Progression of axonal excitability abnormalities with increasing clinical severity of diabetic peripheral neuropathy
Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved..
OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a frequent complication for persons with type 2 diabetes. Previous studies have failed to demonstrate any significant impact of treatment for DPN. The present study assessed the role of axonal ion channel dysfunction in DPN and explored the hypothesis that there may be a progressive change in ion channel abnormalities that varied with disease stage.
METHODS: Neurophysiological studies were conducted using axonal excitability techniques, a clinical method of assessing ion channel dysfunction. Studies were conducted in 178 persons with type 2 diabetes, with participants allocated into four groups according to clinical severity of neuropathy, assessed using the Total Neuropathy Grade.
RESULTS: Analysis of excitability data demonstrated a progressive and stepwise reduction in two parameters that are related to the activity of Kv1.1 channels, namely superexcitability and depolarizing threshold electrotonus at 10-20 ms (p < 0.001), and mathematical modelling of axonal excitability findings supported progressive upregulation of Kv1.1 conductances with increasing greater disease severity.
CONCLUSION: The findings are consistent with a progressive upregulation of juxtaparanodal Kv1.1 conductances with increasing clinical severity of diabetic peripheral neuropathy.
SIGNIFICANCE: From a translational perspective, the study suggests that blockade of Kv1.1 channels using 4-aminopyridine derivatives such as fampridine may be a potential treatment for DPN.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:160 |
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| Enthalten in: |
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology - 160(2024) vom: 18. Apr., Seite 12-18 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Dhanapalaratnam, Roshan [VerfasserIn] |
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| Links: |
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| Themen: |
4-Aminopyridine |
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| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 11.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.clinph.2024.02.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Dhanapalaratnam, Roshan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Progression of axonal excitability abnormalities with increasing clinical severity of diabetic peripheral neuropathy |
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| 500 | |a Date Revised 11.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a OBJECTIVE: Diabetic peripheral neuropathy (DPN) is a frequent complication for persons with type 2 diabetes. Previous studies have failed to demonstrate any significant impact of treatment for DPN. The present study assessed the role of axonal ion channel dysfunction in DPN and explored the hypothesis that there may be a progressive change in ion channel abnormalities that varied with disease stage | ||
| 520 | |a METHODS: Neurophysiological studies were conducted using axonal excitability techniques, a clinical method of assessing ion channel dysfunction. Studies were conducted in 178 persons with type 2 diabetes, with participants allocated into four groups according to clinical severity of neuropathy, assessed using the Total Neuropathy Grade | ||
| 520 | |a RESULTS: Analysis of excitability data demonstrated a progressive and stepwise reduction in two parameters that are related to the activity of Kv1.1 channels, namely superexcitability and depolarizing threshold electrotonus at 10-20 ms (p < 0.001), and mathematical modelling of axonal excitability findings supported progressive upregulation of Kv1.1 conductances with increasing greater disease severity | ||
| 520 | |a CONCLUSION: The findings are consistent with a progressive upregulation of juxtaparanodal Kv1.1 conductances with increasing clinical severity of diabetic peripheral neuropathy | ||
| 520 | |a SIGNIFICANCE: From a translational perspective, the study suggests that blockade of Kv1.1 channels using 4-aminopyridine derivatives such as fampridine may be a potential treatment for DPN | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Nerve ultrasonography | |
| 650 | 4 | |a Peripheral neuropathy | |
| 650 | 4 | |a Potassium channel | |
| 650 | 4 | |a Type 2 diabetes | |
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| 650 | 7 | |a Ion Channels |2 NLM | |
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| 700 | 1 | |a Milner, Kerry-Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Kwai, Natalie C G |e verfasserin |4 aut | |
| 700 | 1 | |a Krishnan, Arun V |e verfasserin |4 aut | |
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