Abstract
Background:
Mozart’s Sonata for Two Pianos in D Major (K448) is a classic double piano work. This study investigated its effect on children with epilepsy (EP) and analyzed the changes in electroencephalography (EEG) among children on the basis of acoustic quality.
Methods:
The clinical data of 150 children with EP in the Affiliated Hospital (Group) of Putian University from March 2020 to March 2023 were retrospectively analyzed. They were divided into group A (n = 73, antiepileptic drug therapy) and group B (n = 77, antiepileptic drug therapy + Mozart K448) in accordance with the treatment methods. The seizure frequency, frequency of epileptic discharges (EDs), and Quality of Life in Childhood Epilepsy Questionnaire-16 in both groups were compared before and after treatment. The changes in EEG before, during, and after music appreciation were observed. The effects of the acoustic characteristics (rhythm, root mean square value, roughness, and spectral flux) of Mozart K448 on EDs in children were explored.
Results:
After treatment, group A had a higher seizure frequency (P < 0.001), a higher frequency of EDs (P < 0.05), and significantly lower scores of cognition and emotion than group B (P < 0.001), without significant difference in the scores of social function and physical function (P > 0.05). The frequency of EDs before music appreciation was significantly higher than that during music appreciation (P < 0.01). Spearman correlation analysis showed that the rhythm, spectral flux, and roughness in Mozart K488 were related to the decrease in EDs among children with EP (P < 0.001).
Conclusion:
This study confirmed the application effect of Mozart K448 in children with EP. Mozart K448 can decrease the seizure frequency, reduce the ED occurrence, and improve the quality of life. The acoustic characteristics of K448 may be the reason for improving EP in children.
Keywords: music therapy, epilepsy, child, electroencephalogram
KEY MESSAGES:
-
(1)
Mozart K448 can be used as a non-pharmacological adjuvant therapy for children with EP.
-
(2)
Mozart K448 improves the quality of life of children with EP.
-
(3)
Mozart K448 provides a low-cost and safe non-drug treatment for children with EP.
-
(4)
The acoustic characteristics of Mozart K448 may be the reason for improving EP in children.
Introduction
Epilepsy (EP), characterized by an enduring predisposition for epileptic seizures,[1] can affect the quality of life of patients.[2] Approximately 70% of patients with EP can be fully controlled by antiepileptic drugs (AEDs),[3] but nearly one-third of patients cannot achieve the desired effect through simple drug therapy.[4] The effect of some drugs on the development of pediatric patients is still unclear.[5] In addition, children with EP often need to avoid epileptic seizures when receiving drug treatment. Ioannou et al.[6] have considered that when single therapy cannot control the epileptic seizures, actively finding a safer and more effective adjuvant therapy is necessary.
Music therapy, as a non-invasive treatment, has been widely used in clinical practice. Sesso G et al.[7] have included 12 studies for meta-analysis and found that music-based neuromodulation can be used as a non-drug complementary approach for the treatment of EP and epileptic discharges (EDs). Multiple studies have shown that Mozart K448 can improve epileptic seizures, which may have a bearing on the acoustic characteristics of music.[8,9] A study has pointed out that daily listening to Mozart K448 is associated with a reduction in seizure frequency in adults with EP.[10] However, studies on the application of Mozart K448 in children with EP are relatively few, and a specific analysis of the impact of acoustic quality of Mozart K488 on electroencephalography (EEG) is lacking. On the basis of the above theory, this retrospective study aimed to explore the application effect of Mozart K448 in children with EP and analyze EEG changes on the basis of acoustic quality, hoping to provide further directions for the treatment of such children.
METHODS
Research Subjects
In this study, 162 children with EP from March 2020 to March 2023 in the Affiliated Hospital (Group) of Putian University were selected as the research subjects. Seven cases with incomplete clinical data, three cases with abnormal hearing, and two cases with malignant tumors were excluded, and finally, 150 children with EP were included. This study has been approved by the hospital’s Ethical Committee. The guardians who were aware of the purpose and significance signed an informed consent form.
EP is defined as a chronic brain disease characterized by recurrent attacks with or without loss of consciousness, with or without neurological, mental, cognitive, and sociological dysfunction.[11] The definition of EP requires the occurrence of at least one epileptic seizure (one epileptic seizure, two epileptic seizures, or more than two times [interval between two episodes > 24 hours]).
Inclusion and Exclusion Criteria
The inclusion criteria were as follows: (1) Children aged ≤18 years old; (2) children with complete clinical data; (3) children with normal hearing function; and (4) children who took one kind of AED only after diagnosis.
The exclusion criteria were as follows: (1) Children with metabolic disorders and malignant tumors; (2) children with a history of brain resection (EP surgery); (3) children with acoustic nerve damage or hearing impairment; and (4) children with congenital mental retardation.
Research Methods
The clinical data of 150 children with EP in the Affiliated Hospital (Group) of Putian University from March 2020 to March 2023 were retrospectively analyzed. Seventy-three children who received antiepileptic drug therapy from March 2020 to August 2021 were classified as group A, and the remaining 77 cases who were treated with conventional drug therapy and Mozart K448 music therapy from September 2021 to March 2023 were assigned into group B [Figure 1].
Figure 1.
Patient inclusion and grouping.
The medical records of children were retrieved from the medical record management system, including sex, age, age of first onset, place of birth, family history, seizure types, therapeutic drugs, seizure frequency before treatment, EEG examination data (ED occurrence), and Quality of Life in Childhood Epilepsy Questionnaire-16 (QOLCE-16) scores before and after treatment.
The equipment and materials used in this study were as follows: (1) Dynamic EEG apparatus (model: PI400A-B, Shanghai Quntian General Electric Appliance Co., Ltd., Shanghai, China) and (2) The QOLCE-16 scale[12] included four dimensions: cognition (four items), emotion (four items), social function (four items), and physical function (four items). The five-point Likert scale was used to calculate the scores of each dimension and the scores of the total scale (1 = often, 2 = quite frequent, 3 = sometimes, 4 = hardly ever, 5 = never). A notable detail that the scale also included a sixth option (6 = not applicable), but this option was not adopted. The numerical value of the items was encoded as 0–100 points. The higher the score was, the better the quality of life.
Mozart K448 Music Therapy
The equipment included a Ruizu M7 MP5 music player with a full version of Mozart K448 (batch no.: 2014010805675246, Shenzhen Ruizu Digital Technology Co., Ltd., Shenzhen, Guangdong, China), and FINGERTIME headphones (batch no.: 10079359400092, Shenzhen Century Digital Technology Co., Ltd., Shenzhen, Guangdong, China). Mozart K448 was played daily for 10 minutes each time at 35–40 dB. The treatment was continued for 3 months. Children who have been hospitalized for <3 months could take away the music player and headphones after paying the deposit and continue their treatment outside the hospital. The children were followed up for 3 months, and telephone or outpatient follow-up was carried out once a week to understand their seizure situation and urge them to adhere to music therapy.
EEG Analysis Based on Acoustic Quality
A total of 500 seconds were selected before, during, and after the appreciation of K488 music. The seconds of ED occurrence (peak, peaked wave or multiple peaked waves in EEG) in different time periods were manually counted by professional doctors and extracted once every 10 seconds for comparison. The same method was used to calculate the frequency of EDs before and after treatment. Acoustic analysis of Mozart K488 was conducted. EEG was observed in accordance with rhythm, root mean square value, roughness, and spectral flux; and the relationship between acoustic quality and EDs was explored.
Statistical Analysis
The Statistical Package for the Social Sciences (SPSS software version 27.0, International Business Machines Corporation, Armonk, New York, USA) was utilized for data analysis and processing in this study. Categorical variables were presented as n (%), and the appropriate test was selected based on the “minimum expected count” criterion. Specifically, chi-square test was employed when the “minimum expected count” was ≥5, whereas Fisher’s exact test was utilized when the “minimum expected count” was < 5. The continuous variables that did not follow normal distribution were tested by Mann–Whitney U test and expressed as M (P25, P75). A P value of < 0.05 indicated statistically significant difference. Spearman correlation analysis was used to evaluate the relationship between the acoustic quality of Mozart K488 and the ED occurrence in children with EP. Figure 1 was created using Microsoft Office Word 2006 (Microsoft Corporation, Redmond, Washington State, USA).
RESULTS
Comparison of General Data in Both Groups
No significant difference existed in sex, age, age of first onset, place of birth, family history, seizure types, therapeutic drugs, seizure frequency, and frequency of EDs before treatment between the two groups (P > 0.05), as detailed in Table 1.
Table 1.
Comparison of General Data in Both Groups (M (P25, P75), n (%))
| Items | Group A (n = 73) | Group B (n = 77) | Statistics | P |
|---|---|---|---|---|
| Sex | χ2 = 0.203 | 0.652 | ||
| Male | 40 (54.79) | 45 (58.44) | ||
| Female | 33 (45.21) | 32 (41.56) | ||
| Age (years) | 8.00 (6.00, 11.00) | 9.00 (6.00, 11.00) | Z = −0.353 | 0.724 |
| Age of first onset (years) | 5.00 (3.00, 7.00) | 5.00 (4.00, 7.00) | Z = −0.376 | 0.707 |
| Place of birth | χ2 = 0.030 | 0.863 | ||
| Urban areas | 35 (47.95) | 38 (49.35) | ||
| Rural areas | 38 (52.05) | 39 (50.65) | ||
| Family history | χ2 = 0.135 | 0.714 | ||
| Yes | 15 (20.55) | 14 (18.18) | ||
| No | 58 (79.45) | 63 (81.82) | ||
| Seizure types | Fisher = 0.296 | 0.947 | ||
| Generalized seizure | 34 (46.58) | 37 (48.05) | ||
| Partial seizure | 38 (52.05) | 38 (49.35) | ||
| Others | 1 (1.37) | 2 (2.60) | ||
| Therapeutic drugs | χ2 = 0.294 | 0.961 | ||
| Levetiracetam | 27 (36.99) | 27 (35.06) | ||
| Sodium valproate | 18 (24.66) | 22 (28.57) | ||
| Oxcarbazepine | 22 (30.14) | 22 (28.57) | ||
| Others | 6 (8.22) | 6 (7.79) | ||
| Seizure frequency before treatment (times/months) | 12.00 (9.00, 16.00) | 11.00 (8.00, 17.00) | Z = −0.085 | 0.932 |
| Frequency of EDs before treatment (times) | 38.00 (18.50, 55.50) | 36.00 (19.00, 61.00) | Z = −0.111 | 0.912 |
EDs = epileptic discharges.
Comparison of seizure frequency and ED occurrence in both groups after treatment
After treatment, the seizure frequency and the frequency of EDs in group A were 3.00 (2.00, 5.00) times/month and 27.00 (18.00, 48.50) times, respectively, and those in group B were 2.00 (1.00, 3.00) times/month and 20.00 (12.00, 39.50) times, respectively. Group A had a higher seizure frequency (Z = −4.317, P < 0.001) and a higher frequency of EDs (Z = −2.338, P = 0.019) than group B.
Comparison of QOLCE-16 Scores in Both Groups Before and After Treatment
Before treatment, no significant difference was found in the QOLCE-16 scores between the two groups (P > 0.05). After treatment, the QOLCE-16 scores of all dimensions increased significantly in the two groups (P < 0.05). The scores of cognition and emotion in group A were significantly lower than those in group B (P < 0.001), with no significant difference in the scores of social function and physical function between the two groups (P > 0.05, Table 2).
Table 2.
Comparison of QOLCE-16 Scores in Both Groups Before and After Treatment (M (P25, P75), Points)
| Times | Groups | Cognition | Emotion | Social function | Physical function |
|---|---|---|---|---|---|
| Before treatment | Group A (n = 73) | 61.00 (54.00, 66.50) | 60.00 (56.00, 66.00) | 61.00 (55.00, 66.00) | 48.00 (44.00, 52.00) |
| Group B (n = 77) | 60.00 (54.00, 64.50) | 61.00 (57.00, 65.00) | 60.00 (55.00, 65.50) | 49.00 (44.00, 52.00) | |
| Z | −0.462 | −0.396 | −0.315 | −0.577 | |
| P | 0.644 | 0.692 | 0.753 | 0.564 | |
| After treatment | Group A (n = 73) | 69.00 (63.50, 74.00)* | 71.00 (67.00, 74.50)* | 68.00 (63.00, 73.50)* | 56.00 (53.50, 59.50)* |
| Group B (n = 77) | 73.00 (67.00, 81.50)* | 76.00 (73.00, 80.00)* | 68.00 (64.50, 75.00)* | 57.00 (53.00, 61.00)* | |
| Z | −4.731 | −6.026 | −1.007 | −1.565 | |
| P | < 0.001 | < 0.001 | 0.314 | 0.118 |
* indicated a significant difference compared with the same group before treatment (P < 0.05).
EEG Analysis of Children with EP Based on Acoustic Quality
The median and quartiles of ED occurrence before, during and after appreciation of Mozart K488 in children with EP were 29.00 (17.50, 48.50), 17.00 (11.00, 35.50), and 20.00 (12.00, 39.50), respectively. The frequency of EDs before appreciation was significantly higher than that during appreciation, with no significant difference during and after appreciation (Pbefore appreciation vs. during appreciation = 0.001, Pduring appreciation vs. after appreciation = 0.398). Spearman correlation analysis showed that the rhythm, spectral flux, and roughness in Mozart K488 were related to the reduction in EDs among children with EP (P < 0.001), as shown in Table 3.
Table 3.
EEG Analysis of Children with EP Based on Acoustic Quality
| EDs |
||
|---|---|---|
| R | P | |
| Rhythm | 0.871 | <0.001 |
| Root mean square value | −0.253 | 0.120 |
| Roughness | −0.795 | <0.001 |
| Spectral flux | 0.856 | <0.001 |
DISCUSSION
EP has a high incidence in early childhood, with one in every 400 children diagnosed in the first 3 years of life.[13] Currently, EP activity (whether epileptic seizures or EDs) is well recognized to have a detrimental effect on the developing brain.[14] Therefore, in this retrospective study, the clinical data of 150 children with EP were analyzed to seek an effective and safe adjuvant therapy and minimize the damage of EP to patients. The results revealed that group A had a higher seizure frequency, a higher frequency of Eds, and significantly lower scores of cognition and emotion than group B after treatment (P < 0.05), indicating that listening to Mozart K488 can significantly reduce the epileptic activity in EEG, enhance the curative effect of single antiepileptic drug therapy, and improve the quality of life of children with EP. Paprad et al.[15] have held similar views and obtained similar results, but statistical significance could not be reached due to small study population.
The results of this study were analyzed in combination with the following data: When music is unpredictable, protecting the brain network may be necessary to generate higher brain frequencies, thereby inhibiting epileptic seizures via gamma-aminobutyric acid (GABA) interneurons.[16] Many AEDs exert their effects by increasing the inhibitory activity of GABA.[17] Mozart K488 music therapy and AEDs are speculated to have a synergetic relationship, further producing a more ideal antiepileptic effect. Rafiee et al.[18] have considered that listening to music works containing the most unpredictable rhythm structure through the entrainment and 1/f resonance mechanism may reduce the self-similarity of brain activity, regulate low-frequency power and situate the brain in a more “noise-like” state. In other words, epileptic seizures have something to do with the increase in synchrony and predictability, so the entrainment and resonance mechanism in brain state with low indices can increase the resiliency of the brain activity to epileptic seizure states.
In a clinical study, 45 children with epileptic activity in EEG were recruited, and Mozart K488 and control music were played in turn. The results confirmed the antiepileptic effect of Mozart music on EEG in children, whereas control music had no such effect.[19] However, the influence mechanism of music on EP is still unclear, and the basic parameters of music, such as rhythm and roughness, have not been fully explored. Therefore, in the present study, EEG analysis was further carried out on the basis of the acoustic analysis results of Mozart K488. The results showed that the rhythm, spectral flux and roughness in Mozart K488 were related to the decrease in EDs among children with EP (P < 0.001), suggesting that the acoustic characteristics of Mozart K488 may have an antiepileptic effect on children with EP. The reason may be attributed to that Mozart K448 changes the relative spectrum powers of EEG, indicating that it may affect hippocampal neural activity.[20]
Under a short period and low cost, this study confirmed that Mozart K448, as an effective adjuvant therapy in children with EP, can improve the efficacy and quality of life, thereby providing a basis for non-drug treatment of children with EP. However, this study still has some shortcomings. Firstly, as a single-center retrospective study, it cannot guarantee the randomness of the samples and may introduce selective bias, thereby limiting the general applicability of the results. Secondly, this study involved a limited number of variables, possibly lacking in controlling factors such as the children’s family background, socioeconomic status, and biomarkers. Lastly, a retrospective study cannot develop an observation plan in advance. It cannot regularly and continuously monitor epileptic seizures and EEG changes. Therefore, follow-up studies need to perform prospective randomized controlled trials, improve the control of research variables and the design of observation indicators, and further investigate the clinical efficacy of the acoustic characteristics of Mozart K448 in children with EP.
CONCLUSION
This study confirmed the antiepileptic effect of Mozart K448 on EEG in children. Mozart K448 can decrease the seizure frequency, reduce the ED occurrence, and improve the quality of life of children. The acoustic characteristics of Mozart K448 may be the reason for improving EP in children.
Financial support and sponsorship
This research received no external funding.
Conflict of interest
The authors have no conflicts of interest to declare.
Availability of data and materials
The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
Author contributions
Liping Zheng: Conceptualization, Methodology, Writing − original draft, experimental studies, editing, Project administration.
Lin Lin: Writing − original draft, editing, Data curation, experimental studies, literature search.
Qinghuang Zeng: Data curation, experimental studies, Visualization, editing, Supervision.
Ethics approval and consent to participate
This study has been approved by the Medical Ethics Committee of the Affiliated Hospital (Group) of Putian University. Approval No.: 202477.
The guardians who were aware of the purpose and significance signed an informed consent.
Acknowledgment
Not applicable.
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Associated Data
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Data Availability Statement
The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.