Cerebellar learning distinguishes inflammatory neuropathy with and without tremor

Abstract

Objectives: This study aims to investigate if patients with inflammatory neuropathies and tremor have evidence of dysfunction in the cerebellum and interactions in sensorimotor cortex compared to nontremulous patients and healthy controls.

Methods: A prospective data collection study investigating patients with inflammatory neuropathy and tremor, patients with inflammatory neuropathy without tremor, and healthy controls on a test of cerebellar associative learning (eyeblink classical conditioning), a test of sensorimotor integration (short afferent inhibition), and a test of associative plasticity (paired associative stimulation). We also recorded tremor in the arms using accelerometry and surface EMG.

Results: We found impaired responses to eyeblink classical conditioning and paired associative stimulation in patients with neuropathy and tremor compared with neuropathy patients without tremor and healthy controls. Short afferent inhibition was normal in all groups.

Conclusions: Our data strongly suggest impairment of cerebellar function is linked to the production of tremor in patients with inflammatory neuropathy.

Figure 1. Eyeblink classical conditioning in the 3 groups

Mean percentage of conditioned responses of each group of subjects over the 7 conditioning blocks (C1–C7). E1 and E2 represent extinction blocks. Error bars represent standard error. *Significantly lower rate of conditioned blink responses in tremulous patients compared to healthy controls and to nontremulous patients.

Figure 2. Short afferent inhibition in the 3 groups

Effect of short afferent inhibition on mean conditioned/unconditioned motor evoked potential (MEP) area. *Significant inhibition at N20 and N20−2 ms among all groups. Relative values are used for the figure. Error bars represent standard error.

Figure 3. Paired associative stimulation in the 3 groups

Effect of paired associative stimulation (PAS) on mean motor evoked potential (MEP) areas in healthy controls (white), patients with inflammatory neuropathies without tremor (gray), and patients with inflammatory neuropathies with tremor (black). The data are plotted as a ratio to the baseline MEP area. Error bars represent standard deviation. Ratios higher than 1 indicate facilitation and ratios below 1 indicate inhibition of MEP area. The effect of PAS on MEP area for the abductor pollicis brevis (target) muscle (A), on the first dorsal interossei (B), and on the abductor digiti minimi (C). *p < 0.05 paired t test comparing MEP area with baseline (corrected for multiple comparisons by Bonferroni method).