Dysfunction of the basal ganglia, but not the cerebellum, impairs kinaesthesia
习惯的力量 The Power of Habit
習慣的力量The Power of HabitSo if you're like me you probably have at least a few bad habits you would like to break. But it's tough cause no matter how hard I try, I seem to slip back into the same old routines again and again. In the last decade we've learned a lot about how habits work. That's Charles Duhigg, author of the book, "The Power of Habit." In particular we've learned the neurological structure of a habit. He says we tend to think of a habits as a single thing, but actually, each habit has three components. There's a cue which is a trigger for a behavior to start, and then there is a routine which is the behavior itself, and then finally a reward, which is how our brain learns to encode that automatic behavior for the future. And one of the big differences is that for years when people thought about habits, theyfocused in on the routine, on the behavior. But what we now know is that it's these cues and these rewards that really shape how habits occur and how to change them. And Charles says whether we like it or not, this kind of habit formation is endemic to our brain. And what it will do is our brain will latch on to a cue that it associates with a behavior and a particular reward. And over time, that queue and that reward become more and more and more sort of intertwined. The inner part of your brain, the basal ganglia will relate them together. And the behavior that is associated with that, that will just sort of happen automatically. But Charles says the good news is we can also use this knowledge to ouradvantage. There was a big study that was done about how to create exercise habits. And so what they did is they told a group of people, "Okay, first of all choose an obvious cue: always go running at the same time every day or put your workout clothes next to your bed so that you see them first thing when you wake up." And then they said, "Go for a run or go workout and when you get back from exercising, give yourself a small piece of chocolate." Now this is kind of counterintuitive, right? Because people who are exercising are trying to lose weight, not eat more chocolate. And yet what the researchers knew is that their brain needed that reward. The basal ganglia needed some reward. But what they found was that people who ate a small piece of chocolate after coming home from a run or a workout, they were much more likely to start exercising habitually. So according to Charles, whether you want to break a habit, or start a new habit, the key is to divide the habit into its component parts: cue, routine and reward, and design it for the result that you want.Hey guys, my name is Kirsten from Epipheo and we would love to hear from you about what you think a great reward is for you to make or break a habit. So, leave us a comment down below in the comment section and let us know. We come out with a video every week that wehope will change your life. And next week we are talking about how you can say, "No," to pretty much anything. So hit subscribe and we will see you next week!。
世界不完美英语作文初三
As a high school student, Ive come to realize that the world is far from perfect. Its a lesson that has been etched into my consciousness through various experiences and observations. The world is a complex tapestry woven with threads of beauty and imperfection, and understanding this has been a journey of growth for me.Growing up, I was surrounded by a loving family and a community that seemed to be the epitome of harmony. However, as I ventured out of my comfort zone and interacted with a broader spectrum of society, I encountered the stark reality of the worlds imperfections. The first time I truly grasped this was during a school trip to a less fortunate neighborhood. The contrast between the lives of my peers and the children living there was jarring. It was a stark reminder that not everyone has the same opportunities or access to resources, and this disparity is a glaring imperfection in our world.Another instance that highlighted the worlds imperfections was when I volunteered at a local animal shelter. The number of abandoned and abused animals was heartbreaking. It was a stark reminder of the cruelty and negligence that exists in society. The fact that these innocent creatures suffer at the hands of humans is a testament to the flaws in our moral compass.In school, we are often taught about the wonders of the world and the potential for greatness. However, the reality is that the world is plagued with issues such as poverty, inequality, and environmental degradation. These are not just distant problems they are issues that affect people inour own communities. The news is filled with stories of natural disasters, wars, and social injustices, painting a picture of a world that is far from the utopia we often envision.Despite these imperfections, I believe that it is important to acknowledge and address them rather than ignore them. It is through recognizing the flaws in our world that we can strive to make a difference. For instance, I have seen classmates and friends take initiative to raise awareness about social issues, volunteer for community service, and advocate for environmental conservation. These actions, no matter how small they may seem, contribute to the collective effort to make the world a better place.Moreover, the worlds imperfections can also serve as a source of inspiration and motivation. They remind us of the work that still needs to be done and the potential for positive change. It is through these challenges that we can grow as individuals and as a society. The pursuit of perfection may be an unattainable goal, but the journey towards it can lead to significant progress and personal development.In conclusion, the worlds imperfections are a reality that we must confront and learn from. They are a call to action for us to contribute to the betterment of society and the environment. While the world may not be perfect, it is our collective responsibility to strive for improvement and work towards creating a more just and harmonious world. It is through acknowledging and addressing these imperfections that we can hope to make a positive impact and leave a legacy for future generations.。
英语专业八级考前拉力赛答案与详解（2）
KEY PART Ⅰ LISTENING COMPREHENSION. SECTION A 1 答案B 「解题思路」了解讲话者的⾝份。
「详细解答」⽂中讲的是slang的使⽤，以及与native speakers的交流，涉及的都是language.应该选B. 2 答案D 「解题思路」了解“hip”在这个talk中的含义。
「详细解答」the talk中指出：hip在六、七⼗年代指的是社会潮流的追随者，但在本⽂来⾃更加久远的⽤法。
3 答案C 「解题思路」了解俚语以及时髦语存在的问题。
「详细解答」“trendy”为“in accord with the latest fashion；fashionable”时髦，潮流的。
the talk中有： the problem with slang and trendy expressions in general is that they change fast， so that only those who are using them all the time can keep up. 4 答案D 「解题思路」掌握在Newcastle“hinny”的意思。
「详细解答」讲话者指出：If you are in Newcastle， you might hear people refer to each other as“hinny”—a common term of endearment. 表亲近的称呼。
“endearment”为“an expression of affection.”亲近，亲热，友好。
5 答案B 「解题思路」掌握讲话者对听众的要求。
「详细解答」The talker在最后指出：既然英语不是本族语，⼈们会觉得奇怪，如果你使⽤。
但你仍旧需要花时间与⼈交流，来学习本地⼈，从⽽理解不同的表达。
SECTION B 6 答案D 「解题思路」了解在上个世纪道路建设的材料。
新世纪海外英语Unit7课文翻译
She challenged mice to solve a maze that involved turning either left or right to find a water reward. A visual clue, such as a star, along with the texture of the maze's surface, showed the correct direction to turn.
对人类而言，他说，向FOXP2基因的变异可 能帮助了我们这一物种掌握复杂的肌肉运动， 这种肌肉运动用来形成基本声音然后把基本 声音合成为字然后再合成为句子。
Another MPI team member, Ulrich Bornschein, presented work at the neuroscience meeting showing that the changes to brain circuitry that lead to quicker learning come about with just one of the two amino-acid changes in the human form of FOXP2. The second mutation may do nothing.
但是她没有找到如何用（负责学习的）脑部 变化来解释FOXP2基因是如何帮助人类自觉 地而且毫不费力地把想法转换成口头语言的。
“You are not deciding how you are going to move your muscles to form these sounds,” she says.
亚历山大病2型
ＩＩ ＡｘＤ
ａｒｅ
ｔｈａｌａｍｕｓ ｗｅｒｅ ａｌｓｏ ｃｏｍｍｏｎｌｙ ｓｈｏｗｎ ｉｎ ｔｈｅ ＭＲＩ．Ｃｏｎｃｌｕｓｉｏｎｓ Ｔｈｅ ｐａ— ｌａｔｅ—ｏｎｓｅｔ．Ｔｈｅ ｃｌｉｎｉｃａｌ ｍａｎｉｆｅｓｔａｔｉｏｎ ｍａｉｎｌｙ ｃｏｎｔａｉｎｓ ｂｕｌｂａｒ ａｎｄ／ｏｒ ｐｓｅｕｄｏｂｕｌｂａｒ ｐａｒａｌｙｓ—
男，初次于北京大学第一医院就诊年龄为９岁。就诊时 主要表现：（１）肢体无力。患儿７岁时在感染后１０ ｄ出 现左下肢无力跛行，５个月后出现右下肢无力，随后出现 左手活动不灵，逐渐加重发展至不能独走及独站。（２） 躯干肌无力及呼吸肌无力。从平卧位不能自行坐起，不 能翻身；呼吸浅促，活动后明显。（３）吞咽困难、饮水呛 咳、语音低弱、语速慢，呈进行性加重。（４）尿便障碍。 排尿前需等待７～８ ｍｉｎ，大便每２～３
ＤＯＩ：１０．３７６０／ｃｍａ．Ｊ．ｉｓｓｎ．２０９５—４２８Ｘ．２０１６．０９．０１５
【摘要】 目的通过分析Ⅱ型亚历山大病（ＡｘＤ）患者的临床及头颅ＭＲＩ特点，提高临床医师对本病的认 识，以利于早期识别。方法以北京大学第一医院胶质纤维酸性蛋白基因确诊的４例及文献报道的１２８例Ⅱ 型ＡｘＤ患者为研究对象，对其临床表型及头颅ＭＲＩ特征进行总结。结果１．基因确诊的４例Ⅱ型ＡｘＤ患者中 有２例仅头颅ＭＲＩ异常但尚无临床症状的成年患者；２例患ＪＬｌ临］床表现为下肢运动障碍、锥体束症状、发作性 加重、癫痫发作等，其中ｌ例患儿病程中出现球麻痹症状。４例患者头颅ＭＲＩ均出现异常，但仪１例符合本病 典型ＭＲＩ诊断标准，余３例ＭＲＩ表现为逐渐出现的延髓及卜部颈髓的萎缩或脑ｆ病灶、脑室旁白质异常信号 或基底核区异常，其中ｌ例无明显自质骨常？２．文献报道的１２８例Ⅱ型ＡｘＤ患者：发病年龄为（３２±１９）岁，主 要以球麻痹和／或假性球麻痹（３２．４８％，３８／１１７例）、下肢运动障碍（３Ｉ．６２％，３７／１１７例）、自主神经功能障碍 （１３．６７％，１６／１１７例）等为发病症状，病程中出现球麻痹和／或假性球麻痹（７３．５０％。８６／１１７例）、锥体束症状 （６０，６８％，７１／１１７例）、共济失调（５１．２８％，６０／１１７例）等表现。头颅ＭＲＩ特点为脑干（主要为延髓）及脊髓部 位萎缩或异常信号，／ｂＮ齿状核、白质、基底核及丘腩信号异常亦较常见。结论 Ⅱ型ＡｘＤ发病较晚，临床表 现主要为球麻痹和／或假性球麻痹、下肢运动障碍、锥体束征等，头颅ＭＲＩ主要表现为脑干（主要为延髓）及脊 髓萎缩、异常信号等。 【关键词】亚历山大病；胶质纤维酸性蛋白基因 基金项目：国家自然科学基金（８１１７１０６５）；国家科技支撑计划（２０１２ＢＡｌ０９８０４）
英语文章听力：鸟类智商不算太糟
英语文章听力：鸟类智商不算太糟esearch Shows Bird Brains Aren’t So BadThe next time someone calls you a “bird brain,” you should thank them.Changing OpinionsNeuroscientists’ opinions about the brains of birds have changed. In humans and other mammals, the roof of theforebrain has evolved into the cerebral cortex, a structure responsible for flexible learning and reasoning.Early neuroanatomists thought that the forebrain roof was small and simple in birds, with its forebrain instead being dominated by structures in its base, called the basal ganglia. Without an elaborate forebrain roof, it seemed that birds couldn’t be very smart.New ResearchRecent research shows that birds are a lot smarter than scientists once thought. To give just a few examples, the New Caledonian crow can manufacture and use tools. The Africangrey parrot can learn to classify objects into categories,and the Florida scrub jay stores food in dozens of caches and can remember their locations for future use.It turns out that neuroanatomists had it all wrong about bird forebrains. During more than 300 million years of separate evolution, the forebrain roofs of birds and of mammals each grew larger and more elaborate, but in different ways. The roof of a bird’s forebrain is so different fromthe cerebral cortex of a mammal that the neuroanatomists had confused most of it with enlarged basal ganglia.。
怪诞行为学英文版
怪诞行为学英文版Peculiar Behavior Studies: A Guide to the Strange and UnusualIntroduction:Humans are fascinating creatures, capable of exhibiting a wide variety of behaviors, both normal and strange. These behaviors have been studied and analyzed for decades, in an effort to better understand our complex nature. One such study is the field of Peculiar Behavior Studies, which seeks to explore and decipher the mysteries of bizarre human behavior. In this article, we will be taking a closer look at some of the most unusual behaviors observed by researchers, as well as their possible causes and implications.Category 1: Echolalia and PalilaliaEcholalia refers to the repetition of words, phrases, or sounds spoken by someone else, often without understanding their meaning. Palilalia, on the other hand, is the repetition of one's own words, often as a form of self-stimulation or to ease anxiety. Both of these behaviors are commonly seen in individuals with autism spectrum disorders, Tourette's Syndrome, or other neurological conditions. While the exact causes of these behaviors are not yet fully understood, researchers have proposed various theories, such as a dysfunction in the brain's language processing centers or an overactive mirror neuron system.Category 2: TrichotillomaniaTrichotillomania is a compulsive disorder characterized by the urge to pull out one's own hair, often resulting in bald patches or even complete hair loss. Although the exact cause of trichotillomania is still unknown, it is thought to be related to anxiety, stress, or other emotional disturbances. Treatment typically involves cognitive-behavioral therapy or medications to reduce anxiety.Category 3: Self-Injurious BehaviorSelf-injurious behavior, or self-harm, refers to the intentional infliction of harm or injury on oneself, often as a form of coping mechanism or to alleviate emotional pain. This behavior is commonly observed in individuals with mental health issues such as depression, anxiety, or borderline personality disorder. Treatment often involves addressing the underlying emotional issues and developing healthier coping strategies.Category 4: CoprolaliaCoprolalia is a type of vocal tic characterized by the uncontrollable utterance of socially inappropriate or offensive words or phrases. While coprolalia is most commonly associated with Tourette's Syndrome, it can also be seen in individuals with other neurological disorders. The exact cause of coprolalia is not yet known, but it is thought to be related to a dysfunction in the brain's frontal lobes or basal ganglia.Conclusion:In conclusion, the field of Peculiar Behavior Studies offers a fascinating glimpse into the inner workings of the human mind. Although the behaviors we have explored in this article may seem strange or even unsettling, they are a testament to the complexity and diversity of the human experience. By continuing to study and better understand these behaviors, we can hopefully develop more effective treatments and interventions for those who struggle with them.。
亨廷顿舞蹈症概述
亨廷顿舞蹈症概述摘要亨廷顿舞蹈症（HD）是由携带了更多扩增的多聚谷氨酰胺的突变亨廷顿蛋白所造成的。
在神经细胞的水平，野生型亨廷顿蛋白功能的丧失与突变亨廷顿蛋白毒性功能的获得被认为是亨廷顿病的病因。
进一步而言，兴奋性毒性，多巴胺毒性，代谢损伤，线粒体功能紊乱，细胞凋亡以及自体吞噬涉及于亨廷顿病的渐进性病理发展过程。
尽管提出了多种治疗策略，目前对于这种破坏性的神经退行性病变还没有有效的治疗。
随着对亨廷顿病的病理机制的进一步认识，以及相关技术的进一步发展，我们可能会找到一种有效的治疗方案。
1.简介亨廷顿舞蹈症（HD）是一种渐进性的常染色体显性的神经退行性病变，是由在亨廷顿蛋白基因的CAG三核苷酸序列发生扩增所致（>35个重复序列）。
这就使亨廷顿蛋白N末端带有一个扩增的多聚谷氨酰胺束（形成突变亨廷顿蛋白）。
亨廷顿病最显著的特征是不能控制的舞蹈样运动，痴呆，精神异常，以及早期死亡，这通常发生在中年时期。
这些症状与在纹状体的中等棘状神经元（神经细胞）更倾向于发生退行性病变密切相关，当然这种病变在晚期也会累及其它脑区。
2.神经退行性病变的机制野生型亨廷顿蛋白（htt）被认为具有许多细胞内的功能，比如蛋白运输，囊泡转运，与细胞骨架的锚定等。
当它发生了突变（加上了一个扩增的多聚谷氨酰胺束），亨廷顿蛋白将赋予一个新的对细胞具有毒性的功能（毒性功能的获得），同时原有的功能丧失（野生型功能的丧失）。
相关的胞内信号通路的失调包括蛋白酶的活化[1]，蛋白质错折叠与蛋白质降解途径的抑制[2]，转录失调，轴突运输的干扰[3]，以及突触功能紊乱[4]。
由突变亨廷顿蛋白介导的细胞内功能紊乱逐渐造成在不同脑区的神经元发生神经退行性病变与死亡，这包括纹状体。
已经发现多种机制涉及于亨廷顿病的病理过程，诸如兴奋性毒性，多巴胺毒性，代谢损伤，线粒体功能紊乱，细胞凋亡以及自体吞噬。
2.1 皮质纹状体功能紊乱与兴奋性毒性纹状体接收来自整个大脑皮质的兴奋性谷氨酸能信号输入，因此在亨廷顿病中所表现的纹状体神经元选择性的易损性可能归因于它们接收了大量的谷氨酸能信号输入，以及（或者）是由于这些细胞所表达的谷氨酸受体类型的特殊性。
英文版一氧化碳中毒Carbon monoxide poisoning
Carbon monoxide poisoningThe deadly effect of carbon monoxide was known as long ago as Greek and Roman times, when the gas was used for executions. In 1857 Claude Bernard postulated that its noxious effect was caused by reversible displacement of oxygen from haemoglobin to form carboxyhaemoglobin. In 1926 it became apparent that hypoxia was caused not only by deficient oxygen transport but also by poor tissue uptake. Warberg used yeast cultures to show that cellular uptake of oxygen was inhibited by exposure to a large amount of carbon monoxide.Carbon monoxide is known as the silent killer since it has no colour or smell. Each year in Britain about 50 people die and 200 are severely injured by carbon monoxide poisoning4. Some poisonings are caused by self-harm but most are accidental. It is the commonest cause of accidental poisoning and, according to one estimate, as many as 25000 people in the UK have symptoms due to faulty gas appliance. In the 1960s and 1970s the conversion from coal gas to carbon-monoxide-free natural gas caused a dramatic reduction in poisoning. In this review I discuss modern approaches to management and preventionSOURCESCarbon monoxide is produced endogenously in small amounts as a byproduct of haem catabolism. Together with nitric oxide it affects cellular function and acts as a neurotransmitter. Environmental carbon monoxide is produced by incomplete combustion of any carboncontaining fuel (coal, petroleum, peat, natural gas). In Britain most accidents arise through central heating faults. By contrast, in the USA most deaths are caused by inhalation of exhaust fumes. In the United Kingdom car exhaust emissions of carbon monoxide have been reduced by catalytic convertors in all new cars. Surprisingly, when deaths occur in garages there have usually been open doors and windows9. There are even reports of poisoning occurring from carbon monoxide inhalation in the open air. Methylene chloride (paint stripper) fume inhalation is a rare cause of poisoning. In the liver it is converted to carbon monoxidePATHOPHYSIOLOGYCarbon monoxide has 210 times greater affinity for haemoglobin than oxygen. A small environmental concentration will thus cause toxic levels of carboxyhaemoglobin. After the carbon monoxide has selectively bound to haemoglobin the oxygen-haemoglobin dissociation curve of the remaining oxyhaemoglobin shifts to the left, reducing oxygen release .The affinity of carbon monoxide for myoglobin is even greater than for haemoglobin. Binding to cardiac myoglobin causes myocardial depression, hypotension and arrhythmias. Cardiac decompensation results in further tissue hypoxia and is ultimately the cause of death.Carbon monoxide shifts the oxygen-haemoglobin saturation curve to the left and changes it to a more hyperbolic shape. Less oxygen is available for the tissues. Shown is the oxygen diffusion gradient difference at 50% saturation.Cellular uptake of oxygen is blocked by binding of carbon monoxide with mitochondrial cytochrome aa3. The hypoxia precipitates endothelial cell and platelet release of nitric acid, which forms the free radical peroxynitrate. In the brain this causes further mitochondrial dysfunction, capillary leakage, leukocyte sequestration andapoptosis. The pathological changes occur mainly during the recovery (reperfusion) phase when lipid peroxidation (degradation of unsaturated fatty acids) occurs. The net result is reversible demyelination in the brain. Such changes are clearly evident on magnetic resonance imaging. Carbon monoxide has a predilection for ‘watershed’ areas of the brain where there is a meagre blood supply. The basal ganglia, with their high oxygen consumption, are most often affected. Other commonly affected areas are the cerebral white matter, hippocampus and cerebellum.CLINICAL SIGNS AND DIAGNOSISThe signs of carbon monoxide poisoning vary with concentration and length of exposure. Subtle cardiovascular or neurobehavioural effects occur at low concentrations. Lengthy exposure or acute exposure to high concentrations often causes coma and death. The onset of chronic poisoning is usually insidious and easily mistaken for 'flu, depression, food poisoning or in children gastroenteritis. Other family members may have a similar illness.The most common symptoms are headache, nausea and vomiting, dizziness, lethargy and a feeling of weakness. Infants may be irritable and feed poorly. Neurological signs include confusion, disorientation, visual disturbance, syncope and seizures. In acute poisoning, common abnormalities of posture and tone are cogwheel rigidity, opisthotonus and flaccidity or spasticity. Adults with coronary heart disease may experience angina, arrhythmias and myocardial infarction. Retinal haemorrhages and the classic cherry red skin colour are seldom seen. Other organs such as the kidney, liver and pancreas are rarely affected. A rise in creatine phosphokinase follows muscle necrosis. Hypoxaemia causes lactic acidaemia. Carbon monoxide poisoning is diagnosed by measuring carboxyhaemoglobin in a heparinized blood sample (arterial or venous. Symptoms usually begin when the concentration rises above 10%. There is a poor correlation between the blood level and the clinical condition. Symptoms reflect the dissolved concentration, which may be low in the face of a high carboxyhaemoglobin. In general, levels below 40% are not associated with coma or death. In a normal non-smoker the average is about 1%, rising to 15% in a heavy smoker. Levels of 5% are found in haemolytic anaemias and pregnancy. Pulse oximeters are not suitable for the diagnosis of carbon monoxide poisoning. The wavelength of most cannot distinguish between oxyhaemoglobin and carboxyhaemoglobin. A carbon monoxide breathalyser is a simple bedside screening test but its practical value is limited by numerous confounders such as smoking and alcoholThe fetus is particularly vulnerable to carbon monoxide poisoning. Fetal haemoglobin shifts the oxygen-haemoglobin dissociation curve to the left. Chronic exposure to carbon monoxide in pregnancy causes growth retardation, fetal distress and death. Survivors may have developmental disorders and brain damage. The risk is compounded by smoking in pregnancy. In the first months of infancy, while fetal haemoglobin remains raised, the risk is greater. People with sickle cell anaemia and thalassaemia who have a raised fetal haemoglobin are likewise at excess risk.TREATMENT AND PROGNOSISThe mainstay of treatment is 100% oxygen administration until the carboxyhaemoglobin level is normal. On this regimen the half-life of carboxyhaemoglobin is 74 minutes (compared with 320 minutes breathing air. Lactic acidosis facilitates tissue oxygen diffusion and should not be corrected unless extreme (pH<7.15). When the patient is stable enough to be transported, hyperbaric oxygen should be considered. This treatment is safe and well tolerated, the main complication being ear barotrauma. The decision about hyperbaric oxygen will often depend on ease of access to a hyperbaric facility.Hyperbaric oxygen has many benefits. The half-life of carboxyhaemoglobin at 3 ATA (absolute atmospheres) of oxygen is only 23 minutes. Other benefits are improved mitochondrial function, impairment of platelet adhesion in the capillaries and inhibition of lipid peroxidation12. But contrary to expectation, clinical trials of hyperbaric oxygen have given conflicting results. A recent Cochrane review of three major randomized controlled trials concluded that there is as yet no evidence of neurological benefit at one month. Ongoing trials will soon provide further information. In the absence of firm evidence most centres continue using hyperbaric oxygen if the carboxyhaemoglobin is above 25-30%. Myocardial ischaemia and neurological signs, especially coma, are treated with hyperbaric oxygen irrespective of the concentration. There is general agreement that prolonged hyperbaric oxygen is the treatment of choice in pregnancy. This is because fetal carboxyhaemoglobin is higher and clearance slower than in the mother. Carbon monoxide poisoning is unique in that neuropsychiatric signs can appear insidiously weeks after the patient appears to have recovered. These signs, which are most common in the elderly, occur within a month in 10-30%. Some of the frank neurological signs such as parkinsonism are easily detected. Personality, cognitive and memory changes are not readily apparent and can be missed unless specifically targeted. Children may present with behaviour or education problems. Most neuropsychiatric signs resolve within a year. In one study, review at 3 years revealed persistent signs in 11% There is no means of predicting recovery. However, patients with permanent signs are likely to have presented in comaPREVENTIONPublic education about the danger of carbon monoxide, with emphasis on safety in the home and workplace, is the key to effective prevention. Professional education targeted at community workers is also needed. This could be achieved through a media campaign when risk is greatest, during the winter. Because of the high incidence of gas-related poisoning, there is a role for the gas industry in public education. Close liaison between public health physicians and leaders of the building, gas and home heating industries is a prerequisite for an effective prevention strategy. Such collaboration ensures safety through proper standards for home ventilation, central heating installation and maintenance. Cheap batteryoperated carbon monoxide detectors are now widely available. They should be installed in new homes and in buildings such as garages where workers are at risk from exhaust fumes. In old properties, particularly where there is solid fuel heating, carbon monoxide detectors should be located in sleeping areas. In Britain only BSI standard detectors should be installed. In the USA, where detectors are mandatory in some cities, their value in preventing home poisoning has been well demonstrated.。
间脑-大脑的发生
脑垂体的发生
垂体发育异常
腺垂体发育不良
双重垂体 异位神经垂体
端脑的发生
外形的发生
皮质的发生
髓质的发生
Each cerebral hemisphere has 3 zone (from outer to inner layer)
Cortical part : the outermost of cerebral cortex Medullary part : consisted of numerous fiber (white matter) Nuclear part : the constituencies of deep gray matter e.g.. Basal ganglia.
眼的发生
a | The neural plate is the starting point for the development of the vertebrate eye cup. b | The neural plate folds upwards and inwards. c | The optic grooves evaginate. d | The lips of the neural folds approach each other and the optic vesicles bulge outwards. e | After the lips have sealed the neural tube is pinched off. At this stage the forebrain grows upwards and the optic vesicles continue to balloon outwards: they contact the surface ectoderm and induce the lens placode. f | The optic vesicle now invaginates, so that the future retina is apposed to the future retinal pigment epithelium (RPE), and the ventricular space that was between them disappears. Developing retinal ganglion cells send axons out across the retinal surface. The surface ectoderm at the lens placode begins to form the lens pit. This section is midline in the right eye, through the choroid fissure, so only the upper region of the retina and the RPE are visible. g | The eye cup grows circumferentially, eventually sealing over the choroidal fissure and enclosing the axons of the optic nerve (as well as the hyaloid/retinal vessels; not shown). The ectodermal tissue continues to differentiate and eventually forms the lens.
caudate and putamen structures的英文
Abstract:The caudate nucleus and putamen, collectively known as the dorsal striatum, are integral components of the basal ganglia, playing crucial roles in motor control, reward processing, learning, and cognitive function. This comprehensive analysis delves into their anatomical features, neurochemical organization, functional connectivity, involvement in various neurological and psychiatric disorders, and their significance in clinical practice. By examining these structures from multiple angles, this article aims to provide a thorough understanding of their complex interplay and contributions to human behavior.1. IntroductionThe basal ganglia, nestled deep within the cerebral hemispheres, constitute a network of interconnected subcortical nuclei that regulate movement, motivation, and cognitive processes. Among these, the caudate nucleus and putamen stand out as central players, forming the dorsal striatum, a primary input station for cortical information and a critical gateway in the cortico-basal ganglia-thalamo-cortical loop. This loop is fundamental to the modulation of voluntary movements, habit formation, and the integration of sensory, emotional, and cognitive signals. This article explores the intricate anatomy, neurochemistry, functional connectivity, pathophysiological involvement, and clinical implications of the caudate and putamen.2. Anatomical Features and Neurochemical Organization**Caudate Nucleus**: The caudate nucleus, named for its resemblance to a tail (Latin: cauda), is a C-shaped structure extending along the lateral wall of the lateral ventricle. It can be divided into three segments: the head, body, and tail, each with distinct connections to different brain regions. The caudate receives dense projections from the prefrontal cortex, particularly the dorsolateral prefrontal cortex and anterior cingulate gyrus, reflecting its involvement in higher-order cognitive functions.Neurochemically, the caudate is primarily composed of GABAergic medium spiny neurons (MSNs), which constitute over 90% of its neuronal population. These MSNsexpress either dopamine D1 receptors (D1R) or D2 receptors (D2R), giving rise to two parallel pathways: the direct (D1R-expressing) and indirect (D2R-expressing) pathways. The direct pathway facilitates movement by disinhibiting the thalamus, while the indirect pathway inhibits movement through increased inhibition of the thalamus via the globus pallidus externa (GPe) and substantia nigra pars reticulata (SNr).**Putamen**: Located posterior to the caudate and separated from it by the internal capsule, the putamen forms the bulk of the dorsal striatum. It is involved primarily in motor control and receives inputs from the primary motor cortex, premotor cortex, and somatosensory cortex. The putamen also shares similar neurochemical organization with the caudate, being predominantly composed of GABAergic MSNs expressing D1Rs or D2Rs, which give rise to the direct and indirect pathways.3. Functional Connectivity and Roles in Behavior**Motor Control**: Both the caudate and putamen play critical roles in the planning, initiation, and execution of voluntary movements. They integrate sensorimotor information from the cortex and facilitate the selection and execution of appropriate motor responses. The direct and indirect pathways dynamically balance each other, ensuring smooth and coordinated movements. Disruptions in this balance underlie motor symptoms observed in disorders such as Parkinson's disease (PD) and Huntington's disease (HD).**Reward Processing and Learning**: The caudate and putamen are integral to reinforcement learning and the processing of rewards and punishments. They receive dopaminergic projections from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), which convey reward prediction error signals that drive learning and adaptation of behavior. The striatal reward system is involved in addiction, where substance-related cues trigger dopamine release, reinforcing drug-seeking behavior.**Cognitive Functions**: The caudate, particularly its anterior portion, is involved in executive functions such as working memory, decision-making, andcognitive flexibility. Its connectivity with the prefrontal cortex suggests a role in integrating cognitive and emotional information for goal-directed behavior. The putamen, though primarily associated with motor functions, also contributes to non-motor cognitive processes like response inhibition and attention.4. Pathophysiological Involvement and Associated Disorders**Movement Disorders**: The caudate and putamen are prominently affected in several movement disorders. In PD, the degeneration of dopaminergic neurons in the SNc leads to reduced dopamine levels in the striatum, causing motor symptoms like bradykinesia, rigidity, and tremors. HD is characterized by the progressive loss of GABAergic MSNs, leading to choreiform movements, cognitive decline, and psychiatric disturbances. In dystonia, abnormal activity in the striatum contributes to involuntary muscle contractions and postures.**Psychiatric Disorders**: The striatum's involvement in reward processing and executive functions renders it susceptible to dysregulation in psychiatric conditions. For instance, in obsessive-compulsive disorder (OCD), hyperactivity in the striatum may underlie repetitive behaviors and intrusive thoughts. In addiction, altered striatal dopamine signaling fosters compulsive drug seeking. In depression and anxiety, dysfunctional cortico-striatal circuits may contribute to anhedonia and maladaptive stress responses.5. Clinical Implications and Therapeutic TargetsUnderstanding the caudate and putamen's functions and pathophysiological roles has significant clinical implications. Neuromodulatory techniques like deep brain stimulation (DBS) target specific striatal regions to alleviate motor symptoms in PD and dystonia. In psychiatric disorders, pharmacological interventions often aim to modulate striatal neurotransmitter systems. For example, dopamine agonists are used in PD, while serotonin reuptake inhibitors are employed in OCD and depression.Moreover, advanced imaging techniques like functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) allow for the in vivoassessment of striatal function and neurochemistry, facilitating diagnosis and monitoring disease progression. Genetic studies focusing on striatal pathways have also provided insights into disease etiology and potential therapeutic targets.6. ConclusionThe caudate nucleus and putamen, as integral parts of the basal ganglia, exhibit a remarkable complexity in their anatomy, neurochemistry, and functional connectivity. Their involvement in motor control, reward processing, learning, and cognition underscores their centrality in shaping human behavior. A thorough understanding of these structures' normal functioning and pathophysiological roles is essential for advancing our knowledge of various neurological and psychiatric disorders and informing the development of targeted therapeutic interventions.Acknowledging the word count constraint, this abstract provides a concise overview of the proposed in-depth analysis, which would delve into each topic with greater detail, supported by relevant research findings and illustrative examples. The complete article would meet the 1448-word requirement, offering a comprehensive, multi-angle exploration of the caudate and putamen structures.。
锥体外系病
• 辅助检查
脑脊液中多巴胺的代谢产物高香草酸(HVA)含量降 低,其余脑脊液常规检查正常,尿中多巴胺及其代 谢产物高香草酸含量降低. CT检查正常,MRI可见黑质变薄或消失
六. Diagnosis
Main points of diagnosis(诊断要点 )
1.Onset in middle-age, no etiological factor can be found.
masked face , micrographia , hypophonia 常感肢体乏力和僵硬 导致动作缓慢和始动困难 面具脸 小写症 声音低沉 吞咽困难
4. abnormal gait and posture(姿势步态异常): festinating gait flexed posture
慌张步态 屈曲体态
• hypertonia-hypokinetic syndrome 肌张 力 增高-动 作 减 少 综 合 征
肌 张 力 降 低 动 作 增 多 综 合 征
Manifestation(表现)： chorea(舞蹈症) athetosis(手足徐动症) torsion spasm(扭转痉挛) Locus(部位)：
trembling palsy(震颤麻痹)
-
Locus(部位)：
substanti nigra (黑质)
Basic pathology of movement disorders (运动障碍疾病的病理基础)
1. Biochemical abnormality of the neurotransmitters ( 递质生化异常)
substantia nigra（黑质）
red nucleus （红核）
Transverse section of the brain (大 脑 横 切 面)
英文个案--1例高空坠落伤患者的护理
Care of a patient with a fall from heightinjury【Abstract】To summarize the care of a patient with fall from height injury, close attention to vital signs pupillary changes after admission, maintaining circulatory stability, having resuscitation supplies ready, and proper and timely emergency care can shorten the number of hospital days and improve quality of life and prolong life. 【Key words】falling from height injury, first aid, nursing Fall from height injury refers to people in daily life and work, falling from a high place, due to the high-speed impact of human tissue, organs will be damaged to a certain extent caused by damage, generally have more than one organ damage, serious cases can lead to death[1] . The severity of the injury is related to factors such as weight, impacted parts, thickness of clothing, fall height, fall speed, the nature of the object hit, etc. Lighter cases only have a slight pain, heavy cases can form fractures, internal organ rupture, limb severance and other injuries, and even immediate death. Falling from height injuries are characterized by a wide range of injuries, light surface injuries and serious visceral injuries, mostly resulting in fractures[2] . Therefore, good care is more important to reduce complications and improve survival rate, which can greatly help patients' recovery. On June 13, 2021, a patient with fall injury was admitted to our department. Through active treatment and careful care, the patient's condition improved and rehabilitation was carried out:1Clinical informationCheng Xiquan, male, 75 years old, was found by neighbors falling from the second floor balcony early in the morning of 06-13, causing his head to bleed, confused, and unable to respond to calls, so his family called 120 and sent him to the rescue room for emergency treatment of "fall from height injury". At the time of admission, the patient was unconscious,with unequal pupils bilaterally. The left pupil was about 4 mm in diameter with a sensitive light reflex, while the right pupil was about 3 mm in diameter with no light reflex, grade 0 muscle strength of the extremities, positive Babinski's sign, head trauma, scattered bleeding spots on the skin mucosa, MEWS score of 3, GLS score of 4, Braden score of 13, catheter slip risk factor score of 10. The trauma score could not be measured due to the patient's coma, and the patient's family denied past history and had no history of medications or other allergies.2First aid experienceAt 06:54, the patient was admitted to the resuscitation room, nursing check: T35.5ºC, HR 69 times/min, BP 116/59mmHg, SPO2 96%; medical advice was given to the sickness, cardiac monitoring, rapid establishment of two-way venous access, blood specimen collection, bedside electrocardiogram, observation of consciousness, facial color, mouth and lips, pupil changes. 07:10, the green emergency channel was opened, risk assessment was done, the family was informed of the risks on the way of transfer. At 07:20, the patient returned to the resuscitation room and was closely observed for ejection vomiting, mental and pupillary changes and other signs of increased cranial pressure during the transfer. 07:30, the imaging department reported that the emergency CT showed: 1. right frontotemporal epidural hematoma, subarachnoid hemorrhage, right zygomatic arch fracture, right temporoparietal fracture, right shoulder dislocation with humeral tuberosity fracture; The right femoral neck fracture, right iliac bone, right sacrum, right pubic bone upper and lower branches and pubic symphysis fracture; a little cavity infarction in the basal ganglia on both sides; several tiny nodules in both lungs. 07:35 After bedside manipulation of the right shoulder joint by the attending physician, a multidisciplinary consultation was contacted. He was treated with haemostasis, gastric protection, dehydration and cranial pressure reduction, volume expansion and rehydration. Ancillary tests: routine blood: WBC 19.05×109 /L, neutral 90.10%, HGB 109g/L; biochemistry: CO2 31.5mmol/l, urea 15.06mmol/l, creatinine 128.1umol/l, glucose 9.05mmol/l,rapid glucose 9.2mmol/l. 09:00 transferred to the intensive care medicine department for further treatment. . The patient was detained in the resuscitation room for 2 hours and 6 minutes, the vital signs were still stable, 1100ml were into intravenous rehydration fluid, 500ml were out, including 200ml of urine, 300ml of gastric fluid, and 600ml of balance positive.3Nursing measuresCare of first aidClosely observe the change of condition, monitor the vital signs, observe the consciousness, pupil change and reflex to light every hour, and discover the brain herniation aura in time. Quickly cooperate with the doctor for trauma assessment and initial wound treatment, apply pressure dressing to the head wound and elevate the head of the bed by 15°-30°[3] . Apply ice cap to the head for cerebral protection[4] . Assist the doctor with bedside manipulation to reset the right shoulder joint. Open the green emergency channel, make risk assessment, determine the transfer classification level 2, bring the transfer first aid kit, determine the transfer route, and accompany the medical nurse out for CT examination to ensure the safety during the transfer.Care of the airwayKeep the airway unobstructed, protect the neck, use a neck brace for fixation, prevent posterior tongue drop and ventricular rest, remove vomitus and oral and nasal secretions in a timely manner[5] . Administer oxygen by nasal cannula at 2 L/min. Keep tracheotomy kit, ventricular puncture and drainage kit, ventilator and resuscitation drugs at bedside. Care of drainage tubesGastric tube and urinary catheter were kept in place to avoid bending and pressure, and the color, nature and amount of drainage fluid were observed. After admission, the patient was given gastrointestinal decompression after the gastric tube was left in place, and about 300ml of coffee-colored gastric contents were drained.Care with medicationUse a large trocar needle, establish two intravenous accesses, rapid static drip of mannitol 250ml should be finished within 15 minutes, observe the patient's urine volume after use, pay attention to the protection of blood vessels and local tissues to prevent extravasation.[6]Pay attention to whether the patient has excessive dehydration and adverse reactions. Tranexamic acid injection 100ml, 0.9% sodium chloride 100ml + spearhead viper hemagglutinase for injection 2u, sodium lactate Ringer's solution 500ml IV to ensure sufficient blood perfusion to vital organs and to prevent acidosis occurring in shock, monitor renal function and blood electrolyte concentration, and dynamically evaluate the effect of drug administration.Management of blood pressureIntensify blood pressure monitoring, maintain the patient's target blood pressure, prevent sudden rise or fall, adjust the drip rate according to blood pressure, and strictly control the dosing rate using an infusion pump.Psychological careFaced with a sudden and huge blow, the patient changed from a healthy to a critically ill and potentially life-threatening patient, the family could not accept it psychologically and the pessimism was obvious. Stabilize the patient's emotion, help treat the disability correctly, comfort and explain the knowledge about the disease, treatment plan, nursing measures and prognosis, encourage the family to care more about and love the patient, comfort and communicate with the patient's family to ensure that the family fully cooperates with the medical care with enough enthusiasm and positive attitude. During the treatment period, we encouraged the patients and their families to build up their confidence in overcoming the disease, and the patients gradually changed from being negative and disappointed when they learned about their illness to being positive and courageous in overcoming the disease.Nursing ExperienceIn addition to the care and treatment of trauma, a series of symptoms and complications brought about by the injury should not be underestimated. Patients with fallen injuries are often combined with multiple organ injuries, and in the process of rescue treatment, the principle of saving life first is emphasized, and the first time to have a comprehensive observation of the patient, medical and nursing staff must master skilled first aid techniques, maintain the patient's basic life support, have a keen and meticulous observation, and use critical thinking to comprehensive analysis of the patient's care problems. Use critical thinking to comprehensively analyze the patient's care problems, observe the changes in the pupils of the mind, be alert to the occurrence of various complications, multiple injuries, cerebral hemorrhage patients are developing rapidly, even if there is improvement, we should not relax our vigilance, closely observe changes in the course of treatment, keep the patient in bed, reduce various stimuli, avoid mood swings, try to avoid unnecessary movements and operations, keep the airway open, and prevent complications. And prevent the occurrence of complications[7] , after the condition is stable, encourage patients to establish confidence, do a good job of functional exercise of the limbs, keep a relaxed mood, and promote the early recovery of patients, the implementation of comprehensive emergency care for patients with multiple injuries can shorten the rescue time, improve patient satisfaction, and improve the success rate of rescue.[8]References[1]Han Yajuan,Yin Lijuan,Wang Aiping. Observation of the effect of first aid nursing intervention on children's fall from height injuries[J]. Contemporary Nurse (Upper Journal),2016,5:91-92[2]Chen YJ, Hu LJ, Zeng SJ. Clinical care of children with fall-at-height injuries[J]. Qilu Journal of Nursing.2019,5,25,10:110-111[3]Liu Xinyan. Observation of the effect of clinical care pathway in the application of nursing towels for patients with cerebral hemorrhage [J]. Chinese practical medicine, 2019, 14(18): 136-137[4]Li Y, Zhang JT, Liang Y. Nursing countermeasures of subcritical cerebral protection in the application of hypertensive cerebral hemorrhage treatment[J],Huaihai Medicine,2015,33(1):104-105[5]Zhang Yanhong. The application experience of clinical care pathway in cerebral hemorrhage care [J]. Journal of Cardiovascular Surgery, 20l 9, 8(2): 182.[6]Zhang Bo. Acute and critical care nursing [M]. People's Health Publishing House,2012.[7]Miao Jinyun. Analysis of the role of applying nursing health education in the treatment of emergency cerebral hemorrhage [J]. Shanxi Journal of Medicine,2017,46(19):2380-2382.[8]Wu Jing. Effect of integrated emergency care on resuscitation time and nursing satisfaction of patients with multiple injuries[J]. China Disability Medicine,2019,27(17):51-52.。
运动障碍和帕金森病(英文版)课件
Movement Disorders
Introduction:
Extrapyramidal system: Basal ganglia: Corpus striatum:
Movement Disorders
Introduction:
pyramidal system Extrapyramidal system
demonstrated a strong genetic contribution to PD.
• About 15% of PD cases are inherited, and 17 PD susceptibility
chromosomal loci (PARK1-17) and at least 10 specific PD susceptibility genes for familial PD have now been identified.
• The remaining 85% of PD cases are “idiopathic,” (i.e., of
unknown cause), but PD susceptibility genes have also been implicated in a small percentage of sporadic cases.
Movement Disorders
* Tics: Repetitive brief contraction of a muscle or
group of muscles. Gilles de la Tourette syndrome
* Habit spasms: Habitual movements that a
Movement disorders
Movement-Disorders
Parkinson’s disease---Differential diagnosis
Parkinsonism: postencephalitic parkinsonism, drug or toxin-induced parkinsonism(CO, Mn), arteriosclerotic parkinsonism.
2. EEG: unspecific.
3. Image test: 29~85% patients present low density focus in caudate nucleus on CT.
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Sydenham Chorea---
第14页，共31页。
Parkinson’s disease---Treatment
Begin from low dose and individualized. Anticholinergic drugs: helpful in alleviating tremor and rigidity. Artane(1~2mg, tid).
第11页，共31页。
Parkinson disease’s--Clinical findings
▪ Other features: Myerson’s sign, oily face,
intractable constipation, postural hypotension, cognitive disturbance, hallucination, depression
Depression: a trial of antidepressant drug treatment may be helpful.
大动脉粥样硬化型和穿支动脉疾病型卒中扩大的血管周围间隙主要部位与左心房、左心室增大的相关性
·论著·大动脉粥样硬化型和穿支动脉疾病型卒中扩大的血管周围间隙主要部位与左心房、左心室增大的相关性涂宇1，彭芥微1，张城滔1，李百株1，刘雨琦1，黄蓉1，朱培培1，曾秀丽2，卓文燕1作者单位1.珠海市人民医院（暨南大学附属珠海医院）神经内科广东珠海5190002.暨南大学附属第一医院神经内科广州510630基金项目珠海市科技计划项目（No.20191208E 030034）；珠海市人民医院临床科研提升计划项目（No.2023LCTS-32）收稿日期2022-12-22通讯作者卓文燕zhuhaizwy@163. com 摘要目的：探讨基于中国缺血性卒中亚型（Chinese ischemic stroke subclassification，CISS）分型的大动脉粥样硬化（large artery atherosclerosis，LAA）型卒中和穿支动脉疾病（penetrating artery disease，PAD）型卒中扩大的血管周围间隙（enlarged perivascular spaces，EPVS）与左心房、左心室增大的相关性。
方法：前瞻性收集176例急性缺血性卒中（acute ischemic stroke，AIS）患者的临床资料。
所有入组患者完善颅脑磁共振成像和B型彩色超声心动图检查。
以EPVS在脑内分布的严重部位不同分为2组，最严重部位在基底节区（basal ganglia，BG）的被认为EPVSⅠ型为主型，共67例；最严重部位在半卵圆中心（centrum semiovale，CSO）的被认为EPVSⅡ型为主型，共109例。
比较两组患者的基线资料和超声心动图参数。
采用多因素Logistic回归分析AIS患者EPVSⅠ主型的独立危险因素。
结果：EPVSⅡ主型组的左心房内径指数（left atrial diame-ter index，LADI）低于EPVSⅠ主型组[18.48(17.15,20.60)vs.19.43(18.44,21.17)，Z=－2.113，P=0.035]；左心室质量指数（left ventricular mass index，LVMI）低于EPVSⅠ主型组[92.92(82.16,109.08)vs.102.61 (85.15,121.32)，Z=－2.342，P=0.019]；左心室射血分数（left ventricular ejection fractions，LVEF）%显著高于EPVSⅠ主型组[66.00(63.00,70.00)vs.64.00(61.00,68.00)，Z=－2.914，P=0.004]。
三明治发明故事英语作文
The story of the sandwich is a delightful tale that intertwines culinary creativity with a touch of aristocratic whimsy.It is a story that has been told and retold,but its origins remain as fascinating as ever.The tale begins in the late18th century,in the heart of England.The protagonist of this story is John Montagu,the4th Earl of Sandwich,a man known for his love of gambling and his disdain for leaving the gaming table.It was during one of these gambling sessions that the sandwich was born.Montagu was an avid player of a game called Hazard,a dice game that required intense concentration and a lot of time.As the hours passed,the Earl found himself growing hungry but was reluctant to leave the game to eat.He needed a solution that would allow him to eat without interrupting his play.The solution came in the form of a simple yet ingenious idea.Montagu asked for some meat to be placed between two slices of bread.This way,he could eat with one hand while continuing to play with the other.The Earls culinary creation was a hit among his fellow gamblers,and soon,others began to request the same dish.The name sandwich was a natural choice,given that it was the Earls idea.The term quickly spread beyond the gaming tables and into the wider public sphere.The sandwich, in its various forms,became a popular dish in England and eventually made its way across the Atlantic to the United States.The sandwichs versatility is one of its most appealing qualities.It can be made with a wide range of ingredients,from simple bread and butter to more elaborate combinations of meats,cheeses,and vegetables.The sandwich has evolved over the centuries,adapting to different cultures and tastes.In America,the sandwich became a staple of the working class,providing a quick and convenient meal for those on the go.The humble sandwich has also made its way into the realm of haute cuisine,with chefs creating gourmet sandwiches that showcase their culinary skills.The sandwichs journey from a gambling table to a global phenomenon is a testament to the power of a simple idea.It is a story that reminds us that sometimes,the best solutions are the ones that are right under our noses.And so,the sandwich continues to be a beloved part of our culinary heritage,a delicious reminder of the Earl of Sandwichs gamble that paid off in more ways than one.。
狒狒巴拉姆希阿米巴合并人疱疹病毒6A脑炎一例
•论著.狒狒巴拉姆希阿米巴合并人疱疹病毒6A脑炎一例袁冬娟姜虹肖禧蕾刘琳温雅蒋晋博郑禄禄田新英【摘要】目的狒狒巴拉姆希阿米巴、人疱疹病毒6A脑炎临床少见，均可致死，两者合并感染更为少见。
本文分析狒狒巴拉姆希阿米巴合并人疱疹病毒6A脑炎的临床特点c方法报道1例狒狒巴拉姆希阿米巴合并人疱疹病毒6A脑炎患者，并结合文献分析其临床特点和预后。
结果患者老年男性，急性起病,主要临床表现为意识障碍、四肢活动障碍、癫痫发作，先后2次脑脊液二代测序均检测出狒狒巴拉姆希阿米巴及人类疱疹病毒6A,头颅MRI示中脑左侧份、脑桥左侧份、右侧基底核区、丘脑DWI弥散受限信号，予以抗细菌、抗病毒、抗真菌综合治疗后，患者症状稍有缓解，后逐渐加重，且出现全身多器官功能障碍、脓毒性休克，自动出院后死亡。
结论狒狒巴拉姆希阿米巴感染及人疱疹病毒6A感染脑炎的临床表现均复杂多样，两者合并感染极为少见，且病情凶险，预后极差。
早期诊断，多种药物(如喷他眯羟乙磺酸盐、米替福辛、氟康哇、氟胞喀除、磺胺嚅唳和大环内酯类抗生素抗狒狒巴拉姆希阿米巴感染；更昔洛韦、西多福韦及麟甲酸抗HHV-6感染)联合治疗至关重要。
【关键词】狒狒巴拉姆希阿米巴；人疱疹病毒6A；脑炎中图分类号：R531.12文献标识码：A文章编号：1006-351X(2020)06-0345-05Balamuthia mandrillaris combined with Human herpes virus6A encephalitisYuan Dongjuan,Jiang Hong,Xiao Beilei,Liu Lin,Wen Ya,Jiang Jinbo,Zheng Lulu,Tian Xinying.Department ofNeurology,the Second Hospital of H ebei University,Shijiazhuang050000,ChinaCorresponding author:Tian Xinying,Email:*************[Abstract]Objective Balamuthia mandrillaris combined with Human herpes virus6A encephalitis areclinically rare,both of which can be fatal,and co-infection of both is even rarer,and no related cases have beenreported.This article aims to analyze the clinical characteristics of Balamuthia mandrillaris combined with Humanherpes virus6A encephalitis.Method A case of Balamuthia mandrillaris combined with Human herpes virus6Aencephalitis was reported and the clinical characteristics and prognosis was analyzed hy literature.Results Thepatient was an elderly male and presented with acute onset,with main clinical manifestations of disturbance ofconsciousness,limb mobility disorders and epileptic seizure,while Balamuthia mandrillaris and Human herpes virus6A were detected twice in cerebrospinal fluid by Next-Generation Sequence.Cranial MRI showed DWI diffusionlimited signals in left midbrain,left pons,right basal ganglia and thalamus.After the comprehensive treatment of antibacterial,anti-virus and anti-fungus,the clinical symptoms were slightly relieved and gradually aggravated,thendeveloped systemic multi-organ dysfunction and septic shock,and died after discharge.Conclusion The clinicalmanifestations of Balamuthia mandrillaris infection and Human herpes virus6A encephalitis are complex and diverse.Co-infection is rare,and the condition is dangerous and the prognosis is extremely poor.Early diagnosis and multidrug(such as pentamidine isethionate,miltefosine,fluconazole,flucytosine,sulfadiazine and macrolide antibioticsto anti-Balamuthia mandrillaris;ganciclovir,cidofovir and foscarnet to anti-Human herpes virus6A)combinationtherapy are very important.[Key words]Balamuthia mandrillaris;Human herpes virus6A;Encephalitis阿米巴原虫可分为自由生活的阿米巴和溶组织作者单位：0500005家庄，河北医科大学第二医皖神经内科，河北省神经病学重点实验室通信作者：田新英，Email：*************阿米巴。
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Dysfunction of the basal ganglia,but not the cerebellum,impairs kinaesthesiaMatthias Maschke,1,3Christopher M.Gomez,2Paul J.Tuite2and JuÈrgen Konczak1,21Sensorimotor Control Laboratory,2Department of Neurology,University of Minnesota,Minneapolis,MN, USA and3Department of Neurology,University of Duisburg-Essen,Essen,Germany Correspondence to:Matthias Maschke,MD,Department of Neurology,University of Duisburg-Essen, Hufelandstrasse55,45122Essen,GermanyE-mail:matthias.maschke@uni-essen.deSummaryPrecise knowledge about limb position and orientation is essential for the ability of the nervous system to plan and control voluntary movement.While it is well established that proprioceptive signals from peripheral receptors are necessary for sensing limb position and motion,it is less clear which supraspinal structures mediate the sig-nals that ultimately lead to the conscious awareness of limb position(kinaesthesia).Recent functional imaging studies have revealed that the cerebellum,but not the basal ganglia,are involved in sensory processing of pro-prioceptive information induced by passive and active movements.Yet psychophysical studies have suggested a prominent role of the basal ganglia in kinaesthesia.This study addresses this apparent dichotomy by investigating the contributions of the cerebellum and the basal ganglia to the perception of limb ing a passive move-ment task,we examined the elbow position sense in patients with a dysfunction of the basal ganglia (Parkinson's disease,n=9),patients with cerebellar degeneration[spinocerebellar ataxia(SCA)types6and 8,n=6]and age-matched healthy control subjects (n=11).In comparison with healthy control subjects,Parkinson's disease patients,but not SCA patients,were signi®cantly impaired in the ability to detect displace-ments correctly.A1°forearm displacement was cor-rectly recognized in>75%of trials by control subjects and SCA patients,but only in55%of Parkinson's disease patients.Only at6°displacement did Parkinson's disease patients exhibit a response rate similar to those of the two other groups.Thresholds for 75%correct responses were1.03°for controls,1.15°for cerebellar patients and2.10°for Parkinson's disease patients.This kinaesthetic impairment signi®cantly cor-related with the severity of disease in Parkinson's disease patients,as determined by the Uni®ed Parkinson's Disease Rating Scale(r=±0.7,P=0.03)and duration of disease(r=±0.7,P=0.05).In contrast,there was no signi®cant correlation between performance and the daily levodopa equivalent dose.These results imply that an intact cerebro-basal ganglia loop is essential for awareness of limb position and suggest a selective role of the basal ganglia but not the cerebellum in kinaesthesia.Keywords:kinaesthesia;Parkinson's disease;spinocerebellar ataxia;basal ganglia;cerebellumAbbreviations:SCA=spinocerebellar ataxia;MMSE=Mini-Mental State Examination;UPDRS=Uni®ed Parkinson's Disease Rating Scale;WFN score=World Federation of Neurology Ataxia ScoreIntroductionSince the excellent work of Goldscheider(1898),muscle sense has been divided into(i)passive motion sense,(ii) active motion sense,(iii)position sense,and(iv)gravito-inertial sense.Kinaesthesia is de®ned as the conscious perception of active or passive motion and direction of movements.It relies on the processing of proprioceptive information derived mainly from muscle spindles and joint and cutaneous receptors(Goodwin et al.,1972;Burgess et al.,1982;Hasan and Stuart,1988;Bosco and Poppele, 2001).In contrast to the abundance of information about the neuroanatomical and neurophysiological characteristics of proprioceptive pathways(Bloedel and Courville,1981; Burgess et al.,1982;Wiesendanger and Miles,1982;Hasan, 1992;Bosco and Poppele,2001),there is limited knowledge about which neural structures play a role in the advanced processing of proprioceptive information that ultimately lead to awareness of body position and motion.Passive movements are one method of inducing proprio-ceptive stimulation for the investigation of human kinaesthe-sia.Several functional MRI and PET studies have revealedBrain126ãGuarantors of Brain2003;all rights reservedDOI:10.1093/brain/awg230Advanced Access publication June23,2003Brain(2003),126,2312±2322activations of the contralateral primary and secondary sensorimotor cortex,supplementary motor area and bilateral inferior parietal lobes during passive movements,identifying these areas as sites of central processing of proprioceptive information(Gao et al.,1996;Weiller et al.,1996;Jueptner et al.,1997).In addition,passive movements induced activations in the same parts of the cerebellar hemispheres and dentate nuclei as active movements(Gao et al.,1996; Jueptner et al.,1997).However,passive movements were not accompanied by activations in the basal ganglia,which led to the conclusion that the basal ganglia are not involved in proprioceptive information processing(Jueptner and Weiller, 1998).The®nding that the cerebellum but not the basal ganglia are selectively involved in central processing of propriocep-tive signals contradicts results from several clinical and psychophysical studies.Although the cerebellum receives major sensory input from the spinocerebellar tracts(Bloedel and Courville,1981;Bosco and Poppele,2001),sensory de®cits were not found in patients with acute cerebellar injury (Holmes,1917).Patients with a degeneration of the cerebellum exhibited impairments in perceiving durations and velocities,but not amplitudes,of kinaesthetic stimuli (Grill et al.,1994).In contrast,recent studies have suggested that a dysfunction of the basal ganglia leads to proprioceptive de®cits(Schneider et al.,1986,1987).Zia and colleagues showed that patients with Parkinson's disease were impaired in unilateral elbow-joint position sense(Zia et al.,2000, 2002).However,it remained unclear whether their®ndings could be attributed solely to impaired kinaesthesia.In their studies,participants had to visually match the actual angle of the elbow joint on a scale or to compare the position of one elbow with the other under time restriction.Knowing that Parkinson's disease patients may exhibit disturbances of visual processing and cognitive slowing(Antal et al.,1998; Diederich et al.,2002;Sawamoto et al.,2002),such dysfunctions might,at least in part,have contributed to the above results.The aim of the present study was to investigate the contributions of the cerebellum and the basal ganglia to the perception of limb position.We employed a psychophysical paradigm to examine the ability to detect a change in elbow joint position without involving time computations or visuospatial processes.The study population consisted of nine patients with a diagnosis of idiopathic Parkinson's disease,six patients with spinocerebellar ataxia(SCA)type6 or8,which is characterized by hereditary pure or predom-inant cerebellar degeneration,and11healthy,age-matched control subjects.Patients with SCA6and8are especially suited for testing cerebellar involvement in upper limb kinaesthesia.Autopsy studies revealed intact dorsal columns and spinocerebellar tracts and nerve conduction studies have shown only a mild sensorimotor neuropathy of the lower(but not upper)limbs in50%of patients with SCA6(Gomez et al., 1997).Also,patients with SCA8showed no signs of sensory nerve or tract involvement(Day et al.,2000).MethodsSubjectsSix patients with degenerative cerebellar disorders(mean T SD age47.3T7.1years,range42±63years;two females, four males),nine Parkinson's disease patients(mean T SD age52.3T9.8years,range38±70years;two females,seven males)and11age-matched healthy control subjects(mean T SD age50.3T8.1years,range39±65years;®ve females,six males)with no neurological or general medical limitations participated.Prior to testing,each subject underwent a neurological examination including sensory testing(vibration sense,light touch,pinprick sensation and position sense at index®nger and®rst toe),and patients were scored according to the standardized clinical rating scales described below. All patients with cerebellar disease were recruited from the cerebellar ataxia outpatient clinic at the University of Minnesota and were diagnosed as having a genetically de®ned spinocerebellar ataxia of type6(n=4)or type8 (n=2).Each had moderate to severe cerebellar ataxia based on the International Cooperative Ataxia Rating Scale of the World Federation of Neurology(WFN scale)(Trouillas et al., 1997).The main symptoms were gait and stance instability, limb ataxia predominantly involving the lower limbs, cerebellar dysarthria,and a variable severe cerebellar oculomotor dysfunction(gaze-evoked nystagmus,saccadic dysmetria).Neurological examination revealed no extra-cerebellar signs,such as peripheral nerve disease or motor neuron involvement.Descriptive characteristics of the SCA patients are summarized in Table1.Parkinson's disease patients were recruited from the movement disorders outpatient clinic at the University of Minnesota.All were diagnosed as having idiopathic Parkinson's disease with young(21±40years,n=3)or late (>40years,n=6)onset of disease.None of them had juvenile onset(<20years)or a known mutation in the parkin gene. According to their Hoehn and Yahr classi®cation,the Parkinson's disease patients were at a mild(n=6)or moderate(n=3)stage(Hoehn and Yahr,1967).Severity of disease was further determined by use of the Uni®ed Parkinson's Disease Rating Scale(UPDRS)(Fahn and Elton,1987).None of the patients had intellectual impairment exceeding mild forgetfulness.Formal neuropsychological testing[Mini-Mental State Examination(MMSE)(Folstein et al.,1975)]was performed in seven Parkinson's disease patients and did not reveal a cognitive decline in them(mean T SD MMSE score29.3T0.8points,range28±30points). Neurological examination did not reveal signs or symptoms of peripheral nerve disorders.All patients were tested on medication,i.e.they were told to take the medication with the same dose and time schedule as regularly.Daily doses of medications were standardized by the use of a formula for levodopa-equivalent doses using the following equation: 100mg standard levodopa=125mg sustained-release levodopa,1.5mg pramipexole,6mg ropinirole,10mg bromocriptine or1mg pergolide(Pahwa et al.,1997;Thobois Parkinson's disease impairs kinaesthesia2313et al .,2002).The mean T SD levodopa equivalent dose was 644T 533mg.Descriptive data for Parkinson's disease patients,including their medication,are summarized in Table 2.All study subjects except one Parkinson's disease patient were right-handed on the basis of results of the Edinburgh Handedness Inventory (Old®eld,1971).All patients and healthy subjects gave their informed consent to participation in the study.The study was approved by the institutional review board of the University of Minnesota.Testing apparatusThe apparatus consisted of a rectangular wooden splint (50Q 7.5cm),on which the subject's forearm was rested (Fig.1).The splint was connected via a short rod to an aluminium sled.The sled glided linearly on two tracks in the frontoparallel plane of the subject.The tracks were mounted to the base of a table.The joint between the splint and the rodallowed rotation of the splint around the rod's longitudinal axis.Three ceiling suspension points supported the weight of the arm on the splint through nylon rope ®xed to the splint.A torque motor (DC motor,24V,torque capacity 17.5cm/500mg;RAE Corporation)provided the necessary force via an interlocking gear system and a gear belt.The direction of sled motion (left or right)was controlled by two buttons.Sled speed was constant and initial accelerations from 0°/s 2were not detected by the subjects.Top speed varied slightly with the weight of the subject's arm.Therefore,measurements were taken in both directions in the loaded position for each subject at the conclusion of testing.The mean T SD angular velocity was 0.5T 0.1°/s and did not differ between the two patient groups and healthy subjects (P >0.2).Positioning of subjectsFirst,the correct vertical chair position was established by adjusting the height until the subject's shoulder reached 90°Table 2Basic characteristics of Parkinson's disease patientsnAgeSexHandedness aDisease duration UPDRS Hoehn and Yahr stageLevodopaequivalent dose c Medication(years)Total score b Mentation,behaviour and mood ADLMotorexamination (mg/day)170M 14228/1920/1614/6814/108 1.5100Ro 243M -15436/1921/1615/6820/108 2.51150C-Dp342F 131253/1925/1621/6827/1083800C-Dp,AH,En 455M 15634/1922/1612/6820/108 1.51550C-Dp,PH 553M 20533/1920/1610/6823/108 1.5100AH,Ro 649M 19316/1920/164/6812/1081100PH738F 20647/1925/1616/6826/108 2.51142C-Dp,AH,PH 859M 18532/1921/1612/6819/108 1.5450C-Dp,AH 962M 20525/1921/1611/6813/1082.5450C-DpM =male;F=female;UPDRS =Uni®ed Parkinson's Disease Rating Scale;ADL =activities of daily living.Medication:AH =amantadine hydrochloride;C-Dp =carbidopa/levodopa;En =entacapone;PH =pramipexole hydrochloride;Ro =ropinirole.a According to the Edinburgh Handedness Inventory [range 20(right handed)to ±20(left handed)](Old®eld,1971);b range 0±192,the higher the score,the severe the disease)(Fahn and Elton,1987);c levopa equivalent dose =100mg standard levodopa equals 125mg sustained-release levodopa,1.5mg pramipexole,6mg ropinirole,10mg bromocriptine or 1mg pergolide (Pahwa et al .,1997;Thobois et al .,2002).Table 1Basic characteristics of cerebellar patientsnAgeSexHandedness aSCA typeDisease duration Walking aidWFN (years)Total score b Posture and gait Upper limb ataxia Lower limb ataxia Speech Oculomotor dysfunction 143M 19813No 38/10013/3411/364/164/84/6245M 20818Cane 56/10025/3415/368/164/84/6342F 18614No 31/1009/349/364/164/85/6445M 1769No 35/10012/347/368/163/85/6546M 16612Cane 47/10013/3415/3610/164/85/6663F 2067Walker51/10017/3418/367/164/85/6M =male;F =female;SCA =spinocerebellar ataxia;WFN =World Federation of Neurology ataxia score.a According to the Edinburgh Handedness Inventory [range 20(right-handed)to ±20(left-handed)](Old®eld,1971);b range 0±100;the higher the score,the more severe the ataxia (Trouillas et al .,1997).2314M.Maschke et al .abduction while the arm lay on the splint.Then,an elbow joint position of 90°of ¯exion was ascertained using a goniometer while the sled and the splint were in the starting position.The surface of the splint was padded with foam (4cm)to ensure the subject's comfort and to prevent any motor vibrations being transmitted to the subject's arm.Subjects were instructed to maintain a loose ®st throughout testing to exclude the possible use of haptic information.This hand posture prevented haptic sensations from the sensitive palmar aspect of the hand.EMG recordingsTo ensure that the subjects did not actively move the arm during trials,EMGs of the biceps and triceps muscles of the tested arm were recorded via silver chloride surface elec-trodes (gain 2500,bandwidth 30±500Hz,sampling rate 200Hz).EMG recordings were monitored online by one of the investigators.Any trial exhibiting EMG activity was excluded from further analysis and repeated.ProcedureBoth arms were tested in each subject.Each forearm was moved passively in 80trials consisting of 40¯exion and 40extension movements with elbow joint angular displacements of 0.2,0.6,1,2,3,4,5,6,7and 8°.Angular displacements and their directions were presented pseudorandomly,twice in both directions for every displacement.The right arm was tested ®rst.Each trial was signalled to the subject by a tactilecue on the subject's shoulder prior to the start of the movement.The end of each trial was announced by administering a second tactile cue on the left forearm.After each passive movement,subjects had to judge and express verbally whether the forearm was moved `towards'or `away'from their body or if they `could not tell'.There were no time limitations for subjects to respond.Both incorrect responses and `could not tell'responses were scored as an incorrect response.Subjects were further instructed to give full concentration to the task after experiencing the ®rst cue.If,at any time,a loss of concentration was experienced,a break in testing could be taken at the subject's request.Subjects wore goggles to exclude all visual input,and headphones with pink noise masked all auditory cues during testing.The total testing time was ~40min.MeasurementsThe exact amount of movement of the sled (millimetres)required to achieve a distinct angular displacement (°)was calculated individually for each subject using the formula:required sled displacement (mm)={tan[desired arm displacement(p /180)]}forearm length (mm).To initiate sled motion,the experimenter pressed a button and tracked its movement on a rule attached to the metal base of the apparatus and a high-precision potentiometer.The potentiometer signal was calibrated and fed to a digital reader that provided an exact value for the linear displace-ment of the sled.The accuracy of the reading was determined to be 0.1mm.For each trial the subject's verbal response and the precise sled movement were recorded.Statistical analysesThe percentage of correct responses for each degree of angular displacement was calculated for each of the three groups (Parkinson's disease patients,SCA patients,controls).Group differences in the percentage of correct responses were determined using separate Kruskal±Wallis tests for each displacement (SPSS for Windows 10.0.7â;SPSS,Chicago,IL,USA).The performance data for both arms of the Parkinson's disease patients were entered in this analysis.Following Fechner's (1860)technique for determining sens-ory thresholds,we de®ned as the threshold for correct responses the point midway between guessing and a perfect response.A curve-®tting procedure (Box Lucas exponential ®t)was performed to determine the threshold for 75%correct responses.The model equation was as follows:y =a [1±e (±bx )]where y is the number of correct responses (%),x is the displacement (°),a and b are coef®cients and e is Euler's number(2.718¼).Fig.1Testing apparatus.The subject's forearm was rested on a rectangular wooden splint (50Q 7.5cm)(A )The splint was connected via a short rod (B )to an aluminium sled (C ).The sled glided linearly on two tracks in the frontoparallel plane of the subject.The tracks were mounted on the base of a table.The joint between the splint and the rod allowed rotation of the splintaround the rod's longitudinal axis.Three ceiling suspension points supported the weight of the arm on the splint by the use of nylon ropes ®xed to the splint (D ).To prevent the use of acoustic or visual information,the subject wore headphones and goggles.Parkinson's disease impairs kinaesthesia 2315In a second analysis,separate Kruskal±Wallis tests for each displacement were used to determine the within-group differences in the Parkinson's disease group for percentages of correct response between the two arms and between each of the arms and the performance of the control group.If signi®cant differences were found,Mann±Whitney U tests were performed to further elucidate which difference (affected arm versus less affected arm;affected arm versus control subjects,less affected arm versus control subjects)was signi®cant.Thresholds were calculated using the same curve-®tting procedure as that described above.Moreover,the severity of disease as expressed by the total UPDRS score in Parkinson's disease patients,the duration of disease and the daily levodopa-equivalent dose were correlated with the percentage of correct responses over all displacements (bivariate correlations,computing Spearman's r ).For this analysis,the percentage of correct responses for both arms of all Parkinson's disease patients was used,given that the motor score of the UPDRS also included both arms in the analysis.P values <0.05were taken to be signi®cant.ResultsComparison of kinaesthetic thresholds between groupsWe found no differences in the percentage of correct responses between passive forearm extension and ¯exion movements (P >0.2).For the sake of simplicity,we therefore collapsed these two data sets and report all results for the combined ¯exion/extension movements.Control subjects had dif®culty detecting very small displacements (0.2°),but rapidly showed improvement incorrect responses with increasing angular displacement (Fig.2,Table 3).A 0.6°displacement was detected in 51%of trials and a 1°displacement in >82%of trials by the control subjects.SCA patients had a similar rate of detection compared with control subjects.In contrast,Parkinson's disease patients were clearly impaired.They detected angular displacements of 0.6°in only 22%of trials and of 1°in only 55%.At 2°displacement,SCA patients and control subjects showed b 94%correct responses,whereas Parkinson's disease patients showed only 76%correct responses.Although the differences in the performance between Parkinson's disease patients and SCA patients and control subjects were smaller at 4and 5°displacements,only at b 6°displacement was the mean percentage of correct responses not signi®cantly different between groups.Re¯ecting these observations,differences between the three groups were signi®cant for 0.6,2,3,4and 5°displacements (all P values <0.05)and showed a trend for the 1°displacement (P =0.078)(Table 3).In keeping with these results,thresholds for 75%correct responses were different between the three groups.Parkinson's disease patients had approximately a twofold higher threshold (2.10°)compared with control subjects (1.03°)and cerebellar patients (1.15°)(Fig.2,Table 4).The mean percentage of correct responses over all displacements underlined the impairment of Parkinson's disease patientsinFig.2Percentage of correct responses for each displacement and group.Parkinson's disease (PD)patients showed a clearimpairment in detection of joint displacements,whereas SCA patients showed a performance similar to that of control subjects.The threshold for 75%correct responses of Parkinson's disease patients (2.10°)was twice that of SCA patients (1.15°)and control subjects (1.03°).Table 3Percentages of correct responses per group and displacementDisplacementCorrect responses [mean T SD (%)]ControlsSCA patients Parkinson's disease patients P a 0.2°17T 2611T 1411T 26n.s.0.6°51T 2050T 3422T 260.0041°82T 2075T 2355T 370.0782°96T 1394T 1576T 270.0053°97T 897T 982T 250.0354°10010096T 90.0445°99T 710089T 160.0096°97T 1410098T 7n.s.7°98T 9100100n.s 8°99T 410097T 8n.s Total84T 3083T 3273T 37n.s.a P <0.05=signi®cant (Kruskal±Wallis test).Table 4Results of curve-®tting procedureThresholda b R 2Controls 1.03°99.397 1.3700.979SCA patients 1.15°100.728 1.1840.982PD patients Total2.10°97.9420.69150.971Less affected arm 1.50°102.2980.8830.941Affected arm2.50°99.2080.5710.933PD =Parkinson's disease.a and b are coef®cients.2316M.Maschke et al .detecting changes of their elbow-joint position.Parkinson's disease patients had an overall accuracy of 73%and SCA patients and control subjects showed 83and 84%accuracy,respectively.Percentages of `could not tell'responses and incorrect responses concerning directions (`away'instead of `towards')were different between the three groups.Control subjects and cerebellar patients gave only 14.9and 15.2%`could not tell responses',respectively,whereas Parkinson's disease patients were indecisive in 25.3%of trials.Differences in overall accuracy and `could not tell'responses were statistically signi®cant (P <0.0001).Comparison of kinaesthetic thresholds between the affected and less affected arms of Parkinson's disease patients and control subjectsFive of the Parkinson's disease patients showed a prominent clinical difference between the more affected and less affected arms,and were therefore included in this analysis.Three patients had symptoms only or predominantly on the right side,two on the left side.The ability to detect changes of elbow position appeared to be impaired in the affected arm compared with the less affected arm (Fig.3,Table 5).Angular displacements of 2and 3°were detected correctly in 95%of trials with the less affected arm,but in only 70%of trials with the affected side.At 4°displacement,Parkinson's disease patients exhibited almost a similar response rate on the two sides.Differences in performance between the affected arm and the less affected arm of Parkinson's disease patients and both arms of control subjects were signi®cant for 0.6,2and 3°(all P values <0.05).Further analysis showed that the percentage of correctresponses was signi®cantly different between the affected arm of Parkinson's disease patients and control subjects for 0.6,2,3,4and 5°displacements.In contrast,differences between the less affected arm and control subjects were only signi®cant for 0.6and 5°displacements.Signi®cant differences between the affected arm and the less affected arm of Parkinson's disease patients were identi®ed for 2and 3°displacements (P =0.006).The corresponding thresholds for 75%correct responses were 1.50°for the less affected arm and 2.50°for the affected arm (Fig.3,Table 4).Percentages of indecisive responses (`could not tell')were also higher for the affected arm compared with the less affected arm (28.5versus 22.2%).Correlation of performance with severity and duration of disease,medication and cognitive function in Parkinson's disease patientsThe severity of disease in Parkinson's disease patients,as measured by the UPDRS total score,correlated signi®cantly and inversely with the percentage of correct responses over all displacements (r =±0.7,P =0.03).Figure 4shows this correlation in relation to the performance of all SCA patients and control subjects.Three of the Parkinson's disease patients revealed percentages of correct responses that were within the range of performance of the control subjects and SCA patients.The remaining six Parkinson's disease patients exhibited response rates that were clearly below those of the control subjects and SCA patients.However,one SCA patient (Subject 4,Table 1)had a response rate that was below the range of the other ®ve SCA patients but within the range of the more severely affected Parkinson's disease patients.Moreover,there was a signi®cant inverse correlation between the duration of Parkinson's disease and correct responses over all displacements (r =±0.7,P =0.05),indicating that longer disease duration was accompanied by poorerperformance.Fig.3Comparison of percentages of correct responses between the less affected arm,the affected arm of Parkinson's disease patients and control subjects.Impairments of kinaesthesia were most prominent in the affected arm for displacements between 0.6and 4°.The threshold for 75%correct responses was 2.5°for the affected arm and 1.5°for the less affected arm.Table 5Percentages of correct responses per arm and for each displacement for Parkinson's disease patients with unilateral disease or bilateral disease with a clear predominance of one arm in comparison with healthy controlsDisplacementCorrect responses [mean T SD (%)]ControlsAffected arm Less affected arm P a 0.2°17T 2624T 370.0n.s.0.6°51T 2013T 1722T 230.0041°82T 2053T 4359T 29n.s.2°96T 1364T 3186T 200.0033°97T 875T 2989T 200.0274°10096T 996T 9n.s.5°99T 793T 1286T 20n.s 6°97T 1496T 9100n.s.7°98T 9100100n.s 8°99T 496T 9100n.s Total84T3071T 3874T37n.s.a P<0.05=signi®cant (Kruskal±Wallis test).Parkinson's disease impairs kinaesthesia 2317。