Central involvement in peripheral disease: melanopsin pathway impairment in chronic inflammatory demyelinating polyneuropathy

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) compromises functions of the peripheral nervous system (PNS). Recently, however, symptoms such as cognitive deficits, visual dysfunction and circadian disorders were reported, compatible with additional involvement of the central nervous system (CNS) in CIDP. Against this background, we were interested in the functional state of melanopsin-expressing retinal ganglion cells (mRGCs) as a potential biomarker for sleep-wake abnormalities and CNS involvement in CIDP. Based on a chromatic pupillometry protocol, we examined the integrity of the melanopsin system in a prospective case-control study in 20 persons with CIDP compared to 20 controls without CIDP. The results were referred to clinical measures of disease severity and sleep behaviour. Patients with CIDP had a significantly reduced melanopsin-mediated post-illumination pupil response (PIPR) compared to healthy controls (25% versus 36%; P < 0.01). This reduction correlated with disease severity (r = 0.478, P < 0.05). Further, patients with CIDP reported diminished sleep quality (P < 0.05); however, there was no significant correlation with the melanopsin-mediated PIPR. The results demonstrate an impairment of mRGC function related to CIDP. Since the PIPR reduction correlated with disease severity, it could be an easily available biomarker for CNS affection in CIDP, a condition defined as PNS disorder.

Keywords: CNS manifestations; chromatic pupillometry; chronic inflammatory demyelinating polyneuropathy; melanopsin.

Graphical Abstract

Figure 1

Chromatic pupillometry in CIDP. A Pupillary reactions to red (632 nm) and blue (462 nm) light for a healthy subject (i, ii) and a patient with CIDP (iii, iv). B 46-second pupil tracings for red and blue light, comparing responses from healthy subjects (n = 20, i) and patients with CIDP (n = 20, ii). Dashed lines mark the timing of the PIPR. T-tests showed significant differences between healthy subjects and patients with CIDP for blue, but not for red light: PIPR_red (t = −0.615, P = 0.543); PIPR_blue (t = 2.561, P = 0.015). C Aggregate data: i: pupil response disparity between groups (thick line = mean; transparent line = standard error); ii: violin plot comparing CIDP (n = 20) with healthy (n = 20), highlighting the median (white dot) and quartiles (grey bars); t = 3.095, P = 0.004, 95% CI: 0.036–0.171; and iii: correlation with R-ODS scores; r = 0.478, P < 0.05, 95% CI: 0.044–0.760.