Actigraphic assessment of periodic leg movements in patients with restless legs syndrome.

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non-responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs-like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age-matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work-up. We examined 12 responders to dopaminergic treatment and 12 non-responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non-responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post-hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non-responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non-responders. PLMI day-to-day variability did not differ between responders and non-responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine-responsive restless legs syndrome.

Vitamin D and central hypersensitivity in patients with chronic pain.

BACKGROUND Low vitamin D is implicated in various chronic pain conditions with, however, inconclusive findings. Vitamin D might play an important role in mechanisms being involved in central processing of evoked pain stimuli but less so for spontaneous clinical pain. OBJECTIVE This study aims to examine the relation between low serum levels of 25-hydroxyvitamin D3 (25-OH D) and mechanical pain sensitivity. DESIGN We studied 174 patients (mean age 48 years, 53% women) with chronic pain. A standardized pain provocation test was applied, and pain intensity was rated on a numerical analogue scale (0-10). The widespread pain index and symptom severity score (including fatigue, waking unrefreshed, and cognitive symptoms) following the 2010 American College of Rheumatology preliminary diagnostic criteria for fibromyalgia were also assessed. Serum 25-OH D levels were measured with a chemiluminescent immunoassay. RESULTS Vitamin deficiency (25-OH D < 50 nmol/L) was present in 71% of chronic pain patients; another 21% had insufficient vitamin D (25-OH D < 75 nmol/L). After adjustment for demographic and clinical variables, there was a mean ± standard error of the mean increase in pain intensity of 0.61 ± 0.25 for each 25 nmol/L decrease in 25-OH D (P = 0.011). Lower 25-OH D levels were also related to greater symptom severity (r = -0.21, P = 0.008) but not to the widespread pain index (P = 0.83) and fibromyalgia (P = 0.51). CONCLUSIONS The findings suggest a role of low vitamin D levels for heightened central sensitivity, particularly augmented pain processing upon mechanical stimulation in chronic pain patients. Vitamin D seems comparably less important for self-reports of spontaneous chronic pain.

What does local tenderness say about the origin of pain? An investigation of cervical zygapophysial joint pain

BACKGROUND: Mechanical pain sensitivity is assessed in every patient with pain, either by palpation or by quantitative pressure algometry. Despite widespread use, no studies have formally addressed the usefulness of this practice for the identification of the source of pain. We tested the hypothesis that assessing mechanical pain sensitivity distinguishes damaged from healthy cervical zygapophysial (facet) joints. METHODS: Thirty-three patients with chronic unilateral neck pain were studied. Pressure pain thresholds (PPTs) were assessed bilaterally at all cervical zygapophysial joints. The diagnosis of zygapophysial joint pain was made by selective nerve blocks. Primary analysis was the comparison of the PPT between symptomatic and contralateral asymptomatic joints. The secondary end points were as follows: differences in PPT between affected and asymptomatic joints of the same side of patients with zygapophysial joint pain; differences in PPT at the painful side between patients with and without zygapophysial joint pain; and sensitivity and specificity of PPT for 2 different cutoffs (difference in PPT between affected and contralateral side by 1 and 30 kPa, meaning that the test was considered positive if the difference in PPT between painful and contralateral side was negative by at least 1 and 30 kPa, respectively). The PPT of patients was also compared with the PPT of 12 pain-free subjects. RESULTS: Zygapophysial joint pain was present in 14 patients. In these cases, the difference in mean PPT between affected and contralateral side (primary analysis) was −6.2 kPa (95% confidence interval: −19.5 to 7.2, P = 0.34). In addition, the secondary analyses yielded no statistically significant differences. For the cutoff of 1 kPa, sensitivity and specificity of PPT were 67% and 16%, respectively, resulting in a positive likelihood ratio of 0.79 and a diagnostic confidence of 38%. When the cutoff of 30 kPa was considered, the sensitivity decreased to only 13%, whereas the specificity increased to 95%, resulting in a positive likelihood ratio of 2.53 and a diagnostic confidence of 67%. The PPT was significantly lower in patients than in pain-free subjects (P < 0.001). CONCLUSIONS: Assessing mechanical pain sensitivity is not diagnostic for cervical zygapophysial joint pain. The finding should stimulate further research into a diagnostic tool that is widely used in the clinical examination of patients with pain.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.

[Eosinophilia, diarrhea and asthma in a young woman]

We present the case of a young woman that was diagnosed with Churg-Strauss syndrome. The classical as well as the atypical symptoms, signs and findings are discussed in the context of clinically relevant differential diagnoses. The diagnostic criteria and the relevant aspects of pathogenesis, clinical course and treatment are reviewed. In addition, the similarities and differences with respect to the other idiopathic interstitial eosinophilic pneumopathies are described.

Neurokinin-2 receptor levels correlate with intensity, frequency, and duration of pain in chronic pancreatitis

OBJECTIVE: Generation and maintenance of pain in chronic pancreatitis (CP) have been shown to be partially attributable to neuroimmune interactions, which involve neuropeptides such as substance P (SP). So far, expression of SP receptors NK-2R, NK-3R, the SP-encoding gene preprotachykinin A (PPT-A), and the SP degradation enzyme neutral endopeptidase (NEP) and their relation to pain in CP have not been determined. METHODS: Tissue samples from patients with CP (n = 25) and from healthy donors (n = 20) were analyzed for PPT-A, NK-2R, NK-3R, and NEP expression using quantitative RT-PCR. NEP protein levels were examined by immunoblot analysis and its localization was determined using immunohistochemistry. A scoring system was used to grade the extent of fibrosis on hematoxylin and eosin- and Masson-Trichrome-stained sections. Messenger RNA levels and the extent of pain were analyzed for correlations. RESULTS: In CP tissues, NK-2R and PPT-A expression was increased, whereas NK-3R and NEP mRNA levels were comparable with normal pancreas. Overexpression of NK-2R was related to the intensity, frequency, and duration of pain in CP patients. NK-1R and NEP expression was significantly related to the extent of fibrosis. CONCLUSIONS: Expression of NK-2R and PPT-A is increased in CP and is associated with pain. Failure to up-regulate NEP may contribute to the disruption of the neuropeptides loop balance in CP and thus may exacerbate the severe pain syndrome.

Allergic bronchopulmonary aspergillosis: the hunt for a diagnostic serological marker in cystic fibrosis patients

The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis patients remains challenging, mainly owing to overlapping symptoms of the underlying lung disease with clinical symptoms of ABPA. In addition, a varying mixture of diagnostic criteria, including clinical status, radiological findings and immunological measurements, has led to confusion and differing recommendations. In order to help simplify as well as standardize the diagnostic criteria for ABPA, different serological markers have been evaluated in the last 20 years and their usefulness has been assessed in many clinical studies. This review presents current diagnostic criteria of ABPA, with a special focus on serum markers supporting the diagnosis and explains why the hunt for a serological marker for ABPA is still ongoing.

Neoplastic invasion of laryngeal cartilage: reassessment of criteria for diagnosis at MR imaging

PURPOSE: To evaluate whether proposed diagnostic criteria applied to magnetic resonance (MR) images of patients with laryngeal and hypopharyngeal carcinoma may be used to distinguish neoplastic from inflammatory involvement of the laryngeal cartilages. MATERIALS AND METHODS: The radiologic and histopathologic data in 121 consecutive patients with primary squamous cell carcinoma of the larynx (n = 63) or hypopharynx (n = 58) who underwent MR imaging before laryngectomy formed the basis of this retrospective study. Patient consent for retrospective chart review was waived by the institutional review board. All laryngectomy specimens were processed with a dedicated histopathologic whole-organ slice technique. MR images were evaluated by two readers according to established ("old") and proposed ("new") diagnostic criteria on the basis of the signal intensity behavior of cartilage on T2-weighted images and contrast material-enhanced T1-weighted images compared with that of the adjacent tumor. Specifically, with the new criteria, T2-weighted or postcontrast T1-weighted cartilage signal intensity greater than that of the adjacent tumor was considered to indicate inflammation, and signal intensity similar to that of the adjacent tumor was considered to indicate neoplastic invasion. The results of the MR image interpretation were compared with the histologic reference standard. RESULTS: The area under the receiver operating characteristic curve for the new criteria (0.94) was nominally but significantly larger than that for the old criteria (0.92) (P = .01). Overall specificity was significantly improved (82% for new vs 74% for old criteria, P < .001) and was greatest for the thyroid cartilage (75% for new vs 54% for old criteria, P < .001) with the new criteria. The sensitivities of the established and the proposed criteria were identical. CONCLUSION: The proposed MR imaging criteria enable improved differentiation of neoplastic cartilage invasion from peritumoral inflammation.

Decision making in patients with acute abdominal pain at a university and at a rural hospital: Does the value of abdominal sonography differ?

Introduction and objectives Abdominal sonography is regarded as a quick and effective diagnostic tool for acute abdominal pain in emergency medicine. However, final diagnosis is usually based on a combination of various clinical examinations and radiography. The role of sonography in the decision making process at a hospital with advanced imaging capabilities versus a hospital with limited imaging capabilities but more experienced clinicians is unclear. The aim of this pilot study was to assess the relative importance of sonography and its influence on the clinical management of acute abdominal pain, at two Swiss hospitals, a university hospital (UH) and a rural hospital (RH). Methods 161 patients were prospectively examined clinically. Blood tests and sonography were performed in all patients. Patients younger than 18 years and patients with trauma were excluded. In both hospitals, the diagnosis before and after ultrasonography was registered in a protocol. Certainty of the diagnosis was expressed on a scale from 0% to 100%. The decision processes used to manage patients before and after they underwent sonography were compared. The diagnosis at discharge was compared to the diagnosis 2 – 6 weeks thereafter. Results Sensitivity, specificity and accuracy of sonography were high: 94%, 88% and 91%, respectively. At the UH, management after sonography changed in only 14% of cases, compared to 27% at the RH. Additional tests were more frequently added at the UH (30%) than at the RH (18%), but had no influence on the decision making process-whether to operate or not. At the UH, the diagnosis was missed in one (1%) patient, but in three (5%) patients at the RH. No significant difference was found between the two hospitals in frequency of management changes due to sonography or in the correctness of the diagnosis. Conclusion Knowing that sonography has high sensitivity, specificity and accuracy in the diagnosis of acute abdominal pain, one would assume it would be an important diagnostic tool, particularly at the RH, where tests/imaging studies are rare. However, our pilot study indicates that sonography provides important diagnostic information in only a minority of patients with acute abdominal pain. Sonography was more important at the rural hospital than at the university hospital. Further costly examinations are generally ordered for verification, but these additional tests change the final treatment plan in very few patients.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Therapeutic modalities influencing neuropathic pain in hand surgery patients

The treatment of neuropathic pain challenges not only doctors but also hand therapists, since a majority of patients don't experience a significant pain relief despite systemic pain treatment. Early diagnosis of neuropathic pain and a therapeutic concept is crucial to meet the individual needs of the patient. The complexity of a pain syndrome calls for a multidisciplinary approach using patient education, pharmacological and non-pharmacological therapies, such as graded motor imagery or somatosensory rehabilitation, behavioral therapy and physical measures. The evidence of the above mentioned therapies with regards to neuropathic pain is not yet completely established. Possible reasons are the lack of complete understanding of the pain causing mechanisms and the fact of treating the symptoms rather than the cause.

Safe refeeding management of anorexia nervosa inpatients: an evidence-based protocol.

OBJECTIVE Anorexia nervosa is associated with several serious medical complications related to malnutrition, severe weight loss, and low levels of micronutrients. The refeeding phase of these high-risk patients bears a further threat to health and potentially fatal complications. The objective of this study was to examine complications due to refeeding of patients with anorexia nervosa, as well as their mortality rate after the implementation of guidelines from the European Society of Clinical Nutrition and Metabolism. METHODS We analyzed retrospective, observational data of a consecutive, unselected anorexia nervosa cohort during a 5-y period. The sample consisted of 65 inpatients, 14 were admitted more than once within the study period, resulting in 86 analyzed cases. RESULTS Minor complications associated with refeeding during the first 10 d (replenishing phase) were recorded in nine cases (10.5%), four with transient pretibial edemas and three with organ dysfunction. In two cases, a severe hypokalemia occurred. During the observational phase of 30 d, 16 minor complications occurred in 14 cases (16.3%). Six infectious and 10 non-infectious complications occurred. None of the patients with anorexia nervosa died within a follow-up period of 3 mo. CONCLUSIONS Our data demonstrate that the seriousness and rate of complications during the replenishment phase in this high-risk population can be kept to a minimum. The findings indicate that evidence-based refeeding regimens, such as our guidelines are able to reduce complications and prevent mortality. Despite anorexia nervosa, our sample were affected by serious comorbidities, no case met the full diagnostic criteria for refeeding syndrome.

Childhood Trauma and Complex Posttraumatic Stress Disorder Symptoms in Older Adults: A Study of Direct Effects and Social-Interpersonal Factors as Potential Mediators

Childhood traumatic events may lead to long-lasting psychological effects and contribute to the development of complex posttraumatic sequelae. These might be captured by the diagnostic concept of complex posttraumatic stress disorder (CPTSD) as an alternative to classic posttraumatic stress disorder (PTSD). CPTSD comprises a further set of symptoms in addition to those of PTSD, namely, changes in affect, self, and interpersonal relationships. Previous empirical research on CPTSD has focused on middle-aged adults but not on older adults. Moreover, predictor models of CPTSD are still rare. The current study investigated the association between traumatic events in childhood and complex posttraumatic stress symptoms in older adults. The mediation of this association by 2 social-interpersonal factors (social acknowledgment as a survivor and dysfunctional disclosure) was investigated. These 2 factors focus on the perception of acknowledgment by others and either the inability to disclose traumatic experiences or the ability to do so only with negative emotional reactions. A total of 116 older individuals (age range = 59–98 years) who had experienced childhood traumatic events completed standardized self-report questionnaires indexing childhood trauma, complex trauma sequelae, social acknowledgment, and dysfunctional disclosure of trauma. The results showed that traumatic events during childhood were associated with later posttraumatic stress symptoms but with classic rather than complex symptoms. Social acknowledgment and dysfunctional disclosure partially mediated this relationship. These findings suggest that childhood traumatic stress impacts individuals across the life span and may be associated with particular adverse psychopathological consequences.

A new eosinophilic esophagitis (EoE)-like disease without tissue eosinophilia found in EoE Families

BACKGROUND Eosinophilic esophagitis (EoE) is a rapidly emerging, chronic inflammatory, genetically impacted disease of the esophagus, defined clinically by symptoms of esophageal dysfunction and, pathologically, by an eosinophil-predominant tissue infiltration. However, in four EoE-families, we have identified patients presenting with EoE-typical and corticosteroid-responsive symptoms, but without tissue eosinophilia. It was the aim of this study to clinically and immunologically characterize these patients with EoE-like disease. METHODS Five patients suffering from an EoE-like disease were evaluated with endoscopic, histologic, functional and quantitative immunohistologic examinations, and mRNA expression determination. RESULTS The frequency of first generation offspring of EoE-like disease patients affected by EoE or EoE-like disease was 40%. Immunofluorescence analysis confirmed an almost complete absence of eosinophils in the esophageal tissues of patients with EoE-like disease, but revealed a considerable T cell infiltration, comparable to EoE. In contrast to EoE, eotaxin-3 mRNA and protein were markedly reduced in EoE-like disease (P < 0.05). The mRNA expression levels of three selected EoE genes (eotaxin-3, MUC4 and CDH26) allowed to discriminate between EoE-like disease, EoE and normal epithelium. CONCLUSIONS Patients suffering from "EoE without eosinophilia" do not fulfill formally the diagnostic criteria for EoE. However, their clinical manifestation, immunohistology and gene-expression pattern, plus the fact that they bequeath EoE to their offspring, suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, therefore appears to be only one phenotype of a broader "inflammatory dysphagia syndrome" spectrum. In this light, the role of the eosinophils, the definition of EoE, and its diagnostic criteria must likely be reconsidered. This article is protected by copyright. All rights reserved.

Linear sclerodermic lupus erythematosus, a distinct variant of linear morphea and chronic cutaneous lupus erythematous

Overlap syndromes represent disorders that combine diagnostic criteria of two or more different connective tissue diseases.