Repeat trigeminal nerve radiosurgery for refractory cluster headache fails to provide long-term pain relief

OBJECTIVE/BACKGROUND: Medically refractory cluster headache (MRCH) is a debilitating condition that has proven resistant to many modalities. Previous reports have indicated that radiosurgery for MRCH provides little long-term pain relief, with moderate/significant morbidity. However, there have been no reports of repeated radiosurgery in this patient population. We present our findings from the first reports of repeat radiosurgery for MRCH. METHODS: Two patients with MRCH underwent repeat gamma knife radiosurgery at our institution. Each fulfilled clinical criteria for treatment, including complete resistance to pharmacotherapy, pain primarily localized to the ophthalmic division of the trigeminal nerve, and psychological stability. Both patients previously received gamma knife radiosurgery (75 Gy) for MRCH with no morbidity, but no long-term improvement of pain relief (Patient 1 = 5 months, Patient 2 = 10 months) after treatment. For repeat radiosurgery, each patient received 75 Gy to the 100% isodose line delivered to the root entry zone of the trigeminal nerve, and was evaluated postretreatment. Pain relief was defined as: excellent (free of MRCH with minimal/no medications), good (50% reduction of MRCH severity/frequency with medications), fair (25% reduction), or poor (less than 25% reduction). RESULTS: Following repeat radiosurgery, long-term pain relief was poor in both patients. Neither patient sustained any immediate morbidity following radiosurgery. Patient 2 experienced right facial numbness 4 months postretreatment, while Patient 1 experienced no morbidity. CONCLUSION: Repeat radiosurgery of the trigeminal nerve fails to provide long-term pain relief for MRCH. Given the reported failures of initial and repeat radiosurgery for MRCH, trigeminal nerve radiosurgery should not be offered for MRCH.     

Complete but transient relief of chronic cluster headache with mycophenolate mofetil

Chronic cluster headache is one of the most disabling of all neurologic conditions. New effective therapies for refractory chronic cluster headache are needed. The unique sensitivity of most cluster headache patients to corticosteroid treatment suggests that steroid-sparing immunosuppressive drugs may show benefit as cluster headache preventives. A patient is presented who had complete but transient relief of chronic cluster headache with mycophenolate mofetil.     

Cluster headache and the sympathetic nerve

OBJECTIVE: To determine the effect of a sympathetic block at C7 on cluster headache. BACKGROUND: Eleven patients presenting to a pain control unit with cluster headache were included in the study after giving informed consent. METHODS: In all patients, a mixture of 5 mL of 0.5% bupivacaine hydrochloride and 1 cc of methylprednisolone acetate was injected onto the base of the C7 transverse process. RESULTS: The injection was applied during the acute phase of headache in 6 patients and all experienced immediate and complete relief. The other 5 patients received the injection between attacks. Of the 11 patients treated, 8 went into remission by aborting the cluster. In some patients, repeated injections were given before the cluster was aborted. Three patients did not respond to treatment. One patient with chronic paroxysmal hemicrania experienced pain relief of the acute attack after treatment, but the procedure did not abort the subsequent attacks. A surgical sympathectomy removing the stellate ganglion rendered him pain-free for 15 months after which he was lost to follow-up. CONCLUSION: Blocking the sympathetic nerve aborts an acute attack of cluster headache and may play a major role in aborting the cluster. Although only one patient with chronic paroxysmal hemicrania responded to surgical sympathectomy, this procedure may be considered as an alternative if there is poor response to oral medication or a sympathetic block.     

The surgical management of chronic cluster headache

OBJECTIVE: Chronic cluster headache occurs in less than 10% of cluster headache sufferers, but remains an intractable medical problem. Surgical treatments have also been limited in their effectiveness. The authors describe their experience with attempted surgical amelioration of chronic cluster headache. DESIGN: Twenty-eight patients, including two with bilateral cluster headache, underwent 39 operations for microvascular decompression of the trigeminal nerve, alone or in combination with section and/or microvascular decompression of the nervus intermedius. Follow-up averaged 5.3 years. RESULTS: Initial postoperative success described as 50% relief or greater was achieved in 22 (73.3%) of 30 first-time procedures and greater than 90% relief in half (15 of 30) of these. Long-term follow-up saw this success rate (excellent or good) drop to 46.6%. Repeat procedures have little success, with 7 of 8 failing at long-term follow-up. Morbidity and neurological deficit from the operations was minimal. CONCLUSIONS: Chronic cluster headache remains a debilitating and poorly controlled syndrome. Although various surgical treatments have had limited success, microvascular decompression of the trigeminal nerve with section of the nervus intermedius compares very favorably to other destructive techniques without the accompanying neurologic deficits. It is, therefore, our recommendation as the first-line operative treatment of chronic cluster headache.     

Prostaglandin analog mechanisms are not effective in refractory chronic cluster headache

Prostaglandin E analogs have been shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis. Prostaglandin E inhibits the functions of T lymphocytes which are involved in the pathophysiology of cluster headache. Therefore, a double-blind, placebo-controlled, crossover study on the efficacy of misoprostol in chronic refractory cluster headache was performed. Eight patients were treated with 600 micrograms misoprostol and with placebo for a 2-week period. No differences in attack frequency, intensity, global impression, and side effects could be detected, suggesting that prostaglandin E analogs are not effective in the treatment of chronic cluster headache.     

Response to occipital nerve block is not useful in predicting efficacy of occipital nerve stimulation

Occipital nerve stimulation (ONS) may be effective for the treatment of headaches that are recalcitrant to medical therapy. The objective of this study was to determine if response to occipital nerve block (ONB) predicts response to ONS in patients with chronic, medically intractable headaches. We evaluated 15 patients who underwent placement of occipital nerve stimulators for the treatment of chronic headaches. Data were collected regarding analgesic response to ONB and to ONS. Nine of 15 patients were ONS responders (> or =50% reduction in headache frequency or severity). Thirteen patients had ONB prior to stimulator implantation. Ten of 13 who had ONB had significant relief of head pain lasting at least 24 h, and three were ONB non-responders. Of the three ONB non-responders, two were ONS responders. Of the two patients who did not have ONB prior to ONS, one was an ONS responder and one was an ONS non-responder. In conclusion, analgesic response to ONB may not be predictive of the therapeutic effect from ONS in patients with medically refractory chronic headaches.     

伽玛刀治疗原发性三叉神经痛疗效观察

目的 探讨伽玛刀治疗原发性三又神经痛的疗效.方法 2003年1月至2008年3月,我院应用伽玛刀治疗原发性三又神经痛120例;治疗靶点为三叉神经根,用4 mm准直器,靶点中心计量为80～90 Gy.疗效评估采用患者自我报告疼痛的控制程度及药物用量的变化.结果 所有患者进行了随访,平均随访期(20.0±4.5)个月.本组病例中治愈69例(57.5%);显效34例(28.3%)、有效12例(10.0%)、无效5例(4.2%);总有效率为95.8%.5例患者疼痛复发后行其他治疗.83例患者(69.2%)曾出现一过性、局限性的面部麻木.14例患者(11.7%)在疼痛缓解后留下持续性的面部麻木;部分患者还伴有味觉减退、口嚼无力等主诉.结论 伽玛刀治疗原发性三又神经痛能够显著缓解疼痛、提高生活质量,不良反应发生率较低:是一种较为理想的治疗方法.     

Dynamic mechanical (brush) allodynia in cluster headache

OBJECTIVE: To examine the occurrence of dynamic mechanical (brush) allodynia (BA) in patients with cluster headache (CH). BACKGROUND: Cutaneous allodynia was described in migraine. It was related to sensitization of neurons in the trigeminal nucleus caudalis (TNC). This phenomenon has not been previously described in cluster headache. METHODS: We examined adult patients with episodic or chronic CH for the presence of BA. Demographic data and the characteristics of CH were obtained through a questionnaire. Allodynia testing was performed by repetitively applying a 4x4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia was measured on a 100-mm visual analog scale (VAS). The relations between the location and severity of headache and allodynia were assessed. RESULTS: Ten patients (all male, mean age 39.3) were included in the study. Seven had episodic CH (ECH) and 3 had chronic CH (CCH). Two patients were in acute attack when tested for BA. In total, 4 (40%) of the 10 patients had BA (2 [28.6%] of the 7 with ECH and 2 [66.7%] of the 3 with CCH). Median disease duration was 22 years for patients with BA and 12 years for patients without BA. Of the two patients in acute attack, one had BA, ipsilateral to the headache, which was reduced 20 minutes after treatment, along with reduced headache severity. CONCLUSIONS: This is the first report on the occurrence of cutaneous allodynia in CH. The presence of BA in CH may be related to CH type (episodic vs. chronic) and to the duration of disease. These results support the concept that allodynia in CH may result from a time-dependent process of neuronal sensitization.     

CLUSTER AND TACS

Background: Since the initial report of Ford et al in 1998, no further study has evaluated radiosurgery of the trigeminal nerve in chronic cluster headache (CCH).
Methods: We carried out a prospective open trial of neurosurgery and enrolled 10 patients (9 men, 1 woman; mean age 49.8 years, range 32-77) presented with severe and drug-resistant CCH (mean duration 9 years, range 2-33). The cisternal segment of the nerve was targeted with a single 4-mm collimator (80-85 Gy max).
Results: The mean follow-up was 13.2 months. No improvement was observed in two patients and three patients had no further attacks. Three patients showed dramatic improvement with a few attacks per month or very few attacks over the last 6 months. Two patients were pain free for only 1 and 2 weeks and their headaches recurred with the same severity as before. Three patients developed paraesthesia with no hypoaesthesia, one developed hypoaesthesia, and one developed deafferentation pain.
Conclusions: The rate and severity of trigeminal nerve injury appeared to be significantly higher than in trigeminal neuralgia, and this study does not support the positive results of the study of Ford et al. We consider the morbidity to be significant for the low rate of pain cessation, making this procedure less attractive even for the more severely affected subgroup of patients.
Comment: I, too, have had disappointing results when I referred patients for gamma knife for refractory cluster. I believe for those rare cases requiring surgery, radiofrequency trigeminogangliorhizolysis is the appropriate treatment, pending further study on the safety of implantation of hypothalamic radiostimulators.—Stewart J. Tepper, MD     

2. Cluster Headache

Cluster headache is a strictly unilateral headache that is associated with ipsilateral cranial autonomic symptoms and usually has a circadian and circannual pattern. Prevalence is estimated at 0.5 to 1.0/1,000. The diagnosis of cluster headache is made based on the patient's case history. There are two main clinical patterns of cluster headache: the episodic and the chronic. Episodic is the most common pattern of cluster headache. It occurs in periods lasting 7 days to 1 year and is separated by at least a 1-month pain-free interval. The attacks in the chronic form occur for more than 1 year without remission periods or with remission periods lasting less than 1 month.
Conservative therapy consists of abortive and preventative remedies. Ergotamines and sumatriptan injections, sublingual ergotamine tartrate administration, and oxygen inhalation are effective abortive therapies. Verapamil is an effective and the safest prophylactic remedy. When pharmacological and oxygen therapies fail, interventional pain treatment may be considered. The effectiveness of radiofrequency treatment of the ganglion pterygopalatinum and of occipital nerve stimulation is only evaluated in observational studies, resulting in a 2 C+ recommendation.
In conclusion, the primary treatment is medication. Radiofrequency treatment of the ganglion pterygopalatinum should be considered in patients who are resistant to conservative pain therapy. In patients with cluster headache refractory to all other treatments, occipital nerve stimulation may be considered, preferably within the context of a clinical study.     

Gamma Knife Stereotactic Radiosurgery in the Management of Cluster Headache

Gamma knife stereotactic radiosurgery (SRS) has proven to be an effective management approach for trigeminal neuralgia and as a minimally invasive alternative management option for cluster headache (CH). In CH, patients undergo single-session focused irradiation of the trigeminal nerve root (TN), sometimes coupled with irradiation of the sphenopalatine ganglion (SPG) as well. SRS provides early pain relief in most patients, but is associated with trigeminal sensory dysfunction in some patients. In the future, a prospective trial that compares a single target of TN to dual targets of both the TN and SPG may provide further understanding of the value of SRS for CH.     

影响原发性三叉神经痛伽玛刀治疗效果的相关因素分析

目的探讨伽玛刀治疗原发性三叉神经痛的疗效及影响预后的因素。方法回顾性分析75例原发性三叉神经痛的患者行伽玛刀治疗的效果,均经OUR-XGD旋转式伽玛刀治疗,采用4—8mm准直器,半月节照射采用多靶点,三叉神经根照射采用单靶点或双靶点,中心剂量70—90Gy,脑干表面受量〈15Gy。通过随访患者疼痛发作的频率和程度的减轻评价疗效。结果随访时间为3～72个月,平均37．6个月,总有效率90．7％。4例患者2～3年后复发,6例在伽玛刀治疗后半年出现患侧面部麻木感,无其他并发症。经统计学分析,某些因素与疗效相关。结论伽玛刀治疗原发性三叉神经痛一种安全有效的方法,靶点选择、剂量选择、照射部位是影响预后的因素,而病史长短及疼痛分布与预后无相关性。     

伽玛刀对神经根与毗邻血管不同解剖关系的原发性三叉神经痛的治疗疗效分析

目的探讨原发性三叉神经痛患者三叉神经根与毗邻血管的不同解剖关系对伽玛刀治疗疗效的影响。方法回顾性分析2004年1月至2009年1月山西医科大学第二医院伽玛刀中心治疗原发性痛患者82例，依据MR定位影像显示三叉神经根与毗邻血管的不同解剖关系（无接触、可疑接触、明确接触、推移），评估对伽玛刀治疗疗效的影响。结果随访6～18个月，平均随访12．5个月，依据BNI疼痛量表评分Ⅲ级以上70例，总有效率85．4％，三叉神经根与血管无接触组有效率89．7％，可疑接触组有效率86．4％，明确接触78．9％，推移组81．8％，复发8例（9．7％）。结论三叉神经根与毗邻血管的不同解剖关系对伽玛刀治疗疗效差别无统计学意义，推移组复发率较其他组高，远期疗效有待进一步评估。     

原发性三叉神经痛伽玛刀放射外科治疗的有效性评估

目的:评价伽玛刀放射外科治疗原发性三叉神经痛的安全性、有效性和心理状态。方法:2004年8月~2010年9月,98例经药物和其他方法治疗无效的原发性三叉神经痛患者接受伽玛刀放射外科治疗。放射剂量中位值是80 Gy(75~85 Gy)。采用患者自我报告疼痛的控制、生活满意度指数A(1ife satisfaction index A,LSI-A)的变化进行疗效评估。结果:治疗后89例(90.8%)患者获得随访,平均随访期35个月(13~60个月)。本组病例中治愈51例(57.3%);显效19例(21.3%);有效11例(12.4%);无效8例(9%),总有效率为91%;伽玛刀治疗后LSI-A总分平均值(36.25±3.87)高于治疗前(25.67±3.5);其中67例以往未接受过手术治疗患者中62例获得随访,58例有效,总有效率为93.5%。11例患者感觉患侧面部麻胀感,1例(二次治疗者)张口轻度受限。结论:伽玛刀放射外科治疗三叉神经痛显著缓解疼痛,提高生存质量。     

The cluster-tic syndrome and its surgical therapy

The term cluster-tic syndrome (CTS) is used to designate a clinical pain pattern in which symptoms of cluster headache (CH) and tic douloureux (TD) coexist. The TD elements of the attack occur in paroxysms of many seconds or minutes, always affect the maxillary or mandibular divisions of the trigeminal nerve, with spread into the ophthalmic division in some cases, and may be triggered by slight superficial stimuli. These features may occur independent of CH elements but more often the two blend together. Four patients with CTS unresponsive to medication underwent surgery. Blood vessels were found to cross compress the trigeminal nerve in all four patients and the nerve was decompressed. A similar condition was found affecting the facial nerve in two of the three patients in whom that nerve was explored and the facial nerve was decompressed in these two. The TD component of the CTS disappeared after surgery in all four patients. The CH component of the syndrome returned after surgery but in a modified form. In three patients, the CH changed from what had been chronic cluster to infrequent episodic cluster periods; additionally in two patients, the duration of cluster was shorter and the pain was of lesser severity.     

Long-term Results of Radiofrequency Rhizotomy in the Treatment of Cluster Headache

Although the primary treatment of chronic cluster headache is medical, surgical treatment is sometimes used. The authors reviewed the charts of seven patients (ages 36 to 68 years) with chronic cluster headache to identify who responded best to percutaneous stereotactic radiofrequency rhizotomy after medical treatment failed. All patients had immediate pain relief after surgery. At follow-up (median 5 years, range 2 to 20 years), two patients remained pain-free 7 and 20 years later (excellent results); three patients had mild pain recurrence that was well controlled on medications (good results) 6 to 12 months after surgery; and two patients had major pain recurrence 4 days and 2 months after surgery (poor results). Six patients had relief of vasomotor symptoms. One patient had transient diplopia and keratitis without permanent sequelae. Both patients with excellent results had pre-operative major pain around the eye; both patients with poor results had major pain around the temple, ear, and cheek; and the three patients with good results had pain equally severe in the eye, temple, and cheek. There was no association between patient age or sex, pain duration, preoperative response to lidocaine blockade, or previous surgery with pain relief. No differences occurred in pain relief between patients with dense hypalgesia and patients with analgesia. The authors conclude that (1) some patients with chronic cluster headache treated by percutaneous stereotactic radiofrequency rhizotomy achieve long-term pain relief, and (2) surgery on the trigeminovascular system alone may not cure the condition in patients with major pain around the temple, ear, and cheek.     

Chronic Cluster Headache Managed by Nervus Intermedius Section

Cluster headache sufferers who become candidates for surgical treatment are those relatively rare patients who are refractory to all attempts at pharmacological relief. Ablative surgical procedures have been directed against either the trigeminal nerve or the nervus intermedius/greater superficial petrosal (NI/GSP) pathway. Both carry nociceptive impulses from the head and face, and the NI also carries parasympathetic fibres which appear to be responsible for the autonomic concomitants of cluster headache. Trigeminal operative procedures are not consistently helpful in chronic cluster headache, while NI section has been shown to give potentially long lasting relief but carries the potential risks of cerebellopontine angle surgery. In eight selected cases of chronic cluster headache we have demonstrated a high early success rate for pain relief, with few complications, in the performance of NI section, combined, when indicated, with microvascular decompression of the trigeminal main sensory root. We believe that cochlear nerve monitoring helps prevent postoperative hearing impairment. An intimate relationship between the NI and arterial loops of the anterior inferior cerebellar artery (AICA) or the internal auditory artery has been frequently observed in our chronic cluster headache patients.     

Clomiphene citrate for treatment refractory chronic cluster headache

A treatment refractory chronic cluster headache patient is presented who became cluster-free on clomiphene citrate. The author has previously reported a SUNCT patient responding to clomiphene citrate. Hypothalamic hormonal modulation therapy with clomiphene citrate may become a new preventive choice for trigeminal autonomic cephalalgias. The possible mechanism of action of clomiphene citrate for cluster headache prevention will be discussed.     

Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection

Cluster headache is the most severe of the primary headaches. Positron emission tomography and functional MRI studies have shown that the ipsilateral posterior hypothalamus is activated during cluster headache attacks and is structurally asymmetric in these patients. These changes are highly specific for the condition and suggest that the cluster headache generator may be located in that brain area; they further suggest that electrical stimulation of that region might produce clinical improvement in chronic cluster headache sufferers refractory to medical therapy. In five patients with severe intractable chronic cluster headache, hypothalamic electrical stimulation produced complete and long-term pain relief with no relevant side-effects. We therefore consider it essential to propose criteria for selecting chronic cluster headache patients for hypothalamic deep brain stimulation before this procedure is undertaken at other academic medical centres.     

Outpatient intravenous dihydroergotamine for refractory cluster headache

Objective.—To evaluate the efficacy and safety of outpatient intravenous dihydroergotamine (DHE) for treatment of refractory cluster headache.
Method.—Medical records were retrospectively reviewed of all patients with cluster headache who received outpatient intravenous DHE for treatment of refractory cluster headache between January 1992 and May 2000.
Results.—One hundred four treatments were identified in 70 patients. There were 7 dropouts. Of the 97 completed treatments, 60 were for episodic cluster headache and 37 were for chronic cluster headache. Results for all treatments showed complete resolution of pain during the intravenous phase at 1 month in 61 (63%) of 97 cases, partial resolution in 13 cases (15%), and failure in 23 cases (24%). For the treatment of episodic cluster headache, there was complete resolution in 44 (73%) of 60 cases, partial resolution in 9 cases (13%), and failure in 7 cases (12%). For treatment of chronic cluster headache, there was complete resolution in 17 (46%) of the 37 cases, partial resolution in 4 cases (11%), and 16 failures (43%). As regards side effects and safety, the treatment triggered chest pain suspected of being vasospastic angina in 1 patient on day 7 of the treatment, when she was in the subcutaneous phase. Two patients dropped out due to fear of the injection, 1 because of palpitations, 1 because of chest tightness, and 2 others because of leg cramps, nausea, and diarrhea.
Conclusions.—Outpatient intravenous DHE is a safe treatment. It is useful for refractory cluster headache, is more effective for the episodic form than the chronic form, and has a rapid onset of action. It did not change the evolution of the episodic form, but it did appear to induce remission in the chronic form or transform it to the episodic form. We advance a hypothesis to explain this.