[Treatment of chronic migraine with botulinum neurotoxin A : Expert recommendations of the German Migraine and Headache Society]. / Therapie der chronischen Migräne mit Botulinumneurotoxin A : Expertenempfehlung der Deutschen Migräne- und Kopfschmerzgesellschaft.

BACKGROUND: Injection of botulinum neurotoxin A (BoNT-A) according to the PREEMPT (Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy) paradigm has been approved for the treatment of refractory chronic migraine in Germany in 2011. OBJECTIVE: The practical application raises some questions, such as the choice of dose and injection intervals during the course of the treatment, and the appropriate time point for discontinuation of BoNT-A treatment. MATERIAL AND METHODS: Taking into account the existing literature, the German Migraine and Headache Society (Deutsche Migräne- und Kopfschmerzgesellschaft, DMKG) gives recommendations for the treatment of chronic migraine with BoNT-A. RESULTS: Treatment is usually started with a dose of 155 U BoNT-A. During the first year of treatment, 3­month injection intervals are recommended. Goal of the treatment is an improvement of migraine by ≥30%. If needed, dose escalation up to 195 U can be used to reach this goal. If improvement by ≥30% is not reached after the third injection cycle, the treatment is usually considered to be insufficiently efficient and discontinuation is recommended. If a stable success is reached during the first year of treatment, prolongation of injection intervals to 4 months can be considered. If success continues to be stable for at least two 4­month intervals, discontinuation of BoNT-A treatment can be tried. CONCLUSION: The literature on these points is insufficient for recommendations at the guideline level. The present recommendations are based on an expert consensus of the DMKG for the structured approach to the treatment of chronic migraine with BoNT-A.

[Therapy of migranes]. / Therapie der Migräne.

In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory drugs and triptans can be utilized. The efficacy of acute attack treatment is relevant to prevent migraine chronification. For prophylactic treatment ß­blockers, tricyclic antidepressants, flunarizine, antiepileptics and onabotulinumtoxin A are available. There is evidence that some other substances (e. g. sartans) are also efficacious in this regard. Furthermore, nondrug approaches are essential in migraine therapy. Early education and prophylactic treatment of patients at risk may prevent from medication overuse headache. Noninvasive neuromodulatory approaches as supraorbital or vagal nerve stimulation are emerging methods for prophylactic treatment. Ongoing clinical trials investigate an oral calcitonin gene-related peptide (CGRP) antagonist for acute treatment and several prophylactic monoclonal CGRP or CGRP receptor-antibodies regarding safety, side effects and efficacy as new therapeutic options.

[Relaxation techniques and behavioural therapy for the treatment of migraine : Guidelines from the German Migraine and Headache Society]. / Entspannungsverfahren und verhaltenstherapeutische Interventionen zur Behandlung der Migräne : Leitlinie der Deutschen Migräne- und Kopfschmerzgesellschaft.

Besides pharmacological and interventional possibilities nonpharmacological options, deriving from behavioural approaches may be helpful in the treatment of migraine. Already consulting a patient reduces frequency of attacks. Relaxation (especially progressive muscle relaxation), endurance sports, and biofeedback as well as cognitive behavioural therapy are effective in treatment of migraine. The combination of these treatment options also with pharmacological treatment increase the positive effects.

Resonant Rydberg Dressing of Alkaline-Earth Atoms via Electromagnetically Induced Transparency.

We develop an approach to generate finite-range atomic interactions via optical Rydberg-state excitation and study the underlying excitation dynamics in theory and experiment. In contrast to previous work, the proposed scheme is based on resonant optical driving and the establishment of a dark state under conditions of electromagnetically induced transparency (EIT). Analyzing the driven dissipative dynamics of the atomic gas, we show that the interplay between coherent light coupling, radiative decay, and strong Rydberg-Rydberg atom interactions leads to the emergence of sizable effective interactions while providing remarkably long coherence times. The latter are studied experimentally in a cold gas of strontium atoms for which the proposed scheme is most efficient. Our measured atom loss is in agreement with the theoretical prediction based on binary effective interactions between the driven atoms.

[Botulinum toxin type A in headache treatment : Established and experimental indications]. / Botulinumtoxin A in der Kopfschmerztherapie : Bewährte und experimentelle Indikationen.

In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities.

[Pain - a neglected neurological issue]. / Schmerz - ein vernachlässigtes neurologisches Thema.

Chronic pain represents a great challenge; according to epidemiological data increasing numbers of patients should be expected. Based on recent advances, a better understanding of the pathophysiology of chronic pain has been achieved and neurologists have made a major contribution to this understanding. Chronic pain is accompanied by substantial maladaptive plastic alterations in both the peripheral and central nervous systems; therefore, neurological knowledge is of paramount importance for pain therapists but this contrasts with the current treatment situation of pain patients in Germany. There are basically too few departments and practices undertaking treatment, and neurologists are an exception in most pain centers. Furthermore, due to economic reasons neurological hospitals are currently experiencing a dearth of inpatients suffering from chronic pain. Diagnostic and/or treatment procedures for neurological pain entities (e.g. headaches or neuropathic pain) are insufficiently represented in the German diagnosis-related groups (DRG) reimbursement system and the obstacles for an efficient pain therapy in neurological practices are too high. Finally, there are too few academic positions for pain medicine in neurological hospitals; therefore, career opportunities for motivated young neurologists with an interest in pain are lacking. In order to address the unmet therapeutic needs of patients with chronic pain there is a high demand for (i) establishment of departments for neurological pain medicine, (ii) modification of the German DRG system and (iii) education of young neurologists with expertise in pain. Pain medicine in particular should be especially appealing to neurologists .

[Headache. Current status of research and treatment]. / Kopfschmerz. Aktueller Stand der Forschung und Versorgung.

The starting point for German headache research and clinical education was the engagement of D. Soyka in the 1970s, which enabled the foundation of the German Headache Society (DMKG) on 28 June 1979 and, some years later, the founding congress of the International Headache Society (IHS) in Munich 1982. As a result of these activities, in 1988 the first international classification of headache disorders was published. This classification was one of the major milestones in the development of basic as well as clinical headache research. In the following years, epidemiological studies all over the world showed a 1-year prevalence for headache of approximately 60%, making headaches one of the most frequent medical complaints. Basic research showed an involvement of serotonergic mechanisms in migraine pain and triptans were one of the first drugs designed to influence these mechanisms. Functional brain imaging studies in migraine patients further showed a cyclic modulation of the activity of brainstem areas independent of the current pain state. Various research groups were involved in the clarification of the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache. A specific development in the German headache scene is the establishment of integrated headache centers and reflects the primarily multimodal treatment approach in Germany which contrasts with the settings in other countries. These successful developments are increasingly being undermined by the fact that the low financial support of headache research, for example, by the German science council is causing a decreasing interest in headache research, with the consequence that the clinical education of students as well as young medical doctors shows increasing deficits. The consequence for the future will be a deficit in the clinical care of the population.

[Headache: patient education as part of a multidisciplinary treatment. Are there reliable results?]. / Kopfschmerzen - Patientenschulung als Baustein multimodaler Therapieprogramme. Was ist gesichert?

Patient education is an important part of successful headache therapy. Patient education can enhance self-efficacy and influence the locus of control. Motivation and adherence to nonpharmacological therapy (aerobic endurance training and relaxation training) as well as pharmacological therapy may be improved by headache-specific patient education. Patients with specific knowledge of their headache disorder and headache treatment may be more self-confident and successful in handling their disease. In moderately affected headache patients, education alone may result in improvement, whereas education as part of a multidisciplinary treatment is superior in severely affected and chronic patients. All components of a multidisciplinary treatment program should be harmonized toward a comprehensive concept. Patients should take an active part in the therapy.

[The role of opioids in the treatment of primary headache disorders]. / Stellenwert von Opioiden in der Therapie von primären Kopfschmerzerkrankungen.

There is no sufficient evidence for opioids in the acute treatment of primary headache disorders. Controlled clinical trials using triptans as comparator are missing. Data show high frequent headache recurrence, typical side effects of opioids, increased risk of chronification, and development of addiction in primary headache patients treated with opioids. Chronic headache patients with opioid therapy often experience lengthy withdrawal treatment. On the basis of the current scientific data, opioids should be avoided in acute and prophylactic treatment of primary headache disorders.

[Update on trigeminal autonomic cephalalgia]. / Neues zu trigeminoautonomen Kopfschmerzen.

Cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome) are classified under trigeminal autonomic cephalalgia (TAC). The proposed revision of the international classification of headache disorders (ICDH-3 beta) adds hemicrania continua to this diagnostic group. Moreover, diagnostic criteria of the other TACs were modified and are characterized by persistent headache or headache attacks accompanied by cranial autonomic symptoms. The main difference between the various TACs is the duration of attacks. Differentiation is important because different pharmacological strategies are necessary.

[Therapy and care of patients with chronic migraine: expert recommendations of the German Migraine and Headache Society/German Society for Neurology as well as the Austrian Headache Society/Swiss Headache Society]. / Therapie und Versorgung bei chronischer Migräne : Expertenempfehlung der Deutschen Migräne- und Kopfschmerzgesellschaft/Deutsche Gesellschaft für Neurologie sowie der Österreichischen Kopfschmerzgesellschaft/Schweizerischen Kopfwehgesellschaft.

Chronic migraine (CM) was first defined in the second edition of the International Headache Society (IHS) classification in 2004. The definition currently used (IHS 2006) requires the patient to have headache on more than 15 days/month for longer than 3 months and a migraine headache on at least 8 of these monthly headache days and that there is no medication overuse. In daily practice the majority of the patients with CM also report medication overuse but it is difficult to determine whether the use is the cause or the consequence of CM. Most the patients also have other comorbidities, such as depression, anxiety and chronic pain at other locations. Therapy has to take this complexity into consideration and is generally multimodal with behavioral therapy, aerobic training and pharmacotherapy. The use of analgesics should be limited to fewer than 15 days per month and use of triptans to fewer than 10 days per month. Drug treatment should be started with topiramate, the drug with the best scientific evidence. If there is no benefit, onabotulinum toxin A (155-195 Units) should be used. There is also some limited evidence that valproic acid and amitriptyline might be beneficial. Neuromodulation by stimulation of the greater occipital nerve or vagal nerve is being tested in studies and is so far an experimental procedure only.

[Neurostimulation for treatment of headaches]. / Neurostimulation zur Behandlung von Kopfschmerzen.

Only a small portion of patients with primary headaches are refractory to treatment concerning relief of headache episodes and prophylactic therapy of headaches. New methods of central and peripheral neurostimulation have been developed for these patients during the last few years and experience was mostly gained in small case series. The following overview gives a description of new stimulation methods, such as deep brain stimulation, occipital nerve stimulation, vagal nerve stimulation, neurostimulation of the sphenopalatine ganglion and transcranial magnetic stimulation.

C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.

Mutations in C19orf12 have been recently identified as the molecular genetic cause of a subtype of neurodegeneration with brain iron accumulation (NBIA). Given the mitochondrial localization of the gene product the new NBIA subtype was designated mitochondrial membrane protein-associated neurodegeneration. Frequent features in the patients described so far included extrapyramidal signs and pyramidal tract involvement. Here, we report three C19orf12-mutant patients from two families presenting with predominant upper and lower motor neuron dysfunction mimicking amyotrophic lateral sclerosis with juvenile onset. While extrapyramidal signs were absent, all patients showed neuropsychological abnormalities with disinhibited or impulsive behavior. Optic atrophy was present in the simplex case. T2-weighted cranial MRI showed hypointensities suggestive of iron accumulation in the globi pallidi and the midbrain in all patients. Sequence analysis of C19orf12 revealed a novel mutation, p.Gly66del, compound heterozygous with known mutations in all patients. These patients highlight that C19orf12 defects should be considered as a differential diagnosis in patients with juvenile onset motor neuron diseases. Patients have to be examined carefully for neuropsychological abnormalities, optic neuropathy, and signs of brain iron accumulation in MRI.

Differences in clinical characteristics and frequency of accompanying migraine features in episodic and chronic cluster headache.

INTRODUCTION: Data on clinical differences between episodic (eCH) and chronic cluster headache (cCH) and accompanying migraine features are limited. METHODS: History and clinical features of 209 consecutive cluster headache patients (144 eCH, 65 cCH; male:female ratio 3.4 : 1) were obtained in a tertiary headache centre by face-to-face interviews. Relationship between occurrence of accompanying symptoms, pain intensity, comorbid migraine, and circannual and circadian rhythmicity was analysed. RESULTS: 99.5% of patients reported a minimum of one ipsilateral cranial autonomic symptom (CAS); 80% showed at least three CAS. A seasonal rhythmicity was observed in both eCH and cCH. A comorbid headache disorder occurred in 25%. No significant difference was detected between patients with comorbid migraine and without regarding occurrence of phonophobia, photophobia or nausea during cluster attacks. Patients with comorbid migraine reported allodynia significantly (p = 0.022) more often during cluster attacks than patients without comorbid migraine. CONCLUSION: Occurrence of CAS and attack frequency, as well as periodic patterns of attacks, are relatively uniform in eCH and cCH. Multiple CAS are not related to pain intensity. Allodynia during cluster attacks is a frequent symptom. The unexpectedly high rate of accompanying migrainous features during cluster attacks cannot be explained by comorbid migraine.

Lateralized central facilitation of trigeminal nociception in cluster headache.

OBJECTIVE: To investigate whether central facilitation of trigeminal pain processing is part of the pathophysiology of cluster headache (CH). METHODS: Sixty-six patients with CH (18 episodic CH inside bout, 28 episodic CH outside bout, 20 chronic CH) according to the International Classification of Headache Disorders-II classification, as well as 30 healthy controls, were investigated in a case-control study using simultaneous recordings of the nociceptive blink reflex (nBR) and pain-related evoked potentials (PREP) following nociceptive electrical stimulation on both sides of the forehead (V1). RESULTS: nBR latency ratio (headache side/nonheadache side) was decreased in all CH patients independent from CH subtype compared with healthy controls indicating central facilitation at brainstem level. Area under the curve ratio was increased in patients with episodic CH inside bout only. PREP showed decreased N2 latency ratio in patients with chronic CH indicating central facilitation at supraspinal (thalamic or cortical) level. CONCLUSIONS: Asymmetric facilitation of trigeminal nociceptive processing predominantly on brainstem level was detected in patients with CH. This alteration is most pronounced in the acute pain phase of the disease, but appears to persist in remission periods. Only chronic CH patients show additional changes of PREP prompting to supraspinal changes of pain processing related to the chronic state of disease in regard to neuronal plasticity, which exceeds changes observed in episodic CH.

Classifying orofacial pains: a new proposal of taxonomy based on ontology.

We propose a new taxonomy model based on ontological principles for disorders that manifest themselves through the symptom of persistent orofacial pain and are commonly seen in clinical practice and difficult to manage. Consensus meeting of eight experts from various geographic areas representing different perspectives (orofacial pain, headache, oral medicine and ontology) as an initial step towards improving the taxonomy. Ontological principles were introduced, reviewed and applied during the consensus building process. Diagnostic criteria for persistent dento-alveolar pain disorder (PDAP) were formulated as an example to be used to model the taxonomical structure of all orofacial pain conditions. These criteria have the advantage of being (i) anatomically defined, (ii) in accordance with other classification systems for the provision of clinical care, (iii) descriptive and succinct, (iv) easy to adapt for applications in varying settings, (v) scalable and (vi) transferable for the description of pain disorders in other orofacial regions of interest. Limitations are that the criteria introduce new terminology, do not have widespread acceptance and have yet to be tested. These results were presented to the greater conference membership and were unanimously accepted. Consensus for the diagnostic criteria of PDAP was established within this working group. This is an initial first step towards developing a coherent taxonomy for orofacial pain disorders, which is needed to improve clinical research and care.

[Facial and eye pain - Neurological differential diagnosis]. / Augenschmerzen aus neurologischer Sicht.

Head and facial pain are common in neurological practice and the pain often arises in the orbit or is referred into the eye. This is due to the autonomic innervation of the eye and orbit. There are acute and chronic pain syndromes. This review gives an overview of the differential diagnosis and treatment. Idiopathic headache syndromes, such as migraine and cluster headache are the most frequent and are often debilitating conditions. Trigemino-autonomic cephalalgias (SUNCT and SUNA) have to be taken into account, as well as trigeminal neuralgia. Trigemino-autonomic headache after eye operations can be puzzling and often responds well to triptans. Every new facial pain not fitting these categories must be considered symptomatic and a thorough investigation is mandatory including magnetic resonance imaging. Infiltrative and neoplastic conditions frequently lead to orbital pain. As a differential diagnosis Tolosa-Hunt syndrome and Raeder syndrome are inflammatory conditions sometimes mimicking neoplasms. Infections, such as herpes zoster ophthalmicus are extremely painful and require rapid therapy. It is important to consider carotid artery dissection as a cause for acute eye and neck pain in conjunction with Horner's syndrome and bear in mind that vascular oculomotor palsy is often painful. All of the above named conditions should be diagnosed by a neurologist with special experience in pain syndromes and many require an interdisciplinary approach.