Chronic Idiopathic Axonal Polyneuropathy Is Associated With the Metabolic Syndrome

Visser, Nora A.; Vrancken, Alexander F.J.E.; Schouw, Yvonne T. van der; Berg, Leonard H van den; Notermans, Nicolette C.

doi:10.2337/dc12-0469

Cited by 53 publications

(78 citation statements)

References 39 publications

(49 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The diagnosis of cryptogenic axonal polyneuropathy was based on diagnostic criteria as detailed previously. 11 Briefly, patients had to have 'glove and/or sock' like distribution of sensory or sensorimotor symptoms (self-reported as well as on neurological examination) compatible with polyneuropathy. The onset of polyneuropathy should have occurred in the feet and after the age of 40, as in younger patients a hereditary polyneuropathy should always be suspected.…”

Section: Patientsmentioning

confidence: 99%

“…In approximately 25% of patients with polyneuropathy, no cause can be found, the so-called cryptogenic axonal polyneuropathy, which is also associated with cardiovascular disease and the metabolic syndrome. [8][9][10][11] In view of shared comorbidities, an increased prevalence of COPD among patients with cryptogenic axonal polyneuropathy may be expected if polyneuropathy truly is a complication or extrapulmonary manifestation of COPD. This prospective case-control study aims to investigate the association between COPD and polyneuropathy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic obstructive pulmonary disease is not a risk factor for polyneuropathy: A prospective controlled study

et al. 2016

View full text Add to dashboard Cite

Polyneuropathy has been observed in patients with chronic obstructive pulmonary disease (COPD). If polyneuropathy occurs as a complication or extrapulmonary manifestation of COPD, one would expect an increased prevalence among patients with a cryptogenic axonal polyneuropathy. This case-control study aimed to investigate the association between COPD and polyneuropathy. We prospectively included 345 patients with cryptogenic axonal polyneuropathy and 465 controls. A standardized questionnaire assessed the presence of COPD and we verified this diagnosis by contacting the family physician. The severity of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease classification. The prevalence of COPD did not differ between patients with polyneuropathy and controls (15/345 vs. 12/465 respectively; odds ratio (OR) 1.7; 95% confidence interval (CI) [0.8-3.7]). Adjusting for age, gender and possible confounders did not affect these results (adjusted OR 1.7, 95% CI 0.7-4.1). The severity of COPD was similar between patients with polyneuropathy and controls. This study does not support the hypothesis that COPD is a risk factor for polyneuropathy.

show abstract

Section: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic obstructive pulmonary disease is not a risk factor for polyneuropathy: A prospective controlled study

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Diabetic Neuropathymentioning

confidence: 99%

“…Chronic idiopathic axonal polyneuropathy (CIAP) is a common disease in elder people in their 60s with unknown etiology [47,48]. The symptoms are mainly sensory affecting small nerve fibers, and they include numbness, pins and needles, coldness, tightness, muscle cramps, unsteadiness, and muscle weakness [47]. Risk factors that contribute to development of CIAP include hypertension, impaired glucose tolerance, obesity, hypercholesterolemia, and environmental toxins [47,[49][50][51].…”

Section: Diabetic Neuropathymentioning

confidence: 99%

“…The symptoms are mainly sensory affecting small nerve fibers, and they include numbness, pins and needles, coldness, tightness, muscle cramps, unsteadiness, and muscle weakness [47]. Risk factors that contribute to development of CIAP include hypertension, impaired glucose tolerance, obesity, hypercholesterolemia, and environmental toxins [47,[49][50][51]. All these risk factors cause oxidative stress [46].…”

Section: Diabetic Neuropathymentioning

confidence: 99%

See 1 more Smart Citation

Autophagy in Peripheral Neuropathy

Osman¹

2017

Linköping University Medical Dissertations

View full text Add to dashboard Cite

Peripheral neuropathy includes a wide range of diseases affecting millions around the world, and many of these diseases have unknown etiology. Peripheral neuropathy in diabetes represents a large proportion of peripheral neuropathies. Nerve damage can also be caused by trauma. Peripheral neuropathies are a significant clinical problem and efficient treatments are largely lacking. In the case of a transected nerve, different methods have been used to repair or reconstruct the nerve, including the use of nerve conduits, but functional recovery is usually poor. Autophagy, a cellular mechanism that recycles damaged proteins, is impaired in the brain in many neurodegenerative diseases affecting animals and humans. No research, however, has investigated the presence of autophagy in the human peripheral nervous system. In this study, I present the first structural evidence of autophagy in human peripheral nerves. I also show that the density of autophagy structures is higher in peripheral nerves of patients with chronic idiopathic axonal polyneuropathy (CIAP) and inflammatory neuropathy than in controls. The density of these structures increases with the severity of the neuropathy. In animal model, using Goto-Kakizaki (GK) rats with diabetes resembling human type 2 diabetes, activation of autophagy by local administration of rapamycin incorporated in collagen conduits that were used for reconnection of the transected sciatic nerve led to an increase in autophagy proteins LC3 and a decrease in p62 suggesting that the autophagic flux was activated. In addition, immunoreactivity of neurofilaments, which are parts of the cytoskeleton of axons, was increased indicating increased axonal regeneration. I also show that many proteins involved in axonal regeneration and cell survival were up-regulated by rapamycin in the injured sciatic nerve of GK rats four weeks after injury. Taken together, these findings provide new knowledge about the involvement of autophagy in neuropathy and after peripheral nerve injury and reconstruction using collagen conduits. 6 Populärvetenskaplig sammanfattningNervskador (neuropati) orsakade av sjukdomar eller olycksfall påverkar miljontals individer runt om i världen. Nervskador som orsakas av diabetes kallas diabetesneuropati och drabbar varannan patient med diabetes. Neuropati kan också orsakas av kronisk inflammation i nerven eller uppstå utan känd orsak, så kallad kronisk idiopatisk axonal polyneuropati. Patienterna som drabbas av neuropati uppvisar varierande symptom beroende på vilka nerver som drabbas men domningar, stickningar, smärta, känselbortfall och muskelsvaghet finns ofta i symptombilden. Nervskador efter trauma kräver oftast kirurgisk rekonstruktion. För närvarande finns det ingen behandling för diabetesneuropati. Allt fler människor i fysiskt aktiv ålder drabbas av åldersdiabetes (typ 2 diabetes). Detta leder till att fler patienter med diabetes drabbas av traumatiska nervskador som kräver nervreparation. Det är därför viktigt att utveckla reparationsmetoder som fungerar br...

show abstract

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome

Smith,

Singleton,

Aperghis

et al. 2023

JAMA Neurol

View full text Add to dashboard Cite

ImportanceCryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence.ObjectiveTo determine whether topiramate can slow decline in intraepidermal nerve fiber density (IENFD) and/or neuropathy-specific quality of life measured using the Norfolk Quality of Life–Diabetic Neuropathy (NQOL-DN) scale.Design, Setting, and ParticipantsTopiramate as a Disease-Modifying Therapy for CSPN (TopCSPN) was a double-blind, placebo-controlled, randomized clinical trial conducted between February 2018 and October 2021. TopCSPN was performed at 20 sites in the National Institutes of Health–funded Network for Excellence in Neurosciences Clinical Trials (NeuroNEXT). Individuals with CSPN and metabolic syndrome aged 18 to 80 years were screened and randomly assigned by body mass index (&lt;30 vs ≥30), which is calculated as weight in kilograms divided by height in meters squared. Patients were excluded if they had poorly controlled diabetes, prior topiramate treatment, recurrent nephrolithiasis, type 1 diabetes, use of insulin within 3 months before screening, history of foot ulceration, planned bariatric surgery, history of alcohol or drug overuse in the 2 years before screening, family history of a hereditary neuropathy, or an alternative neuropathy cause.InterventionsParticipants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day.Main Outcomes and MeasuresIENFD and NQOL-DN score were co-primary outcome measures. A positive study was defined as efficacy in both or efficacy in one and noninferiority in the other.ResultsA total of 211 individuals were screened, and 132 were randomly assigned to treatment groups: 66 in the topiramate group and 66 in the placebo group. Age and sex were similar between groups (topiramate: mean [SD] age, 61 (10) years; 38 male [58%]; placebo: mean [SD] age, 62 (11) years; 44 male [67%]). The difference in change in IENFD and NQOL-DN score was noninferior but not superior in the intention-to-treat (ITT) analysis (IENFD, 0.21 fibers/mm per year; 95% CI, −0.43 to ∞ fibers/mm per year and NQOL-DN score, −1.52 points per year; 95% CI, −∞ to 1.19 points per year). A per-protocol analysis excluding noncompliant participants based on serum topiramate levels and those with major protocol deviations demonstrated superiority in NQOL-DN score (−3.69 points per year; 95% CI, −∞ to −0.73 points per year). Patients treated with topiramate had a mean (SD) annual change in IENFD of 0.56 fibers/mm per year relative to placebo (95% CI, −0.21 to ∞ fibers/mm per year). Although IENFD was stable in the topiramate group compared with a decline consistent with expected natural history, this difference did not demonstrate superiority.Conclusion and RelevanceTopiramate did not slow IENFD decline or affect NQOL-DN score in the primary ITT analysis. Some participants were intolerant of topiramate. NQOL-DN score was superior among those compliant based on serum levels and without major protocol deviations.Trial RegistrationClinicalTrials.gov Identifier: NCT02878798

show abstract

Chronic Idiopathic Axonal Polyneuropathy Is Associated With the Metabolic Syndrome

Cited by 53 publications

References 39 publications

Chronic obstructive pulmonary disease is not a risk factor for polyneuropathy: A prospective controlled study

Chronic obstructive pulmonary disease is not a risk factor for polyneuropathy: A prospective controlled study

Autophagy in Peripheral Neuropathy

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome

Contact Info

Product

Resources

About