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Brain & Heart Impact of ketogenic diet in adults with drug-resistant epilepsy

As a high-fat, low-carbohydrate diet, the most common EEG characteristics for analysis. The GPFA was initially
adverse effects may include gastrointestinal symptoms such recognized as a characteristic discharge of Lennox-Gastaut
as diarrhea, abdominal pain, vomiting, and constipation. syndrome and was often associated with axonal muscle
However, the symptoms are mostly mild and can tonic seizures, drug resistance, and poor prognosis, such as
generally be managed and prevented with intervention. 15,28 developmental retardation. Now, it is observed not only in
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Furthermore, hyperlipidemia is a common adverse effect patients with epileptic encephalopathy but also in patients
of all types of KD therapy, but the lipid levels typically with generalized idiopathic epilepsy and serves as an EEG
increase temporarily; they often remain within the normal indicator of poor prognosis. 38,39 GPT was first discovered as
range after 12 months. 29-31 The adverse effect rate in our a predictor of drug-resistant idiopathic generalized seizures
study is 37.5%, but the symptoms were mild, and all could by Sun et al. and confirmed by multiple studies. In patients
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be managed with minimal intervention. No significant with refractory epilepsy, we aimed to explore whether the
difference was found between serum metabolism presence of GPT or GPFA is associated with poor clinical
indicators and MAD treatment, except for the level of total efficacy of KD. Interestingly, our results showed that three
cholesterol. Thus, in agreement with previous studies, the patients have GPT, two patients have GPFA, and they are
safety of MAD treatment in adult patients is confirmed in all non-responders, while no GPT or GPFA was found in
the present study. the responder group. Further meaningful insights may
Previous studies have identified objectively that be gained through additional analysis with an expanded
KD treatment has a positive impact on behavioral and sample size.
cognitive function in children and adolescents with The primary limitation of our study is the small sample
refractory epilepsy. The results include improved gross size. It is possible that the observed results could represent
motor and adaptation, as well as decreased anxiety and a placebo effect or regression to the mean. Enhancing the
depression mood. However, the positive cognitive effects accuracy and reliability of our findings would necessitate a
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of KD treatment in adults have been reported subjectively larger sample size and a more extended follow-up period.
by patients and their parents in previous studies, which A well-designed prospective randomized controlled study,
include improved alertness and concentration. Our results incorporating comprehensive laboratory tests, global
showed that MAD treatment can improve the scores of neuropsychological assessments, and EEG at baseline and
the AVLT instant recall scale. However, we found no key time points, would provide the most robust evidence. In
significant difference between MAD treatment on choice addition, the absence of detailed neuropsychological tests
reaction time and visual searching task scale scores. pertaining to overall cognition function is a noteworthy

The KD treatment has been shown to significantly limitation that might result in overlooking other positive
improve EEG epileptiform discharge activity in patients results. It would be valuable to include global cognitive
with drug-refractory epilepsy, leading to improved assessments and explore comorbidities such as anxiety
background rhythm in the occipital region 33,34 and a and depression in more detail. Moreover, investigating
decreased IED index. 35,36 Our results demonstrated that the mechanisms underlying seizure worsening after MAD
MAD treatment significantly reduces the IED index in treatment is an avenue that warrants further exploration.
NREM2. However, whether these changes in the IED index 5. Conclusion
predict the clinical efficacy of KD treatment is still under
debate. A study has indicated a correlation between the While KD has garnered recognition as an effective
reduction of epileptiform discharge activity and clinical treatment for patients grappling with refractory epilepsy,
seizure improvement. However, similar to other studies, the intricacies of its impact on epileptiform discharge
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we found no significant correlation between the change in activity remain unclear. The early clinical predictors and
the IED index and the clinical efficacy of MAD. This lack EEG characteristics indicative of KD efficacy warrant
of correlation may be related to the small sample size of our further exploration.
study, and further confirmation is required by expanding
the sample size. Acknowledgments

At present, there is no unified conclusion regarding We are truly grateful to the patients and their family members.
early predictive factors of KD efficacy. In our study, we Funding
found no predictive relationship between baseline EEG
general features, baseline seizure frequency, changes in This research was supported by the Beijing Hospitals
epileptic discharge activity, and the clinical efficacy of Authority Clinical Medicine Development of special
MAD. In addition, GPFA and GPT were included in the funding (Grant Number: XMLX202117).

Volume 2 Issue 1 (2024) 8 https://doi.org/10.36922/bh.1978