Final Project in "Understanding the Brain: The Neurobiology of Everyday Life" Course

Cluster headache

Understanding the Brain: The Neurobiology of Everyday Life - Final Project

● Cluster headaches are excruciating attacks of neurovascular pain in one side of the head, often felt behind the eye.

● Cluster headaches occur in cyclical patterns or clusters, which gives the condition its name.

What are cluster headaches (CH)?

● CH are much more painful than migraines or any other type of headache. Sufferers often call them 'suicidal headaches' because they're so severe.

● Cluster headaches may be the most painful condition known to medical science.

● The pain is described as stabbing, drilling, burning or squeezing.

Characteristics of Pain

● The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.

● Descriptions of CH date to 1745 and probably earlier.

A Little Bit of History

● The condition was originally named Horton's cephalalgia after B.T. Horton, a US neurologist who postulated the first theory as to their pathogenesis.

● His original paper describes the severity of the headaches as being able to take normal men and force them to attempt or complete suicide.

A Little Bit of History

Our patients were disabled by the disorder and suffered from bouts of pain from two to twenty times a week. They had found no relief from the usual methods of treatment. Their pain was so severe that several of them had to be constantly watched for fear of suicide. Most of them were willing to submit to any operation which might bring relief. [B.T. Horton, 1939 ]

● Bouts of frequent attacks (cluster periods), may last from weeks to months, usually followed by remission periods when the headache attacks stop completely.

● The starting date and the duration of each cluster period may be consistent from period to period. For example, cluster periods may occur seasonally, such as every spring or every fall.

● Chronic cluster periods may continue for more than a year, or pain-free periods may last less than one month.

Characteristics of the Bouts: chronic CH

Cluster period example

● A cluster headache strikes quickly, usually without warning.

● Most people (~90%) have only episodic cluster headaches.

● In episodic cluster headaches, the cluster headaches occur for one week to a year, followed by a pain-free remission period, that may last as long as 12 months before another cluster headache develops.

● Some people have a single cluster headache cycle and never have another one.

Characteristics of the Bouts: episodic CH

● Headaches usually occur every day during a cluster periods, sometimes up to 8 times a day.

● A single attack may last from 15 minutes to 3 hours.

● The attacks often happen at the same time within each 24-hour day.

● The majority of attacks occur at night, usually one to two hours after you go to bed.

● The pain usually ends as suddenly as it begins, with rapidly decreasing intensity.

Periodicity and Duration of the Attacks

● Cluster attacks usually occur with clocklike regularity during a 24-hour day, and the cycle of cluster periods often follows the seasons of the year.

● These patterns suggest that the body's biological clock is involved. In humans, the biological clock is located in the hypothalamus.

● Hypothalamic dysfunction may explain the timing and cyclical nature of cluster headache.

Cause: Hypothalamic dysfunction?

● Positron emission tomography (PET) and voxel-based morphometry have identified the posterior hypothalamic gray matter as the key area for the basic defect in Cluster attacks.

● Research suggests that the hypothalamus becomes overactive during each attack.

● However, it is not known what causes this overactivity.

Cause: Hypothalamic dysfunction?

● Average activation across nine cluster headache patients during an acute right-sided attack compared to the headache-free resting state. PET demonstration of hypothalamic activation in cluster headache:

Cause: PET and MRA findings

● During an attack, the hypothalamus is thought to release neurotransmitters (such as histamin).

● These activate a nerve pathway in the base of the brain (the trigeminal-autonomic reflex pathway) causing the pain and other symptoms.

● The trigeminal nerve is the main nerve of the face responsible for sensations (such as heat or pain).

Cause: Hypothalamic overactivity

● When activated, the trigeminal nerve causes the eye pain associated with cluster headaches.

● The trigeminal nerve also stimulates another group of nerves that causes the eye tearing and redness, nasal congestion, and discharge associated with cluster attacks.

Cause: activation of trigeminal nerve

● The nerve overactivity may also cause vasolidation of the arteries (such as internal carotid and superior cerebellar arterys) in the affected side of the brain.

● These blood vessels then press on nearby brain tissues and nerves, which can cause pain.

Cause: vasodilation of the arteries

● Cluster headaches affect around 60 up to 280 per 100,000.

● E.g.: up to ~170'000 people in Italy or up to ~880'000 in USA

● Males are two to four times more likely to develop cluster headache than females

● The first cluster typically develops between the ages of 20 to 40 years, but it can start at any age!

Epidemiology: who gets cluster headaches?

● Smoking. Many people (~80%) who get cluster headache attacks are smokers.

● Alcohol use. Alcohol can trigger an attack if you're at risk of cluster headache.

● A family history. If a parent or sibling has ever had a cluster headache, you may have an increased risk of cluster headaches.

● Anyone can be affected!

● They were diagnosed with CH: Franz Kafka, Frank Carpa, Thomas Jefferson, Harry Potter (Daniel Radcliffe :)

Risk factors

● There's no cure for cluster headaches, ordinary painkillers do not work.

● The goal of treatment is to decrease the severity of pain, shorten the headache period and prevent the attacks.

Management & Prevention

Preventive therapy starts at the onset of the cluster episode with the goal of suppressing attacks.

● Calcium channel blockers,

● Corticosteroids,

● Lithium carbonate,

● Nerve block,

● Ergots (vasoconstricting agent),

● Melatonin,

● others.

Attack prevention

● Oxygen. Briefly inhaling 100 percent oxygen through a mask at a minimum rate of at least 12 liters a minute provides dramatic relief for most who use it.

● Triptans, it causes blood vessels to narrow, reducing bloodflow to the brain.

● Octreotide, an injectable synthetic version of the brain hormone somatostatin.

● Local anesthetics. The numbing effect of local anesthetics, such as lidocaine, may be effective against cluster headache pain in some people when given intranasal.

● Dihydroergotamine.

Acute attack treatment

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● Rarely doctors recommend surgery for peoplewho don't find relief with aggressive treatment or who can't tolerate the medications.

● Surgical procedures (such as radiofrequency thermocoagulation or gamma knife radiosurgery) for CH attempt to damage the nerve pathways thought to be responsible for pain.

● The long-term benefits of surgery are disputed. Also, because of the possible complications, including muscle weakness in the jaw or sensory loss in certain areas of the face and head

Surgery Treatment

As scientists learn more about the causes of cluster headache, they're able to develop more-selective treatments for the condition.

● Neurostimulation: a procedure in which a wire electrode is burrowed under the skin in the back of the neck region near the occipital nerve, and when electrical stimulation is provided, the cluster headaches can be turned off.

New methods: neurostimulation

● In this procedure, stimulator is placed into the hypothalamus and connected to a generator that changes brain's electrical impulses.

● DBS of the hypothalamus may provide relief for people with severe, chronic CH that haven't been successfully treated with other medications.

New methods: deep brain stimulation

The end

Appendix: cluster headache attacks

● Hypothalamus controls the autonomic nervous system, that is responsible for maintaining homeostasis

– heart rate, blood pressure, body temperature, fluid and electrolyte balance, including thirst, appetite and body weight, glandular secretions of the stomach and intestines, sleep cycles, circadian rhythm.

● Hypothalamus controls the hypophysis (pituitary)

– Pituitary is the most important endocrine gland and is often referred to as the "master gland", it controls most of the other endocrine glands in the body such as the thyroid, adrenal gland, testis and ovaries. By controlling the hypophysis the hypothalamus exerts control over most endocrine system. It is considered to be the link between the nervous system and the endocrine system.

● Emotion and behavior are a function of the hypothalamus, the limbic system, and the prefrontal cortex

– Hypothalamus may be the integrator of afferent information received from other areas of the nervous system and brings about the physical expression of emotion; it can produce an increase in the heart rate, elevate the blood pressure, cause dryness of the mouth, flushing or pallor of the skin, sweatingand massive peristaltic activity of the GIT.

Appendix: Hypothalamus functions

Images & photos

● Slide 1: http://gnes-cecile.deviantart.com/art/The-pain-of-cluster-headache-281297639● Slide 2 left: http://www.clusterkopf.de/● Slide 2 right: http://www.drbradeli.com/causes-of-headaches.html● Slide 3: http://www.ck-wissen.de/ckwiki/index.php?title=Datei:Clusterhead.jpg● Slide 4: http://dana-w.deviantart.com/art/Cluster-Headache-291329288● Slide 5: http://de.academic.ru/pictures/dewiki/66/BT_Horton.jpg● Slide 7: http://www.miqel.com/clusterheadaches/cluster-head-mushroom.html● Slide 9: http://www.clusterattack.com/blog/do-chronic-patients-cycle/● Slide 10: http://www.anatomy.plcnet.org● Slide 11: http://www.medicalassessment.com/images/Hypothalamus.gif● Slide 12: http://www.neurology.org/content/52/7/1522.full● Slide 13: wikimedia● Slide 14 left: http://uvahealth.com● Slide 14 right: http://connecttoresearch.com● Slide 15 left: http://swedish.org● Slide 15 right: Henry Gray, Anatomy of the Human Body, 1918● Slide 16: http://physio-pedia.com● Slide 18: http://healthcentral.com● Slide 21: http://e-algos.com● Slide 22: http://neurotechzone.com● Slide 23 left: http://bbc.co.uk● Slide 23 right: http://nuffieldbioethics.org● Slide 24: http://agnes-cecile.deviantart.com/art/drawing-restraint-II-262017331● Slide 25: http://youtube.com

References

1. Diseases and Conditions: Cluster headache, http://www.mayoclinic.org2. Cluster headaches, http://www.nhs.uk3. Cluster Headache, http://emedicine.medscape.com4. Migraines & Headaches Health Center, http://www.webmd.com5. Cluster Headaches, http://www.patient.co.uk6. Surgical options for cluster headache, http://www.mhni.com7. Cluster headaches, http://wikipedia.org8. Matharu M, Goadsby P (2001). "Cluster Headache". Practical Neurology 1: 42.9. Noshir Mehta, etl. Head, Face, and Neck Pain Science, Evaluation, and Management. John Wiley & Sons. pp. 19910. PET and MRA findings in cluster headache and MRA in experimental pain A. May, MD etl.11. PET demonstration of hypothalamic activation in cluster headache, Peter J. Goadsby, MD, PhD, DSc, and Arne May, MD12. Symptomatic cluster headache: a review of 63 cases, Bengt Edvardssoncorresponding author, Springerplus. 2014; 3: 64.13. Hypothalamic Involvement and Activation in CH, Arne May, MD etl., Current Pain and Headache Reports 2001, 5:60–6614. Cluster headache: what has changed since 1999? Massimo Leone etl. Springer-Verlag Italia 201315. An Overview of the Hypothalamus, http://www.endocrineweb.com16. Functions of the Hypothalamus, http://courses.cvcc.vccs.edu