㈿-6 AF

群発頭痛発作期の予防療法にはどのような薬剤があり，どの程度有効か

The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days' run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.

反復性群発頭痛におけるベラパミルの予防効果．プラセボ対照二重盲検試験

群発頭痛におけるスマトリプタンの効果と安全性を検討．

プラセボ対照二重盲検試験（ double-blind, placebo-controlled study ）

Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.

30 人の群発頭痛患者．

15 人がベラパミル 360mg/ 日， 15 人が placebo を 2 週間内服 .

ベラパミル群で発作頻度の減少を認めた．副作用はほとんどなし．

中規模の無作為二重盲検プラセボ対照試験．

Publication Types:
・ Clinical Trial
・ Randomized Controlled Trial

MeSH Terms:
・Adult
・Cluster Headache/drug therapy*
・Double-Blind Method
・Female
・Human
・Male
・Middle Aged
・Verapamil/adverse effects
・Verapamil/therapeutic use*

Substances:
・Verapamil

清水利彦，鈴木則宏

OBJECTIVE: To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period. SUBJECTS AND METHODS: This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States . Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg. MAIN OUTCOME MEASURES: The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed. RESULTS: Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01). CONCLUSION: Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.

反復性群発頭痛に対する civamide 点鼻薬の効果

群発頭痛発作期における civamide 点鼻薬による予防効果と安全性を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

Michigan Headache Pain and Neurological Institute, 3120 Professional Dr, Ann Arbor , MI 48104 , USA .

28 人の群発頭痛患者．

治療中と，治療後で週ごとの，頭痛の頻度，強度，随伴症状，副作用の出現を見た．

Civamide 群は placebo 群と比較し頭痛回数が減少．治療開始 1 日から 7 日で有意に減少 (-55.5% vs -25.9%; P =.03) ， 8 日から 14 日 (-66.9% vs -32.3%; P =.07) および 15 日から 20 日で減少傾向 (-70.6% vs -34.9%; P =.07) ．強度，随伴症状に差はなかった．副作用は鼻が焼ける感じ ( civamide 群で 14/18 ， placebo で 1/10 ； P =.001 ) ，流涙があった．

中規模の無作為二重盲検プラセボ対照試験．副作用強い．

清水利彦，鈴木則宏

We evaluated the efficacy of intravenous boluses of methylprednisolone followed by prednisone as a prophylactic treatment for episodic cluster headache. Fourteen male patients (mean age, 42.54 years) with episodic cluster headache were treated with 250-mg boluses of methylprednisolone on 3 consecutive days, followed by prednisone (90 mg/day orally) with gradual tapering in four weeks. Headache parameters of the active phases treated with methylprednisolone were compared with those of previous active phases in the same patients treated with other prophylactic medications. The primary efficacy criterion was decrease in the frequency of attacks during the first month of treatment. The statistical differences were calculated using Wilcoxon's test. The attacks were significantly less frequent in the active phases treated with methylprednisolone boluses than those treated with other medications ( p<0.05). This treatment seems to be more effective than the usual prophylactic treatments for episodic cluster headache.

群発頭痛におけるメチルプレドニゾロンの大量静注療法の予防効果

群発頭痛におけるメチルプレドニゾロンの大量静注療法とその後ステロイド治療の効果を検討．

Department of Neurology, University Hospital Virgen del Rocio, Avda. Manuel Siurot s/n, 41013 Seville , Spain .

14 人（平均年齢 42.54 歳）の男性反復性群発頭痛患者．

発作期に発作回数は，他の予防薬と比較し有意に減少した ( p<0.05).

無作為二重盲検プラセボ対照交差試験が必要か？

清水利彦，鈴木則宏

This multinational, multicenter, randomized, double-blind, placebo-controlled study in 169 patients investigated the effect of a 7-day period of preemptive treatment with oral sumatriptan (100 mg tid) on the frequency and severity of cluster headache attacks occurring during an established cluster headache period. Safety and tolerability were also assessed. Cluster headache patients who were not taking prophylactic medication and had experienced seven or more attacks in the preceding observation week, treated a cluster headache attack at home with subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7-day period. Cluster headaches occurring during this period could be treated 5 minutes after onset with rescue medication (100% oxygen or simple analgesics). Diary cards were used to record details of the cluster headache pattern during the observation and study treatment weeks. Preemptive oral treatment with sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the number or severity of cluster headache attacks occurring during an established cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day period was not associated with an increased or altered adverse event profile from that previously reported.

群発頭痛患者発作期の経口 Sumatriptan 予防内服投与．

群発頭痛発作期におけるスマトリプタン内服による予防効果．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

Nevrologisk avd, Hedmark Sentralsykehus, Elverum , Norway .

169 人の群発頭痛患者．今まで予防薬を内服せず， 7 回以上発作あり，スマトリプタン皮下注射を自己管理できる患者．

日記を渡し，頭痛のパターンを記載．

7 日間スマトリプタン 300 ｍｇ / 日は，頭痛の頻度，重症度に有意な減少を示さず．

大規模の無作為二重盲検プラセボ対照試験．

Publication Types:
・Clinical Trial
・Multicenter Study
・Randomized Controlled Trial

MeSH Terms:
・Administration, Oral
・Adult
・Cluster Headache/drug therapy*
・Comparative Study
・Female
・Human
・Injections, Subcutaneous
・Male
・Middle Aged
・Serotonin Agonists/administration & dosage*
・Serotonin Agonists/adverse effects
・Sumatriptan/administration & dosage*
・Sumatriptan/adverse effects

Substances:
・Serotonin Agonists
・Sumatriptan

清水利彦，鈴木則宏

BACKGROUND: A beneficial prophylactic effect from eletriptan 40 mg given to a single patient with cluster headache was observed. OBJECTIVE: To further evaluate the efficacy of eletriptan in the short-term prophylaxis of cluster headache. METHODS: We treated 18 patients; mean age, 40.5 years (standard deviation [SD], 9.9). The number of cluster headache attacks was recorded during a baseline period of 6 days, and during 6 days of treatment with eletriptan 40 mg twice daily. The primary outcome measure was the reduction in the number of attacks during the treatment period. RESULTS: In the 16 patients who completed the study (2 patients were lost to follow-up), the mean total number of attacks decreased from 10.9 (SD, 5.6) during baseline to 6.3 (SD, 3.7) during treatment with eletriptan (P=.01) The reduction in the number of attacks exceeded 50% in 6 patients. CONCLUSION: This small open-label study suggests that eletriptan 40 mg twice daily may be useful for the short-term prophylaxis of cluster headache.

群発頭痛に対する eletriptan の予防効果．

群発頭痛におけるエルトリプタンの予防効果を検討．

非盲検試験（ open label study ）　

Department of Neurology, University of Vienna ( Austria ) Medical School .

16 人の群発頭痛患者（平均年齢 40.5 歳）．

治療期間中に発作回数の減少の有無を調べる．

16 人の患者で発作の回数は 10.9 回から治療後 6.3 回に減少．

Preemptive oral treatment with sumatriptan during a cluster period. Headache. 1995 Nov-Dec;35(10):607-13. に対抗するには無作為二重盲検プラセボ対照試験が必要．

清水利彦，鈴木則宏

A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n = 10) or placebo (n = 10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p < 0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p < 0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.

群発頭痛患者におけるメラトニンの予防効果．
二重盲検プラセボ対照比較試験

群発頭痛におけるメラトニンの予防効果を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

Centro Cefalee, Istituto Neurologico Carlo Besta, Milan , Italy .

20 人の群発頭痛患者（２人慢性，１８人反復性）．

頭痛の頻度と重症度

メラトニン群で頭痛頻度は有意に減少し (ANOVA, p < 0.03) し，鎮痛薬の使用頻度は減少傾向 (ANOVA, p < 0.06) ．１０人中５人はメラトニン内服３ - ５日後に頻度の減少あり，メラトニンを中止するまで発作なし .
慢性群発頭痛と placebo は効果なし．副作用なし．

中規模の無作為二重盲検プラセボ対照試験．

清水利彦，鈴木則宏

BACKGROUND: The periodicity of cluster headache suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. The secretion of melatonin, a hormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, is altered in patients with cluster headache. Melatonin shifts circadian rhythms. A previous study of melatonin for primary prophylaxis of cluster headache demonstrated a 50% response rate. OBJECTIVE: To evaluate the use of melatonin as adjunctive therapy in patients with cluster headache who have incomplete relief of their headaches on conventional therapy. METHODS: Nine patients participated in the study, six with chronic cluster headache and three with episodic cluster headache. Patients with chronic cluster headache completed a baseline diary for 1 month, followed by 1 month of melatonin treatment, then 1 month of placebo. Patients with episodic cluster headache received placebo for 1 month, then melatonin for 1 month. Patients continued their usual prophylactic and abortive treatments during the study. Headache frequency, intensity, and use of analgesics were recorded. The primary endpoint of the study was the mean number of headaches per day, with mean daily analgesic consumption and percentage of mild, moderate, and severe headaches as secondary endpoints. RESULTS: There were no significant differences between means on analysis of variance and t testing for the melatonin, placebo, and baseline months for all primary and secondary endpoints. There were no side effects reported. CONCLUSIONS: Patients with chronic cluster headache or patients with episodic cluster headache whose headaches are uncontrolled on conventional therapy do not appear to gain therapeutically from the addition of melatonin to their usual treatment regimens. It is perhaps the phase-shifting properties of melatonin that mediate its effect in patients with episodic cluster headache, and it may be necessary to treat from the beginning of the cluster bout to reset the circadian pacemaker, thus producing a more positive outcome.

群発頭痛患者における補助療法としてのメラトニンの予防効果．準備研究．

群発頭痛患者で予防治療の効果のない患者にメラトニンを追加すると効果があるか．

臨床試験 (Controlled Clinical Trial)

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal , Canada .

9 人の群発頭痛患者（ 6 人慢性， 3 人反復性）．

頭痛の頻度，強度，鎮痛剤の使用頻度を記載．エンドポイントは，鎮痛剤の使用と頭痛の数，そして軽度，中等度，強度頭痛の頻度．

メラトニンと placebo 群で変化なし．

清水利彦，鈴木則宏

Chronic Cluster Headache (CCH) treatment is troublesome; since there are no pain-free periods, it must be continuous. The most effective CCH prophylactic drug today is lithium carbonate but long-term use of this drug is limited by the possibility of side effects. Recently, calcium antagonists have been successfully employed to prevent migraine, and preliminary studies also indicate that verapamil in particular is an efficacious treatment for CCH. We have conducted a multicenter trial employing a double-dummy, double blind, cross-over protocol, comparing verapamil with the established efficacy of lithium carbonate, in preventing CCH attacks. Both lithium carbonate and verapamil were effective in preventing CCH but verapamil caused fewer side effects and had a shorter latency period. We did not observe any correlation between plasma levels of the two drugs and their clinical efficacy. Both the drugs tested here may exert their effect by restoring a normal inhibitory tone to the pain modulating pathways from the trigemino-vascular system, a circuit putatively implicated in CCH.

Headache Centre, C. Besta Neurological Institute of Milan , Italy .

We report the result of a double-blind placebo controlled study of sodium valproate (SV) (1000-2000 mg/day) in the prophylaxis of cluster headache CH. Episodic and chronic CH were defined according to the International Headache Society classification. Ninety-six patients were included, 50 in the SV group and 46 in the placebo group. After a 7-day run-in period, patients were treated for 2 weeks. The primary efficacy criterion was the percentage of patients successfully improved, i.e having an at least 50% reduction in the average number of attacks per week between the run-in period and the last week of treatment. Whatever the type of CH, there was no difference between the two groups: 50% of subjects in the SV group and 62% in the placebo group were successfully improved (P = 0.23). This high success rate observed in the placebo group, which is likely to be due to the spontaneous remission of the episode, does not allow us to draw any valid conclusion with regard to the true efficacy of SV in the prophylaxis of CH.

群発頭痛患者に対しバルプロ酸が無効：方法に問題．

群発頭痛におけるバルプロ酸の予防効果を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

Service de Neurologie, Hopital Lariboisiere, Paris , France

96 人の群発頭痛患者．

効果は，頭痛の回数などが前後で何％変化したか．

バルプロ酸投与群と placebo 群で頭痛の改善度に変化なし（バルプロ酸群で 50% ， placebo 群で 62% の改善 (P = 0.23) ）．

中規模の無作為二重盲検プラセボ対照試験．

清水利彦，鈴木則宏

Prompted by the results of gabaergic drugs, such as valproate and topiramate, we performed this pilot study to assess the effect of gabapentin in cluster headache. Eight patients suffering from episodic cluster headache and four suffering from chronic cluster headache were studied. All of them had failed to respond to traditional prophylactic drugs. The design of the study was an open trial. The main parameter for effectiveness was the number of daily attacks. Gabapentin was given at the daily dosage of 900 mg. All patients were pain free after a maximum of 8 days after starting therapy, with a bout duration thus reduced to 16-40% of the average previous bouts (only applies to episodic cluster patients). We hypothesize that the gabaergic action of gabapentin, perhaps combined with other mechanisms, such as calcium channel blockade, may be responsible for its remarkable effects on cluster headache.

難治性群発頭痛に対する gabapentin の効果．準備研究．

群発頭痛における gabapentin の予防効果を検討．

臨床研究 ( open trial)

Dipartimento di Oncologia, Biologia e Genetica, Universita di Genova and Centro Interuniversitario per la Neurofisiologia del Dolore, Genova , Italy

通常の群発頭痛の予防治療に効果を示さない 8 人の反復性群発頭痛と 4 人の慢性群発頭痛患者．

効果判定は発作回数の変化で判定．

全ての患者で最大 8 日後までに痛みがなくなった．
発作の期間は以前と比べ 16-40% 減少した．

清水利彦，鈴木則宏

OBJECTIVE: The role of topiramate in the prophylactic treatment of cluster headache is still unclear. The aim of this study was to evaluate the effectiveness of topiramate in a group of patients with refractory episodic or chronic cluster headache. BACKGROUND: Proof of efficacy of preventive treatment of cluster headache is limited, especially for the chronic form of the disorder. There are very few randomized clinical trials on this condition with topiramate or other new anticonvulsant agents. Recent case reports and series involving topiramate have shown good results. The mechanism of action of topiramate is unknown, but is presumably mediated by gamma-aminobutyric acid. METHODS: Twenty-six patients with episodic (n = 12) or chronic (n = 14) cluster headache were studied prospectively. All patients had been treated with some preventive treatment, with poor or no response. Treatment with topiramate was initiated with 25 mg once a day, and the dose was titrated every 3 to 7 days to a maximum of 200 mg, according to clinical response and tolerability. RESULTS: Topiramate rapidly induced cluster remission in 15 patients, reduced the number of attacks more than 50% in 6 patients, and reduced the cluster period duration in 12. The mean time to remission was 14 days (range, 1 to 27), but in 7 patients remission was obtained within the first days of treatment with very low doses (25 to 75 mg a day). Tolerability was good within the lower range of doses used. Six patients discontinued treatment due to side effects (all with daily doses over 100 mg) or lack of efficacy. CONCLUSIONS: Our results confirm that topiramate can be an effective option for the preventive treatment of episodic and chronic cluster headache.

群発頭痛に対する Topiramate の予防効果患者を対象としたプラセボ注射液との二重盲検比較試験

群発頭痛における Topiramate の予防効果を検討．

Department of Neurology, Hospital Clinico Universitario, Universidad de Valencia, Avenida Blasco Ibanez 17, 46-010 Valencia, Spain.

26 人の群発頭痛患者（ 12 人の反復性群発頭痛と 14 人の慢性群発頭痛）．

15 人が突然寛解， 6 人は発作回数が 50% 以下に減少． 12 人は群発の持続期間が減少．
寛解まで平均は 14 日間だが， 7 人は初日に寛解した．
6 人は 100mg 以上で副作用が出て中止した．

清水利彦，鈴木則宏

Cluster headache is a rare, clinically well-characterized disabling disorder that occurs in both episodic and chronic forms. The very painful short-lived unilateral headache attacks are associated with autonomic dysfunction. A large number of drugs such as ergotamines, steroids, methysergide, lithium carbonate, verapamil, valproate, capsaicin, leuprolide, clonidine, methylergovine maleate, methylphenidate, and melatonin are considered beneficial for prophylaxis. Nevertheless, this extremely painful condition is occasionally refractory to conventional treatment. The antispastic agent baclofen has been shown to possess an antinociceptive activity. Its efficacy in neuralgias, central pain following spinal lesions, painful strokes, migraine, and medication misuse chronic daily headache suggests that it may be useful for prevention of cluster headache attacks. Therefore, we treated 16 symptomatic patients with cluster headache with daily baclofen, 15 to 30 mg, in three divided doses for the cluster period and 2 weeks after. Within a week, 12 patients reported the cessation of attacks. One was substantially better and became attack free by the end of the following week. In the remaining three patients, the attacks worsened and corticosteroids were prescribed. One of these was also given verapamil. Three of the 16 patients had an additional cluster period, which cleared with a second course of baclofen. In this pilot study, baclofen seemed to be effective, safe, and well tolerated for cluster headache, and seemed to retain its efficacy on repeated clusters.

群発頭痛におけるバクロフェンの効果

群発頭痛におけるバクロフェンの効果を検討．

二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）

Department of Neurology, Meir General Hospital, Sapir Medical Center, 59 Jabotinski Street, Kfar Saba 44288, Israel.

16 人の群発頭痛患者．

発作の回数と重症度

12 人は一週間以内に発作が終了．
1 人はかなり改善し，次週までに発作がなくなった．
その他 3 人は発作は悪化しステロイドを処方．
16 人中 3 人は次の群発期を向えバクロフェンのみで乗り切った．

清水利彦，鈴木則宏

The discovery of a new class of effective migraine-abortive medications, the triptans, has sparked a new interest in the study of vascular headache. Over the past few years, the Food and Drug Administration (FDA) has approved six new abortive pharmacologic therapies, with several others in various stages of clinical trials. Unfortunately, concurrent pharmacologic changes in headache prophylaxis have not kept pace with their abortive counterparts. However, divalproex sodium (Depakote), which is approved by the FDA as a migraine prophylactic agent, is the first in the anticonvulsant class of medication for migraine headache and has expanded the options in headache treatment. The objective of this retrospective multicenter study of 284 patients with migraine or cluster headaches was to examine the clinical efficacy and safety of divalproex sodium as prophylaxis in monotherapy and in polytherapy. Sixty-one percent of migraineurs and 73% of cluster patients noted a decrease in pain with divalproex sodium and continued that therapy for more than 3 months. Reported negative side effects included weight gain, nausea, somnolence, tremor, alopecia, dysequilibrium, and rash. However, only 14% of subjects discontinued therapy due to these side effects. Overall, divalproex sodium was found to be an effective and generally well-tolerated prophylactic treatment option as monotherapy or in polytherapy for migraine and cluster headache.

片頭痛と群発頭痛に対する divalproex sodium による治療

群発頭痛に対する divalproex sodium による予防効果を検討．

University Headache Center , Moorestown , NJ 08057-1550 , USA .

284 人の片頭痛と群発頭痛患者．

頭痛の重症度の減少．

群発頭痛患者の 73% が頭痛の痛みが減少．
副作用は体重増加，悪心，傾眠，振戦，脱毛などで 14% が副作用で継続中止．

清水利彦，鈴木則宏

Cluster headache is perhaps the most painful of the primary headache disorders. Its treatment includes acute, transitional, and preventive therapy. Despite the availability of many treatments, cluster headache patients can still be difficult to treat. We treated 14 cluster headache patients with greater occipital nerve block as transitional therapy (treatment initiated at the same time as preventive therapy). The mean number of headache-free days was 13.1 + 23.6. Four patients (28.5%) had a good response, five (35.7%) a moderate, and five (35.7%) no response. The greater occipital nerve block was well tolerated with no adverse events. Headache intensity, frequency and duration were significantly decreased comparing the week before with the week after the nerve block (P < 0.003, P = 0.003, P < 0.005, respectively). Greater occipital nerve blockade is a therapeutic option for the transitional treatment of cluster headache.

群発頭痛患者における大後頭神経ブロック

群発頭痛における大後頭神経ブロックの効果と安全性を検討．

Jefferson Headache Center , Thomas Jefferson University , Philadelphia , PA , USA .

14 人の群発頭痛患者．

頭痛の強度，頻度，持続時間をブロック前後の週で比較する．

4 人は良好． 5 人は中程度， 5 人は効果なし．副作用はなし．頭痛の強度，頻度，持続時間はブロックにより有意に低下した ( それぞれ P < 0.003, P = 0.003, P < 0.005).

清水利彦，鈴木則宏

This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy

群発頭痛患者６６人における翼口蓋神経節ブロック． 12 から 70 ヶ月の評価．

群発頭痛における翼口蓋神経節ブロックの効果と安全性を検討．

Department of Anesthesiology, Spaarne Hospital , Haarlem , The Netherlands

薬物療法が無効な， 56 人反復性群発頭痛 Group A ,10 人の慢性群発頭痛患者 Group B ．

Group A で 56 人中 34 人 (60.7%) ， Group B で 10 人中 3 に痛みが完全に消失．無効例は Group A で 8 人 (14.3%) Group B で 4 人 (40%). 経過観察期間は Group A で 29.1 +/- 10.6 ヶ月， Group B で 24 +/- 9.7 ヶ月（ 12 から 70 ヶ月）．副作用は一次的な鼻出血が 8 例，頬の血腫 11 例．口蓋の感覚低下が 9 例あったが 3 ヶ月で消失．

MeSH Terms:
・Acute Disease
・Adult
・Autonomic Nerve Block/adverse effects
・Autonomic Nerve Block/methods*
・Catheter Ablation/adverse effects
・Cheek
・Chronic Disease
・Cluster Headache/drug therapy
・Cluster Headache/surgery*
・Epistaxis/etiology
・Evaluation Studies
・Female
・Follow-Up Studies
・Ganglia, Parasympathetic/surgery*
・Ganglionectomy/adverse effects
・Hematoma/etiology
・Human
・Hypesthesia/etiology
・Male
・Maxillary Nerve/injuries
・Palate/innervation
・Remission Induction
・Treatment Outcome

清水利彦，鈴木則宏

Four men and two women were treated for refractory cluster headache by gamma knife radiosurgery of the trigeminal nerve root entry zone. The maximum dose of radiation was 70 Gy to the isocenter. Of five patients treated who had refractory chronic cluster headache and one with refractory episodic cluster headache, four had relief judged excellent. Of the two remaining patients with refractory chronic cluster headache, one had relief judged good and the other fair. Five of the six patients treated had relief within a few days to a week following gamma knife radiosurgery. Three with chronic cluster headache had remissions allowing cessation of all preventive and abortive medication. Although one patient experienced complete relief of chronic cluster headache, he continued to have migraine requiring medication. None of the patients treated developed significant postradiation side effects during a follow-up period of 8 to 14 months. The authors conclude that gamma knife radiosurgery of the trigeminal nerve affords great promise in the management of chronic and refractory cluster headache. The technique seemingly carries negligible short- and long- term risk.

難治性群発頭痛患者におけるガンマナイフ治療

難治性群発頭痛患者でガンマナイフの効果を見る．

Ford Headache Clinic, Birmingham , AL 35213 , USA .

6 人（男４，女２）の群発頭痛患者． 5 人は慢性群発頭痛，一人は反復性群発頭痛

4 人は効果はすばらしと判定． 2 人の難治性群発頭痛で一人はよい，もう一人はまあまあと判定． 5 人は数日から 7 日以内に疼痛は改善． 3 人の慢性群発頭痛は予防薬と発作薬がやめられた．重大な副作用は照射後なし． .

Publication Types:
• Case Reports

MeSH Terms:
• Adult
• Chronic Disease
• Cluster Headache/surgery*
• Female
• Human
• Male
• Middle Aged
• Pain, Intractable/surgery
• Radiosurgery/instrumentation*
• Trigeminal Nerve/surgery
• Trigeminal Neuralgia/surgery

清水利彦，鈴木則宏

OBJECTIVE: To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. METHODS: Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. RESULTS: Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. CONCLUSION: These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.

Department of Neurosurgery, Istituto Nazionale Neurologico C. Besta, Milan , Italy .

1) Leone M, D'Amico D, Frediani F, Moschiano F, Grazzi L, Attanasio A, 　 Bussone G. Verapamil in the prophylaxis of episodic cluster 　 headache: a double-blind study versus placebo.Neurology. 　 2000 Mar 28;54(6):1382-5.
論文抄録	The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days' run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.
文献 PubMed−ID	PMID: 10746617
エビデンスレベル	㈼
文献タイトル (日本語)	反復性群発頭痛におけるベラパミルの予防効果．プラセボ対照二重盲検試験
目的	群発頭痛におけるスマトリプタンの効果と安全性を検討．
研究デザイン	プラセボ対照二重盲検試験（ double-blind, placebo-controlled study ）
研究施設	Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.
研究期間	不明
対象患者	30 人の群発頭痛患者．
介入	15 人がベラパミル 360mg/ 日， 15 人が placebo を 2 週間内服 .
主要評価項目とそれに用いた統計学的手法	15 人がベラパミル 360mg/ 日， 15 人が placebo を 2 週間内服 .
結果	ベラパミル群で発作頻度の減少を認めた．副作用はほとんどなし．
結論	反復性群発頭痛の予防にベラパミルは有効．
コメント -1	中規模の無作為二重盲検プラセボ対照試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 18
備考	Publication Types: ・ Clinical Trial ・ Randomized Controlled Trial MeSH Terms: ・Adult ・Cluster Headache/drug therapy* ・Double-Blind Method ・Female ・Human ・Male ・Middle Aged ・Verapamil/adverse effects ・Verapamil/therapeutic use* Substances: ・Verapamil
作成者	清水利彦，鈴木則宏

2) Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, 　 Bernstein JE.Intranasal civamide for the treatment of episodic 　 cluster headaches. Arch Neurol. 2002 Jun;59(6):990-4.
論文抄録	OBJECTIVE: To evaluate the safety and efficacy of intranasal civamide solution for preventive treatment during an episodic cluster headache period. SUBJECTS AND METHODS: This was a multicenter, double-blind, randomized, vehicle-controlled study with a 7-day treatment period and a 20-day posttreatment period performed at 14 headache/neurology centers in the United States . Twenty-eight subjects were randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received civamide and 10 received the vehicle. Subjects received 100 microL of 0.025% civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper once daily for 7 days. The total daily dose of civamide was 50 microg. MAIN OUTCOME MEASURES: The number of cluster headaches per week during the treatment and posttreatment periods, pain intensity, presence of associated symptoms, and the incidence of adverse events were assessed. RESULTS: Subjects in the civamide group had a significantly greater percent decrease in the number of headaches from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03) and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near-significant decrease during the entire posttreatment period (days 1 through 20 [P =.054]) compared with the vehicle group. There were larger decreases in the number of headaches per week during the posttreatment period in the civamide-treated group, with trends toward significance during posttreatment days 8 through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07). There were no significant differences between groups in cluster headache pain intensity, number of severe headaches, or associated symptoms. The most common adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of 10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated subjects, 0 of 10 vehicle-treated subjects; P =.01). CONCLUSION: Intranasal civamide solution at a dose of 50 microg may be modestly effective in the preventive treatment of episodic cluster headache.
文献 PubMed−ID	PMID: 12056936
エビデンスレベル	㈵ b
文献タイトル (日本語)	反復性群発頭痛に対する civamide 点鼻薬の効果
目的	群発頭痛発作期における civamide 点鼻薬による予防効果と安全性を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究施設	Michigan Headache Pain and Neurological Institute, 3120 Professional Dr, Ann Arbor , MI 48104 , USA .
研究期間	不明
対象患者	28 人の群発頭痛患者．
介入	群発頭痛患者 18 人が civamide 点鼻薬（ 100 m ｌ of 0.025% civamide (25 m g) ）， 10 人が placebo( 100 m ｌ ) を 7 日間点鼻し， 20 日間経過観察．
主要評価項目とそれに用いた統計学的手法	治療中と，治療後で週ごとの，頭痛の頻度，強度，随伴症状，副作用の出現を見た．
結果	Civamide 群は placebo 群と比較し頭痛回数が減少．治療開始 1 日から 7 日で有意に減少 (-55.5% vs -25.9%; P =.03) ， 8 日から 14 日 (-66.9% vs -32.3%; P =.07) および 15 日から 20 日で減少傾向 (-70.6% vs -34.9%; P =.07) ．強度，随伴症状に差はなかった．副作用は鼻が焼ける感じ ( civamide 群で 14/18 ， placebo で 1/10 ； P =.001 ) ，流涙があった．
結論	civamide 点鼻薬は群発頭痛発作期に有効かもしれない．
コメント	中規模の無作為二重盲検プラセボ対照試験．副作用強い．
備考	Publication Types: ・Clinical Trial ・Multicenter Study ・Randomized Controlled Trial MeSH Terms: ・Administration, Intranasal ・Adult ・Aged ・Aged, 80 and over ・Anti-Arrhythmia Agents/administration & dosage* ・Anti-Arrhythmia Agents/adverse effects ・Capsaicin/administration & dosage* ・Capsaicin/adverse effects ・Capsaicin/analogs & derivatives* ・Cluster Headache/drug therapy* ・Cluster Headache/physiopathology ・Comparative Study ・Double-Blind Method ・Female ・Human ・Male ・Middle Aged ・Pilot Projects ・Self Administration/statistics & numerical data ・Statistics, Nonparametric ・Support, Non-U.S. Gov't Substances: ・Anti-Arrhythmia Agents ・civamide ・Capsaicin
作成者	清水利彦，鈴木則宏

3) Mir P, Alberca R, Navarro A, Montes E, Martinez E, Franco E, 　 Cayuela A, Lozano P. Prophylactic treatment of episodic cluster 　 headache with intravenous bolus of methylprednisolone. Neurol Sci. 　 2003 Dec;24(5):318-21.
論文抄録	We evaluated the efficacy of intravenous boluses of methylprednisolone followed by prednisone as a prophylactic treatment for episodic cluster headache. Fourteen male patients (mean age, 42.54 years) with episodic cluster headache were treated with 250-mg boluses of methylprednisolone on 3 consecutive days, followed by prednisone (90 mg/day orally) with gradual tapering in four weeks. Headache parameters of the active phases treated with methylprednisolone were compared with those of previous active phases in the same patients treated with other prophylactic medications. The primary efficacy criterion was decrease in the frequency of attacks during the first month of treatment. The statistical differences were calculated using Wilcoxon's test. The attacks were significantly less frequent in the active phases treated with methylprednisolone boluses than those treated with other medications ( p<0.05). This treatment seems to be more effective than the usual prophylactic treatments for episodic cluster headache.
文献 PubMed−ID	PMID: 14716526
エビデンスレベル	㈿
文献タイトル (日本語)	群発頭痛におけるメチルプレドニゾロンの大量静注療法の予防効果
目的	群発頭痛におけるメチルプレドニゾロンの大量静注療法とその後ステロイド治療の効果を検討．
研究デザイン	臨床試験
研究施設	Department of Neurology, University Hospital Virgen del Rocio, Avda. Manuel Siurot s/n, 41013 Seville , Spain .
研究期間	不明
対象患者	14 人（平均年齢 42.54 歳）の男性反復性群発頭痛患者．
介入	群発頭痛の発作期に 3 日間連続で 250mg メチルプレドニゾロンの静注，その後プレドニン 90mg 経口を 4 週間で漸減．頭痛のパラメーターとして以前に他の予防薬での効果と比較．効果としては，はじめの 1 ヶ月で発作頻度の減少の程度．
結果	発作期に発作回数は，他の予防薬と比較し有意に減少した ( p<0.05).
結論	メチルプレドニゾロンの静注は群発頭痛発作期に有効と思われる．
コメント	無作為二重盲検プラセボ対照交差試験が必要か？
備考	Publication Types: ・Clinical Trial MeSH Terms: ・Adult ・Cluster Headache/drug therapy* ・Cluster Headache/physiopathology ・Cluster Headache/prevention & control* ・Comparative Study ・Drug Administration Schedule ・Drug Therapy, Combination ・Ergotamine/therapeutic use ・Human ・Injections, Intravenous ・Male ・Methylprednisolone/administration & dosage ・Methylprednisolone/therapeutic use* ・Middle Aged ・Prednisone/administration & dosage ・Prednisone/therapeutic use ・Recurrence/prevention & control ・Sumatriptan/therapeutic use ・Support, Non-U.S. Gov't ・Treatment Outcome ・Verapamil/therapeutic use Substances: ・Sumatriptan ・Ergotamine ・Verapamil ・Prednisone ・Methylprednisolone
作成者	清水利彦，鈴木則宏

4) Monstad I, Krabbe A, Micieli G, Prusinski A, Cole J, Pilgrim A, 　 Shevlin P.Preemptive oral treatment with sumatriptan during a 　 cluster period. Headache. 1995 Nov-Dec;35(10):607-13.
論文抄録	This multinational, multicenter, randomized, double-blind, placebo-controlled study in 169 patients investigated the effect of a 7-day period of preemptive treatment with oral sumatriptan (100 mg tid) on the frequency and severity of cluster headache attacks occurring during an established cluster headache period. Safety and tolerability were also assessed. Cluster headache patients who were not taking prophylactic medication and had experienced seven or more attacks in the preceding observation week, treated a cluster headache attack at home with subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7-day period. Cluster headaches occurring during this period could be treated 5 minutes after onset with rescue medication (100% oxygen or simple analgesics). Diary cards were used to record details of the cluster headache pattern during the observation and study treatment weeks. Preemptive oral treatment with sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the number or severity of cluster headache attacks occurring during an established cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day period was not associated with an increased or altered adverse event profile from that previously reported.
文献 PubMed−ID	PMID: 8550362
エビデンスレベル	無効
文献タイトル (日本語)	群発頭痛患者発作期の経口 Sumatriptan 予防内服投与．
目的	群発頭痛発作期におけるスマトリプタン内服による予防効果．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究施設	Nevrologisk avd, Hedmark Sentralsykehus, Elverum , Norway .
研究期間	不明
対象患者	169 人の群発頭痛患者．今まで予防薬を内服せず， 7 回以上発作あり，スマトリプタン皮下注射を自己管理できる患者．
介入	群発頭痛患者は無作為に 7 日間スマトリプタン 300 ｍｇ / 日（ 100mg/8 時間ごと）または placebo を内服．内服期間中に頭痛が起きたら 100 ％酸素か鎮痛剤で対処．発作期の頭痛頻度と重症度と比較．認容性と安全性も検討．
主要評価項目とそれに用いた統計学的手法	日記を渡し，頭痛のパターンを記載．
結果	7 日間スマトリプタン 300 ｍｇ / 日は，頭痛の頻度，重症度に有意な減少を示さず．
結論	スマトリプタン予防内服は群発頭痛発作予防に無効．
コメント -1	大規模の無作為二重盲検プラセボ対照試験．
コメント -2	2002 年神経学会頭痛ガイドライン文献 21
備考	Publication Types: ・Clinical Trial ・Multicenter Study ・Randomized Controlled Trial MeSH Terms: ・Administration, Oral ・Adult ・Cluster Headache/drug therapy* ・Comparative Study ・Female ・Human ・Injections, Subcutaneous ・Male ・Middle Aged ・Serotonin Agonists/administration & dosage* ・Serotonin Agonists/adverse effects ・Sumatriptan/administration & dosage* ・Sumatriptan/adverse effects Substances: ・Serotonin Agonists ・Sumatriptan
作成者	清水利彦，鈴木則宏

5) Zebenholzer K, Wober C, Vigl M, Wessely P. Eletriptan for the 　 short-term prophylaxis of cluster headache.Headache. 　 2004 Apr;44(4):361-4.
論文抄録	BACKGROUND: A beneficial prophylactic effect from eletriptan 40 mg given to a single patient with cluster headache was observed. OBJECTIVE: To further evaluate the efficacy of eletriptan in the short-term prophylaxis of cluster headache. METHODS: We treated 18 patients; mean age, 40.5 years (standard deviation [SD], 9.9). The number of cluster headache attacks was recorded during a baseline period of 6 days, and during 6 days of treatment with eletriptan 40 mg twice daily. The primary outcome measure was the reduction in the number of attacks during the treatment period. RESULTS: In the 16 patients who completed the study (2 patients were lost to follow-up), the mean total number of attacks decreased from 10.9 (SD, 5.6) during baseline to 6.3 (SD, 3.7) during treatment with eletriptan (P=.01) The reduction in the number of attacks exceeded 50% in 6 patients. CONCLUSION: This small open-label study suggests that eletriptan 40 mg twice daily may be useful for the short-term prophylaxis of cluster headache.
文献 PubMed−ID	PMID: 15109360
エビデンスレベル	㈿
文献タイトル (日本語)	群発頭痛に対する eletriptan の予防効果．
目的	群発頭痛におけるエルトリプタンの予防効果を検討．
研究デザイン	非盲検試験（ open label study ）
研究施設	Department of Neurology, University of Vienna ( Austria ) Medical School .
研究期間	不明
対象患者	16 人の群発頭痛患者（平均年齢 40.5 歳）．
介入	6 日間，エルトリプタン 40mg を 1 日 2 回連日服用．
主要評価項目とそれに用いた統計学的手法	治療期間中に発作回数の減少の有無を調べる．
結果	16 人の患者で発作の回数は 10.9 回から治療後 6.3 回に減少．
結論	エルトリプタン 40mg ， 1 日 2 回の内服は群発頭痛発作の予防に有効かもしれない．
コメント	Preemptive oral treatment with sumatriptan during a cluster period. Headache. 1995 Nov-Dec;35(10):607-13. に対抗するには無作為二重盲検プラセボ対照試験が必要．
備考	Publication Types: ・Clinical Trial MeSH Terms: ・Adult ・Cluster Headache/prevention & control* ・Female ・Human ・Indoles/therapeutic use* ・Male ・Middle Aged ・Pilot Projects ・Pyrrolidines/therapeutic use* ・Serotonin Agonists/therapeutic use* ・Time Factors ・Treatment Outcome Substances: ・Indoles ・Pyrrolidines ・Serotonin Agonists ・eletriptan
作成者	清水利彦，鈴木則宏

6) Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G. 　 Melatonin versus placebo in the prophylaxis of cluster headache: 　 a double-blind pilot study with parallel groups. Cephalalgia. 　 1996 Nov;16(7):494-6
論文抄録	A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n = 10) or placebo (n = 10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p < 0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p < 0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.
文献 PubMed−ID	PMID: 8933994
エビデンスレベル	㈿
文献タイトル (日本語)	群発頭痛患者におけるメラトニンの予防効果．二重盲検プラセボ対照比較試験
目的	群発頭痛におけるメラトニンの予防効果を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究施設	Centro Cefalee, Istituto Neurologico Carlo Besta, Milan , Italy .
研究期間	不明
対象患者	20 人の群発頭痛患者（２人慢性，１８人反復性）．
介入	メラトニン 10 mg (n = 10) と placebo (n = 10) を 14 日間就前内服．
主要評価項目とそれに用いた統計学的手法	頭痛の頻度と重症度
結果	メラトニン群で頭痛頻度は有意に減少し (ANOVA, p < 0.03) し，鎮痛薬の使用頻度は減少傾向 (ANOVA, p < 0.06) ．１０人中５人はメラトニン内服３ - ５日後に頻度の減少あり，メラトニンを中止するまで発作なし . 慢性群発頭痛と placebo は効果なし．副作用なし．
結論	効果は弱いがメラトニンは有効かもしれない．
コメント	中規模の無作為二重盲検プラセボ対照試験．
備考	Publication Types: ・Clinical Trial ・Randomized Controlled Trial MeSH Terms: ・Adult ・Analysis of Variance ・Cluster Headache/prevention & control* ・Double-Blind Method ・Drug Administration Schedule ・Female ・Human ・Male ・Melatonin/administration & dosage ・Melatonin/therapeutic use* ・Pilot Projects Substances: ・Melatonin
作成者	清水利彦，鈴木則宏

7) Pringsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. 　 Melatonin as adjunctive therapy in the prophylaxis of cluster 　 headache: a pilot study. Headache. 2002 Sep;42(8):787-92.
論文抄録	BACKGROUND: The periodicity of cluster headache suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. The secretion of melatonin, a hormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, is altered in patients with cluster headache. Melatonin shifts circadian rhythms. A previous study of melatonin for primary prophylaxis of cluster headache demonstrated a 50% response rate. OBJECTIVE: To evaluate the use of melatonin as adjunctive therapy in patients with cluster headache who have incomplete relief of their headaches on conventional therapy. METHODS: Nine patients participated in the study, six with chronic cluster headache and three with episodic cluster headache. Patients with chronic cluster headache completed a baseline diary for 1 month, followed by 1 month of melatonin treatment, then 1 month of placebo. Patients with episodic cluster headache received placebo for 1 month, then melatonin for 1 month. Patients continued their usual prophylactic and abortive treatments during the study. Headache frequency, intensity, and use of analgesics were recorded. The primary endpoint of the study was the mean number of headaches per day, with mean daily analgesic consumption and percentage of mild, moderate, and severe headaches as secondary endpoints. RESULTS: There were no significant differences between means on analysis of variance and t testing for the melatonin, placebo, and baseline months for all primary and secondary endpoints. There were no side effects reported. CONCLUSIONS: Patients with chronic cluster headache or patients with episodic cluster headache whose headaches are uncontrolled on conventional therapy do not appear to gain therapeutically from the addition of melatonin to their usual treatment regimens. It is perhaps the phase-shifting properties of melatonin that mediate its effect in patients with episodic cluster headache, and it may be necessary to treat from the beginning of the cluster bout to reset the circadian pacemaker, thus producing a more positive outcome.
文献 PubMed−ID	PMID: 12390642
エビデンスレベル	無効
文献タイトル (日本語)	群発頭痛患者における補助療法としてのメラトニンの予防効果．準備研究．
目的	群発頭痛患者で予防治療の効果のない患者にメラトニンを追加すると効果があるか．
研究デザイン	臨床試験 (Controlled Clinical Trial)
研究施設	Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University , Montreal , Canada .
研究期間	不明
対象患者	9 人の群発頭痛患者（ 6 人慢性， 3 人反復性）．
介入	慢性群発頭痛患者は１ヶ月観察し，１ヶ月メラトニン，１ヶ月 Placebo ．反復性群発頭痛患者は１ヶ月 placebo ，１ヶ月メラトニン．患者はこの間通常の予防治療または急性期の治療を続ける．
主要評価項目とそれに用いた統計学的手法	頭痛の頻度，強度，鎮痛剤の使用頻度を記載．エンドポイントは，鎮痛剤の使用と頭痛の数，そして軽度，中等度，強度頭痛の頻度．
結果	メラトニンと placebo 群で変化なし．
結論	メラトニンを他の予防薬に追加しても変わらず．
備考	Publication Types: ・Clinical Trial ・Controlled Clinical Trial MeSH Terms: ・Adjuvants, Immunologic/therapeutic use* ・Adolescent ・Aged ・Analgesics/therapeutic use ・Chronic Disease ・Circadian Rhythm ・Cluster Headache/classification ・Cluster Headache/drug therapy* ・Cluster Headache/physiopathology ・Delayed-Action Preparations ・Drug Therapy, Combination ・Female ・Human ・Male ・Melatonin/therapeutic use* ・Middle Aged ・Pilot Projects ・Single-Blind Method ・Treatment Outcome Substances: ・Adjuvants, Immunologic ・Analgesics ・Delayed-Action Preparations ・Melatonin
作成者	清水利彦，鈴木則宏

8) Bussone G, Leone M, Peccarisi C, Micieli G, Granella F, Magri M, 　 Manzoni GC, Nappi G. Double blind comparison of lithium and 　 verapamil in cluster headache prophylaxis . Headache. 　 1990 Jun;30(7):411-7.
論文抄録	Chronic Cluster Headache (CCH) treatment is troublesome; since there are no pain-free periods, it must be continuous. The most effective CCH prophylactic drug today is lithium carbonate but long-term use of this drug is limited by the possibility of side effects. Recently, calcium antagonists have been successfully employed to prevent migraine, and preliminary studies also indicate that verapamil in particular is an efficacious treatment for CCH. We have conducted a multicenter trial employing a double-dummy, double blind, cross-over protocol, comparing verapamil with the established efficacy of lithium carbonate, in preventing CCH attacks. Both lithium carbonate and verapamil were effective in preventing CCH but verapamil caused fewer side effects and had a shorter latency period. We did not observe any correlation between plasma levels of the two drugs and their clinical efficacy. Both the drugs tested here may exert their effect by restoring a normal inhibitory tone to the pain modulating pathways from the trigemino-vascular system, a circuit putatively implicated in CCH.
文献 PubMed−ID	PMID: 2205598
エビデンスレベル	㈽
研究施設	Headache Centre, C. Besta Neurological Institute of Milan , Italy .
結論	リチウムは群発頭痛に有効である．
コメント	2002 年治療ガイドライン文献 23

9) El Amrani M, Massiou H, Bousser MG. A negative trial of sodium 　 valproate in cluster headache: methodological issues. Cephalalgia. 　 2002 Apr;22(3):205-8
論文抄録	We report the result of a double-blind placebo controlled study of sodium valproate (SV) (1000-2000 mg/day) in the prophylaxis of cluster headache CH. Episodic and chronic CH were defined according to the International Headache Society classification. Ninety-six patients were included, 50 in the SV group and 46 in the placebo group. After a 7-day run-in period, patients were treated for 2 weeks. The primary efficacy criterion was the percentage of patients successfully improved, i.e having an at least 50% reduction in the average number of attacks per week between the run-in period and the last week of treatment. Whatever the type of CH, there was no difference between the two groups: 50% of subjects in the SV group and 62% in the placebo group were successfully improved (P = 0.23). This high success rate observed in the placebo group, which is likely to be due to the spontaneous remission of the episode, does not allow us to draw any valid conclusion with regard to the true efficacy of SV in the prophylaxis of CH.
文献 PubMed−ID	PMID: 12047460
エビデンスレベル	無効
文献タイトル (日本語)	群発頭痛患者に対しバルプロ酸が無効：方法に問題．
目的	群発頭痛におけるバルプロ酸の予防効果を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究施設	Service de Neurologie, Hopital Lariboisiere, Paris , France
研究期間	不明
対象患者	96 人の群発頭痛患者．
介入	群発頭痛患者を 50 人のバルプロ酸 ( 1000-2000 mg/day ) 投与群と 46 人の placebo 群に分類． 7 日間の観察期間のあと 2 週間の治療．
主要評価項目とそれに用いた統計学的手法	効果は，頭痛の回数などが前後で何％変化したか．
結果	バルプロ酸投与群と placebo 群で頭痛の改善度に変化なし（バルプロ酸群で 50% ， placebo 群で 62% の改善 (P = 0.23) ）．
結論	placebo 群での高い改善率は群発頭痛の自然寛解によるのでパルプロ酸の効果を判定するのに適切でない．
コメント	中規模の無作為二重盲検プラセボ対照試験．
備考	Publication Types: ・Clinical Trial ・Controlled Clinical Trial ・Multicenter Study MeSH Terms: ・Adult ・Chi-Square Distribution ・Cluster Headache/drug therapy* ・Comparative Study ・Double-Blind Method ・Female ・Human ・Male ・Middle Aged ・Placebo Effect ・Statistics, Nonparametric ・Support, Non-U.S. Gov't ・Valproic Acid/therapeutic use* Substances: ・Valproic Acid
作成者	清水利彦，鈴木則宏

10) Leandri M, Luzzani M, Cruccu G, Gottlieb A. Drug-resistant cluster 　 headache responding to gabapentin: a pilot study. Cephalalgia. 　 2001 Sep;21(7):744-6
論文抄録	Prompted by the results of gabaergic drugs, such as valproate and topiramate, we performed this pilot study to assess the effect of gabapentin in cluster headache. Eight patients suffering from episodic cluster headache and four suffering from chronic cluster headache were studied. All of them had failed to respond to traditional prophylactic drugs. The design of the study was an open trial. The main parameter for effectiveness was the number of daily attacks. Gabapentin was given at the daily dosage of 900 mg. All patients were pain free after a maximum of 8 days after starting therapy, with a bout duration thus reduced to 16-40% of the average previous bouts (only applies to episodic cluster patients). We hypothesize that the gabaergic action of gabapentin, perhaps combined with other mechanisms, such as calcium channel blockade, may be responsible for its remarkable effects on cluster headache.
文献 PubMed−ID	PMID: 11595003
エビデンスレベル	㈽
文献タイトル (日本語)	難治性群発頭痛に対する gabapentin の効果．準備研究．
目的	群発頭痛における gabapentin の予防効果を検討．
研究デザイン	臨床研究 ( open trial)
研究施設	Dipartimento di Oncologia, Biologia e Genetica, Universita di Genova and Centro Interuniversitario per la Neurofisiologia del Dolore, Genova , Italy
研究期間	不明
対象患者	通常の群発頭痛の予防治療に効果を示さない 8 人の反復性群発頭痛と 4 人の慢性群発頭痛患者．
介入	1 日 900mg の gabapentin を処方
主要評価項目とそれに用いた統計学的手法	効果判定は発作回数の変化で判定．
結果	全ての患者で最大 8 日後までに痛みがなくなった．発作の期間は以前と比べ 16-40% 減少した．
結論	Gabapentin は GABA 作用の他にカルシウムチャネル阻害などの多様な機能を持ち群発頭痛に効果を発する．
備考	Publication Types: ・Clinical Trial MeSH Terms: ・Acetic Acids/therapeutic use* ・Adult ・Analgesics/therapeutic use* ・Cluster Headache/drug therapy* ・Drug Resistance/physiology ・Human ・Male ・Middle Aged ・Pilot Projects ・Support, Non-U.S. Gov't Substances: Acetic Acids Analgesics gabapentin
作成者	清水利彦，鈴木則宏

11) Lainez MJ, Pascual J, Pascual AM, Santonja JM, Ponz A, 　 Salvador A. Topiramate in the prophylactic treatment of cluster 　 headache. Headache. 2003 Jul-Aug;43(7):784-9.
論文抄録	OBJECTIVE: The role of topiramate in the prophylactic treatment of cluster headache is still unclear. The aim of this study was to evaluate the effectiveness of topiramate in a group of patients with refractory episodic or chronic cluster headache. BACKGROUND: Proof of efficacy of preventive treatment of cluster headache is limited, especially for the chronic form of the disorder. There are very few randomized clinical trials on this condition with topiramate or other new anticonvulsant agents. Recent case reports and series involving topiramate have shown good results. The mechanism of action of topiramate is unknown, but is presumably mediated by gamma-aminobutyric acid. METHODS: Twenty-six patients with episodic (n = 12) or chronic (n = 14) cluster headache were studied prospectively. All patients had been treated with some preventive treatment, with poor or no response. Treatment with topiramate was initiated with 25 mg once a day, and the dose was titrated every 3 to 7 days to a maximum of 200 mg, according to clinical response and tolerability. RESULTS: Topiramate rapidly induced cluster remission in 15 patients, reduced the number of attacks more than 50% in 6 patients, and reduced the cluster period duration in 12. The mean time to remission was 14 days (range, 1 to 27), but in 7 patients remission was obtained within the first days of treatment with very low doses (25 to 75 mg a day). Tolerability was good within the lower range of doses used. Six patients discontinued treatment due to side effects (all with daily doses over 100 mg) or lack of efficacy. CONCLUSIONS: Our results confirm that topiramate can be an effective option for the preventive treatment of episodic and chronic cluster headache.
文献 PubMed−ID	PMID: 12890134
エビデンスレベル	㈽
文献タイトル (日本語)	群発頭痛に対する Topiramate の予防効果患者を対象としたプラセボ注射液との二重盲検比較試験
目的	群発頭痛における Topiramate の予防効果を検討．
研究デザイン	臨床研究
研究施設	Department of Neurology, Hospital Clinico Universitario, Universidad de Valencia, Avenida Blasco Ibanez 17, 46-010 Valencia, Spain.
研究期間	不明
対象患者	26 人の群発頭痛患者（ 12 人の反復性群発頭痛と 14 人の慢性群発頭痛）．
介入	topiramate は 1 日 1 回 25 mg から始まり， 3 日から 7 日間隔で漸増し最大 1 日 200 mg まで効果と認容性を見ながら変化
結果	15 人が突然寛解， 6 人は発作回数が 50% 以下に減少． 12 人は群発の持続期間が減少．寛解まで平均は 14 日間だが， 7 人は初日に寛解した． 6 人は 100mg 以上で副作用が出て中止した．
結論	Topiramate は群発頭痛の予防に有効である．
コメント	臨床研究
備考	Publication Types: ・Case Reports MeSH Terms: ・Adult ・Aged ・Anticonvulsants/therapeutic use* ・Chronic Disease ・Cluster Headache/prevention & control* ・Female ・Fructose/analogs & derivatives* ・Fructose/therapeutic use* ・Human ・Male ・Middle Aged ・Prospective Studies ・Recurrence ・Treatment Outcome Substances: ・Anticonvulsants ・Fructose ・topiramate
作成者	清水利彦，鈴木則宏

12) Hering-Hanit R, Gadoth N.The use of baclofen in cluster headache. 　 Curr Pain Headache Rep. 2001 Feb;5(1):79-82.
論文抄録	Cluster headache is a rare, clinically well-characterized disabling disorder that occurs in both episodic and chronic forms. The very painful short-lived unilateral headache attacks are associated with autonomic dysfunction. A large number of drugs such as ergotamines, steroids, methysergide, lithium carbonate, verapamil, valproate, capsaicin, leuprolide, clonidine, methylergovine maleate, methylphenidate, and melatonin are considered beneficial for prophylaxis. Nevertheless, this extremely painful condition is occasionally refractory to conventional treatment. The antispastic agent baclofen has been shown to possess an antinociceptive activity. Its efficacy in neuralgias, central pain following spinal lesions, painful strokes, migraine, and medication misuse chronic daily headache suggests that it may be useful for prevention of cluster headache attacks. Therefore, we treated 16 symptomatic patients with cluster headache with daily baclofen, 15 to 30 mg, in three divided doses for the cluster period and 2 weeks after. Within a week, 12 patients reported the cessation of attacks. One was substantially better and became attack free by the end of the following week. In the remaining three patients, the attacks worsened and corticosteroids were prescribed. One of these was also given verapamil. Three of the 16 patients had an additional cluster period, which cleared with a second course of baclofen. In this pilot study, baclofen seemed to be effective, safe, and well tolerated for cluster headache, and seemed to retain its efficacy on repeated clusters.
文献 PubMed−ID	PMID: 11252142
エビデンスレベル	㈽
文献タイトル (日本語)	群発頭痛におけるバクロフェンの効果
目的	群発頭痛におけるバクロフェンの効果を検討．
研究デザイン	二重盲検プラセボ対照試験（ double-blind, placebo-controlled study ）
研究施設	Department of Neurology, Meir General Hospital, Sapir Medical Center, 59 Jabotinski Street, Kfar Saba 44288, Israel.
研究期間	不明
対象患者	16 人の群発頭痛患者．
介入	バクロフェン 15 から 30 mg を群発期（ 3 つの量に分ける）とその後 2 週間内服させる．
主要評価項目とそれに用いた統計学的手法	発作の回数と重症度
結果	12 人は一週間以内に発作が終了． 1 人はかなり改善し，次週までに発作がなくなった．その他 3 人は発作は悪化しステロイドを処方． 16 人中 3 人は次の群発期を向えバクロフェンのみで乗り切った．
結論	この研究ではバクロフェンは群発頭痛に有効で，繰り返す群発にも有効かもしれない．
コメント	臨床検査．
備考	Publication Types: ・Clinical Trial MeSH Terms: ・Adrenal Cortex Hormones/administration & dosage ・Adult ・Aged ・Autonomic Nervous System/physiopathology ・Baclofen/administration & dosage* ・Cluster Headache/drug therapy* ・Cluster Headache/physiopathology ・Cluster Headache/prevention & control ・Drug Administration Schedule ・Human ・Male ・Middle Aged ・Pilot Projects ・Treatment Outcome ・Verapamil/administration & dosage Substances: ・Adrenal Cortex Hormones ・Baclofen ・Verapamil
作成者	清水利彦，鈴木則宏

13) Gallagher RM, Mueller LL, Freitag FG. Divalproex sodium in the 　 treatment of migraine and cluster headaches. J Am Osteopath Assoc. 　 2002 Feb;102(2):92-4.
論文抄録	The discovery of a new class of effective migraine-abortive medications, the triptans, has sparked a new interest in the study of vascular headache. Over the past few years, the Food and Drug Administration (FDA) has approved six new abortive pharmacologic therapies, with several others in various stages of clinical trials. Unfortunately, concurrent pharmacologic changes in headache prophylaxis have not kept pace with their abortive counterparts. However, divalproex sodium (Depakote), which is approved by the FDA as a migraine prophylactic agent, is the first in the anticonvulsant class of medication for migraine headache and has expanded the options in headache treatment. The objective of this retrospective multicenter study of 284 patients with migraine or cluster headaches was to examine the clinical efficacy and safety of divalproex sodium as prophylaxis in monotherapy and in polytherapy. Sixty-one percent of migraineurs and 73% of cluster patients noted a decrease in pain with divalproex sodium and continued that therapy for more than 3 months. Reported negative side effects included weight gain, nausea, somnolence, tremor, alopecia, dysequilibrium, and rash. However, only 14% of subjects discontinued therapy due to these side effects. Overall, divalproex sodium was found to be an effective and generally well-tolerated prophylactic treatment option as monotherapy or in polytherapy for migraine and cluster headache.
文献 PubMed−ID	PMID: 11866398
エビデンスレベル	㈽
文献タイトル (日本語)	片頭痛と群発頭痛に対する divalproex sodium による治療
目的	群発頭痛に対する divalproex sodium による予防効果を検討．
研究デザイン	臨床試験
研究施設	University Headache Center , Moorestown , NJ 08057-1550 , USA .
研究期間	不明
対象患者	284 人の片頭痛と群発頭痛患者．
介入	？
主要評価項目とそれに用いた統計学的手法	頭痛の重症度の減少．
結果	群発頭痛患者の 73% が頭痛の痛みが減少．副作用は体重増加，悪心，傾眠，振戦，脱毛などで 14% が副作用で継続中止．
結論	divalproex sodium は群発頭痛の予防に有効．
備考	MeSH Terms: ・Cluster Headache/drug therapy* ・Cluster Headache/prevention & control* ・Comparative Study ・Dose-Response Relationship, Drug ・Drug Administration Schedule ・Female ・Follow-Up Studies ・Human ・Male ・Migraine/drug therapy* ・Migraine/prevention & control* ・Pain Measurement ・Patient Satisfaction ・Retrospective Studies ・Support, Non-U.S. Gov't ・Treatment Outcome ・Valproic Acid/administration & dosage* ・Valproic Acid/adverse effects Substances: ・Valproic Acid
作成者	清水利彦，鈴木則宏

14) Peres MF, Stiles MA, Siow HC, Rozen TD, Young WB, 　 Silberstein SD. Greater occipital nerve blockade for cluster 　 headache. Cephalalgia. 2002 Sep;22(7):520-2.
論文抄録	Cluster headache is perhaps the most painful of the primary headache disorders. Its treatment includes acute, transitional, and preventive therapy. Despite the availability of many treatments, cluster headache patients can still be difficult to treat. We treated 14 cluster headache patients with greater occipital nerve block as transitional therapy (treatment initiated at the same time as preventive therapy). The mean number of headache-free days was 13.1 + 23.6. Four patients (28.5%) had a good response, five (35.7%) a moderate, and five (35.7%) no response. The greater occipital nerve block was well tolerated with no adverse events. Headache intensity, frequency and duration were significantly decreased comparing the week before with the week after the nerve block (P < 0.003, P = 0.003, P < 0.005, respectively). Greater occipital nerve blockade is a therapeutic option for the transitional treatment of cluster headache.
文献 PubMed−ID	PMID: 12230593
エビデンスレベル	㈽
文献タイトル (日本語)	群発頭痛患者における大後頭神経ブロック
目的	群発頭痛における大後頭神経ブロックの効果と安全性を検討．
研究デザイン	症例研究
研究施設	Jefferson Headache Center , Thomas Jefferson University , Philadelphia , PA , USA .
研究期間	不明
対象患者	14 人の群発頭痛患者．
介入	群発頭痛患者に大後頭神経ブロックを行う．
主要評価項目とそれに用いた統計学的手法	頭痛の強度，頻度，持続時間をブロック前後の週で比較する．
結果	4 人は良好． 5 人は中程度， 5 人は効果なし．副作用はなし．頭痛の強度，頻度，持続時間はブロックにより有意に低下した ( それぞれ P < 0.003, P = 0.003, P < 0.005).
結論	大後頭神経ブロックは群発頭痛の一次的な治療のオプションとなる．
コメント	症例研究．
備考	MeSH Terms: ・Adult ・Aged ・Cluster Headache/drug therapy ・Cluster Headache/physiopathology ・Cluster Headache/therapy* ・Comparative Study ・Female ・Human ・Lidocaine/pharmacology ・Lidocaine/therapeutic use ・Male ・Middle Aged ・Nerve Block/methods* ・Occipital Lobe/drug effects ・Occipital Lobe/physiology ・Statistics, Nonparametric ・Triamcinolone/pharmacology ・Triamcinolone/therapeutic use Substances: ・Triamcinolone ・Lidocaine
作成者	清水利彦，鈴木則宏

15) Sanders M, Zuurmond WW.Efficacy of sphenopalatine ganglion 　 blockade in 66 patients suffering from cluster headache: 　 a 12- to 70-month follow-up evaluation. J Neurosurg. 　 1997 Dec;87(6):876-80.
論文抄録	This study was conducted to evaluate the efficacy, based on 12- to 70-month follow-up data, of radiofrequency (RF) lesions of the sphenopalatine ganglion made in patients suffering from cluster headache. Sixty-six patients suffering from either episodic (Group A, 56 patients) or chronic (Group B, 10 patients) cluster headache who were not responsive to pharmacological management were treated by RF lesioning in the sphenopalatine ganglion. Complete relief of pain was achieved in 34 (60.7%) of 56 patients in Group A and in three (30%) of 10 patients in Group B. No relief was found in eight patients (14.3%) in Group A and in four (40%) in Group B. The mean time of follow up was 29.1 +/- 10.6 months in Group A and 24 +/- 9.7 months in Group B, ranging from 12 to 70 months. With regard to side effects and complications, temporary postoperative epistaxis was observed in eight patients and a cheek hematoma in 11 patients; a partial RF lesion of the maxillary nerve was inadvertently made in four patients. Nine patients complained of hypesthesia of the palate, which disappeared in all cases within 3 months. The authors conclude that RF lesioning in the sphenopalatine ganglion via the infrazygomatic approach may be performed in patients suffering from cluster headache that does not respond to pharmacological therapy
文献 PubMed−ID	PMID: 9384398
エビデンスレベル	㈽
文献タイトル (日本語)	群発頭痛患者６６人における翼口蓋神経節ブロック． 12 から 70 ヶ月の評価．
目的	群発頭痛における翼口蓋神経節ブロックの効果と安全性を検討．
研究デザイン	症例研究
研究施設	Department of Anesthesiology, Spaarne Hospital , Haarlem , The Netherlands
研究期間	不明
対象患者	薬物療法が無効な， 56 人反復性群発頭痛 Group A ,10 人の慢性群発頭痛患者 Group B ．
介入	群発頭痛患者にラジオ波による翼口蓋神経節のブロックを行う．
主要評価項目とそれに用いた統計学的手法	疼痛の変化
結果	Group A で 56 人中 34 人 (60.7%) ， Group B で 10 人中 3 に痛みが完全に消失．無効例は Group A で 8 人 (14.3%) Group B で 4 人 (40%). 経過観察期間は Group A で 29.1 +/- 10.6 ヶ月， Group B で 24 +/- 9.7 ヶ月（ 12 から 70 ヶ月）．副作用は一次的な鼻出血が 8 例，頬の血腫 11 例．口蓋の感覚低下が 9 例あったが 3 ヶ月で消失．
結論	薬物療法が無効な群発頭痛にラジオ波による翼口蓋神経節のブロックは有効かもしれない．
コメント	症例研究．
備考	MeSH Terms: ・Acute Disease ・Adult ・Autonomic Nerve Block/adverse effects ・Autonomic Nerve Block/methods* ・Catheter Ablation/adverse effects ・Cheek ・Chronic Disease ・Cluster Headache/drug therapy ・Cluster Headache/surgery* ・Epistaxis/etiology ・Evaluation Studies ・Female ・Follow-Up Studies ・Ganglia, Parasympathetic/surgery* ・Ganglionectomy/adverse effects ・Hematoma/etiology ・Human ・Hypesthesia/etiology ・Male ・Maxillary Nerve/injuries ・Palate/innervation ・Remission Induction ・Treatment Outcome
作成者	清水利彦，鈴木則宏

16) Ford RG, Ford KT, Swaid S, Young P, Jennelle R. 　 Gamma knife treatment of refractory cluster headache.Headache. 　 1998 Jan;38(1):3-9.
論文抄録	Four men and two women were treated for refractory cluster headache by gamma knife radiosurgery of the trigeminal nerve root entry zone. The maximum dose of radiation was 70 Gy to the isocenter. Of five patients treated who had refractory chronic cluster headache and one with refractory episodic cluster headache, four had relief judged excellent. Of the two remaining patients with refractory chronic cluster headache, one had relief judged good and the other fair. Five of the six patients treated had relief within a few days to a week following gamma knife radiosurgery. Three with chronic cluster headache had remissions allowing cessation of all preventive and abortive medication. Although one patient experienced complete relief of chronic cluster headache, he continued to have migraine requiring medication. None of the patients treated developed significant postradiation side effects during a follow-up period of 8 to 14 months. The authors conclude that gamma knife radiosurgery of the trigeminal nerve affords great promise in the management of chronic and refractory cluster headache. The technique seemingly carries negligible short- and long- term risk.
文献 PubMed−ID	PMID: 9504996
エビデンスレベル	㈽
文献タイトル (日本語)	難治性群発頭痛患者におけるガンマナイフ治療
目的	難治性群発頭痛患者でガンマナイフの効果を見る．
研究デザイン	症例研究
研究施設	Ford Headache Clinic, Birmingham , AL 35213 , USA .
研究期間	不明
対象患者	6 人（男４，女２）の群発頭痛患者． 5 人は慢性群発頭痛，一人は反復性群発頭痛
介入	三叉神経根のエントリーゾーンにガンマナイフをかける．最大 70 Ｇｙ．
主要評価項目とそれに用いた統計学的手法	疼痛の改善．
結果	4 人は効果はすばらしと判定． 2 人の難治性群発頭痛で一人はよい，もう一人はまあまあと判定． 5 人は数日から 7 日以内に疼痛は改善． 3 人の慢性群発頭痛は予防薬と発作薬がやめられた．重大な副作用は照射後なし． .
結論	ガンマナイフは群発頭痛に有効である．
コメント -1	症例研究．
コメント -2	2002 年治療ガイドライン文献 31
備考	Publication Types: • Case Reports MeSH Terms: • Adult • Chronic Disease • Cluster Headache/surgery* • Female • Human • Male • Middle Aged • Pain, Intractable/surgery • Radiosurgery/instrumentation* • Trigeminal Nerve/surgery • Trigeminal Neuralgia/surgery
作成者	清水利彦，鈴木則宏

17) Franzini A, Ferroli P, Leone M, Broggi G. Stimulation of the 　 posterior hypothalamus for treatment of chronic intractable cluster 　 headaches: first reported series. Neurosurgery. 　 2003 May;52(5):1095-9; discussion 1099-101.
論文抄録	OBJECTIVE: To describe the results of deep brain stimulation of the ipsilateral posterior hypothalamus for the treatment of drug-resistant chronic cluster headaches (CHs). A technique for electrode placement is reported. METHODS: Because recent functional studies suggested hypothalamic dysfunction as the cause of CH bouts, we explored the therapeutic effectiveness of posterior hypothalamic stimulation for the treatment of CHs. Five patients with intractable chronic CHs were treated with long-term, high-frequency, electrical stimulation of the posterior hypothalamus. Electrodes were stereotactically implanted in the following position: 3 mm behind the midcommissural point, 5 mm below the midcommissural point, and 2 mm lateral to the midline. RESULTS: Since this treatment, all five patients continue to be pain-free after 2 to 22 months of follow-up monitoring. Two of the five patients have remained pain-free without any medication, whereas three of the five required low doses of methysergide (two patients) or verapamil (one patient). No adverse side effects of chronic, high-frequency, hypothalamic stimulation have been observed, and we have not encountered any acute complications resulting from the implant procedure. There have been no tolerance phenomena. CONCLUSION: These preliminary results indicate a role for posterior hypothalamic stimulation, which was demonstrated to be safe and effective, in the treatment of drug-resistant chronic CHs. These data point to a central pathogenesis for chronic CHs.
文献 PubMed−ID	PMID: 12699552
エビデンスレベル	㈽
研究施設	Department of Neurosurgery, Istituto Nazionale Neurologico C. Besta, Milan , Italy .
結論	視床下部後部の電気刺激は群発頭痛に有効である．