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Indian Pediatr 2009;46: 669-673 |
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Ketogenic Diet in Indian Children with
Uncontrolled Epilepsy |
JK Nathan, AS Purandare, ZB Parekh and HV Manohar
From the Department of Neurology, Shushrusha Hospital,
Mumbai, India.
Correspondence to: Dr J Nathan, Sanjeev Clinic, B-1, 1st
floor, Rajeev Co-op Society, Gopi Tank Road,
behind Citylight Theatre, Mahim (West), Mumbai, India.
E-mail: [email protected]
Manuscript received: August 31, 2006;
Initial review: December 29, 2006;
Accepted: September 5, 2008.
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Abstract
Objective: To evaluate the efficacy of the
ketogenic diet in Indian children with uncontrolled epilepsy.
Study Design: Prospective observational study.
Setting: Hospital based.
Patients: 105 children (age 4 months to 18 years)
with uncontrolled epilepsy enrolled in the ketogenic diet program over a
period of 9 years and followed up for 25.7 ± 20.3 months (median:17
months) on the ketogenic diet.
Main outcome measures: Reduction in seizure
frequency and comparison of improvement in two main groups of
epilepsies, namely epileptic encephalopathies and localization related
epilepsies.
Results: Thirty seven (35%) out of 105 children
dropped out of the study and 68 remained on the diet. Thirty nine (37%)
achieved 100% control, 23 (22%) achieved between 90 and 99% control, 7
(6.8%) achieved between 75 and 90% control, and 16 (15.2%) achieved
between 50 and 75% control. Twenty (19%) achieved less than 50% control.
Epileptic encephalopathies had a better response than localization
related epilepsies.
Conclusion: The Indian version of ketogenic diet
used is well tolerated and efficacious in controlling
difficult-to-control epilepsy in children. Epileptic encephalopathies
respond better than localization related epilepsies
Key Words: Children, Ketogenic diet, India, Treatment,
Uncontrolled Epilepsy.
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T he ketogenic diet has been used in
difficult-to-control epilepsy since the 1920s. The diet is used in several
countries(1). We present the first Indian version of the classic ketogenic
diet. The objective was to fashion a culturally acceptable diet with
regional food changes and to determine whether this ‘Indianization’ would
be as successful as the original diet. We also looked at whether a
particular type of epilepsy responded better.
Methods
This was an open, non-blinded, prospective study of 105
consecutive patients ( £18
year age) who had entered the program between 1996-2005. Inclusion
criteria were children with difficult-to-control epilepsy as per ILAE
guidelines, namely those who had tried a minimum of 2 appropriate
first-line anti-epileptic drugs (AEDs) in a maximally tolerated dose and
still had a minimum of 2-3 seizures per month(2), and children who had a
follow-up of atleast 6 months. Exclusion criteria were inappropriate or
ineffective dosage of AEDs, any other serious systemic disease and those
living in distant places, thus making regular follow-up difficult.
Informed consent was taken from caregivers of all patients. Approval of
the Ethics Committee of the Shushrusha Hospital was obtained for the above
intervention and the study.
Patients were enrolled from the Shushrusha Hospital
clinic and a private clinic. Total patients assessed for eligibility were
174, of whom 69 were excluded. A total of 105 patients were thus included
in the study (Fig.1). Duration of follow-up ranged from 6
months to 60 months with an average follow-up of 25.7+20.3 months (median,
17 mo).
We followed the Johns Hopkins Hospital protocol with
few changes(3). Detailed counseling was given including a recipe
demonstration. The counseling included the scientific basis of the diet,
the rigid nature of the diet (only prescribed food could be taken),
demonstration of the urine ketone testing and the possible side effects.
Sugar-containing medications for any other incidental illness were not
allowed. Sugar-free toothpaste was used. Caregivers were taught how to
weigh different foods using digital weighing scales. The scales were
either bought by parents or provided on loan. Before starting the diet,
complete blood count, blood sugar, renal and liver function tests, lipid
profile, serum electrolytes, uric acid and urine (routine and microscopic)
examination were done. These were repeated every three months in the first
year and every six months thereafter. EEG was recorded prior to commencing
the diet using the standard 10-20 protocol and repeated at the above
intervals. All patients had a prior computed tomography (CT) or Magnetic
Resonance Imaging (MRI) of head.
Initially, patients (42 in all) were admitted for four
to six days and during the fasting phase of between 2 to 3 days (only
water being allowed), blood sugar, vital parameters and urine ketones were
checked every four hours. Once urine ketone level reached four plus (4+)
(160 mg/dL), they were started on the ketogenic diet. One-third of the
calculated calories were given on the first day, two-third on the second
and full calories on the third usually on a 4:1 to 3:1 ketogenic ratio.
Later, patients (63 in all) were not admitted or fasted due to parental
resistance. After a carbohydrate washout (food with only up to 10 grams
carbohydrate) and on achieving urine ketone level of 4+, full calories
were started at lower ratios.
The ketogenic diet was calculated for each patient
individually with 75% of the RDA (Recommended Daily Allowance)
calories being given(4). The ketogenic ratio refers to the ratio of the
fat amount in grams to the combined protein and carbohydrate amount in
grams and initial ratio ranged from 2:1 to 4:1. Protein is given as per
the World Health Organization recommendation for the age of the person. To
Indianize the diet, we developed a recipe book of 100 Indian meals of
different communities. For vegetarians, protein substitutes like soy and
whey powder were included. A list of food ingredients was developed with
typical Indian foods and their local names. The basic food products like
cream, butter and milk and commercial products were sent for macronutrient
analysis. An extensive dietetic history was taken including family food
habits, taboos and food preferences. Water quota was calculated at
approximately 1 mL/calorie. The caregivers maintained a daily urine ketone
level chart, the urine being checked 3-4 times a day. A daily seizure
chart was maintained. Initially follow-ups were at intervals of two weeks
and the calorie and ketogenic ratio fine-tuned to achieve a stable urine
ketone level of four plus (4+) throughout the day. At every follow-up the
seizure frequency was recorded. Also, the height, weight, urine ketone
level and a routine urine examination was noted. After the initial fine
tuning, follow-ups were less frequent. Caloric adjustments were made to
bring the person as close to the ideal height and weight as possible (as
per Indian Council for Medical Research standards). Water was adjusted to
ensure patient passes urine at least 5-6 times per day. If crystals were
found in the urine or the patient passed urine infrequently, the water
quota was increased.
Statistical analysis
For the purposes of data analysis, the patient data was
primarily grouped based on the type of seizure and epilepsy syndrome. The
data was classified based on the extent of seizure control in to 5 groups:
100%, 90 to 99%, 75 to 90%, 50 to 75%, and 50% or less seizure control,
respectively. The c2
test was used to determine whether the differences in the frequency of
patients in each of the groups for seizure control were statistically
significant. A Pearson’s
c2
test was performed to determine whether the differences in frequency of
seizure control were significant across the two largest syndrome groups,
namely, Epileptic encephalo-pathies and Localization related epilepsies.
The data on number of antiepileptic drugs (AEDs) received by patients
prior to starting the ketogenic diet and post-diet was also analyzed. A
paired samples t test was performed to compare the difference
between the number of medicines pre and post-diet. The data on AEDs was
further analyzed to determine the number of patients for whom the AEDs
were stopped, reduced or remained the same. A
c2
test was used to determine if the differences between these numbers were
significant. The data was analyzed with the Statistical Package for Social
Sciences program (version 12.0) (SPSS, Chicago, IL, USA).
Results
Of the 105 patients, 40 were below 3 years age, 50 were
between 3 and 15 years age and, 15 were between 12 and 18 years age.
Twelve children had simple partial seizures, 11 had complex partial
seizures, 44 had primary generalized seizures, 7 had secondary generalized
seizures, 46 had myoclonic seizures and 17 had atonic seizures. Of these,
82 (78%) had mixed types of seizures. Seizure frequency ranged from 2 to 3
per day to 300 per day. Thirty three patients (31%) had tried two
AEDs, 35 (33%) had tried three AEDs, 20 (19%) had tried four AEDs and
17(16%) had tried more than four AEDs. Mean number of AEDs tried was 3.67
(±2.94). Twenty-two discontinued the diet after following the protocol for
periods from 2 to 10 months and one child after 2 years and 6 months.
Those who dropped out after informing us (18) were taken off the diet in a
graded manner similar to those who were successfully withdrawn from the
diet. Four were lost to follow-up.
Thirty seven (34%) achieved 100% control, 18 (17%)
achieved 90 to 99% seizure control, 13 (12%) achieved 75 to 90% seizure
control, 10 (9%) had 50 to 75% seizure control, and 31 (28%) achieved
seizure control of 50% or less (P<0.05). Comparison of the two
largest syndrome groups indicated that the differences in frequency of
seizure control were significant (P<0.05) implying that 100%
seizure control was achieved more frequently in epileptic encephalopathies
than localization related epilepsies. In contrast, localization related
epilepsies showed more frequency of patients with up to 99%, 90%, and 50%
seizure control compared to epileptic encephalopathies (Table I).
The results indicate that patients were on an average of 3.67 (SD,
1.47) medicines prior to beginning of the diet. At the end of the study,
the number of medicines reduced to an average of 1.95 (SD, 0.96). The
results of the paired samples t test indicated that these
differences are significant (P<0.005). AEDs were stopped for 11 of
the patients, while the number was reduced for 70 and remained the same
for 23 patients. These differences were found to be statistically
significant (P <0.005).
TABLE I
Seizure Control Based on Epilepsy Syndrome
|
Seizure control |
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≤ 50% |
50-75% |
75-90% |
90-99% |
100% |
Epileptic encephalopathies (n = 46) |
9 |
6 |
5 |
4 |
22 |
Localization related epilepsies (n = 53) |
16 |
3 |
8 |
13 |
13 |
Side effects of the diet were minor and temporary.
Seven (7%) had nausea at the onset, 8 (7%) had diarrhea, 41(39%) had
temporary constipation, 33(31%) had temporary vomiting, and 2 had
steatorrhea. Many had transient trace albuminuria (71%). None had low
glucose levels during the fasting phase. Those who achieved 100% control
were tapered off the diet over few months; the ratio being slowly reduced
by 0.5, every month till they reached 1:1.
Discussion
The ketogenic diet is an alternative therapy useful in
difficult-to-control epilepsy. Although there has been no double-blind
controlled study, numerous studies have prospectively documented the
efficacy of this diet. A recent review came to the following conclusion,
"The diet’s effectiveness in providing seizure control for children with
difficult-to-control seizures has remained as good as or better than any
of the newer medications"(5).
The responder rate (those with more than 50% decrease
in seizure frequency) was 72%. Of these a large proportion had over 90%
control (57%) with a significant number becoming seizure free (34%). Our
results of seizure reduction are comparable to those achieved in other
centers around the world (Table II). Similar to our
results, other studies have also noted that the generalized epilepsies
respond better than the focal epilepsies(13).
TABLE II
Comparison of Seizure Control in the Present Study with Published Data from Other Centers
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Seizure control |
Study |
Country |
No. of
Patients |
<50% |
50-75% |
75-90% |
90-99% |
100% |
Freeman, et al.(6) |
USA |
150 |
22% |
34% |
|
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43%(>90%) |
Batchelor, et al.(7) |
USA |
27 |
35% |
40% |
– |
– |
25% |
Hassan(8) |
Canada |
49 |
– |
67.3% |
– |
– |
12.2% |
Francois(9) |
France |
29 |
– |
41.3% |
– |
– |
– |
Kang, et al.(10) |
Korea |
129 |
27.9% |
44.2% |
– |
– |
27.9% |
Mak, et al.(11) |
Taiwan |
13 |
23.1% |
23.1% |
53.8% |
– |
– |
Kankirawatana(12) |
Thailand |
32 |
– |
– |
– |
66.07% |
– |
Present study |
India |
105 |
19% |
15.2% |
6.8% |
22% |
37% |
Side effects in our series were mild and reversible.
Nausea seen at the onset was probably due to the high content of fat.
Eight had diarrhea and 41 had temporary constipation, which was corrected
by increasing the intake of insoluble fiber and the daily water allowance.
Thirty-three had temporary vomiting due to either gastroenteritis (usually
due to inadequate boiling of water) or deep ketosis. The latter was easily
resolved by immediately giving 30-100 mL plain orange juice before each
meal and then reducing the ratio. Two had steatorrhea which was resolved
by reducing the ratio. Many had transient trace albuminuria. Forty one
(39%) had mild crystalluria, usually during the summer season, which was
overcome by increasing the water quota.
Problems during the Indianization of the diet included;
large percentage of vegetarians; religious taboos with consequential ban
on several foods; non-availability of packaged foods; absence or rare
labeling of basic foods like milk, butter and cream; wide variety of foods
used by Indians in various ethnic and religious categories; frequent
non-availability of basic foods like cream, cheese, etc.; over-protection
of children with epilepsy; and, interference in diet instructions by
relatives. There was difficulty in changing to high fat diet as routine
Indian food has higher proportion of carbohydrate (65-70%) and less fat
(12%) as compared to American food (40% carbohydrates and 18-20% fat)(14).
This study shows that the use of the ketogenic diet is
feasible in India and is effective in reducing seizures in those with
difficult to control seizures.
Contributors: JKN was involved in the study
design and manuscript preparation. ASP, ZBP and HVM were involved in data
collection. KD analyzed the data. All authors contributed to drafting of
the manuscript.
Funding: None.
Competing interests: None stated.
What is Already Known?
• The ketogenic diet is effective in uncontrolled
epilepsy.
What this Study Adds?
• An Indian adaptation of the ketogenic diet is
safe and efficacious in uncontrolled epilepsy.
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