Motor evoked potential polyphasia: a novel endophenotype of idiopathic generalized epilepsy

Abstract

Objective: We compared the motor evoked potential (MEP) phases using transcranial magnetic stimulation in patients with idiopathic generalized epilepsy (IGE), their relatives, and healthy controls, hypothesizing that patients and their unaffected relatives may share a subtle pathophysiologic abnormality.

Methods: In a cross-sectional study, we investigated 23 patients with IGE, 34 first-degree relatives, and 30 matched healthy controls. Transcranial magnetic stimulation was performed to produce a series of suprathreshold single-pulse MEPs. A semiautomated method was used to count phases. We compared between groups the mean number of MEP phases, the stimulus-to-stimulus variability in MEP phases, and the proportion of polyphasic MEPs within subjects.

Results: Patients with IGE and their relatives had a significantly increased number of MEP phases (median for patients 2.24, relatives 2.17, controls 2.01) and a significantly higher proportion of MEPs with more than 2 phases than controls (median for patients 0.118, relatives 0.088, controls 0.013). Patients had a greater stimulus-to-stimulus variability in number of MEP phases than controls. There were no differences between patients and relatives.

Conclusion: Increased MEP polyphasia in patients with IGE and their first-degree relatives may reflect transient abnormal evoked oscillations. The presence of polyphasic MEPs in relatives as well as patients suggests that MEP polyphasia is not related to treatment, and is in isolation insufficient to predispose to epilepsy. Polyphasic MEP may be a novel endophenotype in IGE.

Figure 1. Motor evoked potential (MEP) from single transcranial magnetic stimulation pulse over contralateral motor cortex, recorded using surface EMG from first dorsal interosseus muscle

(A) A polyphasic MEP from a patient with idiopathic generalized epilepsy with a count of 4 phases. (B) A normal MEP from a healthy control subject.

Figure 2. Patients with idiopathic generalized epilepsy and first-degree relatives have significantly more polyphasic motor evoked potentials (MEPs) than healthy controls

(A) Within-subjects mean number of MEP phases across the 20 MEPs, illustrated for the patient, relative, and control groups. Box-and-whisker plot showing group median (horizontal line in box), 25th and 75th centiles (bottom and top of box), and minimum and maximum values (lower and upper whiskers). (B) Within-subjects interquartile range of the number of MEP phases across the 20 MEPs, illustrated for the patient, relative, and control groups. Box-and-whisker plot showing group median (horizontal line in box), 25th and 75th centiles (bottom and top of box), and minimum and maximum values (lower and upper whiskers). (C) Within-subjects proportion of MEPs with >2 phases across the 20 MEPs, illustrated for the patient, relative, and control groups. Box-and-whisker plot showing group median (horizontal line in box), 25th and 75th centiles (bottom and top of box), and minimum and maximum values (lower and upper whiskers).

Figure 3. Motor evoked potential (MEP) data for all subjects are summarized

For each subject, the proportion of MEPs with each specific number of phases (1 phase to 6 phases) was calculated; across each group of subjects, the median proportion of MEPs with each specific number of phases was estimated, and in addition the group minimum, 25th centile, 75th centile, and maximum. The data are displayed as box-and-whisker for each group and each number of MEP phases. The horizontal line in the box indicates the median proportion across the group, lower and upper limits of the box represent group 25th and 75th centiles, and the lower and upper whiskers represent the group minimum and maximum. Note that for most subjects in all groups, the proportion of MEPs with 2 phases is >0.8, whereas for most subjects in all groups, the proportion of MEPs with 1, 5, or 6 phases is zero. Note that compared with healthy control subjects, patients and relatives have a reduced proportion of MEPs with 2 phases, and an increased proportion of MEPs with >2 phases (especially 4 phases).