Studies highlight benefits and risks of ketogenic diet for refractory epilepsy

WASHINGTON – The ketogenic diet is well established as an effective treatment for patients with refractory epilepsy, and although studies presented at the annual meeting of the American Epilepsy Society confirm its value for both children and adults, others raise important concerns.

Researchers from the University of Missouri – Kansas City (UMKC), for example, reported that adhering to a ketogenic diet (KGD) reduced the number of emergency department visits and hospitalizations, and decreased the length of epilepsy-related hospital stays in children with pharmacologically refractory epilepsy.

In 98 children from the Children’s Mercy Hospital–UMKC database who had complete records available and who remained on the diet for at least 6 months, the number of ED visits decreased by 64%, and the charges associated with those visits decreased by 50% from the 12 months before diet initiation to the 12 months after, Dr. Anastasia Luniova reported in a poster at the meeting.

After an initial increase in the total number of hospitalizations and the number of hospital days, due largely to stays associated with diet initiation, the number of hospitalizations decreased by 61% and the number of hospital days decreased by 66%. Associated charges decreased by 47%.

Children in this retrospective chart study from a level IV pediatric epilepsy center included 62 boys and 36 girls with an average age of 4.4 years at initiation of the ketogenic diet. The average diet duration was 31.7 months.

"This study provides evidence that the KGD has a positive impact in children with pharmacologically refractory epilepsy by reducing the number of ED visits, numbers of hospitalizations, as well as length of hospital stay related to epilepsy, and associated comorbidities. ... Further data analysis is necessary for detailed cost-effectiveness assessment of the KGD," Dr. Luniova wrote.

The KGD was also safe and effective in a study of 10 adults with refractory status epilepticus, Dr. John C. Probasco of Johns Hopkins University, Baltimore, reported in a poster.

While further studies are needed to determine the applicability of a KGD in adult patients, as well as the long-term outcomes, the findings suggest it is safe and feasible, Dr. Probasco said.

The retrospective case study at four medical centers included patients over age 17 years with status epilepticus that continued for at least 24 hours after initiation of general anesthetic medication, or that recurred following weaning from, or discontinuation of, the treatment. The patients, including four men and six women, had a median age of 33 years, and seven had encephalitis. Prior to KGD initiation, the median duration of status epilepticus was 21.5 days, and the median number of antiepileptic drugs (AEDs) used was seven.

Nine of the 10 patients achieved ketosis within a median of 3 days, and all patients had cessation of status epilepticus within 3 days. Furthermore, seven had clinical and/or electrographic seizure resolution within 7 days, and nine had such resolution within 1 month. At discharge, the median number of antiepileptic drugs prescribed was four, Dr. Probasco reported.

Another study demonstrated the beneficial effects of a KGD on immunoglobulin levels and infection frequency.

"In addition to its known side effects, the [KGD] is considered to lead to an increase in infection frequency causing possible neutrophil function impairment and the reason behind this has not yet been explained completely," wrote Dr. Orkide Güzel of Izmir (Turkey) Dr. Behçet Uz Children’s Hospital.

But a review of the records of 36 children with resistant epilepsy, including 17 girls and 19 boys with a mean age of 39.5 months, showed no significant differences with respect to the number and severity of infections before and after KGD initiation, and immunoglobulin levels remained normal for the patients’ ages. At the same time, their number of seizures and AED usage decreased. Epileptic encephalopathy in five patients also went away after KGD treatment.

However, several other studies found that in children, the diet may be linked with decreases in growth and bone health.

Delayed growth is considered a potential side effect of the KGD, and UMKC investigators set out to assess growth related to caloric intake in infants and children being treated with a KGD. In another retrospective chart study of 76 children treated at Children’s Mercy Hospital, Kansas City, mean weight- and height-for-age percentiles and z scores declined over a period of 12 months, though not statistically significantly, Dr. Lindsey Thompson of Children’s Mercy reported in a poster.

For example, the weight percentile declined from 49.48% at baseline to 42.94% at 12 months, and the height percentile decreased from 52.08% to 45.06%. These decreases occurred despite an increase in caloric intake from 999 kcal at baseline to 1,134 kcal at 12 months.

The results require further prospective evaluation, Dr. Thompson said.

Another study found a significant risk of developing osteopenia among patients on a KGD, compared with matched controls.

Of 132 children included in the retrospective matched cohort study, 66 were treated with AEDs and a KGD (initiated at a mean age of 4.3 years), and 66 were treated with AEDs alone.

The KGD group had fractures – often unrelated to trauma – more often than did those on AEDs alone (14% vs. 8%, respectively). The incidence of both osteopenia and fractures increased in tandem with the duration of the KGD, according to the group of investigators from the University of British Columbia, Vancouver, led by Dr. Mary B. Connolly.

There was a history of trauma in one-third of the KGD patients with fracture, compared with 100% of those in the AED-only group. In addition, all patients in the KGD group had osteopenia, compared with 60% of those in the control group.

Nonambulatory status was a risk factor for osteopenia and fractures in both groups, and a longer duration of KGD was associated with greater risk. For instance, among those treated for 1-3 years, 4% had fractures and 27% had osteopenia, and among those treated for 4 or more years, 20% had fractures and 43% had osteopenia.

"Our results suggest that prolonged treatment with the KD may be associated with significant morbidity, including osteopenia and fractures," Dr. Connolly wrote, noting that the incidence of osteopenia in the study was likely underestimated because of the retrospective design.

The findings, which support those of prior long-term studies, suggest that monitoring of bone health and vitamin D and calcium supplementation is important in this population, she said.

WASHINGTON – The ketogenic diet is well established as an effective treatment for patients with refractory epilepsy, and although studies presented at the annual meeting of the American Epilepsy Society confirm its value for both children and adults, others raise important concerns.

Researchers from the University of Missouri – Kansas City (UMKC), for example, reported that adhering to a ketogenic diet (KGD) reduced the number of emergency department visits and hospitalizations, and decreased the length of epilepsy-related hospital stays in children with pharmacologically refractory epilepsy.

In 98 children from the Children’s Mercy Hospital–UMKC database who had complete records available and who remained on the diet for at least 6 months, the number of ED visits decreased by 64%, and the charges associated with those visits decreased by 50% from the 12 months before diet initiation to the 12 months after, Dr. Anastasia Luniova reported in a poster at the meeting.

After an initial increase in the total number of hospitalizations and the number of hospital days, due largely to stays associated with diet initiation, the number of hospitalizations decreased by 61% and the number of hospital days decreased by 66%. Associated charges decreased by 47%.

Children in this retrospective chart study from a level IV pediatric epilepsy center included 62 boys and 36 girls with an average age of 4.4 years at initiation of the ketogenic diet. The average diet duration was 31.7 months.

"This study provides evidence that the KGD has a positive impact in children with pharmacologically refractory epilepsy by reducing the number of ED visits, numbers of hospitalizations, as well as length of hospital stay related to epilepsy, and associated comorbidities. ... Further data analysis is necessary for detailed cost-effectiveness assessment of the KGD," Dr. Luniova wrote.

The KGD was also safe and effective in a study of 10 adults with refractory status epilepticus, Dr. John C. Probasco of Johns Hopkins University, Baltimore, reported in a poster.

While further studies are needed to determine the applicability of a KGD in adult patients, as well as the long-term outcomes, the findings suggest it is safe and feasible, Dr. Probasco said.

The retrospective case study at four medical centers included patients over age 17 years with status epilepticus that continued for at least 24 hours after initiation of general anesthetic medication, or that recurred following weaning from, or discontinuation of, the treatment. The patients, including four men and six women, had a median age of 33 years, and seven had encephalitis. Prior to KGD initiation, the median duration of status epilepticus was 21.5 days, and the median number of antiepileptic drugs (AEDs) used was seven.

Nine of the 10 patients achieved ketosis within a median of 3 days, and all patients had cessation of status epilepticus within 3 days. Furthermore, seven had clinical and/or electrographic seizure resolution within 7 days, and nine had such resolution within 1 month. At discharge, the median number of antiepileptic drugs prescribed was four, Dr. Probasco reported.

Another study demonstrated the beneficial effects of a KGD on immunoglobulin levels and infection frequency.

"In addition to its known side effects, the [KGD] is considered to lead to an increase in infection frequency causing possible neutrophil function impairment and the reason behind this has not yet been explained completely," wrote Dr. Orkide Güzel of Izmir (Turkey) Dr. Behçet Uz Children’s Hospital.

But a review of the records of 36 children with resistant epilepsy, including 17 girls and 19 boys with a mean age of 39.5 months, showed no significant differences with respect to the number and severity of infections before and after KGD initiation, and immunoglobulin levels remained normal for the patients’ ages. At the same time, their number of seizures and AED usage decreased. Epileptic encephalopathy in five patients also went away after KGD treatment.

However, several other studies found that in children, the diet may be linked with decreases in growth and bone health.

Delayed growth is considered a potential side effect of the KGD, and UMKC investigators set out to assess growth related to caloric intake in infants and children being treated with a KGD. In another retrospective chart study of 76 children treated at Children’s Mercy Hospital, Kansas City, mean weight- and height-for-age percentiles and z scores declined over a period of 12 months, though not statistically significantly, Dr. Lindsey Thompson of Children’s Mercy reported in a poster.

For example, the weight percentile declined from 49.48% at baseline to 42.94% at 12 months, and the height percentile decreased from 52.08% to 45.06%. These decreases occurred despite an increase in caloric intake from 999 kcal at baseline to 1,134 kcal at 12 months.

The results require further prospective evaluation, Dr. Thompson said.

Another study found a significant risk of developing osteopenia among patients on a KGD, compared with matched controls.

Of 132 children included in the retrospective matched cohort study, 66 were treated with AEDs and a KGD (initiated at a mean age of 4.3 years), and 66 were treated with AEDs alone.

The KGD group had fractures – often unrelated to trauma – more often than did those on AEDs alone (14% vs. 8%, respectively). The incidence of both osteopenia and fractures increased in tandem with the duration of the KGD, according to the group of investigators from the University of British Columbia, Vancouver, led by Dr. Mary B. Connolly.

There was a history of trauma in one-third of the KGD patients with fracture, compared with 100% of those in the AED-only group. In addition, all patients in the KGD group had osteopenia, compared with 60% of those in the control group.

Nonambulatory status was a risk factor for osteopenia and fractures in both groups, and a longer duration of KGD was associated with greater risk. For instance, among those treated for 1-3 years, 4% had fractures and 27% had osteopenia, and among those treated for 4 or more years, 20% had fractures and 43% had osteopenia.

"Our results suggest that prolonged treatment with the KD may be associated with significant morbidity, including osteopenia and fractures," Dr. Connolly wrote, noting that the incidence of osteopenia in the study was likely underestimated because of the retrospective design.

The findings, which support those of prior long-term studies, suggest that monitoring of bone health and vitamin D and calcium supplementation is important in this population, she said.

WASHINGTON – The ketogenic diet is well established as an effective treatment for patients with refractory epilepsy, and although studies presented at the annual meeting of the American Epilepsy Society confirm its value for both children and adults, others raise important concerns.

Researchers from the University of Missouri – Kansas City (UMKC), for example, reported that adhering to a ketogenic diet (KGD) reduced the number of emergency department visits and hospitalizations, and decreased the length of epilepsy-related hospital stays in children with pharmacologically refractory epilepsy.

In 98 children from the Children’s Mercy Hospital–UMKC database who had complete records available and who remained on the diet for at least 6 months, the number of ED visits decreased by 64%, and the charges associated with those visits decreased by 50% from the 12 months before diet initiation to the 12 months after, Dr. Anastasia Luniova reported in a poster at the meeting.

After an initial increase in the total number of hospitalizations and the number of hospital days, due largely to stays associated with diet initiation, the number of hospitalizations decreased by 61% and the number of hospital days decreased by 66%. Associated charges decreased by 47%.

Children in this retrospective chart study from a level IV pediatric epilepsy center included 62 boys and 36 girls with an average age of 4.4 years at initiation of the ketogenic diet. The average diet duration was 31.7 months.

"This study provides evidence that the KGD has a positive impact in children with pharmacologically refractory epilepsy by reducing the number of ED visits, numbers of hospitalizations, as well as length of hospital stay related to epilepsy, and associated comorbidities. ... Further data analysis is necessary for detailed cost-effectiveness assessment of the KGD," Dr. Luniova wrote.

The KGD was also safe and effective in a study of 10 adults with refractory status epilepticus, Dr. John C. Probasco of Johns Hopkins University, Baltimore, reported in a poster.

While further studies are needed to determine the applicability of a KGD in adult patients, as well as the long-term outcomes, the findings suggest it is safe and feasible, Dr. Probasco said.

The retrospective case study at four medical centers included patients over age 17 years with status epilepticus that continued for at least 24 hours after initiation of general anesthetic medication, or that recurred following weaning from, or discontinuation of, the treatment. The patients, including four men and six women, had a median age of 33 years, and seven had encephalitis. Prior to KGD initiation, the median duration of status epilepticus was 21.5 days, and the median number of antiepileptic drugs (AEDs) used was seven.

Nine of the 10 patients achieved ketosis within a median of 3 days, and all patients had cessation of status epilepticus within 3 days. Furthermore, seven had clinical and/or electrographic seizure resolution within 7 days, and nine had such resolution within 1 month. At discharge, the median number of antiepileptic drugs prescribed was four, Dr. Probasco reported.

Another study demonstrated the beneficial effects of a KGD on immunoglobulin levels and infection frequency.

"In addition to its known side effects, the [KGD] is considered to lead to an increase in infection frequency causing possible neutrophil function impairment and the reason behind this has not yet been explained completely," wrote Dr. Orkide Güzel of Izmir (Turkey) Dr. Behçet Uz Children’s Hospital.

But a review of the records of 36 children with resistant epilepsy, including 17 girls and 19 boys with a mean age of 39.5 months, showed no significant differences with respect to the number and severity of infections before and after KGD initiation, and immunoglobulin levels remained normal for the patients’ ages. At the same time, their number of seizures and AED usage decreased. Epileptic encephalopathy in five patients also went away after KGD treatment.

However, several other studies found that in children, the diet may be linked with decreases in growth and bone health.

Delayed growth is considered a potential side effect of the KGD, and UMKC investigators set out to assess growth related to caloric intake in infants and children being treated with a KGD. In another retrospective chart study of 76 children treated at Children’s Mercy Hospital, Kansas City, mean weight- and height-for-age percentiles and z scores declined over a period of 12 months, though not statistically significantly, Dr. Lindsey Thompson of Children’s Mercy reported in a poster.

For example, the weight percentile declined from 49.48% at baseline to 42.94% at 12 months, and the height percentile decreased from 52.08% to 45.06%. These decreases occurred despite an increase in caloric intake from 999 kcal at baseline to 1,134 kcal at 12 months.

The results require further prospective evaluation, Dr. Thompson said.

Another study found a significant risk of developing osteopenia among patients on a KGD, compared with matched controls.

Of 132 children included in the retrospective matched cohort study, 66 were treated with AEDs and a KGD (initiated at a mean age of 4.3 years), and 66 were treated with AEDs alone.

The KGD group had fractures – often unrelated to trauma – more often than did those on AEDs alone (14% vs. 8%, respectively). The incidence of both osteopenia and fractures increased in tandem with the duration of the KGD, according to the group of investigators from the University of British Columbia, Vancouver, led by Dr. Mary B. Connolly.

There was a history of trauma in one-third of the KGD patients with fracture, compared with 100% of those in the AED-only group. In addition, all patients in the KGD group had osteopenia, compared with 60% of those in the control group.

Nonambulatory status was a risk factor for osteopenia and fractures in both groups, and a longer duration of KGD was associated with greater risk. For instance, among those treated for 1-3 years, 4% had fractures and 27% had osteopenia, and among those treated for 4 or more years, 20% had fractures and 43% had osteopenia.

"Our results suggest that prolonged treatment with the KD may be associated with significant morbidity, including osteopenia and fractures," Dr. Connolly wrote, noting that the incidence of osteopenia in the study was likely underestimated because of the retrospective design.

The findings, which support those of prior long-term studies, suggest that monitoring of bone health and vitamin D and calcium supplementation is important in this population, she said.