作者：Allison Gandey
出處：WebMD醫學新聞
May 27, 2010 — 研究者表示，對於對其他治療無反應、持續有癲癇抽搐情況的小兒病患，生酮飲食(ketogenic diet)是一種有效的替代療法。約翰霍普金斯兒童醫學中心的大型分析結果顯示，約三分之二的難治型病患對於高脂、低碳水化合物飲食有反應。
資深研究者、約翰霍普金斯生酮飲食計畫主任、小兒神經科Eric Kossoff醫師在新聞稿中表示，停止或減少抽搐次數是保留神經功能的長遠之計，生酮飲食將是我們用在那些藥物無法改善之持續嬰兒點頭痙攣(infantile spasms)孩童的下一道防線。
這篇新研究是2002年一篇報告的追蹤，當時的分析顯示這種飲食對少數嬰兒點頭痙攣孩童有效，目前的報告線上登載於Epilepsia期刊，則是包括了104名小兒病患。
生酮飲食提供了剛好足夠的蛋白質供身體生長與修補，以及提供足夠的熱量來維持健康的體重，典型的生酮飲食以4比1的比率包含脂質和蛋白質及碳水化合物。
研究作者指出，我們發現，難治型嬰兒點頭痙攣病患被指定使用生酮飲食的案例顯著增加，他們也開始對一些新發生的案例使用這種飲食。本研究的目的是，以更多病患來評估治療成功的預測因素，比較隨著時間變化的結果，評估長期的抽搐、腦電圖與發展結果。
研究者指出，將近40%的小孩有至少6個月沒有抽搐，其中多數達到至少2年無抽搐。
表、每段追蹤期間時的抽搐減少情況
| 減少百分比、% | 3個月，% | 6個月，% | 9個月，% | 1年，% | 2年，% |
| 完全無抽搐 | 18 | 28 | 32 | 30 | 33 |
| >90 | 13 | 11 | 14 | 13 | 11 |
| 50 – 90 | 32 | 25 | 27 | 34 | 33 |
| <50 | 37 | 36 | 27 | 23 | 23 |
研究者另外報告指出，發育和腦電圖也有顯著改善，同時使用的抗痙攣藥物數量也減少。
病患的平均年紀是1.2歲，之前的治療包括了使用平均3.6種抗痙攣藥物，多數病患曾經嘗試使用皮質類固醇或者vigabatrin。
研究者對18名未曾以藥物治療的新抽搐病患使用飲食作為第一線治療，其中10名病患在飲食治療開始後兩週內變成沒有抽搐。
研究發現認為，對某些孩童而言，飲食療法可有效作為第一線治療。去年12月，在美國癲癇協會第63屆年度科學研討會中，專家們對此方式的利弊進行辯論。
其中一位發言者、加拿大安大略多倫多兒童醫院的Elizabeth Donner醫師認為，生酮飲食有效且應考慮作為嬰兒點頭痙攣的第一線治療，特別是GLUT1和丙酮酸鹽脫氫酵素(pyruvate dehydrogenase)不足者。
【GLUT1和丙酮酸鹽脫氫酵素不足的第一線治療】
Donner醫師表示，抗癲癇藥物對孩童有傷害，有相當多副作用— 許多嚴重的副作用且有些會影響認知。她表示，在一些案例中，抗癲癇藥物甚至會惡化抽搐。
Donner醫師認為，既然生酮飲食可以有迅速作用，它應可試著被第一線使用。
另一位發言者、伊利諾州芝加哥兒童紀念醫院的Douglas Nordli醫師表示，同意生酮飲食可以作為GLUT1和丙酮酸鹽脫氫酵素不足孩童的第一線治療，不過，他認為，在其他方面，這類飲食好處的證據有限。
Nordli醫師表示，對營養師和家人而言，並不容易立即開始使用生酮飲食，所以他會繼續先試用一、兩種藥物。
他指出，這種飲食並非完全無害，對於有代謝缺損的病患可能特別危險。
常見的副作用包括便秘、胃灼熱、腹瀉、行為問題、腎結石、膽固醇值暫時性攀升。在本研究中，有三分之一的孩童觀察到副作用，有一些也發生成長減少(6%)。
Nordli醫師表示，我們若無足夠的前瞻比較資料就提議將生酮飲食作為第一線治療，將會對其產生傷害。顯示可能有效果的文章，並不等同於優於現有的製劑。
第一作者、霍普金斯的醫學生Amanda Hong向Medscape Neurology表示，她們同意需要進行前瞻式的多中心研究。
約翰霍普金斯大學以及國家健康研究中心資助該研究。Kossoff 醫師接受Nutricia Inc公司的財務支持為其他產品進行研究。
Epilepsia. 線上發表於2010年4月30日。
New Finding Adds Weight to Ketogenic Diet for Childhood Seizures
By Allison Gandey
Medscape Medical News
May 27, 2010 — The ketogenic diet is an effective alternative for pediatric patients with persistent seizures who have not responded to other therapies, say investigators. Reporting results from the largest analysis to date, researchers from Johns Hopkins Children's Center, Baltimore, Maryland, show that about two-thirds of refractory patients respond to the high-fat, low-carbohydrate diet.
"Stopping or reducing the number of seizures can go a long way toward preserving neurological function, and the ketogenic diet should be our immediate next line of defense in children with persistent infantile spasms who don’t improve with medication," senior investigator Eric Kossoff, MD, a pediatric neurologist and director of the ketogenic diet program at Hopkins, said in a news release.
The new study is a follow-up of a 2002 report that showed the diet worked well in a small number of children with infantile spasms. The current report, published online in Epilepsia, includes 104 pediatric patients.
The ketogenic diet provides just enough protein for body growth and repair and sufficient calories to maintain a healthy weight. The classic ketogenic diet contains a 4:1 ratio of fat to combined protein and carbohydrate.
"We have seen a significant increase in referrals for the ketogenic diet for intractable infantile spasms," note the study authors. They have also started using the diet in new-onset cases. "The purpose of this study was to use the increased patient cohort to evaluate for predictive factors for success, compare results over time, and evaluate long-term seizure, electroencephalogram, and developmental outcomes."
The researchers show that nearly 40% of children became seizure free for at least 6 months. Most of these have remained seizure free for at least 2 years.
Table. Spasm Reduction at Each Follow-up
| Reduction, % | 3 Months, % | 6 Months, % | 9 Months, % | 1 Year, % | 2 Years, % |
| Seizure free | 18 | 28 | 32 | 30 | 33 |
| >90 | 13 | 11 | 14 | 13 | 11 |
| 50 – 90 | 32 | 25 | 27 | 34 | 33 |
| <50 | 37 | 36 | 27 | 23 | 23 |
The investigators also report significant improvements in development and electroencephalograms, as well as a reduction in the number of concurrent anticonvulsants.
The mean age of patients was 1.2 years. Previous therapy included on average 3.6 anticonvulsants. Most patients had tried corticosteroids or vigabatrin.
The researchers used the diet first line in 18 patients with newly diagnosed seizures never treated with drugs. Ten of these patients became seizure free within 2 weeks of starting the diet.
The finding suggests that in some children the diet may work well as first-line therapy. Debating at the American Epilepsy Society 63rd Annual Scientific Conference in December, experts weighed the pros and cons of this approach.
Speaker Elizabeth Donner, MD, from the Hospital for Sick Children in Toronto, Ontario, Canada, argued at the meeting that the ketogenic diet is effective and should be considered first line in infantile spasms and especially in GLUT1 and pyruvate dehydrogenase deficiency.
First Line In GLUT1 and Pyruvate Dehydrogenase Deficiency
"Antiepileptic drugs do bad things to children," Dr. Donner said, naming a long list of adverse effects — many serious and some involving cognitive impairment. "In some cases, antiepileptic drugs can even make seizures worse," she said.
Dr. Donner suggested that since the ketogenic diet works quickly, it makes sense to try it first line.
Speaker Douglas Nordli, MD, from the Children's Memorial Hospital in Chicago, Illinois, agreed the ketogenic diet can be used first line in patients with GLUT1 or pyruvate dehydrogenase deficiency. However, he argued there is otherwise limited evidence confirming the benefits of the diet.
Dr. Nordli says it is not easy for dieticians and families to start a ketogenic diet emergently, so he will continue to try 1 or 2 medications first.
"The diet is not completely innocuous," he added, noting that it can be especially dangerous for patients with underlying metabolic defects.
Common adverse effects include constipation, heartburn, diarrhea, behavior problems, kidney stones, and temporary spikes in cholesterol levels. In this study, adverse effects were observed in a third of children. Some also experienced diminished growth (6%).
"We would do a disservice to the ketogenic diet to propose it first line without sufficient prospective comparative data," Dr. Nordli said. "Articles showing a probable beneficial effect are not the same as comparative superiority to existing agents."
Speaking to Medscape Neurology, lead study author Amanda Hong, a medical student at Hopkins, said her team agrees. "Additional prospective, multicenter studies are needed."
This study was funded by Johns Hopkins University and the National Institutes of Health. Dr. Kossoff has received financial support from Nutricia Inc for unrelated research pertaining to their products.
Epilepsia. Published online April 30, 2010.
