Introduction
Multimodal evoked potentials (EPs) include brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), and somatosensory evoked potentials (SEPs). EPs can indicate lesions in the central nervous system (CNS) in an objective and sensitive manner [
1]. BAEPs are recorded in superficial bipolar electrodes (A1or A2, relative to Cz) through the auditory conduction pathway after applying a sound stimulus [
2]. A VEP is the evoked response recorded in the visual center after applying a light stimulus, and is the total response of visual signal generation, transduction, and final transmission to the visual center [
3]. Furthermore, and an SEP is the evoked response recorded in the corresponding sensory cortex through the deep sensory conduction pathways following electrical stimulation of the limbs [
4].
Acute disseminated encephalomyelitis (ADEM) is an immune-mediated idiopathic inflammatory demyelinating disease of the CNS and is characterized by an encephalopathy ranging from behavioral change to alteration in consciousness [
5]. Many studies have shown that ADEM is associated with a favorable outcome [
6], whereas other studies revealed a mortality rate of 20% and considerable neurologic sequelae in survivors [
7,
8]. Therefore, it is critical to identify ADEM through clinical presentations, imaging findings, neurophysiological techniques and immunological testing at the acute stage. Many researchers have investigated multimodal EPs of CNS demyelinating diseases such as multiple sclerosis [
9], neuromyelitis optica spectrum disorder [
10], and other diseases with clinical features of CNS damage; the latter include chronic HCV infection [
11], and primary Sjögren’s Syndrome [
12]. However, relatively few studies on multimodal EPs have been conducted on ADEM, particularly in children. Thus, we herein comprehensively investigated the diagnostic value of multimodal EPs in ADEM from auditory, visual, and sensory aspects and thereby retrospectively analyzed the BAEP, VEP, and SEP characteristics of 34 children with ADEM.
Discussion
ADEM is a multifocal monophasic inflammatory disease of the CNS that tends to primarily affect children and young adults [
16]. In the present study, 23.5% of our patients reflected a history of infection or vaccination, and the proportion of men was higher, but not significant. ADEM manifests a rapid onset and presents with diverse clinical symptoms, with a small subset of children with ADEM experiencing more than one event, making the diagnosis of pediatric ADEM relatively difficult. There is a paucity of biomarkers for the early diagnosis of ADEM other than typical imaging [
17]; and as brain and spinal imaging are normal in the early course of the disease, it is essential to seek sensitive and objective neurophysiological markers that can be applied to identify ADEM at the acute stage.
Recording EPs can detect clinical or subclinical lesions in visual, auditory, sensory, and motor pathways; and they are particularly suitable for young children who cannot cooperate fully with the examination. Characteristic findings of BAEPs are primarily manifested as absent or delayed latencies in CNS demyelinating disorders [
18],such as MS/NMOSD,or other diseases with clinical features of CNS damage [
19]. In addition, prolonged latency and interpeak intervals of waves were expressions of demyelinating damage and are highly accurate in identifying demyelinating diseases [
20]. Another finding of BAEPs encompasses amplitudes and morphological abnormalities, which are expressions of axonal damage that is considered the most important factor in determining disability [
21]. The BAEPs of children with ADEM in the present study exhibited prolonged latencies of waves III and V, and a significantly higher rate of abnormalities, whereas the latency of wave I did not change significantly. This indicates that the damage to the auditory conduction pathway in children with ADEM was primarily at the level of the superior olivary complex and inferior colliculus, abnormalities observed corresponded to the clinical localization of the lesion, consistent with most studies [
17].
In routine practice, VEPs are proven to be useful in the diagnosis of neurological disorders affecting the visual pathways, including optic neuritis [
22], multiple sclerosis, Leber’s hereditary optic neuropathy [
23], and central nervous system tumors [
24].The P100 latency of pattern VEPs indicated myelin damage while flash VEPs indicated axonal pathology; pattern VEPs were also more sensitive than flash VEPs in detecting optic nerve demyelination [
25].Abnormal VEP patterns with preserved normal flash VEPs indicated isolated myelin damage, and abnormalities in both pattern VEPs and flash VEPs indicated myelin and axonal damage in the optic nerve [
26].Among 34 children with ADEM, there were five patients with optic neuritis, of whom four showed abnormal pattern VEPs and one manifested abnormal flash VEPs; 19 cases showed abnormal subclinical VEPs. These results agree with a previous report showing that the characteristic VEP finding of patients with ADEM was a delay or a loss of P100/P1, indicating that ADEM primarily affected the central portion of the visual conduction pathway.
With respect to SEPs, (which are used to evaluate the function of afferent sensory pathways), the N20 of upper-limb SEPs originates in the primary sensory cortex of the contralateral parietal lobe, while the N9 notch is generated in the brachial plexus and N13 is a synaptic potential generated in the cervical spinal cord where sensory afferents connect with the posterior spinal cord horn [
27], Higher abnormal SEPs thus indicated that the afferent sensory conduction pathway in CNS demyelinating diseases, (such as MS and ADEM) primarily involved the central part of the sensory nerve [
28].The high sensitivity of SEPs in this study was similar to that of other demyelinating diseases and indicated the poor differentiation of cortical waves and nearly normal latency in peripheral recording sites.
The present results also supported the diagnostic value of BAEPs/VEPs/SEPs in ADEM. In addition, the combined application of multimodal EPs exhibited statistically significant differences compared with BAEPs or VEPs alone; thus, the combination of multimodal EPs can increase the early diagnostic value of children with ADEM.
Our study was also subject to some limitations. First, we only analyzed the latencies of EPS in this study, and did not evaluate wave amplitudes. Second, this was a small retrospective study that only comprised 34 pediatric ADEM patients. In the future, we will also conduct some prospective clinical studies on the prognosis of children with ADEM based on the present study.
In conclusion, we herein analyzed the EP characteristics of pediatric patients with ADEM and demonstrated that the combined application of multimodal EPs was superior to BAEPs, VEPs, or SEPs alone in detecting central nervous system involvement. We recommend that these EPs would be conducted in all patients with ADEM.
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