Differential Diagnosis of Headache:
A. Unilateral headache is an invariable feature of cluster headache and occurs in the majority of migraine
attacks; most patients with tension-type headache report bilateral pain.
B. Ocular or retroorbital pain suggests a primary ophthalmic disorder such as acute iritis or glaucoma, optic
(II) nerve disease (eg, optic neuritis), or retroorbital inflammation (eg, Tolosa–Hunt syndrome). It is also
common in migraine or cluster headache.
C. Paranasal pain localized to one or several sinuses, often associated with tenderness of the overlying periosteum and skin, occurs with acute sinus infection or outlet obstruction.
D. Focal headache may result from intracranial mass lesions, but even in such cases it is replaced by bioccipital and bifrontal pain when the intracranial pressure becomes elevated.
E. Bandlike or occipital discomfort is commonly associated with tension-type headache. Occipital localization can also occur with meningeal irritation from infection or hemorrhage and with disorders of the joints, muscles, or ligaments of the upper cervical spine.
F. Pain within the first (V1) division of the trigeminal nerve, characteristically described as burning in quality,
is a common feature of postherpetic neuralgia.
G. Lancinating pain localized to the second (V2) or third (V3) division of the trigeminal (V) nerve suggests
trigeminal neuralgia (tic douloureux).
H. The pharynx and external auditory meatus are the most frequent sites of pain caused by glossopharyngeal neuralgia.
Trigeminal autonomic cephalalgias
Meningitis or encephalitis (see Approach to Meningitis and Encephalitis)
Benign intracranial hypertension (pseudotumor cerebri)
Hx: Bilateral, pressing (or tightening) pain of mild to moderate intensity not aggravated by physical activities and without nausea.
Tx: Drug treatment usually begins with NSAIDs. The addition of caffeine to aspirin or NSAIDs increases treatment efficacy. Prophylaxis, often with a tricyclic antidepressant, may be needed.
Migraine With Aura (Classic Migraine): In 30% of migraine patients, headache is preceded by transient neurologic symptoms (aura). The most common auras are visual alterations, particularly hemianopic field defects and scotomas (blind spots) and scintillations (flickerings) that enlarge and spread peripherally. Photopsia (sparks or flashes of light), fortification spectra (arcs of flashing light that often form a zigzag pattern), or a scotoma (blind spots), scintillations (flickerings). Tingling is also possible A throbbing unilateral (hemicranial) headache ensues. The duration of episodes is greater than 2 hours and less than 1 day in most patients. During the headache, prominent associated symptoms include nausea, vomiting, photophobia, phonophobia, irritability, osmophobia, and lassitude. Vasomotor and autonomic symptoms are also common. Light-headedness, vertigo, ataxia, or altered consciousness may occur in basilar migraine, which can be distinguished from stroke by both the gradual onset (“migrainous march”) and spontaneous resolution of symptoms. Migraine occasionally produces neurologic deficits that persist into or beyond the pain phase (eg, hemiplegic migraine) and may rarely cause stroke.
Migraine without aura (Common Migraine): is much more common than migraine with aura and produces headache that is most often bilateral and periorbital in location. The pain may be described as throbbing, particularly when severe. Nausea, vomiting, and photophobia are common.
Common dietary triggers include caffeine; nitrates or nitrite preservatives; phenylethylamine, tyramine, and xanthine in aged cheese, red wine, beer, champagne, and chocolate; monosodium glutamate (food additive); dairy products; and fatty foods.
POUND: Pulsatile quality (headache described as pounding or throbbing), One-day duration (episode may last 4-72 hours if untreated), Unilateral in location, Nausea or vomiting, and Disabling intensity (altered usual daily activities during headache episode).
Tx: Divided into measures used to abort attacks in progress (abortive) and to prevent future episodes (prophylactic).
Abortive: Mild attacks are effectively treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen; more severe attacks are treated with a triptan (selective serotonin receptor agonist) [contraindicated in the presence of ischemic vascular disease and uncontrolled hypertension]. Ergot alkaloids (Dihydroergotamine) is an alternative (contraindicated in CAD and pregnancy).
Prevention (prophylactic): β-blockers (such as propranolol, metoprolol, or timolol), tricyclic antidepressants (such as amitriptyline), and anticonvulsants (such as valproate, topiramate, or gabapentin).
Some herbal products such as feverfew, butterbur root, the mineral magnesium, the vitamin riboflavin, and the antioxidant coenzyme Q10 may have some efficacy in migraine prevention.
Trigeminal autonomic cephalalgias:
Rare. Group of primary headache disorders characterized by excruciating unilateral headache that occurs in association with prominent cranial autonomic features (lacrimation, nasal congestion, rhinorrhea, and conjunctival injection).
Disorders include cluster headache, paroxysmal hemicrania, and SUNCT syndrome.
Hx: Cluster headaches are characterized by unilateral, severe, boring pain that is usually orbital, supraorbital, and/or temporal in location
The time from onset to peak intensity is usually minutes, with the pain lasting 15 minutes to 3 hours.
Accompanying autonomic symptoms include lacrimation, nasal congestion, rhinorrhea, miosis, ptosis, and conjunctival injection. The attacks occur in clusters that last weeks to months, with remissions lasting months to years.
Often associated with unilateral tearing and nasal congestion or rhinitis. Pain is severe, unilateral, and periorbital. More common in men but relatively uncommon overall.
Tx: 100% Oxygen inhalation delivered via a non-rebreather face mask at a flow rate of 6 to 12 L/min for 10 minutes is often effective in terminating the attack. Subcutaneous sumatriptan and nasal zolmitriptan are also effective in treating a cluster headache. Verapamil can be effective in preventing cluster headaches.
Usually worse when lying down. Associated with nasal congestion. Tenderness overlies affected sinus.
Chronic headache with few features of migraine. Tends to occur daily in patients who frequently use headache medications.
Sudden, explosive onset of severe headache (“worst headache of my life”). Preceded by “sentinel” headache in 10%.
Dx: In a minority of patients with a small amount of blood in the subarachnoid space, computed tomography (CT) of the head may initially be normal.
Aneurysm formation is the most common etiology for subarachnoid bleeds, and smoking is considered the most important modifiable risk factor. The most sensitive diagnostic test is the lumbar puncture (LP). The finding one would expect with a subarachnoid hemorrhage is a yellowing of the fluid from the hemolysis of red blood cells. This is known as xanthochromia. Although xanthochromia may be seen through visual inspection (choice E) of CSF, where the CSF is held against a bright white light compared to a tube of water, the most sensitive diagnostic method is spectrophotometry. Spectrophotometry detects blood breakdown products as they progress from oxyhemoglobin to bilirubin. The sensitivity is >95% when a lumbar puncture is performed more than 12 hours after the initial hemorrhage.
Tx: Medical treatment is directed toward preventing elevation of arterial or intracranial pressure that might re-rupture the aneurysm or AVM. Typical measures include absolute bed rest with the head of the bed elevated 15 to 20 degrees, mild sedation, and analgesics for headache (antiplatelet drugs should be avoided). Because patients who are hypertensive on admission have increased mortality, reducing blood pressure (to approximately 160-170/100 mm Hg) is prudent, but bed rest and mild sedation are often adequate in this regard.
Pressure not too low because some of the elevated pressure may represent a compensatory mechanism to maintain cerebral perfusion pressure in the face of increased intracranial pressure or cerebral arterial narrowing. IV nitroprusside is a good agent to use because it can be titrated with the blood pressure. If the pressure drops too low, the IV can be turned off.
Meningitis or encephalitis
Meningitis is associated with fever and meningeal signs.
Encephalitis is associated with neurologic abnormalities, confusion, altered mental state, or change in level of consciousness.
Post–lumbar-puncture headache is diagnosed by a history of a dural puncture (eg, spinal tap, spinal anesthesia) and is characteristically a postural headache, with marked increase in pain in the upright position and relief with recumbency. The pain is typically occipital, comes on within 48 to 72 hours after the procedure, and lasts 1 to 2 days. Nausea and vomiting may occur. Headache is caused by persistent leak of CSF from the spinal subarachnoid space, with resultant traction on pain-sensitive structures at the base of the brain. The risk of this complication can be reduced by using a small-gauge needle (22 gauge or smaller) for the puncture. Lying flat afterward, for any length of time, does not lessen the risk. Low-pressure headache syndromes are usually self limited.
Cerebrospinal fluid (CSF) rhinorrhea or otorrhea - Leakage of CSF from the nose or ear. CSF rhinorrhea must be distinguished from other causes of rhinorrhea, such as allergic rhinitis. Glucose concentration does not reliably distinguish CSF from nasal mucus, but beta-2 transferrin is unique to CSF, and its presence documents a CSF source of rhinorrhea.
Trigeminal Neuralgia (tic douloureux)
Hx: Characterized by usually unilateral, severe pain in the face in the distribution of the maxillary (V2) and/or mandibular (V3) branches of the fifth cranial nerve (trigeminal nerve). It typically has a stabbing or electric shock-like nature, which lasts briefly for a few seconds and can recur several times. It can be accompanied by a brief facial spasm.
Multiple sclerosis (MS) is one of the few conditions that may present with trigeminal neuralgia bilaterally. This occurs due to demyelination of the nucleus of the trigeminal nerve or the nerve root, which leads to improper signaling of the nerve and paroxysms of severe pain.
Px: Physical examination is typically normal and with the typical history and in the absence of any physical findings,
Tx: It is appropriate to initiate therapy with carbamazepine, which is considered the treatment of choice. In the presence of any neurologic signs on examination, imaging and other studies should be obtained to rule out secondary causes. Other medications which can be effective include phenytoin, gabapentin and baclofen. Surgical decompression can be considered in refractory cases.
DDx: Intracranial Hyprtension
Brain parenchyma, cerebrospinal fluid, and blood are contained within a rigid skull and increased volume of any of these 3 components may cause ICH. Potential etiologies include trauma, space-occupying lesions, hydrocephalus, impaired central nervous system venous outflow, and idiopathic ICH (pseudotumor cerebri).
Hx: Patients typically present with headache (worse at night), nausea/vomiting, and mental status changes (eg, decreased level of consciousness, cognitive dysfunction). Patients may also have focal neurologic symptoms (eg, vision changes, unsteady gait) and seizure. Symptoms can worsen with maneuvers that further increase intracranial pressure (eg, leaning forward, Valsalva, cough).
Px: Signs may include papilledema and focal neurologic deficits. Cushing reflex (hypertension, bradycardia, respiratory depression) is a worrisome finding suggestive of brainstem compression.
Benign intracranial hypertension (pseudotumor cerebri)
The pathology involves impaired absorption of CSF by the arachnoid villi.
Hx: Patients with IIH typically present with holocranial headache, vision changes (blurry vision and diplopia), and pulsatile tinnitus ("whooshing" sound in the ears). Although IIH is frequently seen in young obese women, it has also been associated with certain medications (eg, isotretinoin, tetracyclines, growth hormone, excessive vitamin A). Can lead to blindness.
Px: Neurologic examination is normal but may reveal sixth cranial nerve palsy. Headache aggravated by coughing, straining, or changing position. Cerebrospinal fluid pressure is elevated.
Dx: Initial evaluation of IIH includes complete ocular examination and neuroimaging to exclude secondary causes of intracranial hypertension (eg, mass, hemorrhage, cerebral vein thrombosis). Magnetic resonance imaging (MRI) possibly with magnetic resonance venography (to rule out cerebral vein thrombosis) is the preferred imaging modality. Empty sella is present in about 70% of patients but is not diagnostic. Lumbar puncture (LP) is then indicated to document elevated opening pressure.
Papilledema is not a contraindication to LP unless the patient has evidence of obstructive or noncommunicating hydrocephalus and/or a space-occupying lesion with/without mass effect or midline shift. Pseudotumor cerebri causes a communicating hydrocephalus (ie, pressures in the ventricular and subarachnoid spaces are equilibrated with the lumbar cistern) and therefore LP is considered safe. LP is performed with the patient in the lateral decubitus position with legs extended. An opening pressure of >250 mm H2O is considered abnormal and in the appropriate clinical setting is diagnostic of IIH. Cerebrospinal fluid studies are normal in IIH patients.
Tx: The treatment includes weight reduction and acetazolamide (if weight reduction fails). When medical measures fail or visual field defects are progressive, shunting or optic nerve sheath fenestration is done to prevent blindness, which is the most significant complication of this otherwise benign disorder.
Worse on awakening; generally progressive. Headache aggravated by coughing, straining, or changing position.
"Red flag" symptoms: Awakening from sleep due to headache; focal neurologic findings; more general neurologic findings such as dizziness, lack of coordination, or tingling; fever; neck stiffness or meningeal signs; tenderness or diminished pulse over the temporal artery; diastolic blood pressure >120 mm Hg; or papilledema or decreased visual acuity.
Dx: MRI of the brain is preferable to computed tomography of the head in the evaluation of subacute or chronic headache because of improved sensitivity resulting from superior anatomic resolution.
Occurs almost exclusively in patients aged >50 y. Associated with tenderness of the scalp and temporal artery, jaw claudication, and visual changes.
Fever, headache, focal neurologic deficits; multiple ring-enhancing lesions on CNS imaging; positive toxoplasma serology
All patients newly diagnosed with HIV should be tested for latent infection with serology for T gondii IgG antibody. If serology is positive and CD4 count is <100/mm3, primary prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) reduces the risk of toxoplasmosis dramatically (to 0%-2%).
Patients on antiretroviral treatment can discontinue TMP-SMX when CD4 count is >200/mm3 for 3 months (and there is adequate viral suppression). TMP-SMX is also used for primary prophylaxis against Pneumocystis pneumonia.