الفهرس 
Pediatric EpilepsyOnly 14 pages are availabe for public view
 |  | from | 199 |  |  |
| | | from | 199 | | |
Abstract
Up to 65 million people worldwide are affected by epilepsy.
Approximately one third of epileptic patients still have difficulty being
treated, even though two-thirds of them can control their seizures with
current Anti-Seizure Medication (ASM).
The International League Against Epilepsy (ILAE) defines
Drug-Resistant Epilepsy (DRE) as the failure of adequate trials of two
tolerated, properly selected and utilized antiepileptic drug schedules to
achieve sustained relief of seizures.
Therefore, one should initially attempt surgical therapies, if a
patient is eligible and if surgery is not a possibility for a patient with
DRE, Dietary therapy like the Ketogenic Diet (KD) is an alternative.
KD (a high-fat, adequate-protein, and low carbohydrate diet) is
an effective, non-invasive, and non-pharmacologic treatment for
refractory childhood epilepsy used since 1920s with few to no
neurotoxic effects when compared to multiple ASM.
Despite the KD’s effectiveness, most patients discontinue the
diet because of its unpalatable and restrictive features.
So, new variants of KD have emerged, including the Modified
Atkins Diet (MAD) and the low-glycemic-index diet. MAD provides a
more palatable and less restrictive dietary treatment option.
However, since KD is not a physiological diet, it is important
to identify and carefully monitor any AEs. AEs can happen at the start
of the diet as well as months after KD initiation. Dehydration, altered
electrolytes, hypoglycemia, tiredness, abdominal pain,
nausea/vomiting, diarrhea, and constipation are short-term AE, while
hypoproteinemia, hypocalcemia, hypercalciuria, urolithiasis,
Summary
122
alterations in lipid profiles, an increase in transaminases or
cardiomyopathy are possible long-term AE.
Electroencephalographic (EEG) features are improved by KD
in addition to significantly reducing clinical seizures in epileptic
patients.
The aim of this study:
This study aimed to assess short and long-term efficacy, safety,
and tolerability of KD (classic KD and MAD) in childhood DRE and
to investigate the effect of KD on EEG features of children with DRE.
Patients and Methods:
We initially enrolled forty patients with DRE attending
Pediatric KD outpatient clinic at Menoufia University Hospital and an
informed (written) consent was obtained from each parent or
caregiver. Our inclusion criteria were patients who had received two
or more types of regular antiepileptic drugs, but frequent seizures
continued regardless their age. Patients with chronic diseases,
congenital metabolic disorders, liver diseases, and systemic diseases
were excluded from the study.
Patients were randomly assigned to two groups, group 1 (classic
KD group): 20 patients received classic KD and group 2 (MAD
group): 20 patients kept on MAD.
Before starting KD, we collected demographic and clinical data
of studied patients including age, sex, age of start of seizures,
anthropometric measurements (weight, length/height, weight for
length/height, and BMI) according to Egyptian Z score growth
references for Egyptian children, etiology, type of seizures, , seizure
Summary
123
frequency, and seizure severity. Number of antiepileptic drugs used,
and baseline EEG were also documented.
Morning blood samples were taken after 8–12 hours fasting.
Triglycerides (TG), total cholesterol, low-density lipoprotein (LDL-C)
and high-density lipoprotein (HDL-C) were measured.
Parents or caregivers were educated about diet preparation at
home with close monitoring of blood glucose and urinary ketones.
Multivitamins, calcium, and vitamin D were given as supplements
Patients were requested to attend their regular monthly outpatient
visits for six months, then every three months for 24 months.
After one month of KD initiation, two patients of classic KD
group and one patient of MAD group were excluded from the study
due to non-compliance of their caregivers. At 3 months follow up
visit, six patients were excluded from the study as they did not tolerate
the MAD and the ketogenic liquid formula. Also, one patient of MAD
group died secondary to infection in COVID19 epidemic, so only 30
patients completed the study for two years, 15 in each group.
The clinical efficacy of KD was evaluated regarding seizures
frequency and severity prior to and 3 and 6 months after the KD
treatment were analyzed.
By comparing EEG before and 3 and 6 months after the KD
therapy regarding the background rhythm and variations of inter-ictal
epileptiform activity, the effect of KD on EEG features was assessed.
Anthropometric measurements, lipid profile, and the
development of AE were monitored at 3 months intervals up to 24
months. In addition, we assessed the possibility of antiepileptic drugs
withdrawal in seizure free patients after the first 6 months.
Summary
124
Results:
Out of 40 patients enrolled initially in our study, 30 patients
with median age 3 years (36 months) in classic KD group versus 6
years (72 months) in MAD group tolerated this study for 24 months,
11 patients (36.67%) were under weight, 3 patients (10%) were
overweight, and 7 patients (23.33%) were wasted with non-significant
difference between the two groups.
According to ILAE 2017, epilepsy of unknown etiology was the
commonest etiology among the participants [12 patients (40%)] and
Myoclonic seizures was the most prevalent type [10 cases (33.33%)].
The median of seizures severity scale and seizures frequency per day
of 165 and 10 respectively.
There was statistically significant decrease in seizure severity
by -100 % percent change after 3 and 6 months of KD compared to
baseline with non-significant difference between both groups. Six
months after initiation of KD, 60 % of patients in classic KD group
and 46.67% of patients in MAD group became seizure free and the
other 40 % and 53.33% had ≥ 50% seizure reduction with median
percent decrease of -83.33% and -75% after 3 months in classic KD
and MAD respectively and -100% after 6 months in both groups.
The best seizures control was observed in genetic epilepsy. On
the other hand, the efficacy of KD for epilepsy of unknown etiology
was poor.
The better EEG before treatment, the better seizures control as
there was a statistically significant difference regarding seizures
control between patients with initially normal EEG and patients with
abnormal EEG after 3 and 6 months of KD and normal EEG before
treatment was associated with better seizures control.
Summary
125
As the length of the KD treatment was increased, significant
changes in the background rhythms of the children were observed.
Our results did not find any correlation between the level of
urinary ketones and seizure control 3 and 6 months after KD.
Our results revealed that gastrointestinal (GI) complications
were frequent in our studied cases and constipation was the
commonest with the same occurrence in the two groups (33.33%). We
didn‘t document renal/genitourinary complications in our study.
In our study, median level of HDL decrease did not reach the
low level till the end of the study for 24 months. Also, median level of
LDL, total cholesterol, and triglycerides increase did not reach high
level (remained in the acceptable level) throughout the study period,
without significant difference between classic KD group and MAD
group.
Upon regular follow up visits every 3 months after the first 6
months, it was possible to withdraw one AEDs in 3 patients (20%) of
classic KD group and 5 patients (33.33%) of MAD groups, in addition
to withdrawal of two AEDs in 3 patients (20%) in classic KD group
and 2 patients (13.33%) in MAD group leading to less AEDs side
effects and better quality of life while on adequate seizure control by
KD.
The current study found a positive impact of KD on growth of
studied cases (weight loss and BMI reduction were minimal) except in
patients who were significantly overweight at diet initiation.
Conclusion:
1. Both common types of KD (classic KD and MAD) are effective for
treatment of DRE.
Summary
126
2. MAD was more palatable for children with less restrictive options
than classic KD with no significant difference regarding efficacy
and safety.
3. High serum lipid profile (cardiovascular AE) is often suspected in
children following a high fat diet, but lipid profile remained in the
acceptable level up to 24 months. Therefore, KD constitutes a safe
treatment.
4. KD had a positive impact on growth despite, inconsistent results of
the KD‘s effect on growth.
5. In addition to showing strong clinical effectiveness, KD also
showed significant improvement in EEG by decreasing the
frequency of interictal epileptic discharges and enhancement of the
background rhythm.
Recommendation:
1. Although no serious complications were recorded, long-term
follow-up and larger scale studies are recommended to further
ensure the safety of KD in childhood period.
2. The role of KD as a single line of therapy, whether from the
beginning or after withdrawal of all other medications once full
control is established, is also recommended to be clarified by more
research.
3. More research on evaluation of efficacy, tolerability and safety of
other types of KD like low glycemic index treatment (LGIT) and
medium- chain triglycerides diet (MCTD) is recommended.
4. Lastly, further studies are needed to identify predictors of KD
efficacy, studies to find any correlation between type of seizures,
etiology of epilepsy, EEG findings and favorable seizure outcomes
to assess if the KD can be considered as a first line of treatment of
epilepsy in specific situations.