Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematic...

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Published inDiagnostics (Basel) Vol. 11; no. 7; p. 1247
Main Authors Worthington, Anne, Kalteniece, Alise, Ferdousi, Maryam, D'Onofrio, Luca, Dhage, Shaishav, Azmi, Shazli, Adamson, Clare, Hamdy, Shaheen, Malik, Rayaz A, Calcutt, Nigel A, Marshall, Andrew G
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Published Switzerland MDPI AG 12.07.2021
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Abstract Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.
AbstractList Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.
Author Dhage, Shaishav
Marshall, Andrew G
Ferdousi, Maryam
Hamdy, Shaheen
Worthington, Anne
Azmi, Shazli
Malik, Rayaz A
Calcutt, Nigel A
D'Onofrio, Luca
Adamson, Clare
Kalteniece, Alise
AuthorAffiliation 2 Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK; alise.kalteniece@manchester.ac.uk (A.K.); maryam.ferdousi@manchester.ac.uk (M.F.); Shaishav.Dhage@christie.nhs.uk (S.D.); shazli.azmi@manchester.ac.uk (S.A.); ram2045@qatar-med.cornell.edu (R.A.M.)
4 Diabetes Centre, Manchester University NHS Foundation Trust, Manchester M13 0JE, UK; clare.adamson@mft.nhs.uk
5 Weill Cornell Medicine-Qatar, Research Division, Qatar Foundation, Education City, Doha 24144, Qatar
6 Department of Pathology, University of California, San Diego, CA 92093-0612, USA; ncalcutt@health.ucsd.edu
1 Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK; anne.worthington@postgrad.manchester.ac.uk (A.W.); Shaheen.Hamdy@manchester.ac.uk (S.H.)
3 Department of Experimental Medicine, Sapienza University, 00185 Rome, Italy; luca.donofrio@uniroma1.it
7 Divisio
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CitedBy_id crossref_primary_10_1093_braincomms_fcad051
crossref_primary_10_1097_MD_0000000000031046
crossref_primary_10_2337_db21_0960
crossref_primary_10_3389_fendo_2023_1206552
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Keywords pain
spinal disinhibition
H-reflex
diabetic neuropathy
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Snippet Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic...
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SubjectTerms Biomarkers
Chloride
Cornea
Demographics
Diabetes
Diabetic neuropathy
Ethics
H-reflex
Microscopy
Pain
Software
Spinal cord injuries
spinal disinhibition
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Title Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy
URI https://www.ncbi.nlm.nih.gov/pubmed/34359330
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Volume 11
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