Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability

Stephen A. Johnson; Kamal Shouman; Shahar Shelly; Paola Sandroni; Sarah E. Berini; P. James B. Dyck; Ernest Matthew Hoffman; Jay Mandrekar; Zhiyv Niu; Christopher J. Lamb; Phillip A. Low; Wolfgang Singer; Michelle L. Mauermann; John Mills; Divyanshu Dubey; Nathan P. Staff; Christopher J. Klein

doi:10.1212/WNL.0000000000012894

Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability

Stephen A. Johnson, Kamal Shouman, Shahar Shelly, Paola Sandroni, Sarah E. Berini, P. James B. Dyck, Ernest Matthew Hoffman, Jay Mandrekar, Zhiyv Niu, Christopher J. Lamb, Phillip A. Low, Wolfgang Singer, Michelle L. Mauermann, John Mills, Divyanshu Dubey, Nathan P. Staff, Christopher J. Klein

Research output: Contribution to journal › Article › peer-review

Abstract

Background and Objectives There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. Methods Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). Results Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sj¨ogren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications.

Original language	English (US)
Pages (from-to)	E2236-E2247
Journal	Neurology
Volume	97
Issue number	22
DOIs	https://doi.org/10.1212/WNL.0000000000012894
State	Published - Nov 30 2021

ASJC Scopus subject areas

Clinical Neurology

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10.1212/WNL.0000000000012894

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Johnson, S. A., Shouman, K., Shelly, S., Sandroni, P., Berini, S. E., Dyck, P. J. B., Hoffman, E. M., Mandrekar, J., Niu, Z., Lamb, C. J., Low, P. A., Singer, W., Mauermann, M. L., Mills, J., Dubey, D., Staff, N. P., & Klein, C. J. (2021). Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability. Neurology, 97(22), E2236-E2247. https://doi.org/10.1212/WNL.0000000000012894

Johnson, SA, Shouman, K, Shelly, S, Sandroni, P, Berini, SE, Dyck, PJB, Hoffman, EM, Mandrekar, J , Niu, Z, Lamb, CJ, Low, PA , Singer, W , Mauermann, ML, Mills, J, Dubey, D , Staff, NP & Klein, CJ 2021, 'Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability', Neurology, vol. 97, no. 22, pp. E2236-E2247. https://doi.org/10.1212/WNL.0000000000012894

@article{db8a225429eb4388878be2e319ff09d5,

title = "Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability",

abstract = "Background and Objectives There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. Methods Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). Results Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sj¨ogren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications.",

author = "Johnson, {Stephen A.} and Kamal Shouman and Shahar Shelly and Paola Sandroni and Berini, {Sarah E.} and Dyck, {P. James B.} and Hoffman, {Ernest Matthew} and Jay Mandrekar and Zhiyv Niu and Lamb, {Christopher J.} and Low, {Phillip A.} and Wolfgang Singer and Mauermann, {Michelle L.} and John Mills and Divyanshu Dubey and Staff, {Nathan P.} and Klein, {Christopher J.}",

note = "Funding Information: Dr. Johnson, Dr. Shouman, Dr. Shelly, Dr. Sandroni, and Dr. Berini report no disclosures relevant to the manuscript. Dr. Dyck reports honorarium from Akcea for talks on TTR amyloid. Dr. Hoffman, Dr. Mandrekar, Dr. Niu, Dr. Lamb, and Dr. Low report no disclosures relevant to the manuscript. Dr. Singer reports serving on the scientific advisory board for Lundbeck and Catalyst Pharmaceuticals and has consulted for Biohaven and Astellas pharmaceuticals. He has received grant support from the NIH (U54NS65736, R01NS092625), Food and Drug Administration (R01FD4789), Boston Scientific, and the American Dysautonomia Institute. He holds a patent on the use of 3,4 diaminopyridine in the treatment of orthostatic hypotension and postural tachycardia syndrome. He is associate editor for Clinical Autonomic Research and serves on the editorial board of Autonomic Neuroscience—Basic and Clinical. Dr. Mauermann reports research support from IONIS, Alnylam, and EIDOS Pharmaceutical. She has received royalties from Oxford Publishing. She serves on the Editorial Board for Mayo Clinic Proceedings. Dr. Mills holds patents on the use of mass spectrometry to measure monoclonal immunoglobulins and has received royalties related to these patents from The Binding Site. Dr. Dubey reports consultation for UCB, Alexion, and Immunovant pharmaceuticals. All compensation for consulting activities is paid directly to Mayo Clinic. He has patents pending for KLHL11 and LUZP4 as biomarkers of neurologic autoimmunity and germ cell tumor. Dr. Staff reports research funding from the NIH (R01CA211887), ALS Association, Target ALS, and Regenerative Medicine Minnesota. He has served as investigator on clinical trials sponsored by Brainstorm Therapeutics, Orion Pharmaceuticals, Biogen, and Medicinova but received no personal compensation for this. He serves as an associate editor for Stem Cell Research & Therapy. Dr. Klein has received teaching honorarium from Akcea pharmaceuticals for lectures on hereditary transthyretin amyloidosis and Fabry disease. He has consulted for Pfizer regarding tafamidis (all compensation for consulting activities is paid directly to Mayo Clinic) and participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. Go to Neurology.org/N for full disclosures. Publisher Copyright: {\textcopyright} 2021 Lippincott Williams and Wilkins. All rights reserved.",

year = "2021",

month = nov,

day = "30",

doi = "10.1212/WNL.0000000000012894",

language = "English (US)",

volume = "97",

pages = "E2236--E2247",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "22",

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TY - JOUR

T1 - Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability

AU - Johnson, Stephen A.

AU - Shouman, Kamal

AU - Shelly, Shahar

AU - Sandroni, Paola

AU - Berini, Sarah E.

AU - Dyck, P. James B.

AU - Hoffman, Ernest Matthew

AU - Mandrekar, Jay

AU - Niu, Zhiyv

AU - Lamb, Christopher J.

AU - Low, Phillip A.

AU - Singer, Wolfgang

AU - Mauermann, Michelle L.

AU - Mills, John

AU - Dubey, Divyanshu

AU - Staff, Nathan P.

AU - Klein, Christopher J.

N1 - Funding Information: Dr. Johnson, Dr. Shouman, Dr. Shelly, Dr. Sandroni, and Dr. Berini report no disclosures relevant to the manuscript. Dr. Dyck reports honorarium from Akcea for talks on TTR amyloid. Dr. Hoffman, Dr. Mandrekar, Dr. Niu, Dr. Lamb, and Dr. Low report no disclosures relevant to the manuscript. Dr. Singer reports serving on the scientific advisory board for Lundbeck and Catalyst Pharmaceuticals and has consulted for Biohaven and Astellas pharmaceuticals. He has received grant support from the NIH (U54NS65736, R01NS092625), Food and Drug Administration (R01FD4789), Boston Scientific, and the American Dysautonomia Institute. He holds a patent on the use of 3,4 diaminopyridine in the treatment of orthostatic hypotension and postural tachycardia syndrome. He is associate editor for Clinical Autonomic Research and serves on the editorial board of Autonomic Neuroscience—Basic and Clinical. Dr. Mauermann reports research support from IONIS, Alnylam, and EIDOS Pharmaceutical. She has received royalties from Oxford Publishing. She serves on the Editorial Board for Mayo Clinic Proceedings. Dr. Mills holds patents on the use of mass spectrometry to measure monoclonal immunoglobulins and has received royalties related to these patents from The Binding Site. Dr. Dubey reports consultation for UCB, Alexion, and Immunovant pharmaceuticals. All compensation for consulting activities is paid directly to Mayo Clinic. He has patents pending for KLHL11 and LUZP4 as biomarkers of neurologic autoimmunity and germ cell tumor. Dr. Staff reports research funding from the NIH (R01CA211887), ALS Association, Target ALS, and Regenerative Medicine Minnesota. He has served as investigator on clinical trials sponsored by Brainstorm Therapeutics, Orion Pharmaceuticals, Biogen, and Medicinova but received no personal compensation for this. He serves as an associate editor for Stem Cell Research & Therapy. Dr. Klein has received teaching honorarium from Akcea pharmaceuticals for lectures on hereditary transthyretin amyloidosis and Fabry disease. He has consulted for Pfizer regarding tafamidis (all compensation for consulting activities is paid directly to Mayo Clinic) and participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. Go to Neurology.org/N for full disclosures. Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.

PY - 2021/11/30

Y1 - 2021/11/30

N2 - Background and Objectives There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. Methods Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). Results Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sj¨ogren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications.

AB - Background and Objectives There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. Methods Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). Results Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sj¨ogren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications.

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Small fiber neuropathy incidence, prevalence, longitudinal impairments, and disability

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