Metabolic syndrome, neurotoxic 1-deoxysphingolipids and nervous tissue inflammation in Chronic Idiopathic Axonal Polyneuropathy (CIAP)

AIM: Chronic 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. METHODS: We 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). RESULTS: One 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. CONCLUSIONS: A 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.status: publishe

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

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

Plasma sphingolipid profile in CIAP patients and controls.

<p>Plasma sphingolipid profile 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

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