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Cluster Headache

  • Author: Michelle Blanda, MD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
 
Updated: Dec 07, 2015
 

Background

Cluster headache (CH), also known as histamine headache, is a primary neurovascular headache disorder, the pathophysiology and etiology of which are not well understood.[1] As the name suggests, CH involves a grouping of headaches, usually over a period of several weeks. According to the diagnostic criteria developed by the International Headache Society (IHS), CH has the following characteristics:[2, 3]

  • The patient experiences attacks of severe or very severe, strictly unilateral pain (orbital, supraorbital, or temporal pain) that last 15-180 minutes and occur from once every other day to 8 times a day
  • The attacks are associated with 1 or more of the following (all ipsilateral): conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis, or eyelid edema

CH may be usefully classified into 2 main forms as follows:

  • Episodic CH, in which at least 2 cluster phases lasting 7 days to 1 year are separated by a cluster-free interval of 1 month or longer
  • Chronic CH, in which the clusters occur more than once a year without remission or the cluster-free interval is shorter than 1 month
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Pathophysiology

The underlying pathophysiology of CH is incompletely understood.[4, 5] The periodicity of the attacks suggests the involvement of a biologic clock within the hypothalamus (which controls circadian rhythms), with central disinhibition of the nociceptive and autonomic pathways—specifically, the trigeminal nociceptive pathways. Positron emission tomography (PET) and voxel-based morphometry have identified the posterior hypothalamic gray matter as the key area for the basic defect in CH.[1] See the images below.

Cluster headache: Functional imaging shows activat Cluster headache: Functional imaging shows activation of specific brain areas during pain. Courtesy of Wikipedia Commons.
Cluster headache (CH): Voxel-based morphometry (VB Cluster headache (CH): Voxel-based morphometry (VBM) structural imaging shows specific brain area of CH patients' (hypothalamus) being different to non-CH patients' brains. Courtesy of Wikipedia Commons.

Altered habituation patterns and changes have been observed within the trigeminal-facial neuronal circuitry secondary to central sensitization, in addition to dysfunction of the serotonergic raphe nuclei-hypothalamic pathways (though the latter is not as striking as in migraine). Functional hypothalamic dysfunction has been confirmed by abnormal metabolism based on the N-acetylaspartate neuronal marker in magnetic resonance spectroscopy.[6]

Substance P neurons carry sensory and motor impulses in the maxillary and ophthalmic divisions of the trigeminal nerve. These connect with the sphenopalatine ganglion and interior carotid perivascular sympathetic plexus. Somatostatin inhibits substance P and reduces the duration and intensity of CH.

Vascular dilatation may play a role in the pathogenesis of CH, but blood flow studies are inconsistent. Extracranial blood flow (hyperthermia and increased temporal artery blood flow) increases, but only after the onset of pain. Vascular change is considered secondary to primary neuronal discharge.

Although the evidence supporting a causative role for histamine is inconsistent, cluster headaches may be precipitated with small amounts of histamine. Antihistamines do not abort cluster headaches. Increased numbers of mast cells have been found in the skin of painful areas of some patients, but this finding is inconsistent.

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Etiology

The exact cause of CH is unknown. The disorder is sporadic, though rare cases of an autosomal dominant pattern within a single family have been reported.

Several factors have been shown to provoke CH attacks. Subcutaneous injection of histamine provokes attacks in 69% of patients. Stress, allergens, seasonal changes, or nitroglycerin may trigger attacks in some patients. Alcohol induces attacks during a cluster but not during remission. About 80% of CH patients are heavy smokers, and 50% have a history of heavy ethanol use.

Risk factors for CH include the following:

  • Male sex
  • Age older than 30 years
  • Small amounts of vasodilators (eg, alcohol)
  • Previous head trauma or surgery (occasionally)
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Epidemiology

The exact prevalence of CH in the United States is unknown; Kudrow estimated it to be 0.4% in men and 0.08% in women.[7] Compared with classic migraine, CH is relatively uncommon, with an incidence equivalent to only 2-9% of that of migraine. Prevalence in males is 0.4-1%. In an extensive study of 100,000 inhabitants of the republic of San Marino, the prevalence was 0.07%. The incidence of CH in the United Kingdom is equivalent to that of multiple sclerosis.

Age-, sex-, and race-related demographics

CH usually begins in middle adult life (eg, in the 30s); however, it has been reported in patients as young as 1 year and as old as 79 years.

CH is more common in males than in females; the male-to-female ratio was 6:1 in the 1960s but is now closer to 2:1. Presentations in females may differ from those in males, according to data from the United States Cluster Headache Survey.[8] For example, women tend to develop CH at an earlier age and are also more likely to exhibit a second peak of CH incidence after the age of 50.

Racial and ethnic differences have not been well studied, but CH may be slightly more prevalent in African Americans and may be underdiagnosed in black women.

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Prognosis

Generally, CH is a lifelong problem. Potential outcomes include the following:

  • Recurrent attacks
  • Prolonged remissions
  • Possibility of transformation of an episodic cluster to a chronic cluster and vice versa

About 80% of patients with episodic CH maintain the episodic form of the disorder. In 4-13%, episodic CH eventually transforms into chronic CH. Intermediate (mixed) forms may also develop. Prolonged, spontaneous remissions occur in as many as 12% of patients, particularly in those with episodic CH. Chronic CH is more relentless and may persist in this form in as many as 55% of cases. Less frequently, chronic CH may remit into an episodic form.

No reported mortality is directly associated with CH. However, patients with CH are at increased risk for self-injury during attacks, suicide attempts, alcohol use (and other forms of substance abuse), cigarette smoking, and peptic ulcer disease. Suicides have been reported in cases where attacks are frequent and severe. The intensity of the attacks often leads CH patients to miss time from activities such as work or school. Medications used may have side effects, including the unmasking of coronary artery disease.

Pharmacologic intervention may play a part in the transformation of chronic CH into the episodic form; otherwise, it does not influence outcome. Late onset of the disorder, male sex, and previous episodic CH all predict a less favorable course.

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Patient Education

Patients should be educated regarding the need to avoid known precipitants of CH. In addition, they should be instructed to avoid high altitudes.

For patient education resources, see the Headache Center, as well as Causes and Treatments of Migraine and Related Headaches, Cluster Headache, Alternative and Complementary Approaches to Migraine and Cluster Headaches, Cluster Headache FAQs, and Understanding Migraine and Cluster Headache Medications .

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Contributor Information and Disclosures
Author

Michelle Blanda, MD Chair Emeritus, Department of Emergency Medicine, Summa Health System Akron City/St Thomas Hospital; Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine

Michelle Blanda, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Rima M Dafer, MD, MPH, FAHA Associate Professor, Department of Neurology and Neurological Surgery, Loyola University, Chicago Stritch School of Medicine

Rima M Dafer, MD, MPH, FAHA is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Headache Society

Disclosure: Nothing to disclose.

Chief Editor

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

Joseph Carcione Jr, DO, MBA Consultant in Neurology and Medical Acupuncture, Medical Management and Organizational Consulting, Central Westchester Neuromuscular Care, PC; Medical Director, Oxford Health Plans

Joseph Carcione Jr, DO, MBA is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Steven C Dronen, MD, FAAEM Chair, Department of Emergency Medicine, LeConte Medical Center

Steven C Dronen, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Ragasri Kumar, DO Resident Physician, Department of Neurology, Loyola University Medical Center

Disclosure: Nothing to disclose.

Edward A Michelson, MD Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems in Cleveland

Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Lori K Sargeant, MD Consulting Staff, Summa Emergency Associates, Inc

Lori K Sargeant, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Ohio State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Cluster headache: Functional imaging shows activation of specific brain areas during pain. Courtesy of Wikipedia Commons.
Cluster headache (CH): Voxel-based morphometry (VBM) structural imaging shows specific brain area of CH patients' (hypothalamus) being different to non-CH patients' brains. Courtesy of Wikipedia Commons.
Non-rebreather oxygen mask with reservoir for the acute treatment of cluster headache. Courtesy of Wikipedia Commons.
 
 
 
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