Evaluation of Small-Fiber Polyneuropathy in Youth

青年小纤维多发性神经病的评估

• 批准号: 10674977
• 负责人: Anne Louise Oaklander
• 金额: $ 63.86万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674977
• 关键词: 21 year old; Address; Adult; Age; Age Reporting; Analgesics; Award; Biological Markers; Biopsy; Blood Tests; Candidate Disease Gene; Cellular Phone; Child; Childhood; Clinical; Clinical Trials; Collaborations; Communities; Complement; Computerized Medical Record; DNA Sequence Alteration; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Distress; Elderly; Epidemiology; Epigenetic Process; Etiology; Evaluation; Examinations and Diagnoses; Exertion; Family; Family member; Fiber; Fibromyalgia; Funding; Future; Genes; Genetic; Genetic Risk; Genome; Genomics; Genotype; Goals; Hereditary Sensory and Autonomic Neuropathies; Immune; Immunoglobulins; Individual; Internet; Knowledge; Leg; Letters; Life; Link; Manuscripts; Maps; Measurement; Measures; Medical; Modeling; Monitor; Names; Natural History; Nerve Endings; Nerve Fibers; Neuropathy; Outcome; Pain; Pain Measurement; Pain Research; Participant; Pathogenicity; Pathway interactions; Patient Care; Patient Recruitments; Patient Selection; Patients; Peripheral Nerves; Peripheral Nervous System Diseases; Persons; Pharmacodynamics; Phenotype; Physicians; Polyneuropathy; Population; Predictive Value; Prevalence; Probability; Procedures; Productivity; PubMed; Public Health; Publishing; Qualifying; Recommendation; Registries; Reporting; Research; Research Personnel; Risk; Safety; Sampling; Schools; Secure; Site; Skin; Source; Specificity; Standardization; Surveys; Symptoms; Testing; Toxicant exposure; United States Food and Drug Administration; United States National Institutes of Health; Untranslated RNA; Variant; Visit; Withdrawal; Work; Youth; aged; chemotherapy; chronic pain; chronic widespread pain; cohort; density; diagnostic accuracy; diagnostic tool; early onset; effective therapy; ethnic diversity; evidence base; foot; gastrointestinal; genome wide screen; genome-wide; health disparity; healthy volunteer; improved; lectures; meetings; neurogenetics; neuropathology; painful neuropathy; patient registry; programs; recruit; relational database; research study; response; risk variant; tool; treatment effect; web site; whole genome; young adult

Project Summary/Abstract This is a renewal application for the R01NS093653 award that has been funding the Oaklander lab's research on small-fiber neuropathy. SFN is a recently recognized peripheral nerve illness that causes chronic pain, usually starting in the feet and spreading up, difficulty completing routine activities and gastrointestinal distress. In 2013, the team studied 41 children and young adults, unexpectedly reporting evidence of SFN in most. Until then, SFN was known only in older adults with diabetes, chemotherapy or other toxic exposures and serious diseases. The lab had discovered a new condition–early onset SFN (eoSFN). For many, it forced withdrawal from school or work, derailing young patients' life trajectories. When the lab then reported that 41% of adults with fibromyalgia also had objective evidence of SFN, implying there might be > 100,000 SFN patients globally, R01NS093653 funded them to develop standardized tools for collecting data about symptoms (the SSS small- fiber symptom survey) and exam abnormalities (the MAGNET Mass General Neuropathy Exam Tool) and a list of best blood tests to screen for potential causes. The PI also directs Mass General's neuropathology lab that confirms SFN diagnoses by examining tiny skin biopsies from patients' lower leg to measure the density of small-fiber nerve endings and compare it to biopsies from normal. So the lab built the Neuropathy Registry, a relational database now containing downloaded electronic medical records plus clinical and research testing from >6500 people evaluated for SFN. It currently includes 6394 biopsy results and >1000 SSS and MAGNETs with more than 1000 new patients added yearly. The PI is also part of the NIH and FDA funded CONCEPPT committee of experts now publishing the 1st formal case definition for SFN, with inclusion requirements for research. These require specific abnormalities that are already captured by the SSS, MAGNET, and skin biopsy. Now Aim 1 proposes to use Registry participants plus new patients and healthy volunteers to adapt and validate the SSS and MAGNET for general medical use by any doctor and for use in children. Aim 2 will collaborate with the Food and Drug Administration's Biomarker Qualification Program to obtain an FDA ruling on lab requirements to improve the quality and accuracy of skin biopsy testing. Aim 3 begins whole-genome study of causes and risks for SFN. It recruits Registry patients with CONCEPPT-defined SFN and adds more via the lab's NeuropathyCommons website and its global collaborators. Dr. Züchner's U. Miami neurogenetics lab will analyze the genomes of qualifying participants to study known and unknown genes that cause or increase risk for SFN. More genetic neuropathies are becoming treatable and Dr. Oaklander helped publish the 1st effective treatment for HSAN1. The final and future goal is to track large numbers of SFN patients and families using secure web and cell-phone versions of the SSS and MAGNET and mailed-in skin biopsies. These will allow them to map SFN's symptoms and natural history, identify new causal pathways and potential treatments, and track children and newly treated patients to monitor long-term outcomes and treatment effects.

项目总结/文摘

项目成果

Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy.

• DOI: 10.1111/ene.12717
• 发表时间: 2015-07
• 期刊: European journal of neurology
• 影响因子: 5.1
• 作者: Treister R;O'Neil K;Downs HM;Oaklander AL
• 通讯作者: Oaklander AL

Epidermal Neurite Density in Skin Biopsies From Patients With Juvenile Fibromyalgia.

• DOI: 10.3899/jrheum.200378
• 发表时间: 2021-04
• 期刊: The Journal of rheumatology
• 作者: Boneparth A;Chen S;Horton DB;Moorthy LN;Farquhar I;Downs HM;Lee H;Oaklander AL
• 通讯作者: Oaklander AL

Advances in diagnosis and management of distal sensory polyneuropathies.

远端感觉多发性神经病的诊断和治疗进展。

• DOI: 10.1136/jnnp-2021-328489
• 发表时间: 2023
• 期刊: Journal of neurology, neurosurgery, and psychiatry
• 作者: Silsby,Matthew;Feldman,EvaL;Dortch,RichardD;Roth,Alison;Haroutounian,Simon;Rajabally,YusufA;Vucic,Steve;Shy,MichaelE;Oaklander,AnneLouise;Simon,NeilG
• 通讯作者: Simon,NeilG

Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia.

• DOI: 10.1016/j.pain.2013.06.001
• 发表时间: 2013-11
• 期刊: Pain
• 影响因子: 7.4
• 作者: Oaklander AL;Herzog ZD;Downs HM;Klein MM
• 通讯作者: Klein MM

Characterization of mononeuropathy of the lateral cutaneous nerve of the calf.

• DOI: 10.1002/mus.27367
• 发表时间: 2021-10
• 期刊: Muscle & nerve
• 影响因子: 3.4