Abstract
IntroductionIn early multiple sclerosis (MS) patients, cognitive changes and fatigue are frequent and troublesome symptoms, probably related to both structural and functional brain changes. Whether there is a common cause of these symptoms in MS is unknown. In theory, an altered regulation of central neuropeptides can lead to changes in regulation of autonomic function, cognitive difficulties, and fatigue. Direct measurements of central neuropeptides are difficult to perform, but measurements of the eye pupil can be used as a reliable proxy of function.MethodsThis study assesses pupil size during problem‐solving in early MS patients versus controls. A difference in pupil size to a cognitive challenge could signal altered activity within the autonomic system because of early functional brain changes associated with cognitive load. We recruited MS patients (mean disease duration: 2.6 years, N = 41) and age‐matched healthy controls (N = 43) without eye pathology. Neurological impairment, magnetic resonance imaging, visual evoked potentials, depression, and fatigue were assessed in all of the patients. In both groups, we assessed processing speed and retinal imaging. Pupil size was recorded with an eye‐tracker during playback of multiplication tasks.ResultsBoth groups performed well on the cognitive test. The groups showed similar pupillary responses with a mean of 0.55 mm dilation in patients and 0.54 mm dilation in controls for all the tasks collapsed together. However, controls (N = 9) with low cognitive scores (LCS) had an increased pupillary response to cognitive tasks, whereas LCS MS patients (N = 6) did not (p < .05). There was a tendency toward a smaller pupillary response in patients with fatigue.ConclusionsThis is the first study to investigate pupillary responses to cognitive tasks in MS patients. Our results suggest that MS‐related changes in cognition and fatigue may be associated with changes in arousal and the autonomic regulation of task‐related pupillary responses. This supports the theory of a link between cognition and fatigue in MS.
Highlights
In early multiple sclerosis (MS) patients, cognitive changes and fatigue are frequent and troublesome symptoms, probably related to both structural and functional brain changes
We investigated the pupillary response to problem- solving in early MS patients and healthy controls
We conclude that the early MS patients as a group had similar task-evoked pupillary responses as their healthy controls
Summary
Multiple sclerosis (MS) patients frequently suffer from cognitive difficulties and fatigue, often present early in the disease course (Amato, Ponziani, & Pracucci, 1995; Krupp, Alvarez, LaRocca, & Scheinberg, 1988). Functional MRI (fMRI) studies have indicated that patients with MS or clinically isolated syndromes (CIS) show a different cerebral ‘resting state’ activation as well as task-related cerebral activation patterns compared to healthy controls (Audoin et al, 2003; Forn et al, 2006; Penner, Rausch, Kappos, Opwis, & Radü, 2003; Rocca, Parisi, et al, 2014; Roosendaal et al, 2010; Staffen et al, 2002). The pupil size in general depends on arousal, sleepiness and sleep-deprivation, demands on attention, and surrounding light conditions as well as visual acuity and refractional errors It is governed by the autonomic nervous system, and alterations in the sympathetic or parasympathetic nervous system possibly affects the task-evoked pupillary response as well. As we had no a priori knowledge of the direction of the possible group differences, we used an exploratory approach with two-tailed statistical testing
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