Update On Cluster Headache

Cluster headache is considered among the most severe recurrent headache conditions known to humans. People with cluster headache experience severe one-sided headaches in or around the eye that usually last from 15 to 180 minutes without treatment. The headache is accompanied by several of the following symptoms on the side of the head pain: eye tearing, eyelid drooping, eye redness, nasal congestion or nasal discharge. During a cluster attack, cluster patients cannot and do not want to remain still because doing so seems to worsen the pain. Typically, they pace the floors or even bang their head against the wall to try and ease their pain.

Cluster headaches generally occur in cycles or “clusters” of daily headaches that last weeks or months, followed by remission periods in which the headaches go away for weeks to months. During an active cycle, cluster patients will usually have between one and three attacks per day. These headaches often strike during a specific stage of sleep (REM sleep), causing the sufferer to awaken with a severe headache 60 to 90 minutes after falling asleep.

1. An alarming trend
   Even though the symptoms of cluster headache are very distinct from migraine and tension-type headache, cluster patients are often not getting the correct diagnosis from their physicians. A recent study determined that, on average, it takes 6.6 years for a cluster patient to be diagnosed correctly. This delay is unacceptable, given the pain and suffering cluster patients must endure, especially when they are being inappropriately treated for something other than cluster headache.It is absolutely important to get a correct diagnosis of cluster headache because the treatment of cluster is unique and differs from the treatment strategies for other headache conditions. Once a correct diagnosis of cluster is made, then the correct therapy can be given. Treatment of cluster can be difficult and sometimes cluster patients need to see headache specialists to get proper therapy. Fortunately, our knowledge about the underlying cause of cluster headache is expanding and with this knowledge has come new cluster treatments, both medicinal and surgical.
2. What causes cluster headache
   The exact cause of cluster headache is still unknown but what we do know is that cluster headache evolves from activation of the trigeminal nerve (which supplies sensation to the face) and the autonomic nervous system (which regulates many bodily processes, including heart rate, body temperature and gland secretion). Activation of the trigeminal nerve causes pain in and around the eye. Activation of the autonomic nervous system produces the other symptoms of a cluster headache, such as eye tearing and nasal discharge. The activation of the trigeminal nerve and autonomic nervous system seems to be triggered in a region deep inside the brain called the hypothalamus, which regulates the sleep/wake cycle, among other important functions. The hypothalamus is likely the generator of cluster headaches and has recently become a new treatment target for difficult-to-treat cluster patients (see illustration).
3. Acute care therapy
   The goal of acute care therapy for cluster headache is fast, effective and consistent relief. Because an individual cluster headache is relatively short in duration, the acute treatment should work within 10 to 15 minutes to be considered adequate therapy.Sumatriptan. Injectable sumatriptan is the most effective medication for the acute relief of an individual cluster headache. Most patients will have complete relief within 15 minutes. The nasal spray formulation of sumatriptan is not as effective as the injection, and oral sumatriptan tablets have no role in cluster therapy because by the time the drug has kicked in (1 to 2 hours after administration) typically that individual headache is over. Even though sumatriptan has been known to effectively treat cluster headache for several years now, many cluster patients have still never tried this agent. There are some important contraindications for sumatriptan and the other triptans, so not everyone can take sumatriptan.
4. OxygenOxygen is an excellent abortive therapy for cluster headache and surprisingly many cluster patients have never been exposed to it. Typical dosing is 100% oxygen given via a face mask at 7 to 10 liters per minute for 20 minutes. This has been shown to work in up to 70% of cluster patients. Most patients will achieve pain relief within 10-20 minutes after starting oxygen. This is a nice therapy because it is safe and easy to use. Many cluster patients will have two oxygen tanks: one at home and one at work. It is very important that the oxygen is given correctly (no nasal cannula) or it will not be effective.
5. Zolmitriptan.Zolmitriptan is the first oral triptan (the class of drugs that includes sumatriptan) to be shown effective in episodic cluster headache. Doses for cluster are higher than those used for migraine. The response rates for zolmitriptan are not as good as those seen with oxygen or injectable sumatriptan, but it is a treatment option for patients who cannot tolerate injections and who either have not responded to oxygen or find oxygen difficult to use in their social or work situations.
6. Transitional therapy
   Transitional cluster therapy is a short-term preventive treatment that bridges the time between the onset of a cluster cycle and the time when the true preventive agent becomes effective. Transitional preventives are started at the same time the standard preventive is begun (see below). The transitional preventive should provide the cluster patient with almost immediate pain relief and allows the patient to be headache-free or nearly headache-free while the maintenance preventive dose is being increased to an effective level. When the transitional agent is tapered off (typically in 1 to 2 weeks), the maintenance preventive will have taken effect; thus, the patient will have no gap in headache prevention.Steroids. A short course of steroids (for example, prednisone) is the best transitional therapy for cluster headache. Patients frequently become cluster free within 24 to 48 hours on steroids and hopefully by the time the steroid is discontinued (usually after 8 to 10 days), the patient’s main preventive agent has started to become effective. Long-term steroid use is not recommended to treat cluster because of very severe side effects with extended usage of this class of drugs.
7. Occipital nerve blockade.

A recent study has shown that injecting an anesthetic agent and a small dose of steroid into the region of the greater occipital nerve (at the base of the skull) can provide cluster patients with an average of 13 days pain-free time after a single injection. This type of nerve block is comparable to the use of novocaine by dentists. It can be carried out by headache specialists and certain anesthesiologists in an outpatient setting with minimal pain for the patient. More studies are necessary to prove this approach as a legitimate transitional treatment for cluster headache.

1. • Preventive therapy
     Preventive agents are absolutely necessary in cluster headache. The main goal of cluster headache preventive therapy should be to make the individual headache-free even in a cluster cycle. Sometimes very large dosages, much higher than suggested in the drug’s labeled indications, are necessary when treating cluster headache. It is not uncommon for cluster patients to require several preventive medications at once to get better results. Standard preventive therapies include verapamil, lithium, methysergide, and valproate. Two new preventive treatments for cluster have been identified in the last several years.Topiramate. Topiramate is a newer anti-seizure drug that appears to be effective in both migraine and cluster headache. There have been several small studies showing that topiramate, in fairly low dosage, can turn off cluster headaches within 1 to 2 weeks after starting the medication. Topiramate can cause side effects so discussion with a physician will be necessary before starting this medication for cluster headache.Melatonin. Melatonin is a natural sleep hormone that we all produce in our own bodies. For some reason cluster patients do not produce normal levels of melatonin. This lack of melatonin may play a role in cluster headache production. Two small studies and clinical experience have indicated that fairly large doses of melatonin could prevent attacks of cluster headache, but the results of another small study, using a small dose of melatonin, suggest that it may not add any benefit to standard preventive therapies. This agent is purchased over the counter and appears to have minimal side effects. Because it is a supplement rather than a drug, it is not regulated by the US Food and Drug Administration (FDA). A number of supplements have been tested and found to contain much less of the active ingredient than claimed. So, if one brand does not appear to be helping, trying another brand of melatonin may be worthwhile. As yet no specific brand of melatonin can be suggested. Before staring melatonin a physician should be consulted. As we are learning more about melatonin and its effects on the body, some individuals with cluster may not be able to take melatonin because of possible side effects. The suggested dose of melatonin is 6 to 9 mg at bedtime.Newer treatments for cluster headache
     All cluster headache patients require treatment. Other headache syndromes can sometimes be managed non-medicinally, but for cluster headache, medication, sometimes even multiple medications at one time, is indicated. Cluster headache treatment can be divided into three classes. Acute care therapy is treatment given at the time of an attack to treat the individual headache. Transitional therapy can be considered an intermittent or short-term preventive treatment. Preventive therapy consists of daily medication given to reduce the frequency of cluster headache attacks, lower headache pain intensity, and decrease headache duration.
2. New surgical treatments for cluster headache
   Surgical treatment for cluster headache should only be considered after a patient has exhausted all medicinal options. In some instances the surgery can produce side effects that are worse than the cluster headaches themselves. New surgical treatments that are less invasive to the patient have recently been reported.Gamma knife radiosurgery. Gamma knife is a form of neurosurgery in which the trigeminal nerve (the nerve that causes cluster headache) is injured by a beam of radiation (see illustration). This can be done as an outpatient procedure and typically only takes several hours to complete. At present only a handful of medical institutions have gamma knife capabilities. Only one study has looked at the use of gamma knife in cluster and the results were promising. Four men and two women with cluster headache were treated. Five of the patients had chronic cluster headache (daily cluster headaches without periods of remission) and one had episodic cluster headache (daily attacks for weeks or months and then headache-free time for weeks or months). Four patients demonstrated excellent pain relief after gamma knife. Of the two remaining patients one had relief judged good and the other fair. Five of the six patients had relief within a few days to a week following gamma knife radiosurgery. None of the patients developed significant post-radiation side effects during a follow-up period of 8 to 14 months. What is attractive about this technique is that it can be done as an outpatient procedure, and it appears to have a low complication rate. No one yet knows, though, what the delayed complications of gamma knife might be, especially in young patients. Gamma knife is being utilized for cluster by headache centers across the country; reports suggest that it works initially but there are high relapse rates (return of cluster pain). More studies are necessary to determine if this treatment strategy is indeed useful in cluster headache.Deep brain /hypothalamic stimulation. A very exciting but experimental surgical treatment for treatment-resistant cluster headache has been carried out by an Italian group. Based upon the studies suggesting the hypothalamus as the generator of cluster headache, a stimulator was placed into the hypothalamus of 6 study patients with refractory cluster headache to see if stimulating the hypothalamus could stop a patient from having cluster headaches (see illustration). The researchers found that once the stimulator was turned on, the cluster headaches started to disappear. In some patients pain relief was immediate, while in others it took up to 4 months to become pain free. So far the patients have had no side effects with the stimulator. This treatment is completely experimental at present and is not available anywhere in the United States because it needs to be better studied for safety issues. What this study does represent is that a better understanding of what causes cluster headache can lead to better treatment options for patients.
3. Conclusion
   Exciting times are ahead in regard to cluster headache. We are continually learning more about what causes cluster and new treatments are being reported all the time. It is important for cluster patients to be properly diagnosed by a physician who understands how severe their pain really is and who will make all efforts to find safe and effective treatment.

–Todd D. Rozen, MD. Michigan Head-Pain and Neurological Institute. Ann Arbor, MI

From Headache, The Newsletter of ACHE. Winter 2002-03, vol. 13, no. 4.