Influence of the Ketogenic Diet on 24-Hour Electroencephalogram in Children With Epilepsy

doi:10.1016/j.pediatrneurol.2007.09.002

Pediatric Neurology

Volume 38, Issue 1, January 2008, Pages 38-43

https://doi.org/10.1016/j.pediatrneurol.2007.09.002 Get rights and content

The ketogenic diet is a therapeutic diet used to treat medically refractory epilepsy in children. It was found to be effective and safe. Apart from a reduced number of seizures, positive cognitive effects were described. The mechanisms of action are not fully understood, but both antiseizure and antiepileptogenic effects were proposed. Among other changes ascribed to the introduction of the diet, changes in electroencephalogram patterns might contribute to an understanding of the effects of the ketogenic diet. In this study, 23 children (mean age, 6.5 years) with pharmacoresistant epilepsy were started on the diet. They were examined via 24-hour ambulatory electroencephalogram directly before starting the diet, and after 3 months of treatment. The changing electroencephalogram pattern was evaluated qualitatively and semiquantitatively. Background activity, interictal epileptiform activity, ictal activity, and seizure reduction were evaluated. Quality of life was estimated on a visual analog scale. In 15 of 23 patients, the electroencephalogram indicated improvement in terms of more normal background activity or decreased interictal epileptiform activity. This improvement was seen in both seizure-reduction responders and nonresponders, and was not predictive of response to treatment.

Introduction

The ketogenic diet is used to treat medically resistant epilepsy in children [1]. It is a high-fat, low-carbohydrate diet usually extracting energy from fat related to energy from carbohydrates and protein at a ratio of 4:1. It effectively reduces the number of seizures [2], and seems to affect all types of seizures [2], [3], even if there seems to be a slightly better effect on generalized compared with partial seizures [3], [4]. Many mechanisms of action were described [5], and they are still not fully understood. Both an antiseizure effect and an antiepileptogenic effect were proposed [6]. Furthermore, effects on cognition and behavior were observed [7].

In the framework of understanding its effects, the influence of the ketogenic diet on interictal and ictal electroencephalogram activity is of interest. The information obtained so far is rather limited regarding electroencephalogram changes during treatment with the ketogenic diet [8], [9], [10], [11], [12], [13], [14]. Usually, these reports contain information from routine short electroencephalograms before and during treatment.

In this study, we evaluated the changing electroencephalogram pattern in 23 children treated with the ketogenic diet, using 24-hour electroencephalogram recordings prior to starting the diet, and again after 3 months of treatment. Qualitative and semiquantitative evaluations of all recordings focused on background activity, interictal epileptiform discharges, and ictal epileptiform activity. The electroencephalogram pattern after introduction of the diet was related to seizure reduction and to a quality-of-life evaluation using a visual analog scale.

Section snippets

Patients

The present study was part of a larger prospective, open trial on the efficacy and safety of the ketogenic diet in children with epilepsy. The children were enrolled in the study consecutively while they attended the Epilepsy Outpatient Department of Karolinska Hospital (Stockholm, Sweden), and the ketogenic diet was initiated because of pharmacologically refractory epilepsy. The study was conducted at the Department of Neuropediatrics of Karolinska Hospital. The study was approved by the

Results

Seizure reduction was >50% for 16 of 23 patients (responders), and <50% for 7 of 23 patients (nonresponders). Response related to age of onset, seizure type, or etiology was not possible to evaluate statistically because of the small number of patients in each group. However, response was significantly more likely than nonresponse in those with a duration of epilepsy <5 years before treatment (12 of 14 such children were responders; sign test positive, P = 0.05). The quality-of-life evaluation,

Discussion

In this study, we made qualitative and semiquantitative evaluations of changes in 24-hour electroencephalogram patterns when recordings were compared before and after starting the ketogenic diet. The recordings were concealed to the electroencephalogram reader upon evaluation. During the period between examinations, minor reductions of habitual antiepileptic drug doses were undertaken. These changes are usually not reported to influence electroencephalogram activity.

Comparing

References (18)

B.V. Maydell et al.
Efficacy of the ketogenic diet in focal versus generalised seizures
Pedatr Neurol
(2001)
P.A. Schwartzkroin
Mechanisms underlying the anti-epileptic efficacy of the ketogenic diet
Epilepsy Res
(1999)
S. Farasat et al.
The importance of parental expectations of cognitive improvement for their children with epilepsy prior to starting the ketogenic diet
Epilepsy Behav
(2006)
D.L. Ross et al.
Early biochemical and EEG correlates of the ketogenic diet in children with atypical absence epilepsy
Pediatr Neurol
(1985)
S.H. Eun et al.
Ketogenic diet for treatment of infantile spasms
Brain Dev
(2006)
T.D. Swink et al.
The ketogenic diet: 1997
Adv Pediatr
(1997)
M. Dahlin et al.
Variability of epileptiform activity in long-term EEGs with short and long intervals in children with epilepsy
Clin Neurophysiol
(2000)
R. Levy et al.
Ketogenic diet for epilepsy
Cochrane Database Syst Rev
(2003)
J.M. Freeman et al.
The efficacy of the ketogenic diet—1998: A prospective evaluation of intervention in 150 children
Pediatrics
(1998)

There are more references available in the full text version of this article.

Cited by (20)

QEEG indices are associated with inflammatory and metabolic risk factors in Parkinson's disease dementia: An observational study
2022, eClinicalMedicine
Citation Excerpt :
Interestingly, the ketogenic diet is an effective alternative therapy to control intractable seizures, especially in those with abnormal lipid profile. Qualitative and semiquantitative EEG evaluations showed an improvement in normal background activity or a decrease interictal epileptiform activity after the ketogenic diet in patients with epilepsy.15 Whether lipid metabolism is related to the EEG activity in patients with PD remains largely unknown.
Quantitative electroencephalography (QEEG) is a reliable and non-invasive diagnostic tool to quantify cortical synaptic injury or loss in the clinical assessment of neurodegenerative diseases, and may be able to differentiate various types of dementia. We investigated if QEEG indices can differentiate Parkinson's Disease (PD) with nondementia (PD-ND) from PD with dementia (PDD), and to determine if QEEG indices correlate with inflammation and lipid metabolism markers in PD.
This clinical study collected data between July 1, 2018 and July 1, 2021 in Zhujiang Hospital of Southern Medical University in China and data was analysed. A total of 125 individuals comprising of 31 PDD, 47 patients with PD-ND and 47 healthy controls were included. We calculated the absolute spectral power (ASP) of frequency bands and the slow-to-fast frequency ratios of specific brain regions. Plasma levels of hypersensitive C-reactive protein (Hs-CRP), superoxide dismutase (SOD), and high-density lipoprotein cholesterol (HDL-C) were measured and correlations with QEEG indices were examined.
A significantly higher ASP of delta frequency especially in the frontal region was observed in patients with PDD compared to PD-ND (P=0.004) and controls (P=0.000). Decreased HDL-C (OR=0.186, P=0.030), and increased Hs-CRP (OR =2.856, P=0.015) were associated with PDD. Frontal-delta ASP was negatively correlated with plasma HDL-C (r=−0.353, P=0.000) and SOD (r=−0.322, P=0.001), and positively correlated with Hs-CRP (r=0.342, P=0.000).
We highlight novel correlations between QEEG indices and inflammation and lipid metabolism markers in PD-ND and PDD. QEEG indices, HDL-C and Hs-CRP are potentially useful for the evaluation of PDD. Our current findings suggest that peripheral inflammation might contribute to the pathogenesis of cognitive impairment and EEG slowing in PDD. The mechanism underlying frontal-delta ASP and its correlation with neuro-inflammatory and metabolic markers in PDD should be further investigated.
The National Natural Science Foundation of China (NO: 81873777, 82071414); the Scientific Research Foundation of Guangzhou (NO: 202206010005); the Science and Technology Program of Guangdong of China (NO: 2020A0505100037); the High-level Hospital Construction Research Project of Maoming People's Hospital (NO: xz2020009); the Science and Technology Program of Maoming City (NO: 2021S0026). Dr EK Tan is supported by the National Medical Research Council, Singapore.
Efficacy of the ketogenic diet in Chinese adults versus children with drug-resistant epilepsy: A pilot study
2022, Epilepsy and Behavior
We compared the efficacy and safety of ketogenic diet (KD) therapy as a treatment for Chinese adults versus children with drug-resistant epilepsy.
The classic KD was initiated in 19 adults and 29 children with drug-resistant epilepsy. The KD ratio and the dosage of antiseizure medication (ASM) were delicately modulated by the ketogenic team.
At 12 months after diet initiation, 11 adults (8 on a KD ratio of 3:1 and 3 on a ratio of 2:1) and 20 children (9 on a ketogenic diet ratio of 3:1 and 11 on a ratio of 2:1) remained on the diet. The retention rate for adult KD therapy recipients was 79.0% at 6 months and 57.9% at 12 months after diet initiation, which was not significantly different from the retention rate for children (82.8% at 6 months and 68.9% at 12 months; P > 0.05). The efficacy rate of KD therapy (seizure freedom or ≥50% reduction in seizure frequency) did not significantly differ between adults (63.2%) and children (75.8%, P = 0.517). Alleviation of seizure severity was observed in 68.4% of adults and 63.6% of children who were not seizure free on KD therapy. Antiseizure medication was reduced in 34 out of all 48 individuals at the final follow-up.
Our study demonstrated that KD therapy is a safe and effective treatment for Chinese adults as well as children with drug-resistant epilepsy.
Core outcome set development for childhood epilepsy treated with ketogenic diet therapy: Results of a scoping review and parent interviews
2022, Seizure
Citation Excerpt :
Nine children achieved complete seizure freedom and the remaining 12 experienced seizure reduction. A total of 921 verbatim outcomes were measured and reported in 147 articles [10–17,34–172] Considerable repetition and overlap existed in outcomes and the terminology used to describe these, so these were stratified into 90 discrete outcomes. Only 52% of identified outcomes were reported in more than one study.
Clinical trials on childhood epilepsy treated with ketogenic diet (KD) use a wide range of outcomes, however, patients and decision-makers often do not perceive the outcomes used as the most important. We sought parental opinion on outcomes of importance and compared these to outcomes reported in published research.
Ethical approval (London-Surrey-REC19/LO/1680). A scoping review identified outcomes reported in previous studies of childhood epilepsy and KD. Parents were recruited from nine KD centres (UK), charities and social media (international), then interviewed (Jan-April 2020) to explore priority outcomes. Content analysis identified all outcomes in transcripts. Parent identified outcomes were compared with those in the scoping review. Outcomes were collated and grouped into domains according to the COMET Taxonomy.
Of 2663 articles;147 met inclusion criteria. 921 verbatim outcomes were sorted into 90 discrete outcomes, reduced to 70 in consultation with the study advisory group, then classified into 21 domains. Parents (n = 21) identified 39 outcomes as important from the scoping review and seven new outcomes. They prioritised both physiological and functional outcomes in contrast to past studies, which prioritised physiological outcomes.
Little consistency exists in the outcomes used in childhood epilepsy and KD research. Those traditionally used do not adequately reflect parents’ important outcomes for their child. Clinical trials should consider the broader priorities of parents when choosing outcomes, in particular, functional outcomes. Identified outcomes will inform an international two-round Delphi-study with parent, professional and researcher participants to develop a core outcome set for this clinical area (COMET registration #1116).
Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis
2020, Seizure
Citation Excerpt :
As KD affects some essential biochemical pathways that influence the function of the central nervous system, this finding supports the premise that KD improves cognitive function and behavioral impairment [36]. Only two of the included studies reported improvement of EEG abnormalities, but other studies have also demonstrated that KD can significantly reduce the frequency of interictal epileptic discharges and improve the EEG background rhythm [37,38]. It is believed that EEG changes result from the favorable electrical physiological effects of KD [39].
Dravet syndrome is an infantile epilepsy syndrome with drug resistant seizures and cognitive impairment. The aim of this meta-analysis was to summarize the findings of relevant published studies to identify the efficacy of a ketogenic diet in patients with Dravet syndrome and their compliance thereof, and to provide useful information for clinical practice.
The PubMed, Embase, Wanfang, and CNKI databases were searched for relevant studies published up to September 25, 2019; the included studies were reviewed. Meta-analyses were performed using R software to determine the combined efficacy rates and retention rate for the ketogenic diet in patients with Dravet syndrome.
Seven studies involving 167 patients met the inclusion criteria: four were retrospective studies, and three were prospective studies. The meta-analysis revealed that 63 %, 60 %, and 47 % of responder patients achieved ≥50 % seizure reduction at month 3, 6, and 12, respectively. The pooled retention rate of the ketogenic diet at month 6 and month 12 was 78 % and 49 %, respectively.
Our meta-analysis indicates that the ketogenic diet is a treatment option for patients with Dravet syndrome. The ketogenic diet is safe and its adverse effects are mostly acceptable. However, further investigations, especially high-quality controlled trials with large samples, are required.
Effectiveness of ketogenic diet in pentylenetetrazol-induced and kindling rats as well as its potential mechanisms
2016, Neuroscience Letters
The effects and mechanisms of ketogenic diets (KD) are unclear. In this study, we aimed to reveal electrographic and behavioral thresholds in responses to the KD in pentylenetetrazol (PTZ)-induced seizures, as well as its antiepileptogenic effects on PTZ-kindling rats. Additionally, we investigated the potential link between KD and expression levels of two cation chloride co-transporters: K⁺–Cl⁻ co-transporter 2 (KCC2) and Na⁺–K⁺–Cl⁻ co-transporter 1 (NKCC1). The KD group had significantly higher electrographic thresholds than the control (ND) group for the first spike-and-wave, subcontinuous spike-and-wave, high amplitude spike-and-wave, and polyspikes both in the cortex and hippocampus. Compared to the ND group, the KD group had higher behavioral thresholds for behavioral absence, first jerk, first overt myoclonia, and generalized seizures. In the PTZ-kindling model, KD not only prolonged the latency of myoclonic and clonic convulsions, but shortened clonic and generalized duration. In addition, KD rats had higher KCC2 protein expression before kindling, during myoclonic jerks, and GTCS compared with ND rats. There were no significant differences in NKCC1 protein levels between both groups following the four-week dietary intervention without PTZ exposure (before kindling). Moreover, KD inhibited the upregulation of NKCC1 expression induced by kindling in myoclonic jerks and GTCS. Therefore, our findings demonstrated that KD had antiepileptic features in elevating thresholds to most electrographic and behavioral seizure patterns in PTZ-induced rats, as well as delaying the progression and alleviating the severity of seizure in PTZ-kindling model. The antiepileptogenic effects of KD may be attributed to its regulatory properties on KCC2 and NKCC1 protein expression.
Can an early 24-hour EEG predict the response to the ketogenic diet? A prospective study in 34 children and adults with refractory epilepsy treated with the ketogenic diet
2014, Seizure
We examined whether early EEG changes in a 24-h EEG at 6 weeks of treatment were related to the later clinical response to the ketogenic diet (KD) in a 6-month period of treatment.
We examined 34 patients with heterogeneous epilepsy syndromes (21 children, 13 adults) and found 9 clinical responders (≥50% seizure reduction); this is a responder rate of 26%. We visually counted the interictal epileptic discharge index (IED index) in % during 2 h of wakefulness and in the first hour of sleep (method 1), and also globally reviewed EEG changes (method 2), while blinded to the effect of the KD.
At group level we saw a correlation between nocturnal reduction of IED-index at 6 weeks and seizure reduction in the follow-up period. A proportional reduction in IED index of 30% from baseline in the sleep EEG, was associated with being a responder to the diet (Pearson Chi-square p = 0.04). EEG scoring method 2 observed a significantly larger proportion of patients with EEG-improvement in sleep in KD responders than in non-responders (p = 0.03). At individual level, however, EEG changes did not correlate very strongly to the response to the diet, as IED reduction in sleep was also seen in 15% (method 1) to 26% (method 2) of the non-responders.
Nocturnal reduction of IEDs is related to the response to the KD, however in daily clinical practice, an early EEG to predict seizure reduction should not be advised for individual patients.

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Original articleInfluence of the Ketogenic Diet on 24-Hour Electroencephalogram in Children With Epilepsy

Introduction

Section snippets

Patients

Results

Discussion

Pedatr Neurol

Epilepsy Res

Epilepsy Behav

Pediatr Neurol

Brain Dev

Adv Pediatr

Clin Neurophysiol

Ketogenic diet for epilepsy

Cochrane Database Syst Rev

The efficacy of the ketogenic diet—1998: A prospective evaluation of intervention in 150 children

Pediatrics

Original article
Influence of the Ketogenic Diet on 24-Hour Electroencephalogram in Children With Epilepsy