作者：Allison Gandey
出處：WebMD醫學新聞
June 3, 2010 — 研究者們報告，最近發生的癲癇可能改變腦部發育，且延遲腦部白質體積增加的速度。這些新發現對於新診斷罹患癲癇且可能體驗到腦部連結下降與執行功能受損兒童們的認知功能發展是有意義的。
主要研究者，來自麥德遜威斯康辛州立大學的Bruce Hermann博士向Medscape神經學表示，罹患慢性癲癇的成人已經被報告有些許異常的情形。我們這項研究的眾多目的之一在於尋找這些異常的來源。顯然地，這些變化可以在兒童時期癲癇的初期病程中看到。
這些研究結果已經線上發表，且將刊登於7月號的癲癇（Epilepsy）期刊。
研究者們評估了38位新診斷癲癇的兒童，並與34位健康的親戚進行比對。超過一半有癲癇問題的兒童有定位相關異常，而其他兒童有先天性全身性疾病。
受試者們在試驗前與2年後接受1.5T核磁共振造影。研究者們比較整體大腦與頁灰質還有白質的體積。
他們發現，灰質體積的變化在癲癇患者與控制組是相當的。整體大腦灰質顯著下降主要是因為前葉與頂葉的下降。
但是在白質體積上就不是那麼一回事，不同組之間是有差異的。控制組的整體大腦白質體積是顯著增加的（P=0.0012）。這些體積在額葉、頂葉以及顳葉增加的最多（P<0.001）。相對的，癲癇患者的整體大腦白質體積並未顯著改變（P=0.51），且不同葉之間也是如此（P>0.06）。
表格 白質葉體積前瞻性變化
| 葉 | 控制組 | 癲癇患者 |
| 額葉 | 3.97 | 1.54 |
| 頂葉 | 2.42 | 1.02 |
| 顳葉 | 1.71 | 0.74 |
| 枕葉 | 0.03 | -1.21 |
研究者報告，從這項研究中產生的兩項核心發現是，第一，大腦灰質體積的變化，相較於健康控制組，罹患癲癇兒童顯然是以正常速度進行。其次，相較於控制組受試者，罹患癲癇兒童的白質體積增加速度顯然是延遲的。
他們附帶表示，這些腦部發育的些微異常在罹患先天性全身性癲癇的兒童身上是最明顯的。
在訪談中，Hermann博士指出，這項研究的樣本數目並不大，且2年的後續追蹤是很短的。他們表示，問題之一是這項發現的持久性。如果癲癇變得可以完全控制或是消退，且不在需要使用藥物，發育是否將會是正常的？
Hermann博士提議，在了解這些發現的來源上，將會有許多人抱持高度興趣，是因為癲癇、藥物或是其他原因？他的團隊目前正在研究這些發育異常將會帶來哪些實際的意義。
【癲癇腦病變的風險】
發育異常是大部份臨床醫師擔憂的。來自洛杉磯加州大學的Gary Mathern醫師最近向Medscape神經學談到他的新文獻，有關於兒童癲癇患者接受手術的預後，他對於這個議題也是相當關心的。
Mathern醫師表示，這些兒童處於癲癇腦病變與IQ（智商）低於50的風險。我們知道當藥物在數個月內無法控制癲癇，儘管我經常在4或5年後看到患者。我們必須中止癲癇，並給予腦部其他部位有機會發育。
Mathern醫師的新文獻發表於6月1日的神經學期刊。他是國際對抗癲癇聯盟任務小組的一員，且發表了第一個抗藥性癲癇的全球共識定義。
該任務小組極力主張臨床醫師們應該考慮這個方法：在使用兩次適當且耐受性良好的藥物之後，仍然有癲癇的患者們應該轉介給專家。
任務小組主席，來自香港中文大學的Patrick Kwan醫師在一項訪談中表示，當該團隊的新定義第一次於12月揭露時，兩次打擊後他們將被轉介。目標在於避免改變疾病進程不必要的延遲。
研究者們表示沒有相關資金上的往來。Mathern醫師表示，他是Neuropace有限公司的資料處理委員會成員。Kwan表示沒有相關利益衝突。
Children With New Epilepsy Often Have Delayed Brain Development
By Allison Gandey
Medscape Medical News
June 3, 2010 — Recent-onset epilepsy can alter brain development and delay increases in white matter volume, report researchers. These new findings have implications for the cognitive development of children with newly diagnosed epilepsy who may experience reduced brain connectivity and impairments in executive function.
Modest abnormalities have already been reported in adults with chronic epilepsy. "One of the purposes of our research has been to search for the origin of such abnormalities," lead investigator Bruce Hermann, PhD, from the University of Wisconsin at Madison, told Medscape Neurology. "It does appear that these changes can be seen early on in the course of childhood epilepsy."
The results are available online and will appear in the July issue of Epilepsia.
The researchers evaluated 38 children with newly diagnosed epilepsy and compared them to 34 healthy cousins. More than half of the children with epilepsy had localization-related disorder, and the remainder had idiopathic generalized disease.
Participants underwent 1.5T magnetic resonance imaging at baseline and 2 years later. Investigators compared total cerebral and lobar gray and white matter volumes.
They found changes in gray matter volume were comparable for epilepsy and control groups. There was a significant reduction in total cerebral gray matter primarily due to decreases in the frontal and parietal lobes.
This was not the case with white matter volume, where changes differed between groups. Controls experienced a significant increase in total cerebral white matter volume (P = .0012). These volume increases were greatest in the frontal, parietal, and temporal lobes (P < .001). In contrast, epilepsy patients experienced a nonsignificant white matter volume change in the total cerebrum (P = .51) and across all lobes (P > .06).
Table. Prospective Change in White Matter Lobar Volumes
| Lobe | Control | Epilepsy |
| Frontal | 3.97 | 1.54 |
| Parietal | 2.42 | 1.02 |
| Temporal | 1.71 | 0.74 |
| Occipital | 0.03 | ?1.21 |
"Two core findings emerge from this investigation," the investigators report. "First, prospective changes in cerebral gray matter volumes appear to be proceeding at a normal rate in children with epilepsy compared to healthy controls," they note. "Second, there appears to be a significant delay in the rate of white matter volume increase among children with epilepsy compared to controls."
These modest abnormalities in brain development are more evident, they add, in children with idiopathic generalized epilepsies.
During an interview, Dr. Hermann pointed out the sample size for the study is modest and the 2-year follow-up short. "One question is the permanence of the findings," he noted. "If the epilepsy becomes completely controlled or remits and medications are no longer needed, will there be normalization of development?"
Dr. Hermann proposes that interest will be high in understanding the origin of these findings — is it due to seizures, medications, or other factors? His team is currently researching what the practical complications of these developmental abnormalities will be.
Risk for Epileptic Encephalopathy
Developmental abnormalities are something most clinicians are concerned about. Gary Mathern, MD, from the University of California at Los Angeles, who recently spoke to Medscape Neurology about his new paper on surgical outcomes for pediatric epilepsy patients, was emphatic about the issue.
"These children are at risk for epileptic encephalopathy and an IQ less than 50," Dr. Mathern said. "We know when a medication has failed within months, yet I'm often seeing patients 4 or 5 years later. We have to get in there to stop the seizures and give the rest of the brain a chance to develop," he said.
Dr. Mathern's new paper appears in the June 1 issue of Neurology. He is a member of an International League Against Epilepsy task force that developed the first-ever global consensus definition of drug-resistant epilepsy.
The task force is urging clinicians to consider this approach: after 2 adequate trials of appropriate and well-tolerated drugs, patients who continue to have seizures should be referred to a specialist.
"Two strikes and they're in for referral," Patrick Kwan, MD, task force chair, from the Chinese University of Hong Kong, said in an interview when the group's new definition was first unveiled in December. The goal, he said, is to avoid unnecessary delays in altering the course of disease.
The researchers have disclosed no relevant financial relationships. Dr. Mathern reports he is on the data management committee of Neuropace Inc. Dr. Kwan has disclosed no competing interests.
Epilepsia. Published online April 2, 2010.
