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在公众眼中；广为人知的；受公众瞩目的。, 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；连续不断的。care.

作为著名的理论物理学家，霍金向大众普及了他关于黑洞和量子引力的观念。然而，因患有一种运动神经元疾病——肌萎缩侧索硬化症（ALS），在公众眼中他大部分时间被限制在轮椅上。自1985年开始，他讲话也不得不通过他标志性的计算机系统——他用脸颊来操作这个系统——而他本人也需要全天候的看护。

[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神经变性的。disease. Each muscle is controlled by motor neurons that reside in the brain in the frontal lobe8frontal lobe大脑额叶。. These are controlled electrically and are synaptically9synaptically突触地。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]不过，和他的头脑一样，霍金的疾病似乎也很奇特。大多数ALS患者在50岁后被确诊并于诊断后5年内死亡。霍金是在21岁时首次被确诊患病，同时医生认为他活不过25岁。

[3]为什么其他许多患者在确诊后很快就死亡了，而霍金却能带病生存这么久？我们采访了宾夕法尼亚大学ALS中心的神经学副教授和医疗主任利奥·麦克拉斯基，了解了更多关于此病的知识，以及霍金及其神奇的大脑得以幸免速亡的原因。

ALS是什么——它还有其他类型吗？

[4] ALS是一种神经变性疾病，也被称为运动神经元病——在美国俗称卢伽雷氏症。人体的每块肌肉受控于大脑额叶中的运动神经元。这些运动神经元受电位控制，通过突触与位于大脑低位的运动神经元和脊髓中的运动神经元相连。大脑中的神经元被称为上运动神经元，脊柱中的被称为下运动神经元。该病常累及上运动神经元或下运动神经元，或两者兼而有之。

[5] It’s been known for quite some time that there are variants10variant变异型；变体。of ALS.One is referred to as11be referred to as被称为……。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〉尸体解剖，尸检；验尸。of a patient, they will have evidence of deterioration14deterioration恶化；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。—or 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几乎。always spreads to limb muscles.

[5]我们很早就知道，ALS有变异型。一种被称为进行性肌肉萎缩（PMA）。这似乎是一种独立的下运动神经元疾病。然而，如果对该病患者做尸检，其病理结果将证明上运动神经元也出现退化迹象。

[6]还有一种原发性侧索硬化（PLS）。临床上看起来像是一种独立的上运动神经元障碍。然而，病理显示也有下运动神经元障碍。

[7]另一个典型综合征称为进行性延髓性麻痹（PBP）——或进行性核上性麻痹（PSP），累及颅部肌肉，如舌、面部和吞咽肌肉。然而，患者几乎总是会出现四肢肌肉功能障碍。

[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颞叶。. 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预期寿命，平均寿命。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令人惊讶的，令人震惊的。. He’s certainly an outlier.

[8]上述是四种典型的运动神经元障碍。在相当长一段时间内，我们认为这些障碍仅限于运动神经元。现在发现，事实并非如此。目前我们充分认识到，10%患者大脑的另一部分可能发生退行性变，例如大脑额叶不含运动神经元的其他部分或大脑颞叶。因此，一些患者实际可能发展成痴呆，称为额颞叶痴呆。

[9]人们认为ALS只是一种运动神经元疾病，这种认识是不对的，纯属误解。

关于该病，霍金的病例表明了什么？

[10]霍金的病例凸显了一个问题，即这种疾病在许多方面变幻莫测。病人在确诊后平均可存活两到三年。这就意味着有一半病人活得更长，而且确实有人存活了很久很久。

[11]患者的预期寿命取决于两个方面：一是控制横膈膜即呼吸肌的运动神经元，因此，病人常常死于呼吸衰竭；另一个是吞咽肌肉的退化，这可能导致患者营养不良和脱水。如果没有这两方面的问题，你就可能存活很长时间——即使病情在不断恶化。发生在霍金身上的事确实令人震惊。他绝对是个例外。

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.

他存活这么久是否因为他年轻时就患病，属青少年发病型？

[12]青少年发病型是指在十几岁时被确诊患病，我对霍金的病程了解很少，说不出什么。但很可能是类似青少年发病型的疾病，病程发展极其缓慢。我的诊所里有一些十几岁时就确诊的患者，他们现在已40多、50多或60多岁了，都还在世。我没有给霍金检查过，也没看过他的病史，所以不好说。

[13]霍金是大脑非运动神经元部分幸免发生病变的极佳案例。

这种发展极缓型ALS的病例发生率是多少？

[14]我会说大概不到几个百分点。

您认为霍金的长寿应该归因于哪一方面，是更多归因于他受到的极佳护理，还是他所患上的这种ALS自身发展决定的？

[15]或许都有一点点。我只是从电视上认识他，所以不知道他接受了什么样的干预措施。如果他真的不用呼吸机,那就是他自身的病情如此——决定他存活多久的是他罹患的这种神经退行性疾病的发展状况。如果吞咽困难，可以选择放置饲管，这基本上可以避免营养不良和脱水。但最主要的还是疾病本身的发展。

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.

虽然霍金身患绝症，但显然他的思维相当活跃，之前所做的各种声明似乎也表明他的精神状态非常积极。是否有证据表明，生活方式和心理健康会对病人预后有很大帮助？或是这种疾病通常发展太快而看不出有什么影响？

[16]我不相信那会增加病人的寿命。

ALS仍然无法治愈。最近针对此病的研究是否有什么进展，可能帮助我们找到一种治愈的方法——或者至少更好的治疗方法？

[17]从2006年开始，我们就清楚地发现，像其他很多神经退行性疾病一样，ALS是由大脑中的异常蛋白质积累所致。10%的ALS是遗传和基因突变所致。我相信还存在ALS的高危基因，而现在已确认有多个基因可能导致该病。它们中的每一个都会积极参与并导致大脑中不同蛋白质的积累。认知特定的基因可以让我们了解大脑特定的作用机制,并可能给我们提供治疗的标靶。但是，这些目前都还没有形成任何强有效的治疗方法。

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.霍金的病例对该病其他患者有什么借鉴意义吗？

[18]那只是体现该病变异性的一个极其不可思议的病例——同时也给了其他患者希望，自己或许也能长寿。遗憾的是，真正能够如愿的患者不会太多。