A mind untouched: An ALS expert explains how the disease affects various patients differently--and leaves some mentally debilitated by dementia.
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Stephen Hawking turns 70 on Sunday, beating the odds of a daunting diagnosis by nearly half a century.
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 eye, 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-clock care.
But his disease seems hardly to have slowed him down. Hawking spent 30 years as a full professor of mathematics at the University of Cambridge. And he is currently the director of research at the school's Center for Theoretical Cosmology.
But like his mind, Hawking's illness seems to be singular. Most patients with ALS—also known as Lou Gehrig's disease, for the famous baseball player who succumbed to the disease—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.
Why has Hawking lived so long with this malady 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.
[An edited transcript of the interview follows.]
What is ALS—and is there more than one form of it?
ALS, which is also known as a motor-neuron disease—and colloquially as Lou Gehrig's disease in the U.S.—is a neurodegenerative disease. Each muscle is controlled by motor neurons that reside in the brain in the frontal lobe. These are controlled electrically and are synaptically 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.
It's been known for quite some time that there are variants of ALS. One is referred to as progressive muscular atrophy, or PMA. It appears to be an isolated illness of the lower motor neurons. However, pathologically, if you do an autopsy of a patient, they will have evidence of deterioration of upper motor neurons.
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.
The other classic syndrome is called progressive baldor palsy—or progressive supranuclear palsy—which is weakening of cranial muscles, like the tongue, face and swallowing muscles. But it pretty much always spreads to limb muscles.
Those are the four classic motor-neuron 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 lobe. So some of these patients can actually develop dementia, called frontal-temporal lobe dementia.
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Add Commentdo you think that just maybe that superb round-the-clock "best of" medical care might have had something to do with it? How may other victims of ALS have that kind of care? Maybe a clinical study relating these variables should be undertaken (sarcasm alert for the light-minded).
Reply | Report Abuse | Link to thisSo lifestyle has nothing to do with longevity from his perspective eh? I have a great uncle who just recently retired (from a job) at age 96 and my Grandfather will be turning 88 shortly who still plows a field. It's obvious that biology is the primary contribution but they have also grown their own vegetables, worked hard, and never (aside from the occasional swig of whiskey) succumb to habitual vices. It is absurd to state (especially as a doctor of health) that lifestyle plays no contribution to longevity, mental health included. I appreciate SA's effort and it is a well done article, but it certainly could have been reinforced by a more intelligent professional perspective.
Reply | Report Abuse | Link to thisIt's a shame that a science writer can get away with "On average people live two to three years after diagnosis. But that means that half the people live longer".
Reply | Report Abuse | Link to thisI feel like I should sign this "Disgusted of Tumbridge Wells"!
The writer didn't say that. Prof. McCluskey said it.
Reply | Report Abuse | Link to thisI don't believe that Prof. McCluskey ever said that lifestyle had nothing to do with it. What he said was that he didn't think that a positive outlook had anything to do with it. This position has come up in several recent studies showing that people with positive and negative outlooks who receive the same treatment have statistically identical results.
Reply | Report Abuse | Link to thisRather than there being a 'paradox' with his diagnosis of ALS , he has most likely been misdiagnosed. He most likely has NBIA which is treatable.
Reply | Report Abuse | Link to this"We report the results of iron chelating treatment with deferiprone in a 61-year-old woman with signs and symptoms of neurodegeneration with brain iron accumulation (NBIA)"
"After 6 months of therapy the patient's gait had improved and a reduction in the incidence of choreic dyskinesias was observed,"
"Her gait returned to normal after an additional 2 months of therapy, at which time there was a further reduction in involuntary movements and a partial resolution of the blepharospasm."
May be he is a great guy inherited by lot of intelligence and power of imagination.But i dont want choose to be like him.I am happy with what(healthy) i have inherited with.
Reply | Report Abuse | Link to thisThat's not a treatment. That's a study from only a few months ago, and an unblind one at that. Only nine individuals were involved.
Reply | Report Abuse | Link to thisAside from that, you probably have less diagnostic information than McCluskey about Hawking's condition. If he hesitates to opine on the patient's exact condition, what makes you suitable to make a likely diagnosis?
I didn't know he was diagnosed at such an early age. I am curious whether the long survival has anything to do with the early onset. Another example of someone diagnosed with ALS early in life is virtuoso guitarist Jason Becker. Diagnosed in his late teens/early twenties, and still alive well into his forties. Still composing with the use of a computer as well.
Reply | Report Abuse | Link to thisMaybe early onset ALS is an indicator of being gifted in some field.
The second page of the interview covers that. It's a combination of good care and being in the lucky few percent that have a slow-progressing form of the disease. McCluskey mentions that he has several patients who have lived into their 40s, 50s, and 60s. Some people just get lucky.
Reply | Report Abuse | Link to this"How Has Stephen Hawking Lived to 70 with ALS?"
Reply | Report Abuse | Link to thisI'd say that perhaps he made a pact with the devil, but he doesn't believe in the devil...
Name a neurodegenerative disease which ISN'T considered to have a 'possible' neurodegeneration with brain iron accumulation (NBIA). Alzheimers' , Parkinsons' , ALS , MS are ALL , at the moment , being 'looked into' with iron being THE player IN the neurodegeneration. The hemosiderotic mouse is presently considered to be a 'mouse model of ALS'.
Reply | Report Abuse | Link to this"Prevention of motor neuron degeneration by novel iron chelators in SOD1(G93A) transgenic mice of amyotrophic lateral sclerosis."
"Iron has been implicated in Alzheimer's disease, but until now no direct proof of Fe(II) binding to the amyloid-β peptide (Aβ) has been reported."
"The anti-Parkinson iron chelator brain selective monoamine oxidase (MAO) AB inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline] was shown to possess neuroprotective activities in vitro and in vivo, against several insults applicable to several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease (PD) and ALS."
"Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla"
Riluzole is the only drug at the moment having any results in ALS. The mode of operation is not known. Studies have shown Riluzole results in the same markers as those found by a similar drug in iron induced neurodegenerative disease , epilepsy.
Reply | Report Abuse | Link to this"Riluzole elevates GLT-1 activity and levels in striatal astrocytes"
"The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy"
"Since formation of free radicals may be involved in epileptogenesis after brain trauma and hemorrhage the effects of the nitrone radical scavenger E1-phenyl-tert-N-butyl nitrone (PBN) were also studied."
"Our results suggest that astrocytic uptake of glutamate is oxidatively impaired in iron-induced epileptogenesis and that the administration
of a radical scavenger can attenuate this process."
I would venture a guess , based on the animal model of iron induced epilepsy , that Riluzole chelates / targets iron thereby reducing the oxidation / radical scavenger.
A previous study shows iron raises and Riluzole lowers.
Reply | Report Abuse | Link to this"Iron alters glutamate secretion by regulating cytosolic aconitase activity"
"We provide the first evidence that, in addition to secreting glutamate, retinal pigment epithelial cells express the vesicular glutamate transporter VGLUT1 and that regulated vesicular release of glutamate from these cells can be inhibited by riluzole."
This study showed reversal AFTER established lesion.
Reply | Report Abuse | Link to this"Decreasing nigral iron levels "
Neurorescue Effect of Rosmarinic Acid on 6-Hydroxydopamine-Lesioned Nigral Dopamine Neurons in Rat Model of Parkinson's Disease.
J Mol Neurosci. 2011 Dec 29.
Wang J, Xu H, Jiang H, Du X, Sun P, Xie J.
Department of Neurosurgery, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China.
Abstract
Rosmarinic acid (RA) is a naturally occurring polyphenolic compound.
It has been reported that RA possessed antioxidant and anti-inflammatory properties.
Our previous study showed that RA could protect MES23.5 dopaminergic cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro.
The purpose of this study was to explore the neuroreparative (neurorescue) effect of RA on 6-OHDA-lesioned rat model of Parkinson's disease (PD) in vivo.
In this study, the rats were given RA orally after intrastriatal 6-OHDA lesion.
Results showed that the dopamine content in the striatum decreased and the numbers of tyrosine hydroxylase-immunoreactive neurons reduced
after 6-OHDA treatment.
RA treatment after 6-OHDA administration could restore these changes.
Further studies demonstrated that 6-OHDA treatment increased the iron-staining positive cells, which were markedly decreased by RA treatment.
Moreover, RA suppressed the increased ratio of Bax/Bcl-2 at gene level induced by 6-OHDA.
This indicates that the neurorescue effects of RA against 6-ODHA-induced degeneration of the nigrostriatal dopaminergic system were achieved by decreasing nigral iron levels and regulating the ratio of Bcl-2/Bax gene expression.
PMID:22205146
Stephen shares a birthday with Elvis Presley. One day after my own... I'm 38 this today.
Reply | Report Abuse | Link to thisIf he was referring to median survival time (rather than mean), then he is correct. Such estimates are usually based on medians. But perhaps you are belittling him for stating the obvious...
Reply | Report Abuse | Link to thishow can I write to a scientist ?
Reply | Report Abuse | Link to thishow can I write to a scientist
Reply | Report Abuse | Link to this"how can I write to a scientist"
Reply | Report Abuse | Link to thisBill Nye the Science Guy
http://www.billnye.com/contact-bill-nye/
"Is there any evidence that lifestyle and psychological well-being do much to help with patients' outcomes?"
Reply | Report Abuse | Link to this"I don't believe that adds to longevity."
Ha! Experts can never summon the scientific honesty to say, "I don't know". By his own stringent scientific code and criteria, there's no basis for him to dismiss the possibility.
Instead we get an rebuff that is evinced not by the knowledgeable force of scientific authority but instead, is ironically based purely on his personal anathema towards anything "touchy-feely" that is non statistically-derived.
I worry that clever people, with practice, seem to remorselessly delineate and extrapolate until they fall into reflexive, machine-like thinking...
The will to live free with fate.
Reply | Report Abuse | Link to thisThe human mind and body are wonderful and each individual may react differently to disease. Physicians can only generalize according to the statistics presented to them
Reply | Report Abuse | Link to thisI wonder if Professor Hawking may have Multifocal Motor Neuropathy with Conduction Block (MMMNCB) rather than Motor Neurone Disease? MMMNCB can mimick MND but carries a better prognosis and is potentially treatable. MMMNCB can be tested for by electrodiagnostic tests. Unfortunately these tests were in their infancy at the time of Professor Hawking's initial diagnosis. Although it is probably too late to test for MMMNCB now I wonder if Professor Hawing has ever been tested for it?
Reply | Report Abuse | Link to thismany thanks for your help KSama, I am so happy :D
Reply | Report Abuse | Link to this"Experts can never summon the scientific honesty to say, 'I don't know'. By his own stringent scientific code and criteria, there's no basis for him to dismiss the possibility."
Reply | Report Abuse | Link to thisActually, there is a basis for it. Multiple studies have discounted positive outlooks as a predictor of survival in cancer. There's a good write-up about them at http://scienceblogs.com/insolence/2007/10/does_a_positive_attitude_prolong_cancer.php.
This long time of life is one mytery because this disease is mortal.
Reply | Report Abuse | Link to thisthe doctors don t know why the dr. Stephen be alive.
How may other victims of ALS have that kind of care? Maybe a clinical study relating these variables should be undertaken
Then I shall rescue what little dignity I can from a losing argument and say.. "Fine then, I'm wrong.."
Reply | Report Abuse | Link to this(Curse Youuu!)
Having lost a sister to ALS, I know more than a little about the disease, but not that much. Ultimately, an ALS diagnosis is symptom based; neurologists do not immediately conduct biopsies to see if specific neurons are wasting away. Thus, patients could have multiple causative factors that present as "ALS". (It can run in some families, and may be caused by environmental factors) Professor Hawking, like my sister - who lived ~17 years - developed it early. Thus, whatever caused the loss of his motor function may have been offset by another protective mechanism. It has certainly been better for our species that he has survived for so long, whether he feels his imprisonment was worth it is another question.
Reply | Report Abuse | Link to thisdbtinc said: "do you think that just maybe that superb round-the-clock "best of" medical care might have had something to do with it?"
Reply | Report Abuse | Link to thisDo you think, just maybe, you would have the expert answer to this question if you read as far as the 5th question in the interview? (sarcasm alert for your light mind)
Dickon, learn about different ways to compute/express "average" If dr quoted median, then it means exactly what he said.
Reply | Report Abuse | Link to thisStart with: http://en.wikipedia.org/wiki/Average
hello again, there are other scientist I can write to ?
Reply | Report Abuse | Link to this"Travis Brown, 12, is the second child to receive deferiprone in an FDA-approved clinical trial to treat NBIA—Neurodegeneration with Brain Iron Accumulation. He is now able to move his arms and sit in a wheelchair, rather than lie in a wagon"
Reply | Report Abuse | Link to thishello KSama, are there another scientist I can write to ?
Reply | Report Abuse | Link to thiswhy answer in me not, please, this is a important
Reply | Report Abuse | Link to thisWhereas u have to explain a sarcasm (even for the poor ol "light-minded")...better not to use one. LOL.
Reply | Report Abuse | Link to thisHe, like all of us wants to know how the story ends and the only way to accomplish that is to be there for the ending.
Reply | Report Abuse | Link to thisHope to see you there Stephen, hang on as long as it takes.
Dr. Hawking's condition seems ripped from the pages of a sci-fi story. Brilliant scientist keeps devoting more and more of his brain power to problem solving by sacrificing motor functions.The fact it does not compromise his breathing or digestion makes it seem that there is an element of control. That he seems content in his skin, and does not fixate on a cure makes me think Dr. Hawking is an aberation who prefers intellectual freedom to personal mobility.
Reply | Report Abuse | Link to thisMaybe he is an idle dreamer, of the highest order.
I don’t know why I have lived so long with ALS, but I do know one thing. Since I was diagnosed in 1981, it has been critically important to stay open to the lessons that ALS has been teaching me and to pass them on. In essence, the presence of death has become my great advisor. I now have a much clearer vision of what’s important and what really matters, knowing that we can be healthy one minute and dying the next, here one minute and gone the next. Embraced in this awareness, I am more able to seize the day and fully live in the wonder of the moment.
Reply | Report Abuse | Link to thisI also look at life through a very special lens. ALS has humbled me and forced me to give up the illusions of perfection and control. It has brought home how crucial it is to accept with compassion all of who I am and who you are. It has given me a prospective of how it is possible to live a magnificent life even if infinitely flawed or wounded. I share the lessons with my clients and students about the dichotomy of how fragile we are and yet how powerful and enduring we can be. I offer myself as living proof that real transformation and ‘beating the odds’ is always possible, and that hope is the engine of change. I'm guessing that Stephen Hawking would too.
I think he's referring to the longevity of ALS patients, not to people in general.
Reply | Report Abuse | Link to this"do you think that just maybe that superb round-the-clock "best of" medical care might have had something to do with it? "
Reply | Report Abuse | Link to thisStephen Hawking has been, and is being, treated by the service described by Sarah Palin as "evil" - the British national Health Service.
Well said Brandon. As an "expert" in medicine, I would imagine you would not make it a point to undermine an entire field within the healthcare industry (let's see...mental health was it?). Well I am glad this guy has cleared it up for us...the century old debate of nature versus nurture can finally be put to rest!
Reply | Report Abuse | Link to thisSeriously? When I read this statement I thought it was a joke. I hope he's not involved in the research side of things. If he is, might I suggest SPSS? It's the latest innovation for the statistically challenged.
Reply | Report Abuse | Link to thisAre you working with the same kind of statistical analysis as this "doc"?
Reply | Report Abuse | Link to thisAnd many other studies have shown that a positive outlook can slow the progression of the patient's disease. It may not be a cure, but the benefits of keeping a healthy state of mind should not be written off so easily. It his opinion and he is entitled to that, but to say science backs his statement is naive. The psychology of science is unattainable. We are not one entity, but individuals who are affected differently by our environment and our emotions.
Reply | Report Abuse | Link to thisI absolutely love your outlook on life and believe it has everything to do with why you are still here to share with us your wonderful story. I commend you for your strength, your wisdom and your beautiful heart. I do not have a disease or any big difficulties in my life and yet, I find it hard to put on a smile most days; I find the world to be cruel and often unfair. But you, you are nothing like me. You can find beauty and happiness when you are living with a disease that IS cruel and unfair. So again, I commend you and your amazing outlook on life. Never forget, the smallest gesture often make the biggest impact. Thank you.
Reply | Report Abuse | Link to thisönemli bilgi asks:
Reply | Report Abuse | Link to this"how can I write to a scientist?"
First determine the scientific discipline your query falls into. Now google that field and determine who is involved in the research you are interested in and what university they work with. Now google the university for faculty members to obtain contact information. Now, compose an e-mail which outlines yourself, reason for inquiry and why it is important to you. Be polite and interested (keep it short) and most scientists will respond, if they think you are genuine.
Some scientists are extremely busy, so don't expect an instant answer. If your e-mail merely expounds your own far out theories, don't expect any answer at all. Hope this helps. GK
I hope I don't sound too ridiculous with this thought.
Reply | Report Abuse | Link to thisHas anyone looked at Dr. Hawking's slow progressing ALS as a quantum phenomenon? Really, what if living only in his mind, years on end, conceptualizing and reasoning the conditions around, near, and in a black hole allowed him to experience a benifit of quantum entanglement. To simplify; what if he used the gravity of black holes to slow the progress of his condition? I am not suggesting he was conscious of the effect and mindfully utilized it himself; it just happened.
I forgot to add this to the previous post; this is just a thought experiment. Let us not degrade into derision or insults. Let's just discuss the thought as a thought.
Reply | Report Abuse | Link to thisI am interested to know what medicines does he take? Has he done any specific dietary changes?
Reply | Report Abuse | Link to thisThe couple of ALS patients I've encountered in life, I've seen get excellent care, both with insurance and without. Families take care of their own, and the patient dies before the family burns out -- and/or before the money or coverage runs out. The short survival period for ALS means less resources used in total, so anyone with insurance can get taken care of -- but ALS patient care is intensive. I don't think there are any actual treatments for this disease, so the idea of "superb, best-of care" means being able to afford more people on the payroll to wipe your butt quicker? Maybe get to use Charmin Wet Wipes instead of dry Scott Tissue? I don't think money (or level of care for that matter) makes much of a difference with the dismal ALS survival rates. 2 years typically? Does anything else really matter at that point? Sorry I couldn't be more sarcastic...
Reply | Report Abuse | Link to thisI believe there are two, related errors in this article.
Reply | Report Abuse | Link to thisFirst, I think the author meant to say "progressive bulbar palsy" in describing one type of ALS. Second, "progressive supranuclear palsy" is an entirely different disorder and unrelated to ALS. ALS is a neuromuscular disorder. PSP is a neurological disorder.