[Trigeminal neuralgia: drug therapy : The new German guideline]. / Medikamentöse Therapie der Trigeminusneuralgie : Die neue Leitlinie.

Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.

[Gender-specific results of the Dresden children and adolescents headache program DreKiP]. / Geschlechtsspezifische Ergebnisse des Dresdner Kinder- und Jugendkopfschmerzprogrammes DreKiP.

BACKGROUND: Girls and women are more frequently affected by headache than boys and men. The influence of gender on the effectiveness of headache therapies has so far been hardly investigated. We examined gender differences in the outpatient multimodal Dresden Child and Adolescent Headache Program DreKiP. METHODS: We treated 140 patients with primary headache in a 15-hour structured group program. At baseline (T0) and six (T1) and twelve months (T2) after the end of the program, data on headache-related limitation of daily activities (PedMIDAS) as well as headache frequency, intensity, and pain-related disability (P-PDI) were collected. Retrospectively, these data were analyzed separately for girls and boys. RESULTS: For 91 patients (9-19 years, median = 15; 71.4 % female) data were available for at least two measurement time points. Girls showed significantly higher headache frequency than boys at all time points (median headache days/last three months at T0: ♀ 43, ♂ 20; T1: ♀ 32, ♂ 12; T2: ♀ 28, ♂ 9) as well as numerically higher headache-related limitation of daily life. There were significant effects over time with a decrease in headache frequency (F (2.88) = 5.862; p = 0.004) and improvement in daily functioning (F (2.92) = 5.340; p = 0.006). There was no gender-specific treatment response. DISCUSSION: The DreKiP therapy shows effects in girls and boys with primary headache. Higher headache frequencies and everyday life restrictions in girls may have hormonal but also psychosocial causes and should be addressed in educational measures.

What do patients' efficacy and tolerability ratings of acute migraine medication tell us? Cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Most migraine patients need an effective acute medication. Real-world data can provide important information on the performance of acute migraine medication in clinical practice. METHODS: We used data from the German Migraine and Headache Society Headache Registry, where patients rate efficacy and tolerability of and satisfaction with each of their acute headache medications. RESULTS: A total of 1756 adult migraine patients (females: 85%, age: 39.5 ± 12.8 years, headache days per month: 13.5 ± 8.1) were included. Of these, 93% used acute medication, most frequently triptans (59.3%) and/or non-opioid analgesics (56.4%), and 58.5% rated efficacy as good or very good. This was more frequent for triptans (75.4%) than for non-opioid analgesics (43.6%, p < 0.001). Among non-opioid analgesics, naproxen was rated most effective (61.9% very good or good, p < 0.001 compared to ibuprofen, acetylsalicylic acid and paracetamol). Patient-rated efficacy significantly declined with higher headache frequencies (p < 0.001), and this effect remained significant after omitting patients overusing acute medication. CONCLUSION: In the present population recruited at specialized headache centers, patients rated triptans as more effective than non-opioid analgesics, naproxen as more effective than ibuprofen, and acute medication efficacy decreased with increasing headache frequency.Trial registration: The German Migraine and Headache Society Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Migraine Type-Dependent Patterns of Brain Activation After Facial and Intranasal Trigeminal Stimulation.

In migraine, the trigeminal nerve is intimately involved in the pathophysiology of the disease. We hypothesized that alterations in the sensory trigeminal activation in migraine would be reflected by EEG-derived event-related potentials (ERP). We aimed to investigate differences in the temporal and spatial processing of trigeminal stimuli between interictal migraine patients and healthy subjects. ERP to trigeminal stimuli were recorded at 128-channels to allow localization of their cortical sources with high temporal resolution. Seventeen patients with episodic migraine without aura, 17 subjects with episodic migraine with aura, and 17 healthy subjects participated in the study. The first branch of the trigeminal nerve was stimulated using intranasal chemical (CO2), cutaneous electrical, and cutaneous mechanical (air puff) stimuli. Analyses were performed with regard to micro-state segmentation, ERP source localization, and correlation with the patients' clinical characteristics. Topographical assessments of EEG configurations were associated with the pathological condition. The source analysis revealed altered trigeminal-sensory response patterns in the precuneus, temporal pole, and cerebellum for both migraine groups during the interictal phase. The estimated current source density was positively correlated with migraine disease duration, indicating brain functional and structural changes as a consequence of the disease. Hyperactivity of the cerebellar posterior lobe was observed as a specific trigeminal response of migraine patients with aura. In conclusion, our results suggest the presence of brain changes accompanying the advancement of migraine as an expression of dysfunctional central pain processing. Hence, we identified EEG patterns in response to mechano-/chemosensory stimuli that can serve as biomarkers of migraine.

[Complementary and supplementary procedures in the treatment of headache]. / Komplementäre und ergänzende Verfahren in der Kopfschmerztherapie.

In Germany, headache is one of the illnesses that most frequently leads to health impairments and to consultation with physicians. Even in children, headache is often associated with restricted activities of daily life. Nevertheless, the level of care for headache disorders is disproportionate to the medical needs. As a result, patients regularly use complementary and supportive therapeutic procedures. This review shows the procedures currently used for primary headache in childhood and adulthood, the methodological approaches and existing scientific evidence. The safety of the therapeutic options is also classified. These methods include physiotherapy, neural therapy, acupuncture, homeopathy, phytotherapy and the intake of dietary supplements. For children and adolescents with headaches, there are studies in the field of dietary supplements for coenzyme Q10, riboflavin, magnesium and vitamin D, which indicate specific effects in the reduction of headaches.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

[Consensus statement of the migraine and headache societies (DMKG, ÖKSG, and SKG) on the duration of pharmacological migraine prophylaxis]. / Konsensusstatement der Migräne- und Kopfschmerzgesellschaften (DMKG, ÖKSG & SKG) zur Therapiedauer der medikamentösen Migräneprophylaxe.

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here.

Migraine with aura: less control over pain and fragrances?

BACKGROUND: Accumulating data emphasizes the importance of olfaction in migraine pathophysiology. However, there are only a few studies evaluating how the migraine brain processes olfactory stimulation, and virtually no studies comparing patients with and without aura in this context. METHODS: This cross-sectional study recorded event-related potentials from 64 electrodes during a pure olfactory or pure trigeminal stimulus in females with episodic migraine with aura (n = 13) and without aura (n = 15), to characterize the central nervous processing of these intranasal stimuli. Patients were tested in interictal state only. Data were analyzed in the time domain and in the time-frequency domain. Source reconstruction analysis was also performed. RESULTS: Patients with aura had higher event-related potentials amplitudes for left-sided trigeminal and left-sided olfactory stimulations, and higher neural activity for right-sided trigeminal stimulation in brain areas related to trigeminal and visual processing. Following olfactory stimulations patients with aura displayed decreased neural activity in secondary olfactory structures compared to patients without aura. Oscillations in the low frequency bands (< 8 Hz) differed between patient groups. CONCLUSIONS: Altogether this may reflect hypersensitivity to nociceptive stimuli in patients with aura relative to patients without aura. Patients with aura have a bigger deficit in engaging secondary olfactory-related structures, possibly leading to distorted attention and judgements towards odors. The cerebral overlap between trigeminal nociception and olfaction might explain these deficits.

Triptan non-response in specialized headache care: cross-sectional data from the DMKG Headache Registry.

BACKGROUND: Triptans are effective for many migraine patients, but some do not experience adequate efficacy and tolerability. The European Headache Federation (EHF) has proposed that patients with lack of efficacy and/or tolerability of ≥ 2 triptans ('triptan resistance') could be considered eligible for treatment with the novel medications from the ditan and gepant groups. There is little data on the frequency of 'triptan resistance'. METHODS: We used patient self-report data from the German Migraine and Headache Society (DMKG) Headache Registry to assess triptan response and triptan efficacy and/or tolerability failure. RESULTS: A total of 2284 adult migraine patients (females: 85.4%, age: 39.4 ± 12.8 years) were included. 42.5% (n = 970) had failed ≥ 1 triptan, 13.1% (n = 300) had failed ≥ 2 triptans (meeting the EHF definition of 'triptan resistance'), and 3.9% (n = 88) had failed ≥ 3 triptans. Compared to triptan responders (current use, no failure, n = 597), triptan non-responders had significantly more severe migraine (higher frequency (p < 0.001), intensity (p < 0.05), and disability (p < 0.001)), that further increased with the level of triptan failure. Responders rates were highest for nasal and oral zolmitriptan, oral eletriptan and subcutaneous sumatriptan. CONCLUSION: In the present setting (specialized headache care in Germany), 13.1% of the patients had failed ≥ 2 triptans. Triptan failure was associated with increased migraine severity and disability, emphasizing the importance of establishing an effective and tolerable acute migraine medication. Acute treatment optimization might include switching to one of the triptans with the highest responder rates and/or to a different acute medication class. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081).

Interictal osmophobia is associated with longer migraine disease duration.

BACKGROUND: Sensitization to sensory stimuli is an essential feature of migraine attacks. The relationship between the clinical course of migraine and increased sensitivity to olfactory stimuli has been little studied so far. METHODS: We analyzed the frequency and quality of osmophobia depending on the phase of migraine in patients with episodic and chronic migraine treated in an tertiary headache center with regard to gender, age, medical history and migraine disability assessment score (MIDAS). Standardized diagnostic questions were used for the assessment of osmophobia. RESULTS: In our cross-sectional investigation (n = 113), 38.1% of the patients showed an increased preictal hypersensitivity to odors, whereas 61.9% described ictal and 31.9% interictal hypersensitivity to odors, odor-triggered migraine was described in 30.1%. Median migraine disease duration has been statistically significantly longer in patients who suffered from interictal hypersensitivity to odors (28.5 years vs. 20 years; p = 0.012). There was a significant correlation between interictal hypersensitivity and higher age (54.50 vs. 45; p = 0.015). Patients with higher migraine disability in MIDAS experienced more frequently preictal and interictal olfactory sensitization and odor triggered migraine attacks. CONCLUSIONS: In patients with longer migraine disease duration and higher migraine-related impairment, osmophobia was more frequently observed. These results might support the hypothesis of increasing sensitization with increasing burden of migraine.

The headache registry of the German Migraine and Headache Society (DMKG): baseline data of the first 1,351 patients.

BACKGROUND: Although good treatment options exist for many headache disorders, not all patients benefit and disability continues to be large. To design strategies for improving headache care, real-world data observing standard care is necessary. Therefore, the German Migraine and Headache Society (DMKG) has established the DMKG Headache Registry. Here we present methods and baseline data. METHODS: Accredited German headache centers (clinic-based or private practice) can offer participation to their patients. Patients provide headache history, current headache load (including a mobile headache diary), medication and comorbidities and answer validated questionnaires, prior to their physician appointment. Physicians use these data as the base of their history taking, and add, change or confirm some central information. Before the next visit, patients are asked to update their data. Patients will continuously be included over the next years. RESULTS: The present analysis is based on the first 1,351 patients (1110 females, 39.6 ± 12.9 years) with a completed first visit. Most participants had a migraine diagnosis. Participants had 14.4 ± 8.5 headache days and 7.7 ± 6.1 acute medication days per month and 63.9% had a migraine disability assessment (MIDAS) grade 4 (severe disability). 93.6% used at least one acute headache medication, most frequently a triptan (60.0%) or non-opioid analgesic (58.3%). 45.0% used at least one headache preventive medication, most frequently an antidepressant (11.4%, mostly amitriptyline 8.4%) or a CGRP(receptor) antibody (9.8%). Most common causes for discontinuation of preventive medication were lack of effect (54.2%) and side effects (43.3%). CONCLUSION: The DMKG Headache Registry allows to continuously monitor headache care at German headache centers in both a cross-sectional and a longitudinal approach. TRIAL REGISTRATION: The DMKG Headache Registry is registered with the German Clinical Trials Register (DRKS 00021081 ).

Functional improvement in children and adolescents with primary headache after an interdisciplinary multimodal therapy program: the DreKiP study.

BACKGROUND: More than 2/3 of children and adolescents in Germany regularly suffer from headaches. Headache-related limitations in everyday life, school drop-out and educational impairment are common. Structured therapy programs for young headache patients are widely missing. METHODS: One hundred eleven patients with frequent migraine and/or tension type headache were treated in a 15 hour group program in afternoons, parallel with school, parents received 7 hours of therapy. At the beginning of the program (T0), 6 (T1) and 12 months (T2) after completion, data on headache related disability (PedMidas), headache frequency, intensity, and pediatric pain disability score (PPDI) were prospectively collected to investigate the effects of the therapy. RESULTS: Seventy-five patients (9-19 years, median = 14; 66.7% female) and their parents provided patient reported outcome measures showing at T1 (65 patients) and T2 (47 patients) reduced headache frequency (last 3 months headache days median T0: 30 days; T1: 18 days, reduction of median 12 days since T0; T2: 13 days, reduction of median 17 days since T0). Linear mixed models revealed significant reduction (T0/T1 p = 0,002; T0/T2 p = 0,001). Reduced headache disability has been reported at T1 and T2 (PedMidas median T0 = 30, T1 = 15, T2 = 7; p < 0,001, p < 0,001 respectively). Follow up data of a subgroup of patients 24 months after the treatment point to sustainable effects. CONCLUSIONS: The interdisciplinary multimodal headache therapy program DreKiP reduces headache frequency and headache related disability significantly 6-12 months following its completion. TRIAL REGISTRATION: DRKS00027523, retrospectively registered.

C-tactile touch perception in migraineurs - a case-control study.

BACKGROUND: Migraine is characterized by sensory hypersensitivity and habituation deficits. Slow brushing over the skin activates C-tactile nerve fibers, which mediate pleasant touch and analgesic effects in healthy subjects. As this function is altered in painful conditions, we aimed to examine whether the C-tactile processing is disrupted in migraines. METHODS: To psychophysically assess C-tactile function, we applied optimal and suboptimal C-tactile stroking stimuli on the dorsal forearm (body reference area) and the trigeminally innervated skin of 52 interictal migraineurs and 52 matched healthy controls. For habituation testing, 60 repeated C-tactile optimal stimuli were presented in both test areas. The participants rated each stimulus on a visual analogue scale by intensity, pleasantness, and painfulness. RESULTS: Regarding C-tactile function, migraineurs showed unphysiological rating patterns but no significantly different pleasantness ratings than controls. During repeated stimulation, controls showed stable pleasantness ratings while migraineurs' ratings decreased, especially in those experiencing tactile allodynia during headaches. Migraineurs taking triptans responded like controls. CONCLUSION: The C-tactile function of migraineurs is subclinically altered. Repeated C-tactile stimulation leads to altered habituation but differs from previous work by the direction of the changes. Although the pathophysiology remains unknown, causative mechanisms could include central and peripheral neuronal sensitization, tactile allodynia and hedonic stimulus attributions.

Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts.

OBJECTIVE: To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. BACKGROUND: Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. METHODS: Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. RESULTS: The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2-11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by -9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody (p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (-6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (-9.8 ± 7.6, p < 0.001) and pain intensity during attacks (-1.2 ± 2.0, numerical rating scale (NRS) [0-10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was -8.0 ± 8.4 (p = 0.004) and -9.1 ± 10.0 (p = 0.024), respectively. CONCLUSION: Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

Exposure to Odors Increases Pain Threshold in Chronic Low Back Pain Patients.

OBJECTIVES: Structured exposure to odors is an acknowledged therapy in patients with smell loss but has also been shown to be effective in depression. The latter might rely on connections between olfactory and emotional structures, suggesting possible effects of a similar approach in pain patients. Based on neuroanatomy, there are several interfaces between the "pain matrix" and olfactory system, such as the limbic system, hypothalamus, and mediodorsal thalamus. We aimed to investigate whether structured exposure to odors may impact perceived pain in patients with chronic low back pain. DESIGN: Randomized controlled parallel-group design. Subjects were tested on two occasions, at baseline and after four weeks. SETTING: Ambulatory. SUBJECTS: Forty-two patients with chronic low back pain. METHODS: For all patients, olfactory function (using the "Sniffin'Sticks" test kit), detection, and pain thresholds for cutaneous electrical stimuli (applied to the forearm) were tested at baseline and after four weeks. Twenty-eight patients exposed themselves to four odors (rose, vanilla, chocolate, peach) every two hours over a period of four weeks (training group). Control patients (N = 14) underwent no such "olfactory training" (nontraining group). RESULTS: Pain thresholds were significantly increased in patients who performed olfactory training compared with patients who did not train with odors. Detection thresholds and olfactory function remained unchanged. CONCLUSIONS: The present results indicate that regular exposure to odors increases pain thresholds in patients with chronic back pain and could be useful for general pain control in these patients. Furthermore, olfactory training in chronic pain patients might help to reduce chronification of pain by desensitization.

Epidemiology of Headache in Children and Adolescents-Another Type of Pandemia.

PURPOSE OF REVIEW: Headaches are not only responsible for restrictions in everyday life in adults. In children and adolescents, regular headaches lead also to reduced life quality and limitations in the social sphere, in school education, and in professional careers. Here, we provide an overview on the frequency of headache in children and adolescents with the aim of increasing awareness about this particular health issue. RECENT FINDINGS: Overall, headache prevalence in children and adolescents has been increasing in recent years. From various regions worldwide, data describing headache, its forms, and consequences are growing. In addition, factors frequently correlated with headache are repeatedly investigated and named: besides genetic factors, psychosocial and behavioral factors are linked to the prevalence of headache. Increasing evidence indicates that headache is underestimated as a common disorder in children and adolescents. Accordingly, too little emphasis is placed by society on its prevention and treatment. Thus, the extent of the social and health economic burden of frequent headaches in children and adolescents needs to be better illustrated, worldwide. Furthermore, the data collected in this review should support the efforts to improve outpatient therapy paths for young headache patients. Factors correlating with headache in pupils can draw our attention to unmet needs of these patients and allow physicians to derive important therapy contents from this data.

The prevalence of headache in German pupils of different ages and school types.

BACKGROUND/OBJECTIVE: Headache in pupils is underestimated and has a negative impact on learning and life. The aim of this study was to investigate headache prevalence and its collateral effects, in pupils of different ages and school types in a German city. METHODS: Anonymized questionnaires were distributed to 5419 pupils attending primary and secondary schools. Demographics, headache frequency, analgesic use, school absence and, for secondary school children, data on lifestyle were collected. RESULTS: The questionnaire was returned by 2706 children (49%), 1362 (50.3%) girls, 1344 (49.7%) boys. Of these, 36.6% indicated a frequency of 1, and 31.5% a frequency of ≥ 2 headache days per month within the last 3 months. Headache prevalence increased with school grade, age and secondary school type: 63.6%, 67.2% and 79.5% for primary school children, pupils attending 8-year and pupils attending 6-year secondary schools, respectively. With secondary school level I certificates, pupils are prepared for general professional training in 6 years. Secondary school level II results, after 8 years of training, in university entrance level II certificates, which are the precondition for university studies. Girls reported significantly more headache than boys (73% vs. 63.1%). A significant relationship has been observed between headache frequency and school absence and between headache intensity and headache frequency. Of pupils with headache at least twice a month, 48.1% reported analgesic intake. Ibuprofen (49.1%) and paracetamol (32.8%) were the most frequently used analgesics. Of those pupils with headache ≥ 2 days/month, 68.3% did not have a specific headache diagnosis. Concomitant diseases and regular drug intake, analgesic intake for another reason than headache, caffeine consumption and lack of participation in sports were positively correlated with headache. CONCLUSIONS: The majority of pupils suffer from headache at least once a month. Since frequent headache results in educational and social limitations, pupils at risk should be identified and referred to headache education programs. Efforts are needed to improve the management of juvenile headache patients.