The current study included all patients following in pediatric Ketoclinic, Children´s hospital ASU since it started in 2013. Those patients were recruited and received KD therapy according to the clinic protocol.
Regarding the frequency of complaints and complications in our patients, the major causes were gastrointestinal troubles as well as diet refusal and unavailability. This agrees with Jagadish et al.19 who studied 59 children with epilepsy on KD and found that adverse effects included vomiting in 24% of his patients and refusal to feed in 11%.
Regarding frequency of convulsions, there was a significant decrease after 3 months of KD and highly significant decreases after 24 and 36 months. This comes in agreement with Armeno et al.20 who studied 45 patients on KD and found 73% of them were responders after only three months of KD. On the other hand, Jagadish et al.19 initially reported a response rate of 63% at the end of the first month among his studied series but this number showed a gradual decline to 41% by the end of second year therapy.
On applying Chalfont seizure severity scale on our patients there was significant decrease in the severity of the seizure after KD. Similar finding was reported by Hallböök and collaborators21 who studied 18 children diagnosed as DRE on KD for 12 months, the seizure severity significantly improved at three and twelve months. The latter authors mainly attributed their findings to the decrease in duration of the convulsions.
Vineland test results of the series of studied patients showed that 65% of them had a significant increase after using the KD. Similarly, in 2001, Pulsifer and collaborators22 used the Child Behavior Checklist to assess behavioral and emotional problems in 65 pediatric patients with DRE after 1 year of KD therapy and reported that their mean developmental quotient showed statistically significant improvement (p < 0.05), with significant behavioral improvements in attention and social functioning. Additionally, Garcias-Penas5, reported that the positive neurocognitive and behavioral effect of KD in pediatric patients with epilepsy is most evident in aspects of mood, alertness and activity level, sustained attention, and reciprocal social interaction, and is not related to seizure control or a reduction in the dose or number of anti-epileptic drugs.
From another perspective, in 2016 Wu and collaborators23, reported that there was a positive correlation between increased cognition and the efficacy of a KD after 3 months. This is also in concordance with van Berkel et al.24; who conducted a systematic overview and reported that cognitive improvements are frequently reported during KD treatment in the domains of alertness, attention, and global cognition. The latter authors added that studies which used objective neuropsychological tests confirmed benefits on alertness but not in global cognition. Regarding the cause of these improvements van Berkel and associates24 reported that they are caused by both seizure reduction and direct effects of KD on cognition.
In the current study 11% of patients remained on KD for ≤ 1 month, 25% of patients remained on KD for 1–3 months 18% remained on KD for 3–6 months, 13% remained on KD for 6–12 months, 20% remained on KD for 12–24 months and 13% remained on KD for more than 24 months. Sharma et al.25 who studied 27 Indian children with epilepsy similarly reported that 37% remained on the KD after 1 year.
Concerning lipid profile of the patients there was no significant difference in any of its components after KD therapy. This agrees with a Danish study performed by Miranda et al.26 in which patients with refractory epilepsy received MAD showed no significant increase in free cholesterol, triglycerides, LDL and HDL cholesterol. Nevertheless, Chen27, who studied 47 children with intractable epilepsy found that after 3 months of KD the triglycerides and total cholesterol levels were slightly higher than the initial levels. Additionally, the HDL levels were slightly lower, and the LDL levels were significantly higher after KD therapy.
Weight assessment in our patients showed significant increase in the weight, z score for weight. On the other hand, Neal et al.9 found that weight z scores decreased significantly between baseline and 3, 6, and 12 months of KD therapy for their series of children with intractable epilepsy. This was attributed mainly to the caloric restriction of the KD. Weight loss was documented earlier by Sirven and collaborators28 who studied 11 intractable epileptic patients under treatment with KD and decrease in weight was apparent in 5 patients after 8 months on KD. Weight loss may be a result of decrease caloric intake or increased satiety effect of protein29.
Height/length assessment in the current patients showed significant increase in its value as well as the z score for age. This agrees with Vining and collaborators30 who reported that children grew taller during the first year on KD. In contrast, Tagliabue et al.31 studied 18 refractory epileptic children and they found a non-significant difference in height after 6 months KD. Additionally, Neal et al.9 found that height z scores showed no change at 3 months but decreased significantly by 6 and 12 months.
One suggested explanation to the improvements in the anthropometric measurements of the studied series of patients could be the fact that they were initially malnourished due to socioeconomic causes and when the KD was provided to them during the whole study period their caloric and micronutrient intakes improved which reflected well on their anthropometric measurements. Worth noting here is that although Armeno and collaborators20 found growth deceleration in 4 of their patients (9%) after 4 months KD therapy, the nutritional status was maintained or even improved upon follow up.
Regarding BMI, the studied series of patients showed no significant increase in BMI and in z score BMI for age and this can be explained by the proportionate increase in weight and length. This is in concordance with Perna and collaborators32 who found no significant changes in BMI after 12 months of KD usage in their 24 studied children.
In conclusion, registration of the Ketoclinic patients’ data using software program helped us identify the characteristics of patients on KD and highlighted the factors precluding their compliance and those ensuring their promising management outcome. ASU Children’s Hospital Ketoclinic data further proves that KD is an effective line of therapy for DRE with significant improvements in the frequency as well as the severity of convulsions without affecting their growth parameters or laboratory results. Finally, the enhancement in adaptive behavior is a promising finding and perhaps wider scale studies and longer duration of KD usage can demonstrate further cognitive benefits in treated patients.
Study limitations
This study has its own limitations. More patients should have been subjected to the Vineland test for adaptive behavior assessment and more tests to show the cognitive benefits would have completed the picture.