A mind untouched: An ALS expert explains how the disease affects various patients differently--and leaves some mentally debilitated by dementia.
Image: Wikimedia Commons/rubberpaw
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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30 Comments
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-� peptide (A�) 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)