High-Risk Headaches

High-risk headaches, sometimes also referred to as red-flag headaches, encompass secondary causes of headache that can result in irreversible end-organ damage, neurologic deficits, loss of vision, and even death. Entities such as subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH), meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis/ encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. Diagnosis of a high-risk headache requires a high degree of clinical suspicion and is made by conducting a thorough clinical evaluation followed by a targeted workup for the most likely etiology. Management depends on the etiology but consists of prompt treatment of the underlying cause and stabilization of accompanying organ dysfunction.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Overview

Definition

A high-risk headache is any new and sudden onset, typically severe, headache with the potential to cause damage to cerebral or precerebral structures or functions.

Etiology

There are many etiologies of high-risk headache that the clinician should be aware of and work to rule out when a severe headache is encountered. The most common etiologies are presented here, separated into vascular, infectious, neoplastic, and miscellaneous causes.

Table: Vascular etiologies of high risk headaches
Clinical entity Historical clues/risk factors Clinical features
Subarachnoid hemorrhage ( SAH SAH Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH))
  • Sudden onset
  • Severe intensity at onset
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope/near syncope
  • Neck pain Neck Pain Neck pain is one of the most common complaints in the general population. Depending on symptom duration, it can be acute, subacute, or chronic. There are many causes of neck pain, including degenerative disease, trauma, rheumatologic disease, and infections. Neck Pain/stiffness
  • Diplopia
  • Meningeal signs
  • Nausea and vomiting
Reversible cerebral vasoconstriction syndrome (RCVS)
  • Sudden onset
  • Severe intensity at onset
  • Short duration
  • Recurrent
  • Associated with triggers
  • Transient neurologic deficits from vasospasm
  • Neurologic deficits may persist (if vasospasm persists)
Cervical artery dissection/vertebral artery dissection
  • Associated with head and/or neck trauma
  • Prominent neck pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • New-onset dizziness
  • New-onset tinnitus
  • Cranial nerve palsy:
    • Nystagmus
    • Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome
  • Cervical artery bruit
  • Presents with cerebrovascular accident Cerebrovascular accident An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke/ transient ischemic attack Transient ischemic attack Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) ( TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA))
Cerebral vein thrombosis/dural sinus thrombosis
  • Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state/risk factors
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • Postpartum
  • Neurologic deficits inconsistent with arterial ischemia
  • Associated with seizure
  • Papilledema on fundoscopy
  • Encephalopathy
Subdural hematoma/epidural hematoma
  • Associated with head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma
  • Anticoagulant therapy
  • Gradual progression of neurologic deficit and/or mental status
  • Posterior fossa hematoma →
    • Nausea/vomiting
    • Visual changes
    • Ataxia
    • Dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia
    • Anisocoria
    • Nuchal rigidity
Intraparenchymal hemorrhage (IPH)
  • Sudden onset
  • Associated with severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Anticoagulant therapy
Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables presentation depending on site of bleed (much like cerebrovascular accident Cerebrovascular accident An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke/ TIA TIA Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA))
Idiopathic intracranial hypertension Idiopathic Intracranial Hypertension Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a clinical disorder that presents with symptoms due to increased intracranial pressure (ICP; ≥ 20 mm Hg) or CSF pressure (> 250 mm H2O), with no structural changes or other attributable causes. Idiopathic Intracranial Hypertension
  • Overweight/obese female
  • Childbearing age
  • Transient/intermittent visual symptoms
  • Papilledema on fundoscopy
  • Abducens nerve palsy
  • Other cranial nerve palsies
  • Visual deficit
  • Tinnitus
Spontaneous intracranial hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Severe headache in upright position
  • Headache improves with caffeine and while lying flat
  • Headache worsens with Valsalva maneuver
  • Common after dural puncture
  • Neurologic findings may be absent or widely variable
  • Tinnitus
  • Cervical pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Nausea and vomiting
Giant-cell arteritis
  • Age > 50 years
  • Sudden-onset visual disturbances (often monocular)
  • Jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint claudication
  • Palpable or nodular temporal arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries
  • Fever
  • Elevated acute-phase reactants:
    • CRP
    • Erythrocyte sedimentation rate (ESR)
Hypertensive encephalopathy
  • Gradual-onset headache in the setting of severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Seizures
  • Altered mental status
  • Severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Papilledema and retinal hemorrhage on fundoscopy
  • Hematuria and proteinuria on urinalysis
  • Encephalopathy
Posterior reversible encephalopathy syndrome
  • Gradual-onset headache inconsistently associated with severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Seizures
  • Nausea and vomiting
  • Visual changes
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care or postpartum period
  • Hypertension may or may not be present
  • Papilledema and retinal hemorrhage on fundoscopy
  • Hematuria and proteinuria on urinalysis
  • Encephalopathy
Table: Infectious etiologies of high-risk headaches
Clinical entity Historical clues/risk factors Clinical features
Meningitis and/or encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Toxic-appearing
  • Fever
  • Neck pain Neck Pain Neck pain is one of the most common complaints in the general population. Depending on symptom duration, it can be acute, subacute, or chronic. There are many causes of neck pain, including degenerative disease, trauma, rheumatologic disease, and infections. Neck Pain/stiffness
  • Altered mental status/level of consciousness
  • Fever
  • Meningism
  • Altered mental status/level of consciousness
  • Seizure
  • Cranial nerve palsies
  • Petechiae or purpura
Brain abscess Brain abscess Brain abscess is a life-threatening condition that involves the collection of pus in the brain parenchyma caused by infection from bacteria, fungi, parasites, or protozoa. The most common presentation is headache, fever with chills, seizures, and neurological deficits. Brain Abscess
  • Onset of headache may be sudden or gradual
  • Recent history of infection:
    • Direct spread ( sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis, otitis)
    • Distant spread ( endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis, bacteremia)
  • Fever may be variable
  • Neck pain Neck Pain Neck pain is one of the most common complaints in the general population. Depending on symptom duration, it can be acute, subacute, or chronic. There are many causes of neck pain, including degenerative disease, trauma, rheumatologic disease, and infections. Neck Pain/stiffness may be variable
  • Papilledema on fundoscopy
  • Insidious onset of focal neurologic deficits or cranial nerve palsies
Table: Neoplastic etiologies of high-risk headaches
Clinical entity Historical clues/risk factors Clinical features
Brain tumor
  • Cancer
  • Headache worsens with cough, Valsalva maneuver
  • Insidious headache onset, but may be sudden if tumor bleeds
  • Nausea and vomiting
  • Papilledema on fundoscopy
  • Seizure
  • Altered mental status/level of consciousness
  • Neurologic deficits corresponding to tumor location
Colloid cyst of 3rd ventricle
  • Headache worsens in upright position, improves with lying flat
  • Altered mental status
  • Symptoms may fluctuate
  • Altered mental status
  • Diplopia
  • Memory issues
  • Vertigo Vertigo Vertigo is defined as the perceived sensation of rotational motion while remaining still. A very common complaint in primary care and the ER, vertigo is more frequently experienced by women and its prevalence increases with age. Vertigo is classified into peripheral or central based on its etiology. Vertigo
Pituitary apoplexy
  • Associated with pituitary tumors (most often benign)
  • Sudden-onset headache associated with infarction/bleeding into tumor
  • Nausea and vomiting
  • Altered mental status
  • Visual/oculomotor defect
  • Endocrine dysfunction
Table: Other etiologies of high-risk headaches
Clinical entity Historical clues/risk factors Clinical features
Acute narrow-angle glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
  • Ocular pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Ocular injection
  • Loss of vision
  • Nausea and vomiting
  • Conjunctival injection
  • Corneal clouding; fixed
  • Pupillary dilation with lack of constriction
  • Elevated intraocular pressure
CO toxicity
  • Acute CO exposure
  • Headache improves with separation from CO
  • Nausea/vomiting
  • Light-headedness/dizziness
  • Fatigue/malaise
  • Seizure
  • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Red macula on fundoscopy
Preeclampsia/eclampsia
  • Pregnant woman at > 20 weeks
  • Sudden-onset headache associated with blood pressure > 140/90 mm Hg
  • Tinnitus
  • Visual disturbance
  • Seizure
  • Proteinuria
  • Brisk deep tendon reflexes (DTRs)
  • Placental abruption
  • Symptoms abate on delivery of the fetus

Clinical Presentation

Historical clues

  • Sudden onset (variable onset among causes):
    • Peaks to maximum intensity in > 1 minute (thunderclap headache)
    • Generally lasts > 5 minutes; may persist or wax and wane
  • Severe intensity
  • No history of similar headaches:
    • “1st headache of my life”
    • “Worst headache of my life”
  • Active or recent source of infection:
    • Direct spread from cranial/extracranial structures (e.g., ears, eyes, mouth)
    • Bacteremic spread (e.g., endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis)
  • Altered mental status:
    • Altered level of consciousness
    • Personality change
    • Confusion
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope or seizure
  • Visual disturbance:
    • Visual loss
    • Visual-field deficit
    • Diplopia
  • Associated with exertion:
    • Walking
    • Climbing stairs
    • Sexual intercourse
    • Jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint claudication
  • Associated with trauma:
    • Motor vehicle accident
    • Fall
    • Cervical manipulation (chiropractic or osteopathic)
  • Age > 50 years
  • Immunosuppression (↑ risk of infection, lymphoma, and leukemia):
    • Autoimmune disease
    • HIV/AIDS
    • Chronic steroids
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care/postpartum
  • Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state
  • Bleeding diathesis 
  • Medications/illicit drugs:
    • Anticoagulants
    • Sympathomimetics 
  • Toxin exposure:
    • CO
    • Sodium hypochlorite (bleach)
    • Formaldehyde
  • Insect vector exposure (or travel to endemic areas):
    • Ticks
    • Mosquitos

Physical examination findings

  • Vital sign abnormalities:
    • Severe hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension/ hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Severe tachycardia/bradycardia
    • Fever/ hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia
    • Hypoxia 
  • Neurologic findings:
    • Cranial nerve palsy
    • Focal neurologic deficits
    • Mental status changes
  • Altered level of consciousness
  • Meningeal signs: neck stiffness
  • Ophthalmologic findings:
    • Papilledema
    • Retinal hemorrhage
    • Visual deficit
    • Elevated intraocular pressure (acute glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma)
    • Corneal clouding (acute glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma)
  • Palpatory temporal artery findings ( temporal arteritis Temporal arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis):
    • Diminished pulses
    • Firmness/ edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Nodularity
  • Rash:
    • Erythema migrans (Lyme meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis)
    • Petechiae/purpura (bacterial meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Evidence of active purulent infection:
    • Sinusitis
    • Otitis
    • Facial/ orbital cellulitis Orbital cellulitis Orbital and preseptal cellulitis are infections differentiated by the anatomic sites affected in the orbit. Infection posterior to the septum is orbital cellulitis. Inoculation with the pathogen can occur through trauma or surgery. Cellulitis also occurs via extension from a nearby structure (such as from sinus infection or sinusitis). Orbital and Preseptal Cellulitis
    • Gingivitis

Diagnosis and Management

History

It is important to take a focused, thorough history: 

  • Headache descriptors:
    • Onset
    • Location
    • Duration
    • Intensity
    • Similarity to previous headaches
  • To narrow etiology, ask about:
    • Recent trauma
    • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care/postpartum
    • Recent/current infection
    • Vascular risk factors/comorbidities
    • Cancer history 
    • Immunocompromised states

Physical examination

It is important to do a focused, thorough examination:

  • Vital signs, especially:
    • Temperature
    • Blood pressure
  • Neurologic exam:
    • Level of consciousness
    • Mental status/orientation/cognition
    • Cranial nerves Cranial nerves There are 12 pairs of cranial nerves (CNs), which run from the brain to various parts of the head, neck, and trunk. The CNs can be sensory or motor or both. The CNs are named and numbered in Roman numerals according to their location, from the front to the back of the brain. Overview of the Cranial Nerves
    • Screen limbs for motor/sensory deficit
    • Gait/coordination
  • Extracranial exam:
    • Carotid bruit
    • Meningismus
    • Ear infection
    • Sinus tenderness
    • Facial/ orbital cellulitis Orbital cellulitis Orbital and preseptal cellulitis are infections differentiated by the anatomic sites affected in the orbit. Infection posterior to the septum is orbital cellulitis. Inoculation with the pathogen can occur through trauma or surgery. Cellulitis also occurs via extension from a nearby structure (such as from sinus infection or sinusitis). Orbital and Preseptal Cellulitis
    • Visual-field testing
    • Fundoscopic exam: papilledema, hemorrhage
    • Intraocular pressure testing
    • Temporal artery palpation
  • Other pertinent exam findings:
    • Heart murmur
    • Abnormal heart rhythm
    • Splinter hemorrhages
    • Osler nodes
    • Janeway lesions
    • Homan’s sign
    • Rash
    • Evidence of distant infection

Laboratory evaluation

Suspected infectious etiology:

  • WBC count with differential
  • Cultures:
    • Blood
    • CSF
    • Purulent nasal/otic/optic/ skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin discharge
    • Wound, urine, sputum, etc., of distant spread is suspected
  • CSF studies (obtained via lumbar puncture (LP)):
    • Opening pressure
    • Protein 
    • Glucose 
    • Cell counts
    • Gram stain

Suspected hematologic/vascular etiology:

  • Temporal arteritis:
    • ESR
    • CRP
  • Venous sinus/cerebral vein thrombosis:
    • D-dimer
    • Hypercoagulation workup 
  • Intracerebral/intracranial hemorrhage:
    • PT/PTT for evaluate for bleeding diathesis (native or iatrogenic)
    • CSF for the presence of erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes (obtained via LP)
      • Performed after initial CT if negative for bleeding in suspected SAH SAH Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH)
      • Beware misinterpretation of a traumatic tap
      • If traumatic tap is suspected, opening pressure > 20 mm Hg indicates a pathologic intracranial process

Suspected neoplastic etiology:

  • CSF examination for presence of malignant cells
  • May consider liquid biopsy for metastatic markers (approximately 1-week turnaround time)
  • May consider measuring pituitary hormone levels if suspected pituitary involvement

Neuroimaging

  • CT of the head without contrast:
    • Rapidly available in most emergency triage settings
    • Often the 1st test performed regardless of suspected etiology 
    • Test of choice for thunderclap headaches to rule out SAH SAH Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage (SAH)
    • Perform before LP if the following restrictions exist:
      • Papilledema on fundoscopy
      • Altered level of consciousness
      • Presence of new-onset neurologic deficit
      • Immunocompromised state
      • Known or suspected intracranial mass effect
      • Headache presents with new-onset seizure
    • 2nd-line method for head imaging in pregnancy:
      • Radiation is generally avoided in pregnancy
      • Radiation scatter for head CT is distant from the fetus
  • CT of the head/brain with contrast
  • CTA
  • MRI of the head with and without contrast
  • MRA

Evaluation and management of specific high-risk headaches

Thunderclap headache: 

  • CT without contrast: initial test of choice
  • LP should be performed if CT negative:
    • Evaluate for presence of erythrocytes Erythrocytes Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes
    • Measure opening pressure
  • If CT or LP suggests hemorrhage, further imaging is warranted to evaluate for source:
    • CTA
    • MRA
    • Traditional fluoroscopic angiography 
  • If any of the above suggest hemorrhage/vasospasm → immediate consultation with a neurosurgeon or vascular interventionist 

Meningitis or encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis:

  • On initial suspicion, obtain blood cultures 
  • Begin antibiotics:
    • Antibacterials for common bacterial entities
    • Antivirals, antifungals, antiprotozoals, antirickettsials as guided by clinical suspicion
  • Prior to performing LP, CT without contrast to evaluate for contraindications to LP:
    • Mass lesion
    • Hydrocephalus
  • LP if no contraindications to obtain CSF and evaluate for:
    • Opening pressure
    • Protein 
    • Glucose 
    • Cell counts
    • Gram stain
  • Consider neurology and/or infectious disease consultation

Increased ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP):

  • MRI without and with contrast preferred to evaluate for intracranial mass/pathology:
    • Neoplasm
    • Metastasis
    • Abscess
    • Hematoma
    • Hydrocephalus
    • Cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema from ischemia/infarction
  • CT with and without contrast if MRI is contraindicated/unavailable
  • LP for opening pressure and to evaluate for underlying infection if imaging negative

CO toxicity:

  • Administer high-flow supplemental oxygen
  • Obtain arterial blood gas (ABG) sample 
  • Symptoms generally improve as CO levels diminish

Headache with neck pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain:

  • Stabilize any instability related to head/neck trauma
  • Neurologic exam for Horner syndrome Horner syndrome Horner syndrome is a condition resulting from an interruption of the sympathetic innervation of the eyes. The syndrome is usually idiopathic but can be directly caused by head and neck trauma, cerebrovascular disease, or a tumor of the CNS. Horner Syndrome/cranial nerve palsies
  • CT without contrast is the initial test of choice to evaluate for intracranial pathology
  • CT and CTA of head and neck with contrast if initial CT negative to evaluate for:
    • Carotid artery dissection
    • Vertebral artery dissection

Headache in adults > 50 years of age:

  • Examine for temporal artery abnormalities
  • MRI with and without contrast to evaluate for:
    • Mass
    • Hemorrhage
    • Elevated intracranial pressure ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)
  • CT with and without contrast, if MRI contraindicated/unavailable 
  • Start corticosteroids and obtain immediate ophthalmology consultation if temporal arteritis Temporal arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis suspected
  • Further management/consultation depending on findings

Headache in immunosuppressed individuals:

  • CT without contrast to evaluate for:
    • Infection
    • Lymphoma
    • Leukemia 
  • MRI with and without contrast to evaluate for:
    • Abscess 
    • Encephalitis
    • Causes of elevated ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)
      • Hydrocephalus
      • Hemorrhage
      • Mass effect
    • LP if imaging is negative to evaluate for:
      • Opening pressure
      • Infection
      • Malignant cells
    • Consider infectious disease, neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery, neurology consultation depending in findings

Headache in individuals with cancer:

  • MRI with and without contrast to evaluate for metastases and infection 
  • CT with and without contrast if MRI contraindicated or unavailable 
  • Consider oncology, neurosurgery Neurosurgery Neurosurgery is a specialized field focused on the surgical management of pathologies of the brain, spine, spinal cord, and peripheral nerves. General neurosurgery includes cases of trauma and emergencies. There are a number of specialized neurosurgical practices, including oncologic neurosurgery, spinal neurosurgery, and pediatric neurosurgery. Neurosurgery, neurology consultation depending in findings

Headache during pregnancy/postpartum:

  • Evaluate for preeclampsia/eclampsia 
  • Blood pressure management/seizure stabilization as indicated
  • Immediate obstetrics/maternal-fetal medicine consultation
  • MRI without contrast is preferred method of neuroimaging to evaluate for:
    • Cerebral vein or venous sinus thrombosis
    • Causes of elevated ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)
      • Hydrocephalus
      • Hemorrhage
      • Mass effect
  • LP if neuroimaging negative and increased ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP) or if infection suspected

Headache with visual impairment, periorbital pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, ophthalmoplegia: 

  • MRI of the head and orbits to evaluate for:
    • Glaucoma
    • Infection
    • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
    • Tumor 
  • Measure intraocular pressure
  • Start corticosteroids and obtain immediate ophthalmology consultation if temporal arteritis Temporal arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis is suspected.
  • Immediate ophthalmology consultation if glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma suspected
  • Outpatient ENT consultation if sinus involvement suspected
  • Outpatient dental consultation if temporomandibular joint (TMJ), gingival, or dental disorder suspected 
  • Outpatient neurology or pain management Pain Management Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective experience. Acute pain lasts < 3 months and typically has a specific, identifiable cause. Pain Management consultation if trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia suspected

Clinical Relevance

  • Cluster headache: may be of sudden onset and may be severe, but sufferers are generally very aware that frequent, sudden, and severe headaches are to be expected during a cluster period. Although neurologic symptoms are typical of cluster headache, they are autonomic in nature, predictable, reproducible, and transient. Thorough clinical evaluation with neuroimaging is indicated at the initial workup for cluster headache to rule out high-risk etiologies. A change in the pattern of headaches warrants emergent reevaluation. 
  • Migraine headache Migraine Headache Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache: Although typically gradual in onset, migraine headaches may be severe and accompanied by neurologic symptoms. These neurologic symptoms are often part of the typical migraine milieu for the individual; they are predictable, reproducible, and transient. Clinical evaluation with neuroimaging is indicated at the initial occurrence of migraine headache with neurologic symptoms to rule out high-risk etiologies. A change in the pattern of headaches warrants emergent reevaluation.
  • Cervicogenic headache: headache caused by referred pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain from the upper cervical joints. Typically unilateral, of moderate to severe intensity, and increased by movement of the head, with radiation from the occipital to the frontal regions. Many high-risk headaches also present with cervical symptoms. The distinguishing feature is the absence of structural cervical disease.

References

  1. Potter T, Schaefer TJ. (2021). Hypertensive encephalopathy. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK554499/
  2. Hobson EV, Craven I, Blank SC. (2012). Posterior reversible encephalopathy syndrome: a truly treatable neurologic illness. Perit Dial Int 32:590–594. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524908/
  3. Tenny S, Thorell W. (2021). Colloid brain cyst. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK470314/
  4. Ranabir S, Baruah MP. (2011). Pituitary apoplexy. Indian Journal of Endocrinology and Metabolism 15(Suppl 3):S188–S196. https://doi.org/10.4103/2230-8210.84862
  5. Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi JM. (2011). Pre-eclampsia: pathophysiology, diagnosis, and management. Vascular Health and Risk Management 7:467–474. https://doi.org/10.2147/VHRM.S20181
  6. Cutrer F. (2021). Evaluation of the adult with nontraumatic headache in the emergency department. Retrieved August 11, 2021, from https://www.uptodate.com/contents/evaluation-of-the-adult-with-nontraumatic-headache-in-the-emergency-department?search=emergency%20headaches&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H25

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