Disease-a-Month 61 (2015) 236–239
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Cluster headache and trigeminal autonomic cephalgias Steven L. Meyers, MD
The trigeminal autonomic cephalgias (TACs) consist of a group of primary headache disorders that share the features of relatively short-duration, unilateral headache associated with cranial autonomic features. Cranial autonomic features include signs of parasympathetic activation including lacrimation, rhinorrhea, nasal congestion, eye lid edema, and sympathetic hypofunction, ptosis and miosis. As a group, they are much less common than the other primary headache disorders, migraine and tension headache, but they are important to recognize due to the severity of the pain, frequency of attacks, and in most cases, specific treatment options are available. The group consists of cluster headache, paroxysmal hemicranias, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).
Cluster headache Cluster headache is the most common of the TACs. The prevalence of cluster headache is approximately 50 per 100,000 with an overall male to female ratio of 3–4:1.1 Cluster headache can begin at any age with most beginning between ages 20 and 40 years. Cluster headache is characterized by severe attacks of pain located in or about the eye. Attacks are side locked in the majority, but attacks can switch sides in up to 14%. The pain is typically described as boring or stabbing with maximum severity peaking within 5–10 min. Patients frequently pace or sit holding their heads and tend to avoid lying quietly in bed as is more typical in migraine. Autonomic features occur ipsilateral to the pain and consist of ptosis, miosis, lacrimation, conjunctival injection, nasal congestion, and rhinorrhea.2 Attacks are usually brief lasting between 15 and 180 min, an important distinction with migraine where attacks last greater than 4 h. Attacks can occur from once every other day up to 8 per day, though 1–2 attacks per day is most typical. Attacks tend to occur at the same time each day and very commonly will wake the patient from sleep. Onset about 90 min after falling asleep is common and suggests an association with REM sleep. Seasonal variability has been reported with attacks more common in the spring and autumn. Attacks occur in clusters lasting weeks to months separated by pain-free remissions. Cluster headache occurs in 2 forms, episodic and chronic. In episodic cluster, the cluster periods last less than 1 year and are separated by remission periods of at least 1 month, though typically lasting http://dx.doi.org/10.1016/j.disamonth.2015.03.007 0011-5029/& 2015 Mosby, Inc. All rights reserved.
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months to years. Chronic cluster is defined as cluster periods lasting greater than 1 year or remission periods of less than 1-month duration. Episodic cluster is by far the more common form affecting 80–90% of patients.3 Recognition of the classic pattern of cluster headache should be straightforward. The differential diagnosis includes the other trigeminal autonomic disorders discussed later in this article and trigeminal neuralgia. Patients with trigeminal neuralgia lack autonomic features and typically have specific pain triggers not seen in cluster. There are rare reports of cranial pathology associated with attacks resembling cluster headache. Vascular lesions such as vertebral dissection, large artery intracranial aneurysms, and occipital lobe arteriovenous malformations, sphenoid wing meningiomas, and pituitary tumors have all been reported, though evidence of a direct causal relationship between the lesions and headache is usually poor.4 It is therefore recommended that all patients with suspected cluster headache be screened with MRI of the brain with contrast. MR or CT angiography can be considered if suspicion of a vascular lesion is high. Treatment of cluster attacks is divided into acute abortive therapies of individual attacks and preventative treatments. Due to the rapid onset and short duration of attacks, parenteral therapies are generally recommended as first-line agents. Subcutaneous sumatriptan 4–6 mg is the drug of choice for abortive treatment. Pain relief can be seen within 10 min, and the majority of patients respond.5 Unlike the situation in migraine, the long term, daily use of sumatriptan for cluster headache has not resulted in tachyphylaxis or rebound headache.6 Alternative abortive treatments include intranasal sumatriptan, intranasal zolmitriptan, or intranasal dihydroergotamine, though these are of slower onset and lower efficacy compared to subcutaneous sumatriptan. Inhalation of 100% oxygen by face mask at a rate of 7–10 l/min is a safe and effective abortive therapy in a large proportion of patients. Oxygen is usually used for 15–20 min and typically aborts the attack quickly. A minority of patients report that oxygen merely delays the onset of the attack for minutes to hours. Oxygen therapy is safe and can be used multiple times per day with no known adverse effect. However, the equipment is cumbersome and expensive, and many patients do not use oxygen long term.3 The goal of preventative therapies is to produce rapid suppression of attacks and to maintain this for the duration of the cluster period. Choice of preventative treatment is partially determined by the duration of the cluster episode. Shorter cluster periods can usually be effectively managed with brief courses of corticosteroids. Doses of 60–80 mg of prednisone will usually result in marked improvement very rapidly. However, due to the well-known adverse effects of long-term steroid use, courses are usually limited to 3–4 weeks. This may be sufficient for patients with short-duration cluster episodes but in those with longer-duration cluster periods or chronic cluster recurrence is likely. Steroids can be used in conjunction with other preventatives which may take weeks to become effective.3 Verapamil has become the drug of choice for longer-term prophylaxis of cluster headache. Doses higher than those typically used for cardiac reasons are commonly used in cluster patients. Doses between 160 and 960 mg have been reported to be effective.7 Verapamil is typically started at 80 mg 3 times daily, with dose increases every 10–14 days until attacks are suppressed, adverse effects are encountered, or a maximum dose of 960 mg daily is reached.8 Verapamil can cause arrhythmias and periodic ECG monitoring is recommended. Other common adverse effects include constipation and peripheral edema. Lithium has been found to be effective at doses between 600 and 1500 mg daily. Evidence suggests greater efficacy in chronic versus episodic cluster. Plasma levels should be monitored and kept between 0.6 and 1.2 mmol/l. Routine monitoring of liver, kidney, and thyroid functions is recommended.7 Drugs with limited evidence of efficacy which can be used when verapamil and lithium are ineffective include valproic acid, topiramate, and melatonin.7 Doses are similar to those used in treating migraine. Frequently combinations of medications will be necessary to achieve adequate prophylaxis.9
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Paroxysmal hemicranias Paroxysmal hemicrania is a rare headache disorder first described in 1974.10 The original description was of a chronic disorder characterized by daily headaches without remissions which the authors termed chronic paroxysmal hemicrania (CPH). Subsequent reports documented that some patients experienced prolonged remissions now termed episodic paroxysmal hemicranias (EPH). Unlike the situation with cluster, CPH is more common than EPH, making up 80% of cases. Attacks of paroxysmal hemicrania are strictly unilateral involving the ophthalmic division of the trigeminal nerve. The pain is centered in or behind the eye, temple, or frontal region. The pain is very severe and typically described as sharp, stabbing, or boring.3 The headaches typically last between 2 and 30 min with an average of approximately 15 min. Attack frequency is high between 1 and 40 attacks per day with a mean of 11, which helps to differentiate the hemicranias from cluster. Ipsilateral autonomic symptoms typically accompany the headache and commonly include lacrimation, conjunctival injection, rhinorrhea, nasal congestion, or facial flushing.11 Secondary or symptomatic cases of paroxysmal hemicrania are relatively common in the literature. The differential is similar to that described earlier for cluster headache. Pituitary tumors and pathology near the pituitary fossa are particularly common.4 Therefore, imaging is recommended in all cases of suspected paroxysmal hemicrania. The paroxysmal hemicranias are by definition indomethacin responsive, which is the treatment of choice. Complete response is typically seen within 2 days of beginning treatment. Dose ranges from 25 to 300 mg daily. Indomethacin is usually started at a dose of 25 mg 3 times per day, which can be doubled if there has been no response in 3 days. If there has not been complete relief, the dose is further increased to a maximum of 300 mg daily. Once a maximal response is achieved, improvements can usually be maintained on lower doses.7 Gastrointestinal prophylaxis with proton pump inhibitors is recommended due to the common GI adverse effects of indomethacin. No other treatment is as effective as indomethacin. Patients who do not respond to adequate doses of indomethacin should be re-evaluated for alternative diagnoses or secondary causes of PH. Patients who do not tolerate indomethacin have few alternatives. The data on alternative therapies is commonly based on single-case reports or small case series. Other NSAIDs including aspirin, ibuprofen, naproxen, and diclofenac have been reported to be effective.3 Other medications with limited data of efficacy include verapamil, acetazolamide, prednisone, carbamazepine, lithium, and topiramate.3
SUNCT syndrome SUNCT syndrome is a very rare headache syndrome first fully described in 1989. The name, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, defines the common features of this disorder. Like the other TACs, the pain is typically in the orbital or retro orbital region, forehead, or temple. The pain has a more neuralgia-like character with descriptors such as sharp, stabbing, burning, or electric shock being common. Duration of the pain is very brief between 5 and 240 s and can occur up to hundreds of time per day with an average around 60. The paroxysms can occur as isolated stabs or in groups of stabs. Cranial autonomic features consist primarily of conjunctival injection and tearing ipsilateral to the pain. The other autonomic features can be seen but less commonly.3 In many patients with SUNCT, attacks can be triggered in ways similar to trigeminal neuralgia. The most common triggers include touching specific areas innervated by the trigeminal nerve, chewing, washing the face, or brushing the teeth. Unlike trigeminal neuralgia, there is no refractory period meaning that an attack can be triggered immediately after a prior one. This is an important distinction that can help differentiate SUNCT from trigeminal neuralgia.3
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Table Differentiating features between the TACs.
Cluster headache Paroxysmal hemicrania SUNCT
Attack frequency
Attack duration
Indomethacin response
1–8 per day 1–40 per day 3–200 per day
15–180 min 2–30 min 5–240 s
þ
The differential of SUNCT is similar to the other TACs. Differentiation from trigeminal neuralgia has already been discussed. Secondary causes, primarily pituitary and posterior fossa abnormalities, have been described necessitating imaging in all patients. Data on treatment of SUNCT syndrome is limited to small case series, and randomized controlled studies do not exist. Lamotrigine appears to be the most effective medication.12 Other treatment options include gabapentin and topiramate. Intravenous lidocaine has been reported to be very effective in producing temporary remissions lasting weeks to months.12
Conclusion Recognizing and differentiating the various TACs have important implications for diagnostic work-up and treatment. Differentiating amongst the TACs can be difficult due to common features such as unilateral orbital pain location and presence of autonomic features. Helpful differentiating features are listed in Table. Duration of individual pain attacks and number of attacks per day are the most useful features to differentiate cluster headache from paroxysmal hemicranias and SUNCT syndrome. References 1. Fischera M, Marziniak M, Graslow I, Evers S. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia. 2008;28:64. 2. Nesbitt AD, Goadsby PJ. Cluster headache. Br Med J. 2012;344:e2407. 3. Matharu MS, Goadsby PJ. Trigeminal autonomic cephalalgias: diagnosis and management. In: Silberstein SD, Lipton RB, Dodick DW, eds. Wolff's Headache. 8th ed. New York: Oxford University Press; 2008:P379–P430. 4. Favier I, van Vliet JA, Roon KI, et al. Trigeminal autonomic cephalalgias due to structural lesions: a review of 31 cases. Arch Neurol. 2007;64:25. 5. Ekbom K, Monstad I, Prusinski A, et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan cluster Headache Study Group. Acta Neurol Scand. 1993;88:63–69. 6. Ekbom K, Krabbe A, Micieli G, et al. Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Study Group. Cephalalgia. 1995;15:230–256. 7. May A, Leone M, Afra J, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol. 2006;13:1066–1077. 8. Cohen AS, Martharu MS, Goadsby PJ. EKG changes associated with the use of verapamil in cluster headache. Neurology. 2006;66(suppl 2):A131. 9. May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet. 2005;366:843–855. 10. Sjaastad O, Dale I. Evidence for a new(?) treatable headache entity. Headache. 1974;14:105. 11. Cittadine E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a prospective clinical study of 31 cases. Brain. 2008;131:1142. 12. Cohen A, Matharu MS, Goadsby P. Suggested guidelines for treating SUNCT and SUNA. Cephalalgia. 2005;25:1200.
Contents lists available at ScienceDirect
Disease-a-Month journal homepage: www.elsevier.com/locate/disamonth
Cluster headache and trigeminal autonomic cephalgias Steven L. Meyers, MD
The trigeminal autonomic cephalgias (TACs) consist of a group of primary headache disorders that share the features of relatively short-duration, unilateral headache associated with cranial autonomic features. Cranial autonomic features include signs of parasympathetic activation including lacrimation, rhinorrhea, nasal congestion, eye lid edema, and sympathetic hypofunction, ptosis and miosis. As a group, they are much less common than the other primary headache disorders, migraine and tension headache, but they are important to recognize due to the severity of the pain, frequency of attacks, and in most cases, specific treatment options are available. The group consists of cluster headache, paroxysmal hemicranias, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).
Cluster headache Cluster headache is the most common of the TACs. The prevalence of cluster headache is approximately 50 per 100,000 with an overall male to female ratio of 3–4:1.1 Cluster headache can begin at any age with most beginning between ages 20 and 40 years. Cluster headache is characterized by severe attacks of pain located in or about the eye. Attacks are side locked in the majority, but attacks can switch sides in up to 14%. The pain is typically described as boring or stabbing with maximum severity peaking within 5–10 min. Patients frequently pace or sit holding their heads and tend to avoid lying quietly in bed as is more typical in migraine. Autonomic features occur ipsilateral to the pain and consist of ptosis, miosis, lacrimation, conjunctival injection, nasal congestion, and rhinorrhea.2 Attacks are usually brief lasting between 15 and 180 min, an important distinction with migraine where attacks last greater than 4 h. Attacks can occur from once every other day up to 8 per day, though 1–2 attacks per day is most typical. Attacks tend to occur at the same time each day and very commonly will wake the patient from sleep. Onset about 90 min after falling asleep is common and suggests an association with REM sleep. Seasonal variability has been reported with attacks more common in the spring and autumn. Attacks occur in clusters lasting weeks to months separated by pain-free remissions. Cluster headache occurs in 2 forms, episodic and chronic. In episodic cluster, the cluster periods last less than 1 year and are separated by remission periods of at least 1 month, though typically lasting http://dx.doi.org/10.1016/j.disamonth.2015.03.007 0011-5029/& 2015 Mosby, Inc. All rights reserved.
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months to years. Chronic cluster is defined as cluster periods lasting greater than 1 year or remission periods of less than 1-month duration. Episodic cluster is by far the more common form affecting 80–90% of patients.3 Recognition of the classic pattern of cluster headache should be straightforward. The differential diagnosis includes the other trigeminal autonomic disorders discussed later in this article and trigeminal neuralgia. Patients with trigeminal neuralgia lack autonomic features and typically have specific pain triggers not seen in cluster. There are rare reports of cranial pathology associated with attacks resembling cluster headache. Vascular lesions such as vertebral dissection, large artery intracranial aneurysms, and occipital lobe arteriovenous malformations, sphenoid wing meningiomas, and pituitary tumors have all been reported, though evidence of a direct causal relationship between the lesions and headache is usually poor.4 It is therefore recommended that all patients with suspected cluster headache be screened with MRI of the brain with contrast. MR or CT angiography can be considered if suspicion of a vascular lesion is high. Treatment of cluster attacks is divided into acute abortive therapies of individual attacks and preventative treatments. Due to the rapid onset and short duration of attacks, parenteral therapies are generally recommended as first-line agents. Subcutaneous sumatriptan 4–6 mg is the drug of choice for abortive treatment. Pain relief can be seen within 10 min, and the majority of patients respond.5 Unlike the situation in migraine, the long term, daily use of sumatriptan for cluster headache has not resulted in tachyphylaxis or rebound headache.6 Alternative abortive treatments include intranasal sumatriptan, intranasal zolmitriptan, or intranasal dihydroergotamine, though these are of slower onset and lower efficacy compared to subcutaneous sumatriptan. Inhalation of 100% oxygen by face mask at a rate of 7–10 l/min is a safe and effective abortive therapy in a large proportion of patients. Oxygen is usually used for 15–20 min and typically aborts the attack quickly. A minority of patients report that oxygen merely delays the onset of the attack for minutes to hours. Oxygen therapy is safe and can be used multiple times per day with no known adverse effect. However, the equipment is cumbersome and expensive, and many patients do not use oxygen long term.3 The goal of preventative therapies is to produce rapid suppression of attacks and to maintain this for the duration of the cluster period. Choice of preventative treatment is partially determined by the duration of the cluster episode. Shorter cluster periods can usually be effectively managed with brief courses of corticosteroids. Doses of 60–80 mg of prednisone will usually result in marked improvement very rapidly. However, due to the well-known adverse effects of long-term steroid use, courses are usually limited to 3–4 weeks. This may be sufficient for patients with short-duration cluster episodes but in those with longer-duration cluster periods or chronic cluster recurrence is likely. Steroids can be used in conjunction with other preventatives which may take weeks to become effective.3 Verapamil has become the drug of choice for longer-term prophylaxis of cluster headache. Doses higher than those typically used for cardiac reasons are commonly used in cluster patients. Doses between 160 and 960 mg have been reported to be effective.7 Verapamil is typically started at 80 mg 3 times daily, with dose increases every 10–14 days until attacks are suppressed, adverse effects are encountered, or a maximum dose of 960 mg daily is reached.8 Verapamil can cause arrhythmias and periodic ECG monitoring is recommended. Other common adverse effects include constipation and peripheral edema. Lithium has been found to be effective at doses between 600 and 1500 mg daily. Evidence suggests greater efficacy in chronic versus episodic cluster. Plasma levels should be monitored and kept between 0.6 and 1.2 mmol/l. Routine monitoring of liver, kidney, and thyroid functions is recommended.7 Drugs with limited evidence of efficacy which can be used when verapamil and lithium are ineffective include valproic acid, topiramate, and melatonin.7 Doses are similar to those used in treating migraine. Frequently combinations of medications will be necessary to achieve adequate prophylaxis.9
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S.L. Meyers / Disease-a-Month 61 (2015) 236–239
Paroxysmal hemicranias Paroxysmal hemicrania is a rare headache disorder first described in 1974.10 The original description was of a chronic disorder characterized by daily headaches without remissions which the authors termed chronic paroxysmal hemicrania (CPH). Subsequent reports documented that some patients experienced prolonged remissions now termed episodic paroxysmal hemicranias (EPH). Unlike the situation with cluster, CPH is more common than EPH, making up 80% of cases. Attacks of paroxysmal hemicrania are strictly unilateral involving the ophthalmic division of the trigeminal nerve. The pain is centered in or behind the eye, temple, or frontal region. The pain is very severe and typically described as sharp, stabbing, or boring.3 The headaches typically last between 2 and 30 min with an average of approximately 15 min. Attack frequency is high between 1 and 40 attacks per day with a mean of 11, which helps to differentiate the hemicranias from cluster. Ipsilateral autonomic symptoms typically accompany the headache and commonly include lacrimation, conjunctival injection, rhinorrhea, nasal congestion, or facial flushing.11 Secondary or symptomatic cases of paroxysmal hemicrania are relatively common in the literature. The differential is similar to that described earlier for cluster headache. Pituitary tumors and pathology near the pituitary fossa are particularly common.4 Therefore, imaging is recommended in all cases of suspected paroxysmal hemicrania. The paroxysmal hemicranias are by definition indomethacin responsive, which is the treatment of choice. Complete response is typically seen within 2 days of beginning treatment. Dose ranges from 25 to 300 mg daily. Indomethacin is usually started at a dose of 25 mg 3 times per day, which can be doubled if there has been no response in 3 days. If there has not been complete relief, the dose is further increased to a maximum of 300 mg daily. Once a maximal response is achieved, improvements can usually be maintained on lower doses.7 Gastrointestinal prophylaxis with proton pump inhibitors is recommended due to the common GI adverse effects of indomethacin. No other treatment is as effective as indomethacin. Patients who do not respond to adequate doses of indomethacin should be re-evaluated for alternative diagnoses or secondary causes of PH. Patients who do not tolerate indomethacin have few alternatives. The data on alternative therapies is commonly based on single-case reports or small case series. Other NSAIDs including aspirin, ibuprofen, naproxen, and diclofenac have been reported to be effective.3 Other medications with limited data of efficacy include verapamil, acetazolamide, prednisone, carbamazepine, lithium, and topiramate.3
SUNCT syndrome SUNCT syndrome is a very rare headache syndrome first fully described in 1989. The name, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, defines the common features of this disorder. Like the other TACs, the pain is typically in the orbital or retro orbital region, forehead, or temple. The pain has a more neuralgia-like character with descriptors such as sharp, stabbing, burning, or electric shock being common. Duration of the pain is very brief between 5 and 240 s and can occur up to hundreds of time per day with an average around 60. The paroxysms can occur as isolated stabs or in groups of stabs. Cranial autonomic features consist primarily of conjunctival injection and tearing ipsilateral to the pain. The other autonomic features can be seen but less commonly.3 In many patients with SUNCT, attacks can be triggered in ways similar to trigeminal neuralgia. The most common triggers include touching specific areas innervated by the trigeminal nerve, chewing, washing the face, or brushing the teeth. Unlike trigeminal neuralgia, there is no refractory period meaning that an attack can be triggered immediately after a prior one. This is an important distinction that can help differentiate SUNCT from trigeminal neuralgia.3
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239
Table Differentiating features between the TACs.
Cluster headache Paroxysmal hemicrania SUNCT
Attack frequency
Attack duration
Indomethacin response
1–8 per day 1–40 per day 3–200 per day
15–180 min 2–30 min 5–240 s
þ
The differential of SUNCT is similar to the other TACs. Differentiation from trigeminal neuralgia has already been discussed. Secondary causes, primarily pituitary and posterior fossa abnormalities, have been described necessitating imaging in all patients. Data on treatment of SUNCT syndrome is limited to small case series, and randomized controlled studies do not exist. Lamotrigine appears to be the most effective medication.12 Other treatment options include gabapentin and topiramate. Intravenous lidocaine has been reported to be very effective in producing temporary remissions lasting weeks to months.12
Conclusion Recognizing and differentiating the various TACs have important implications for diagnostic work-up and treatment. Differentiating amongst the TACs can be difficult due to common features such as unilateral orbital pain location and presence of autonomic features. Helpful differentiating features are listed in Table. Duration of individual pain attacks and number of attacks per day are the most useful features to differentiate cluster headache from paroxysmal hemicranias and SUNCT syndrome. References 1. Fischera M, Marziniak M, Graslow I, Evers S. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia. 2008;28:64. 2. Nesbitt AD, Goadsby PJ. Cluster headache. Br Med J. 2012;344:e2407. 3. Matharu MS, Goadsby PJ. Trigeminal autonomic cephalalgias: diagnosis and management. In: Silberstein SD, Lipton RB, Dodick DW, eds. Wolff's Headache. 8th ed. New York: Oxford University Press; 2008:P379–P430. 4. Favier I, van Vliet JA, Roon KI, et al. Trigeminal autonomic cephalalgias due to structural lesions: a review of 31 cases. Arch Neurol. 2007;64:25. 5. Ekbom K, Monstad I, Prusinski A, et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: a dose comparison study. The Sumatriptan cluster Headache Study Group. Acta Neurol Scand. 1993;88:63–69. 6. Ekbom K, Krabbe A, Micieli G, et al. Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Study Group. Cephalalgia. 1995;15:230–256. 7. May A, Leone M, Afra J, et al. EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias. Eur J Neurol. 2006;13:1066–1077. 8. Cohen AS, Martharu MS, Goadsby PJ. EKG changes associated with the use of verapamil in cluster headache. Neurology. 2006;66(suppl 2):A131. 9. May A. Cluster headache: pathogenesis, diagnosis, and management. Lancet. 2005;366:843–855. 10. Sjaastad O, Dale I. Evidence for a new(?) treatable headache entity. Headache. 1974;14:105. 11. Cittadine E, Matharu MS, Goadsby PJ. Paroxysmal hemicrania: a prospective clinical study of 31 cases. Brain. 2008;131:1142. 12. Cohen A, Matharu MS, Goadsby P. Suggested guidelines for treating SUNCT and SUNA. Cephalalgia. 2005;25:1200.
