【Epilepsy】新症状 “点头综合症”在乌干达流行
发布于 2011-12-26 · 浏览 1413 · IP 美国美国
这个帖子发布于 13 年零 141 天前，其中的信息可能已发生改变或有所发展。
1
African outbreak stumps experts
With few leads to go on, researchers pursue the childhood malady nodding syndrome.
Published online 13 July 2011 | Nature 475, 148-149 (2011) | doi:10.1038/475148a
http://www.nature.com/news/2011/110713/full/475148a.html
The boy was perhaps seven or eight, although he could have been older: among other things, the disease that afflicts him stunts growth. When a seizure began, his mother summoned Sudhir Bunga, who found the boy sitting under a tree in a school playground. "The child was staring blankly and his head was intermittently nodding every five to eight seconds," Bunga says. "This lasted about three minutes."
Bunga was not surprised by what he saw. A physician and epidemiologist with the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, he was in rural southern Sudan in May as part of an emergency-response team trying to assess a mysterious illness seen in children in the region. But despite his preparation, Bunga was deeply affected by his first encounter with 'nodding syndrome'. "Actually seeing it out in the community was overwhelming and distressing," he says. "The burden of the disease looked really high."
Nodding syndrome is a poorly understood and seemingly growing problem in eastern Africa, where it is devastating communities in South Sudan and northern Uganda. It has existed separately for decades in a secluded mountainous area of southern Tanzania1. In South Sudan, "it's affecting thousands of children," says Abdinasir Abubakar, a physician for the World Health Organization (WHO) based in South Sudan who coordinated the recent CDC trip. "Of course, the question is whether this syndrome is spreading to new communities."
For South Sudan, which achieved political independence only on 9 July, the syndrome raises the additional fear that the new nation's limited capacity to deal with an emerging medical threat will be quickly overwhelmed without outside resources and expertise.
"Nodding syndrome cannot be left with the nascent government in South Sudan," says Martin Opoka, an epidemiologist with the WHO's eastern Mediterranean regional office in Cairo. "They will certainly need assistance from the international community."
Opoka helped to investigate the occurrence of nodding syndrome in southern Sudan as part of a WHO team in 2002, and returned to the region this year to assist the CDC investigators. The CDC team — consisting of four physician-epidemiologists with specialities in paediatrics, neurology and nutrition — was dispatched by the US agency's Division of Global Disease Detection and Emergency Response (GDDER). The division undertakes a number of missions each year at the invitation of local health authorities, to plumb mysterious or troublesome outbreaks. "Most commonly, we know the cause either before we go out or by the time we come back," says Scott Dowell, the GDDER director. "But we do have a handful of enigmatic outbreaks."
Nodding syndrome is one such enigma. Most children it strikes are aged between 5 and 15. It impairs both physical growth and cognitive development. Its hallmark head nodding — often brought on by eating, and sometimes by cold — occurs when abnormal brain activity causes a brief lapse in neck muscle tone, causing the head to fall forwards. Electroencephalograms conducted by CDC investigators and others have shown subtler, sub-clinical seizures in many children, and some magnetic resonance imaging scans have revealed brain atrophy and damage to the hippocampus and to supportive brain cells known as glia.
Once the seizures begin, the health of children with the disease goes downhill. Perhaps because the onset of seizures inhibits eating, they suffer from malnutrition. They are also prone to accidents such as drowning and burning. Many stop attending school, and some are isolated because of fears of contagion. "Once they have it, they are going to die with it, and much earlier than they would have otherwise," says Dowell.
The condition was first documented in 1962 in southern Tanzania1, but its incidence now seems to be rising rapidly in South Sudan (see map) and in a non-contiguous area of northern Uganda where, in late 2009, the ministry of health reported that more than 2,000 children were affected. In May, the CDC team arrived in Juba, now South Sudan's capital, and journeyed in armoured vehicles to villages where nodding syndrome is making its presence felt.
The poorest children seem to be the most susceptible. Community focus groups convened by CDC teams have not turned up any changes in dietary or cultural practices that could account for the syndrome's emergence. In South Sudan, the CDC is probing whether population displacements and associated chemical exposures during wartime could have played a part. And although a study in southern Tanzania showed familial clustering2, genetics alone cannot explain the rapid emergence of so many cases. In one village that the CDC team visited during the recent trip, almost every family had an affected child. "We have chased a lot of dead ends," says Dowell.
Investigators have wondered whether Onchocerca volvulus, the blackfly-borne parasite that is best known for causing river blindness, might be the culprit. The CDC's work in northern Uganda showed a higher prevalence of nodding in children whose blood samples revealed infection with the parasite. However, the recent Tanzanian study2 failed to find significantly elevated antibodies to the parasite in cerebrospinal fluid samples from affected children.
"We could not establish any hint that Onchocerca volvulus is actually going into the brain," says Andrea Winkler, first author on the study2 and a consultant neurologist at the Technical University of Munich in Germany. "But what we cannot exclude is that there is an autoimmune mechanism going on." Even if that were the case, an association between the parasitic disease and nodding syndrome would not explain why adults and people in other areas where onchocerciasis is endemic are not affected by nodding syndrome.
The CDC team is also investigating whether deficiency of vitamin B6, or pyridoxine — which is common in children with nodding syndrome — could be the cause. Dowell notes that a rare genetic disease called pyridoxine-responsive epilepsy causes infants to have seizures, which disappear when the babies are given high-dose vitamin B6. In a return trip planned for late this year, the team hopes to run a clinical trial examining whether the vitamin can also alleviate nodding syndrome.
Opoka hopes that the increased attention will finally shed light on the condition and, ultimately, point the way to a treatment. Nodding syndrome "is silently increasing", he says. "If nothing is done we don't know what the end result will be." Bunga remains optimistic that something will come out of the data that the team gathered. "Did I come back with any clear answers? No," he says. "But there are still multiple paths of investigation open."
2
症状发作的视频
CDC 对此症状的介绍，（CDC Responds to Nodding Disease in Uganda）
http://www.youtube.com/watch?v=LwOUzE03xm0&noredirect=1
中间有孩子进食发病的视频，很短，很不典型的低头侧身。发言人说的一个内容很值得注意 “患儿出现注意力缺失，（以前聪明的孩子因为注意力缺失所以学习退步了）”
***南部的一个新闻介绍
http://www.youtube.com/watch?v=mbjQu_g17OE
最开始时段有晚期患病的患儿发病视频，很奇怪的身体倾斜抽搐，还有一个孩子整个倒地的视频（Near by, 15 year old Lili clasped... after about 5 minutes later, she wakes up）我不能说昏倒，因为似乎还是有意识的，5分钟后她起来，（这一段的表情很奇怪，像是痴呆或者淡漠）
我们从视频中也发现，患儿的发育比实际年龄看起来要小的多。这段介绍中说，发病以后的孩子就停止发育了。
3
新闻上对此的评价。
Mysterious nodding syndrome spreading through Uganda
http://www.newscientist.com/article/dn21316-mysterious-nodding-syndrome-spreading-through-uganda.html
http://www.medsoso.cn/text/2863/%E4%B9%8C%E5%B9%B2%E8%BE%BE%E6%9A%B4%E5%8F%91%E7%82%B9%E5%A4%B4%E7%BB%BC%E5%90%88%E7%97%87.html
乌干达北部大面积暴发点头综合症。这种神秘的疾病会让少年儿童在进食时剧烈点头，它也许是一种怪异的癫痫，可能与导致盘尾丝虫病的寄生虫有关。盘尾丝虫病折磨着大约1800万人，其中大多数在非洲。
此次暴发集中在基特古姆、帕代尔和古卢地区。仅帕尔代一个地方就有66名少儿死亡。今年8月12月中旬共有1000多个病例确认。
盘尾丝虫病是一种线虫。此前人们已经知道上述三个地区都深受其害。几乎所有患点头综合症的孩子都住在永久性河流附近，这也暗示出它与盘尾丝虫病有关联。
不过，这种联系并不明确。斯科特道尔专门研究儿科传染病，在美国疾病控制和预防中心负责点头综合症调研。他说：“我们知道（与盘尾丝虫）有某种关联，但有点令人困惑的是，这种线虫在没有出现点头病的地方也很常见.”
点头综合症尚无药可治，因此乌干达卫生部已经着手使用抗惊厥药物如2-丙基戊酸钠来治疗其体征和综合症。与此同时，帕代尔的卫生部门官员珍妮特奥拉和该区的医学昆虫学专家萨姆·威廉·奥耶特表示，点头综合症在继续蔓延。
我的评：
1
我是先看新科学家（新闻3），发现这个新的症状，继续刨出来原始文献，原来是昨天（非洲儿童的圣诞节真不幸啊）Nature杂志纸板出版最新期的内容（新闻1）。在线倒是7月13号就发表的，不知道为什么这么有意义的信息我当时竟然错过了，实在是惭愧。这里补一下。 原文一句话看了让人很难过“很多家庭已经因此绝户了”
2
简单翻译摘要：
5~15岁开始发病，症状是在进食的时候发作点头，有时伴有恶寒，发生时的大脑活动异常，颈部肌肉张力消失，导致头部下降。由疾病预防控制中心的调查和其他人进行的脑电图显示，许多亚临床发作儿童磁共振成像扫描显示脑萎缩，海马和神经胶质细胞的脑细胞损害。
因为儿童期发病，癫痫发作影响进食，导致营养不良带来的儿童身体发育障碍，智力障碍。因为病因不明，可能是传染病，所以孩子会被辍学。最后孩子就饿死，或者因为发作带来的意外溺水或者烧死了。
文中说症状像癫痫的抽搐，“先是发呆，再抽搐点头，一次5~15秒，持续3分钟”
病因不明，因为和河盲症的流行一致，所以暂时怀疑盘尾丝虫为致病源。但是也有怀疑自身免疫性疾病的，这样解释了为什么部分病人盘尾丝虫脑脊液样本抗体是阴性的。也有怀疑是遗传病的，这样可以解释为什么成年人不发病。他们还真的找出来一个吡哆醇反应性癫痫（这也太小概率罕见了）的遗传病，可能导致婴儿癫痫发作。所以尝试给患者大剂量维生素B6尝试治疗。目前也没有有效治疗手段，发作时候按照癫痫发作用抗惊厥药物，如丙戊酸钠和苯巴比妥对症治疗。
3
1962年在南部Tanzania1，首次报道这个病例，但是一直没有后续，直到2003年柳叶刀有个正式一些报道。中间的报道都很零星不连续。在2009年年底，联合国卫生部报告超过2,000名儿童受到影响。今年五月，CDC团队抵达朱巴，7月Nature 在线发表新闻报道。8月流行病学杂志对此疾病正式报道。 昨天圣诞节12月25日，一系列的科技文章都报道。
全园检索应该是首发
reference reading
Clinical characteristics of people with head nodding in southern Tanzania
http://www.td.rsmjournals.com/content/40/3/173.short
CDC 对此症状的描述 CDC Responds to Nodding Disease in Uganda
http://www.youtube.com/watch?v=LwOUzE03xm0&noredirect=1
Nodding disease: mystery of southern Sudan
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(03)00599-4/fulltext#article_upsell
African outbreak stumps experts，With few leads to go on, researchers pursue the childhood malady nodding syndrome.
http://www.nature.com/news/2011/110713/full/475148a.html
点头病
http://www.hudong.com/wiki/%E7%82%B9%E5%A4%B4%E7%97%85
当点头等同死亡
http://www.msf.org.hk/blogs/index.php/rhitam-chakraborty/1881/?lang=zh-hans
The Lancet Neurology, Volume 2, Issue 12, Page 714, December 2003 <Previous Article|Next Article>doi:10.1016/S1474-4422(03)00599-4
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(03)00599-4/fulltext#article_upsell
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC214014/
Investigation into the Nodding syndrome in Witto Payam, Western Equatoria State in 2010
Winkler AS, Friedrich K, K?nig R, Meindl M,Helbok R, Unterberger I, Gotwald T, Dharsee J, Velicheti S, Kidunda South Sudan Medical Journal (SSMJ) （见附件）
A,Jilek-Aall L, Matuja W, Schmutzhard E. The head nodding syndrome-clinicalclassification and possible causes. Epilepsia. 2008; 49 (12). Epub 2008 May 21 （见附件）
African outbreak stumps experts
With few leads to go on, researchers pursue the childhood malady nodding syndrome.
Published online 13 July 2011 | Nature 475, 148-149 (2011) | doi:10.1038/475148a
http://www.nature.com/news/2011/110713/full/475148a.html
The boy was perhaps seven or eight, although he could have been older: among other things, the disease that afflicts him stunts growth. When a seizure began, his mother summoned Sudhir Bunga, who found the boy sitting under a tree in a school playground. "The child was staring blankly and his head was intermittently nodding every five to eight seconds," Bunga says. "This lasted about three minutes."
Bunga was not surprised by what he saw. A physician and epidemiologist with the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, he was in rural southern Sudan in May as part of an emergency-response team trying to assess a mysterious illness seen in children in the region. But despite his preparation, Bunga was deeply affected by his first encounter with 'nodding syndrome'. "Actually seeing it out in the community was overwhelming and distressing," he says. "The burden of the disease looked really high."
Nodding syndrome is a poorly understood and seemingly growing problem in eastern Africa, where it is devastating communities in South Sudan and northern Uganda. It has existed separately for decades in a secluded mountainous area of southern Tanzania1. In South Sudan, "it's affecting thousands of children," says Abdinasir Abubakar, a physician for the World Health Organization (WHO) based in South Sudan who coordinated the recent CDC trip. "Of course, the question is whether this syndrome is spreading to new communities."
For South Sudan, which achieved political independence only on 9 July, the syndrome raises the additional fear that the new nation's limited capacity to deal with an emerging medical threat will be quickly overwhelmed without outside resources and expertise.
"Nodding syndrome cannot be left with the nascent government in South Sudan," says Martin Opoka, an epidemiologist with the WHO's eastern Mediterranean regional office in Cairo. "They will certainly need assistance from the international community."
Opoka helped to investigate the occurrence of nodding syndrome in southern Sudan as part of a WHO team in 2002, and returned to the region this year to assist the CDC investigators. The CDC team — consisting of four physician-epidemiologists with specialities in paediatrics, neurology and nutrition — was dispatched by the US agency's Division of Global Disease Detection and Emergency Response (GDDER). The division undertakes a number of missions each year at the invitation of local health authorities, to plumb mysterious or troublesome outbreaks. "Most commonly, we know the cause either before we go out or by the time we come back," says Scott Dowell, the GDDER director. "But we do have a handful of enigmatic outbreaks."
Nodding syndrome is one such enigma. Most children it strikes are aged between 5 and 15. It impairs both physical growth and cognitive development. Its hallmark head nodding — often brought on by eating, and sometimes by cold — occurs when abnormal brain activity causes a brief lapse in neck muscle tone, causing the head to fall forwards. Electroencephalograms conducted by CDC investigators and others have shown subtler, sub-clinical seizures in many children, and some magnetic resonance imaging scans have revealed brain atrophy and damage to the hippocampus and to supportive brain cells known as glia.
Once the seizures begin, the health of children with the disease goes downhill. Perhaps because the onset of seizures inhibits eating, they suffer from malnutrition. They are also prone to accidents such as drowning and burning. Many stop attending school, and some are isolated because of fears of contagion. "Once they have it, they are going to die with it, and much earlier than they would have otherwise," says Dowell.
The condition was first documented in 1962 in southern Tanzania1, but its incidence now seems to be rising rapidly in South Sudan (see map) and in a non-contiguous area of northern Uganda where, in late 2009, the ministry of health reported that more than 2,000 children were affected. In May, the CDC team arrived in Juba, now South Sudan's capital, and journeyed in armoured vehicles to villages where nodding syndrome is making its presence felt.
The poorest children seem to be the most susceptible. Community focus groups convened by CDC teams have not turned up any changes in dietary or cultural practices that could account for the syndrome's emergence. In South Sudan, the CDC is probing whether population displacements and associated chemical exposures during wartime could have played a part. And although a study in southern Tanzania showed familial clustering2, genetics alone cannot explain the rapid emergence of so many cases. In one village that the CDC team visited during the recent trip, almost every family had an affected child. "We have chased a lot of dead ends," says Dowell.
Investigators have wondered whether Onchocerca volvulus, the blackfly-borne parasite that is best known for causing river blindness, might be the culprit. The CDC's work in northern Uganda showed a higher prevalence of nodding in children whose blood samples revealed infection with the parasite. However, the recent Tanzanian study2 failed to find significantly elevated antibodies to the parasite in cerebrospinal fluid samples from affected children.
"We could not establish any hint that Onchocerca volvulus is actually going into the brain," says Andrea Winkler, first author on the study2 and a consultant neurologist at the Technical University of Munich in Germany. "But what we cannot exclude is that there is an autoimmune mechanism going on." Even if that were the case, an association between the parasitic disease and nodding syndrome would not explain why adults and people in other areas where onchocerciasis is endemic are not affected by nodding syndrome.
The CDC team is also investigating whether deficiency of vitamin B6, or pyridoxine — which is common in children with nodding syndrome — could be the cause. Dowell notes that a rare genetic disease called pyridoxine-responsive epilepsy causes infants to have seizures, which disappear when the babies are given high-dose vitamin B6. In a return trip planned for late this year, the team hopes to run a clinical trial examining whether the vitamin can also alleviate nodding syndrome.
Opoka hopes that the increased attention will finally shed light on the condition and, ultimately, point the way to a treatment. Nodding syndrome "is silently increasing", he says. "If nothing is done we don't know what the end result will be." Bunga remains optimistic that something will come out of the data that the team gathered. "Did I come back with any clear answers? No," he says. "But there are still multiple paths of investigation open."
2
症状发作的视频
CDC 对此症状的介绍，（CDC Responds to Nodding Disease in Uganda）
http://www.youtube.com/watch?v=LwOUzE03xm0&noredirect=1
中间有孩子进食发病的视频，很短，很不典型的低头侧身。发言人说的一个内容很值得注意 “患儿出现注意力缺失，（以前聪明的孩子因为注意力缺失所以学习退步了）”
***南部的一个新闻介绍
http://www.youtube.com/watch?v=mbjQu_g17OE
最开始时段有晚期患病的患儿发病视频，很奇怪的身体倾斜抽搐，还有一个孩子整个倒地的视频（Near by, 15 year old Lili clasped... after about 5 minutes later, she wakes up）我不能说昏倒，因为似乎还是有意识的，5分钟后她起来，（这一段的表情很奇怪，像是痴呆或者淡漠）
我们从视频中也发现，患儿的发育比实际年龄看起来要小的多。这段介绍中说，发病以后的孩子就停止发育了。
3
新闻上对此的评价。
Mysterious nodding syndrome spreading through Uganda
http://www.newscientist.com/article/dn21316-mysterious-nodding-syndrome-spreading-through-uganda.html
http://www.medsoso.cn/text/2863/%E4%B9%8C%E5%B9%B2%E8%BE%BE%E6%9A%B4%E5%8F%91%E7%82%B9%E5%A4%B4%E7%BB%BC%E5%90%88%E7%97%87.html
乌干达北部大面积暴发点头综合症。这种神秘的疾病会让少年儿童在进食时剧烈点头，它也许是一种怪异的癫痫，可能与导致盘尾丝虫病的寄生虫有关。盘尾丝虫病折磨着大约1800万人，其中大多数在非洲。
此次暴发集中在基特古姆、帕代尔和古卢地区。仅帕尔代一个地方就有66名少儿死亡。今年8月12月中旬共有1000多个病例确认。
盘尾丝虫病是一种线虫。此前人们已经知道上述三个地区都深受其害。几乎所有患点头综合症的孩子都住在永久性河流附近，这也暗示出它与盘尾丝虫病有关联。
不过，这种联系并不明确。斯科特道尔专门研究儿科传染病，在美国疾病控制和预防中心负责点头综合症调研。他说：“我们知道（与盘尾丝虫）有某种关联，但有点令人困惑的是，这种线虫在没有出现点头病的地方也很常见.”
点头综合症尚无药可治，因此乌干达卫生部已经着手使用抗惊厥药物如2-丙基戊酸钠来治疗其体征和综合症。与此同时，帕代尔的卫生部门官员珍妮特奥拉和该区的医学昆虫学专家萨姆·威廉·奥耶特表示，点头综合症在继续蔓延。
我的评：
1
我是先看新科学家（新闻3），发现这个新的症状，继续刨出来原始文献，原来是昨天（非洲儿童的圣诞节真不幸啊）Nature杂志纸板出版最新期的内容（新闻1）。在线倒是7月13号就发表的，不知道为什么这么有意义的信息我当时竟然错过了，实在是惭愧。这里补一下。 原文一句话看了让人很难过“很多家庭已经因此绝户了”
2
简单翻译摘要：
5~15岁开始发病，症状是在进食的时候发作点头，有时伴有恶寒，发生时的大脑活动异常，颈部肌肉张力消失，导致头部下降。由疾病预防控制中心的调查和其他人进行的脑电图显示，许多亚临床发作儿童磁共振成像扫描显示脑萎缩，海马和神经胶质细胞的脑细胞损害。
因为儿童期发病，癫痫发作影响进食，导致营养不良带来的儿童身体发育障碍，智力障碍。因为病因不明，可能是传染病，所以孩子会被辍学。最后孩子就饿死，或者因为发作带来的意外溺水或者烧死了。
文中说症状像癫痫的抽搐，“先是发呆，再抽搐点头，一次5~15秒，持续3分钟”
病因不明，因为和河盲症的流行一致，所以暂时怀疑盘尾丝虫为致病源。但是也有怀疑自身免疫性疾病的，这样解释了为什么部分病人盘尾丝虫脑脊液样本抗体是阴性的。也有怀疑是遗传病的，这样可以解释为什么成年人不发病。他们还真的找出来一个吡哆醇反应性癫痫（这也太小概率罕见了）的遗传病，可能导致婴儿癫痫发作。所以尝试给患者大剂量维生素B6尝试治疗。目前也没有有效治疗手段，发作时候按照癫痫发作用抗惊厥药物，如丙戊酸钠和苯巴比妥对症治疗。
3
1962年在南部Tanzania1，首次报道这个病例，但是一直没有后续，直到2003年柳叶刀有个正式一些报道。中间的报道都很零星不连续。在2009年年底，联合国卫生部报告超过2,000名儿童受到影响。今年五月，CDC团队抵达朱巴，7月Nature 在线发表新闻报道。8月流行病学杂志对此疾病正式报道。 昨天圣诞节12月25日，一系列的科技文章都报道。
全园检索应该是首发
reference reading
Clinical characteristics of people with head nodding in southern Tanzania
http://www.td.rsmjournals.com/content/40/3/173.short
CDC 对此症状的描述 CDC Responds to Nodding Disease in Uganda
http://www.youtube.com/watch?v=LwOUzE03xm0&noredirect=1
Nodding disease: mystery of southern Sudan
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(03)00599-4/fulltext#article_upsell
African outbreak stumps experts，With few leads to go on, researchers pursue the childhood malady nodding syndrome.
http://www.nature.com/news/2011/110713/full/475148a.html
点头病
http://www.hudong.com/wiki/%E7%82%B9%E5%A4%B4%E7%97%85
当点头等同死亡
http://www.msf.org.hk/blogs/index.php/rhitam-chakraborty/1881/?lang=zh-hans
The Lancet Neurology, Volume 2, Issue 12, Page 714, December 2003 <Previous Article|Next Article>doi:10.1016/S1474-4422(03)00599-4
http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(03)00599-4/fulltext#article_upsell
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC214014/
Investigation into the Nodding syndrome in Witto Payam, Western Equatoria State in 2010
Winkler AS, Friedrich K, K?nig R, Meindl M,Helbok R, Unterberger I, Gotwald T, Dharsee J, Velicheti S, Kidunda South Sudan Medical Journal (SSMJ) （见附件）
A,Jilek-Aall L, Matuja W, Schmutzhard E. The head nodding syndrome-clinicalclassification and possible causes. Epilepsia. 2008; 49 (12). Epub 2008 May 21 （见附件）
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