Dynamic mechanical (brush) allodynia in cluster headache: a prevalence study in a tertiary headache clinic

Cutaneous allodynia (CA) has been described in migraine and has been related to treatment failure. There are little data about the incidence of CA in other primary headache syndromes such as cluster headache (CH). The objectives of this study are to evaluate the prevalence of dynamic mechanical (brush) allodynia (BA) in CH patients attending a tertiary headache clinic, and to assess its relation to disease characteristics. Adult patients with episodic or chronic CH were recruited. We obtained demographic data and data on disease characteristics through a structured questionnaire, and tested the patients for brush allodynia BA by applying a 4 × 4 gauze pad over the V₁, C₂/C₃ and C₈ skin areas bilaterally. The prevalence of allodynia in the entire study population and in the different sub-groups was calculated. We also examined the association between CA and demographic parameters, and its association with disease characteristics. Forty-one patients were recruited (22 men, 19 women; mean age 44.9 years). Twenty-two had chronic CH (CCH) and 19 had episodic CH (ECH). Mean disease duration was 14.1 years (12.3 the CCH group and 15.7 in the ECH group). Overall, 20 (49%) patients were allodynic. There was no statistically significant association between the presence of allodynia and age, gender, diagnosis (episodic vs. chronic CH), disease duration or disease severity. In conclusion, BA was common in this CH patient sample. The therapeutic implications of the presence of BA in CH need to be further studied.     

Depression and anxiety in episodic and chronic cluster headache: a pilot study

Background.— In contrast to migraine and tension‐type headache, the psychiatric comorbidities of cluster headache (CH) have not been well‐studied. Objective.— We assessed the presence of depression and anxiety in groups of episodic CH (ECH) and chronic CH (CCH) patients and compared CH patients with and without depression and anxiety. Methods.— Sociodemographics, comorbidities, and selected headache features were ascertained from a clinic‐based sample in a cross‐sectional fashion from January 2007 to July 2010. Active depression and anxiety were assessed using the Patient Health Questionnaire (PHQ‐9) and the Generalized Anxiety Disorder 7‐item (GAD‐7) scales. Results.— Of 49 CH patients, ECH patients (n = 32) had an earlier age of onset and consumed less caffeine than CCH patients (n = 17). Rates of depression as defined by a PHQ‐9 score ≥10 were low in both ECH (6.3%) and in CCH (11.8%) with similar mean PHQ‐9 scores (3.1 vs 3.7, P = .69). Rates of anxiety as defined by a GAD‐7 score ≥10 were also low in both ECH (15.6%) and CCH (11.8%) with similar mean GAD‐7 scores (3.8 vs 3.4, P = .76). ECH patients in and out of active attack periods had similar levels of depression and anxiety. Depression and anxiety usually occurred together in ECH and CCH patients. CH patients who were depressed or anxious were more likely to present at a younger age and have attack‐related nausea and prodromal symptoms. Depressed CH patients were also more likely to have another pain disorder and had undertaken twice as many prophylactic medication trials. Conclusion.— In this clinic‐based cross‐sectional study, ECH and CCH patients had similarly low rates of depression and anxiety. Rates were lower than those reported for both episodic and chronic migraine.     

Age at onset and sex ratio in cluster headache: observations over three decades

Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male : female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.     

Asymmetrical reduction of the nociceptive flexion reflex threshold in cluster headache

The nociceptive flexion reflex (NFR) of the lower limbs (RIII reflex) was examined bilaterally in 54 cluster headache (CH) patients suffering from episodic CH (ECH) and chronic CH (CCH). Fifteen ECH patients were examined in both remission and active phases. The RIII reflex threshold (Tr) and the threshold of pain sensation (Tp) were significantly reduced on the symptomatic side in patients with episodic CH during the bout. During the active phase of episodic CH an inverse correlation was found between the severity of CH (ratio: number of cluster periods/years of illness duration) and the Tp, which may suggest a role for secondary central sensitization in pain pathways. The lower Tr and Tp on the symptomatic side is in keeping with previous observations exploring pain mechanisms using different methods (i.e. corneal reflex, pain pressure threshold). On the whole, these data tie in with the view of an impairment of the pain control system, which parallels the periodicity of the disorder in the episodic form.     

Laser-evoked cortical potentials in cluster headache

Craniofacial nociceptive processing in patients (n = 25) suffering from unilateral cluster headache was assessed by laser-evoked cortical potentials (LEPs). Latencies and amplitudes of late (N2, P2) and middle-latency (N1) LEPs were measured in chronic (CCH, n = 9) and episodic cluster headache (ECH, n = 17). In CCH patients on headache side N1c occurred later and P2 amplitude was smaller than on the healthy control side. In active periods of ECH patients P2 latency was shorter on the headache side. In remission periods of ECH patients the N2P2 ratio was lower on the headache side. In 19 out of 26 examinations in 25 headache patients LEP deviated from normative data in healthy controls (n = 10) without any specific pattern of altered parameters. LEPs document pathological changes in craniofacial nociception in cluster headache. However, there seems to be no pathognomonic deviation pattern that enables reliable diagnosis of cluster headache and application of LEPs in further studies of pathophysiological mechanisms.     

Allodynia in Cluster Headache

Cutaneous allodynia (CA), the perception of pain when a non-noxious stimulus is applied to normal skin, has been described in various pain syndromes. The pathophysiology of CA in headache is thought to be related to central sensitization of brainstem, and possibly thalamic, neurons. The recognition of CA in cluster headache (CH) is recent, and available data are scant. Some studies suggest the occurrence of CA in a significant proportion of CH patients. However, one study that examined sensory thresholds in CH failed to confirm this. CA in CH is characterized by rapid onset and termination, suggesting different mechanisms compared with CA in migraine. CA in CH is common in trigeminal areas but may spread to cervical dermatomes and beyond. The relations between the type of CH (episodic vs chronic) and CA are unknown. Further studies are needed to determine the mechanism of CA in CH, and its clinical implications.     

Sleep features and central sensitization symptoms in primary headache patients

Background

Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain.

Methods

One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM).

Results

Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration.

Conclusion

Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.     

Suboccipital injection with a mixture of rapid- and long-acting steroids in cluster headache: a double-blind placebo-controlled study

Oral steroids can interrupt bouts of cluster headache (CH) attacks, but recurrence is frequent and may lead to steroid-dependency. Suboccipital steroid injection may be an effective 'single shot' alternative, but no placebo-controlled trial is available. The aim of our study was to assess in a double-blind placebo-controlled trial the preventative effect on CH attacks of an ipsilateral steroid injection in the region of the greater occipital nerve. Sixteen episodic (ECH) and seven chronic (CCH) CH outpatients were included. ECH patients were in a new bout since no more than 1 week. After a one-week run-in period, patients were allocated by randomization to the placebo or verum arms and received on the side of attacks a suboccipital injection of a mixture of long- and rapid-acting betamethasone (n=13; Verum-group) or physiological saline (n=10; Plac-group). Acute treatment was allowed at any time, additional preventative therapy if attacks persisted after 1 week. Three investigators performed the injections, while four others, blinded to group allocation, followed the patients. Follow-up visits were after 1 and 4 weeks, whereafter patients were followed routinely. Eleven Verum-group patients (3 CCH) (85%) became attack-free in the first week after the injection compared to none in the Plac-group (P=0.0001). Among them eight remained attack-free for 4 weeks (P=0.0026). Remission lasted between 4 and 26 months in five patients. A single suboccipital steroid injection completely suppresses attacks in more than 80% of CH patients. This effect is maintained for at least 4 weeks in the majority of them.     

Brush allodynia in hospitalized headache patients

OBJECTIVE: To describe the incidence and time course of dynamic mechanical allodynia (brush allodynia, BA) in an inpatient headache population. BACKGROUND: Four types of cutaneous allodynia (heat, cold, static mechanical [pressure], and dynamic mechanical [brush] allodynia) can be studied in headache patients. In episodic migraineurs, the development of cutaneous allodynia heralds a change in treatment response. However, little is known about the functional significance of BA, and little is known about the frequency of any type of cutaneous allodynia among patients with chronic or more severe headache disorders. Methods.-The protocol was approved by the institutional review board of our university hospital. A total of 78 subjects were tested for allodynia on days 1, 3, and 5 of an inpatient hospital stay using a 4 x 4 folded gauze pad stroked 10 times at three bilateral sites (forehead, jaw, and forearm). Subjects were queried about the signs and symptoms of their headaches. Headache intensity was graded with a verbal 11-point scale and the intensity of allodynia was graded using a 10 cm visual analog scale. RESULTS: A total of 61 patients had transformed migraine (TM). BA was present at some point during the hospitalization in 32 subjects (41%). Neither age nor duration of daily headache correlated with headache severity. Headache intensity, a history of sensory symptoms or weakness, and subjective blurred vision accompanying the headache correlated with the presence of BA (P< or = .05). Unilateral headaches were more likely to be associated with BA (P = .01), independent of headache severity. When headache was unilateral, BA was greatest ipsilateral to the headache. BA did not influence outcome as measured by length of stay or the likelihood of being discharged headache-free. The rate of decline of headache intensity and allodynia score were similar. CONCLUSION: BA is common in hospitalized headache patients. Subjects with more severe unilateral headaches were more likely to have BA. The presence of BA did not predict treatment failure in an inpatient setting.     

General trigeminospinal central sensitization and impaired descending pain inhibitory controls contribute to migraine progression

Migraine is a chronic disease with episodic manifestations. In a subgroup, attack frequency increases over time, leading to chronic migraine. One of the most important risk factors for migraine progression is frequency of headache attacks at baseline. Unfortunately, the actual effects of repeated activation of dural nociceptors are poorly known. We investigated the behavioral, anatomical, and electrophysiological changes induced by repeated low- and high-intensity stimulation of meningeal nociceptor by injecting an inflammatory soup in rats. Single high-intensity, but not low-intensity, stimulation produces a reversible cephalic allodynia. Upon repetition, however, low-intensity stimulation, too, induces a reversible cephalic allodynia, and high-intensity, reversible cephalic and extracephalic allodynia. Moreover, cephalic allodynia becomes, in part, persistent upon repeated high-intensity stimulation. Fos expression reveals that a single high-intensity stimulation already leads to widespread, trigeminal, and spinal central sensitization, and that such general central sensitization potentiates upon repetition. Trigeminovascular nociceptive neurons become persistently sensitized and their diffuse noxious inhibitory controls (DNIC) concomitantly impaired. Thus, compared with single stimulation, repeated dural nociceptor activation specifically leads to: 1) a gradual worsening of cutaneous hypersensitivity and general neuronal hyperexcitability and 2) spreading of cutaneous hypersensitivity superimposed on 3) persistent cephalic cutaneous hypersensitivity and trigeminal central sensitization. Such repetition-induced development of central sensitization and its consequence, cutaneous allodynia, may arise from both the general neuronal hyperexcitability that results from DNIC impairment and hyperexcitability that likely develops in trigeminal nociceptive neurons in response to their repetitive activation. These neuronal changes may in turn elevate the risk for developing chronic migraine.     

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.     

The effects of greater occipital nerve block and trigger point injection on brush allodynia and pain in migraine

OBJECTIVE: To evaluate the effect of GONB, with or without trigger point injection (TPI), on dynamic mechanical (brush) allodynia (BA) and on head pain in migraine. Background.-Patients with migraine often have cutaneous allodynia that is related to sensitization of central pain neurons. Greater occipital nerve block (GONB) is an effective treatment for migraine headache; however, its effect on cutaneous allodynia in migraine is unknown. METHODS: We studied patients with migraine and BA who were treated with GONB with or without TPI. Demographic data, migraine history, and headache features were documented. Allodynia was evaluated using a structured questionnaire and by applying a 4 x 4-inch gauze pad to skin areas in the trigeminal and cervical dermatomes. Degree of allodynia (the allodynia score) was measured on a 100-mm visual analog scale (VAS) before treatment and 10 and 20 minutes thereafter. Headache levels were assessed using an 11-point verbal scale. Allodynia scores, as well as headache levels, before and after treatment were compared. RESULTS: Nineteen patients were studied. Mean age was 43.6+/-11.8 years. Twenty minutes after treatment, headache was reduced in 17 patients (89.5%) and did not change in 2 (10.5%). The average headache level was 6.53 before treatment and 3.47, 20 minutes after it. The average allodynia score decreased after 20 minutes in all patients. Average allodynia score per site was reduced by 18.69 mm and 13.74 mm in the trigeminal and cervical areas, respectively. There was a positive correlation between allodynia index, obtained through the questionnaire, and allodynia score, obtained by examination. CONCLUSION: GONB, with or without TPI, reduced both head pain and brush allodynia in this migraine patient group.     

Botulinum toxin type-A therapy in cluster headache: an open study

The objective of this open single-centre study was to evaluate the efficacy and tolerability of botulinum toxin type-A (BTX-A) as add-on in the prophylactic treatment of cluster headache (CH). Twelve male patients with episodic (n=3) or chronic (n=9) CH, unresponsive to common prophylactic medications, were treated with a cumulative dose of 50 International Units (IU) BTX-A according to a standardised injection scheme into the ipsilateral pericranial muscles. One patient with chronic CH experienced a total cessation of attacks and in 2 patients attack intensity and frequency improved. In another patient with chronic CH typical attacks were not influenced, but an ipsilateral continuous occipital headache significantly improved. Patients with episodic CH did not benefit from BTX-A treatment. Tolerability was excellent. These findings provide evidence that BTX-A may be beneficial as an add-on prophylactic therapy for a limited number of patients with chronic CH.     

Osmophobia in primary headaches

This study evaluates osmophobia (defined as an unpleasant perception, during a headache attack, of odours that are non–aversive or even pleasurable outside the attacks) in connection with the diagnosis of primary headaches. We recruited 775 patients from our Headache Centre (566 females, 209 males; age 38±12 years), of whom 477 were migraineurs without aura (MO), 92 with aura (MA), 135 had episodic tension–type headache (ETTH), 44 episodic cluster headache (ECH), 2 chronic paroxysmal hemicrania (CPH) and 25 other primary headaches (OPHs: 12 primary stabbing headaches, 2 primary cough headaches, 3 primary exertional headaches, 2 primary headaches associated with sexual activity, 3 hypnic headaches, 2 primary thunderclap headaches and 1 hemicrania continua). Among them, 43% with MO (205/477), 39% with MA (36/92), and 7% with CH (3/44) reported osmophobia during the attacks; none of the 135 ETTH and 25 OPH patients suffered this symptom. We conclude that osmophobia is a very specific marker to discriminate adequately between migraine (MO and MA) and ETTH; moreover, from this limited series it seems to be a good discriminant also for OPHs, and for CH patients not sharing neurovegetative symptoms with migraine. Therefore, osmophobia should be considered a good candidate as a new criterion for the diagnosis of migraine.     

Possible predictive factors in the evolution of episodic to chronic cluster headache

The purpose of our study was to identify general factors and distinctive clinical features differentiating patients with chronic cluster headache (CH) evolved from episodic CH and patients with episodic CH. Our study sample included 28 patients suffering from chronic CH evolved from episodic CH and 258 patients with episodic CH; all were referred to the Headache Center of Parma between December 1975 and June 1998. Patients with episodic CH were selected from all episodic CH referrals (n = 485) and selection was based on the duration of the disorder, which was to exceed the average period needed for an episodic form to turn into a chronic form (4.5 years for females and 7.0 years for males). At CH onset, the mean age for patients with chronic CH evolved from episodic CH was older than for those with episodic CH. Among patients with chronic CH, more were smokers or heavy drinkers, and had suffered a head injury. Clinically, episodic CH evolving into chronic CH was characterized by a high frequency of cluster periods, a larger proportion of patients with attacks not occurring strictly within cluster periods, and remission periods lasting less than 6 months. Possible predictive factors in the development of chronic CH appear to be CH onset from the third decade of life onward, the occurrence of more than one cluster period a year, and the short-lived duration of remission periods. The role played by head injury and cigarette smoking in the evolution of the disorder still cannot be established with certainty.     

Subcutaneous sumatriptan induces changes in frequency pattern in cluster headache patients

OBJECTIVES: To document the relationship between the use of subcutaneous (SQ) sumatriptan (sum) and a change in frequency pattern of cluster headache (CH) in six patients. To discuss the clinical and pathophysiological implications of this observation in the context of available literature. BACKGROUND: Treatment with SQ sum may cause an increase in attack frequency of CH but data from literature are scant and controversial. METHODS: Six CH sum-na?ve patients (three episodic and three chronic according to the International Headache Society (IHS) criteria) are described. RESULTS: All six patients had very fast relief from pain and accompanying symptoms from the drug but they developed an increase in attack frequency soon after using SQ sum. In all patients, the CH returned to its usual frequency within a few days after SQ sum was withdrawn or replaced with other drugs. Five patients were not taking any prophylactic treatment and SQ sum was the only drug prescribed to treat their headache. CONCLUSIONS: Physicians should recognize the possibility that treatment of CH with SQ sum may be associated with an increased frequency of headache attacks.     

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.     

Cluster headache and lifestyle: remarks on a population of 374 male patients

To investigate the relation between cluster headache (CH) and lifestyle, some lifestyle factors were considered in a population of 374 CH male patients consecutively referred to the same headache center, including 306 with episodic CH, 22 with chronic CH unremitting from onset, 20 with chronic CH evolved from episodic, and 26 with CH periodicity undetermined CH patients had jobs involving greater responsibilities and were more frequently self-employed than controls. In addition, their past medical histories often reported head injury, either with loss of consciousness (13.4%) or without loss of consciousness (23.5% of cases). As regards nonessential consumption habits, both cigarette-smoking and coffee and alcohol intake were more frequently reported in CH patients than in the general population, with a higher prevalence in chronic CH as opposed to episodic CH sufferers. In particular, smokers accounted for 78.9% of episodic CH patients and 87.8% of chronic CH patients--12.9% of episodic CH patients and 19.6% of chronic CH patients smoked over 30 cigarettes a day. Alcohol abuse was reported in 16.2% of episodic and 26.8% of chronic CH patients, while coffee abuse was reported in 6.9% of episodic and in 36.6% of chronic CH patients. Rather than pointing to a single lifestyle factor directly implicated in CH onset, my review suggests a common trend among CH patients to overindulge in certain living habits.     

Identifying cutaneous allodynia in chronic migraine using a practical clinical method

Cutaneous allodynia is common in migraine. In the majority of previous studies on allodynia in migraine, only patients with episodic migraine (EM) were included. Little is known on patterns of allodynia in chronic migraine (CM). Since the presence of allodynia is associated with a poor response to triptans, a clinically practical method to test migraine patients for allodynia would be useful to the clinician. The aim of this study was to assess the prevalence of dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical method. Eighty-nine CM patients were prospectively recruited. Patients were given a structured questionnaire regarding demographic data and migraine characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush various areas of the skin lightly. The prevalence of BA in the entire study population and in different patient subgroups was calculated. BA was present in 42.7% (38/89) of the patients. The presence of allodynia was unrelated to age, disease duration or to the occurrence of an acute headache exacerbation at the time of testing. Allodynia was positively associated with a history of migraine aura. BA was most common in the cephalic area, but was also seen in cervical dermatomes. BA is common in CM and, unlike in EM, is not significantly affected by the occurrence of an acute headache exacerbation. This suggests that central trigeminovascular neurons are chronically sensitized in patients experiencing migraine headache >15 days per month. The testing of BA in the clinical setting is possible using a simple and brief approach. It allows the clinician to determine whether the patient is sensitized, a diagnosis that affects treatment decisions.     

Gamma Knife Treatment of Refractory Cluster Headache

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.