G. Bussone

Melatonin versus Placebo in the Prophylaxis of Cluster Headache: A Double-Blind Pilot Study with Parallel Groups

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.

Lessons from 8 years' experience of hypothalamic stimulation in cluster headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.

Tolosa–Hunt syndrome: critical literature review based on IHS 2004 criteria

In 2004, the International Headache Society (IHS) re-defined the diagnostic criteria of Tolosa–Hunt syndrome (THS) specifying that granuloma, demonstrated by magnetic resonance imaging (MRI) or biopsy, is required for diagnosis. We reviewed the literature on THS published from 1988 (year of publication of first IHS criteria) to 2002, analysing individual cases in relation to the new IHS criteria. One hundred and twenty-four cases were identified. As far as it was possible to discern, clinical presentation was similar in all, but 44 (35±) were reported to have inflammation on MRI or bioptic evidence of granuloma, 41/124 (33±) had normal neuroimaging findings and 39 (31±) had a specific lesion, so the THS was secondary. These data confirm that clinical criteria for THS are common to several conditions and their application alone does not guarantee a correct diagnosis. The requirement for inflammation on MRI will result in better classification of painful ophthalmoplegias; nevertheless, an MRI protocol that best defines inflammation should be specified. The status of cases which fulfil the clinical criteria but have normal MRI remains to be clarified.

Prevalence of Primary Headaches in People with Multiple Sclerosis

The aim was to investigate the lifetime prevalence of headache and primary headache (diagnoses according to International Headache Society criteria) in multiple sclerosis (MS). The relationships between headache and clinical features of MS and MS therapy were also investigated. We studied 137 patients with clinically definite MS; 88 reported headache, 21 of whom developed headache after the initiation of interferon. The prevalence of all headaches in the remaining 116 patients was 57.7%. Migraine was found in 25.0%, tension-type headache in 31.9%, and cluster headache in one patient. A significant correlation (P = 0.007, Fishers exact test) between migraine and relapsing-remitting MS was found. Primary headaches are common in MS patients. Further studies are needed to clarify the mechanisms underlying this association, particularly the association between migraine and relapsing-remitting MS, and the role of interferon in the development of new headache.

Sphenopalatine Endoscopic Ganglion Block: A Revision of a Traditional Technique for Cluster Headache

The diagnosis of chronic cluster headache (CH), the most painful form of headache, is based on typical clinical features characterized by strictly unilateral pain with no side shift and ipsilateral oculofacial autonomic phenomena. The attacks occur several times a day for periods of 1 to 2 months in the episodic form of the disease or less frequently on a daily basis in the chronic form. The pathogenesis of CH involves the activation of parasympathetic nerve structures located within the sphenopalatine ganglion (SPG), which explains many of the associated symptoms, whereas the activation of the ipsilateral hypothalamic gray matter may explain its typical circadian and circannual periodicity. A number of surgical approaches have been tried in cases of chronic CH resistant to pharmacologic therapy, of which SPG blockade has been shown to have certain efficacy. We have adopted a new technique based on endoscopic ganglion blockade that approaches the pterigo‐palatine fossa by way of the lateral nasal wall and consists of the injection of a mixture of local anesthetics and corticosteroids, which was performed in 20 selected patients with chronic CH, according to the International Headache Society criteria (18 male, 2 female; mean age 40 yr), who were selected for SPG blockade because they were totally drug resistant. The symptoms improved significantly, but always only temporarily, in 11 cases. These results should be considered rather good because, unlike other frequently used techniques, SPG blockade is not invasive and should therefore always be attempted before submitting patients to more invasive surgical approaches.

Acute hypothalamic stimulation and ongoing cluster headache attacks

Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of ≥50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.

Assessment of International Headache Society diagnostic criteria: a reliability study

In 1988 the International Headache Society (IHS) introduced new diagnostic criteria for headaches and craniofacial pain. Since headaches can be diagnosed solely on the basis of information provided by the patient, it is essential that the criteria are reproducible and consistent. phenomena to a form designed to reflect the IHS criteria. Interobserver concordance (kappa statistics) in the application of the diagnostic hemicrania; kappa = 0.88 for migraine; kappa = 0.75 for tension-type headache; (ii) “almost perfect” to “substantial” for the second digit migraine without aura; kappa = 0.71 for chronic tension-type headache; kappa = 0.66 for cluster headache-like disorder not fulfilling the eria. These results show that the IHS diagnostic criteria are satisfactorily applicable to high quality medical records abstracted by experienced.

Neuroendocrine dysfunction in cluster headache

Current views on cluster headache pathogenesis indicate a primary central nervous system dysfunction, in particular a hypothalamic involvement. To confirm the hypothalamic involvement in cluster headache we evaluated the hypothalamic-pituitary axis responsiveness with the thyrotrophin releasing hormone (TRH) test. A dose of 200 μg of TRH was administered i.v. to nine healthy controls, 32 patients with cluster headache during cluster period and 16 in remission period. Delta maximum thyrotrophin (TSH) was significantly lower in patients with cluster headache during cluster period (p < 0.05 versus healthy controls and cluster headache patients in remission). No difference was observed between healthy controls and cluster headache patients in remission. A monoaminergic dysfunction at the hypothalamic level is hypothesized.

Health‐related quality of life in patients with cluster headache during active periods

Cluster headache is characterized by excruciatingly painful headaches which occur one or several times during the day. Little is known about the functional consequences of this severe headache form. We assessed health-related quality of life in 56 consecutive patients, 34 of whom were episodic cluster headache patients during an active period, and 22 had chronic cluster headache. All patients completed the Short Form-36 (SF-36). We found lower scores in the studied patients than in those reported in the general population for all SF-36 domains. For most scales the difference was significant (P < 0.0001, Students t-test, Bonferroni correction). Our findings suggest that cluster headache has marked functional consequences even when appropriate treatments are used.

Disability in chronic migraine with medication overuse: treatment effects through 5 years

Chronic migraine accompanied by medication overuse is particularly difficult to treat. The number of treatment investigations is limited, few have included follow-up beyond 6 months and almost none has examined whether treatment leads to concurrent improvements in disability and functional impairment. This open-label study addresses these limitations. We have been prospectively following an initial cohort of 84 chronic migraine patients with medication overuse, who at the time of this evaluation had been reduced to 58, for an extended period to assess longer-term maintenance of effects, using measurement procedures identical to those in the original investigation. Thus, the specific aim was to determine the clinical status, with respect to pain indices and disability level, of chronic migraine patients with medication overuse who were treated and followed prospectively for 5 years. All patients completed a brief inpatient treatment programme, in which they were withdrawn from their offending medications and subsequently placed on more appropriate preventive antimigraine medications. Both end-point, wherein missing data points were estimated, and continuer analyses, wherein data analysis was limited to the 58 individuals with complete datasets, revealed significant improvement on all measures studied—headache days per month, analgesic consumption and Migraine Disability Assessment (MIDAS) total score. The percentage reduction from baseline to 5 years for the MIDAS total score was 76.0%, while the percentage of individuals revealing improvements of clinically significant magnitude (≥u200950%) on the MIDAS was 91.9%. MIDAS total scores were lower at 5 years than at some of the intervening follow-up intervals. Comparisons of those who completed the 5-year follow-up (nu2009=u200958) with those who did not revealed no differences at baseline. This finding, coupled with the nearly identical results for the end-point and continuers analyses, suggests that attrition did not have a bearing on outcome. None of the patients completing the 5-year follow-up had relapsed since the prior 3-year follow-up assessment. High levels of maintenance were revealed at 5 years, with disability scores showing some continued improvement over time. The implications of these findings and the limitations of the study are discussed.