Sandroni, Paola

Background/Objectives: Erythromelalgia is a rare condition characterized by burning pain, redness, and warmth primarily in the extremities, usually worsened by heat and alleviated by cold. The objective of this study was to identify the top 10 priorities in pediatric erythromelalgia from multiple perspectives, including clinicians, people with lived experience of childhood-onset erythromelalgia, and their family members. Methods: A modified James Lind Alliance Priority-Setting Process was conducted. The top priorities were identified through four phases: (1) an international online survey to gather priorities, (2) data processing, (3) an interim prioritization online survey, and (4) a virtual workshop to set the final priorities. Results: In phase 1, 185 potential priorities were submitted by 74 respondents (53% patients, 24% family members, and 23% clinicians) that were developed into 68 unique research questions (phase 2). In phase 3, of the 68 questions, 50 were rated for importance by 58 participants (38% patients, 36% family members, and 26% clinicians), reducing the list to 25 questions. In phase 4, the top 10 was reached through consensus by 12 participants (33% patients, 25% family members, and 42% clinicians) across Canada, South Africa, the United States of America, and the United Kingdom. Conclusions: The final priorities focused on the treatment of erythromelalgia, understanding underlying mechanisms, the association of erythromelalgia with various body systems, and generating awareness. This list is the first international patient-centered research agenda for childhood-onset erythromelalgia and a call to action from key partners to improve future research and care.

Autonomic medicine is a rapidly evolving field focused on understanding diseases and processes that affect the autonomic nervous system (ANS). The ANS regulates essential involuntary physiologic processes such as heart rate, blood pressure, and digestion. This review introduces the key anatomical structures, physiological mechanisms, and biochemical processes underlying autonomic function. The anatomy section focuses on the peripheral components of the ANS, including the sympathetic and parasympathetic divisions. The physiological section explores the process of homeostasis and the intricate feedback systems that maintain this balance within the body. Finally, the biochemistry of autonomic signaling, focusing on the neurotransmitters acetylcholine, norepinephrine, and epinephrine, and their receptors, is reviewed. Pertinent clinical points are highlighted throughout, emphasizing the importance of the basic science to the clinical world. This review aims to provide a comprehensive basic science foundation for clinicians and researchers exploring the field of autonomic medicine.

Erythromelalgia is a rare disorder characterized by episodic burning pain with redness and warmth of the extremities. Topical and systemic medications are the mainstay of management. We reviewed the published evidence for using procedural interventions to manage erythromelalgia, including their proposed mechanism of action and possible adverse effects, and included information in this review on epidural infusion, sympathetic ganglion block, sympathectomy, pulsed radiofrequency, spinal cord stimulation, dorsal root ganglion stimulation, brain stimulation, transcranial magnetic stimulation, and botulinum toxin injections. Both successful and unsuccessful outcomes have been reported. Although these procedural interventions extend the therapeutic options for erythromelalgia, the evidence for their use is limited. Case reports and small case series comprise most of the evidence. Based on our review, a multidisciplinary approach to management may be needed for patients with erythromelalgia.

Abstract To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European, and North American samples. In the GWAS stage, rs2303744 on chromosome 19 showed a suggestive association (P = 6.5 × 10− 7) that was replicated in additional Japanese samples (P = 2.9 × 10− 6, odds ratio (OR) = 1.58; 95% confidence interval (CI), 1.30–1.91), and then confirmed as highly significant in a meta-analysis of East Asian population data (P = 5.0 × 10− 15, OR = 1.49; 95% CI 1.35–1.65). The association of rs2303744 with MSA remained significant in combined European/North American samples (P = 0.017, OR = 1.12; 95% CI 1.02–1.23) despite allele frequencies being quite different between these populations. rs2303744 leads to an amino acid substitution in PLA2G4C that encodes the cPLA2γ lysophospholipase/transacylase. The cPLA2γ-Ile143 isoform encoded by the MSA risk allele has significantly decreased transacylase activity compared with the alternate cPLA2γ-Val143 isoform, and may perturb membrane phospholipids and promote oligodendroglial pathology.