Efficacy Against Epilepsy (ILAE) task force, created
Efficacy and Tolerability of Classical Ketogenic Diet
in a Paediatric Patient with Refractory Status Epilepticus (RSE)
Epilepsy is the most prevalent of all serious neurological disorders.
As per International League Against Epilepsy (ILAE) task force, created in
2014, epilepsy is considered to be a disease of the brain defined by any of the
following conditions1 –
At least two unprovoked (or
reflex) seizures occurring >24 hour apart.
One unprovoked (or reflex)
seizure and a probability of further seizures similar to the general recurrence
risk (at least 60%) after two unprovoked seizures occurring over the next 10
Diagnosis of an epileptic
Status epilepticus (prolonged seizure lasting longer than 5 minutes
or recurrent seizures without return to baseline between seizures) that
continues despite appropriate first- and second-line AEDs is classified as
refractory status epilepticus (RSE).
Over the decades of research it has been assured that the classical ketogenic
diet is a safe and convenient mode of alternative therapy for refractory or
pharmacoresistant epileptic patients. The ketogenic diet is a high fat-normal
protein-very less carbohydrate containing diet which is being used as a safe
alternative therapy for paediatric refractory epilepsy. The classical ketogenic
diet has been first studied by Wilder and Peterman, where they have used 1 g
protein/kg ideal body weight of the children/day, 10-15 g of carbohydrate daily
and rest of the energy from fat sources like butter, lard and full fat cream.
In this study, we evaluated the efficacy and tolerability of
classical ketogenic diet in a paediatric patient who has met the criteria for
MATERIALS AND METHODS
The patient was a 26 months old girl, born out of full term pregnancy
with no complication and normal body weight for gestational age. There was no history
of seizure from both the parents. On her 12th day of life she has
started recurrent epileptic jerks. She was put on several anti-epileptic drugs
(AEDs) like, valproic acid, vigabatrin, levetiracetam with poor response or no
response. Her seizure was marked as refractory or pharmacoresistant after
failure of 3 consecutive AEDs. Her neurometabolic investigations, including
blood, urine, and CSF analysis, as well as karyotyping, were normal. Brain MRI
was also normal. EEG was abnormal with generalized spike and wave discharges
during sleep. There was no evidence of SNC1A gene mutation.
At her age of 2 years 2 months the patient’s family have visited our
clinic for diet consultation. There was no need of ICU admission though there
was several episodes of seizures. The diet was administered in two phases –
Carbohydrate wash out phase:
During the washout phase the patient was given > 5 g of
carbohydrate, normal protein as per ideal body weight and increased amount of
fat per day. The phase has ensured desired ketosis (4+ Urine ketone) before
starting the ketogenic diet. Unlike traditional way the child was not kept for
fasting to get recommended ketosis.
Ketogenic diet phase:
After the washout phase, ketogenic diet with 3.5:1 (Fat : Carbohydrate+protein)
ratio was introduced to maintain ketosis. The fixation of ratio, daily calorie
requirement and number of meals was based on the patient’s intake during carbohydrate
wash out period, ideal body weight, age of the child and number of seizures per
day. The family has been given thorough training on ketogenic diet, process of diet
administration, measurement of urine ketone, importance of maintaining 4+ urine
ketone and significance of regular follow up. The urine ketone was measured
with keto-diastix, four times a day. The patient maintained 3+ (+++) or 4+
(++++) throughout the treatment.
Blood parameters were also checked 3 monthly from the starting of
the treatment. One week after the diet administration the child has shown
improvement with 50% seizure reduction. She had become more alert and her
cognition has improved with better eye-contact. After 3rd week she
started responding to her parents and others around. On her 6 monthly follow up
she has shown 85% seizure reduction and improved quality of life. Number of AEDs
was decreased to 1 from 3. The patient was continued to receive the diet.
The study has demonstrated a satisfactory response of the ketogenic
diet in terms of reduction of seizure frequency and tolerability in our refractory
epilepsy patient. There was no reported evidence of side effects like vomiting,
nausea, lose motion, steatorrhoea, dizziness, hyperlipidaemia, constipation
etc. The diet started working within 7 days of administration. Growth parameters
like height and weight are thoroughly monitored. The diet has been fine tuned
as required. Interestingly, patients with non-convulsive SE are also reported
to respond well to the KD as are patients with epileptic encephalopathy with
electrical status epilepticus during slow sleep. These findings support the
benefit of the KD in the management of patients with other types of SE.
The ketogenic diet is highly scientific and calculated diet. The use
of the ketogenic diet for the treatment of SE is rapidly increasing throughout
the world; however, to implement the diet in the management of these critical
patients a ketogenic diet team of experts, including a trained neurologist and
dietitian, is necessary. Such a team will also allow the diet to be continued
and install a longer term treatment when it is successful. Team decision for
each individual shall based on electroclinical aspects considering the quality
of life of both the patient and the family.
From our experience it is recommended that several prospective
studies of patients, both children and adults, with different types of
refractory SE, should be conducted and reported to further define the role of
the diet in the management of these patients.
The ketogenic diet is a promising alternative therapy for RSE in
both paediatric and adult population. Since 1921, ketogenic diet (KD) therapy
has been a recognized effective tool in the treatment of epilepsy. The classic
KD is the original diet introduced into practice in the 1920s. This high-fat,
low-carbohydrate diet induces ketone body production through fat metabolism
with the target of mimicking a starvation state without depriving the body of
necessary calories to sustain growth and development. Thus, the study strongly
recommend that classical ketogenic diet should be practiced worldwide irrespective
of etiology. The diet has a novel approach in controlling seizure frequency,
improving cognition and behavioural aspect.
Fisher RS, Acevedo C,
Arzimanoglou A, Bogacz A, Cross JH et al. How long for epilepsy remission in
the ILAE definition? Epilepsia. 2017; 58(8):1486-1487.
Kantanen AM, Reinikainen M,
Parviainen I, Kälviäinen R. Long-term outcome of refractory status epilepticus
in adults: A retrospective population-based study. Epilepsy Res. 2017;