Strong and aversive cold processing and pain facilitation in fibromyalgia patients relates to augmented thermal grill illusion.

The thermal grill illusion (TGI) is assumed to result from crosstalk between the thermoreceptive and nociceptive pathways. To elucidate this further, we compared 40 female fibromyalgia patients to 20 healthy women in an exploratory cross-sectional study. Sensations (cold, warm/heat, unpleasantness, pain and burning) evoked by 20 °C, 40 °C and alternating 20 °C/40 °C (TGI) and somatosensory profiles according to standardized quantitative sensory testing (QST) were assessed on the palm of the dominant hand. Compared to healthy controls, fibromyalgia patients reported stronger thermal grill-evoked cold, warm, unpleasantness and pain as well as stronger and more aversive 20 °C- and 40 °C-evoked sensations. They showed a loss in warm, mechanical and vibration detection, a gain in thermal pain thresholds and higher temporal summation (TS). Among QST parameters higher TS in fibromyalgia patients was most consistently associated with an augmented TGI. Independently, an increased TGI was linked to cold (20 °C) but less to warm (40 °C) perception. In fibromyalgia patients all thermal grill-evoked sensations were positively related to a higher 20 °C-evoked cold sensation and/or 20 °C-evoked unpleasantness. In conclusion, the TGI appears to be driven mainly by the cold-input. Aversive cold processing and central pain facilitation in fibromyalgia patients seem to independently augment the activation of the pain pathway.

Pain is not the major determinant of quality of life in fibromyalgia: results from a retrospective "real world" data analysis of fibromyalgia patients.

OBJECTIVE: To identify correlates of quality of life (QoL) measured with the Quality of Life Scale (QOLS) in participants of a multidisciplinary day hospital treatment program for fibromyalgia (FM). METHODS: In this cross-sectional, observational study, "real world" data from 480 FM patients including socio-demographics, pain variables and questionnaires such as the SF-36, Beck Depression Inventory (BDI), Multiphasic Pain Inventory (MPI), SCL-90-R and others were categorized according to the components (body structure and function, activities and participation, personal factors, environmental factors) of the International Classification of Functioning (ICF). For every ICF component, a linear regression analysis with QOLS as the dependent variable was computed. A final comprehensive model was calculated on the basis of the results of the five independent analyses. RESULTS: The following variables could be identified as main correlates for QoL in FM, explaining 56% of the variance of the QOLS (subscale/questionnaire and standardized beta in parenthesis): depression (- 0.22), pain-related interference with everyday life (- 0.19), general activity (0.13), general health perception (0.11), punishing response from others (- 0.11), work status (- 0.10), vitality (- 0.11) and cognitive difficulties (- 0.12). Pain intensity or frequency was not an independent correlate. CONCLUSIONS: More than 50% of QoL variance could be explained by distinct self-reported variables with neither pain intensity nor pain frequency playing a major role. Therefore, FM treatment should not primarily concentrate on pain but should address multiple factors within multidisciplinary therapy.

The Importance of Daily Activity for Reducing Fibromyalgia Symptoms: A Retrospective "Real World" Data Comparison of two Multimodal Treatment Programs.

OBJECTIVES: This study aims to evaluate the effectiveness of two multidisciplinary fibromyalgia programs with different intensities. MATERIALS AND METHODS: In this retrospective real-world comparison of patient data, pre- and post-program datasets of Short Form 36 (SF36) and Fibromyalgia Impact Questionnaire (FIQ) were obtained from a total of 210 female patients in two fibromyalgia multidisciplinary day hospital programs including one intensive program with daily treatments summing up to 20 treatment days during four weeks (P20, n=70) versus a less intensive program with 12 treatment days during four weeks (P12, n=140). RESULTS: Multiple subscales of SF36 and FIQ were improved in the pre-post comparison in both groups. In the comparison between the two groups, a statistically significantly higher improvement was found in the P20 group compared to the P12 group for the FIQ subscales of stiffness (p=0.001) and the number of days during which the patient felt "good" (p=0.007). CONCLUSION: An intensive program of daily treatments and activity seems to be more effective in reducing fibromyalgia-associated stiffness and improving the number of days during which patients feel good than a less intensive program.

[Undetected coccyx fracture in a woman with fibromyalgia]. / Unentdeckte Os-coccygis-Fraktur bei Patientin mit Fibromyalgiesyndrom.

This article presents the case of a 46-year-old woman with fibromyalgia with an undetected fracture of the coccyx. The heterogeneity of the symptoms of patients suffering from fibromyalgia including chronic widespread pain, vegetative and functional disorders, mental and physical exhaustion as well as sleep disorders can cause accidentally undetected comorbidities, especially if these are rare and predominantly present with pain as the main symptom. In the present case the reason for symptoms was detected only after 14 months of ineffective therapies and diagnostic procedures. The coccygeal pain was eliminated through a coccygectomy as ultima ratio. It should be nevertheless emphasized that patients with fibromyalgia suffer from a central pain-processing disorder. Indications for operative treatment must be very carefully considered. Surgery should only be considered in consultation with the patient and after failed conservative therapy.

Recommendations of the working group of the Anatomische Gesellschaft on reduction of formaldehyde exposure in anatomical curricula and institutes.

The practice of human and veterinary medicine is based on the science of anatomy and dissection courses are still irreplaceable in the teaching of anatomy. Embalming is required to preserve body donors, for which process formaldehyde (FA) is the most frequently used and well characterized biocidal substance. Since January 2016, a new occupational exposure limit (OEL) for FA of 0.37mg/m3 issued by the European Committee on Hazardous Substances is obligatory since FA has been classified as a human 1B carcinogen. The anatomical institutes in the German-speaking region are called upon to consolidate efforts to reduce use of FA in anatomical curricula and body donations. As a result, the Anatomische Gesellschaft (AG) has formed a "Working Group for Reduction of Formaldehyde Exposure in Dissection Courses" tasked with discussion and recommendation of measures to reduce FA. Based on the assessment of the Working Group, the AG has issued an official opinion to the effect that, at this point in time, embalming of body donors without FA completely is not feasible. Therefore, a combination of approaches are to be used to reduce FA exposure, including technical and structural (architectural) adaptations, modification of protocols for fixation and preservation as well as organizational measures. One structural measure considered unavoidable is the integration of air supply and exhaust of individual dissecting tables into the ventilation system of the anatomy building. To embalm human body donors, intra-arterial perfusion fixation with up to 4% FA and a total fluid volume of 150mL/kg body weight will suffice. For animals where body weights and biology of bodies vary widely (i.e. special needs of fixation for ruminants, large animals as horses) perfusion fixation with up to 4% FA and a quantity of fixative solution of 10-15% of the body weight may be required. Preservation of body donors in storage (immersion) can be done with 40% ethanol or in a full bath preservation containing up to 2% FA. Corpse humidification in the dissecting room is possible with 2% phenoxyethanol, in each case without FA. In veterinary anatomy, microbiological burden is often higher and therefore might lead to a need of FA in long-time storage. Compliance with the current OEL in all institutes would appear to be feasible in combination with various organizational measures.

Electromyogram Biofeedback in Patients with Fibromyalgia: A Randomized Controlled Trial.

BACKGROUND/AIM: Electromyogram (EMG) biofeedback is used in chronic pain but its effectiveness in patients with fibromyalgia is unclear. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of EMG biofeedback in patients with fibromyalgia. METHODS: Patients were recruited from a waiting list at the fibromyalgia day care clinic at the University Hospital Munich. The study intervention comprised 14 sessions of EMG biofeedback during 8 weeks in addition to the usual care. The control intervention was usual care alone. Assessments were scheduled before intervention (T0), after intervention (T1), and 3 months after the end of intervention (T2). The primary outcome measure was the Fibromyalgia Impact Questionnaire (FIQ). Secondary outcome measures included additional patient-oriented measures and the pressure-pain threshold in the trapezius muscles. Effectiveness was analyzed by significance tests and standardized effect sizes (ES). RESULTS: 36 patients completed the study. EMG biofeedback did not improve the health status (FIQ, T1: p = 0.95, ES = 0.02; T2: p = 0.52, ES = 0.26). Among the secondary outcome measures, only the pressure-pain threshold at the trapezius muscles showed an improvement in the intervention group (T1: p = 0.016, ES = 0.84). CONCLUSION: EMG biofeedback showed no health status improvement in patients with fibromyalgia.

Attentional bias toward negative information in patients with fibromyalgia syndrome.

OBJECTIVE: In addition to central nervous sensitization, affect dysregulation constitutes an important factor in the pathogenesis of fibromyalgia syndrome (FMS). The present study is concerned with emotional influences on information processing in FMS. The hypothesis of attentional bias, i.e., selective processing of negatively connoted stimuli, was tested. METHODS: Twenty-seven female FMS patients and 34 healthy women undertook an emotional modification of the Stroop task. Subjects had to decide whether the colors of positive, negative, and neutral adjectives accorded with color words presented in black. Attentional bias was defined as delay in color naming of emotional words relative to neutral words. Affective and anxiety disorders, pain severity, as well as medication were considered as possible factors mediating the expected interference. RESULTS: Patients showed marked attentional bias, manifested in a greater response delay due to negative words compared with the control group. Among the clinical features, pain severity was most closely associated with the extent of the interference. While depression played only a subordinate role, anxiety and medication were without effect. CONCLUSIONS: The study provides evidence of emotionally driven selective attention in FMS. Attentional bias to negative information may play an important role in the vicious circle between negative affective state and pain augmentation. In the management of FMS pain, strategies aiming at conscious direction of attention may be helpful, e.g., imagery techniques or mindfulness training.

Recognition of facially expressed emotions in patients with fibromyalgia syndrome.

The study investigated the ability to identify facially expressed emotions in fibromyalgia syndrome (FMS) and its association with clinical parameters. Thirty-five FMS patients and 35 healthy controls accomplished a face recognition task. Additionally, pain severity, alexithymia, depression, anxiety, psychiatric co-morbidity and medication use were assessed. The patients displayed reduced task performance in terms of more misclassifications of emotional expressions than controls. Pain severity, alexithymia, depression and anxiety were inversely related to recognition performance, with pain severity accounting for the largest portion of test score variance. Psychiatric co-morbidity and medication had no impact on performance. The study documented impaired emotion recognition in FMS, which may contribute to the interpersonal difficulties and reduced social functioning related to this condition. As potential mechanisms mediating the occurrence of the deficits, altered affective processing due to interoceptive impairment as well as interference of central nervous nociceptive activity with cognitive and emotional processing are discussed.

Posttraumatic stress disorder in fibromyalgia syndrome: prevalence, temporal relationship between posttraumatic stress and fibromyalgia symptoms, and impact on clinical outcome.

A link between fibromyalgia syndrome (FMS) and posttraumatic stress disorder (PTSD) has been suggested because both conditions share some similar symptoms. The temporal relationships between traumatic experiences and the onset of PTSD and FMS symptoms have not been studied until now. All consecutive FMS patients in 8 study centres of different specialties were assessed from February 1 to July 31, 2012. Data on duration of chronic widespread pain (CWP) were based on patients' self-reports. Potential traumatic experiences and year of most burdensome traumatic experience were assessed by the trauma list of the Munich Composite International Diagnostic Interview. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV symptom criteria by the Posttraumatic Diagnostic Scale. Age- and sex-matched persons of a general population sample were selected for controls. Three hundred ninety-five of 529 patients screened for eligibility were analysed (93.9% women, mean age 52.3 years, mean duration since chronic widespread pain 12.8 years); 45.3% of FMS patients and 3.0% of population controls met the criteria for PTSD. Most burdensome traumatic experience and PTSD symptoms antedated the onset of CWP in 66.5% of patients. In 29.5% of patients, most burdensome traumatic experience and PTSD symptoms followed the onset of CWP. In 4.0% of patients' most burdensome traumatic experience, PTSD and FMS symptoms occurred in the same year. FMS and PTSD are linked in several ways: PTSD is a potential risk factor of FMS and vice versa. FMS and PTSD are comorbid conditions because they are associated with common antecedent traumatic experiences.

Patient-related predictors of treatment satisfaction of patients with fibromyalgia syndrome: results of a cross-sectional survey.

OBJECTIVES: This study aimed to determine patient-related predictors of treatment satisfaction in fibromyalgia syndrome (FMS)-patients. METHODS: In a cross-sectional survey, participants with self-reported diagnosis of FMS were recruited by FMS-self help organisations and clinical institutions. The patients answered demographic and medical questionnaires, the Fibromyalgia Survey Questionnaire (FSQ) including the Somatic Severity Score (SSS) and Widespread Pain Index (WPI), the Patient Health Questionnaire (PHQ-4), and rated their treatment satisfaction on an 11-point Likert scale. The impact of patient-related variables (age, gender, partnership, educational level, time since onset of pain, time since FMS-diagnosis, health status since diagnosis, membership in FMS self-help organisations, polysymptomatic distress, anxiety and depression) and types of treatment on treatment satisfaction were tested by a multiple regression analysis. RESULTS: The study sample (n=1651 patients) was composed mainly of middle-aged women with a long disease history, and 83.9% fulfilled the American College of Rheumatology diagnostic criteria of 2010. There was considerate variety regarding treatment satisfaction in FMS-patients, 14.8% reported no, 31.7% low, 40.8% moderate and 12.7% high satisfaction. Higher satisfaction was predicted by longer time since FMS diagnosis (p=0.03), improved health status since FMS-diagnosis (p<0.0001), lower depression score (p=0.005) and higher amount of active therapies (p<0.0001). Other sociodemographic (age, gender etc.) and disease-related variables (polysymptomatic distress intensity) did not influence treatment satisfaction. CONCLUSIONS: The results of the study illustrate the influence of patient-related factors on treatment satisfaction. Treating comorbid depression and enabling patients to actively cope with the disease might prove successful in improving treatment satisfaction of FMS-patients.

Health-resource use and costs associated with fibromyalgia in France, Germany, and the United States.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder characterized by widespread, persistent pain. Prospective and retrospective studies have demonstrated substantial health-care costs associated with FM in a number of countries. This study evaluated and compared health-resource use (HRU) and associated costs related to FM in routine clinical practice across the US, France, and Germany. METHODS: Two separate, cross-sectional, observational studies of subjects with FM were conducted: one in the US and one in France and Germany. HRU related to prescription medication, physician office visits, diagnostic tests, and hospitalizations was abstracted from chart review; patient out-of-pocket costs and lost productivity were collected via subject self-report. Costs were assigned to HRU based on standard algorithms. Direct and indirect costs were evaluated and compared by simple linear regression. RESULTS: A total of 442 subjects (203 US, 70 France, 169 Germany) with FM were analyzed. The mean (standard deviation) age in the US, France, and Germany was 47.9 (10.9), 51.2 (9.5), and 49.2 (9.8), respectively (P = 0.085). Most subjects were female (95% US, 83% France, 80% Germany) (P < 0.001). Adjusted annual direct costs per subject for FM were significantly higher in the US ($7087) than in France ($481, P < 0.001) or Germany ($2417, P < 0.001). Adjusted mean annual indirect costs per subject for FM were lower in the US ($6431) than in France ($8718) or Germany ($10,001), but represented a significant proportion of total costs in all countries. CONCLUSION: The significant HRU and costs associated with FM in the US, France, and Germany documented in this study highlight the substantial global economic burden of FM. Indirect costs represented a significant proportion of the total costs, particularly in Europe. Comparisons between the three countries show differences in HRU, with significantly higher direct costs in the US compared with France and Germany.

Implicit memory function in fibromyalgia syndrome.

The study investigated implicit memory function in fibromyalgia syndrome (FMS) and its association with clinical parameters. Implicit memory refers to the influence of past experience on current behavior without conscious awareness of these experiences. Eighteen FMS patients and 25 healthy individuals accomplished a word-stem completion task. As possible factors mediating the expected impairment, pain severity, emotional disorders, and medication were taken into account. The patients displayed markedly reduced task performance and higher levels of depression and anxiety. Among the clinical features, pain severity was most closely associated with performance, whereas depression, anxiety, and medication showed only a minor impact. The study documented reduced implicit memory function in FMS. In contrast to former findings on impaired performance of FMS patients on classical memory tests, lower implicit memory function cannot be ascribed to motivational deficits. Instead, the aberrances may relate to functional inference between central nervous nociceptive activity and cognitive processing.

Cerebral blood flow dynamics during pain processing in patients with fibromyalgia syndrome.

OBJECTIVES: Increased cerebral blood flow during processing of acute pain has repeatedly been observed in fibromyalgia syndrome. The study investigated the time dynamics of the pain-related hemodynamic response in fibromyalgia using transcranial Doppler sonography. METHODS: In 25 women with fibromyalgia and 25 healthy participants, blood flow velocities in the anterior and middle cerebral arteries of both hemispheres were recorded, while heat stimuli of 45°C were applied to their forearms. Thermal pain threshold and subjective pain experience during stimulation were assessed, and the participants completed the McGill Pain Inventory, Beck Depression Inventory, and State-Trait Anxiety Inventory. RESULTS: The early component of the blood flow response in both anterior cerebral arteries, that is, the steep flow increase during the initial stimulation period, was more pronounced in the patients than in the controls (mean [standard deviation] = 1.28% [1.85%] versus 0.24% [1.58%], p = .04). The patients showed lower pain threshold (p = .018), stronger sensory and affective pain experience (p < .001), and increased values on all questionnaire scales (all p values < .001). Although higher scores on each of the scales were associated with a stronger early blood flow response (r values ranging from 0.17 to 0.36), clinical pain severity proved to be the best predictor (ß = .33, p = .02). CONCLUSIONS: The increased blood flow response in the anterior cerebral arteries reflects hyperactivity of medial structures of the neuromatrix of nociception, structures involved in the processing of affective and cognitive aspects of pain. Aberrances in cerebral blood flow related to fibromyalgia and its clinical characteristics become particularly apparent in the enhancement of the initial component of the hemodynamic response.

Validation of the Fibromyalgia Survey Questionnaire within a cross-sectional survey.

The Fibromyalgia Survey Questionnaire (FSQ) assesses the key symptoms of fibromyalgia syndrome. The FSQ can be administrated in survey research and settings where the use of interviews to evaluate the number of pain sites and extent of somatic symptom intensity and tender point examination would be difficult. We validated the FSQ in a cross-sectional survey with FMS patients. In a cross-sectional survey, participants with physician diagnosis of FMS were recruited by FMS-self help organisations and nine clinical institutions of different levels of care. Participants answered the FSQ (composed by the Widespread Pain Index [WPI] and the Somatic Severity Score [SSS]) assessing the Fibromyalgia Survey Diagnostic Criteria (FSDC) and the Patient Health Questionnaire PHQ 4. American College of Rheumatology 1990 classification criteria were assessed in a subgroup of participants. 1,651 persons diagnosed with FMS were included into analysis. The acceptance of the FSQ-items ranged between 78.9 to 98.1% completed items. The internal consistency of the items of the SSS ranged between 0.75-0.82. 85.5% of the study participants met the FSDC. The concordance rate of the FSDC and ACR 1990 criteria was 72.7% in a subsample of 128 patients. The Pearson correlation of the SSS with the PHQ 4 depression score was 0.52 (p<0.0001) and with the PHQ anxiety score was 0.51 (p<0.0001) (convergent validity). 64/202 (31.7%) of the participants not meeting the FSDC criteria and 152/1283 (11.8%) of the participants meeting the FSDC criteria reported an improvement (slightly too very much better) in their health status since FMS-diagnosis (Chi(2) = 55, p<0.0001) (discriminant validity). The study demonstrated the feasibility of the FSQ in a cross-sectional survey with FMS-patients. The reliability, convergent and discriminant validity of the FSQ were good. Further validation studies of the FSQ in clinical and general population settings are necessary.

The German fibromyalgia consumer reports - a cross-sectional survey.

BACKGROUND: Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe. METHODS: The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. RESULTS: 1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems. CONCLUSION: The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines.

Behavioral and neuronal investigations of hypervigilance in patients with fibromyalgia syndrome.

Painful stimuli are of utmost behavioral relevance and thereby affect attentional resources. In health, variable effects of pain on attention have been observed, indicating alerting as well as distracting effects of pain. In the human brain, these effects are closely related to modulations of neuronal gamma oscillations. As hypervigilance as an abnormal increase of attention to external stimuli has been implicated in chronic pain states, we assumed both attentional performance and pain-induced gamma oscillations to be altered in patients with fibromyalgia syndrome (FMS). We recorded electroencephalography from healthy subjects (n = 22) and patients with FMS (n = 19) during an attention demanding visual reaction time task. In 50% of the trials we applied painful laser stimuli. The results of self-assessment questionnaires confirm that patients with FMS consider themselves hypervigilant towards pain as compared to healthy controls. However, the experimental findings indicate that the effects of painful stimuli on attentional performance and neuronal gamma oscillations do not differ between patients and healthy subjects. We further found a significant correlation between the pain-induced modulation of visual gamma oscillations and the pain-induced modulation of reaction times. This relationship did not differ between groups either. These findings confirm a close relationship between gamma oscillations and the variable attentional effects of pain, which appear to be comparable in health and disease. Thus, our results do not provide evidence for a behavioral or neuronal manifestation of hypervigilance in patients with FMS.

An international, randomized, double-blind, placebo-controlled, phase III trial of pregabalin monotherapy in treatment of patients with fibromyalgia.

OBJECTIVE: To evaluate the efficacy and safety of pregabalin monotherapy versus placebo for symptomatic pain relief and improvement of patient global assessment in patients with fibromyalgia (FM) enrolled from countries outside the United States. METHODS: This international, multicenter, double-blind, placebo-controlled trial randomly assigned 747 patients with FM to placebo or 300, 450, or 600 mg/day pregabalin twice daily for 14 weeks. Primary efficacy measures were endpoint mean pain scores and Patient Global Impression of Change (PGIC). Secondary outcomes included assessments of sleep and function. RESULTS: Patients in the 450 mg/day pregabalin group showed significant improvements versus placebo in endpoint mean pain score (-0.56; p = 0.0132), PGIC (73% improved vs 56% placebo; p = 0.0017), and function [Fibromyalgia Impact Questionnaire (FIQ) total score -5.85; p = 0.0012]. PGIC was also significant for 600 mg/day pregabalin (69% improved; p = 0.0227). Results for these endpoints were nonsignificant for pregabalin at 300 mg/day and for pain and FIQ score at 600 mg/day. Early onset of pain relief was seen, with separation from placebo detected by Week 1 in all pregabalin groups. All pregabalin doses demonstrated superiority to placebo on the Medical Outcomes Study-Sleep Scale Sleep Disturbance subscale and the Sleep Quality diary. Dizziness and somnolence were the most frequently reported adverse events. CONCLUSION: Pregabalin demonstrated modest efficacy in pain, global assessment, and function in FM at 450 mg/day, and improved sleep across all dose levels, but it did not provide consistent evidence of benefit at 300 and 600 mg/day in this study. Pregabalin was generally well tolerated for the treatment of FM. (Clinical trial registry NCT00333866).

Impact of fibromyalgia severity on health economic costs: results from a European cross-sectional study.

BACKGROUND: Fibromyalgia (FM) is a chronic disorder characterized by persistent and widespread pain, often accompanied with fatigue, sleep disturbance and other symptoms. FM affects a population mostly of a productive age and is thus associated with significant lost productivity and disability, in addition to healthcare costs for medications and physician office visits. While other studies have examined FM costs in Europe, few, if any, have examined cost by FM severity level. OBJECTIVE: The objective of this study was to examine health resource utilization (HRU) and costs associated with FM in routine clinical practice in France and Germany across disease severity levels. METHODS: A total of 299 patients with FM, previously diagnosed by a rheumatologist, were recruited from physician offices in France and Germany during routine visits. Subjects completed questions about their pain, health-related quality of life, treatment satisfaction, productivity and FM-related out-of-pocket expenses; site staff recorded clinical, treatment and HRU information for the previous 3 months based on a review of medical records. FM severity was defined using subjects' Fibromyalgia Impact Questionnaire (FIQ) total scores. Annual costs from a societal perspective were calculated in €, year 2008 values, and included direct costs (e.g. physician office visits, medications, out-of-pocket expenses) and indirect costs (e.g. missed days of work and lost productivity). The mean annual costs were calculated based on 3-month data. RESULTS: Subjects were reported to have a mean (SD) of 2.9 (1.9) physician office visits in France and 4.9 (3.2) visits in Germany over the past 3 months, corresponding to an average of 11.6 and 19.6 visits a year, respectively. A total of 91% of subjects were receiving prescription medication for their FM. French subjects reported a lower use of anti-inflammatories (39% of subjects) and a higher use of other analgesics (59% of subjects) than German subjects (67% and 34%, respectively). Subjects in full- or part-time employment reported missing a mean (SD) of 2.7 (6.0) days of work due to FM in France and 2.1 (3.8) days in Germany over the last 4 weeks (corresponding to 32.4 and 25.2 days of work missed due to FM per year in France and Germany, respectively). In France, total costs were €7900 (direct €910, indirect €6990). In Germany, total costs were €7256 (direct €1765, indirect €5491). A trend of higher total costs was seen as FM severity increased; however, the results were significant (p = 0.003) only for Germany. CONCLUSIONS: FM imposes a significant economic burden on society. Consistent with other studies, FM subjects were found to have substantial costs, over 75% of which were driven by indirect costs from lost productivity. These costs increased as FM severity increased, resulting in a more than 200% difference in cost between mild and severe FM. Overall FM costs were similar between France and Germany; although lost productivity accounted for a higher proportion of costs in France.

Precision of navigated stereotactic probe implantation into the brainstem.

OBJECT: The indications for stereotactic biopsies or implantation of probes for local chemotherapy in diffuse brainstem tumors have recently come under debate. The quality of performing these procedures significantly depends on the precision of the probes' placement in the brainstem. The authors evaluated the precision of brainstem probe positioning using a navigated frameless stereotactic system in an experimental setting. METHODS: Using the VarioGuide stereotactic system, 33 probes were placed into a specially designed model filled with agarose. In a second experimental series, 8 anatomical specimens were implanted with a total of 32 catheters into the pontine brainstem using either a suboccipital or a precoronal entry point. Before intervention in both experimental settings, a thin-sliced CT scan for planning was obtained and fused to volumetric T1-weighted MR imaging data. After the probe positioning procedures, another CT scan and an MR image were obtained to compare the course of the catheters versus the planned trajectory. The deviation between the planned and the actual locations was measured to evaluate the precision of the navigated intervention. RESULTS: Using the VarioGuide system, mean total target deviations of 2.8 +/- 1.2 mm on CT scanning and 3.1 +/- 1.2 mm on MR imaging were detected with a mean catheter length of 151 +/- 6.1 mm in the agarose model. The catheter placement in the anatomical specimens revealed mean total deviations of 1.95 +/- 0.6 mm on CT scanning and 1.8 +/- 0.7 mm on MR imaging for the suboccipital approach and a mean catheter length of 59.5 +/- 4.1 mm. For the precoronal approach, deviations of 2.2 +/- 1.2 mm on CT scanning and 2.1 +/- 1.1 mm on MR imaging were measured (mean catheter length 85.9 +/- 4.7 mm). CONCLUSIONS: The system-based deviation of frameless stereotaxy using the VarioGuide system reveals good probe placement in deep-seated locations such as the brainstem. Therefore, the authors believe that the system can be accurately used to conduct biopsies and place probes in patients with brainstem lesions.