Primary vs Secondary Headaches

Overview

Definitions

Primary headaches: a headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (or headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder) not attributable to another disorder:
- Generally benign Benign Fibroadenoma; may be severe, recurrent, and potentially disabling
- No dangerous underlying cause is identified.
- The pathophysiology is incompletely understood.
- The pathophysiologic mechanisms involve overactivity of intracranial and extracranial nociceptors Nociceptors Peripheral afferent neurons which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the dorsal root ganglia. Their peripheral terminals (nerve endings) innervate target tissues and transduce noxious stimuli via axons to the central nervous system. Pain: Types and Pathways and/or related vascular structures.
Secondary headaches: a headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (or headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder) attributable to an underlying disorder:
- May be a manifestation of an underlying systemic, vascular, or neurologic disorder
- A potentially life-threatening etiology may underlies the headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder.
- The pathophysiology of the headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess is commonly related to 1 of the following:
  - Identifiable structural lesion
  - Metabolic abnormality
  - Infectious/inflammatory process

Epidemiology

Primary headaches: 50% of the adult population worldwide meets the clinical criteria for at least 1 primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder:
- tension headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess: approximately 40%
- migraine Migraine 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 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess: approximately 10%
- cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess: approximately 1%
Secondary headaches: Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency and incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is difficult to classify due to inconsistent documentation Documentation Systematic organization, storage, retrieval, and dissemination of specialized information, especially of a scientific or technical nature. It often involves authenticating or validating information. Advance Directives and coding practices among clinicians and institutions.

Etiology

Primary headaches: The pathophysiologic mechanisms generally involve overactivity of intracranial and extracranial nociceptors Nociceptors Peripheral afferent neurons which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the dorsal root ganglia. Their peripheral terminals (nerve endings) innervate target tissues and transduce noxious stimuli via axons to the central nervous system. Pain: Types and Pathways and a complex interplay between neural and vascular structures.
Secondary headaches: The pathophysiologic mechanisms are generally related to an identifiable structural lesion, metabolic abnormality, or infectious/inflammatory process.

Classification

All headaches can be classified as either primary or secondary and subclassified into a variety of schemes developed for clinical, epidemiologic, research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest, and coding purposes. The most common and clinically significant will be covered in detail here:

Primary headaches

Subtypes:

Primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorders may be subclassified by clinical diagnosis criteria:

Migraine Migraine 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
Tension-type headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
Cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess

Frequency:

Primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorders may be subclassified based on frequency of occurrence:

Low-frequency episodic Low-frequency episodic < 10 headache days per month. Migraine Headache: < 10 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess days per month
High-frequency episodic High-frequency episodic 10–14 headache days per month. Migraine Headache: 10–14 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess days per month
Chronic: ≥ 15 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess days per month

Secondary headaches

Subtypes:

Secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorders may be subclassified based on pathophysiology:

Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess attributed to any of the following:
- Head and/or cervical spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy trauma
- Cranial or cervical vascular abnormality
- Severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension
- Intracranial structural lesion
- Substance use or withdrawal
- Infection
- Disturbance of homeostasis Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Cell Injury and Death
- Psychiatric disorder
Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess or facial pain Facial pain Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. Trigeminal Neuralgia attributed to:
- Disorder of cranial structure
- Disorder of cervical spinal structure
- Eyes
- Ears
- Nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal)
- Sinuses
- Teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy
- Mouth
- Other facial or cranial structures

Etiology:

Secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorders may be subclassified based on underlying etiology:

Vascular
Infectious
Neoplastic
Metabolic
Other

Clinical Presentation and Diagnosis

Features of primary headaches

Features warranting a conservative clinical evaluation:

Known history of a primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess syndrome
Similar to previous headaches
Absence of focal neurologic signs and symptoms
If present, neurologic signs/symptoms are familiar to the individual:
- Autonomic symptoms Autonomic Symptoms Cluster Headaches are typical of a cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess.
- Reversible neurologic deficits Neurologic Deficits High-Risk Headaches are common in a migraine Migraine 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 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess.

“Red flag” signs and symptoms

Signs and symptoms warranting immediate workup and/or intervention:

Severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension
Focal neurologic findings
Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension
Neck stiffness Neck Stiffness Meningitis
Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis state
Cancer/ malignancy Malignancy Hemothorax
1st headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess of the kind
Sudden (“thunderclap”) onset
Mental status changes
Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess after trauma
Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess with visual changes
New-onset seizure
Exertional headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess

Comparison of primary headaches

Table: Primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess entities
Clinical entity	Historical clues/risk factors	Clinical features
Tension headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess	Bilateral location Mild-to-moderate intensity Tight or squeezing quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement Associated with extracranial muscle tenderness Extracranial Muscle Tenderness Tension Headaches, trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation points	Affects almost everyone at some point in a lifetime Often self-diagnosed and self-managed Generally responds to simple and compound analgesics Can be managed by primary care
Migraine Migraine 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 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess	Unilateral > bilateral Moderate-to-severe intensity Women > men Pulsatile quality Pulsatile Quality Migraine Headache Associated with prodrome Prodrome Symptoms that appear 24–48 hours prior to migraine onset. Migraine Headache, aura Aura Reversible neurological phenomena that often precede or coincide with headache onset. Migraine Headache, and postdrome Postdrome Migraine Headache Associated with nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache, and phonophobia Phonophobia Specific Phobias Associated with triggers	May present with transient neurologic and/or visual symptoms May cause significant quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life impairment and work-related disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment Onset during childhood or puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty (women), wanes during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, and persists until menopause Menopause Menopause is a physiologic process in women characterized by the permanent cessation of menstruation that occurs after the loss of ovarian activity. Menopause can only be diagnosed retrospectively, after 12 months without menstrual bleeding. Menopause May need consultation by a specialist to formulate an effective abortive and preventative strategy
Cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess	Unilateral location Severe intensity Men > women Associated with smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases/ alcohol use disorder Alcohol use disorder Alcohol is one of the most commonly used addictive substances in the world. Alcohol use disorder (AUD) is defined as pathologic consumption of alcohol leading to impaired daily functioning. Acute alcohol intoxication presents with impairment in speech and motor functions and can be managed in most cases with supportive care. Alcohol Use Disorder Accompanied by ipsilateral autonomic symptoms Autonomic Symptoms Cluster Headaches	May experience several severe episodes per day May cause significant quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life impairment and work-related disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment Also known as “ suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide headaches” due to the increased risk of suicidal thoughts during an attack May need consultation by a specialist to formulate an effective abortive and preventative strategy

Comparison of common secondary headaches

The following tables outline the most important secondary headaches based on their etiology.

Table: Vascular etiologies Vascular etiologies Secondary headache disorders attributed to a variety of cranial or cervical vascular disorders, such as brain ischemia; intracranial hemorrhages; and central nervous system vascular malformations. High-Risk Headaches of high risk headaches
Clinical entity	Historical clues/risk factors	Clinical features
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 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)	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 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 Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/stiffness Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis	Meningeal signs Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
Reversible cerebral vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure syndrome (RCVS)	Sudden onset Severe intensity at onset Short duration Recurrent Associated with triggers	Transient neurologic deficits Neurologic Deficits High-Risk Headaches from vasospasm Neurologic deficits Neurologic Deficits High-Risk Headaches may persist (if vasospasm persists)
Cervical artery dissection Cervical artery dissection Splitting of the vessel wall in the vertebral artery. Interstitial hemorrhage into the media of the vessel wall can lead to occlusion of the vertebral artery, aneurysm formation, or thromboembolism. Vertebral artery dissection is often associated with trauma and injuries to the head-neck region but can occur spontaneously. High-Risk Headaches/ vertebral artery Vertebral artery The first branch of the subclavian artery with distribution to muscles of the neck; vertebrae; spinal cord; cerebellum; and interior of the cerebrum. Lateral Medullary Syndrome (Wallenberg Syndrome) dissection	Associated with head and/or neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess trauma Prominent neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways New-onset dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome) New-onset tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies	Cranial nerve palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies: Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism 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 Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus/dural sinus thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus	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 The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care Postpartum	Neurologic deficits Neurologic Deficits High-Risk Headaches inconsistent with arterial ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage Associated with seizure Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension on fundoscopy Fundoscopy Cranial Nerve Palsies Encephalopathy Encephalopathy Hyper-IgM Syndrome
Subdural hematoma Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception/epidural hematoma Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception	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 Hematoma A collection of blood outside the blood vessels. Hematoma can be localized in an organ, space, or tissue. Intussusception → Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia Visual changes Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia 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 Anisocoria Unequal pupil size, which may represent a benign physiologic variant or a manifestation of disease. Pathologic anisocoria reflects an abnormality in the musculature of the iris (iris diseases) or in the parasympathetic or sympathetic pathways that innervate the pupil. Physiologic anisocoria refers to an asymmetry of pupil diameter, usually less than 2mm, that is not associated with disease. Pupil: Physiology and Abnormalities Nuchal rigidity Nuchal Rigidity Meningitis
Intraparenchymal hemorrhage (IPH)	Sudden onset Associated with severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled 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 Idiopathic Dermatomyositis intracranial 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	Overweight/obese women Childbearing age Transient/intermittent visual symptoms	Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension on fundoscopy Fundoscopy Cranial Nerve Palsies Abducens nerve Abducens nerve The 6th cranial nerve which originates in the abducens nucleus of the pons and sends motor fibers to the lateral rectus muscles of the eye. Damage to the nerve or its nucleus disrupts horizontal eye movement control. The 12 Cranial Nerves: Overview and Functions palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies Other cranial nerve palsies Cranial Nerve Palsies Cranial nerve palsy is a congenital or acquired dysfunction of 1 or more cranial nerves that will, in turn, lead to focal neurologic abnormalities in movement or autonomic dysfunction of its territory. Head/neck trauma, mass effect, infectious processes, and ischemia/infarction are among the many etiologies for these dysfunctions. Diagnosis is initially clinical and supported by diagnostic aids. Management includes both symptomatic measures and interventions aimed at correcting the underlying cause. Cranial Nerve Palsies Visual deficit Visual Deficit The Visual Pathway and Related Disorders Tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies
Spontaneous intracranial hypotension Intracranial hypotension Reduction of cerebrospinal fluid pressure characterized clinically by orthostatic headache and occasionally by an abducens nerve palsy; hearing loss; nausea; neck stiffness, and other symptoms. This condition may be spontaneous or secondary to cerebrospinal fluid leak; spinal puncture; neurosurgical procedures; dehydration; uremia; trauma; and other processes. Chronic hypotension may be associated with subdural hematomas or hygromas. Subdural Hemorrhage	Severe headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess in upright position Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess improves with caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants and while lying flat Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess worsens with Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse Common after dural puncture	Neurologic findings may be absent or widely 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 Tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies Cervical pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
Giant-cell arteritis Giant-cell arteritis A systemic autoimmune disorder that typically affects medium and large arteries, usually leading to occlusive granulomatous vasculitis with transmural infiltrate containing multinucleated giant cells. The temporal artery is commonly involved. This disorder appears primarily in people over the age of 50. Symptoms include fever; fatigue; headache; visual impairment; pain in the jaw and tongue; and aggravation of pain by cold temperatures. Vasculitides	Age > 50 years Sudden-onset visual disturbances (often monocular) Jaw claudication Jaw claudication Mandibular pain or fatigue during mastication that is relieved with rest Giant Cell Arteritis	Palpable or nodular temporal arteries Temporal Arteries Arteries arising from the external carotid or the maxillary artery and distributing to the temporal region. Jaw and Temporomandibular Joint: Anatomy Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever Elevated acute-phase reactants Acute-Phase Reactants Inflammation: CRP Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
Hypertensive encephalopathy Encephalopathy Hyper-IgM Syndrome	Gradual-onset headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess in the setting of severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures Altered mental status Altered Mental Status Sepsis in Children	Severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension and retinal hemorrhage on fundoscopy Fundoscopy Cranial Nerve Palsies Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma and proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children on urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children Encephalopathy Encephalopathy Hyper-IgM Syndrome
Posterior reversible encephalopathy syndrome Posterior Reversible Encephalopathy Syndrome High-Risk Headaches	Gradual-onset headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess inconsistently associated with severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia Visual changes Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care or postpartum period Postpartum period In females, the period that is shortly after giving birth (parturition). Postpartum Complications	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 may or may not be present Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension and retinal hemorrhage on fundoscopy Fundoscopy Cranial Nerve Palsies Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma and proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children on urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children Encephalopathy Encephalopathy Hyper-IgM Syndrome

Table: Infectious etiologies Infectious Etiologies High-Risk Headaches of high-risk headaches 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, meningitis/encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. High-Risk Headaches
Clinical entity	Historical clues/risk factors	Clinical features
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 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 Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/stiffness Altered mental status Altered Mental Status Sepsis in Children/level of consciousness	Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever Meningism Altered mental status Altered Mental Status Sepsis in Children/level of consciousness Seizure Cranial nerve palsies Cranial Nerve Palsies Cranial nerve palsy is a congenital or acquired dysfunction of 1 or more cranial nerves that will, in turn, lead to focal neurologic abnormalities in movement or autonomic dysfunction of its territory. Head/neck trauma, mass effect, infectious processes, and ischemia/infarction are among the many etiologies for these dysfunctions. Diagnosis is initially clinical and supported by diagnostic aids. Management includes both symptomatic measures and interventions aimed at correcting the underlying cause. Cranial Nerve Palsies Petechiae Petechiae Primary Skin Lesions or purpura
Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease	Onset of headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess 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 Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides)	Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever may be 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 Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/stiffness may be 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 Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension on fundoscopy Fundoscopy Cranial Nerve Palsies Insidious onset of focal neurologic deficits Neurologic Deficits High-Risk Headaches or cranial nerve palsies Cranial Nerve Palsies Cranial nerve palsy is a congenital or acquired dysfunction of 1 or more cranial nerves that will, in turn, lead to focal neurologic abnormalities in movement or autonomic dysfunction of its territory. Head/neck trauma, mass effect, infectious processes, and ischemia/infarction are among the many etiologies for these dysfunctions. Diagnosis is initially clinical and supported by diagnostic aids. Management includes both symptomatic measures and interventions aimed at correcting the underlying cause. Cranial Nerve Palsies

Table: Neoplastic etiologies Neoplastic Etiologies High-Risk Headaches of high-risk headaches 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, meningitis/encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. High-Risk Headaches
Clinical entity	Historical clues/risk factors	Clinical features
Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tumor Tumor Inflammation	Cancer Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess worsens with cough, Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess often worse 1st thing in the morning or may wake individual at night Insidious headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess onset, but may be sudden if tumor Tumor Inflammation bleeds Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia	Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension on fundoscopy Fundoscopy Cranial Nerve Palsies Seizure Altered mental status Altered Mental Status Sepsis in Children/level of consciousness Neurologic deficits Neurologic Deficits High-Risk Headaches corresponding to tumor Tumor Inflammation location
Colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids cyst of 3rd ventricle	Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess worsens in upright position, improves with lying flat Altered mental status Altered Mental Status Sepsis in Children Symptoms may fluctuate	Altered mental status Altered Mental Status Sepsis in Children Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment 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 Pituitary apoplexy The sudden loss of blood supply to the pituitary gland, leading to tissue necrosis and loss of function (panhypopituitarism). The most common cause is hemorrhage or infarction of a pituitary adenoma. It can also result from acute hemorrhage into sella turcica due to head trauma; intracranial hypertension; or other acute effects of central nervous system hemorrhage. Clinical signs include severe headache; hypotension; bilateral visual disturbances; unconsciousness; and coma. Hypopituitarism	Associated with pituitary tumors Pituitary tumors Neoplasms which arise from or metastasize to the pituitary gland. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties. Pituitary tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. Pituitary Adenomas (most often benign Benign Fibroadenoma) Sudden-onset headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess associated with infarction/bleeding into tumor Tumor Inflammation	Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia Altered mental status Altered Mental Status Sepsis in Children Visual/oculomotor defect Endocrine dysfunction

Table: Other etiologies of high-risk headaches 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, meningitis/encephalitis, and intracranial tumors carry high morbidity and mortality risks if not recognized and treated immediately. High-Risk Headaches
Clinical entity	Historical clues/risk factors	Clinical features
Acute narrow-angle glaucoma Acute narrow-angle glaucoma A form of glaucoma in which the intraocular pressure increases because the angle of the anterior chamber is blocked and the aqueous humor cannot drain from the anterior chamber. High-Risk Headaches	Ocular pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways Ocular injection Loss of vision Vision Ophthalmic Exam Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia	Conjunctival injection Corneal clouding; fixed Pupillary dilation with lack of constriction Elevated intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam
CO toxicity CO toxicity High-Risk Headaches	Acute CO exposure Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess improves with separation from CO Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia Light-headedness/ dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)	Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia/ malaise Malaise Tick-borne Encephalitis Virus 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 Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy on fundoscopy Fundoscopy Cranial Nerve Palsies
Preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders/ eclampsia Eclampsia Onset of hyperreflexia; seizures; or coma in a previously diagnosed pre-eclamptic patient (pre-eclampsia). Hypertensive Pregnancy Disorders	Pregnant woman at > 20 weeks Sudden-onset headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess associated with blood pressure > 140/90 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma Hg Tinnitus Tinnitus A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. Cranial Nerve Palsies Visual disturbance Seizure	Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children Brisk deep tendon reflexes Deep Tendon Reflexes Neurological Examination (DTRs) Placental abruption Placental Abruption Premature separation of the normally implanted placenta from the uterus. Signs of varying degree of severity include uterine bleeding, uterine muscle hypertonia, and fetal distress or fetal death. Antepartum Hemorrhage Symptoms abate on delivery of the fetus

Diagnosis

Laboratory evaluation

Basic lab studies may be warranted with the initial headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess workup:
- CBC
- Basic metabolic panel (BMP) or comprehensive metabolic panel (CMP)
- Coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies: PT, INR, PTT
Basic and specific lab studies may be indicated for secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess evaluation:
- CRP
- Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess)
- Hormone levels
- CSF studies:
  - Cell count
  - Protein
  - Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
  - Gram stain Gram stain Klebsiella
  - Opening pressure

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant evaluation

Primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess syndromes generally do not require neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant for diagnosis; however, neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant may be useful to:
- Rule out secondary causes of headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess at the initial evaluation
- Evaluate headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess severity or clinical features atypical of the individual
- Evaluate neurologic signs or symptoms present with primary headaches (e.g., autonomic phenomena of cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess or focal neurologic phenomena of migraine Migraine 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 headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess)
Head CT without contrast is generally recommended as the initial imaging test of choice if “red flag” signs or symptoms are present.

Management

A wide range of management strategies exist for the various primary and secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorders. Only a broad overview is presented:

Primary headaches

Pharmacological management:

Most primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess episodes and/or disorders are managed conservatively:

Simple or compound oral analgesics to abort isolated headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess attacks:
- Simple analgesics (single ingredient, nonspecific mechanism of action):
  - Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen
  - NSAIDs
- Compound analgesics (more than 1 ingredient, nonspecific mechanism of action):
  - Aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) + butalbital + caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants
  - Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen + NSAID NSAID Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications consisting of aspirin, reversible NSAIDs, and selective NSAIDs. NSAIDs are used as antiplatelet, analgesic, antipyretic, and antiinflammatory agents. Nonsteroidal Antiinflammatory Drugs (NSAIDs) +/- caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants, butalbital, or codeine Codeine An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. Opioid Analgesics
Specialized-mechanism or disease-specific analgesics to abort isolated headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess attacks:
- Triptans Triptans Triptans and ergot alkaloids are agents used mainly for the management of acute migraines. The therapeutic effect is induced by binding to serotonin receptors, which causes reduced vasoactive neuropeptide release, pain conduction, and intracranial vasoconstriction. Triptans and Ergot Alkaloids for migraine Migraine 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 and cluster headaches Cluster headaches Cluster headache is a primary headache disorder characterized by moderate-to-severe unilateral headaches that occur in conjunction with autonomic symptoms. Cluster headache can last from weeks to months, during which the affected individual may experience attacks up to several times a day, followed by a pain-free remission period. Cluster Headaches
- Calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs gene-related peptide ( CGRP CGRP A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Gastrointestinal Neural and Hormonal Signaling) inhibitors for migraines
- O₂ delivery at 100% for cluster headaches Cluster headaches Cluster headache is a primary headache disorder characterized by moderate-to-severe unilateral headaches that occur in conjunction with autonomic symptoms. Cluster headache can last from weeks to months, during which the affected individual may experience attacks up to several times a day, followed by a pain-free remission period. Cluster Headaches

Prevention:

Multiple preventative headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess regimens exist for primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess syndromes:

Antihypertensives Antihypertensives The 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific. Hypertension Drugs
Antidepressants
Anticonvulsants
Botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism
Specialized-mechanism or disease-specific interventions to prevent/reduce headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess attack frequency:
- Monoclonal antibody regimens
- CGRP CGRP A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. Gastrointestinal Neural and Hormonal Signaling inhibitors for migraines
- Interventional nerve blocks/ablations to targeted nerve structures

Secondary headaches

Secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess syndromes may require emergent evaluation and management strategies by consultation from 1 or more specialists:

Neurosurgical consultation
Interventional radiology Interventional radiology Subspecialty of radiology that combines organ system radiography, catheter techniques and sectional imaging. Penetrating Abdominal Injury/vascular intervention consultation
Neurology consultation
Ophthalmology consultation
HEENT surgical consultation
Infectious disease consultation
Medical/surgical oncology consultation

The clinician Clinician A physician, nurse practitioner, physician assistant, or another health professional who is directly involved in patient care and has a professional relationship with patients. Clinician–Patient Relationship should look for the “hidden” cause of secondary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (medication-overuse headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess):

The individual generally has a primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess disorder.
The primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess attack frequency generally qualifies as frequent or chronic.
The individual has developed a pattern of overuse, misuse, or abuse of abortive medications.
A 2nd, “rebound” headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess entity (or disorder) has developed and is difficult to distinguish from the primary headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess.

References

Hainer, B., Matheson, E. (2013). Approach to Acute Headache in Adults. American Family Physician. 87(10), 682–687. Retrieved August 15, 2021, from https://www.aafp.org/afp/2013/0515/p682.html
Beck, E. (2013). Hard-to-Diagnose Headache: Practical Tips for Diagnosis and Treatment. American Family Physician. 87(10), 672–673. Retrieved August 15, 2021, from https://www.aafp.org/afp/2013/0515/p672.html
Headache Classification Committee of the International Headache Society (IHS). (2013). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 33(9), 629–808. Retrieved August 15, 2021, from https://doi.org/10.1177/0333102413485658

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Overview

Definitions

Epidemiology

Etiology

Classification

Primary headaches

Secondary headaches

Clinical Presentation and Diagnosis

Features of primary headaches

“Red flag” signs and symptoms

Comparison of primary headaches

Comparison of common secondary headaches

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Diagnosis

Laboratory evaluation

Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant evaluation

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Management

Primary headaches

Secondary headaches

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References

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