Diagnostic Criteria for Idiopathic Distal Sensory Polyneuropathy and Idiopathic Small Fiber Polyneuropathy (1798)

Objective: To develop standardized diagnostic criteria for research and clinical use for two highly prevalent yet underserved neurological disorders. Background: No cause is identified for distal sensory polyneuropathy (DSP) and small fiber neuropathy (SFN) in approximately 20–30% of cases. These idiopathic (i) DSPs have become attractive disorders for drug-development, given recent advances in identifying underlying genetic mechanisms in some patients, yet no evidence-based treatments exist. One major barrier to therapeutic development is the lack of consensus diagnostic criteria. Design/Methods: The Consortium on Clinical Endpoints and Procedures for Peripheral Neuropathy Trials (CONCEPPT) of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the FDA convened a meeting of experts (i.e., the CONCEPPT DSP working group) to develop consensus diagnostic criteria for iDSP and iSFN. After a series of background presentations including reviews of existing criteria for DSPs, a collaborative approach was used to develop expert consensus for new iDSP and iSFN criteria. Results: Diagnostic criteria were developed that included required symptoms, signs, neurophysiological and neuropathological assessments, and possible etiologies to be excluded. Requirements for an iDSP diagnosis include: one of the following symptoms (1) spontaneous or constant pain, (2) allodynia, (3) a non-painful sensory symptom; one of the following signs: (1) abnormal sensory perception (i.e., pinprick, light touch, vibration, or position sense), (2) allodynia, (3) hyperalgesia; abnormalities in sensory nerve conduction studies or distal intra-epidermal nerve fiber density; and absence of specific causes of DSP. Diagnostic criteria for iSFN are similar, except absence of abnormalities in large fiber clinical signs (e.g., vibration perception) and normal sensory nerve conduction studies are required. Conclusions: We propose that adoption of these standardized criteria will advance research and clinical trials, spur development of therapies for iDSP and iSFN, and facilitate generalization of research results to the clinic. Disclosure: Dr. Gewandter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Disarm, Science Branding, Magnolia Neurosciences, and SK lifesciences. Dr. Gewandter has received personal compensation in an editorial capacity for Pain Medicine. Dr. Freeman has nothing to disclose. Dr. Dworkin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with obert H. Dworkin, PhD, has received in the past 36 months compensation for consulting on clinical trial methods from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Bra. Dr. Faber has received research support from Research support from Grifols and Lamepro for a study outside of this work. Dr. Herrmann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam, Neurogene, Regenacy, Inc., Guidepoint Global, GLG, Sarepta, Slingshot Insights, Clear View Health Partners, Trinity Partners, Schlesinger, Human First Therapeutics, and Narrow River Management. Dr. Herrmann has received royalty, license fees, or contractual rights payments from University of Rochester. Dr. Herrmann has received research support from Acceleron Pharma. Dr. Hoke has nothing to disclose. Dr. Kolb has nothing to disclose. Dr. Lauria has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, Biogen, Vertex, Chromocell, Johnson a Johnson, Grunenthal, GlaxoSmithKline, Chiesi Pharmaceuticals, Kedrion, Pfizer, Mitsubishi Pharma, Shire. Dr. Malik has nothing to disclose. Dr. Oaklander has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Grifols. Dr. Peltier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL Behring, and Lundbeck Pharmaceutical Companies.Dr. Polydefkis has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Pfizer, Alnylam Pharmaceuticals, Akcea, Biogen, Vertex. Dr. Russell has nothing to disclose. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion, Argenx, Disarm Therapeutics, and Regenesis.Dr. Treister has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Medoc LTD (Ramat Yishai, Israel), Medasense LTD (Tel-Aviv, Israel), NEOMED (Montreal, Quebec, Canada), Analgesic Solutions (Wayland, MA, USA). Dr. Uceyler has nothing to disclose.