Metabolic Syndrome, Neurotoxic 1-Deoxysphingolipids and Nervous Tissue Inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

AimChronic idiopathic axonal polyneuropathy (CIAP) is a slowly progressive, predominantly sensory, axonal polyneuropathy, with no aetiology being identified despite extensive investigations. We studied the potential role of the metabolic syndrome, neurotoxic 1-deoxysphingolipids (1-deoxySLs), microangiopathy and inflammation in sural nerve biopsies.MethodsWe included 30 CIAP-patients, 28 with diabetic distal symmetrical polyneuropathy (DSPN) and 31 healthy controls. We assessed standardised scales, tested for the metabolic syndrome, measured 1-deoxySLs in plasma, performed electroneurography and studied 17 sural nerve biopsies (10 CIAP; 7 DSPN).ResultsOne third of the CIAP-patients had a metabolic syndrome, significantly less frequent than DSPN-patients (89%). Although the metabolic syndrome was not significantly more prevalent in CIAP compared to healthy controls, hypercholesterolemia did occur significantly more frequent. 1-deoxySLs were significantly and equally elevated in both patient groups compared to healthy controls. Mean basal lamina thickness of small endoneurial vessels and the number of CD68- or CD8-positive cells in biopsies of CIAP- and DSPN-patients did not differ significantly. However, the number of leucocyte-common-antigen positive cells was significantly increased in CIAP.ConclusionsA non-significant trend towards a higher occurrence of the metabolic syndrome in CIAP-patients compared to healthy controls was found. 1-deoxySLs were significantly increased in plasma of CIAP-patients. Microangiopathy and an inflammatory component were present in CIAP-biopsies

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Endurance and resistance exercise have different effects on skeletal muscle phenotype. Using mouse models and human subjects, the authors show that JNK/Smad2 signaling acts as molecular switch that when activated by resistance exercise leads to hypertrophy, and when inhibited promotes endurance adaptations in muscle

Prevalence of metabolic syndrome and its components in CIAP patients and controls.

<p>Prevalence of metabolic syndrome and its components in CIAP patients and controls.</p

LCA immunohistological stains of sural nerve biopsies in CIAP (A) and DSPN (B).

<p>The number of endoneural (dotted arrows) and perivascular (full arrow) LCA-positive cells is significantly higher in biopsies of CIAP-patients compared to those in DSPN-patients. Magnification bar corresponds to 50 μm.</p

Distribution of 1-deoxySLs in plasma of CIAP-patients and controls.

<p>A significant elevation of 1-deoxySO (A) and 1-deoxySA (B) in plasma of CIAP- or DSPN-patients compared to healthy controls is shown. Not significant (ns): P>0.05; significant: *: P≤ 0.05; **: P≤ 0.01; ***: P≤ 0.001; ****: P≤ 0.0001.</p

Plasma sphingolipid profile in CIAP patients and controls.

<p>Plasma sphingolipid profile in CIAP patients and controls.</p

Demographic and clinical features in CIAP patients and controls.

<p>Demographic and clinical features in CIAP patients and controls.</p

Evaluation of sural nerve biopsies in patients with CIAP or DSPN.

<p>Evaluation of sural nerve biopsies in patients with CIAP or DSPN.</p