How Has Stephen Hawking Lived Past 70 with ALS?

By Katherine Harmon

The famous theoretical physicist has helped to bring his ideas about black holes and quantum gravity to a broad public audience. For much of his time in the public eye4in the public eye在公眾眼中；廣為人知的；受公眾矚目的。, though, he has been confined to a wheelchair by a form of the motor-neuron disease amyotrophic lateral sclerosis (ALS). And since 1985 he has had to speak through his trademark computer system—which he operates with his cheek—and have around-the-clock5around-the-clock日夜不停的；連續不斷的。care.

作為著名的理論物理學家，霍金向大眾普及了他關于黑洞和量子引力的觀念。然而，因患有一種運動神經元疾病——肌萎縮側索硬化癥（ALS），在公眾眼中他大部分時間被限制在輪椅上。自1985年開始，他講話也不得不通過他標志性的計算機系統——他用臉頰來操作這個系統——而他本人也需要全天候的看護。

[2] But like his mind, Hawking’s illness seems to be singular. Most patients with ALS are diagnosed after the age of 50 and die within five years of their diagnosis. Hawking’s condition was first diagnosed when he was 21, and he was not expected to see his 25th birthday.

[3] Why has Hawking lived so long with this malady66 malady疾病；弊病。when so many other people die so soon after diagnosis? We spoke with Leo McCluskey, an associate professor of neurology and medical director of the ALS Center at the University of Pennsylvania, to find out more about the disease and why it has spared Hawking and his amazing brain.

What is ALS—and is there more than one form of it?

[4] ALS, which is also known as a motor-neuron disease—and colloquially as Lou Gehrig’s disease in the U.S.—is a neurodegenerative7neurodegenerative神經變性的。disease. Each muscle is controlled by motor neurons that reside in the brain in the frontal lobe8frontal lobe大腦額葉。. These are controlled electrically and are synaptically9synaptically突觸地。connected to motor neurons that reside lower down in the brain—as well as motor neurons that reside in the spinal cord. The guys in the brain are called the upper motor neurons,and the guys in the spine are called the lower motor neurons. The disease causes weakness of either upper motor neurons or lower motor neurons or both.

[2]不過，和他的頭腦一樣，霍金的疾病似乎也很奇特。大多數ALS患者在50歲后被確診并于診斷后5年內死亡?；艚鹗窃?1歲時首次被確診患病，同時醫生認為他活不過25歲。

[3]為什么其他許多患者在確診后很快就死亡了，而霍金卻能帶病生存這么久？我們采訪了賓夕法尼亞大學ALS中心的神經學副教授和醫療主任利奧·麥克拉斯基，了解了更多關于此病的知識，以及霍金及其神奇的大腦得以幸免速亡的原因。

ALS是什么——它還有其他類型嗎？

[4] ALS是一種神經變性疾病，也被稱為運動神經元病——在美國俗稱盧伽雷氏癥。人體的每塊肌肉受控于大腦額葉中的運動神經元。這些運動神經元受電位控制，通過突觸與位于大腦低位的運動神經元和脊髓中的運動神經元相連。大腦中的神經元被稱為上運動神經元，脊柱中的被稱為下運動神經元。該病常累及上運動神經元或下運動神經元，或兩者兼而有之。

[5] It’s been known for quite some time that there are variants10variant變異型；變體。of ALS.One is referred to as11be referred to as被稱為……。progressive muscular atrophy, or PMA. It appears to be an isolated illness of the lower motor neurons. However, pathologically12pathologically病理上；病理地。, if you do an autopsy13autopsy〈病理〉尸體解剖，尸檢；驗尸。of a patient, they will have evidence of deterioration14deterioration惡化；退化。of upper motor neurons.

[6] There is also primary lateral sclerosis—PLS—and clinically it looks like an isolated upper motor-neuron disorder. However, pathologically they also have lower motor-neuron disorder.

[7] The other classic syndrome is called progressive bulbar palsy15bulbar palsy延髓性麻痹，（真性）球麻痹?！猳r progressive supranuclear palsy16supranuclear palsy核上性麻痹，假性球麻痹。—which is weakening of cranial muscles,like the tongue, face and swallowing muscles. But it pretty much17pretty much幾乎。always spreads to limb muscles.

[5]我們很早就知道，ALS有變異型。一種被稱為進行性肌肉萎縮（PMA）。這似乎是一種獨立的下運動神經元疾病。然而，如果對該病患者做尸檢，其病理結果將證明上運動神經元也出現退化跡象。

[6]還有一種原發性側索硬化（PLS）。臨床上看起來像是一種獨立的上運動神經元障礙。然而，病理顯示也有下運動神經元障礙。

[7]另一個典型綜合征稱為進行性延髓性麻痹（PBP）——或進行性核上性麻痹（PSP），累及顱部肌肉，如舌、面部和吞咽肌肉。然而，患者幾乎總是會出現四肢肌肉功能障礙。

[8] Those are the four classic motorneuron disorders that have been described. And it was thought for quite some time that these disorders were limited to motor neurons. It’s now clear that that’s not true. It’s now well recognized that 10 percent of these patients can develop degeneration in another part of the brain, such as other parts of the frontal lobe that don’t contain the motor neurons or the temporal lobe18temporal lobe顳葉。. So some of these patients can actually develop dementia,called frontal-temporal lobe dementia.

[9] One of the misconceptions about ALS is that it’s only a motor-neuron disease, and that’s not true.

What has Stephen Hawking’s case shown about the disease?

[10] One thing that is highlighted by this man’s course is that this is an incredibly variable disorder in many ways. On average people live two to three years after diagnosis. But that means that half the people live longer, and there are people who live for a long, long time.

[11] Life expectancy19life expectancy預期壽命，平均壽命。turns on two things: the motor neurons running the diaphragm—the breathing muscles. So the common way people die is of respiratory failure. And the other thing is the deterioration of swallowing muscles,and that can lead to malnutrition and dehydration. If you don’t have these two things, you could potentially live for a long time—even though you’re getting worse. What’s happened to him is just astounding20astounding令人驚訝的，令人震驚的。. He’s certainly an outlier.

[8]上述是四種典型的運動神經元障礙。在相當長一段時間內，我們認為這些障礙僅限于運動神經元。現在發現，事實并非如此。目前我們充分認識到，10%患者大腦的另一部分可能發生退行性變，例如大腦額葉不含運動神經元的其他部分或大腦顳葉。因此，一些患者實際可能發展成癡呆，稱為額顳葉癡呆。

[9]人們認為ALS只是一種運動神經元疾病，這種認識是不對的，純屬誤解。

關于該病，霍金的病例表明了什么？

[10]霍金的病例凸顯了一個問題，即這種疾病在許多方面變幻莫測。病人在確診后平均可存活兩到三年。這就意味著有一半病人活得更長，而且確實有人存活了很久很久。

[11]患者的預期壽命取決于兩個方面：一是控制橫膈膜即呼吸肌的運動神經元，因此，病人常常死于呼吸衰竭；另一個是吞咽肌肉的退化，這可能導致患者營養不良和脫水。如果沒有這兩方面的問題，你就可能存活很長時間——即使病情在不斷惡化。發生在霍金身上的事確實令人震驚。他絕對是個例外。

Has he lived so long because he got the disease when he was young and had the juvenile-onset type?

[12] Juvenile-onset is diagnosed in the teenage years, and I don’t know enough about his course to say. But it’s probably something similar to juvenileonset disorder, which is something that progresses very, very, very slowly. I have patients in my clinic who were diagnosed in their teens and are still alive in their 40s, 50s or 60s. But not having ever examined him or taken a history,it’s a little hard for me to say.

[13] He’s a very good example of the sparing of the non-motor parts of the brain that can occur.

How frequent are these cases of very slow-progressing forms of ALS?

[14] I would say probably less than a few percent.

How much do you think Stephen Hawking’s longevity has been due to the excellent care that he has received versus the biology of his particular form of ALS?

[15] It’s probably a little bit of both.I just know him from television, so I don’t know what kind of interventions he’s had. If he really isn’t on a ventilator, then it’s his biology—it’s the biology of his form of the neurodegenerative disease that determines how long he will live. For trouble swallowing you can elect to have a feeding tube placed,which basically takes malnutrition and dehydration off the table. But mostly it’s about the biology of the disease.

他存活這么久是否因為他年輕時就患病，屬青少年發病型？

[12]青少年發病型是指在十幾歲時被確診患病，我對霍金的病程了解很少，說不出什么。但很可能是類似青少年發病型的疾病，病程發展極其緩慢。我的診所里有一些十幾歲時就確診的患者，他們現在已40多、50多或60多歲了，都還在世。我沒有給霍金檢查過，也沒看過他的病史，所以不好說。

[13]霍金是大腦非運動神經元部分幸免發生病變的極佳案例。

這種發展極緩型ALS的病例發生率是多少？

[14]我會說大概不到幾個百分點。

您認為霍金的長壽應該歸因于哪一方面，是更多歸因于他受到的極佳護理，還是他所患上的這種ALS自身發展決定的？

[15]或許都有一點點。我只是從電視上認識他，所以不知道他接受了什么樣的干預措施。如果他真的不用呼吸機,那就是他自身的病情如此——決定他存活多久的是他罹患的這種神經退行性疾病的發展狀況。如果吞咽困難，可以選擇放置飼管，這基本上可以避免營養不良和脫水。但最主要的還是疾病本身的發展。

Hawking obviously has quite the active mind, and previous statements that he has made seem to indicate he has a pretty positive mental outlook, despite his condition. Is there any evidence that lifestyle and psychological wellbeing do much to help with patients’outcomes? Or is the disease usually too quick for that to make a difference?

[16] I don’t believe that adds to longevity.

ALS still doesn’t have a cure. What have we learned about the disease recently that might help us find one—or at least better treatments?

[17] Beginning in 2006 it became clear that like a lot of other neurodegenerative diseases, ALS was determined by the accumulation of abnormal proteins in the brain. Ten percent of ALS is genetic and based on a gene mutation.I’m sure there are also at-risk genes for ALS, but there are now multiple genes that have been identified as potentially causing the disease. Each one of them are interesting in that they lead to the accumulation of different proteins in the brain. Knowing specific genes gives us particular mechanisms in the brain, and would potentially give us targets for therapies. But none of this has given us any robust therapies yet.

雖然霍金身患絕癥，但顯然他的思維相當活躍，之前所做的各種聲明似乎也表明他的精神狀態非常積極。是否有證據表明，生活方式和心理健康會對病人預后有很大幫助？或是這種疾病通常發展太快而看不出有什么影響？

[16]我不相信那會增加病人的壽命。

ALS仍然無法治愈。最近針對此病的研究是否有什么進展，可能幫助我們找到一種治愈的方法——或者至少更好的治療方法？

[17]從2006年開始，我們就清楚地發現，像其他很多神經退行性疾病一樣，ALS是由大腦中的異常蛋白質積累所致。10%的ALS是遺傳和基因突變所致。我相信還存在ALS的高?；?，而現在已確認有多個基因可能導致該病。它們中的每一個都會積極參與并導致大腦中不同蛋白質的積累。認知特定的基因可以讓我們了解大腦特定的作用機制,并可能給我們提供治療的標靶。但是，這些目前都還沒有形成任何強有效的治療方法。

What does Stephen Hawking’s case mean for people who have the disease?

[18] It’s just an incredible, incredible example of the variability of the disease—and the hope for patients who have it that they could also live a long life. Unfortunately, it’s a small percentage of people for whom that actually happens.霍金的病例對該病其他患者有什么借鑒意義嗎？

[18]那只是體現該病變異性的一個極其不可思議的病例——同時也給了其他患者希望，自己或許也能長壽。遺憾的是，真正能夠如愿的患者不會太多。