Summary 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.
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.
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").
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To analyse predictors for relapses and number of attacks under different immunotherapies in patients with neuromyelitis optica spectrum disorder (NMOSD).
This is a retrospective cohort study ...conducted in neurology departments at 21 regional and university hospitals in Germany. Eligible participants were patients with aquaporin-4-antibody-positive or aquaporin-4-antibody-negative NMOSD. Main outcome measures were HRs from Cox proportional hazard regression models adjusted for centre effects, important prognostic factors and repeated treatment episodes.
265 treatment episodes with a mean duration of 442 days (total of 321 treatment years) in 144 patients (mean age at first attack: 40.9 years, 82.6% female, 86.1% aquaporin-4-antibody-positive) were analysed. 191 attacks occurred during any of the treatments (annual relapse rate=0.60). The most common treatments were rituximab (n=77, 111 patient-years), azathioprine (n=52, 68 patient-years), interferon-β (n=32, 61 patient-years), mitoxantrone (n=34, 32.1 patient-years) and glatiramer acetate (n=17, 10 patient-years). Azathioprine (HR=0.4, 95% CI 0.3 to 0.7, p=0.001) and rituximab (HR=0.6, 95% CI 0.4 to 1.0, p=0.034) reduced the attack risk compared with interferon-β, whereas mitoxantrone and glatiramer acetate did not. Patients who were aquaporin-4-antibody-positive had a higher risk of attacks (HR=2.5, 95% CI 1.3 to 5.1, p=0.009). Every decade of age was associated with a lower risk for attacks (HR=0.8, 95% CI 0.7 to 1.0, p=0.039). A previous attack under the same treatment tended to be predictive for further attacks (HR=1.5, 95% CI 1.0 to 2.4, p=0.065).
Age, antibody status and possibly previous attacks predict further attacks in patients treated for NMOSD. Azathioprine and rituximab are superior to interferon-β.
Some, but not all, forms of pain reduction by distraction seem to rely on descending pain inhibition.
Distraction from pain reduces pain perception, and imaging studies have suggested that this may ...at least partially be mediated by activation of descending pain inhibitory systems. Here, we used the nociceptive flexor reflex (RIII reflex) to directly quantify the effects of different distraction strategies on basal spinal nociception and its temporal summation. Twenty-seven healthy subjects participated in 3 distraction tasks (mental imagery, listening to preferred music, spatial discrimination of brush stimuli) and, in a fourth task, concentrated on the painful stimulus. Results show that all 3 distraction tasks reduced pain perception, but only the brush task also reduced the RIII reflex. The concentration-on-pain task increased both pain perception and the RIII reflex. The extent of temporal summation of pain perception and the extent of temporal summation of the RIII reflex were not affected by any of the tasks. These results suggest that some, but not all, forms of pain reduction by distraction rely on descending pain inhibition. In addition, pain reduction by distraction seems to preferentially affect mechanisms of basal nociceptive transmission, not of temporal summation.
Objective
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.
Methods
Effects of UVB light were analyzed in a murine model of CNS autoimmunity (experimental autoimmune encephalomyelitis). Additionally, patients with relapsing–remitting MS were treated with narrowband UVB phototherapy. Immunomodulatory effects were examined in skin biopsies, serum samples, and immune cells of the peripheral blood.
Results
Regulatory T cells (Tregs), which are induced locally in the skin‐draining lymph nodes in response to UVB exposure, connect the cutaneous immune response to CNS immunity by migration to the sites of inflammation (blood, spleen, CNS). Here, they attenuate the inflammatory response and ameliorate disease symptoms. Treg‐inducing tolerogenic dendritic cells (DCs) were further necessary for induction of this systemic immune regulation by UVB radiation, because ablation of Langerhans cells abolished the UVB‐induced phenotype. MS patients treated with UVB phototherapy showed an increase in induced Tregs and tolerogenic DCs accompanied by the downregulation of the T‐cell effector cytokine interleukin 21. The treatment further induced elevated serum levels of vitamin D.
Interpretation
Local UVB radiation of the skin influences systemic immune reactions and attenuates systemic autoimmunity via the induction of skin‐derived tolerogenic DCs and Tregs. Our data could have implications for the understanding or therapeutic modulation of environmental factors that influence immune tolerance. Ann Neurol 2014;75:739–758
To further elucidate retinal findings and retinal vessel changes in Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients by means of high ...resolution retinal imaging.
28 eyes of fourteen CADASIL patients and an equal number of control subjects underwent confocal scanning laser ophthalmoscopy (cSLO), spectral-domain optical coherence tomography (SD-OCT), retinal nerve fibre layer (RNFL) measurements, fluorescein and indocyanine angiography. Three vessel measurement techniques were applied: RNFL thickness, a semiautomatic software tool based on cSLO images and manual vessel outlining based on SD-OCT.
Mean age of patients was 56.2 ± 11.6 years. Arteriovenous nicking was present in 22 (78.6%) eyes and venous dilation in 24 (85.7%) eyes. Retinal volume and choroidal volume were 8.77 ± 0.46 mm(3) and 8.83 ± 2.24 mm(3). RNFL measurements showed a global increase of 105.2 µm (
98.4 µm; p = 0.015). Based on semi-automatic cSLO measurements, maximum diameters of arteries and veins were 102.5 µm (106.0 µm; p = 0.21) and 128.6 µm (124.4 µm; p = 0.27) respectively. Manual SD-OCT measurements revealed significantly increased mean arterial 138.7 µm (125.4 µm; p<0.001) and venous 160.0 µm (146.9; p = 0.003) outer diameters as well as mean arterial 27.4 µm (19.2 µm; p<0.001) and venous 18.3 µm (15.7 µm; p<0.001) wall thicknesses in CADASIL patients.
The findings reflect current knowledge on pathophysiologic changes in vessel morphology in CADASIL patients. SD-OCT may serve as a complementary tool to diagnose and follow-up patients suffering from cerebral small-vessel diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous ...top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist.
This study reviewed labeling criteria originally developed for color fundus photography (CFP) images.
The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree.
They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The syndrome of the sinking skin flap (SSSF) with delayed sensorimotor deficits after craniectomy is not well known and often neglected. Among various postulated causes, there is evidence that ...disturbed brain perfusion may be related to the observed symptoms, and that cranioplasty reliably alleviates these symptoms. We report a case of sinking skin flap syndrome (SSFS) with recovery from neurological sensorimotor deficits after cranioplasty correlated with pre- and postsurgical MR brain perfusion studies.
A 42-year-old woman presented with slowly progressive sensorimotor paresis of her left arm after decompressive extensive craniectomy due to subarachnoid hemorrhage four months ago. Her right cranium showed a "sinking skin flap". After cranioplastic repair of her skull defect, the patient fully recovered from her symptoms. Before cranioplasty, reduced brain perfusion in the right central cortical region was observed in MR-perfusion images. After cranioplasty, a marked increase in brain perfusion was observed which correlated with objective clinical recovery.
There is increasing evidence that impaired blood flow is responsible for delayed motor deficits in patients with sinking skin flap syndrome in the area of compressed brain regions. Symptoms should be evaluated by brain perfusion imaging complementing surgical decision-making.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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