The impact of COPD on polyneuropathy: results from the German COPD cohort COSYCONET.

BACKGROUND: Peripheral neuropathy is a common comorbidity in COPD. We aimed to investigate associations between alterations commonly found in COPD and peripheral neuropathy, with particular emphasize on the distinction between direct and indirect effects. METHODS: We used visit 4 data of the COPD cohort COSYCONET, which included indicators of polyneuropathy (repeated tuning fork and monofilament testing), excluding patients with diabetes a/o increased HbA1c. These indicators were analysed for the association with COPD characteristics, including lung function, blood gases, 6-min walk distance (6-MWD), timed-up-and-go-test (TUG), exacerbation risk according to GOLD, C-reactive protein (CRP), and ankle-brachial index (ABI). Based on the results of conventional regression analyses adjusted for age, BMI, packyears and gender, we utilized structural equation modelling (SEM) to quantify the network of direct and indirect relationships between parameters. RESULTS: 606 patients were eligible for analysis. The indices of polyneuropathy were highly correlated with each other and related to base excess (BE), ABI and TUG. ABI was linked to neuropathy and 6-MWD, exacerbations depended on FEV1, 6-MWD and CRP. The associations could be summarized into a SEM comprising polyneuropathy as a latent variable (PNP) with three measured indicator variables. Importantly, PNP was directly dependent on ABI and particularly on BE. When also including patients with diabetes and/or elevated values of HbA1c (n = 742) the SEM remained virtually the same. CONCLUSION: We identified BE and ABI as major determinants of peripheral neuropathy in patients with COPD. All other associations, particularly those with lung function and physical capacity, were indirect. These findings underline the importance of alterations of the micromilieu in COPD, in particular the degree of metabolic compensation and vascular status.

[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.

[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.

[A view on the life course of the most prevalent headache disorders. Spontaneous course, remission, and persistence]. / Life-course-Betrachtung der häufigsten Kopfschmerzformen. Spontanverlauf, Remission und Persistenz.

Symptoms and signs of primary headache disorders can change during one's lifetime. Moreover, the impact and the frequency of attacks can fluctuate in an individual patient over time. Before puberty, boys and girls are equally affected; after puberty most headache disorders predominate in women. The treatment of primary headache disorders always has to take into consideration the severity and the frequency of headache attacks as well as the relevant comorbidities. Prophylactic headache treatment can modulate the course of primary headache disorders. Specific prophylactic treatment is the most important instrument for avoiding headache chronification caused by medication overuse. While primary headache disorders tend to improve in elderly patients, secondary headache disorders peak in elderly people. They are often a symptom of oncologic diseases, vascular disorders, or are linked to side effects of drugs that are prescribed more frequently in the elderly. The treatment and the prognosis of secondary headache disorders always depend on the underlying disease.

[Consensus paper of the German Migraine and Headache Society on the structure of headache care facilities in Germany]. / Konsensuspapier der Deutschen Migräne- und Kopfschmerzgesellschaft zur Struktur von Kopfschmerzzentren und Kopfschmerzschwerpunktpraxen in Deutschland.

This consensus paper introduces a classification of headache care facilities on behalf of the German Migraine and Headache Society. This classification is based on the recommendations of the International Association for the Study of Pain (IASP) and the European Headache Federation (EHF) and was adapted to reflect the specific situation of headache care in Germany. It defines three levels of headache care: headache practitioner (level 1), headache outpatient clinic (level 2) and headache centers (level 3). The objective of the publication is to define and establish reliable criteria in the field of headache care in Germany.

[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.

Quantitative sensory testing in cluster headache: increased sensory thresholds.

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.

Opioidergic changes in the pineal gland and hypothalamus in cluster headache: a ligand PET study.

Using PET with the opioidergic ligand [11C]diprenorphine, the authors demonstrate decreased tracer binding in the pineal gland of cluster headache patients vs healthy volunteers. Opioid receptor availability in the hypothalamus and cingulate cortex depended on the duration of the headache disorder. Therefore, the pathophysiology of cluster headache may relate to opioidergic dysfunction in circuitries generating the biologic clock.

[Motor cortical representation in patients with complex regional pain syndrome: a TMS study]. / Motorkortikale Repräsentation beim komplex regionalen Schmerzsyndrom Typ I: Eine TMS-Studie.

In a group of patients with short- and long-term (chronic) duration of complex regional pain syndrome type I (CRPS I) motor cortical representation was determined, using a transcranial magnetic stimulation (TMS) mapping method. This was done, starting with suprathreshold intensities at the location of the largest MEP amplitude, mapping systematically in all directions. Patients were compared to a group of healthy subjects. In both patient groups we found significantly larger motor cortical representation for the unaffected hand muscles compared to the affected side. This asymmetry was absent in healthy subjects. Such motor cortical representation asymmetry can be considered an effect of altered sensomotor cortical representation. On the other hand, one must also consider the increased use of the unaffected hand and the presence of pain as cortical influencing variables. The real cause must remain speculative at this time.

[Sleeping behaviour and headache attacks in cases of primary headache. Possible pathological mechanisms]. / Schlafverhalten und Kopfschmerzattacken bei primären Kopfschmerzen. Mögliche Pathomechanismen.

Headache is connected with sleep quality, e.g. hypnic headache and chronic paroxysmal headache attacks occur preferentially during REM sleep; this is possibly also true for cluster headache and migraine. REM sleep is typically characterized by the occurrence of ponto-geniculo-occipital spikes (PGOs). These PGOs should be able to trigger cortical spreading depression (CSD), which, although often clinically silent, is assumed to be an essential element of a migraine attack and possibly also of other forms of headache. CSDs are considered a correlate of migraine aura. They could lead to the secondary activation of trigeminovascular afferences, which would then induce a headache. Interestingly, illnesses that are comorbid with migraine cause an increase in the amount of REM sleep; conversely, various drugs administered prophylactically for these illnesses reduce the quantity of REM sleep.