Primary Headache Syndromes
Migraine is the second most common headache syndrome seen in clinical practice. Migraine headache is often characterized as a disabling pain, moderate to severe in intensity, unilateral in location, and pulsatile in quality. In many cases the migraine headache is accompanied by nausea, vomiting, phonophobia, or photophobia. Migraines have been subdivided into 2 main subtypes: migraine with aura and migraine without aura. Migraine with aura is characterized by the presence of reversible focal neurological symptoms that can precede or accompany the headache, often lasting 5 to 20 minutes. The most common aura is visual, which is commonly experienced as a central zig-zag figure traveling into the peripheral vision, transforming into an angulated shape with a scintillating edge (the “scintillating scotoma”).
Migraine headaches have a strong genetic basis. Approximately 80% of migraineurs have a family history of migraines. Multiple theories have been proposed to explain the mechanism of migraine. Historically, the origin was thought to be vasogenic. More recent evidence has suggested a neurogenic theory that hypothesizes the brain itself generates migraine in a susceptible individual and that the vasoconstriction observed is an effect of, rather than a cause of, the migraine. The actual mechanism of migraine seems to be more complex than can be explained just based on the vasogenic or neurogenic theories alone. Local sterile inflammation, spreading cortical depression involving the trigeminovascular pathways, as well as the interaction and effect of multiple neurotransmitters (including atrial natriuretic peptide and serotonin) are also important pathophysiological responses observed in both patients with migraine headaches and animal models of migraine.
Migraine with aura has been shown to be an independent risk factor for ischemic stroke. The association of migraine and ischemic stroke is most prominent in women younger than 45 years of age, in the setting of tobacco use and estrogen-based oral contraceptive agents. A rare complication of migraine is a cerebrovascular accident also known as migrainous infarction. Patients with migraines have a higher probability than the general population of demonstrating nonenhancing white matter lesions on magnetic resonance imaging (MRI). It is believed that these areas of hyperintensities (white matter lesions) represent ischemia, but their long-term clinical significance has not been established.
The treatment of migraine is best managed by a physician experienced in headache management. In general, migraine headache treatment consists of abortive or preventative strategies (Table 1).
A tension, stress, or musculoskeletal headache is the most common headache syndrome encountered in clinical practice, with a lifetime prevalence of 30% to 78%. Recent studies have shown that it is a neurobiological rather than a psychogenic phenomenon. Tension headaches can be divided into episodic (frequent and infrequent) and chronic. They are usually characterized as bilateral, mild to moderate pressure pains. The duration of symptoms varies, from minutes to days. Nausea and vomiting are not experienced with tension headaches, but phonophobia or photophobia can be present, although typically not in combination. In some cases it can be difficult to determine if the patient is suffering from a migraine headache, a tension headache, or both. Some experts believe tension headaches are a mild variant of migraine without aura. The finding of muscle tension is not an exclusive sign of tension headaches and can be seen in patients with migraines.
Trigeminal Autonomic Cephalgias
These cephalgias have features of both a headache and cranial parasympathetic dysautonomia. In many of these syndromes, the ophthalmologist may be the first to see the patient, because the pain is often localized to the eye or periorbital region. Activation of the normal trigeminal–parasympathetic reflex manifests clinically with sympathetic and parasympathetic dysfunction. Some researchers have suggested that the headache originates from the cavernous sinus because of the intersection between the trigeminal, sympathetic, and parasympathetic pathways in this anatomic location. Based on the seasonal nature of attacks experienced by some patients, the suprachiasmatic nucleus and other higher cortical centers have also been implicated in the pathogenesis of the trigeminal autonomic cephalgia syndromes. Table 2 describes clinical findings of short-lasting headaches (trigeminal autonomic cephalgias). Four major types of these headaches have been described: cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, and hemicrania continua.
This headache syndrome manifests as recurrent episodes of excruciating unilateral orbital or temporal pain. The episodes of pain are often between 15 and 180 minutes. Men are more often affected than women. The attacks occur in phases, each phase lasting anywhere from 4 to 16 weeks with about 1 to 2 phases occurring per year. The pain is termed chronic cluster headache when an episode lasts for more than 1 year with remissions of less than 1 month. Administration of 100% oxygen is therapeutic and an excellent diagnostic test in suspected cases of cluster headache. Ophthalmic manifestations of cluster headaches include conjunctival injection, eyelid edema, and Horner syndrome.
This headache syndrome is characterized by frequent, short attacks of unilateral pain in the temporal or supraorbital region. The attacks can last anywhere from 2 to 30 minutes and occur more than 5 times per day. An attack can be associated with symptoms of sympathetic dysfunction that include conjunctival injection, nasal congestion, rhinorrhea, eyelid edema, forehead or facial sweating, Horner syndrome, and a sense of restlessness or agitation. Paroxysmal hemicrania responds exquisitely to nonsteroidal anti-inflammatory medications such as indomethacin.
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)
These attacks are brief (5 to 240 seconds), frequent (3 to 200 times per day), and predominantly seen in men. Anterior segment pathology, such as intermittent angle-closure glaucoma or dry eyes, or a posterior fossa mass can mimic the symptoms of SUNCT and should be excluded. Although response to medical therapy is poor, there is some evidence suggesting benefit from microvascular decompression for patients with intractable SUNCT and neuroimaging evidence of an aberrant arterial loop impinging on the trigeminal nerve.
This is a rare unilateral headache that is continuous but variable in intensity. Its features include brief (less than 1 minute), sharp pains associated with autonomic (conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, ptosis and/or miosis), and migraine-like symptoms (nausea, phonophobia, photophobia). It responds remarkably well to indomethacin.
Miscellaneous Primary Headache Syndromes
Primary thunderclap or stabbing headache is a sudden-onset, high-intensity pain. It is a diagnosis of exclusion and must be differentiated from an intracranial hemorrhage, venous sinus thrombosis, unruptured vascular malformation, arterial dissection, central nervous system angiitis, reversible benign angiitis, cerebrospinal hypotension, paranasal sinusitis, and pituitary apoplexy. Other headache syndromes include primary cough headaches, primary exertional headache (eg, with sexual activity), and hypnic headache, also termed alarm clock headache.
Secondary Headache Syndromes
Post-Traumatic Headache With and Without Brain Damage
A post-traumatic headache begins within 7 days of the incident traumatic event. The features of the headache are variable, often not well defined, and accompanied by a multitude of neuropsychiatric symptoms, including irritability and poor concentration. Interestingly, there has been no definite relationship established between the severity of head trauma and headache, but in general, post-traumatic headache is less frequent after severe head injury. The pathophysiology of chronic post-traumatic headache is believed to be due to a combination of organic and psychological factors. Post-traumatic headache may be more common in patients with pre-existing psychopathology. In addition, financial incentives also seem to increase the rate of disabilities among patients with post-traumatic headaches. However, focal neurological deficits, decreased level of consciousness, and papilledema require neuroimaging and evaluation by a neurologist.
Vascular headaches are temporally related to a major vascular disorder or event. In many of these conditions, the headache can be the initial warning sign of the vascular disorder or event, such as ischemic stroke, intracranial hemorrhage, arteriovenous malformation, or internal carotid artery dissection.
Headache occurs in 17% to 34% of patients with an acute ischemic stroke. The pain is more common in basilar artery rather than carotid artery territory strokes and is usually described as unilateral and moderate in intensity. In some cases, the headache can last more than 24 hours. Because the dural covering of the posterior cranial fossa is innervated by CN V1, patients with an acute occipital lobe infarction may experience pain in and around the ipsilateral eye. Visual field testing will reveal a contralateral homonymous hemianopia in such cases.
Transient ischemic attacks (TIAs) can also be associated with headaches. In some cases, a TIA can mimic the symptoms of a migraine with aura. A previous history of migraine headache, undetermined episodic headaches in the past, scintillating scotoma, and the characteristic “build up” or fortification of visual symptoms lasting for about 20 to 30 minutes are all suggestive of migraine. TIA symptoms are usually shorter in duration (1 to 10 minutes) than migraine symptoms and positive phenomena are quite rare.
Subarachnoid hemorrhage (SAH) is the most common cause of a sudden intense and incapacitating headache (thunderclap headache or “worst headache of my life”). The pain is usually unilateral and associated with nausea, vomiting, nuchal rigidity, and occasionally fever or cardiac dysrhythmia. Such patients may present to the ophthalmologist because of blurred vision and photophobia. Eighty percent of nontraumatic cases of SAH are due to a ruptured intracranial aneurysm. Noncontrast computed tomography (CT) scan of the head will demonstrate hyperintense signal (representing blood) within the subarachnoid and cisternal spaces. A lumbar puncture will confirm the diagnosis—red blood cells that do not clear as more cerebrospinal fluid is removed. An aneurysmal SAH is a neurosurgical emergency associated with a very high morbidity and mortality rate. The headache is caused by the dual mechanism of a momentary increase in intracranial pressure and meningeal irritation from blood introduced into the subarachnoid space. The chemical irritation of SAH can induce seizures and prolonged cerebral vasospasm. Intraretinal or vitreous hemorrhage may be seen (Terson syndrome).
A sentinel headache is a transient (up to 2 days) pain syndrome due to a limited aneurysmal SAH that resolves spontaneously. It has also been termed “a warning leak” because it precedes the onset of a major SAH by a few days and can be misinterpreted as a migraine headache.
Headaches from subdural or epidural hematomas are often underreported because of the associated symptoms of decreased level of consciousness and focal neurologic signs. An acute epidural hematoma can be accompanied by a lucid interval that can later deteriorate into a state of coma. Therefore, a patient with significant head trauma should be observed over time despite being alert immediately after trauma. A chronic epidural or subdural hematoma may cause a headache associated with memory loss and nausea that may be mistaken for a post-traumatic headache syndrome until focal neurologic deficits appear.
Arteriovenous malformation (AVM)
The pain associated with an AVM can be mistaken for a migraine with aura. An important differentiating characteristic of an AVM-associated headache from a migraine headache is the same-side repetitive nature of the pain, which is in contrast to the unilateral pain of a migraine headache that switches sides from attack to attack. Thus, persistent unilateral migraine should be assessed with neuroimaging to exclude the presence of an AVM.
Internal carotid artery (ICA) dissection
ICA dissection presents with sudden-onset neck, head, or facial pain described as moderate to severe in intensity with a throbbing quality. The pain may be the presenting symptom in up to 75% of cases and as many as 60% of patients may have an ipsilateral Horner syndrome. Other neuro-ophthalmic manifestations include transient vision loss, anterior or posterior ischemic optic neuropathy, central retinal artery occlusion, ocular motor cranial nerve palsy, and ocular ischemic syndrome.
ICA dissections can occur after major or minor head and neck trauma. In particular, chiropractic cervical manipulation has been shown to precipitate an ICA dissection. Other underlying etiologies include Marfan syndrome, Ehler-Danlos syndrome, fibromuscular dysplasia, and syphilis. Patients suspected of having an ICA dissection should undergo either a computed tomography angiography (CTA) or magnetic resonance angiography (MRA). A diagnostic conventional catheter angiogram is not typically required given the technical advancements and sensitivity of CTA, MRA, and MRI. An axial, fat suppressed, T1-weighted MRI can show a crescentic hyperintense signal abnormality within the vessel wall, which represents a mural hematoma. In addition, the vessel diameter is enlarged from normal due to the expansion of the vessel wall from the mural hematoma. To date there has been no randomized controlled trial to determine the most efficacious treatment of ICA dissection. However, anticoagulation therapy should be considered especially in patients seen within 2 weeks from symptom onset.
Headaches are common with all types of meningitis. Associated neurologic findings include nuchal rigidity and Kernig or Brudzinski signs. The headache is often times continuous and nonlocalizing. There may be optic disc edema or sixth nerve palsy due to increased intracranial pressure. When meningitis is suspected, urgent neurologic assessment is required.
Pituitary apoplexy is a rare but life-threatening condition. It is caused by a hemorrhage into or infarction of the pituitary gland, usually in the presence of a pre-existing pituitary tumor. The headache is acute, severe (thunderclap), and retro-orbital or frontal in location. Upward expansion of the pituitary gland from the hemorrhage may result in compression of the visual apparatus causing unilateral or bilateral vision loss. Lateral expansion into the cavernous sinus may produce unilateral or bilateral, single or multiple ocular motor cranial neuropathies (Figure 2). MRI is the neuroimaging modality of choice in a suspected case of pituitary apoplexy. Management involves urgent neurosurgical decompression of the optic chiasm and medical therapy of the hypopituitarism.
Giant Cell Arteritis (GCA)
The headache in GCA is the result of inflammation within arteries supplying the scalp. In particular, inflammation of the branches of the superficial temporal artery results in focal scalp tenderness. The head pain can be variable in intensity and imitate any of the primary headache syndromes. Thus, although headache is a nonspecific symptom of GCA, any recent-onset headache or change in character of long-standing headaches in a patient older than 55 years should raise the suspicion for GCA and supporting clinical and/or laboratory data should be obtained. Attacks of transient visual loss may be a harbinger of permanent visual loss. GCA is a medical emergency because of the major risk of irreversible vision loss. An elevated erythrocyte sedimentation rate, in combination with a high C-reactive protein level is highly sensitive but not specific of GCA. The gold standard for confirming the diagnosis of GCA is a superficial temporal artery biopsy.
Suspected cases of GCA should be treated immediately with high-dose oral or intravenous corticosteroids (Figure 3). The superficial temporal artery biopsy can be performed within 7 to 10 days from the initiation of treatment. The headache usually responds dramatically to corticosteroid treatment.
Elevated Intracranial Pressure (ICP)
Increased ICP can be caused by an intracranial space-occupying lesion, communicating hydrocephalus, a meningeal process, venous sinus obstruction, metabolic disorders, or primary and secondary idiopathic intracranial hypertension (IIH) syndromes (Figure 4). The headache associated with increased ICP is often occipital or retro-orbital in location. It is generally worse upon awakening, exacerbated by straining or bending forward, and may have migrainous features. Some patients may describe a pulsatile tinnitus.
IIH is characterized by an increase in ICP in an otherwise neurologically intact person (except for sixth cranial nerve palsy) with normal neuro-imaging and cerebrospinal fluid (CSF) composition. Its incidence is greatest in overweight women in their reproductive years. The initial management of IIH involves weight reduction and/or ICP reduction with oral acetazolamide. In medically unresponsive cases, a CSF diversion procedure or optic nerve sheath fenestration is required to treat the headache or prevent progressive visual loss. Thus, patients with suspected IIH should be referred for timely neuro-ophthalmologic consultation and management.
This condition is usually caused by a spontaneous or iatrogenic (post-lumbar puncture) CSF leak. In contrast to intracranial hypertension, the headache of intracranial hypotension is worse upon standing. The location of the pain can be either focal (frontal or occipital region) or diffuse. The headache is often described as a dull, throbbing pain worsened by straining. Sixth cranial nerve paresis (unilateral or bilateral) has been reported in some patients with intracranial hypotension.
Treatment of intracranial hypotension involves determining the location of the CSF leak followed by either surgical repair or a blood patch. Theophylline, caffeine, and bed rest can minimize the post-lumbar headache.
Medication Overuse Headache (MOH)
MOH has also been termed rebound headache, drug-induced headache, or medication misuse-headache. Typical medications resulting in MOH include ergotamine, triptans, analgesics, opioids, and combination analgesics. The disorder seems to be more prevalent among patients with a predisposition for headaches and in the setting of a chronic daily headache.
Headaches may develop in some patients with systemic hypertension if the autoregulatory mechanisms that maintain a constant cerebral blood flow are affected. Acute elevations in arterial blood pressure cause localized cerebral edema, ischemia, or hemorrhage and result in a headache. In severe cases, optic nerve swelling, often with retinal hemorrhages, can be observed from either papilledema or ischemic optic neuropathy. Headaches occur in about 75% of patients with hypertensive encephalopathy.
High-altitude headaches, diving headaches, and sleep apnea headaches are classified under headaches caused by hypoxia/hypercapnia. Acute mountain sickness is characterized by headaches, nausea, fatigue, sleep disturbance, and anorexia. Low-dose acetazolamide can minimize or prevent symptoms. The headaches usually respond to low-potency analgesics.
Central Facial Pain and Cranial Neuralgia
Neuralgic pain is usually brief, severe and electric or burning in nature. It is caused by compression or irritation of the central nervous system pathways.
Also known as tic douloureux, trigeminal neuralgia is characterized by unilateral, paroxysmal (less than 2 minutes) pain affecting one or more divisions of CN V. Only about 5% of cases involve CN V1. Between attacks, there is no pain or sometimes just a dull, mild background pain. In many cases, the pain is triggered by sensory stimulation of the face. However, sometimes other sensory stimulation such as bright lights or loud sounds can trigger an attack. In some cases, neuroimaging can show compression of the CN V root by a dolichoectatic vessel. Typically, patients with trigeminal neuralgia respond quite well to carbamazepine, although surgical decompression or glycerol rhizotomy may be required in refractory cases.
Occipital neuralgia presents with paroxysms of pain in the distribution of the greater, lesser, and/or third occipital nerve. Tender trigger points involving the cervical muscles or pain from atlantoaxial and upper zygapophysial joint disease may give similar symptoms to occipital neuralgia. MRI of the brain and cervical spine are indicated in suspected cases of neural compression. Treatment options for occipital neuralgia include medical therapy with medications given classically for neuralgic pain such as gabapentin, amitriptyline, carbamazepine, and baclofen. Other treatment options include local anesthetic and corticosteroid injection. The efficacy of botulinum toxin injections has not been fully explored to date. In refractory cases, pulsed radiofrequency treatment can be considered.
This type of neuralgia is the result of trauma, surgery, neoplastic infiltration/compression or idiopathic damage to the supraorbital nerve. The pain is distributed over the course of the supraorbital nerve with tenderness of the region on clinical examination. Pain management can be delivered by a local anesthetic block or corticosteroid injection.
Post-herpetic neuralgia (PHN)
PHN is a sequela of reactivation of dormant varicella zoster virus (shingles). CN V1 is involved in 80% of cases affecting the head. Shingles is most often seen in the elderly (>60 years of age) and immunocompromised patient. The characteristic skin rash with vesicle formation precedes the pain by less than 1 week, but the pain can persist for several months to years. Multiple medications have been used in the treatment of PHN including analgesics, tricyclic antidepressants, gabapentin, and pregabalin.
This type of migraine is characterized by recurrent attacks of headaches associated with paralysis of one or more of the ocular motor cranial nerves. It is a rare condition mostly seen in children. The third cranial nerve (with pupil involvement) is most often affected. The headache lasts about a week and may precede the external ophthalmoplegia by a few days. MRI can show thickening and enhancement of the involved ocular motor nerve. There is no treatment for ophthalmoplegic migraine.
Idiopathic facial pain
This condition is characterized by a persistent facial pain that is not attributed to any other disorder and is not associated with sensory loss. It is often localized to the nasolabial fold or one side of the chin, but may spread to the jaw, face, and neck. It may develop after a dental procedure and is more commonly seen in women between the ages of 30 to 50 years. Psychiatric comorbidities are often present in patients with idiopathic facial pain syndrome.