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Cluster 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 is 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 characterized by moderate-to-severe unilateral headaches that occur in conjunction with autonomic symptoms. 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 can last from weeks to months, during which the affected individual may experience attacks up to several times a day, followed by a pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways-free remission period. Autonomic symptoms typically manifest as ocular and nasal phenomena (e.g., ptosis Ptosis Cranial Nerve Palsies, miosis Miosis Pupil: Physiology and Abnormalities, nasal congestion, rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus) on the same side as 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. Men are more commonly affected by cluster headaches than women. The diagnosis is clinical and often easy to establish owing to the distinct features of the presenting 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 1st-line treatment involves administration of oxygen by nasal cannula Nasal Cannula Respiratory Failure and/or abortive therapy using a triptan. Preventative strategies (e.g., glucortoicoids, verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs) are crucial, as 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 is a chronic condition associated with significant morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and a high rate of 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.

Last updated: 6 Dec, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Cluster headaches are named based on their tendency to occur in clusters lasting from weeks to months, and interrupted by periods of remission. The defining features include:

Classification

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 belongs to 2 distinct classification schemes: 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 and trigeminal autonomic cephalgias (TACs).

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 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
  • 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

Trigeminal autonomic cephalgias:

  • Common features:
    • Suspected similar pathophysiology
    • Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor: trigeminal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways + autonomic activation
  • Examples:
    • 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:
      • Most common of the TACs
      • Has the longest duration of a single attack of the TACs (15 minutes to 3 hours)
      • The lowest frequency in a given day of the TACs (≤ 8 per day)
    • Paroxysmal hemicrania
    • Hemicrania continua
    • Short-lasting unilateral neuralgiform 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 conjunctival injection and tearing (SUNCT)
    • Short-lasting unilateral neuralgiform 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 cranial autonomic symptoms (SUNA)

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 120/100,000
  • 1-year 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 50/100,000 
  • Men > women, 4:1 ratio
  • Mean Mean Mean is the sum of all measurements in a data set divided by the number of measurements in that data set. Measures of Central Tendency and Dispersion age of onset: 20–40 years 
  • Positive family history Family History Adult Health Maintenance in 5%–20% of cases
  • Strong association with cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Strong association with 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 attempts and successful 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

Pathophysiology

The pathophysiology 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 is multifactorial and the precise mechanisms are poorly understood. The prevailing theories of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways mechanisms are outlined below.

Trigeminal-autonomic reflex activation

Afferent Afferent Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology nerves of the trigeminal system have neuronal connections with the ANS ANS The ans is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ans consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System: Anatomy. If stimulated, the trigeminal afferents can activate cranial autonomic outflow via the trigeminal-autonomic reflex.

  • Cranial 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 originate largely from the trigeminal system.
  • Trigeminal nociceptive afferents have a direct connection to cranial autonomic fibers:
    • Between 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 and sphenopalatine ganglion
    • Between the trigeminocervical complex and higher 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 pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways-processing centers 
  • 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 are ipsilateral to the pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
    • Parasympathetic manifestations:
      • Rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus
      • Nasal mucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Lacrimation
      • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Ptosis Ptosis Cranial Nerve Palsies
      • Miosis Miosis Pupil: Physiology and Abnormalities
  • Some degree of autonomic outflow in response to stimulation of trigeminal nociceptive stimulation is normal, for example:
    • Stimulus: being slapped in the face
    • Autonomic response: ipsilateral lacrimation, local hyperemia/subcutaneous edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • In 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, the reflex is centralized, intrinsically triggered, and pathologically tethered to hypothalamic clocklike functions.
  • Trigeminal-autonomic reflex activation and hypothalamic activation mechanisms are interdependent.

Hypothalamic activation

Features 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 suggest the involvement of the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus, which has direct connections to the trigeminal system. Hypothalamic activation also acts as the body’s biological clock and participates in numerous neurohormonal pathways. Factors suggesting hypothalamic involvement include:

  • Relapsing/remitting pattern of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways episodes
  • Seasonal variation in the pattern of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways episodes
  • Predictable regularity of attack intervals
  • Associated hypothalamic hormonal irregularities:
    • Association with low testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens levels
    • Association with abnormal pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types 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 axis Axis The second cervical vertebra. Vertebral Column: Anatomy feedback loop
  • Associated irregularities in the circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies
  • Functional imaging during attacks shows posterior hypothalamic activity.
  • Existence 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 connecting the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus to the trigeminal system
  • Hypothalamic neuropeptides are known to play a role in trigeminal nociception Nociception Sensing of noxious mechanical, thermal or chemical stimuli by nociceptors. It is the sensory component of visceral and tissue pain (nociceptive pain). Pain: Types and Pathways.

Clinical Presentation

There is an overlap in the presenting symptoms and signs 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 and other 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, as well as that of other TACs. The distinguishing features are presented below.

Autonomic manifestations accompanying pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in the trigeminal (V1) distribution are typical of cluster headaches.

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 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:
    • Sharp
    • Severe
    • Boring
    • Burning
    • “Hot poker in the eye”
    • 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 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
  • Autonomic symptoms (ipsilateral to the side of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways):
    • Injected conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy
    • Lacrimation
    • Nasal congestion
    • Rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus
    • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Eyelid ptosis Ptosis Cranial Nerve Palsies
    • Facial diaphoresis
    • Miosis Miosis Pupil: Physiology and Abnormalities
  • Features:
    • Always unilateral
    • Location:
      • Orbital
      • Supraorbital
      • Temporal
    • Not worsened by physical activity:
      • Affected individuals tend to become restless during attacks.
      • Common behaviors: pacing, rocking to-and-fro, fidgeting
    • Frequency: up to 8 attacks per day
    • Duration: 15–180 minutes per attack
    • Attacks often occur overnight, causing sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance.

Physical exam

  • Physical examination may be entirely normal unless the affected individual is acutely experiencing an attack.
  • In the event an acute attack is present, the examiner may observe:
    • Restlessness
    • Pacing
    • Fidgeting
    • Injected conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy
    • Lacrimation
    • Nasal mucosal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus
    • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Eyelid ptosis Ptosis Cranial Nerve Palsies
    • Facial diaphoresis
    • Miosis Miosis Pupil: Physiology and Abnormalities

Subtypes 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

  • Episodic:
    • Most common subtype
    • Regular Regular Insulin daily headaches for days up to several weeks (6–12 on average)
    • Intermittent periods 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 remission (up to 12 months)
    • May progress in frequency/duration to chronic 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
  • Chronic:
    • No associated periods 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 remission (or brief, < 1 month)
    • ≥ 12 months without remission required for diagnosis
    • May arise as 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 or as a progression from episodic 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
  • Secondary causes 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 meet the criteria for 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 but are caused by an associated 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 lesion.

Diagnosis

Diagnostic criteria

General:

  • ≥ 5 attacks meeting the following criteria:
    • Severe intensity
    • Unilateral
    • Temporal, orbital, and/or supraorbital location of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Duration ≥ 15, but ≤ 180 minutes if left untreated
  • Plus ≥ 1 of the following symptoms ipsilateral to the pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways:
    • Injected conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy
    • Lacrimation
    • Nasal congestion
    • Rhinorrhea Rhinorrhea Excess nasal drainage. Respiratory Syncytial Virus
    • Eyelid ptosis Ptosis Cranial Nerve Palsies
    • Eyelid edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Facial diaphoresis
    • Pupillary miosis Miosis Pupil: Physiology and Abnormalities
    • Restlessness or agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Frequency: every 2 days, up to 8 times per day
  • Not better accounted for by another 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 diagnosis

Episodic 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:

Meets the criteria stated above plus the following criteria:

  • Headaches occur in clusters.
  • ≥ 2 clusters lasting ≥ 7 days, but ≤ 1 year if left untreated
  • Clusters separated 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-free periods of remission lasting ≥ 3 months

Chronic 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:

Meets the criteria stated above plus the following criteria:

  • Absence of remission, OR
  • Remissions lasting ≤ 3 months during ≥ 1-year period

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 Infectious Febrile Infant process
  • Laboratory testing should be specific to the suspected underlying cause(s):
    • 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:
      • 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)
      • The presence of 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 Infectious Febrile Infant process:
      • CBC
      • CSF studies

Imaging

  • Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant is indicated at the initial evaluation 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:
    • Rule out the secondary causes of headaches.
    • Evaluate for pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types abnormalities.
  • Repeat imaging is indicated 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 no longer classify 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 modalities:
    • MRI of 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 with and without contrast is the test of choice.
    • CT is 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

While abortive therapy may successfully terminate an isolated attack, preventative therapy is the mainstay 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 management. Preventive strategies should be started at the 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 episodes.

Abortive therapy

  • 1st-line therapies:
    • 100% oxygen:
      • Administered by a nasal cannula Nasal Cannula Respiratory Failure (office setting or ED)
      • May be approved for home use in some cases
      • Immediate onset of action
      • Well tolerated and highly effective
      • Main adverse effect: dry 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 and Nasal Cavity: Anatomy
    • 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):
      • May be administered at home (self-injection) or in the office
      • Rapid onset of action
    • Triptan (intranasal):
      • For individuals who cannot tolerate or self-administer injections
      • Slower onset of action, but more convenient
      • To be administered contralateral to the side 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
  • 2nd-line therapies:
    • Intranasal lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics:
      • Easy to self-administer
      • Well tolerated (no systemic adverse effects)
    • Ergotamines:
      • Administered orally or IV
      • Long half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics → potential bridge to preventative therapy

Preventative therapy

  • Indication:
    • Episodic and chronic 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
    • Prevention/treatment 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 and toxicity Toxicity Dosage Calculation caused by abortive medication overuse
  • Pharmacologic therapy:
    • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
      • Relatively rapid onset to suppress clusters
      • Not indicated for long-term use due to known toxicities
      • Used for suppression Suppression Defense Mechanisms of infrequent episodic bouts
      • Bridge to preventative therapy while slower acting agents are titrated to effective doses
      • Administration: oral, IM, occipital Occipital Part of the back and base of the cranium that encloses the foramen magnum. Skull: Anatomy nerve block
    • Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs:
      • Slow onset of action
      • May need bridge therapy with glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids or ergotamines
      • Inexpensive and usually well tolerated
      • May be tapered and discontinued prior to an expected remission
    • Galcanezumab:
      • Monoclonal antibody against 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) ligand
      • Modestly effective
      • Reserved for individuals refractory to the above preventative therapies
    • Nonpharmacologic therapies:
      • 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, sphenopalatine ganglion 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
    • Neurolytic therapy:
      • Mechanical, thermal, or chemical
      • Targets include culprit somatic and/or autonomic nerves.
      • Reserved for a select subset of individuals
  • Behavioral approaches:
    • Lifestyle modifications:
    • 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

Differential Diagnosis

  • Paroxysmal hemicrania: a rare form 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 and TAC with substantial similarity to 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 in terms of intensity, location, and presence of autonomic symptoms. Attacks occur 5–40 times per day and last 2–30 minutes. The diagnosis is clinical. Paroxysmal hemicrania is responsive to the 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) indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs), which is useful both in diagnosis and treatment. Other NSAIDs NSAIDS Primary vs Secondary Headaches, calcium channel blockers Calcium Channel Blockers Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers), and corticosteroids Corticosteroids Chorioretinitis are also effective.
  • Hemicrania continua: a TAC with substantial similarity to 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 in terms of location and presence of autonomic symptoms. Hemicrania continua is distinguished by a milder intensity but a longer, continuous 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 of several hours. There may be periodic exacerbations of severe intensity, but the underlying moderate 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 does not abate without treatment. The diagnosis is clinical. Hemicrania continua is responsive to the 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) indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs), which is useful both in diagnosis and treatment. 
  • SUNCT and SUNA: rare forms of TAC similar to 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 in pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways location but may also be retroorbital and rarely in other trigeminal and nontrigeminal areas. Attacks of prolonged stabbing pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (1–5 minutes) may occur in isolation or in groups with a total duration of up to 10 minutes. The attacks are often associated with triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency), but may also be spontaneous. Oxygen and indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs) are ineffective in SUNCT and SUNA, but IV lidocaine Lidocaine A local anesthetic and cardiac depressant used as an antiarrhythmic agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. Local Anesthetics may be effective.
  • Primary stabbing 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: while not classified as a TAC, primary stabbing 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 does have some overlapping clinical features. Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways attacks are brief (< 1 second), sharp and stabbing, and unilateral, but are not accompanied by autonomic symptoms. Attacks may be isolated or can occur at irregular intervals with several hours or even days between episodes. Diagnosis is clinical. The attacks usually subside with the administration of indomethacin Indomethacin A non-steroidal anti-inflammatory agent (nsaid) that inhibits cyclooxygenase, which is necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. Nonsteroidal Antiinflammatory Drugs (NSAIDs).
  • Trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia: a rare neuralgiform 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 that manifests in the temporal, orbital, or supraorbital area(s) with extreme sudden burning or shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock-like face pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia may mimic a TAC as it may manifest in any of the trigeminal areas. Attacks generally last < 5 seconds, are unilateral, and not accompanied by autonomic symptoms. Management includes drugs such as anticonvulsants (e.g., carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs) and tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants, and surgery. Typical analgesics and opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics have not been proven effective to treat trigeminal neuralgia Trigeminal neuralgia Trigeminal neuralgia (TN) is an often chronic and recurring pain syndrome involving the sensory distribution of the trigeminal nerve (cranial nerve (CN) V). The pain is typically unilateral and described as an acute, sharp, electric-shock-like pain involving the maxillary or mandibular areas and often associated with spasm of facial muscles. Trigeminal Neuralgia.
  • 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: a type of 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 generally described as unilateral and throbbing. 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 headaches are associated with neurological symptoms such as 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 light and sound sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques. Attacks last between 4 and 72 hours and are more common in women. Individuals may experience an aura Aura Reversible neurological phenomena that often precede or coincide with headache onset. Migraine Headache, such as a visual phenomenon, or experience tingling Tingling Posterior Cord Syndrome on the 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 or difficulty speaking before 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. Diagnosis is clinical and based on the typical symptoms. Migraines do not generally present with autonomic symptoms, but there is a distinct subset that does. Management includes avoiding loud noises and light, and treatment with simple analgesics Simple Analgesics Primary vs Secondary Headaches and/or 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.
  • 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. 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 medications to relieve headaches. 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 drug combinations containing 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 preventative regimen so that the offending abortive agent(s) can 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: 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 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 and Nasal Cavity: Anatomy. 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 and Nasal Cavity: Anatomy, 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.

References

  1. May, A. (2020). Cluster headache: Epidemiology, clinical features, and diagnosis. UpToDate. Retrieved July 23, 2021, from https://www.uptodate.com/contents/cluster-headache-epidemiology-clinical-features-and-diagnosis
  2. May, A. (2020). Cluster headache: Treatment and prognosis. Retrieved July 23, 2021, from https://www.uptodate.com/contents/cluster-headache-treatment-and-prognosis
  3. American Migraine Foundation. (2019). Understanding cluster headache. Retrieved July 19, 2021, from https://americanmigrainefoundation.org/resource-library/cluster-headache-2/
  4. Benoliel, R. (2012). Trigeminal autonomic cephalgias. British Journal of Pain. 6(3), 106–123. https://doi.org/10.1177/2049463712456355
  5. National Institute of Neurological Disorders and Stroke. (2019). Paroxysmal hemicrania information page. Retrieved July 29, 2021, from https://www.ninds.nih.gov/Disorders/All-Disorders/Paroxysmal-Hemicrania-Information-Page 
  6. National Institute of Neurological Disorders and Stroke. (2019). Hemicrania continua information page. Retrieved July 29, 2021, from https://www.ninds.nih.gov/Disorders/All-Disorders/Hemicrania-Continua-Information-Page 

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