Martin Marziniak

Clinical features, pathophysiology, and treatment of medication-overuse headache

Medication-overuse headache (MOH) is a chronic headache disorder defined by the International Headache Society as a headache induced by the overuse of analgesics, triptans, or other acute headache compounds. The population-based prevalence of MOH is 0.7% to 1.7%. Most patients with MOH have migraine as their primary headache and overuse triptans or simple analgesics. The pathophysiology of MOH is still unknown. As well as psychological mechanisms such as operant conditioning, changes in endocrinological homoeostasis and neurophysiological changes have been observed in patients with MOH. Recently, a genetic susceptibility has been postulated. In most cases, treatment of MOH consists of abrupt withdrawal therapy and then initiation of an appropriate preventive drug therapy. There is no clear evidence on which method of withdrawal therapy is the most efficacious. Withdrawal symptoms can be treated with steroids; however, not all data support this concept. As MOH can severely affect the quality of life of patients, it needs to be recognised early to enable appropriate treatment to be initiated.

The incidence and prevalence of cluster headache: a meta‐analysis of population‐based studies

Cluster headache is a trigemino-autonomic cephalgia with a low prevalence. Several population-based studies on its prevalence and incidence have been performed, but with different methodology resulting in different figures. We analysed all available population-based epidemiological studies on cluster headache and compared the data in a meta-analysis. The pooled data showed a lifetime prevalence of 124 per 100 000 [confidence interval (CI) 101, 151] and a 1-year prevalence of 53 per 100 000 (CI 26, 95). The overall sex ratio was 4.3 (male to female), it was higher in chronic cluster headache (15.0) compared with episodic cluster headache (3.8). The ratio of episodic vs. chronic cluster headache was 6.0. Our analysis revealed a relatively stable lifetime prevalence, which suggests that about one in 1000 people suffers from cluster headache, the prevalence being independent of the region of the population study. The sex ratio (male to female) is higher than published in several patient-based epidemiological studies.

Pain sensitivity can be assessed by self-rating: Development and validation of the Pain Sensitivity Questionnaire

ABSTRACT Experimental determination of pain sensitivity has received increasing attention because of emerging clinical applications (including prediction of postoperative pain and treatment response) and scientific implications (e.g. it has been proposed that above‐average pain sensitivity is a risk factor for the development of chronic pain disorders). However, the use of experimental pain sensitivity assessment on a broad scale is hampered by its requirements on time, equipment and human resources and the fact that it is painful for the tested subject. Alternatives to experimental pain testing are currently lacking. Here we developed a self‐rating instrument for the assessment of pain sensitivity, the Pain Sensitivity Questionnaire (PSQ) that is based on pain intensity ratings of daily life situations and takes 5–10 min to complete. Adequate reliability of the PSQ was confirmed in 354 subjects. In a validation study comprising 47 healthy subjects, the results of comprehensive experimental pain testing, including different modalities (heat, cold, pressure, and pinprick) and different measures (pain thresholds, pain intensity ratings), were compared to the results of the PSQ. PSQ scores were significantly correlated to experimental pain intensity ratings (r = 0.56, p < 0.001) but not to pain thresholds (r = 0.03). Prediction of experimental pain intensity ratings by the PSQ was better than by pain‐associated psychological factors (pain catastrophizing, depression, anxiety). This shows that the PSQ may be a simple alternative to experimental pain intensity rating procedures in healthy subjects and makes the PSQ a highly promising tool for clinical and experimental pain research.

Natalizumab Use During the Third Trimester of Pregnancy

IMPORTANCE Natalizumab reduces multiple sclerosis relapses very effectively; however, severe disease activity may return once natalizumab treatment is withdrawn, as recommended during pregnancy. Sometimes restarting natalizumab treatment may be the best option for the mother, but the consequences for the infant are unknown. Except for a few single case reports, to our knowledge, comprehensive data about third-trimester natalizumab exposure are scant. OBSERVATIONS In a case series of 12 women with 13 pregnancies and highly active multiple sclerosis who were treated with natalizumab during their third trimester of pregnancy, we assessed the clinical and laboratory effects on the newborns. We observed mild to moderate hematologic alterations in 10 of 13 infants including thrombocytopenia and anemia. In a subsample of 5 mother-child pairs, we analyzed natalizumab levels in the umbilical cord blood. Natalizumab was detectable in all 5 newborns. CONCLUSION AND RELEVANCE Natalizumab can be a therapeutic option in patients with highly active multiple sclerosis during pregnancy. We recommend that a pediatrician be available at the time of delivery to evaluate for potential complications of anemia and thrombocytopenia in newborns exposed to natalizumab during the third trimester.

Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity

Environmental conditions (eg, latitude) play a critical role in the susceptibility and severity of many autoimmune disorders, including multiple sclerosis (MS). Here, we investigated the mechanisms underlying the beneficial effects of immune regulatory processes induced in the skin by moderate ultraviolet B (UVB) radiation on central nervous system (CNS) autoimmunity.

Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses.

Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks.

Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

Background Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. Methods Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test (“Trier Social Stress Test”). Results Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. Conclusions Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.

Placebo efficacy in childhood and adolescence migraine: an analysis of double-blind and placebo-controlled studies

Studies on the treatment of migraine in children and adolescents are rare and difficult to design. In particular, the high placebo response in some trials makes it difficult to prove efficacy of a verum drug. We analysed all available placebo-controlled trials on acute and on prophylactic migraine treatment in children and adolescents with respect to different placebo rates (pain free and pain relief at 2 h; rate of responders with ≥ 50% attack frequency decrease). We identified eight crossover and 11 parallel group trials on acute treatment. The placebo response rates were considerably lower in crossover trials than in parallel group trials (19.2% vs. 27.1% for pain free after 2 h and 39.4% vs. 56.9% for pain relief after 2 h). In the 10 prophylactic trials included in this analysis, only a small trend towards a lower placebo rate in crossover trials could be observed. Further significant factors associated with a lower placebo rate in childhood and adolescence trials on the acute treatment of migraine were single-centre (vs. multicentre) trials and small sample size. Age and sex were not associated with the placebo response. Our study suggests that parallel group trials on the acute treatment of migraine in children and adolescents show a very low therapeutic gain due to a high placebo rate. The verum response rates, however, are very similar to those seen in adulthood trials. In conclusion, trial designs on the acute and prophylactic treatment of migraine in children and adolescents should consider the specific findings of this analysis in order to exhibit a higher probability of showing significant differences between placebo and verum drug.

Validation of the pain sensitivity questionnaire in chronic pain patients.

Summary Pain Sensitivity Questionnaire scores correlate with results of experimental pain testing and reflect generalized enhancement of pain perception in chronic pain patients. ABSTRACT Recently, a self‐rating measure for pain perception based on imagined painful daily life situations, the Pain Sensitivity Questionnaire (PSQ), has been developed and shown to correlate with experimentally obtained pain intensity ratings in healthy subjects. Here, we assessed the validity of the PSQ for investigation of general pain perception (ie, pain perception outside the site of clinical pain) in chronic pain patients. PSQ scores were obtained in 134 chronic pain patients and compared to those of 185 healthy control subjects. In a subgroup of 46 chronic pain patients, we performed experimental pain testing outside the clinical pain site, including different modalities (heat, cold, pressure, and pinprick) and different measures (pain thresholds, pain intensity ratings). Results show that PSQ scores were significantly correlated with both experimental pain intensity ratings (Pearson’s r = 0.71, P < .001) and experimental pain thresholds (r = −0.52, P < .001). In addition, chronic pain patients exhibited significantly elevated PSQ scores as compared to healthy controls, consistent with the generalized increase of experimentally determined pain perception that has repeatedly been reported in chronic pain patients. These results demonstrate that the PSQ constitutes a valid self‐rating measure of pain perception outside the clinical pain site in chronic pain patients and might serve as an alternative to experimental assessment of pain perception outside the clinical pain site in situations where experimental pain testing is not feasible.

Brachioradial pruritus as a result of cervical spine pathology: The results of a magnetic resonance tomography study

BACKGROUND Brachioradial pruritus (BRP) describes a rare form of itching occurring at the dorsolateral part of the forearms. Recent case reports suggest that BRP may be attributed to cervical lesions or spine neoplasms. OBJECTIVE We sought to determine the incidence of cervical spine changes in BRP and to correlate the localization of spinal lesions with the dermatomal presence of pruritus. METHODS Magnetic resonance tomography (MRT) of the cervical spinal cord, a chest x-ray, and a skin biopsy were performed in 41 patients (28 female, 13 male; 59.0 ± 10.6 years) with BRP. Patients completed an itch questionnaire (NeuroDerm Questionnaire) that included a dermatome chart and the Northwick Park Neck Pain Questionnaire. RESULTS The patients marked the locations C5 (90.2%) and C6 (100%) on the dermatome chart. All patients had detectable MRT changes. In 80.5% of the patients, stenosis of the intervertebral foramen or protrusions of the cervical disk led to nerve compression. The location of the nerve compression lesions correlated significantly with the dermatomal localization of the pruritus (Spearman correlation coefficient 0.893; P < .01). No spinal neoplasm was observed, and 19.5% of the patients had degenerative changes without significant correlation to the dermatomal localization of pruritus. LIMITATION No healthy control group without pruritus was investigated. CONCLUSION BRP may result from cervical nerve compression, and rarely, it may also stem from degenerative changes. Our findings suggest that even slight cervical changes detected on MRT may alter itch afferents and lead to BRP. Spinal cord tumors are rare and should be ruled out by a cervical spine MRT.