Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

Abstract

Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP were lacking. To further epidemiological insight, we determined contemporary hospital-based incidence rates of polyneuropathy in general and CIAP in particular. The incidence of CIAP in the Netherlands in 2010 was 31.6/100,000 in persons ≥ 40 years old. For comparison, the overall incidence of polyneuropathy was 77.0/100,000 in persons ≥ 18 years old. There was a clear increase of the incidence of polyneuropathy and a prominent rise of the proportion of CIAP with advancing age. Diabetic polyneuropathy (32%) and CIAP (26%) were the most frequent diagnoses.

CIAP is a diagnosis of exclusion and encompasses a heterogeneous group of patients. Nevertheless, clinical characteristics as well as disease course show strong similarities between patients, which could suggest a common etiologic background. In the absence of knowledge about risk factors or probable causes, we had nothing to offer in terms of prevention and/or therapy of CIAP. We therefore studied four hypotheses on the etiology of CIAP: 1.CIAP and the metabolic syndrome. We established an association between CIAP and the metabolic syndrome in a prospective case-control study. There was a higher prevalence of the metabolic syndrome in patients with CIAP (adjusted OR 2.2). Multivariate analysis showed that only the individual components of the metabolic syndrome abdominal obesity (adjusted OR 3.3) and hypertension (adjusted OR 2.9) were independently associated with the risk of CIAP. 2.CIAP and chronic obstructive pulmonary disease (COPD). We demonstrated a similar prevalence of COPD in patients with CIAP and controls, and could not confirm COPD as a risk factor for CIAP. 3.CIAP and vitamin B6 (pyridoxine) intoxication. By comparing vitamin B6 blood levels, and supplementary and nutritional intake between patients with CIAP and controls, we investigated an etiological role of vitamin B6 intoxication in CIAP. Patients with CIAP more often used vitamin B6 (pyridoxine) containing supplements, but otherwise there were no differences in vitamin B6 blood levels, duration of supplement use, daily and cumulative dose, or dietary intake, and there was a lack of improvement in patients with CIAP after cessation of supplement use. It is unlikely that CIAP is caused by a vitamin B6 intoxication due to the use of vitamin B6 containing supplements. 4.CIAP, nutrition and alcohol use. We compared the total energy intake and the intake of 28 different nutrients in a case-control study. There were no differences between patients with CIAP and controls. Subgroup analyses within the group of CIAP patients showed that the age of onset in patients with moderate alcohol consumption (<4 alcoholic units/day) is three years earlier than in patients who never drank alcohol suggesting the toxic effect of alcohol to be on a sliding scale.