Annals of Neurosciences, Vol 16, No 3 (2009)
Annals of Neurosciences, Volume 16, Number 3, July 2009
Commentary on Professor Stephen Hawking’s disability advice
Stephen Hawking is the world’s best known theoretical physicist and also its communicator of cosmology and astrophysics to the general public. His books, “A Brief History of Time” and “The Universe in a Nutshell”, are not only eminently readable but also explain the inexplicable in a way that even a layman can understand.
Professor Hawking is Lucasian Professor of Mathematics and Fellow of Gonville and Caius College in Cambridge. He is a Fellow of the Royal Society, the United Kingdom’s highest accolade in the sciences, and also a recipient of the United States highest civilian award, the Presidential Medal of Freedom. For nearly four decades he has led the field of research into theoretical physics, particularly general relativity and black holes.
He has attained these extraordinary heights despite suffering from progressive paralysis due to what is called motor neurone disease (MND) in the UK and amyotrophic lateral sclerosis (ALS) in the USA. His fame in the field of astrophysics has made his name especially significant to patients with ALS. The fact that he has lived 46 years with the disease and yet achieved so much is a beacon in the gloom that the diagnosis of ALS casts over every patient and family. Professor Hawking demonstrates that a patient with the right mind-set can overcome loss of almost every voluntary motor function and still have a happy and productive life.
Professor Hawking’s personal description of his life with the disease is a unique document. He writes that the first symptoms of ALS appeared when he was 20 years old. He underwent investigations to find why he had fallen a number of times and say: “[T]hey didn’t tell me what I had ...... [They told me] that I was an atypical case.” Even today it is common that neurologists do not tell the patient the diagnosis of ALS until they are absolutely certain and by that time many patients have already made their own diagnosis. One reason for this reluctance is that the doctors do not like to reveal to the patient that he has a progressive incurable disease. Another reason is that slow worsening of the symptoms and signs of motor neuron degeneration is a requirement for establishing the diagnosis. The average interval between the first symptoms and diagnosis is about 14 months in the USA.
The average duration of survival of a patient with ALS from first symptoms ranges from 18 to 36 months, which is why the diagnosis is usually considered a death sentence. However, about 20% of patients survive longer than 5 years. My longest surviving patient has had the disease for more than 40 years and was able to work into his mid 70’s. There are reports in the literature of a small number of patients with ALS that was diagnosed by all established criteria who actually stabilized and partially recovered.1,2 1 have personally seen five such patients in whom the disease remained stable for years thereafter. The peak age of onset of ALS is 50 to 60 years. Few cases begin before age 30, which was one of the reasons why Professor Hawking’s doctors told him his case was atypical. My youngest patient is a young woman whose symptoms began at the age of 15.
Many neurologists refuse to accept the diagnosis of ALS if symptoms begin at a young age, if the disease is extremely slow and if the patient survives for decades. Therefore many have questioned whether Professor Hawking really has ALS, suggesting rather that he has adult-onset spinal muscular atrophy.
Very little information about Professor Hawking’s neurological condition has been available to the general medical community until he wrote the piece: “Dr Stephen Hawking’s disability advice”. In this he provides clear support for the diagnosis of ALS. The symptoms first began in the lower limbs causing falls; this suggests upper motor neuron slowness of movements. Publicly available pictures show progressive wasting of muscles, indicating progressive lower motor neuron degeneration. He describes his speech as becoming progressively more slurred to the stage of being almost unintelligible for a period before the age of 43. At that time he developed pneumonia and had a tracheostomy. Publicly available pictures indicate continuing progression of his muscle wasting since that time. He is now age 67 and recently had a further bout of pneumonia.
All these facts are compatible with the diagnosis of MND/ALS. Research criteria for the diagnosis of ALS require the presence of evidence of both lower and upper motor neuron disease.3-5Unfortunately nothing in Professor Hawking’s writings or in what is available to other than his personal physicians tells us about whether at anytime he had signs of upper motor neuron disease. One would be looking for evidence of abnormally brisk and pathological reflexes, increased tone and spasticity. The diagnosis of adult-onset spinal muscular atrophy seems to be unlikely to me because this condition rarely involves bulbar function, that is, speech and swallowing, which is frequently impaired in patients with ALS.
“Dr Stephen Hawking’s disability advice” helps convince me that he truly has ALS, albeit with the uncommon features of early onset and very slow progression. Release of information about the neurological examination during the early years of his condition could help further the clarification of the diagnosis.
Professor Hawking had a tracheostomy at age 43 and has survived on a ventilator for 24 years. Only 5 to 10% of patients in western countries have a tracheostomy, and for most it is an emergency procedure that follows respiratory failure and pneumonia. Few American or British patients with ALS accept tracheostomy as an elective procedure to avoid respiratory failure and death, citing concerns about poor quality of life as the main reason. This is to be compared with Japan where 70% of patients have a tracheostomy when respiratory failure threatens and survive for prolonged periods on a ventilator. There are two reasons for the difference. First is the fact that the medical culture in Japan is more paternalistic than in western countries, so that patients are often not asked if they want the procedure but rather are told that it is now time for them to have it. Second is the fact that the Japanese government provides free healthcare for ventilator-dependent patients at home, while this is virtually not available in the USA or UK.
The cause of ALS is still not known with certainty. In about 5 to 10% of cases there is a family history of the condition and research has revealed genes that are mutated and responsible for the disease in about a half of the families. However, more than 15 years of neurogenetic research has failed to provide any clue to the environmental cause(s) of the 90% of cases that are non-familial, that is, who have sporadic ALS. Recent research, some of which was presented at the 19thInternational Symposium on ALS/MND in Birmingham, UK, in November 2008 and will be more fully described in a forthcoming Supplement of the Journal ALS6, suggests that a neurotoxin produced by cyanobacteria is a major factor responsible for sporadic ALS.
Cyanobacteria are ubiquitous and none of us can escape exposure. Many species of cyanobacteria produce a neurotoxin, β-methylamino-L-alanine (BMAA), a known glutamatergic excitatory non-protein amino acid. There is increasing evidence that BMAA enters the brain of susceptible individuals causing ALS and perhaps other age-related chronic neurodegenerations. The hypothesis of Paul Cox and others6-8 is that susceptible individuals cannot prevent BMAA from being mis-incorporated into brain proteins, where it constitutes a reservoir that continues to recycle, causing repetitive episodes of neuronal damage and eventually death of motor neurons. If this hypothesis proves to be correct, it will open the door to the identification of susceptible individuals, to the possibility of excluding the causative toxin from their diet, preventing its mis-incorporation into brain proteins and eluting already-incorporated BMAA from the brains of patients suffering from ALS.
Professor Hawking writes eloquently about his approach to life with ALS. In fact, he indicates that the diagnosis of the disease gave him the jolt that launched his eminent career. Several of my patients have also found their true calling in life only after having received the diagnosis of ALS.9 He also describes the excruciating process by which he used a spelling card to communicate with his loved ones and caregivers, indicating with movement of his eyebrow each letter of the word he wished to “say.” He then writes about the various upgrades of the use of a micro-switch, computer software and a voice synthesizer that have made it possible for him to write books, give talks and continue his professional and personal life.
For those who have not witnessed patients using spelling boards and computer-assisted devices, the latter process may seem a good replacement for normal speech. However, for those of us who speak at 300 words per minute and type at 100 words per minute, it may come as a shock to realize that Professor Hawking can write at a maximum of about 6 words per minute. It is difficult to conceive of how Professor Hawking, with his brilliant, fertile and quick mind, could have the patience to communicate so slowly. Perhaps only a man, who thinks in terms of tens of billions of years of astronomical time and whose mind is adept at contemplating complex equations, would have the perseverance to do what he has done.
Though at a more mundane level than his achievements in conceptualizing general relativity and black holes, in my opinion Professor Hawking’s victory over ALS is no less deserving of the award of a Nobel Prize.
doi: 10.5214/ans.0972.7531.2009.160303
Walter G Bradley, DM FRCP
Professor and Chairman Emeritus
Miller School of Medicine
University of Miami
References
1. Miyoshi K, Ohyagi Y, Amano T, et al. A patient with motor neuron syndrome clinically similar to amyotrophic lateral sclerosis, presenting spontaneous recovery. Rinsho Shinkeigaku 2000; 40 (11) : 1090-5.
2. Tucker T, Layzer RB, Miller R G, ef al. Subacute, reversible motor neuron disease. Neurology 1992;42(11 ):2229-30.
3. Brooks B R. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/ Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci. 1994;124:96-107.
4. World Federation of Neurology Research Group on Neuromuscular Diseases Subcommittee on Motor Neuron Disease. Airlie House guidelines. Therapeutic trials in amyotrophic lateral sclerosis. Airlie House “Therapeutic Trials in ALS” Workshop Contributors. J Neurol Sci. 1995; 129 Suppl:1-10.
5. Brooks B R, Miller R G, Swash M, ef al. El Escorial revisited: revised criteria forthe diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1 (5):293-9.
6. Cox P A, Bradley W G. ALS and the BMAA hypothesis. ALS 2009.
7. Murch S J, Cox P A, BanackS A, SteeleJC, Sacks OW. Occurrence of β-methylamino-l-alanine (BMAA) in ALS/PDC patients from Guam. Acta Neurol Scand 2004;110(4):267-269.
8. Murch S J, Cox P A, Banack S A. A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proceedings of the National Academy of Sciences 2004; 101:12228-31.
9. Bradley W G. Voyage into the Sunset: The Odyssey of Gib Peters. 2009. (in preparation).
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