind spot with a shimmering edge that advances across the visual field at approximately 3mm/s

b.Fortification spectra (zig-zag lines)

c.Blurred vision with decreased visual acuity

d.Patients may be left with a scotomata often homonymous that supports a visual cortical origin

e.There are rare retinal changes or alterations in optic nerve vessels

19. Other focal neurologic phenomena include:

a.Numbness and tingling of the face, lips and hand (cheiro-oral pattern)

b.Cognitive dysfunction

c.Mild aphasia or dysarthria

d.Slight weakness of an extremity

e.Patients may have one or a few neurologic deficits which in general have the same pattern with each attack

f.The neurologic deficits last for approximately 30 minutes; characteristically weakness or numbness spreads from one part of the body to another slowly (minutes) in contradistinction to an embolus in which all areas are affected simultaneously or with a seizure in which the spread occurs over seconds

g.After the aura, patients experience a dull headache which occurs and evolves in intensity and becomes pulsatile, most often on the side of the affected cerebral hemisphere

h.Patients are relieved with rest in a recumbent posture in a dark room. Most are nauseated but rarely vomit

i.Between attacks patients with migraine are normal although many patients have motion sickness

j.Auras may occur without headaches and rarely precede or accompany the headache

k.Persistent migraine aura:

i.Persistent migraine aura without infarction lasts longer than 1 week. It consists of:

1.Persistent primary visual disturbance (PPVD)

2.Typical aura

l.Recently recognized auras include:

i.Brainstem localizing symptoms

ii.Lateralizing weakness

iii.Monocular visual loss

Hemiplegic Migraine

General Characteristics

1.Two forms are primary:

a.Familial hemiplegic migraine

b.Sporadic hemiplegic migraine

c.The two forms are phenotypically similar

d.Familial hemiplegic migraine-1 (FHM1) is caused by heterozygous mutation in the CACNA1A gene that maps to chromosome 19p13.13 and is autosomal dominant

e.FHM2 is caused by mutation in the ATP1A2 gene and FHM3 is caused by SCN1A gene; a fourth gene for FHM has been mapped to chromosome 1q31

f.Approximately 50% of patients have a defined locus, the most common of which is the CACNA1A gene that encodes the P/Q calcium channel α subunit; the ATP1A2 gene encodes the Na+/K+ -adenosine triphosphatase channel and the SCNA1 gene encodes the α-subunit of the sodium channel

Clinical Manifestations (FHM-1)

1.Recurrent headaches associated with hemiparesis or hemiplegia

2.May be associated with hemisensory numbness and tingling

3.Less frequently associated with speech disturbance

4.The neurologic deficit may precede or be associated with the deficit; the hemiparesis persist for days or weeks or resolves prior to the headache

5.Other migraine symptoms may occur during the episode

6.Disturbances of consciousness and rarely coma has been described

7.The neurologic deficit usually clears in minutes to hours

8.Less frequent neurologic deficits:

a.Cerebellar ataxia

b.Retinal degeneration

c.Nystagmus

9.Age of onset varies from 5 to 30 years of age

Neuropathology

1.Experimental evidence in a transgenic mouse model:

a.Demonstrates increased Cav 1.2 in cultured granule cells

b.Increased susceptibility to cortical spreading depression

2.Ischemic stroke

Laboratory Evaluation

1.Molecular genetic analysis to delineate the mutation

2.Spectroscopy:

a.FHM1 patients demonstrate:

i.Decreased N-acetyl aspartate (NAA)

ii.Increased myoinositol

iii.Decreased glutamate in the cerebellum

Neuroimaging

1.MRI:

a.In patients with cerebellar signs:

i.Less gray matter and less white matter with more CSF in the cerebellum

Alternating Hemiplegia of Childhood

General Characteristics

1.Alternating hemiplegia of childhood-1 (AHC1) is caused by heterozygous mutation in the ATP1A2gene that is autosomal dominant and maps to chromosome 1q23.2

2.It overlaps with familial hemiplegic migraine and GLUT1 deficiency

Clinical Manifestations

1.The onset is before 18 months of age

2.It is chronically progressive

3.Is associated with headache and vomiting

4.Loss of consciousness

5.Autonomic dysfunction

6.Cognitive dysfunction

7.Paroxysmal ocular palsy

8.Choreoathetosis

9.The expanding spectrum of phenotypes with ATP1A3 mutations include:

a.Alternating hemiplegia of childhood

b.Rapid-onset dystonia Parkinsonism and CAPOS

10. Triggering episodes are environmental stress, water exposure, physical activity and possibly specific foods

11. Episodic manifestations cease with sleep and may return shortly after awakening

Neuropathology

1.The α1 isoform for the NA (+)/K(+) ATPase is ubiquitously expressed in the adult CNS whereas α2 isoform is expressed in neurons

2.The α1 and α3 isoforms of the Na+/K+ ATPases restore neuronal membrane potential after depolarization and maintain neuronal excitability

3.The α3 isoform, putatively is important in the re-uptake of neurotransmitters

Laboratory Evaluation

1.Molecular genetic analysis to delineate the mutation in the ATPase gene

2.SPECT:

a.Has demonstrated progressive decrease in cerebral perfusion during attacks

Differential Diagnoses

1.Moyamoya disease

2.MELAS

3.Mutations in CACN1A, ATP1A2 and SCNA1 genes

Migraine with Brainstem Aura (Basilar Artery Migraine)

General Characteristics

1.Most often seen in young women and adolescent girls but is increasingly recognized in all age groups in both males and females with 3:1 ratio of female to males

2.Members of one family have been described with a mutation in the ATP1A2 gene

Clinical Manifestations

1.Patients have:

a.Dysarthria

b.Vertigo

c.Tinnitus

d.Hypacusis

e.Diplopia

f.Ataxia

g.Decreased level of consciousness

h.No motor weakness

2.At least one aura symptom that spreads gradually over 5 minutes or more and / or two or more symptoms occur in succession:

a.Each individual aura symptom lasts 5 to 60 minutes

b.At least one aura symptom is unilateral

c.The aura is accompanied or followed within 60 minutes by headache

Neuropathology

1.The headache and signs and symptoms originate from the brainstem and are neuronal in origin

2.If there is motor weakness the disorder is familial hemiplegic or sporadic hemiplegic migraine

Neuroimaging

1.MRI / MRA:

a.To rule out vascular or other structural lesions

Laboratory Evaluation

1.EEG:

a.To delineate a possible seizure disorder

Retinal Migraine

General Characteristics

1.Retinal migraine is a monocular visual alteration that causes scintillations, scotomas or blindness

2.Typical migraine with aura involves the cerebral cortex and is associated with binocular visual phenomena

3.Retinal migraine affects approximately 1 out of every 200 patients who suffer migraines

4.Approximately 30% of patients have a past history of nonretinal migraine with or without aura. 25% have a relative with retinal migraine

Clinical Manifestations

1.A fully reversible monocular positive and / or negative scintillating scotomata or blindness

2.Monocular visual field defect that occurs during an attack

3.Migraine headache without aura that begins during the visual symptoms or follows them within 60 minutes

4.Normal ophthalmological examination between attacks

5.Patients have been described who have visual symptoms without headaches and have permanent visual scotomas (rare)

6.Negative symptoms:

a.Black, grey, white or shaded areas that vary in size that can appear abruptly or gradually progress inwardly from the peripheral visual field

b.Positive symptoms:

i.Flashing lights or scintillating scotomata

c.Symptoms are always monocular and typically last 5-20 minutes; they may occur several times per day

Neuropathology

1.Direct ophthalmoscopic evaluation during episodes have demonstrated retinal artery attenuation; rarely retinal hemorrhages have been described

2.Retinal nerve fiber analysis:

a.Mean retinal nerve fiber layer (RNFL) thickness for nasal and nasal inferior quadrants were seen to be significantly thinner than controls in patients with migraine

b.Mean choroid thickness at the fovea was also thinner in migraineurs but the macular thickness was equal to control subjects

3.A putative mechanism for retinal migraine is deficient retinal and choroidal blood flow due to activation of the trigeminovascular system and consequent release of vasoactive neuropeptides onto the arterioles that supply the retina and choroid

Laboratory Evaluation

1.CBC, sedimentation rate

2.Coagulation panel

3.EKG

4.Doppler ultrasonography of the carotid

5.Transthoracic echocardiogram

Recurrent Painful Ophthalmoplegic Neuropathy (RPON) (Ophthalmoplegic Migraine)

General Characteristics

1.Most patients have a history of migraine and the headache during the episode has features of migraine

Clinical Manifestations

1.Migrainous-type headache that accompanies or is followed by weakness of cranial nerve III, IV or VI

2.There is often a latent period of up to few days from the onset of the headache to the onset of the ophthalmoplegia

3.A transient third-nerve palsy with ptosis with or without pupillary involvement is usual. Much less frequently, the VIth nerve is involved. It is very rare in adults

4.The ocular paresis may outlast the headache for days or weeks

5.After multiple attacks there may be slight mydriasis and oculomotor paresis

Neuropathology

1.Not ascertained

Laboratory Evaluation

1.LP:

a.To rule out lymphoma, leukemia or other infiltrating pathologies

2.Detailed medical evaluation to rule out the usual causes of IIIrd nerve palsy

Neuroimaging

1.MRI / MRA:

a.Has demonstrated gadolinium enhancement of the cisternal component of the affected nerve

b.MRA:

i.To rule out a posterior communicating artery aneurysm

Differential diagnosis of painful ophthalmoplegia

1.Tolosa-Hunt syndrome

2.Sphenoid sinus mucocele

3.Cavernous sinus thrombosis

4.Sellar and parasellar tumors

5.Sinus infections

Migraine and Stroke

General Characteristics

1.Meta-analyses have consistently demonstrated an association between migraine and stroke. It is particularly well delineated for ischemic stroke and for migraine with aura

2.Neuroimaging studies utilizing MRI have demonstrated:

a.Migraineurs have an increased incidence of subclinical brain infarction in the posterior circulation

b.There is an increased incidence of white matter hyperintensities (putatively arteriolar ischemia) in female patients

3.A controversial relationship exists between patients with migraine and PFO

4.There is also controversy surrounding the relationship of migraine with cervical artery dissection

Clinical Manifestations

1.Case-control studies have shown that ischemic stroke risk parallels an increase in frequency of migraine attacks; possibly patients with greater than 13 attacks / year have a 10-fold higher risk of stroke (patients were 20-44 years of age)

2.Women’s Health study (5,130 women with migraine):

a.Had a higher risk ratio for stroke if they suffered 1 attack with aura / week

3.Migrainous infarction:

a.Occurs in a patient with migrainous aura which is typical of previous attacks with one or more aura symptoms that lasts for >60 minutes

b.Neuroimaging demonstrates the ischemic infarction in the appropriate area

c.Possible prevalence of migrainous infarction is between 0.5 and 1.5% of all ischemic strokes; possibly 10 to 14% of ischemic stroke in young patients in the posterior circulation. Young women with migraine with aura are primarily affected

4.A cross-sectional Dutch study of adults aged 30-60 revealed:

a.High white matter lesions occur in women with migraine which increase with attack frequency but are equal in patients with or without aura

b.Longitudinal studies have demonstrated that migraine sufferers are not at increased risk of cognitive impairment from their white matter lesion load

5.Silent-infarct-like lesions:

a.Are more common in migraine patients than controls; the association is greater in patients with migraine and aura than patients without aura

b.Approximately 90% of the infratentorial infarct-like lesions were in a vascular border zone location in the cerebellum

6.Migraine and hemorrhagic stroke:

a.There is an association of women that have migraine with aura and hemorrhagic stroke at four patients per 10,000 females

7.Migraine and cryptogenic TIA and stroke:

a.In a population-based study, cryptogenic TIA and ischemic stroke have an association with previous migraine. The association is strongest in the patients >65 years of age

b.The risk of ischemic stroke increases with migraine attack frequency, migraine with aura and in young women

c.Most ischemic events that occur in patients with migraine happen many years after their first attack which suggest shared risk factors on a genetic basis shared with both conditions

8.Migraine and patent foramen ovale (PFO):

a.Patent foramen ovale has been documented in 40-60% of patients with migraine and aura and only 25% of the normal population

b.Possibly a 2.5 increased risk of stroke in patients with PFO and migraine

c.Patients with a PFO have a fivefold higher risk of having migraine

Migraine and Stroke from a Common Cause

1.Several vascular disorders are associated with a high risk of both migraine (usually with aura) and stroke:

a.Arteriovenous malformations:

i.The side of the aura is contralateral and the headache is ipsilesional to the AVM

ii.Migraine with aura may be associated with Sturge-Weber syndrome (leptomeningeal angiomatosis)

2.Syndromes associated with migraine include:

a.CADASIL

b.MELAS

c.HERNS (cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy and stroke)

3.General vascular conditions that may occur with migraine with aura and ischemic stroke include:

a.PFO and mitral valve prolapse

b.Essential thrombocythemia, thrombocytopenia, leukemia

c.SLE and antiphospholipid syndrome

4.Monogenic Migraine:

a.The mutations in three well-described genes in familial hemiplegic migraine at the present are the only monogenic cause of migraine. They include:

i.FHM 1:

1.Caused by mutation in the CACN1A gene that maps to chromosome 19p13

2.Encodes the pore forming α1 subunit of the cav2.1 channel (P/Q type)

ii.FHM 2:

1.Caused by mutations in the ATP1A2 gene that maps to chromosome 1q23

2.Encodes the α2 subunit of sodium-potassium pump ATPases

iii.FHM 3:

1.Caused by mutation of the SCN1A gene that maps to chromosome 2q24

2.Encodes the α1 subunit of the neuronal voltage-gated sodium channel Nav1.1

b.A putative mechanism for the association of these mutations with migraine is that they increase the glutamate and potassium concentration in the synaptic cleft that may increase cortical spreading depression (CSD). There is solid support for CSD engaging the trigeminovascular system that has been shown to be a major component of migraine pathogenesis

Migraine Susceptibility Genes and Cerebral Ischemia

1.Genetic variants putatively associated with migraine include:

a.Neurotransmitter pathway genes:

i.Dopamine D2 receptor (DRD2)

ii.Human serotonin transporter (HSERT)

iii.Catechol-o-methyltransferase (COMT) and dopamine b-hydroxylase (DBH)

b.Genes involved in vascular physiology:

i.5, 10-methylenetetrahydrofolate reductase (MTHFR)

ii.Angiotensin1-converting enzyme (ACE)

iii.Endothelin type A (ETA) receptor

c.Genes involved in hormone physiology:

i.Estrogen receptor 1(ESR1)

ii.Progesterone receptor (PGR)

iii.Androgen receptor (AR)

The C6771 polymorphism of the MTHFR gene may be a link between migraine and ischemic stroke due to its effect on homocysteine levels. Low dietary folate in patients with migraine and this MTHFR polymorphism have higher homocysteine levels which has been implicated in endothelial dysfunction

Neuropathology

1.Possible mechanisms for ischemic stroke in patients with migraine:

a.Hemodynamic factors:

i.Cortical spreading depression induces an early increase in cerebral blood flow that is followed by oligemia that causes an increase in vascular resistance. This is manifested by arterial constriction particularly in the posterior circulation

ii.The reduced blood flow may be due to increased vascular resistance rather than active vasoconstriction; neutrally mediated vasodilatation may cause low flow in major intracranial vessels during migraine auras

2.Inflammation:

a.Cortical spreading depression causes vasodilatation of extraparenchymal vessels that induces the release of vasoactive peptides (CGRP and substance P), activates pro-inflammatory cytokines and upregulates adhesion molecules and nitric oxide synthase all of which are prothrombotic

b.Vasospasm was previously thought to be the mechanism for migraine aura from the release of vasoactive agents such as serotonin or endothelin. There is documented evidence that this mechanism may be involved in rare instances of migrainous infarction

3.Coagulation cascades:

a.During a migraine attack there may be activation of thrombotic factors:

i.Platelets and mast cells may release platelet activating factor which induces platelet aggregation

ii.PAF is a component in the release of von Willebrand factor and the activation of the platelet II B/IIIa receptor that is essential for binding fibrinogen

iii.The activation of these coagulation factors occur during migraine attacks

4.Endothelial Dysfunction:

a.Endothelial dysfunction is manifested by:

i.A reduction of the bioavailability of vasodilators (nitric oxide)

ii.An increase of endothelial derived contracting molecules which impairs blood vessel reactivity in both conducting vessels and the microcirculation

iii.Decreased endothelial activation which is characterized by a procoagulant, proinflammatory and proliferative state

iv.A major component of endothelial dysfunction is oxidative stress the markers of which are higher in migraineurs both during attacks and in the interictal period

v.Reduced endothelial repair capacity in migraineurs has been demonstrated by:

1.Decreased levels of endothelial progenitor cells (measured by flow cytometry) predominantly in patients with aura

2.Decreased migratory capacity of endothelial cells

3.Increased markers of senescence

Neuroimaging

1.MRI:

a.Most common lesions are white matter hyperintensities in the deep or periventricular white matter on T2-weighted or Fluid Attenuated Inversion Recovery (FLAIR) sequences

b.The WMH are typically multiple, small and punctate

c.Perfusion weighted MRI deficits in migraineurs’ aura are not limited to a single vascular territory, may be bilateral in approximately 20-25% of patients and have a posterior circulation predominance

d.Strokes with migraine have predominance in the posterior circulation

e.Hypoperfusion in a watershed distribution may be seen in the cerebellar vasculature

Migraine with CSF Pleocytosis

General Characteristics

1.A syndrome of transient headache and neurological deficits with CSF lymphocytosis

2.Is a diagnosis of exclusion

Clinical Manifestations

1.Transient neurologic deficits that last hours

2.Migraine-like headaches

3.Rare fever without stiff neck

4.Transient deficits are primarily sensorimotor and aphasia

5.Small percentage of patients have visual symptomatology

6.Some patients have had a history of prior migraine and others a viral-like illness during the preceding 3 weeks

Neuropathology

1.Possibly aseptic meningitis with an associated migraine headache

2.Possible human herpes virus type 7 (HH-7) infection

Laboratory Evaluation

1.CSF:

a.The CSF may have between 10 to several hundred lymphocytes

b.The protein is mildly to moderately elevated

Neuroimaging

1.MRI:

a.Normal

Menstrual (Catamenial Migraine) Migraine

General Characteristics

1.Definition

a.Attacks of migraine that occur regularly in at least 2 of 3 consecutive menstrual cycles and occur exclusively on day 1 to 2 of menstruation but may range 2 days before to 3 days after with the first day of menstruation as day one

2.The two subtypes are:

a.Pure menstrual migraine

b.Menstrually related migraine

Clinical Manifestations

1.Pure menstrual migraine there are no aura and no migraine other than that which occurs with the menstrual cycle

2.Menstrually related migraine occurs in 2 of 3 consecutive menstrual cycles primarily on days 1 and 2 of menstruation but may also occur outside of the menstrual cycle

Neuropathology

1.“Estrogen withdrawal” migraine-triggering hypothesis posits the cause of the headache is lack of estrogen in the late luteal phase

2.Recent studies of estrogen levels in patients with migraine demonstrate:

a.There is no significant difference in estrogen peak levels or mean daily levels of estrogen between migraineurs and controls

b.There is a significant difference in the rate of estrogen decline in the late luteal phase

c.There is no difference in the rate of decline in the periovulatory phase

d.In patients with migraine, the rate of estrogen decline cannot distinguish cycles with and without an acute headache

Neuroimaging

1.MRI or CT to exclude any structural lesion otherwise normal

Status Migrainosus

General Characteristics

1.Status migrainosus is a debilitating migraine attack that lasts for longer than 72 hours

Clinical Manifestations

1.Migraine attacks may increase in frequency for several months often up to 3 to 4 / week:

a.The scalp may become tender on the side of the headache

b.The pain is initially unilateral and later generalizes

c.The pain may be throbbing but has an associated ache

d.There is a history of migraine

e.The headache is debilitating

Neuropathology

1.Rarely this form of headache is initiated by head trauma or viral infection

2.The headache may be perpetuated by medication rebound

Laboratory Evaluation

1.Rule out narcotic or other medication overuse

Neuroimaging

1.MRI:

a.To rule out a structural lesion

Vestibular Migraine

General Characteristics

1.Vestibular migraine is the most common cause of episodic vertigo in both adults and children

2.The diagnosis depends on the patient’s history as there are no clinically useful biomarkers

3.Vestibular migraine has a lifetime prevalence of approximately 1% and a 1-year prevalence of 0.9% in the general population

4.It occurs 1.5 to 5 times more often in women than men

5.Migraine-related syndromes are the most common cause of vertigo and dizziness in children

Clinical Manifestations

1.Vertigo in patients with migraine may manifest as:

a.Spontaneous vertigo in 21 to 83% of patients

b.Positional vertigo and dizziness in 17 to 65% of patients

c.Head motion intolerance in 31 to 77% of patients

2.Vertigo may be induced by moving visual objects

3.Additional symptoms:

a.Unsteadiness

b.Balance problems

4.Attack duration may vary from seconds to days; diagnostic criteria for vestibular migraine require a 5 min minimum duration

5.Vertigo can precede or occur during or after the headache

6.A small group of patients have isolated vertigo attacks that alternate with migraine

7.Approximately 40% of patients have tinnitus, hearing disturbances and aural pressure

8.Neurological examination between episodes is usually normal

9.Canal paresis and bilateral vestibular failure occur in 8 to 22% and 11% respectively

10. During attacks patients may demonstrate:

a.Central vestibular ocular motor abnormalities

b.Gaze induced nystagmus

c.Deficiencies of saccadic pursuit

d.Central positional nystagmus

11. Interictal ocular motor deficits increase over time

12. During acute attacks:

a.Central vestibular dysfunction occurs in 50% of patients and peripheral dysfunction in 15%

b.Hearing is not affected and the site of pathology may not be determined in 35% of patients

Neuropathology

1.Interactions of vestibular and pain pathways at several levels i.e. from the inner ear to the thalamus and cortex

2.fMRI study:

a.Increased activation of the temporo-parietal-insular areas and bilateral thalami during an attack (2 patients):

i.Possible activation of the vestibulo-thalamo-cortical pathways

b.fMRI of vestibulo migraine patients during cold caloric stimulation

i.Increased thalamic activation

3.FDG-PET study:

a.An increase of metabolic activity was demonstrated bilaterally in the ventral-anterior thalamus during an attack

4.Voxel-based morphometric MRI study demonstrated:

a.Reduction of gray matter volume in the superior, inferior and middle temporal gyri

b.Decreased tissue mid-cingulate, dorsolateral, prefrontal, insula, parietal and occipital cortices

Laboratory Evaluation

1.Posturography, vestibular evoked myogenic potentials (VEMPs) and evaluation of the subjective visual vertical (SVV) have been inconsistent

2.Inner ear MRI study:

a.Utilizing gadolinium contrast transtympanically demonstrated cochlear and vestibular endolymphatic hydrops in 4/19 vestibular migraine patients

Differential Diagnosis of Vestibular Migraine

1.Meniere’s disease

2.Benign paroxysmal positional vertigo (BPPV) in those patients with positional vertigo attacks

3.Anxiety associated migraine with vestibular disorders MARD (migraine anxiety-related dizziness)

Cluster Headache

General Characteristics

1.Cluster headache (CH) is the most common of the autonomic cephalalgias

2.It has a prevalence of 0.1% in the general population and is more frequent in males with a ratio of 2.5 to 7.1:1

3.The lifetime incidence of CH is 124 patients / 100,000 of the population

Clinical Manifestations

1.CH is most frequently seen in adult men between 20 to 50 years of age

2.It is severe unilateral pain typically retro-orbital and fronto-temporal that is associated with:

a.Conjunctival injection

b.Tearing

c.Eyelid edema

d.Miosis

e.Ptosis

f.Nasal congestion

g.Rhinorrhea

h.Facial hyperhidrosis

3.The pain around the eye is felt as deep, extremely intense and is non-throbbing. It may radiate to the forehead, temple, cheek, and less frequently to the ear, occiput, and neck.

4.It occurs typically at night between 1 to 2 hours after sleep onset or several times during the night on several or more consecutive days

5.Less often the headache occurs during the day (up to eight times / day) or during the early evening. There is no aura or vomiting.

6.The headache may occur with the same periodicity each night for periods of weeks; it may cease and not recur for months or rarely for years. In a few patients it may become chronic

7.The autonomic symptoms last for approximately 45 minutes (range of 15 to 180 minutes)

8.There is frequent slight ptosis that may become permanent

9.During an attack the temporal artery on the homolateral side and the scalp may demonstrate mechanical hyperalgesia

10. Few patients can lay quietly during an attack. Most hold their head, sit in a chair or pace. The headache may cease abruptly or back away gradually

11. Usually the same orbit is involved during a particular cluster or in future attacks

Neuropathology

1.The pain of CH is generally thought to occur from activation of the trigeminovascular system:

a.The activation occurs both in the brainstem and in cranio-facial sympathetic neurons that cause the autonomic signs and symptoms

b.It is posited that retrograde activation of trigeminal fibers releases vasoactive neuropeptides, the most important of which is calcitonin gene related peptide (CGRP) that innervate cranial blood vessels. Upon release, CGRP induces intracranial vasodilatation and can cause sterile neurogenic inflammation that consists of edema and protein leakage into the dura. Nociceptive activation from this sterile inflammation are transmitted from the trigeminal ganglion to the trigeminal cervical complex (TCC) and projected to the thalamus and cortex. Substance P, another vasoactive neuropeptide, may also be involved in this process. Both oxygen and sumatriptans lower CGRP levels.

c.Activation of the superior salivatory nucleus may cause the cranial autonomic signs and symptoms of CH:

i.Its parasympathetic outflow is transmitted primarily via the sphenopalatine ganglion

ii.It causes the tearing, conjunctival injection, nasal congestion, and rhinorrhea seen during attacks. These effects are due to the release of acetylcholine and vasoactive intestinal peptide (VIP). During CH attacks CGRP and VIP levels are increased which supports the hypothesis that the trigeminal-parasympathetic reflex is a component of CH pathology.

iii.It is posited that the Vth nerve concomitantly activates the trigeminovascular pain system and the superior salivatory nucleus. At present, it is not known what causes the initial activation of the trigeminovascular system or the trigeminal-parasympathetic reflex.

2.There is evidence that CH has a primary central origin initiated from the hypothalamus:

a.Support for a hypothalamic role is:

i.The circadian periodicity of attacks and that the clusters most often occur during the spring and fall.

ii.There are direct connections from the locus coeruleus and the dorsal raphe nuclei to the hypothalamus and alteration of these monoaminergic nuclei may be a component of hypothalamic regulation

iii.Direct connections from the posterior hypothalamus to the pain TCC (trigeminal) complex have also been demonstrated

iv.Several hypothalamic nuclei are important for pain perception

v.Central sensitization of pain projecting neurons and the pain matrix may play a role in CH

vi.Stimulation of the posterior hypothalamus is effective in controlling CH in some patients

vii.During attacks, the pain matrix demonstrates increased blood flow.

b.These areas are:

i.Anterior cingulate gyrus

ii.Prefrontal cortex

iii.Thalamus

iv.Periaqueductal grey

v.Basal ganglia

vi.Insula

vii.Cerebellum

c.Imaging studies have also demonstrated alterations in the diffuse nociceptive inhibitory complex (DNIC) system in patients with CH

Laboratory Evaluation

1.Cluster headache is a clinical diagnosis; there are no biomarkers

Trigeminal Autonomic Cephalalgias

Overview

Trigeminal autonomic cephalalgias (TAC) are classified as a group due to a common pathophysiology based on activation of the trigeminovascular system, the trigemino parasympathetic reflex, and dysregulation of circadian rhythm. The clinical pain syndromes are in the trigeminal distribution and all have autonomic activation. Clinical features among the syndromes overlap but treatment responses are relatively specific which helps in the diagnosis. TACs may be an expression of an underlying pathologic process.

Paroxysmal Hemicrania

General Characteristics

1.The prevalence of paroxysmal hemicranias is approximately 2-20 per 100,000 of the population

2.There is no male or female predominance

Clinical Manifestations

1.The mean age at onset is between 31-41 years of age; it has been reported in children and in adults up to 81 years of age

2.Approximately 20% of paroxysmal hemicranias are episodic

3.The patient suffers severe orbital or periorbital pain that is unilateral and rarely may become bilateral

4.Pain may also be felt in temporal, periauricular, maxillary and infrequently in occipital areas

5.Pain radiates commonly to the shoulder, neck and arm

6.Severe pain may radiate across the midline

7.Most attacks do not change sides

8.Attacks usually last from 2-20 minutes but have been described for as long as an hour

9.The onset of pain is abrupt and reaches maximum intensity in less than 5 minutes; its quality is throbbing, lancinating or boring

10. It is associated with some of the ipsilateral autonomic phenomena that include:

a.Conjunctival erythema and injection with lacrimation

b.Nasal congestion and rhinorrhea

c.Eyelid edema

d.Forehead and facial hyperhidrosis

e.Miosis and slight ptosis

11. More than 5 attacks per day; a usual frequency may be between 8to 30 episodes over a 24 hour period:

a.One to 5 attacks per 24 hours have been reported

b.Approximately 30% of patients report REM-related nocturnal attacks that awaken patients

12. An absolute response to indomethacin therapy

13. Autonomic phenomena may be seen bilaterally but are worse on the symptomatic side

14. Secondary paroxysmal hemicrania has been described with:

a.Malignant and benign tumors

b.Systemic disease

Neuropathology

1.Activation of the trigeminovascular system has been posited to cause the pain

2.Activation of the trigeminoparasympathetic reflex initiates the autonomic phenomena

Neuroimaging

1.MRI:

a.Imaging of the head to rule out secondary causes of paroxysmal hemicrania

b.Medical evaluation to evaluate for underlying systemic disease

Short-lasting, Unilateral, Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT)

General Characteristics

1.The syndrome in many ways is similar to trigeminal neuralgia and some believe it to be a variant

Clinical Manifestations

1.A unilateral ocular and periocular pain, that is less severe than trigeminal neuralgia and may also involve the temporal, auricular and occipital areas

2.The quality of the pain is lancinating, pulsating and infrequently stabbing or burning

3.It rarely spreads across the midline or changes sides

4.The pain typically lasts from 5 to 240 seconds (mean of 1 minute)

5.Longer-lasting attacks of 250, 600 seconds and to 2-3 hours have been described

6.Rarely SUNCT status pain can last for 1-3 days (occurring most of each day)

7.Low-grade background pain may be a concomitant of the intermittent exacerbations

8.The patterns of attacks are:

a.Single clonic attacks

b.Groups of stabs that occur with a series of attacks

c.“Sawtooth” pattern with stabbing pains that last for minutes

9.The frequency of attacks is from 3 to 200 daily which varies widely both to season and diurnally:

a.The average is 28/day

b.Attacks are bimodal occurring in the morning and late afternoon

c.<2% of attacks occur at night

10. Mechanical stimuli in trigeminal areas can trigger pain. There is a short latency from the stimulus to pain onset

11. Neck movement, out of the trigeminal territory may also trigger pain; alcohol does not exacerbate pain

12. After a painful episode there is no refractory period which differentiates SUNCT from trigeminal neuralgia

13. Ipsilateral conjunctival injection and lacrimation are concurrent with the onset of pain

14. Nasal congestion and rhinorrhea may be similar but hyperhidrosis is less frequent and may be subclinical

Neuropathology

1.Activation of the trigeminovascular system has been posited to cause the pain

2.Activation of the trigeminoparasympathetic reflex initiates the autonomic phenomena

3.Secondary SUNCT has been reported with:

a.Pontine and brainstem infarction

b.Cerebellopontine arteriovenous malformations

c.Cerebellopontine astrocytomas, tumors and cysts

d.Brainstem cavernous hemangioma

e.Tumor of the cavernous sinus

f.Extraorbital cystic mass

g.Vertebral artery dissection

h.Neurofibromatosis

i.Eye trauma

j.In association with HIV and osteogenesis imperfect

k.5% of pituitary tumor patients may have SUNCT

Laboratory Evaluation

l.MRI / CT to rule out secondary causes of SUNCT

Short-lasting Unilateral Neuralgiform Headache Attacks with Cranial Autonomic Features (SUNA)

General Characteristics

1.Similar to SUNCT

2.SUNCT / SUNA may be as common as paroxysmal hemicranias

Clinical Manifestations

1.SUNA may be differentiated from SUNCT by:

a.SUNA may be associated with any autonomic sign

b.Attack duration may be up to 10 minutes

Neuropathology

1.Activation of the trigeminovascular system causes the pain and activation of the trigeminoparasympathetic system; the autonomic phenomena

2.Secondary causes of SUNA are similar to those of SUNCT and include vascular disease, tumors, and malformations of the brainstem and posterior fossa

Laboratory Evaluation

1.MRI / CT to rule out secondary causes

Hemicrania Continua

General Characteristics

1.The female to male ratio is 2.8:1

Clinical Manifestations

1.The headache is unilateral and lasts > than 3 months

2.Pain is localized frontally and in temporal regions as well as periorbitally

3.Rarely the pain can alternate sides. A few bilateral patients have been reported

4.The pain occurs daily and is continuous

5.Pain characteristics:

a.The pain is of moderate severity with a VAS of 4.7

b.74% of patients report fluctuations in pain severity

c.40% of patients have disabling exacerbations with severe pain (VAS 9.3) which may last for 30 minutes for 10 hours and up to 2-5 days

d.During the exacerbations hemicrania continua is very similar to severe migraine

e.Some pain is described as jabs and jolts

f.Approximately 20% of patients describe a foreign body feeling in the eye that may precede or accompany the headache

g.Patients describe throbbing as the severity of the headache increases

h.During exacerbations patients get:

i.Conjunctival injection with lacrimation

ii.Nasal congestion and rhinorrhea

iii.Miosis and ptosis

i.The remitting form of hemicranias continua is characterized by:

i.Headache that lasts for a few days that is followed by a remission from 2-15 days

ii.This pattern is present in approximately 50% of patients; the other 50% have continuous pain from the onset of the headache

iii.Approximately 1/3 of remitting patients evolve to the chronic form in a mean of 7.8 years

j.Nocturnal attacks are seen in approximately 50% of patients

k.Triggers that exacerbate the pain are:

i.Menses

ii.Postural changes

iii.Strong smells

iv.Stress

v.Alcohol (some patients)

l.Autonomic signs are minimal except during exacerbations that suggest that autonomic activation is dependent on pain severity. The most common autonomic phenomena are photophobia, nausea, conjunctival injection, phonophobia, and tearing.

m.Hemicrania continua may be associated with aura

n.Approximately 15-18% of patients report nasal stuffiness or rhinorrhea

o.There is no significant age difference between those with a remitting onset (mean of 32 years) and those with a continuous onset (34 years)

Neuropathology

1.The pattern of activation links the pathophysiology of hemicrania continua to both cluster headache and migraine

2.Secondary hemicrania continua:

a.Medication abuse

b.Mesenchymal tumor of the sphenoid bone

c.Mild to moderate head trauma

Neuroimaging

1.fMRI:

a.Activation of the posterior hypothalamus and the dorsal rostral pons

2.MRI /CT of the head to rule out secondary causes of HC otherwise normal

Differential Diagnosis of TAC

1.Orofacial pain:

a.Pain referral patterns with TACs may involve intraoral and non-trigeminal distributions:

i.Cluster headache and paroxysmal hemicrania may simulate dental pain

2.Regional tumors:

a.May occur in 0.8-5% of facial pain patients

3.Trigeminal neuralgia:

a.Lacrimation may be associated with involvement of any division

b.SUNCT / SUNA and cluster may be misdiagnosed

c.SUNCT:

i.Does not respond to sodium channel blockers

ii.Multiple and obvious autonomic signs

iii.Has no refractory period

iv.Cluster-tic syndrome:

1.The combination of cluster headache and trigeminal neuralgia:

a.Neck movements may be a trigger in approximately 40% of patients

b.A form of cluster-tic syndrome has very short attacks that are difficult to distinguish between SUNCT and paroxysmal hemicranias

2.CPH-tic syndrome and mixed attacks are difficult to discriminate from SUNCT

Major Differential Points that Distinguish TACs

1.Attack duration and frequency:

a.Unilateral headache with ipsilateral autonomic signs of less than 2 minutes is most likely SUNCT:

i.Trigeminal neuralgia with associated autonomic signs is also possible. It would be favored if there is a refractory period

ii.SUNA attacks are longer, lasting in general for minutes (overlap with short paroxysmal hemicranias)

b.Headaches that last for more than 4 hours accompanied by autonomic symptomatology are usually migraine or one of its variants. The diagnosis is more secure if the upper third of the head is involved:

i.Rarely cluster headache may last for up to 48 hours

ii.There are similarities between long lasting cluster headache and migraine

iii.The pain of cluster headache is more severe than migraine and resembles that of trigeminal neuralgia or SUNCT

iv.Migraine attacks may occur in clusters and have a cyclical pattern

v.Circadian pattern or cluster attacks may occur with hemicrania continua and paroxysmal hemicrania. The majority of patients with paroxysmal hemicrania have a chronic rather than episodic pattern that distinguishes them from the usual episodic circadian cluster headache

Coronal Linear Headache

General Characteristics

1.Linear headache is a new form of headache or a variant of migraine

Clinical Manifestations

1.Paroxysmal or chronic fixed headache or head pain

2.Restricted in a linear trajectory that connects the occiput or occipitocervical area to the ipsilateral nasion or forehead

3.A subgroup of patients have associated nausea, vomiting and dizziness

4.Most attacks are spontaneous but triggers include noise, stress, lack of sleep or rest after physical exertion

5.Paroxysms of pain may last for hours to days in the majority of patients; some patient attacks are only of a few minute duration

6.The pain is of moderate intensity and is described as pulsating or pressure-like

7.The frequency of attacks varies from one attack / day to 5 or 6 attacks per year; there are long term remissions in some patients

8.In twenty patients that have been described, the age at onset ranges from 20-73 years of age

9.There is a female predominance of 1:5:1

10. The width of the painful area is between 5 and 10 mm; the linear trajectory is parallel to the sagittal plane of the head

Neuropathology

1.The pathogenesis is unknown but a migraine mechanism has been posited:

a.A linear area of meningeal nociceptors parallel to the superior sagittal sinus is activated by cortical spreading depression (CSD) that activates the trigeminovascular pathway as occurs with migraine

Laboratory Evaluation

1.MRI of the head and cervical spine to rule out an alternate diagnosis

Epicrania Fugax

General Characteristics

1.Epicrania fugax is a recently described primary headache

Clinical Manifestations

2.Paroxysmal, short lasting, 1-10 seconds, of moderate pain

3.Is initiated in a specific area of the posterior scalp and rapidly radiates anteriorly in a linear trajectory to the forehead, eye or nose

4.The quality of the pain is moving, stabbing, electric-like or lancinating

5.The pattern of movement may be zig-zag which may cross the midline

6.At the cessation of the attack, patients may have ipsilateral autonomic signs that include lacrimation, conjunctival injection or rhinorrhea

7.Patients are usually symptom free between attacks

8.The mean age of onset is 49 years (range 34-75 years)

Neuropathology

1.The pathophysiology is not known

2.Probable activation of the trigeminovascular system that causes the pain and the trigeminoparasympathetic reflex that causes the autonomic phenomena

Laboratory Evaluation

1.MRI of the head and cervical spine to rule out structural lesions

Cervicogenic Headache

General Characteristics

1.The incidence and prevalence of cervicogenic headache is not clear. It has been estimated that approximately 4% of the population may at some point suffer cervicogenic headache

2.It may comprise 0.4-15% of the headache population and possibly 15-20% of all chronic and recurrent headaches

3.Possibly women are affected more frequently than men

Clinical Manifestations

1.Unilateral head pain primarily in the parietal and frontal areas that is initiated occipitally; a particular radiation to the brow

2.Provoked by unphysiologic neck positions; limitation of motion of the neck to all planes but particularly to extension

3.Primarily C5, C6, C7 upper arm radiations; no radiation into the hand; atrophy of the deltoid cap and biceps; frequently associated inverted radial reflex

4.Diffuse arm pain primarily C5-C7 distribution

5.Pain is initiated in the occipital area and radiates anteriorly

6.The pain is most often a dull ache

Neuropathology

1.Facet joints, cervical muscles, intervertebral discs, nerve roots, the vertebral arteries and uncovertebral joints have all been associated with cervical headaches

2.The greater, lesser and third occipital nerves cause the headache as does cervical plexus injury from whiplash or surgical procedures

3.Cervicogenic related structures are supplied by the upper cervical nerve roots that relay sensory information into the spinal tract of the trigeminal nucleus that is the anatomical basis for pain radiations to frontal and orbital areas. Recent evidence from anesthetic blocks support an association of cervical headache pain from mid-cervical segments

4.The pain may be triggered by cortical spreading depression activation of meningeal nociceptors that initiates the trigeminovascular pain pathways similar to what has been described with lesser and greater occipital nerve neuralgia

Laboratory Evaluation

1.Cervical spine MRI to delineate specific pathology

2.Diagnostic nerve blocks

Hypnic Headache

General Characteristics

1.Hypnic headache is a rare primary headache disorder with exclusively sleep related headache attacks

Clinical Manifestations

1.The headache occurs only during sleep which awakens the patient

2.It occurs more frequently than 15 times / month

3.It persists for longer than 15 minutes after the patient awakens

4.Starts after age 50

5.The pain is mild to moderate but is severe in approximately 20% of patients

6.The pain is bilateral in 2/3 of patients

7.Attacks are typically 15 to 180 minutes although longer episodes have been described

8.There are no autonomic symptoms and no more than one symptom of nausea, photophobia or phonophobia

9.Spontaneous remissions can occur

10. Most patients show motor activity during attacks

Neuropathology

1.Abnormality of the circadian rhythm; posterior hypothalamic dysregulation of the circadian rhythm possibly similar to that described in cluster headache

Neuroimaging:

1.MRI of the head to rule out any structural lesions

Differential Points in Regard to Sleep-related Headache

1.Headaches that are intrinsically related to sleep include:

a.Migraine with and without aura

b.Cluster headache

c.Hypnic headache

d.Paroxysmal hemicrania

2.Headaches that cause a sleep disorder:

a.Chronic migraine

b.Chronic tension headache

c.Medication overuse headache

3.Headaches that are a symptom of a sleep disorder:

a.Obstructive sleep apnea

4.Headaches from a systemic condition:

a.Anemia

b.Hypoxemia

5.Chronobiological dysfunction:

a.Involvement of the hypothalamus

b.Cluster headache (circadian and circannual rhythmicity)

c.Hypnic headache (an alarm clock pattern)

6.Possible relation of headache to REM sleep:

a.Cluster headache

b.Hypnic headache

c.Paroxysmal hemicrania

7.Headaches associated with obstructive sleep apnea:

a.Cluster headache

b.Hypnic headache

c.Sleep apnea headache

8.Headaches associated with insomnia:

a.Chronic migraine

b.Medication overuse

c.Psychiatric comorbidity

d.Chronic tension-type

Cranio-Facial Pain

Trigeminal Neuralgia (TN)

General Characteristics

1.A new classification proposes 3 diagnostic categories:

a.Classic TN that is caused by morphologic changes in the trigeminal nerve root from vascular compression

b.Secondary TN due to a neurologic disease

c.Idiopathic when the etiology cannot be identified

Clinical Manifestations

1.Onset is usually middle age or later in life

2.There is the sudden onset of severe stabbing pain in the mandibular and maxillary division of the Vth nerve and much less frequently the first division

3.The pain is usually only of seconds duration or rarely a minute and is often accompanied by a wince or “tic”

4.The patient has trigger areas that initiate the pain which are usually around the mouth (lips, gums, cheeks)

5.The paroxysms occur both during the day and night and if untreated may last for weeks to months

6.In general there is no motor or sensory loss in the affected Vth nerve distribution

7.A subgroup of patients have a continuous low level discomfort, itch or sensitivity in affected areas

8.Usually spatial and temporal summation of a mechanical stimulus in a trigger zone is necessary to trigger pain

9.After a paroxysm there is a 2-3 minute refractory period

10. The pain cannot extend to the cervical nerve territory that includes the posterior 1/3 of the scalp, the back of the ear or the angle of the jaw

11. The territory of the mandibular division of the Vth nerve extends to the temple so that patients may experience pain in the lip and the cranium

12. If two trigeminal divisions are involved they are contiguous which occurs most frequently with the mandibular and maxillary divisions

13. First division involvement may be caused by specific neuropathology

14. TN may remit for weeks to years in a significant proportion of patients

15. TN is overwhelmingly unilateral. Bilateral TN is usually caused by multiple sclerosis (possibly 10% of MS associated TN)

16. The sensory quality of pain in TN may change over time

17. Stimulus evoked pain:

a.Innocuous mechanical stimuli in a branch territory of the Vth nerve

b.The stimulus may be a primary touch or a whiff of air. Maneuvers that are more complex usually are a combination of tactile stimuli and facial movement. The evoked pain may not be felt at the site of the stimulation and may radiate

c.In general, the trigger zones are small and may even be punctate and are usually in the central portion of the face that includes the nasolabial fold, nose and the mouth

18. A sensory deficit is most often associated with underlying pathology

19. TN with continuous pain:

a.A subgroup of TN patients has pain between attacks. Its characteristics are:

i.It is continuous

ii.Is not associated with any other cause for facial pain

iii.It is described as dull, burning or tingling

iv.It localizes in the same distribution as the paroxysmal pain, fluctuates in intensity, has periods of remission and exacerbation similar to that of paroxysmal pain

v.Continuous pain occurs in idiopathic, classical or secondary TN

Neuropathology

1.In classic TN, there is dislocation or atrophy of the trigeminal nerve root at its entry zone into the brainstem. Flattening and atrophy of the nerve root are signs of clinically relevant compression

2.Secondary TN is caused by pathologic processes that affect the nerve

a.Cerebellopontine angle tumors or MS cause TN in 15% of patients

b.Tumors are usually benign and include acoustic or trigeminal schwannoma, meningioma, or epidermoids that usually affect the root at the nerve entry zone to the pons. Its mechanism of action is putatively focal demyelination with ephaptic conduction. Malignant tumors infiltrate the nerve, cause axonal degeneration and have a different clinical profile

3.TN occurs in 2-5% of patients with MS and MS occurs in 2-14% of patients with TN. Demyelinating plaques in the pons have been demonstrated

4.Less frequent pathologies that cause TN include:

a.Aneurysm or dolichoectasia of the basilar artery

b.Brain arteriovenous malformations

5.As noted, approximately 80-90% of primary TGN are caused by vascular compression of the TG nerve at the root entry zone by the superior cerebellar or anterior inferior cerebellar arteries

Neuroimaging

1.Morphologic changes of the nerve and the root entry zone rather than mere contact of the artery with the nerve increase diagnostic specificity dramatically

2.3D reconstruction with MRI delineates the anatomy of the trigeminal nerve and its entry zone:

a.3DT2 weighted MRI, driven equilibrium or constructive interference in steady state delineates the external and cavernous portion of the nerve

b.3D time of flight magnetic resonance angiography delineates arteries while 3D T1-weighted MRI with contrast or phase-contrast MRI delineates veins

3.The anatomical changes in the nerve itself can be discerned with diffusion tensor imaging (DTI) and fiber tractography

Glossopharyngeal Neuralgia

General Characteristics

1.Glossopharyngeal neuralgia is rare with an incidence of 0.2 to 0.7 per 100,000 individuals/year

2.It is classified as classical or symptomatic

3.It has many clinical similarities to trigeminal neuralgia

Clinical Manifestations

1.Paroxysmal attacks of pain that usually last for a fraction of a second to rarely up to 2 minutes

2.The pain characteristics include:

a.Localization to the posterior tongue, tonsillar fossa, pharynx, beneath the angle of the jaw and the ear (auricular branch of the vagus nerve)

b.The pain is sharp, lancinating and severe

c.Triggers most commonly are swallowing, chewing, speaking, coughing, fear of eating and yawning

d.Attacks are stereotyped in each patient

e.There is no clinically definable neurologic deficit

f.Rarely, there is varied distribution of the pain with overlap amongst the trigeminal, vagal and facial nerves:

i.Unusual manifestations include:

1.Cardiac arrhythmias associated with pain episodes

2.Fear to eat

3.Syncope

g.The pain often occurs in clusters, is lancinating and most often is initiated in the throat and radiates to the ear (rarely vice versa). Alternatively, pain may radiate from the pharynx, tonsil and posterior tongue base to the eustachian tube and inner ear or mandibular angle

h.The pain may recur after a brief period of remission. There may be residual pain in the affected distributions

i.Attacks usually occur during the day and may occur for weeks or months if untreated:

i.Unusual triggers include:

1.Sudden head movement

2.Swallowing cold liquids

3.Raising the arm on the side of the pain

4.Lateral movement of the jaw

5.Touching the external auditory canal, the side of the neck and the pretragus of the painful side

ii.Unusual manifestations:

1.Tinnitus

2.Vomiting

3.Vertigo

4.Swelling sensation

5.Involuntary movements

j.Vagoglossopharyngeal neuralgia:

i.Is due to the complex anatomy between the nervus intermedius, vagus and glossopharyngeal nerves

ii.It may manifest as cardiac asystole, convulsions or syncope

k.Cardiovascular phenomena occur during the paroxysms of pain or immediately following its cessation

l.There is a subset of patients that have the cardiac manifestations without the neuralgia

Neuropathology

1.Neurovascular nerve compression at the root entry zone is the major pathology of many patients with idiopathic glossopharyngeal neuralgia. The usual arteries that compress the nerve are:

a.Posterior inferior cerebellar artery

b.Vertebral artery

c.The vertebral artery plus the anterior inferior cerebellar artery

2.Secondary pathologies that cause glossopharyngeal neuralgia are:

a.Cerebellar pontine angle mass lesions (benign tumors and cysts)

b.Oropharyngeal tumors

c.Arachnoiditis

d.Stylohyoid ligament ossification

e.Multiple sclerosis

f.Vascular malformations

Laboratory Evaluation

1.Complete blood count, erythrocyte sedimentation rate, anti-nuclear antibody to rule out underlying systemic disease

Neuroimaging

1.MRI, MRA and 3-dimensional computed tomography angiography (3D-CTA) to rule out vascular compression

2.High resolution MRI and image processing with 3D constructive interference in steady state (CISS) to evaluate neurovascular compression

3.Radiological findings suggestive of glossopharyngeal neuralgia from vascular compression:

a.High origin of PICA

b.PICA making an upward loop

c.PICA causing and compressing the supraolivary cistern

4.MRI of the neck is required to rule out tumors of the hypopharynx, larynx or piriform sinus

5.A cervical radiograph will identify an elongated stylohyoid bone (Eagle’s syndrome)

Herpes Zoster

General Characteristics

1.Herpes zoster (HZ) is caused by the reactivation of varicella – zoster virus (VZV) that has established latency in sensory ganglia after initial infection (chicken pox)

2.It will affect approximately 1 in 3 people in the USA during their lifetime. There are approximately 1 million HZ patients annually in the United States

3.Major risk factors are older age and diminished VZV-specific cell-mediated immunity

4.Other risk factors for HZ are:

a.Family history; the association is highest with first-degree or multiple relatives

b.Prior HZ episodes

c.Sleep disturbance

d.Stress

5.HZ is not associated with trauma, smoking, tonsillectomy, diet, exposure to pesticides or herbicides

Clinical Manifestations

1.Neuralgia associated with a vesicular eruption that affects cranial and peripheral nerves (DRG).

2.HZ auricularis:

a.Vesicular eruption of the external auditory meatus and pinna and less frequently the palate and occipital area

b.It may be associated with or without loss of hearing, tinnitus and vertigo

c.Facial paralysis

d.These signs are accompanied by severe neuropathic pain

3.The more common involvement is that of the Gasserian ganglion which usually affects the first division of V (herpes zoster ophthalmicus):

a.The rash usually occurs 4-5 days after the onset of pain. Rarely there is no skin rash

4.Elderly patients are more likely to develop chronic and intractable pain

5.The pain of post herpetic neuralgia:

a.Most often is burning with super-imposed waves of lancinating pain

b.The dermatomes or cranial nerve territory that is affected may demonstrate:

i.Mechanical hyperalgesia and dynamic mechanical allodynia

ii.Increased threshold to pin-prick and thermal sensitivity

Neuropathology

1.The pathologic changes in HZ infections are usually limited to the dorsal root ganglion (DRG) or a sensory nerve or the nerve root close to the affected ganglion

2.In trigeminal ganglia infection, the component of the ganglia that supplies VI is most severely affected:

a.The ganglia is swollen and congested and in severe cases the adjacent spinal cord is affected

b.There is intense primarily lymphocytic infiltration of the affected ganglion; necrosis in the walls of small blood vessels

c.Degenerative changes in sensory neurons

Laboratory Evaluation

1.Direct fluorescent antibody testing of vesicular fluid

2.PCR testing of vesicular fluid or a corneal lesion

Trochlear Headache

General Characteristics

1.The trochlear nerve innervates the superior oblique muscle that depresses and adducts the eye

2.The muscle tendon is located in the trochlea, a cartilaginous structure in the superomedial orbit. Inflammation of the trochlea can occur either idiopathically or from primary autoimmune connective tissue disease

3.Primary trochlear headache has been described

Clinical Manifestations (Primary Trochlear Headache)

1.The headache is not associated with inflammation

2.80% of patients are female of a mean age of 46 years (range of 18 to 77 years)

3.The headache is continuous, dull of moderate-to-severe intensity located periorbitally (medial eyebrow, orbit or forehead)

4.May be associated with photophobia and diplopia

5.The pain is aggravated by eye movement or reading; paradoxically the pain is exacerbated by looking up although the action of the superior oblique muscle is to depress and adduct the eye

Neuropathology

1.Approximately 50% of patients with trochleitis, that demonstrated clinically apparent trochlear edema, had Behcet’s syndrome, granulomatosis polyangiitis (formally Wegener’s syndrome), lymphoma or Tolosa-Hunt syndrome

Laboratory Evaluation

1.Evaluation for systemic autoimmune or neoplastic causes

Neuroimaging

1.MRI:

a.Negative orbital study in patients with primary trochlear headache

b.Trochlear tendon swelling and edema with secondary causes

Occipital Neuralgia

General Characteristics

1.Occipital neuralgia is recurring paroxysmal attacks of pain in the distribution of the greater occipital nerve (GON), lesser occipital nerve (LON) or third occipital nerve

2.There are connections of the C2 dorsal root component of the occipital nerve with cranial nerves VIII, IX, and X which enlarges the spectrum of symptoms from irritation of these nerves

3.The greater occipital nerve is most commonly involved, followed by the LON and rarely the third occipital nerve

4.The GON and LON are involved concomitantly in 9% of patients

5.The anatomy of the GON:

a.The GON takes origin from the dorsal ramus of C2 (medial branch) ascends superiorly between the inferior oblique capitis and the semispinalis capitis muscles. It continues rostrolaterally deep to the trapezius muscle. It pierces the trapezius aponeurosis inferior to the nuchal ridge, becomes subcutaneous, and is located medially to the occipital artery. It provides sensory innervation from the external occipital protuberance to the vertex of the cranium

b.The lesser occipital nerve arises from branches of C2 and C3 of the cervical plexus and extends superiorly along the posterior border of the sternocleidomastoid muscle. Its innervation territory is the lateral scalp and posterior to the ear.

c.The third occipital nerve is a branch of C3, emerges inferiorly to supply sensation to the upper neck and lower portion of the occipital scalp

Clinical Manifestations

1.Most often the pain is unilateral and most severe in the occipital region

2.Pain quality is lancinating and stabbing often initiated from the neck and radiating to the posterior cranium; less frequent radiations are to parietal and temporal scalp and rarely to the fronto-orbital region

3.Due to dorsal root connections of C2 with cranial nerves VIII, IX and X; patients may have:

a.Tinnitus, dizziness and nausea

4.Palpation and percussion of the GON:

a.2cm lateral and 2cm inferior to the external occipital protuberance

b.Tenderness and a positive Tinel’s sign may be elicited along the course of the nerve

c.The LON is lateral to the GON and is most easily percussed along the superior nuchal ridge one-third lateral to the external occipital protuberance and medial to the mastoid

Neuropathology

1.Most injuries of the nerves are neuropractic

2.The usual injuries are concussions, whiplash that occur with motor vehicle accidents, contact sports and falls

3.Secondary pathologies that cause occipital neuralgias are:

a.Compression of the cervical roots from cervical spondylosis

b.Malignant infiltration

c.Giant cell arteritis

d.Bony callus formation after vertebral fractures

e.Atlantoaxial lateral mass osteoarthritis

f.Hypertrophic cervical pachymeningitis

g.Cervical cord tumor

h.C1-C2 arthrosis syndrome

i.Chiari malformation

j.Fracture of the atlas

k.Pachymeningitis cervicalis associated with syphilis

l.Third nerve occipital neuralgia:

i.Degenerative or traumatic arthropathy that involves the C2 and C3 apophyseal joints that impinges on a branch of the C3 dorsal ramus

Neuroimaging

1.Cervical spine radiographs with particular attention to the open mouth view

2.CT scan of the craniocervical junction (high cervical trauma)

3.MRI scan to delineate any spinal cord or soft tissue pathology

Carotidynia and Pain from Extracranial Arterial Dissection

Carotidynia

General Characteristics

1.Cervicofacial pain that can be elicited by pressure over the common carotid artery

Clinical Manifestations

1.Compression of the common carotid artery at or near its bifurcation causes a dull pain that is referred to the ipsilateral face, ear, jaw, orally and into the neck

2.Variant carotidynia (described by Roseman)

a.Occurs in young adults

b.Recurrent and self-limited pain and tenderness at the carotid bifurcation that may last for up to two weeks

c.Exacerbating factors include head movement, chewing and swallowing

3.Carotidynia with migraine headaches:

a.May be seen at any stage of adult life

b.Attacks last for minutes to hours and are associated with a throbbing headache similar to migraine without aura

4.Carotid or vertebral artery dissection:

a.In general, pain is localized to the area of injury in the anterior neck or face (carotid) or the posterior neck and lateral eyebrow (vertebral artery)

b.Some dissections present with “thunderclap headaches” rather than neck pain; many patients have a throbbing headache over days that has been described bilaterally

c.Carotid dissection is often associated with neck pain, pain over the eye and a partial Horner’s syndrome

Neuropathology

1.Causes of carotidynia include:

a.Giant cell arteritis

b.Takayasu’s arteritis

c.Migraine and cluster headache

d.Displacement of the carotid artery by tumor

e.Dissecting aneurysm

f.Fibromuscular dysplasia

g.Atherosclerosis

h.Intraluminal hemorrhage

i.Aneurysm

2.Idiopathic carotidynia:

a.Posited to be caused by edema or inflammation of tissues surrounding the carotid bifurcation

Laboratory Evaluation

1.A thorough medical evaluation to rule out an autoimmune or inflammatory condition

Neuroimaging

1.MRI (cervical):

a.Enhancing tissue surrounding the symptomatic carotid artery at the level of the distal common carotid and carotid bifurcation

b.The enhancing rim of tissue (5 patients) measured 6-8 mm; the length of the enhancing segment varied between 1.5-3.5 cm which included the distal common carotid and portions of the carotid bulb

c.Enhancing tissue was consistent with the fascia of the carotid sheath

d.The caliber of the carotid vessel is normal and demonstrates normal flow voids.

Temporomandibular Joint Disorder

General Characteristics

1.It is estimated that 10 million people in the USA have temporomandibular joint disorder and that a significant portion of individuals in the general population will develop it (~25%) at some point during life

2.The female to male ratio is 4:1

3.Rarely occurs in children

Clinical Manifestations

1.The highest incidence occurs in adults aged 20 to 40

2.The pain generally occurs unilaterally in the muscles of mastication

3.The pain radiates to the ear and jaw and is exacerbated with chewing

4.The jaw may lock with mouth opening

5.If there is displacement of the articular disc patients may have ear clicking or popping

6.Rarely patients complain of unilateral headache without concomitant jaw pain

7.Rarely patients may have back and shoulder pain

8.Bruxism during sleep and teeth clenching during the day

9.There may be progressive pain during the day

10. There is limitation of jaw opening. The normal aperture from lower to upper anterior teeth is 40mm

11. Masseter and internal pterygoid muscle spasm

12. Rarely ipsilateral facial swelling

13. Clicking and popping in the TMJ with jaw movement

14. Tenderness of the TMJ by palpation in the external auditory meatus while the patient opens the mouth

15. Crepitus in the joint

16. Deviation of the jaw to the affected side

Neuropathology

1.Macro and microfacial trauma

2.Malocclusion due to loss of molars or ill-fitting dentures

3.Arthritic changes

4.Repetitive trauma associated with age and tooth loss

5.TMJ disc displacement is associated with mandibular asymmetry

6.Most craniofacial dysmorphisms are not associated with temporomandibular dysfunction; a large study has demonstrated that temporomandibular disorders are not associated with vertical craniofacial morphology

Laboratory Evaluation

1.Complete blood count, calcium, phosphate and alkaline phosphatase (bone disease), uric acid (gout), creatine phosphokinase (muscle disease), sedimentation rate (temporal arteritis) and rheumatoid factor (rheumatoid arthritis)

Neuroimaging

2.MRI:

a.There is a significant correlation between disc length, condyle morphology and disc displacement

b.A series of 794 patients with clinical TMJ demonstrated by MRI (T1 and T2 weighted sequences):

i.62% had physiological disc position

ii.35% have anterior displacement

iii.3% a posterior disc position

Persistent Idiopathic Facial Pain (PIFP)

General Characteristics

1.PIFP is the new terminology for atypical facial pain

2.Definition:

a.A persistent facial pain that does not have the characteristics of the cranial neuralgias and is not attributed to another disorder

3.Atypical odontagia may be a sub-type of atypical facial pain (AFP) in which the pain is confined to the teeth or gums:

a.Definition:

i.It is a pain with no demonstrable cause which is perceived to be coming from a tooth or multiple teeth and is not relieved by standard treatments to alleviate dental pain

4.PIFP or atypical facial pain has been classified as a component of the symptom complex of chronic facial pain that also includes:

a.Burning mouth syndrome

b.Temporomandibular joint dysfunction (TMD)

c.Atypical odontalgia

5.Recent research supports the hypothesis that PIFP is a neuropathic pain

Clinical Manifestations

1.The pain is frequently poorly localized. It occurs more often in the maxilla than the mandible. Both may be affected.

2.The pain is not perceived in the distribution of the trigeminal nerve and is usually unilateral

3.The pain may be located in the socket of an extracted tooth or to an area of a previous surgical procedure

4.The pain may spread to other sites, if the teeth are involved a quadrant of the mouth may be affected

5.The onset is often attributable by the patient to a dental procedure. The pain is continuous for months to years with intermittent exacerbations. It gradually increases with time.

6.The pain is variously described as deep, pressure-like, crushing or burning

7.The pain does not respect the midline or a dermatomal distribution. It may radiate to the temple, neck or occiput

8.The pain is associated with depression and anxiety as well as with other chronic pain syndromes. Xerostomia and dysgusia may be prominent

9.The pain is persistent throughout the day; less frequently it is intermittent

10. There are no precipitating or relieving factors and no “trigger zones”; facial movements do not exacerbate the pain and non-steroidal analgesics are not effective

11. The pain is moderate to severe; usually does not disturb sleep

Neuropathology

1.Putative central sensitization of trigeminal nociceptive neurons in the brainstem

2.Central sensitization has been demonstrated after pulpectomy or transection of dental nerves as well as from inflammation of peripheral tissue

3.Neuralgia-inducing cavitational osteonecrosis (controversial term and entity) refers to degeneration of the bone marrow in the maxilla or mandible on an ischemic basis. Most often, it is painless, but in some patients causes neuropathic pain. Degenerative extracellular cystic spaces are seen in the bone marrow

Laboratory Evaluation

1.Radiographs, cone beam CT, and MRI to exclude other pathology that includes arteriovenous malformation, tumor, temporomandibular joint disorder or MS

Intraoral non-Dental Pain

1.Atypical odontalgia

2.Post-traumatic trigeminal neuropathy

3.Burning mouth syndrome

Extraoral Pain with or without Intraoral Pain

1.Temporomandibular disorders

2.Trigeminal neuralgia

3.Glossopharyngeal neuralgia

4.Persistent idiopathic facial pain

5.Giant cell arteritis

6.Migraine / neurovascular orofacial pain

Sinusitis

General Characteristics

1.Sinusitis is very common and thought to effect 10 to 30% of the USA and European population per year

2.Women are more frequently affected than men

3.Chronic sinusitis affects approximately 12% of the population

4.Sinusitis is inflammation of the mucous membrane of the paranasal sinuses and is classified according to anatomic site:

a.Maxillary

b.Ethmoidal

c.Frontal

d.Sphenoidal

5.Pathogenic organism (viral, bacterial or fungal)

6.Associated factors:

a.Nasal polyposis

b.Immunosuppression

c.Anatomic variants

7.Acute rhinosinusitis:

a.An infection that may be present for four weeks

8.Recurrent acute rhinosinusitis:

a.Four or more separate episodes of acute sinusitis within one year

9.Subacute rhinosinusitis:

a.An infection that persists for four to 12 weeks; posited to be a transition between acute and chronic infection

10. Chronic rhinosinusitis:

a.Signs and symptoms that persist for more than 12 weeks

Clinical Manifestations

1.Headache or facial pain over the affected sinuses is seen in both acute and chronic sinusitis

2.The quality of the pain is constant, dull or aching

3.The pain is typically localized to the involved sinus:

a.Maxillary sinus:

i.The pain is experienced most often in the cheek or as a generalized headache, or toothache

b.Frontal sinus:

i.The pain is experienced in the brow, forehead and above the eyes

c.Ethmoidal sinus:

i.Pain is between or behind the eyes, the medial canthi, and may be associated with generalized headache

d.Sphenoidal sinus:

i.Pain or pressure behind the eyes; frequently radiates to the vertex of the skull, the mastoid process or occipitally

ii.Pain is exacerbated with bending over or with recumbency

iii.Pain may start unilaterally and then progress bilaterally

iv.Tilting the head forward and a Valsalva maneuver exacerbate the pain which are differential points from toothache

v.Less frequent symptoms and signs of sinus infections:

1.Infection of the orbit (most often from ethmoid sinusitis)

2.Osteomyelitis of the forehead and facial bones (Pott’s puffy tumor)

3.Middle ear symptoms:

a.Due to congestion of the nasal passages

b.Pressure in the head or vibrating feeling in the head

4.Halitosis

Neuropathology

Basic Mechanisms of Sinus Pathology

1.Obstruction of sinus drainage

a.Obstruction of sinus ostia prevents normal mucous drainage. Causes of ostial obstruction include:

i.Trauma

ii.Rhinitis

iii.Inflammatory systemic disorders

iv.Immune deficiency

v.Disorders of mucociliary clearance:

1.Cystic fibrosis

2.Respiratory allergies

3.Primary ciliary dyskinesia (Kartagener syndrome)

vi.Patients with immunodeficiency:

1.Agammaglobulinemia

2.Decreased IgG and IgA

vii.Mechanical obstruction of ostia:

1.Nasal polyps

2.Foreign body

3.Deviated septa

4.Anatomical variants that narrow the osteomeatal complex

viii.A combination of anaerobic and aerobic bacteria is associated with chronic sinusitis. Common organisms include:

1.Staphylococcus aureus

2.Coagulase-negative staphylococci

3.Gram negative enteric organisms

4.Chronic rhinosinusitis is a multifactorial inflammatory disorder rather than a persistent bacterial infection

ix.It has been posited that biofilm bacterial infections may be a cause of antibiotic-refractory chronic sinusitis:

1.A biofilm is a complex aggregate of extracellular matrix and inter-dependent microorganisms from multiple species. Bacteria in microfilms have much greater resistance to antibiotics than free-living bacteria

x.Major associated complications of sinusitis:

1.Often involve the frontal, sphenoidal and ethmoidal sinuses include:

a.Brain abscess from invasion of bacteria through affected bones and blood vessels

b.Meningitis

c.Orbital infections from continguous spread from the ethmoid sinus by anterior and posterior ethmoidal veins thrombophlebitis. The infection spreads to the lateral or orbital side of the ethmoid labyrinth

d.Central nervous-system spread to involve the cavernous sinus

2.Maxillary sinusitis from an odontogenic origin is well described

Laboratory Evaluation

1.In context, nasal cytology to delineate:

a.Allergic rhinitis

b.Eosinophilia

c.Nasal polyposis

d.Aspirin sensitivity

2.Recurrent infection:

a.Immunoglobulin evaluation

Neuroimaging

1.CT with frontal and coronal planes

2.MRI with contrast is the method of choice for intraorbital or intracranial complications

Silent Sinus Syndrome (SSS)

General Characteristics

1.A syndrome that is usually painless and demonstrates unilateral enophthalmos and hypoglobus

Clinical Manifestations

1.Enophthalmos is universally present

2.Upper lid retraction, lid lag and restriction of gaze

3.Normal visual acuity but some patients develop diplopia

4.Males and females are affected equally and the disease presents in the third to the fifth decade

5.Facial asymmetry

6.Progressive changes over weeks to months

7.Rarely patients have headaches and nondermatomal facial pain

Neuropathology

1.There is support for the hypothesis that SSS may be a variant of chronic maxillary atelectasis

2.Obstruction of outflow theory:

a.An acquired obstruction of the maxillary infundibulum causes hypoventilation of the sinus with accumulation of secretions. The reabsorption of secretions causes a negative pressure in the maxillary antrum

b.Infundibular obstruction may be caused by aberrant nasal anatomy such as lateral deviation of the middle turbinate

c.Other causes of occlusion are mucous plugging, mucocoele and nasal polyps. Surgery may damage the osteomeatal complex

Laboratory Evaluation

1.CT evaluation:

a.Occlusion of the maxillary infundibulum due to lateral retraction of the uncinate process with apposition against the inferiomedial aspect of the orbital wall

b.The orbital floor is inferiorly displaced and there is increased concavity of the medial and lateral maxillary wall toward the antrum

c.There is a loss of antral volume

Complex Regional Pain Syndrome

General Characteristics

1.Complex regional pain syndrome is a neuropathic pain syndrome that is divided into type I in which no specific large nerve is injured and type II in which a specific nerve injury can be identified

2.Type I CRPS is most common and there is supporting evidence for it as a small fiber neuropathy

3.CRPS characteristically follows injury to an extremity or a surgical procedure

Clinical Manifestations

1.Following soft tissue or nerve injury patients develop:

a.Pain in the injured part out of a nerve root or dermatomal distribution that characteristically:

i.Is spontaneous and more severe than the injury would suggest

ii.Demonstrates mechanical and thermal hyperalgesia, allodynia and when evoked is not stimulus bound

iii.Progressively spreads in most patients

iv.Autonomic dysregulation characterized by either an increase or decrease of blood flow (usually the former in acute injury) and hyper or hypohidrosis

v.Neurogenic edema of the affected part

vi.A movement disorder that includes:

1.Difficulty initiating and sustaining movement

2.Weakness

3.Myoclonic jerks

4.Tremor

5.Spasm

6.Increased reflexes

7.Dystonia

vii.Trophic changes in which nails and hair grow too rapidly and then thin and may fall out (hair); loss of muscle and subcutaneous tissue

viii.If the face is involved there is erythema, neurogenic edema, severe pain with mechanical and thermal hyperalgesia and allodynia:

1.Myokymia of the orbicularis oculi

2.No dystrophy of subcutaneous tissue but frequent poor dentition with loss of teeth

3.Red and hot ears

ix.The upper extremity is frequently involved with the face

Neuropathology

1.The cervical plexus and usually the upper components of the brachial plexus have undergone a neuropractic injury from a motor vehicle accident, fall or surgical procedure (damage to the supra orbital nerve from plastic surgery)

2.The process is thought to occur from a continued peripheral nerve drive on pain projecting neurons of the dorsal root ganglion that causes sensitization of both peripheral and central pain projecting neurons throughout the pain matrix. The process is one of maladaptive neuroplasticity

3.The warmth and neurogenic edema is secondary to release of substance P and calcitonin gene related peptide (vasoactive neuropeptides) that dilate and increase permeability of peripheral blood vessels

Laboratory Evaluation

1.EMG:

a.To evaluate large nerve dysfunction and to delineate any possible relieving factors

2.Skin biopsy:

a.Demonstrates small fiber loss and abnormalities of sweat glands

3.QST:

a.Demonstrates mechanical and thermal decreased perception thresholds in some patients

b.Decreased thresholds for cold and heat pain

c.Increased temporal summation (“wind up”)

4.Autonomic testing:

a.Abnormal quantitative sweat test

Neuroimaging

1.MRI of the cervical spine and the brachial plexus to rule out underlying pathology

Neck-Tongue Syndrome

General Characteristics

1.A rare syndrome that involves the neck and the tongue when suddenly turning the head

Clinical Manifestations

1.Sudden rotation of the neck and head causes lancinating pain of the upper neck or occiput

2.This pain is immediately followed by transient ipsilateral numbness of the tongue. Rarely there is numbness in the back of the palate

3.Symptoms are usually seconds to 1 minute

Neuropathology

1.Abnormal subluxation of one lateral atlanto-axial joint with compression of the C2 ventral ramus against the articular process

2.The posterior cervical plexus joins the first 3 cervical roots. The pain in the occiput suggests stimulation of the second and third cervical roots

3.The C2 root is compressed between the atlas and axis during excessive rotation of the neck

4.The lingual nerve forms a communication with the hypoglossal nerve as they course over the hyoglossus muscle below the tongue. The hypoglossal nerve is connected by a loop between the first and second cervical roots

5.Thus there are anatomical connections from the lingual nerve via the hypoglossal nerve to the second cervical root that may explain tongue numbness when the C2 root is compressed

Laboratory Evaluation

1.CT of the cervical spine and craniocervical junction to evaluate the origin of the C2-C3 cervical roots and the atlanto-axial anatomy

Dry Eye Disease (DED)

General Characteristics

1.DED is also known as keratoconjunctivitis sicca, affects the ocular surface due to alterations in the quality or quantity of the tear film

2.The multiple etiologies cause an unstable tear film

3.A classification divides the syndrome into:

a.Aqueous-deficient dry eye

b.Evaporation dry eye

c.Aqueous deficient dry eye is classified as:

i.Sjogren’s syndrome

ii.Non-Sjogren’s syndrome

Clinical Manifestations

1.Ocular discomfort

2.A feeling of dryness in the eye

3.Photophobia

4.Blurred and fluctuating vision

5.Often associated dry mouth

Neuropathology

1.Sjogren’s syndrome with an autoimmune attack of the salivary and lacrimal glands

2.In normal individuals, the precorneal tear film covers the exposed ocular surface that continuously evaporates. Tears are replenished by the lacrimal glands which moisten the nonkeratinized epithelium of the cornea

3.During interblink intervals, there is a rapid drop of eye surface temperature due to tear evaporation. There is a concomitant increase of osmolality of the tear film.

4.Thinning and disruption of the precorneal tear film causes mechanical stress of the cells and nerve fibers of the superficial epithelial corneal layers which releases inflammatory mediators

5.These physical changes increase excitability of corneal cold trigeminal neurons due to an increase in sodium currents and a decrease of potassium currents

6.Corneal polymodal receptors demonstrate increased sodium currents

7.Experimental evidence shows that cold thermoreceptors contribute to the detection and signaling of ocular surface wetness. Under dry eye conditions, they develop injury-evoked neuropathic discharge that may underlie the ocular discomfort of DED patients

Laboratory Evaluation

1.The biomarkers for primary Sjogren’s disease are anti-SS-A(Ro) or SS-B(La) antibodies

2.Elevated antinuclear antibodies (ANA) or increased rheumatoid factor are found in other autoimmune diseases that are a component of secondary SS

3.Novel autoantibodies for early SS are to:

a.Salivary protein 1 (SP-1)

b.Parotid secretory protein 1 (PSP-1)

c.Carbonic anhydrase VI (CA-6)

Neck Pain

Overview

The primarily neuropathic causes of neck pain have been covered in the discussion of cervical and pharyngeal plexus disorders, congenital anatomical variants of the cranial cervical junction, disc disease, spondylosis, facet and spondylolisthesis, and spinal cord pain.

This discussion is of neck pain caused by myofascial syndromes, retropharyngeal disorders and tendinitis of neck muscles that are associated with pain.

Cervical Myofascial Pain

General Characteristics

1.Myofascial pain is caused by muscles and their surrounding fascia

2.The muscles primarily involved in cervical myofascial pain are the:

a.Trapezius

b.Levator scapulae

c.Rhomboids

d.Supraspinatus

e.Infraspinatus

3.Cervical myofascial pain most often occurs in a setting of overuse or trauma

4.Myofascial pain is common in the general population and maybe 21% of patients seen in orthopedic clinics. It is more common among women and occurs more frequently with increasing age until midlife when its incidence gradually declines

Clinical Manifestations

1.This is a clinical diagnosis with no generally accepted biomarkers

2.Many patients present with a history of trauma and persistent muscle pain. Others have an insidious onset associated with repetitive upper extremity movement, poor posture and stress

3.Poor posture includes dropped and forward flexed shoulders with protracted scapulae

4.Trigger points are found in the trapezius, supraspinatus, infraspinatus, rhomboids and levator scapulae muscles

5.A palpable taut band is noted in the affected skeletal muscle or its surrounding fascia. A local twitch response can be induced with palpation

6.Range of cervical spine movement is usually restricted with pain elicited in positions that stretch the affected muscle

7.Strength of the upper extremity is normal. Radiating pain into the hand and fingers supports an associated brachial plexus involvement

8.Sensation is normal

Neuropathology

1.Myofascial pain is associated with trigger points in the affected skeletal muscle

2.A trigger point is a hyperirritable area that is in a palpable taut band of muscle fibers. Palpation of trigger points elicits local pain and referred pain

3.Trigger points may have associated autonomic phenomena

Neuroimaging

1.MRI to rule out any structural cervical spine lesions

Laboratory Evaluation

1.EMG evaluation of trigger points has been found to be contradictory and controversial

Retropharyngeal Tendinitis

General Characteristics

1.Acute calcific tendinitis of the longus colli muscle is an aseptic inflammatory process that is located in the prevertebral space

2.The longus colli muscle is located in the prevertebral space and is composed of upper oblique, vertical, and lower oblique fibers. The upper oblique fibers take origin from the anterior tubercles of the transverse processes of the C3-C5 vertebrae and insert on the anterior tubercle of the atlas

3.Vertical fibers arise from the bodies of the upper thoracic and lower cervical vertebrae and insert on the bodies of the upper cervical vertebrae

4.Oblique fibers arise from the anterior areas of T1-T3 and insert on the anterior tubercles of the transverse processes of the C5-C6 vertebrae

Clinical Manifestations

1.Acute neck pain and stiffness

2.Odynophagia

3.Less frequent signs and symptoms include:

a.Dysphagia

b.Sore throat

c.Limited range of cervical motion

d.Pharyngeal edema

e.Erythema of the nasopharynx

f.Neck spasm

Neuropathology

1.It has been proposed that the natural history of retropharyngeal calcinosis consists of 5 phases:

a.Precalcific

b.Formative

c.Resting

d.Resorptive

e.Postcalcific

2.Endochondral ossification has been proposed which is similar to that which occurs in the Achilles tendon. This model proposes that fibrocartilaginous metaplasia is the initiating event

3.Erroneous differentiation of tendon-derived stem cells into chondrocytes or osteoblasts may be causative

4.Calcium hydroxyapatite crystal deposition occurs; rupture of these crystals causes an aseptic foreign-body type inflammatory response that leads to formation of fluid in the retropharyngeal space surrounding the longus colli muscle

Laboratory Evaluation

1.Mild elevation of the sedimentation rate with low-grade leukocytosis

Neuroimaging

1.CT scan detects both the prevertebral edema and calcium hydroxyapatite crystals that are deposited in the longus colli tendon. CT is considered more sensitive in distinguishing retropharyngeal tendinitis from abscess

2.MRI demonstrates the prevertebral edema and is less sensitive for depicting the calcific deposits

Differential Diagnosis

1.Meningitis (stiff neck and painful range of motion)

2.Retropharyngeal abscess

3.Neoplasm

4.Cervical disc

5.Fracture dislocation

6.Spondylolisthesis

Ossification of the Posterior Longitudinal Ligament (OPLL)

General Characteristics

1.The ossification of the ligament is most often at cervical levels C2-C4

2.The ratio of males to females is 2:1

3.In Japanese patients, the prevalence of OPLL is 1.8-4%. The prevalence in North America is much lower, possibly 0.12%

4.The genetics is most often sporadic but there have been some familial patients in Caucasian and European populations

Clinical Manifestations

1.The majority of patients are asymptomatic. The posterior longitudinal ligament extends from the occiput to the sacrum and is located posterior to the vertebral bodies and dorsal to the intervertebral discs

2.Ossification and hypertrophy of the ligament presents with a progressive neurologic deficit, pain or acute neurologic symptoms

3.In a large Japanese study, 17% of patients that were followed for 18 years developed myelopathy

4.Cervical myelopathy with neck pain and progressive weakness, sphincter involvement and hyperreflexia comprise its natural history. Radiculopathy may be prominent

Neuropathology

1.Ossification of the posterior longitudinal ligament is a multifactorial and polygenic disease

2.RSPO2 (encoding R-spondin 2) has been identified by genome-wide association studies as a susceptibility gene which is a secreted agonist of canonical Wnt/β-catenin signaling. The most significant SNP in the GWAS locus maps to chromosome 8q23.1 which is located in the chondrocyte promotor region of the RSPO2 gene

3.Ossification and hypertrophy of the ligament decreases the cervical spine diameter, compresses the spinal cord which causes an ischemic myelopathy

4.The cord parenchyma is also damaged by repeated trauma to the ventral spinal cord by the hypertrophied and ossified ligament

Neuroimaging

1.CT:

a.Delineates early OPLL that demonstrates multiple small areas of bone within an enlarged ligament that over time coalesce to form a large bony plaque within the ligament ventral to the spinal cord.

b.A “single-layer sign” signifies dense ossification within the ligament that extends to the periphery

c.A “double-layer sign” in which there is ossification of the ligament behind the vertebral body as well as in the posterior longitudinal ligament

d.The dura may be penetrated by the bony mass in the ligament to cause a CSF leak

2.MRI:

a.Early OPLL is seen dorsal to the interspaces; over time there are areas of new bone formation demonstrated by increased signal on T1-weighted sequences in the ligament. There is no enhancement with gadolinium.

Superior Laryngeal Neuralgia

General Characteristics

1.The superior laryngeal nerve is a branch of the vagus nerve. Its origin is from the middle of the nodose ganglion

2.The cricothyroid muscles are innervated by the superior laryngeal nerve while all other intrinsic laryngeal muscles are innervated by the recurrent laryngeal nerve

3.The nerve descends lateral to the pharynx, behind the internal carotid artery and divides into the external laryngeal and internal laryngeal nerves

Clinical Manifestations

1.The superior laryngeal nerve is the closest nerve contiguous to the bifurcation of the carotid artery

2.Paroxysms of pain along the anterior cervical triangle

3.Radiations may extend to the ipsilateral ear and eye

4.The pain may last for minutes to hours

5.Triggering factors are:

a.Swallowing

b.Straining the voice

c.Head turning

6.A common trigger point is on the lateral aspect of the throat overlying the thyrohyoid membrane. Other trigger points include:

a.At the foramen of the internal branch of the superior laryngeal nerve

b.In the pyriform sinus where the superior laryngeal nerve is superficial

Neuropathology

1.May occur from upper respiratory infection such as influenza

2.Laryngitis

3.Trauma, particularly carotid endarterectomy as the nerve lies in close proximity to the carotid bifurcation

4.Prior tonsillectomy

5.Lateral pharyngeal diverticulum

6.Compression by the superior thyroid artery and / or vein

Laboratory Evaluation

1.EMG to evaluate the function of the laryngeal musculature

Neuroimaging

1.MRI:

a.To rule out pathology of the larynx and perilaryngeal structures

Eagle Syndrome

General Characteristics

1.The disorder is caused by an elongated or misshaped styloid process and / or calcification of the stylohyoid ligament. The incidence of Eagle’s syndrome is approximately 0.16% of the population

Clinical Manifestations

1.Lancinating pain that radiates to the jaw, back of the throat, base of the tongue, face, ear or neck

2.Dysphagia

3.A foreign object sensation in the throat

4.Triggers for pain include:

a.Chewing

b.Swallowing

c.Turning the head

d.Touching the back of the throat

5.Tinnitus

6.The elongated styloid process can at times be palpated behind the tonsillar fossa

7.Vascular Eagle syndrome:

a.The elongated styloid process may compress the internal carotid artery below the skull:

i.Rarely may cause TIA or stroke

Neuropathology

1.The styloid may be elongated, >30 millimeters in length, in approximately 4% of the population (~4% of these patients are symptomatic)

2.Styloid / C1 transverse process juxtaposition may be a cause. In these patients, the distance between the styloid process and the transverse process of C1 ranged from 0.05-0.46 cm; the length of the process ranged from 2.4 – 8.5 cm.

3.Calcification of the stylohyoid ligament

Neuroimaging

1.CT:

a.The normal length of the styloid in an adult is approximately 2.5cm; an elongated process is generally > 3cm in length

b.Lateral deviation of the process may be symptomatic

Cricoid Cartilage Syndrome

General Characteristics

1.The cricoid cartilage is inferior to the thyroid cartilage in the neck at the C6 vertebral level to which it is connected by the median cricothyroid ligament medially and postero-laterally by the cricothyroid joints.

2.The cricoid is attached to the first tracheal ring by the cricotracheal ligament

3.It is a component of the attachment of the cricothyroid muscle, posterior cricoarytenoid muscle and lateral cricoarytenoid muscles

Clinical Manifestation

1.Anterior cervical or throat pain

Neuropathology

1.Calcification with age

2.Composed of hyaline cartilage

Neuroimaging

1.MRI:

a.To rule out any pathology or structural lesion

Hyoid Syndrome

General Characteristics

1.The hyoid bone is the only bone in the human body with no direct contact with any other bone

2.It forms a moveable base for the tongue; it is U shaped and is located between the root of the tongue, mandible and thyroid cartilage

3.Its muscle associations include:

a.Mylohyoid (mandible)

b.Hypoglossus (tongue)

c.Stylohyoid (skull)

d.Thyrohyoid (thyroid cartilage)

e.Sternohyoid (sternum)

f.Omohyoid (the medial border of the scapular notch

Clinical Manifestations

1.Pain on swallowing in the region of the hyoid (anterior cervical pain)

2.Common radiations are to the ear, face, lower jaw and pharynx

3.Less common radiations:

a.Zygomatic arch

b.Temporomandibular joint

c.Mandibular molar teeth

d.Very rarely the sternum

4.Palpation and pressure on the greater cornu of the hyoid bone causes local pain and specific pain radiations

Neuropathology

1.Trauma to the greater cornu of the hyoid bone

2.In a subset of patients, tenosynovitis of the intermediate tendon of the digastric muscle

3.The bone may be involved by chondrosarcoma which presents as a slow-growing painless mass in the neck

4.Osteonecrosis of the hyoid bone after radiation therapy for carcinoma of the head or neck

Neuroimaging

1.MRI:

a.To delineate pathology or structural lesions

b.To rule out a recurrent neoplasm

Ernest Syndrome

General Characteristics

1.Ernest syndrome is insertion tendinosis of the stylomandibular ligament at its insertion into the mandible

2.The function of the ligament is to limit the maximum opening and protrusion of the mandible

3.The ligament is derived from the first branchial arch and is posited to be innervated by a branch of the third division of the trigeminal nerve

Clinical Manifestations

1.Throat pain

2.Pain around the TMJ

3.Ear fullness and pain

4.Anterior temporal pain and headache

5.Pain in the body of the mandible

6.Eye pain

7.Odontalgia

Neuropathology

1.Degenerative changes at the insertion zone in the muscle or ligament; Sharpey’s fibers are affected usually after repetitive movement or trauma

Neuroimaging

1.MRI to rule out any other pathology

Superior Pharyngeal Constrictor Syndrome

General Characteristics

1.A myofascial disorder of the superior pharyngeal constrictor muscle

2.The muscle is large, is quadrilateral and has 4 origins:

a.The inferior medial plate and pterygoid hamulus of the sphenoid bone

b.The pterygomandibular raphe

c.The medial surface of the mandible

d.The lateral surface of the body of the tongue

3.The insertion is into the median raphe of the posterior pharyngeal wall

4.The muscle is innervated by the pharyngeal plexus which is formed by branches of the glossopharyngeal and vagus nerves

Clinical Manifestations

1.Pain in the throat

2.Radiation to the TMJ area

3.Swallowing triggers pain

4.Otalgia

5.Radiation to the temple

6.Dysfunction of the swallowing reflex

7.Pain on mechanical pressure of the posterior and lateral areas of the pharyngeal wall posterior to the pterygoid hamulus

Neuropathology

1.Putatively biomechanical stress of the muscle when the mouth is widely opened

2.May be injured during intubation for general anesthesia

3.Injured during the Halstead technique for injecting the alveolar nerve

Neuroimaging

1.MRI to delineate any other cervical pathology

2.Flexible laryngoscopy

Superior Thyroid Cornu Syndrome

General Characteristics

1.Ossification of a superior thyroid cornu

Clinical Manifestations

1.Throat pain

2.Dysphagia

3.Odynophagia

4.Foreign body sensation in the throat

5.Symptoms may develop years after trauma

Neuropathology

1.Displacement of the superior cornu following neck trauma or congenitally

2.The displacement is usually medial and anterior to its normal position which produces a protruding mass impinging upon the lumen of the pharynx; a similar effect occurs if the superior thyroid cornu is elongated by ossification

3.Strangulation, external compression and endotracheal intubation may cause repositioning of the superior cornu towards the lumen of the larynx

4.Congenital defects are due to maldevelopment of the fourth branchial arch

5.Ossification of thyroid cartilage begins at 20-23 years of age at its inferior margin

Laboratory Evaluation

1.Flexible endoscopy

2.CT scanning with 3D reconstruction

Lateral Thyrohyoid Ligament Syndrome

General Characteristics

1.The lateral thyrohyoid ligament forms the posterior border of the thyrohyoid membrane and passes between the tip of the superior cornu of the thyroid cartilage and greater cornu of the hyoid bone

2.The recurrent laryngeal nerve lies laterally

Clinical Manifestations

1.Chronic unilateral neck pain associated with painful swallowing (some patients)

2.1/3 of patients have a foreign body sensation in the throat

3.Severe pain on palpation either at the superior lateral thyroid cartilage or in the ligament that extends to the hyoid bone

Neuropathology

1.Initiating factors that have been reported are trumpet playing, severe cough, excessive voice use and strenuous physical activity

2.Inflammation of the ligament that is frequently responsive to steroids

Laboratory Evaluation

1.Flexible laryngoscopy

Neuroimaging:

1.MRI to rule out other pathology

Thyroid Cartilage and Mastoid Process Syndromes

General Characteristics

1.The thyroid cartilage is composed of two plates or lamina that connect anteriorly at an angle of 90 to 120 degrees

2.The cartilage is a component of voice production by facilitating vibration of the vocal cords

3.It forms attachments for laryngeal muscles and protects the vocal folds

4.The cricothyroid joint joins the cricoid and thyroid cartilage and changes the tension (assists in this action) and pressure on the vocal cords which helps to adjust the pitch of the voice

Clinical Manifestations

1.Tenderness to mechanical stimuli over the thyroid cartilage and the area of insertion of the sternocleidomastoid muscle on the mastoid process

Neuropathology

1.Fracture of the cartilage

2.Increased tension or stress on the muscles that surround the cartilage

3.Putative inflammation of the cartilage

Laboratory Evaluation

1.Flexible laryngoscopy

Neuroimaging

1.MRI to rule out other pathologies

Rare Syndromes Causing Pain in the Throat

1.Eagle syndrome

2.Ernest syndrome

3.Hyoid bone syndrome

4.Thyroid cartilage and mastoid process syndrome

5.Cricoid cartilage syndrome

6.Superior laryngeal nerve neuralgia

7.Neck tongue syndrome

8.Retropharyngeal tendinitis

9.Posterior longitudinal ligament calcification syndrome

10. Superior cornu of the thyroid cartilage syndrome

11. Superior pharyngeal constrictor syndrome