Acceptability, usability and feasibility of experienced sampling method in chronic secondary pain syndromes

BackgroundIn chronic pain syndromes, symptoms can fluctuate and change over time. Standard questionnaires cannot register these fluctuations. Nonetheless, the experience sampling method (ESM) is developed to collect momentary measurements of everyday complaints, tracing fluctuations in symptoms and disabling factors over time. Although valuable information can be collected in this way, assessment may also be a burden. This study aimed to investigate the acceptability, usability, and feasibility of ESM in chronic secondary pain syndromes, in a single-center study in the Netherlands.MethodsA prospective observational study with repeated measurements was conducted in patients with chronic secondary neuropathic and musculoskeletal pain syndromes, including small fiber neuropathy, spinal cord injury, and rheumatoid disorder.ResultsThirty-four participants were included and filled in the ESM, of whom 19 were diagnosed with small fiber neuropathy, 11 with spinal cord injury, and 4 with a rheumatoid disorder. The mean age was 54.7 ± 13.9 years (range: 23–77) of whom 52.9% were female. In total, 19 participants filled in the general and user-friendliness evaluation about the acceptability and usability of the ESM. The general evaluation showed no influence of ESM on participants’ social contacts (mean 1.47, SD 1.12), activities (mean 1.74, SD 1.44), and mood (mean 1.89, SD 1.59). The answers options of ESM were a good representation of the experiences of participants (mean 4.58, SD 1.77). Regarding feasibility, the overall response rate for answering the beep signals of ESM was 44.5% in total. The missing rate per person varied from 13% to 97% with a median of 54.1%.ConclusionThe general evaluation and the user-friendliness revealed sufficient outcomes in favor of the ESM application. ESM seems a promising measurement tool to use in secondary chronic pain syndromes

Lifestyle Factors and Breast Cancer in Females with PTEN Hamartoma Tumor Syndrome (PHTS)

Simple Summary: Females with PTEN Hamartoma Tumor Syndrome (PHTS) have very high hereditary breast cancer risks up to 76%. The aim of this European cohort study was to the describe the lifestyle in PHTS patients and to assess associations between physical activity, alcohol consumption, tobacco smoking, BMI and breast cancer in female adult PHTS patients. It was observed that of 125 patients who completed the questionnaire, 81% were >= 2 times/week physically active, 86% consumed on average = 2 times (ORtotal-adj = 0.9 (95%CI 0.3-2.6); consumed daily about 1.2-1.8 times more often >= 1 than 0-1 glasses of alcohol (ORtotal-adj = 1.2 (95%CI 0.4-4.0); ORnon-breastcancer-index-adj = 1.8 (95%CI 0.4-6.9); were about 1.04-1.3 times more often smokers than non-smokers (ORtotal-adj = 1.04 (95%CI 0.4-2.8); ORnon-breastcancer-index-adj = 1.3 (95%CI 0.4-4.2)); and overweight or obesity (72%) was about 1.02-1.3 times less common (ORtotal-adj = 0.98 (95%CI 0.4-2.6); ORnon-breastcancer-index-adj = 0.8 (95%CI 0.3-2.7)). Similar associations between lifestyle and breast cancer are suggested for PHTS and the general population. Despite not being statistically significant, results are clinically relevant and suggest that awareness of the effects of lifestyle on patients' breast cancer risk is important

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrimental for muscle function, as found in HCM and MFM. Variants associated with HCM are predominantly missense variants, which cluster in the ROD2 domain. This domain is important for binding to the sarcomere and to ensure appropriate cell signaling. We here review FLNC genotype–phenotype correlations based on available evidence

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrim

Small fiber neuropathies:expanding their etiologies

PURPOSE OF REVIEW: Several conditions have been associated with the development of small fiber neuropathy (SFN). The list of metabolic, immune-mediated, infectious, toxic, drugs-related, and hereditary conditions is still growing and various hypotheses are made about the underlying pathophysiological mechanisms. Understanding these processes is important to provide new targets for treatment. In addition, the specific SFN phenotype can provide direction for the underlying etiology. This review discusses the latest developments concerning the expanding etiologies in SFN. RECENT FINDINGS: In the past 18 months, special attention has been paid to immunological etiologies, partly due to the coronavirus disease 2019 pandemic, but also new auto-antibodies in SFN have been demonstrated. Identifying patients with immune-mediated SFN can be challenging, since contrary to the classical distal sensory phenotype, a nonlength-dependent pattern is more common.Besides the etiologies of classical SFN, small fiber pathology is increasingly described in diseases without the typical neuropathic pain features of SFN, sometimes called syndromic SFN. However, the clinical relevance is not yet fully understood. SUMMARY: The expansion of the etiologies of SFN continues and brings more insight in possible targets for treatment. The clinical presentation may vary as a result of the underlying condition

Channelopathies, painful neuropathy, and diabetes: which way does the causal arrow point?

Diabetes mellitus, a major global health problem, is commonly associated with painful peripheral neuropathy, which can substantially erode quality of life. Despite its clinical importance, the pathophysiology of painful diabetic neuropathy is incompletely understood. It has traditionally been thought that diabetes may cause neuropathy in patients with appropriate genetic makeup. Here, we propose a hypothesis whereby painful neuropathy is not a complication of diabetes, but rather occurs as a result of mutations that, in parallel, confer vulnerability to injury in pancreatic beta cells and pain-signaling dorsal root ganglion (DRG) neurons. We suggest that mutations of sodium channel Na(V)1.7, which is present in both cell types, may increase susceptibility for development of diabetes via beta cell injury and produce painful neuropathy via a distinct effect on DRG neurons

Small-fibre neuropathies-advances in diagnosis, pathophysiology and management

Small-fibre neuropathy (SFN), a disorder of thinly myelinated A-fibres and unmyelinated C-fibres, is clinically characterized by neuropathic pain symptoms and autonomic complaints. Diagnosis of SFN is challenging as the clinical picture can be difficult to interpret and results from nerve conduction studies are often normal. In cases of suspected SFN, measurement of intraepidermal nerve fibre density and/or analysis of quantitative sensory testing can enable diagnosis. New diagnostic techniques (including measurement of nerve fibre density using corneal confocal microscopy, and nociceptive evoked potentials) may contribute to the diagnostic work-up. SFN can be associated with systemic diseases such as immune-mediated disorders, but remains idiopathic in a substantial proportion of patients. Gain-of-function variants in the Na v 1.7 sodium channel have recently been found in nearly 30% of patients with idiopathic SFN, but the mechanisms of axonal degeneration in the disorder remain under investigation. Identification of the systemic diseases underlying SFN will enable development of drugs that target affected pathways to improve the management of neuropathic pain and autonomic dysfunction. In this Review, we discuss recent advances in the diagnosis and pathophysiology of SFN, highlighting how improved understanding of these aspects of the disorder will contribute to better patient management