Migraine Headache

Overview

Definition

Migraine headaches are primary headaches Primary headaches Conditions in which the primary symptom is headache and the headache cannot be attributed to any known causes. Primary vs Secondary Headaches commonly 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, phonophobia Phonophobia Specific Phobias, and exacerbated by physical activity.

Distinguishing features:

• Unilateral, rarely bilateral
• Pulsatile 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
• Moderate to severe intensity
• 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 duration: 4–72 hours
• Worsens with physical activity 
• 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 and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Photophobia and/or phonophobia Phonophobia Specific Phobias

Migraine-related terminology:

• Prodrome: symptoms that appear 24–48 hours prior to migraine onset
  • Yawning
  • Euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy
  • Depression
  • Irritability
  • Cravings
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea/ constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess discomfort
• Aura:
  • Reported by approximately 25% of individuals with migraine
  • Reversible neurological phenomena that often precede or coincide with 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
  • Gradual in onset and progression
  • Positive aura symptoms (“gain of function” in CNS neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology):
    • Visual (e.g., bright lines, shapes, objects)
    • Auditory (e.g., 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, noises, music)
    • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology (e.g., numbness, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, paresthesia, allodynia Allodynia Pain due to a stimulus that does not typically provoke pain. Pain Management)
    • Motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology (e.g., tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies, jerking, repetitive movements) 
  • Negative aura symptoms (“ loss of function Loss of Function Inflammation” in CNS neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology):
    • Visual loss
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology loss (e.g., anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts, numbness)
    • Language loss (e.g., word-finding difficulty, aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke)
• Postdrome:
  • Reported by approximately 75% of individuals with migraine.
  • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the location 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 after 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 abates triggered by head movement
  • Feeling of exhaustion (more common) or euphoria Euphoria An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. Hepatic Encephalopathy encountered after 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 abates

Epidemiology

• Lifetime 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: approximately 12% in the United States
• Women > men: 2–4:1 depending on age
• Equal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria 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 in childhood 
• 75% of those with migraine have symptom onset by age 35. 
• Only about half of U.S. adults with migraine receive an accurate diagnosis. 
• Migraine is a significant cause of 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.

Classification

Migraine 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 classified among 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 disorders as well as having subtypes of its own. 

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:

• Migraine 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
• 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

Subtypes of migraine 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:

• Low-frequency episodic: < 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: 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
• Migraine with and without aura
• Migraine with brainstem aura
• Hemiplegic migraine
• Retinal migraine

Pathophysiology

Current consensus holds that a primary neuronal dysfunction is responsible for a sequence of intracranial and extracranial changes that trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation prodromic and postdromic symptoms, aura, and 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 itself.

Cortical spreading depression

• Self-propagating depolarization Depolarization Membrane Potential of neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology and glial cells Glial Cells The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain barrier and blood-retinal barrier, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Nervous System: Histology that spreads across the cerebral cortex Cerebral cortex The cerebral cortex is the largest and most developed part of the human brain and CNS. Occupying the upper part of the cranial cavity, the cerebral cortex has 4 lobes and is divided into 2 hemispheres that are joined centrally by the corpus callosum. Cerebral Cortex: Anatomy. 
• Assumed to:
  • Trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation the aura of migraine
  • Activate afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology fibers of the trigeminal nerve Trigeminal nerve The 5th and largest cranial nerve. The trigeminal nerve is a mixed motor and sensory nerve. The larger sensory part forms the ophthalmic, mandibular, and maxillary nerves which carry afferents sensitive to external or internal stimuli from the skin, muscles, and joints of the face and mouth and from the teeth. Most of these fibers originate from cells of the trigeminal ganglion and project to the trigeminal nucleus of the brain stem. The smaller motor part arises from the brain stem trigeminal motor nucleus and innervates the muscles of mastication. The 12 Cranial Nerves: Overview and Functions 
  • Increase permeability of the blood–brain barrier Blood–Brain Barrier Meningitis in Children to matrix metalloproteinases Matrix metalloproteinases A family of zinc-dependent metalloendopeptidases that is involved in the degradation of extracellular matrix components. Hypertrophic and Keloid Scars

Trigeminal activation

• Induces inflammatory changes in meningeal 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 responsible for 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
• Projections innervate large cerebral vessels, large venous sinuses Venous sinuses Veins: Histology, and the dura mater Dura mater The outermost of the three meninges, a fibrous membrane of connective tissue that covers the brain and the spinal cord. Meninges: Anatomy, which explains the typical location of migraine pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.

Vasoactive neuropeptides

• Released on stimulation of the trigeminal ganglion Trigeminal ganglion The semilunar-shaped ganglion containing the cells of origin of most of the sensory fibers of the trigeminal nerve. It is situated within the dural cleft on the cerebral surface of the petrous portion of the temporal bone and gives off the ophthalmic, maxillary, and part of the mandibular nerves. Trigeminal Neuralgia 
• Lead to:
  • Neurogenic 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
  • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs of the trigeminovascular system
  • Extravasation of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis into the CSF
• Vasoactive peptides include:
  • Substance P
  • 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 Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics–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)
  • Neurokinin A
  • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS
• 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 Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics–related peptide and serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS are pharmacologic targets of migraine therapy → 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 antagonists and serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS agonists (= 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)

Prolonged and repetitive 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 of the trigeminal system

• Leads to sensitization
• Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology activation occurs at a lower threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction and produces an exaggerated pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways response.

Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics

• 75% of individuals with migraine have 1st-degree relative with migraines.
• Twin studies: monozygotic twin concordance > dizygotic twin concordance 
• Inheritance pattern is multifactorial.
• No single Mendelian model of inheritance has been identified.

Clinical Presentation

History

• Classic pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways descriptors for migraine 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:
  • Throbbing
  • Pounding
  • Pulsatile
• Onset most commonly in teens or early 20s
• A minimum of 5 individual 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 with characteristics typical of migraine is required to establish a diagnosis.
• Features:
  • Most often unilateral, but can be bilateral
  • Moderate to severe intensity
  • Duration: 4–72 hours per attack
  • Location:
    • Entire side of head, including the face
    • May be most intense behind the eye or cheek
    • May include the upper cervical region Cervical region Spinal Cord: Anatomy ipsilateral to 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
  • Physical activity:
    • Individuals often seek a place to lie down.
    • 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 often relieved by sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep.
  • Light and noise:
    • Symptoms worsen with bright lights and loud noises.
    • Individuals often seek a dark, quiet place.
  • Cutaneous allodynia Allodynia Pain due to a stimulus that does not typically provoke pain. Pain Management:
    • Innocuous stimulation of normal 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. Skin: Structure and Functions in the affected area produces pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.
    • May be present during or even between attacks.
  • 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/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Prodrome and postdrome
  • Aura:
    • Most commonly visual
    • The same person may experience migraine attacks with and without an aura. 
    • Aura may be present without being followed by 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.
  • Triggers (precipitating or aggravating stimuli):
    • Stress 
    • Hormonal fluctuation
    • Weather changes
    • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbances 
    • Medications
    • Smells
    • 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 
    • Cervical manipulation
    • Lights
    • Sounds
    • Alcohol 
    • Cigarette/cigar smoke 
    • Heat Heat Inflammation 
    • Food (e.g., cheese, chocolate)
    • Exercise 
    • Sexual activity

Physical exam

Physical examination may be entirely normal unless the individual is currently experiencing an attack.

Aura symptoms:

• Visual
• Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology
• Speech and/or language
• To be diagnosed with migraine with aura, 3 of 6 features must be present:
  • ≥ 1 aura symptom(s) onset/progression over ≥ 5 minutes
  • ≥ 2 aura symptoms occur together
  • Duration: about 5–60 minutes each
  • ≥ 1 aura symptom is unilateral.
  • ≥ 1 aura symptom is a positive visual symptom.
  • Aura accompanies or precedes 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 by ≤ 1 hour.

During an attack:

• Cutaneous allodynia Allodynia Pain due to a stimulus that does not typically provoke pain. Pain Management
• Focal neurologic deficits Neurologic Deficits High-Risk Headaches
• Decreased hearing acuity
• Visual-field deficits
• Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease
• Aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke
• 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
• Altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage
• 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
• Seizure activity

Specific subtypes

• Hemiplegic migraine: aura includes motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology weakness
• Migraine with brainstem aura:
  • Formerly termed “basilar” migraine
  • Aura symptoms arise from the 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 stem and can include:
    • 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/ 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)
    • 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
    • Decreased hearing acuity
    • 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
    • Dysarthria Dysarthria Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from cranial nerve diseases; neuromuscular diseases; cerebellar diseases; basal ganglia diseases; brain stem diseases; or diseases of the corticobulbar tracts. The cortical language centers are intact in this condition. Wilson Disease
    • 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
    • Altered level of consciousness Altered Level of Consciousness Intracerebral Hemorrhage
  • Associated with or preceding 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
• Retinal migraine:
  • Formerly termed “ocular” migraine
  • Aura involves episodes of unilateral scintillation, scotoma Scotoma A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of eye diseases (e.g., retinal diseases and glaucoma); optic nerve diseases, and other conditions. Cranial Nerve Palsies, visual-field deficits, or blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity lasting ≤ 1 hour.
  • Before, during, or after 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
  • Occasionally leads to permanent visual deficits

Diagnosis

Diagnostic criteria

General:

To diagnose migraine, there should have been ≥ 5 attacks meeting ≥ 2 of the following criteria:

• Unilateral 
• Pulsatile 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
• Moderate to severe intensity
• 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 duration: 4–72 hours
• Worsens with physical activity 
• 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 and/or vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Photophobia and/or phonophobia Phonophobia Specific Phobias

Migraine with aura:

To diagnose migraine with aura, 3 of the 6 following features must be present:

• ≥ 1 aura symptom(s) builds in intensity over ≥ 5 minutes.
• ≥ 2 aura symptoms occur together.
• Aura symptoms last 5–60 minutes each.
• ≥ 1 aura symptom is unilateral.
• ≥ 1 aura symptom is a positive visual symptom.
• Aura accompanies or precedes 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 by ≤ 1 hour.

Laboratory evaluation

• Laboratory evaluation is indicated only if the following conditions are suspected:
  • Organ dysfunction
  • Volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration/overload
  • Electrolyte disturbance
  • Infectious process
• Laboratory testing should be specific to suspected underlying cause(s):
  • Organ dysfunction:
    • Cardiac biomarkers
    • BUN, creatinine (renal function)
    • AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests/ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests (hepatic function)
  • Volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration/overload:
    • BUN/creatinine (renal function)
    • AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests/ ALT ALT An enzyme that catalyzes the conversion of l-alanine and 2-oxoglutarate to pyruvate and l-glutamate. Liver Function Tests (hepatic function)
    • BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation (indicates heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR))
    • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy studies
  • Electrolyte disturbance: chemistry panel or electrolyte panel
  • Infectious process:
    • CBC
    • CSF studies

Imaging

• Indication at the initial evaluation of migraine:
  • 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 associated with neurologic symptoms.
  • 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 presents with focal neurologic findings or seizure.
  • 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.
• Repeat imaging only in the following cases:
  • Red flag 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 symptoms
  • Focal neurologic findings 
  • 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 characteristics have changed or can no longer be classified as any of 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 disorders.
• Imaging methods:
  • MRI: test of choice
  • CT: faster for triage of suspected acute intracranial hemorrhage Intracranial 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

Management

Abortive therapy

Regardless of the abortive strategy used, allowing the migraine sufferer to lie down in a dark, quiet room is favorable.

• 1st-line therapies:
  • Simple analgesics Simple Analgesics Primary vs Secondary Headaches (single-ingredient, nonopioid, nonbarbiturate):
    • 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)
    • 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 NSAIDS Primary vs Secondary Headaches ( ibuprofen Ibuprofen A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of rheumatism and arthritis. Nonsteroidal Antiinflammatory Drugs (NSAIDs), naproxen Naproxen An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout. Nonsteroidal Antiinflammatory Drugs (NSAIDs)) 
    • More effective if given early in the course 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 (i.e., onset of prodrome, aura, or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
    • May be more effective if used in combination with 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
    • May need to administer with an antiemetic if 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 are present
  • 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 (oral):
    • More effective if given early in the course 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 (i.e., onset of prodrome, aura, or pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways)
    • May be more effective if used in combination with simple analgesics Simple Analgesics Primary vs Secondary Headaches
    • May need to administer with an antiemetic if 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 are present
  • 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 (subcutaneous, intranasal):
    • May be administered at home (self-injection) or in doctor’s office
    • Rapid onset of action
    • Useful if 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 are present
• 2nd-line therapies:
  • 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 Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics–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) antagonists
    • Rimegepant
    • Ubrogepant
  • Selective serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS 1F receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonist: lasmiditan
  • Dihydroergotamine Dihydroergotamine A 9, 10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. Triptans and Ergot Alkaloids
• Severe, refractory migraines or status migrainosus:
  • IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids
  • Ketorolac ( 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)) +/– dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS antagonist ( antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics that may also abort headaches)
  • Dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics (IM, IV, SC) to prevent 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 rebound
• Antiemetics Antiemetics Antiemetics are medications used to treat and/or prevent nausea and vomiting. These drugs act on different target receptors. The main classes include benzodiazepines, corticosteroids, atypical antipsychotics, cannabinoids, and antagonists of the following receptors: serotonin, dopamine, and muscarinic and neurokinin receptors. Antiemetics, if 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 are present:
  • Prochlorperazine Prochlorperazine A phenothiazine antipsychotic used principally in the treatment of nausea; vomiting; and vertigo. It is more likely than chlorpromazine to cause extrapyramidal disorders. Antiemetics
  • Metoclopramide Metoclopramide A dopamine d2 antagonist that is used as an antiemetic. Antiemetics
  • Chlorpromazine Chlorpromazine The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine’s antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. First-Generation Antipsychotics
• Nonpharmacologic therapy:
  • Interventional pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways therapies:
    • Occipital Occipital Part of the back and base of the cranium that encloses the foramen magnum. Skull: Anatomy nerve blocks (local anesthetic +/– corticosteroid)
    • Sphenopalatine ganglion blocks (local anesthetic +/– corticosteroid)
  • Neuromodulation:
    • Supraorbital nerve, vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy
    • Transcutaneous electrical and/or magnetic stimulation

Preventive therapy

Goals:

• 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 burden (frequency, severity, duration).
• Improve function.
• Reduce 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.
• Prevent progression of migraine chronicity.
• Improve response to abortive therapies. 
• Avoid toxicity Toxicity Dosage Calculation to abortive medications.
• Prevent medication-overuse headache Medication-Overuse Headache Primary vs Secondary Headaches.

Indications:

• Episodic and chronic migraine 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 
• Prevention/treatment of abortive medication-overuse headache Medication-Overuse Headache Primary vs Secondary Headaches and toxicity Toxicity Dosage Calculation
• Frequent or long-lasting migraine headaches
• Significant migraine-associated 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 or diminished 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
• Poor response, intolerance, or contraindication to abortive therapies
• Menstrual migraine

Preventive treatment options:

• Beta blockers:
  • Metoprolol Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat angina pectoris; hypertension; and cardiac arrhythmias. Antiadrenergic Drugs, propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs, timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers) 
  • May be useful in those also diagnosed with:
    • 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
    • Tachyarrhythmia Tachyarrhythmia A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Tachyarrhythmias
    • Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
    • Stable heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
• Antidepressants:
  • Amitriptyline Amitriptyline Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the reuptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. Tricyclic Antidepressants, venlafaxine Venlafaxine A cyclohexanol and phenylethylamine derivative that functions as a serotonin and noradrenaline reuptake inhibitor (SNRI) and is used as an antidepressant agent. Serotonin Reuptake Inhibitors and Similar Antidepressants 
  • May be useful in those also diagnosed with:
    • Depression
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
    • Chronic pain Chronic pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Pain Management disorders (especially neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways)
• Anticonvulsants:
  • Valproate Valproate A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs, topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs, gabapentin Gabapentin A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of partial seizures; neuralgia; and restless legs syndrome. Second-Generation Anticonvulsant Drugs 
  • May be useful in those also diagnosed with:
    • Seizure disorder
    • Chronic pain Chronic pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Pain Management disorders (especially neuropathic pain Neuropathic pain Caused by lesion or disease affecting the nervous system (PNS or CNS). Pain: Types and Pathways)
• 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 antagonists:
  • 2nd-line agents
  • Oral agents (-gepant) or injectable (-mab) available:
    • Rimegepant
    • Atogepant
    • Erenumab
    • Fremanezumab
    • Galcanezumab
    • Eptinezumab
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers:
  • Evidence is conflicting/inadequate to support their use.
  • Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs, nicardipine Nicardipine A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
  • May be useful in those also diagnosed with:
    • 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
    • Tachyarrhythmia Tachyarrhythmia A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Tachyarrhythmias
    • Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
• ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication/ ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication:
  • Lisinopril Lisinopril One of the angiotensin-converting enzyme inhibitors (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure. Renin-Angiotensin-Aldosterone System Inhibitors, candesartan 
  • May be useful in those also diagnosed with:
    • 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
    • Stable heart disease
    • Stable CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
• 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:
  • 2nd-line agent
  • Injected into cranial/cervical musculature
• Neuromodulation:
  • Vagus nerve Vagus nerve The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). Pharynx: Anatomy stimulation
  • Deep 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 stimulation
• Behavioral approaches:
  • Migraine education
  • Trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation desensitization
  • Lifestyle modifications:
    • Avoidance of triggers (e.g., alcohol, strong smells)
    • Regular Regular Insulin sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep
    • Exercise
  • CBT
  • Relaxation techniques
  • Biofeedback Biofeedback The therapy technique of providing the status of one’s own autonomic nervous system function (e.g., skin temperature, heartbeats, brain waves) as visual or auditory feedback in order to self-control related conditions (e.g., hypertension, migraine headaches). Psychotherapy

Complications

• Status migrainosus: severe migraine 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 lasting > 72 hours (rare; < 1% of migraine cases)
• Persistent aura without infarction: aura symptoms (+/– 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) persisting ≥ 1 week without clinical evidence of cerebral infarction
• Migrainous infarction: migraine 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 aura symptoms persisting ≥ 1 hour with clinical evidence of cerebral infarction
• Migraine aura-triggered seizure: seizure activity associated with a migraine with aura

Differential Diagnosis

• Vestibular migraine: episodic vertigo Episodic Vertigo Ménière Disease in individuals with migraines or with symptoms suggestive of migraine (e.g., photophobia, phonophobia Phonophobia Specific Phobias, aura). The association 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 with 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 is 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, even within the same individual. The diagnosis is clinical after exclusion of Ménière disease Ménière disease Ménière disease is a condition characterized by episodes of vertigo, tinnitus, and hearing loss, likely caused by endolymphatic hydrops of the labyrinthine system in the inner ear. The risk factors include a family history of Ménière disease, preexisting autoimmune disorders, allergies, and trauma to the head or ear. Ménière Disease, cerebellar disorders Cerebellar disorders Cerebellar disorders are a specific set of neurologic signs and symptoms caused by local or systemic conditions that affect the cerebellum; the classic sign is ataxia, in addition to several other motor abnormalities that affect coordination. Cerebellar Disorders, 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 stem disorders, and vascular insufficiency Vascular insufficiency Anal Fissure. Treatment is aimed at managing the underlying 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 and 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.
• Menstrual migraine: migraine 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 that occurs in specific phases of the menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle, most commonly right before or during the period. Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy levels are assumed to play a role in pathogenesis. The diagnosis is clinical. Typical migraine therapies should be used for treatment, but a more aggressive approach may be needed. 
• 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: mild to moderate common 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, often bilateral in presentation and without neurologic symptoms. Tension headaches Tension headaches Tension headache is the most common of the primary primary headache disorders and one of the most common disorders presenting for medical evaluation worldwide. Tension headaches are generally described as bilateral, nonthrobbing, and of mild to moderate severity. There is no aura or other associated features. Tension Headaches are often self-diagnosed. Management includes rest and simple analgesics Simple Analgesics Primary vs Secondary Headaches.
• 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: 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 that is severe and unilateral, often around the eye, with a duration of minutes up to 3 hours. More common in men. Individuals typically present with accompanying autonomic symptoms Autonomic Symptoms Cluster Headaches, such as nasal congestion and swelling Swelling Inflammation or watering of the eyes. Diagnosis is clinical based on the typical symptoms. Management includes administration of oxygen and 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 and avoiding triggers, such as smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases and alcohol.
• Medication-overuse headache Medication-Overuse Headache Primary vs Secondary Headaches: also called 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. Medication-overuse headache Medication-Overuse Headache Primary vs Secondary Headaches is a type of secondary headache Secondary headache Conditions with headache symptom that can be attributed to a variety of causes including brain vascular disorders; wounds and injuries; infection; drug use or its withdrawal. Primary vs Secondary Headaches in individuals who have frequent or daily headaches despite, or because of, the regular Regular Insulin use 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 medications. Medication-overuse headache Medication-Overuse Headache Primary vs Secondary Headaches is usually preceded by an episodic 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 that has been treated with excessive amounts of abortive medications, especially combination drugs 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 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. Treatment consists of establishing an effective preventive regimen so that the offending abortive agent(s) may be weaned or discontinued. 
• Sinus 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: 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 that occurs in the setting of acute or chronic 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. The pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways is typically described as constant and deep around the cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma, forehead Forehead The part of the face above the eyes. Melasma, or bridge of the 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). Sinus 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 associated with symptoms including a runny 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), swelling Swelling Inflammation or tearing of the eyes, and 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. Management includes decongestants, antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines in the case of allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction, and antibiotics in the presence of a bacterial infection.  
• Cervicogenic 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: 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 caused by referred pain Referred Pain Spinal Disk Herniation from the upper cervical joints. Cervicogenic 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 typically unilateral, of moderate to severe intensity, and increased by movement of the head, with radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma from occipital Occipital Part of the back and base of the cranium that encloses the foramen magnum. Skull: Anatomy to frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy regions. Diagnosis is clinical based on typical symptoms. Management includes simple analgesics Simple Analgesics Primary vs Secondary Headaches, physical therapy Physical Therapy Becker Muscular Dystrophy, nerve blocks, or spinal manipulation.
• 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)) or 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: neurologic signs, symptoms, or deficits attributable to interrupted blood supply to the 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 parenchyma. 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) may be the result of arterial occlusion or hemorrhage from disrupted vascular integrity. Diagnosis is made via a thorough history and neurologic examination and confirmed with neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant. Treatment is aimed at restoration of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure, prevention of further ischemic events, and treatment of underlying vascular risk factors. 
• Seizure: spectrum of neurologic disorders affecting intracranial structures. Seizure can manifest as an abnormal neuronal discharge causing neurologic changes, tonic-clonic activity, altered mental status Altered Mental Status Sepsis in Children, and/or loss of consciousness. Diagnosis is made with a detailed history and neurologic exam and confirmed with EEG EEG Seizures or neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant. Treatment includes antiepileptics and addressing any underlying structural 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 disease.