3.2.1 Medical evaluation

A medical evaluation should be performed by a pediatric neurologist experienced in managing ketogenic diets in children, and include an assessment of the child's epilepsy, comorbidities, psychological and socioeconomic factors, medications, and investigations [2].

First, the pediatric neurologist must assess the child's baseline epilepsy state and any comorbidities that may complicate a ketogenic diet. Seizure symptomatology and frequency should be documented in sufficient detail so as to later gauge diet

The first randomized controlled trial compared the efficacy of a CKD versus no diet intervention in 145 children with drug-resistant epilepsy [32]. After 3 months, 28 children (38%) in the CKD group had a greater than 50% seizure reduction compared to four children (6%) in the control group. One weakness of the study was its unblinded design, with both patients and assessors aware of the group

ILAE = International League Against Epilepsy; GLUT1 DS = glucose transporter type 1 deficiency syndrome; PDHD = pyruvate dehydrogenase complex deficiency; FIRES = febrile infection-related epilepsy syndrome.

Epilepsy disorders in children for which a ketogenic diet may be strongly indicated.

PDHD

FIRES Formula-fed Infantile spasms Ohtahara syndrome

Doose syndrome Dravet syndrome

Complex I mitochondrial disorders

Super-refractory status epilepticus Tuberous sclerosis complex

The following year, a randomized controlled trial was published in 20 children with drug-resistant Lennox-Gastaut syndrome [33]. All patients were fasted 36 hours and then randomized to receive either a CKD plus a daily solution containing 60 g glucose per day or a solution containing saccharin (an artificial sweetener); the aim of the design was to ensure that both patients and assessors remained blinded to treatment. To the surprise of the investigators, both groups had positive blood BHB levels after 6 days, indicating that the glucose solution did not suppress physiological ketosis. Perhaps as a result of this, the study demonstrated only a borderline, non-

The next randomized controlled trial compared the efficacy of a MAD versus no diet intervention in 102 children with drug-resistant epilepsy [34]. Surgical candidates were not excluded. After 3 months, 52% of children in the MAD group had a greater than 50% seizure reduction compared to 11.5% of those in the control group. A weakness of the study was its unblinded design, with both patients and assessors

The most recent randomized controlled trial compared the efficacy of a ketogenic diet (CKD or MCT diet) versus no diet intervention in 57 children and adolescents with drug-resistant epilepsy [35]. None of the patients were eligible for surgery. After 4 months, 13 children (50%) in the ketogenic diet group had a greater than 50%

statistically significant reduction in seizures in the saccharin arm.

General disorder Specific disorder Drug-resistant epilepsy 2010 ILAE definition

Specific seizure disorders Angelman syndrome

Disorders of brain metabolism GLUT1 DS

Epilepsy - Advances in Diagnosis and Therapy

seizure reduction compared to 4 children (18.2%) in the control group.

Pooling the results from these randomized controlled trials suggests that 40–50% of children experience a greater than 50% seizure reduction after 3–4 months on a ketogenic diet, compared to 10–15% of children receiving no

allocations.

152

Table 3.

aware of the group allocations.


investigations include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, vitamin D, serum acylcarnitine profile, and a urinalysis [2]. Baseline anti-epileptic drug levels can be measured, although few concerns for drug-diet interactions exist. A recent EEG and MRI brain should be obtained to identify potential surgical candidates. Further tests, such as ECG and

A nutritional evaluation should be performed by a dietitian experienced in managing ketogenic diets in children, and include an assessment of baseline physical parameters, selection of the most suitable ketogenic diet, and education of the

Baseline weight, body-mass index, and height are routinely measured (in infants, head circumference is also measured) [2]. The child's recommended calorie and fluid intake should be calculated, as well as the desired fat to protein to carbo-

When selecting a conventional ketogenic diet for a child, the most important factor to consider is the family environment, rather than perceived diet efficacy [2]. The CKD is highly effective for seizure control, but restrictive and time-consuming; depending on the family environment, it may be more feasible to implement the MCT diet, MAD, or LGIT diet. Regarding diet efficacy, the CKD appears to be superior to the MAD in infants under 2 years of age, whereas both are equally effective in older children [27]. For the transition to adolescence, the MAD and LGIT diet are less restrictive and more appropriate; the LGIT diet may not provide an adequate level of ketosis to treat GLUT1 DS and PDHD, although it is highly effective in Angelman syndrome [2, 39]. For infants and children on enteral feeds, ketogenic diets can be administered in liquid form, which may be more convenient and efficacious [2]. Given the limited fruit, vegetable, and calcium content in conventional ketogenic diets, supplementation with a carbohydrate-free multivitamin containing minerals, as well as supplementation with calcium and vitamin D, is considered

hydrate ratio. Food aversions and allergies must be clearly documented.

mandatory in children [26]. No particular recommendations exist for

supplementing a ketogenic diet with magnesium, selenium, carnitine, laxatives,

Caregiver education is essential; the caregiver needs to understand exactly what is required of them to implement the diet. A classroom-based format, with several different caregivers present, can be advantageous [26]. The dietitian should demonstrate how to identify sources of fat, protein, and carbohydrate, how to count net carbohydrate (total carbohydrate minus fiber) for those on a MAD, how to identify foods with a low glycemic index for those on an LGIT diet, and how to navigate potential pitfalls [26]. Helpful additional resources should be provided [40, 41] and

Once the child and caregiver have been prepared, it is time to implement the diet (Table 5) [2]. The pediatric ketogenic service should take on a strong supportive role, aiding the caregiver as much as possible in troubleshooting problems.

Currently, it is recommended that the CKD be initiated with the child in hospital [2]. The advantages of an inpatient admission include the ability to closely observe

renal ultrasound, may be ordered as clinically indicated.

Ketogenic Diet Therapies in Children and Adults with Epilepsy

DOI: http://dx.doi.org/10.5772/intechopen.83711

3.2.2 Nutritional evaluation

caregiver on what to expect with the diet.

probiotics, or exogenous ketones [2, 26].

3.3 Implementing a ketogenic diet in a child

any expectations addressed.

3.3.1 Diet initiation

155

### Table 4.

Preparing a child (and caregiver) for a ketogenic diet.

efficacy on seizure control. Potential complicating comorbidities include gastrointestinal issues (such as gastroesophageal reflux and constipation), hypercholesterolemia, low weight gain, kidney stones, chronic metabolic acidosis, and cardiomyopathy [2]. Once identified, most comorbidities can be preventatively managed.

Second, it is critical to identify psychological, socioeconomic, cultural, and religious factors that may affect the child's diet [2]. Challenging behavior traits in the child or caregiver should be addressed early. Since many patients with epilepsy are of lower socioeconomic status, an appraisal of the family environment, including finances, is essential before deciding to proceed; even if deemed adequate, the caregiver must be made aware of the impact of a ketogenic diet on time and resources, including separate meal preparation from the rest of the family and increased costs [26]. It is also necessary to consider the family's cultural and religious background, which may result in some recipes being more suitable than others [2].

Third, the child's medications should be reviewed. Generally, blood levels of common anti-epileptic drugs are not significantly altered by a ketogenic diet, therefore dose adjustments are not required. However, it may be worth considering dose reductions in the case of valproate, zonisamide, and topiramate; although these drugs are generally safe alongside a ketogenic diet, there have been rare instances of hepatotoxicity and secondary carnitine deficiency with valproate, as well as chronic metabolic acidosis and a slight increase in kidney stones with zonisamide and topiramate [2]. All medications should be reviewed for carbohydrate content, which may necessitate a switch to lower carbohydrate preparations [26].

Fourth, the child and caregiver should be provided with a means of selfmonitoring the diet, which critically provides feedback as to how effectively the child is achieving physiological ketosis [2]. Traditionally, this has been done using urine ketone dipstick testing, but it is now possible to prescribe a blood glucose and ketone monitor in many countries. The former is less expensive and avoids finger pricks, but the latter is easier, more specific, and more accurate [38]. Unless there is a compelling reason to measure urinary ketones, a blood glucose and ketone monitor should be prescribed and the caregiver instructed on its use.

Finally, investigations should be ordered before commencing a ketogenic diet in a child, primarily to rule out contraindications (a ketogenic diet is absolutely contraindicated in disorders of fat metabolism, including carnitine deficiency, carnitine palmitoyltransferase I and II deficiency, any of the short, medium, or longchain acyl dehydrogenase deficiencies, and porphyria) [2]. Basic laboratory

investigations include complete blood count, electrolytes, liver and kidney function tests, fasting lipid profile, calcium, vitamin D, serum acylcarnitine profile, and a urinalysis [2]. Baseline anti-epileptic drug levels can be measured, although few concerns for drug-diet interactions exist. A recent EEG and MRI brain should be obtained to identify potential surgical candidates. Further tests, such as ECG and renal ultrasound, may be ordered as clinically indicated.
