Mozart K.448 listening is reported to diminish the intensity of tinnitus, improve the paper-folding and cutting tests in patients with mild cognitive impairment, and increase weight gain in preterm infants by reducing resting energy expenditure –. Regarding epilepsy, our previous works show that interictal discharges were reduced in most patients with epilepsy when they listened to Mozart K.448 . In addition, 72.7% of the patients with refractory epilepsy became seizure free or had a very good response by listening to Mozart K.448 . Our previous report also demonstrates that Mozart K.448 is not the only piece of music to have beneficial effects on children with epilepsy, and that listening to Mozart K.545 with similar lower harmonics can decrease epileptiform discharges in epileptic children as well .
In this current study, we investigated the effect of Mozart K.448 on seizure recurrence after the first unprovoked seizure. The results showed that listening to Mozart K.448 once daily reduced the seizure recurrence rate and epileptiform discharges. The estimated seizure recurrence rate in the control group was 76.8%, while it was 37.2% in music treated patients. The epileptiform discharges also showed an approximate 70-80% reductions after 1, 2, and 6 months of music listening.
Seizure recurrence after the first unprovoked seizure in pediatric patients ranges from 26-71% . Risk factors for seizure recurrence include a remote symptomatic etiology, an abnormal EEG, a seizure occurring while asleep, a history of prior febrile seizures, and Todd’s paresis . In a large study, 564 patients, including adults and children who had first unprovoked seizures, have been followed up for 2–4 years. Sixty-seven percent of them had a recurrence within 12 months of the first seizure, and 78% had a recurrence within 36 months . In the under the age of 16 group, the seizure recurrence rate was 83% by 36 months . In our study, the seizure recurrence rate was estimated to be 76.8% by 24 months in the control group. An abnormal EEG and an age less than 16 appeared to be risk factors for a higher recurrence rate in our study. However, the seizure recurrence rate did not demonstrate a significant difference in patients with different gender, mentality, seizure type, and etiology. The results were similar to our previous studies which show that gender, mentality, and etiology of epilepsy do not influence the short-term or long-term music effect on epileptiform discharges [9, 21].
The epileptiform discharges were significantly reduced in EEGs performed 1, 2, and 6 months after initiating music listening in patients without seizure recurrence. However, the epileptiform discharges did not decrease in a duration-dependence manner. EEG improvement after one month of listening to Mozart K.448 may serve as an indicator in determining the long term outcome of music intervention. Although it is not possible to predict how long the patients should be treated, the effectiveness of music listening was demonstrable within one month and continued for at least 6 months. We suggest that listening to music daily for 6 months has a beneficial effect in decreasing seizure recurrence in children with first unprovoked seizures.
Recently, several theories have been introduced regarding the effects of sound on the brain. Poor health is reported to be associated with lower parasympathetic tone in several medical conditions, including epilepsy . Lotufo et al. report a sympathovagal imbalance in epilepsy, as shown by lower high frequency (HF), the standard deviation of the RR interval (SDNN), and the square root of the mean squared differences of successive RR intervals (RMSSD) values when compared to controls . One study shows that a two-hour music intervention in cancer patients increases their relaxation scores and parasympathetic activities . Another study shows that forty-five minutes of music therapy once a week in patients with cerebrovascular disease enhances parasympathetic activities and decreases congestive heart failure events by reducing plasma cytokine and catecholamine levels . Our previous data also demonstrates that significant increases in HF, RMSSD, the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute in heart rate variability analysis occurs while listening to Mozart music in children with epilepsy. At the same time, epileptiform discharges are significantly reduced during and right after listening to Mozart music. The results suggest that Mozart music stimuli induces parasympathetic activation . It is possible that musical enhancement of parasympathetic tone may account for the beneficial effects on epilepsy.
Neurotransmitter pathways may also be involved in the effect of Mozart K.448 on epilepsy. Musical exposure is known to increase the expression of dopamine levels in the brain . In recent years, the role of dopamine in the pathophysiology of epilepsy has been well documented. A Positron Emission Tomography study shows that impaired dopamine uptake in the midbrain is hypothesized to contribute to seizures in juvenile myoclonic epilepsy . In a recent animal study, the authors report that pentylenetetrazole induced seizures decrease the dopamine levels in striatal and hippocampal areas, accompanying the induction and propagation of seizures . It is possible that listening to music modifies the dopaminergic pathways contributing to the beneficial effects in epilepsy therapy.
There are limitations to this present study. First, the number of participants was somewhat limited and most of the patients were idiopathic in etiology. The statistical power is 0.74, under alpha error 0.05, based on 22 treatment and 24 control subjects with non-recurrence rates 0.63 and 0.23, respectively. Although the power is not sufficient, our findings may provide preliminary evidence that Mozart K.448 listening is beneficial for children with first unprovoked seizures. Second, the lack of control music made it impossible to say that the effects were specific to Mozart K.448 or to a placebo effect. Third, because we did not follow up the EEG in all patients in the control group, it could not be determined whether time duration itself could have caused the decreases in epileptiform discharges, although we had shown that there were significant decreases in epileptiform discharges after listening to Mozart K.448 in treatment group. Fourth, we used per protocol analysis with compliant patients instead of using intention-to-treat analysis, although the result of intention-to-treat is also significant (p = 0.029).