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Objective Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society. Methods Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours. Results Randomized patients who had a migraine attack ( N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant ( p Conclusion Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.

Background: Unlike the prevalence, the incidence of headache disorders has attracted only little attention in epidemiological research. Different definitions of the ‘population at risk’ among the few published migraine and tension-type headache incidence studies limit their comparability and warrant further research. Therefore, we analysed data from the German Migraine and Headache Society (DMKG). Methods: Incidences were assessed in the general population in Germany via standardized headache questions using the International Classification of Headache Disorders, 2nd Edition (ICHD-2). The population was drawn from a 5-year age-group- stratified and gender-stratified random sample from the population register. Results: Of the 1312 baseline participants examined between 2003 and 2004, 1122 (85.5%) participated in the follow-up in 2006 and were the basis for three different populations at risk. We found that the three populations differed in size, age, gender and incidence estimate. The total sample incidence of migraine ranged between 0% and 3.3% and of tension-type headache between 5.3% and 9.2% depending on the definition of ‘at risk’. Conclusion: We concluded that one significant problem in headache incidence estimation is the definition of ‘at risk’, limiting comparability. Thus, this study supports the need for a common definition for prospective headache incidence estimations.

A close association between pain, depression and disability has been shown. However, the neurometabolic correlates of this association have been barely investigated in disease states. Episodic cluster headache is a severe headache syndrome and represents a suitable disease model for the investigation of episodic pain. The aim of this study was to explore the relationship between depression and disability as well as pain scores and brain metabolism in patients with cluster headache during the disease period with repetitive pain attacks, but outside an acute attack. Thirteen patients with cluster headache underwent 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission (FDG-PET) and completed questionnaires on depression and disability as well as a pain visual analogue rating scale (VAS). A positive correlation between the depression scores and glucose metabolism was observed in the insular cortex. A positive correlation between the pain disability scores and brain metabolism was detected in the amygdala. The same applied to the pain visual analogue rating scores. Our data underline the association between severe episodic pain, depression and disability. In addition to this clinical observation, our results stress the importance of the insula and amygdala in pain processing and suffering.

The prevalence of migraine and tension-type headache (TTH) varies considerably with respect to gender, age group and geographic regions. Methodological differences in the assessment and classification of cases are a major cause of this variability across studies, limiting the ability to perform true regional comparisons. We conducted three population-based studies in different German regions and assessed headache prevalence and headache characteristics in face-to-face interviews, applying standardized methods. We analysed the 6-month prevalence of migraine, TTH and their probable subtypes based on the new criteria of the International Headache Society (IHS). Among the 7417 participants in all three regions, the pooled 6-month prevalence of migraine, probable migraine, TTH and probable TTH was 6.75, 4.40, 19.86 and 11.61%, respectively. Despite the application of standardized classification methods, regional variations between 4.39 and 8.00% for migraine and 15.44 and 23.64% for TTH were observed, indicating differences in the local headache burden. Application of the new IHS criteria yielded headache categories that were not mutually exclusive, indicating a need for further discussion about the value of probable headache types in epidemiological studies.

Ziel der vorliegenden Studie war es, ein aus 3 Fragen bestehendes Screeningtool zu entwickeln, das Arzten, die nicht auf die Diagnose und Therapie von Kopfschmerzerkrankungen spezialisiert sind, wie z. B. dem niedergelassenen Allgemeinmediziner, als Entscheidungshilfe dienen kann, ob bei seinem Migranepatienten eine medikamentose Migraneprophylaxe Erfolg versprechend ist oder nicht. Dafur wurde von 132 Migranepatienten, die bei Kopfschmerzspezialisten vorstellig waren, ein aus 10 Items bestehender Fragebogen zu ihrer Migrane ausgefullt. Unabhangig davon fullten die Arzte einen Fragebogen aus, in dem sie angaben, ob der Patient ihrer Einschatzung nach fur eine Migraneprophylaxe in Frage kommt und wenn ja, welche Grunde sie dazu bewogen haben. Mittels logistischer Regression wurden anschliesend die 3 Fragen identifiziert, die in dem vorliegenden Datensatz den grosten Einfluss auf die Prophylaxeentscheidung hatten und die derzeit an 150 Migranepatienten in Praxen niedergelassener Allgemeinmediziner validiert werden

ZusammenfassungIm Rahmen zweier Anwendungsbeobachtungen in den Jahren 2003 und 2004 zur Beurteilung der Wirksamkeit und Verträglichkeit von 2,5 mg Frovatriptan wurden von 4 241 niedergelassenen Ärzten Daten zur Vortherapie sowie die Therapieverläufe einer einzelnen Migräneattacke unter Frovatriptan bei 16 737 Patienten dokumentiert. Beide Studien schlossen Patienten mit Migräne mit und ohne Aura entsprechend der IHS-Kriterien ein. Frauen waren mit 81% überrepräsentiert. Das Alter der Patienten betrug im Median 42,6 Jahre. Die Dauer der Migräne wurde mit einem Mittelwert von 10,4 Jahren angegeben. Die meisten Patienten (53,7%) gaben an, bis zu 2 Attacken pro Monat zu haben. Die übliche Kopfschmerzstärke wurde von 48,5% der Patienten als schwer beschrieben und von 47,5% als mittelschwer. Die übliche Dauer der gesamten Migräneattacke betrug bei 54,2% der Patienten mehr als 24 Stunden. Die Fravotriptanwirkung setzte innerhalb von 40 Minuten ein (Median), wiederkehrende Kopfschmerzen waren bei 18,8% der Patienten zu beobachten.Die Dauer der gesamten mit Frovatriptan behandelten Attacken betrug bei 84% der Patienten nur noch bis zu 24 Stunden. Im Vergleich zur bisherigen Therapie wurde die Frovatriptan-Behandlung von 87,5% der Patienten als besser wirksam gegen Kopfschmerzen und von 71,2% als besser wirksam gegen Übelkeit/Erbrechen und auch als verträglicher bewertet. Gleiches gilt für die Bewertungen durch die Ärzte hinsichtlich der besseren Wirksamkeit (87,9%) und der besseren Verträglichkeit (73,5%). In beiden Studien wurde der Wunsch zur Fortbehandlung mit Frovatriptan in 92,3% geäußert. Die Rate an Patienten mit unerwünschten Arzneimittelwirkungen lag bei 0,36%.Auf Grund des raschen Wirkeintritts und der langen Wirkungsdauer ist die Frovatriptan-Therapie effektiv und trägt im Zusammenhang mit der guten Verträglichkeit und der geringen Recurrence-Rate zur Compliance bei.

The efficacy and tolerability of a CO2-extract of feverfew (MIG-99, 6.25 mg t.i.d.) for migraine prevention were investigated in a randomized, double-blind, placebo-controlled, multicentre, parallel-group study. Patients ( N = 170 intention-to-treat; MIG-99, N = 89; placebo, N = 81) suffering from migraine according to International Headache Society criteria were treated for 16 weeks after a 4-week baseline period. The primary endpoint was the average number of migraine attacks per 28 days during the treatment months 2 and 3 compared with baseline. Safety parameters included adverse events, laboratory parameters, vital signs and physical examination. The migraine frequency decreased from 4.76 by 1.9 attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group ( P = 0.0456). Logistic regression of responder rates showed an odds ratio of 3.4 in favour of MIG-99 ( P = 0.0049). Adverse events possibly related to study medication were 9/107 (8.4%) with MIG-99 and 11/108 (10.2%) with placebo ( P = 0.654). MIG-99 is effective and shows a favourable benefit-risk ratio.

Nach der neuen IHS-Klassifikation werden der episodische und chronische Cluster-Kopfschmerz, die episodisch und chronische paroxysmale Hemikranie und das SUNCT-Syndrom („short-lasting unilateral neuralgiform headache with conjunctival injection and tearing“) unter dem Begriff trigemino-autonome Kopfschmerzen (TAK) zusammengefasst. Sie unterscheiden sich in Dauer, Frequenz, Rhythmik und Intensitat der Schmerzattacken. Autonome Begleitsymptome wie Lakrimation, konjunktivale Injektion, Rhinorrho, nasale Kongestion und Lidschwellung treten mehr oder weniger stark ausgepragt auf. Ein wesentliches weiteres Unterscheidungsmerkmal liegt in dem unterschiedlichen Ansprechen auf Indometacin. Grundsatzlich unterteilt sich die Therapie, ahnlich wie die der Migrane, in eine Akuttherapie und eine medikamentose Prophylaxe. Aufgrund der relativen Kurze der Attacken ist jegliche Medikation in Tablettenform nicht wirksam genug, das groste Augenmerk liegt auf der Prophylaxe. Die zeitintensive Betreuung der Patienten erfordert eine individuell zugeschnittene Kombination der verschiedenen Therapieoptionen. Obwohl ausreichend gute vergleichende Studien rar sind, kann in der Praxis in der grosen Mehrzahl der Falle eine positive Beeinflussung der Schmerzattacken erreicht werden. Die vorliegenden Therapieempfehlungen stutzen sich auf Kriterien der „evidence based medicine“ (EBM).

ZusammenfassungDie Wirksamkeit, Sicherheit und Verträglichkeit einer Einzelgabe von zwei Tabletten der fixen Dreierkombination mit 250 mg Azetylsalizylsäure (ASS) plus 200 mg Paracetamol plus 50 mg Koffein (Thomapyrin®) gegenüber zwei Tabletten mit 500 mg ASS, oder zwei Tabletten mit 500 mg Paracetamol, oder zwei Tabletten mit 50 mg Koffein beziehungsweise Plazebo wurde in einer klinischen Studie an 1 743 Patienten geprüft, die ihre episodischen Kopfschmerzen vom Spannungstyp oder ihre Migräne mit und ohne Aura üblicherweise erfolgreich mit verschreibungsfreien Analgetika behandeln. Die Dreierkombination war im a priori definierten primären Endpunkt “Zeit bis zu 50% Schmerzreduktion” sowohl der Zweierkombination aus ASS plus Paracetamol (p = 0,0181), als auch den Monoanalgetika ASS (p = 0,0398) und Paracetamol (p = 0,0016), sowie auch der Monotherapie mit Koffein (p < 0,0001) und Plazebo (p < 0,0001) überlegen. Alle Behandlungen außer der Koffein-Monotherapie waren der Plazebobehandlung überlegen (p < 0,0001). Die überlegene Wirksamkeit der Dreierkombination gilt auch für alle sekundären Endpunkte wie beispielsweise der “Verringerung der Kopfschmerzen auf 10 mm VAS (visual analog scale = visuelle Analogskala zur Schmerzmessung), dem gewichteten % SPID (sum of pain intensity difference = aufsummierte Schmerzintensitätsdifferenz gegenüber dem Ausgangsschmerz in Prozent), dem Ausmaß der Beeinträchtigung der alltäglichen Aktivitäten und der globalen Beurteilung der Wirksamkeit durch die Patienten. Alle Behandlungen waren gut verträglich, die Inzidenz von unerwünschten Begleiterscheinungen war gering.

ZusammenfassungIn Rahmen einer Anwendungsbeobachtung zur Beurteilung der Wirksamkeit und Verträglichkeit von 2,5 mg Frovatriptan (Allegro®) in der Behandlung akuter Migräneattacken wurden im Jahr 2003 bei niedergelassenen Ärzten von insgesamt 7107 Patienten die Vortherapie sowie die Therapieverläufe dokumentiert. Die Begleitsymptome ließen eine eindeutige Zuordnung als Migräne mit und ohne Aura entsprechend den IHSKriterien zu. Den Behandlungserfolg einer Akuttherapie bisheriger Migräneanfälle mit Analgetika/NSAR (66%), Triptanen (34%) bzw. Ergotaminen (18%) schätzten die Patienten mit überwiegend »befriedigend« (53%) oder sogar »schlecht« (23%) ein. Rund ein Drittel aller Patienten erhielt mindestens ein weiteres Medikament als Dauermedikation, allerdings nur 3,7% einen Betablocker.Die Dauer der pro Patient bis zu drei dokumentierten, mit Frovatriptan behandelten Migräneattacken (insgesamt 16798) lag im Median bei jeweils 1,0 Tagen. Ein geringfügiger Trend zur Verkürzung der Dauer ab der zweiten Attacke kristallisierte sich dabei heraus. Die Intensität des Kopfschmerzes ging von eingangs überwiegend starken Kopfschmerzen (58%) auf eine meist mittlere Schmerzstärke bei der 3. Attacke zurück (44%). Pro Migräneattacke wurde überwiegend (72-82%) eine Tablette Frovatriptan 2,5 mg eingenommen. Ein Trend zur weiteren Reduktion von zwei auf eine Tablette war klar erkennbar (26-16%). Auch der Anteil der Patienten, die additiv weitere Schmerzmittel (z.B. NSAR) benötigten, reduzierte sich von 33 auf 23%.Ein erneuter Kopfschmerz innerhalb von 24 Stunden war in nur 13% der Fälle nach der ersten und in 8% der Fälle nach der dritten mit Frovatriptan behandelten Attacke aufgetreten. Die Wirksamkeit der Frovatriptanmedikation wurde von den Patienten und den betreuenden Ärzten in über 90% mit »sehr gut« oder »gut« bewertet, die Verträglichkeit in über 95%. Dementsprechend wünschten 90% der Betroffenen eine Fortführung der Behandlung mit Frovatriptan, was u.a. auf die niedrige Rate von unerwünschten Arzneimittelwirkungen mit nur 0,77% zurückzuführen sein dürfte.

Background and Objective: We report the design and essentials of the protocols of two Acupuncture Randomized Trials (ART) investigating whether acupuncture is more efficacious than no treatment and minimal acupuncture in the interval treatment of migraine and tension-type headache. Design: Randomized controlled multicenter trials with three treatment arms and a total observation period of 28 weeks. Setting: 30 practitioners and outpatient units in Germany specialized in acupuncture treatment. Patients: Per study 300 patients with migraine and episodic or chronic tension-type headache, respectively (diagnosis according to the criteria of the International Headache Society). Interventions: Patients are randomly assigned to receive either (1) semi-standardized acupuncture (150 patients), (2) standardized minimal acupuncture (75 patients), or (3) no interval treatment for 12 weeks followed by semi-standardized acupuncture (75 patients, waiting list control). Acupuncture treatment consists of 12 sessions per patient over a period of 8 weeks. Main Outcome Measure: Main outcome measure in the migraine trial is the difference between the number of days with headache of moderate or severe intensity during the 4 weeks before randomization and weeks 9 to 12 after randomization. In the study on tension-type headache the main outcome measure is similar to that described above, but for the number of headache days regardless of intensity. Outlook: The results of these two studies (available in 2004) will provide health care providers and policy makers with the information needed to make scientifically sound assessments of acupuncture therapy.

Trigeminal neuralgia and postherpetic neuralgia are the most relevant neuralgiform facial pain syndromes. Trigeminal neuralgia is characterized by lancinating intensive pain attacks of very short duration, triggered by external cues,whereas postherpetic neuralgia consists predominantly of long-lasting burning pain. Sodium channel blocking drugs are first choice in treatment of trigeminal neuralgia, operative procedures encompass microvascular decompression,thermocoagulation and percutaneous retrogasserian glycerol rhizotomy. In the acute stage postherpetic neuralgia is treated antivirally and analgesically, in the chronic stage by tricyclic antidepressive substances. Other pain syndromes described encompass the Tolosa-Hunt-syndrome, cervicogenic headache, craniomandibular dysfunction syndrome, atypical facial pain and rarer syndromes. Therapeutic recommendations are based on evidence based medicine criteria (EBM).

Kopfschmerzen in Verbindung mit der Halswirbelsaule sind angesichts einer verwirrenden und uneinheitlichen Terminologie ein Tummelplatz fur Fehldiagnosen und inadaquate Therapieversuche. Zu Unrecht werden primare Kopfschmerzen wie der Spannungskopfschmerz und die Migrane alleine aufgrund ihrer okzipitalen Lokalisation als “zervikogen” eingeordnet. Der zervikogene Kopfschmerz (CEK) nach Sjaastad imponiert durch einseitige und seitenkonstante, in der Intensitat fluktuierende Schmerzen mit Verstarkung bei Kopfbewegungen und typischer Ausbreitung von okzipital nach frontal. Definition, Pathophysiologie, Differentialdiagnose und Therapie des CEK werden dargestellt. Eine Abgrenzung gegenuber der Migrane und anderen primaren Kopfschmerzen erlauben ipsilaterale Blockaden der Wurzel C2/C3 und/oder des N. occipitalis major. Weder medikamentose noch operative und manualtherapeutische Intervention fuhren zu einer wesentlichen Besserung oder Remission des CEK. Wahrscheinlich munden Schmerzreize unterschiedlicher anatomischer Provenienz in eine gemeinsame anatomische Endstrecke und bewirken das uniforme Bild des CEK, der damit eher als ein unspezifisches homogenes Reaktionsmuster aufzufassen ist.

Leichte und mittelschwere Migraneattacken werden mit der Kombination eines prokinetischen Antiemetikums wie Metoclopramid oder Domperidon und einem ausreichend dosierten Analgetikum (Azetylsalizylsaure, Paracetamol, Ibuprofen, Naproxen, Diclofenac) behandelt. Mittelschwere und schwere Migraneattacken werden mit den modernen 5-HAT 1B/D -Rezeptoragonisten (“Triptane”) behandelt. Die Kombination eines Antiemetikums und Ergotamintartrat ist weniger wirksam als die “Triptane”. Patienten mit haufigen oder schweren Migraneattacken benotigen eine medikamentose und nicht-medikamentose Prophylaxe. Medikamente der ersten Wahl sind die Beta-Rezeptorenblocker Metoprolol oder Propranolol und der Kalziumantagonist Flunarizin. Substanzen der zweiten Wahl sind Valproinsaure und nicht-steroidale Antirheumatika. Bei den nichtmedikamentosen Therapien sind multimodale Therapieansatze, die Techniken der progressiven Muskelrelaxation, kognitive Techniken, Stress- und Reizverabreitungstraining und Schmerzbewaltigungstechniken verbinden, sowie die Sporttherapie (aerobes Ausdauertraining) wirksam.

In this international, multicentre, double-blind, placebo-controlled, single attack study, ‘triptan naive’ migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P = 0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.

Die Wirksamkeit, Sicherheit und Vertraglichkeit von Sumatriptan s.c. in der Akuttherapie von Clusterkopfschmerzen wurde in einer offenen multizentrischen Studie in einem Untersuchungszeitraum von bis zu einem Jahr uberpruft. Hieran nahmen von Dezember 1992 bis Oktober 1993 52 Patienten mit episodischem (71%) und chronischem (29%) Clusterkopfschmerz teil. Die Patienten konnten wahrend der Studie Clusterattacken selbstandig und auserhalb der Klinik mit 6 mg Sumatriptan behandeln. Die Dokumentation der entsprechenden Zielparameter wurde von den Patienten mit Hilfe eines Schmerzkalenders durchgefuhrt. Insgesamt wurden 2031 Attacken ausgewertet. Eine erfolgreiche Therapie trat bei 88% aller Attacken ein, 57% der Patienten waren innerhalb 15 min nach der Injektion komplett schmerzfrei. Schmerzfreiheit innerhalb von 15 min in uber 90% aller behandelten Attacken wurde von 42% der Patienten erreicht. Ein Nachlassen der Therapierfolgsrate im Behandlungszeitraum trat nicht ein. Wegen mangelnder Wirksamkeit oder unerwunschter Ereignisse wurde die Studie von 10% der Patienten abgebrochen. Uber unerwunschte Ereignisse berichteten 62% der Patienten, davon wurden 3,8% als schwerwiegend eingestuft. Sumatriptan s.c. stellt in der Akuttherapie des Clusterkopschmerzes ein zuverlassiges, schnell wirksames und bei Beachtung von Kontraindikationen sicheres und gut vertragliches Therapeutikum dar.

The migraine prophylactic effect of 10 mmol magnesium twice-daily has been evaluated in a multicentre, prospective, randomized, double-blind, placebo-controlled study. Patients with two to six migraine attacks per month without aura, and history of migraine of at least 2 years, were included. A 4-week baseline period without medication was followed by 12 weeks of treatment with magnesium or placebo. The primary efficacy end-point was a reduction of at least 50% in intensity or duration of migraine attacks in hours at the end of the 12 weeks of treatment compared to baseline. With a calculated total sample size of 150 patients, an interim analysis was planned after completing treatment of at least 60 patients, which in fact was performed with 69 patients (64F, 5M), aged 18–64 years. Of these, 35 had received magnesium and 34 placebo. The number of responders was 1 in each group (28.6% under magnesium and 29.4% under placebo). As determined in the study protocol, this was a major reason to discontinue the trial. With regard to the number of migraine days or migraine attacks there was no benefit with magnesium compared to placebo. There were no centre-specific differences, and the final assessments of treatment efficacy by the doctor and patient were largely equivocal. With respect to tolerability and safety, 45.7% of patients in the magnesium group reported primarily mild adverse events like soft stool and diarrhoea in contrast to 23.5% in the placebo group.

Headache in association with the cervical spine is often misdiagnosed and treated inadequately due to confusing and varying terminology. Primary headaches such as tension-type headache and migraine are incorrectly categorized as "cervicogenic" merely because of their occipital localization. Cervicogenic headache described by Sjastaad presents as a unilateral headache of fluctuating intensity increased by movement of the head and typically radiating from occipital to frontal regions. Definition, pathophysiology, differential diagnosis and therapy of cervicogenic headache shall be demonstrated. Ipsilateral blockades of the C2/ C3 root and/or the major occipital nerve allow a differentiation between migraine and other primary headache syndromes. Neither pharmacological nor surgical or chiropractic procedures lead to an improvement or remission of cervicogenic headache. Pain of various anatomical regions possibly join into a common anatomical pathway then presenting as cervicogenic headache, which should therefore be understood as a homogeneous but also unspecific pattern of reaction.

Atypical facial pain is a collective term used for otherwise unclassifiable pain syndromes of the face. It describes mostly unilateral lancinating and burning pain, which is constantly present but fluctuating in intensity and may be accompanied by dys-or paraesthesias over a period of several years. Women are more often affected than men. A strikingly large number of invasive investigative procedures are performed before the final diagnosis is established. Psychopathological abnormalities are frequent and do not consist solely in masked depression. To date there is no cure for atypical facial pain. Most frequently tricyclic antidepressants such as amitriptyline and imipramine, MAO inhibitors or anticonvulsives such as carbamazepine and phenytoin are used, which only alleviate the pain. This also holds true for behaviour therapy, which should be the first-line treatment. Any invasive intervention should be avoided. In the differential diagnosis atypical facial pain should be distinguished from cervicogenic or cluster headache, and also from intracranial tumours of the trigeminal nerve or the cerebellar-pontine angle, erosive tumors of the base of the skull, orbitas and nasopharynx.

Objective.— This study aims at investigating cortical thickness in cluster headache patients as compared with a healthy control group. Background.— The pathobiology of cluster headache is not yet fully understood, although a dysfunction of the hypothalamus has been suggested to be causal. Previous studies in migraine and trigeminal neuropathic pain have demonstrated changes in cortical thickness using cortex segmentation techniques, but no data have been published on cluster headache. Methods.— We investigated 12 men with episodic cluster headache during a phase without acute headache as well as age and sex-matched healthy controls using high resolution T1-weighted magnetic resonance imaging acquired at 3T and performed a categorical whole-brain surface-based comparison of cortical thickness between groups. Furthermore, a correlation analysis of disease duration and cortical thickness was conducted. Results.— In comparison with control subjects, we found a reduction of cortical thickness in the angular gyrus and the precentral gyrus in cluster headache patients contralaterally to the headache side. These reductions did not correlate with disease duration. The cortical thickness of an area within the primary sensory cortex correlated with disease duration. Conclusions.— This study demonstrates alterations in cortical thickness in cluster headache patients suggesting a potential role of cortical structures in cluster headache pathogenesis. However, it cannot be determined from this study whether the changes are cause or consequence of the disorder. The correlation of cortical thickness with disease duration in the somatosensory cortex may suggest disease-related plasticity in the somatosensory system.

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required. Electronic supplementary material The online version of this article (doi:10.1007/s10194-010-0286-0) contains supplementary material, which is available to authorized users.

Atypical facial pain is a residual category for otherwise unclassifiable pain syndromes in the facial region. In 35 patients (31F, 4M) with a mean age of 53.2 ± 14.9 years and a chronic facial pain syndrome we tested the new diagnostic criteria of the International Headache Society (IHS). There was a marked female preponderance, vague description of symptoms and a long history of incorrect diagnoses. A high number of invasive procedures (3.5 ± 3.0 (1–13)) were performed in this group. In agreement with the IHS criteria, an operaiion or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, our patient sample had dysaesthesiae (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and superficial as well as deep pain. The IHS classification is insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We suggest a modified version of the IHS criteria for atypical facial pain.

Objective.— To compare the superior efficacy of the fixed combination of acetylsalicylic acid, paracetamol, and caffeine over the single substances, which was observed in the randomized, double-blind phase of the clinical trial, with the efficacy of the respective usual nonprescription medication taken by the patients in the open-label pre-phase of the same study. Background.— The “Thomapyrin Study” showed significant superiority of the fixed combination containing acetylsalicylic acid, paracetamol, and caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. Methods.— Prior to the randomized treatment phase, a headache episode treated with the patient's usual nonprescription medication was recorded (open-label pre-phase). Patients assessed their pain intensity on a 100-mm visual analog scale. For the 1734 patients included in the efficacy analysis, we compared the time course of the pain intensity difference (PID) to baseline after the patients took their usual medication with the time course of the PID after intake of the randomized study medication. Results.— Time course of PID after intake of the patient's usual medication was very similar to the time course of PID after intake of the randomized study medication. After 2 hours, pain reduction was on average 43.0, 38.2, 38.1, and 37.7 mm as assessed on the visual analog scale in the group of patients who took their usual triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, paracetamol, and ibuprofen, respectively, in the open-label phase. The corresponding mean pain reduction was 44.7, 40.7, and 39.5 mm in patients allocated to the triple combination containing acetylsalicylic acid, paracetamol, and caffeine, the single agents acetylsalicylic acid, and paracetamol, respectively, in the randomized, double-blind phase. Conclusions.— The efficacy results from double-blind, randomized clinical trials with nonprescription analgesics can be generalized and applied to everyday conditions provided patients and study design are selected carefully.

Population-based epidemiological studies about the prevalence of chronic migraine using the 2004 International Headache Society (IHS) classification definition are rare. We analysed the data of the Deutsche Migräne und Kopfschmerz Gesellschaft headache study, which included 7417 adults in three regions of Germany, with respect to their headache. Additionally, body mass index, alcohol consumption and smoking behaviour were recorded. Using the IHS definition from 2004, chronic migraine was diagnosed in 0.2% of the population. Half of these patients also fulfilled the criteria of medication overuse headache (MOH). The distribution of migraine attacks per subject was highly skewed, with only 14% of all migraine patients having more than six migraine attacks per month. Patients with chronic migraine or MOH seem more often to be active smokers than controls without headache. A body mass index of ≥ 30 was present significantly more often in patients with MOH than in controls or in patients with episodic migraine. The skewed distribution of the numbers of attacks per patient supports the recommendation to differentiate between episodic migraine with low and high attack frequency, as is done in the classification of tension-type headache. It further suggests that migraine with high attack frequency might be biologically different. The higher prevalence of smokers and of patients with a body mass index ≥ 30 in chronic migraine or MOH supports the idea of a frontal dysfunction in these patients.

The role of psychological factors in the course of primary headache syndromes is still controversial. Using the Minnesota Multiphasic Personality Inventory (MMPI) we investigated the personality profiles of 434 headache patients (160 migraineurs, 95 with tension type headache, 30 with cluster headache and 149 with combination headache) in accordance with the IHS criteria. In the first three MMPI scales (hypochondria, depression, hysteria) there was a slight increase in T mean values to over 60, but still in the range of two standard deviations of the normal population. There were no statistically significant differences between the four headache groups and between patients with and without analgesic abuse. It was impossible to distinguish headache groups on the basis of their personality profiles by means of reclassification with discriminant analysis. In a cluster analysis, patients with cluster headache showed the highest number (20%) of abnormalities, but also the highest percentage (13%) of completely normal results. Our findings- a cross section analysis of personality profiles-contradict many other MMPI-based studies.

Previous reports have found an association between coronary vasospasm and migraine. It has been speculated that migraine and variant angina might be manifestations of a generalized vasospastic disorder. To investigate this hypothesis, 74 patients with frequent attacks of migraine were studied using 24-h continuous ambulatory electrocardiography to identify the presence of coronary vasospasm. Control groups consisted of 19 patients with tension headaches, and 38 healthy individuals. All subjects were free of heart disease. One patient in the migraine group and one patient in the control group had symptomless episodes of ST-segment depression not indicative of coronary vasospasm. Our data do not support the hypothesis that migraine and variant angina are components of a generalized vasospastic disorder.

Three oral doses of sumatriptan, 100, 200 and 300 mg, given as dispersible tablets, were compared in the acute treatment of migraine in a double-blind, placebo-controlled, parallel-group study of 1,13

A double-blind, randomized, multicentre, parallel-group study was carried out to compare intranasal sumatriptan with placebo in the treatment of migraine. Seventy-four patients (37 in each treatment group) were recruited into the study. Patients received two insufflations of the same treatment (sumatriptan or placebo) 15 min apart. Sumatriptan (20 mg plus 20 mg) was more effective than placebo at relieving headache, defined as a reduction in severity from moderate (grade 2) or severe (grade 3) to mild (grade 1) or none (grade 0), at 60 and 120 min. At 120 min, 75% of patients in the sumatriptan group reported headache relief, compared with 32% of patients in the placebo group (p

The efficacy and safety of sumatriptan, a selective 5-HT1 like receptor agonist, were studied in a randomized, double-blind, placebo-controlled, parallel-group, multicentre, multinational c

In a multinational, placebo-controlled, double-blind, parallel-group study of oral sumatriptan (GR43175), given as a dispersible tablet, in the acute treatment of migraine, 149 pati

Aim: To determine if botulinum toxin type A (BoNT-A) injections can reduce the frequency and severity of migraines. Methods: Patients (n = 127) were randomized to receive placebo or two doses of BoNT-A (Dysport®). The primary endpoint was reduction in number of migraine attacks up to week 8 and between weeks 8 and 12 after injection. Patient diaries were used to record secondary endpoints, including frequency, severity and duration of migraine attacks. Results: There was a mean reduction of 0.54 and 0.94 attacks/month with placebo and BoNT-A, respectively, and absolute attack count was less in the verum group (3.6 vs. 4.2 attacks/month), but this was not statistically significant. The patients’ global assessment of efficacy was significantly better than placebo in the high-dose group (p = 0.02) but no effects were seen for the other secondary efficacy parameters. Conclusion: Our study showed a trend towards a reduced attack rate with verum but did not show any statistically significant efficacy of BoNT-A in the prophylactic treatment of migraine.

We investigated the consistency between the headache diagnosis based on medical history and three treated headache episodes diagnosed based on a diary. In a randomized double-blind study including individuals with either migraine or tension-type headache (TTH) we showed significant superiority of the fixed combination of acetylsalicylic acid + paracetamol + caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. A neurologist performed a classification of the usual headache episodes and each of the three treated ones in a blinded fashion based on a structured questionnaire. This was done for the 1734 patients included in the efficacy analysis who usually treated their episodic TTH or migraine attacks with non-prescription analgesics. The overall percentage of patients with migraine and TTH remained relatively stable. The treated headache episodes were between 75 and 77% migraine, 18–20% were TTH and 5–7% could not be classified. We observed some shift in headache type within patients from prior history and in treated attacks. In 60% of patients all three treated episodes were of the type initially diagnosed by the neurologist by history (56% migraine and 4% episodic TTH). Of those with an initial diagnosis of migraine, 24% had at least one attack meeting criteria for TTH. Of patients with an initial diagnosis of TTH, 54% had at least one attack meeting the diagnostic criteria for migraine. Our results demonstrate that an initial headache diagnosis does not accurately predict the headache type treated in a randomized trial. Symptom features of treated headaches should be captured to ensure that the attack is of the type targeted by the clinical trial. The International Headache Society Guidelines for controlled clinical trials should be updated accordingly.

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

Increasingly, botulinum type A toxin is used to influence pathologically increased muscle activity in conditions such as dystonia and spasticity. Studies have also assessed its efficacy in tension-type headache, where muscle tenderness may be increased. We undertook a prospective, multicentre, randomized, double-blind, placebo-controlled trial. Patients received injections of Dysport (total dose of 420 or 210 units) or saline placebo in 18 sites on the head and neck. Of 125 patients treated, 118 were included in the intention-to-treat dataset. No significant differences between each verum group and placebo were seen for the primary efficacy parameter - change in the number of headache-free days at 4-8 weeks after injection compared with 4 weeks before injection. The groups receiving 420 or 210 units of Dysport experienced 2.60 and 2.87 more headache-free days respectively, compared with 1.93 more headache-free days for the placebo group (P = 0.66 versus 420 units; P = 0.52 versus 210 units). Treatment with 420 units of Dysport was associated with significant improvements compared with placebo for two secondary efficacy parameters: mean change in headache duration from baseline to weeks 8-12 (P < 0.05) and improved global physician and patient assessment scores (P < 0.05). Further studies should address the possible value of multiple injections with extended observation periods, dose optimization, and whether duration of headache history and number of previous treatments are predictors of patient response.

This population-based cross-sectional study examined the 3-month prevalence of headache, migraine and tension-type headache (TTH) among adolescents aged 12-15 years in Germany Students ( n = 3324) from 20 schools completed a questionnaire on general and headache-specific pain which included a sociodemographic module. The headache-specific questionnaire complied with the respective revised criteria of the International Headache Society (IHS). 'Modified criteria' changed the item 'duration' in migraine (>30 min instead of >4 h). The overall 3-month prevalence of headache was 69.4% (boys 59.5%, girls 78.9%), with 4.4% of the adolescents suffering from frequent (≥ 14 days/3 months) and severe (grade 8-10 on a 10-point visual analogue scale) headache and 1.4% (boys 0.9%, girls 1.9%) from headache ≥15 days/month. The 3-month prevalence of migraine was 2.6% (boys 1.6%, girls 3.5%) applying strict IHS criteria and 6.9% (boys 4.4%, girls 9.3%) with modified criteria; 12.6% (boys 8.3%, girls 16.7%) suffered from probable migraine, 0.07% fulfilled the criteria for chronic migraine, 4.5% (boys 4.6%, girls 4.3%) suffered from TTH, 0.2% from chronic TTH and 15.7% (boys 14.5%, girls 16.9%) from probable TTH. Headache and migraine were more common in girls than in boys and in teenagers, especially in girls, aiming at higher education. Recurrent headache and primary headache disorders are common complaints among German adolescents, especially among girls.

Neuroimaging studies have explored cerebral activation patterns in patients with cluster headache (CH) during attacks and have revealed activation of multiple brain areas known to belong to the general pain-processing network. However, it is still unclear which changes in brain metabolism are inherent to the shift from the ‘in bout’ to the ‘out of bout’ period. We measured cerebral glucose metabolism in 11 episodic CH patients during the cluster and again during the remission period with 18F-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) and compared these data with 11 healthy controls. ‘In bout’ compared with ‘out of bout’ scans were associated with increases of metabolism in the perigenual anterior cingulate cortex (ACC), posterior cingulate cortex, prefrontal cortex, insula, thalamus and temporal cortex. Decreases in metabolism were observed in the cerebellopontine area. Compared with healthy volunteers, hypometabolism in the patient group (‘in bout’ and ‘out of bout’) was found in the perigenual ACC, prefrontal and orbitofrontal cortex. Thus, FDG-PET in CH patients revealed ‘in bout’ activation of brain structures which are involved in descending pain control. Compared with controls, the regional brain metabolism was constitutively decreased in most of these structures, irrespective of the bout. This finding indicates a deficient top-down modulation of antinociceptive circuits in CH patients. We suggest that trigger mechanisms of CH are insufficiently controlled and thus promote the initiation of the bout period and acute attack.

Objectives In a randomized controlled multicenter trial extending over 24 weeks, we investigated whether acupuncture is as effective and safe as metoprolol in the prophylactic treatment of migraine under conditions similar to routine care. Methods One hundred fourteen migraine patients could be randomized to treatment over 12 weeks either with acupuncture (8 to 15 sessions) or metoprolol (100 to 200 mg daily). Main outcome measure was the difference in the number of migraine days between baseline and the weeks 9 to 12 after randomization (derived from a headache diary). Results Two of 59 patients randomized to acupuncture withdrew prematurely from the study compared to 18 of 55 randomized to metoprolol. The number of migraine days decreased by 2.5 +/- 2.9 days (baseline 5.8 +/- 2.5 days) in the acupuncture group compared to 2.2 +/- 2.7 days (baseline 5.8 +/- 2.9 days) in the metoprolol group (P= .721). The proportion of responders (reduction of migraine attacks by > or =50%) was 61% for acupuncture and 49% for metoprolol. Both physicians and patients reported fewer adverse effects in the acupuncture group. Conclusions Due to missing the recruitment target (480 patients) and the high drop-out in the metoprolol group the results must be interpreted with caution. Still, they suggest that acupuncture might be an effective and safe treatment option for patients unwilling or unable to use drug prophylaxis.