Famous British physicist, Stephen Hawking, recently announced that he plans to go to space. He will start by experiencing weightlessness on the “vomit comet” – a plane that can fly in a parabolic arc and provide about 25 seconds of free fall at a time. Stephen Hawking suffers from motor neuron disease – he lives his life in a wheelchair and at this point has barely any motor function. That he still dares to dream of going to space is a testament to his intellectual fortitude, courage, and will.

The story has prompted many questions to me (since this is one of my areas of expertise) about what the nature of his motor neuron disease is. Although I do not have access to Dr. Hawking’s personal medical information, I can discuss the issue in general – which turns out to be quite an interesting medical story.

First, motor neuron disease is not a disease. But to understand this you have to have a working definition of what a disease is. Admittedly, the medical community often uses the term loosely, adding to confusion. Although the definition is fuzzy at the edges, basically a disease is a specific malfunction of one or more parts of an organism. In technical terms, it is a pathophysiological entity. The malfunction must also cause some negative effects – the signs and symptoms of the disease. Symptoms are anything a person with a disease experiences, and signs are those things that an examination would reveal about the disease. So pain is a symptom, while increased deep tendon reflexes on neurological exam is a sign.

Diseases can have a variety of causes. Genetic mutations can cause disease by either resulting in the lack of a protein needed for normal function, or an improperly functioning protein, or perhaps even a protein with new and toxic effects. Genetic mutations can also cause a person to develop abnormally, resulting in anatomical defects. Nutritional deficiencies can cause disease as those biological functions dependent upon a specific deficient nutrient will function poorly or not at all. Toxins may kill certain cell populations or block the function of specific enzymes. Infectious agents (bacteria, viruses, fungus, amoeba, parasites) can cause disease by damaging tissue, releasing toxins, causing inflammation, and causing abscesses which put pressure on vital structures. Neoplastic diseases (cancer) are caused by a specific cell population that starts to reproduce without limit, caused by a mutation that disrupts the normal mechanisms in place to restrict tissue growth. Degenerative diseases are caused by cell populations or anatomical structures that break down over time. Autoimmune diseases are caused by a person’s own immune system having faulty regulation, so that it begins to target their own tissue, causing inflammation and tissue destruction. Environmental diseases are caused by exposure to unfavorable environmental conditions. Metabolic diseases are caused by a biochemical malfunction – usually an excess or insufficiency of some process that requires some balance or homeostasis for normal functioning. Vascular disease results from insufficient or blocked blood flow to a tissue, causing malfunction or damage. Trauma can cause disease and malfunction by damaging tissue directly. And finally, we use the term “idiopathic” to refer to those diseases for which the cause is unknown.

This seems like a pretty long and all-inclusive list of medical ailments. So, what is not a disease? Well, it is common for a disease to first come to medical attention because two or more patients present with a similar list of signs and symptoms that take a particular course over time. This becomes recognized as a “syndrome” (often named after the person who first recognized it, or a famous person with the syndrome, or a simple description of the major signs or symptoms). So, to be clear, a syndrome is simply a constellation of signs and symptoms that are seen to occur together and follow a predictable course. A disease, however, is the underlying pathophysiological cause of the syndrome. (To add to the confusion, geneticists use the term “syndrome” to refer to all the signs and symptoms of a specific genetic mutation or chromosomal abnormality.)

Sometimes a syndrome is a syndrome because it is one specific disease, and the syndrome is upgraded to a disease when the underlying cause is elucidated. However, this is not always the case. It is possible for a syndrome to have more than one cause – to represent more than one underlying disease. For example, the signs and symptoms of a syndrome may result whenever a specific cell population is damaged, but there may be many specific diseases that can cause the damage. So a syndrome may be many diseases that all look the same because the end result is the same.

Another term that is used to label medical conditions is a “disorder.” A disorder occurs when some biological function is sufficiently out of the parameters of optimal functioning that it causes measurable harm or discomfort to the person – but without an identifiable pathophysiological disease. I think an excellent example of this is dyslexia. Dyslexics have very low reading aptitude, to the point that it is difficult for them to read and to function is a literate society. They do not have brain damage or disease, but that part of their brain responsible for the ability to read is hard-wired in such a way that they have very poor reading ability.

Migraine is also another excellent example of a disorder. For many patients with migraines there is no underlying disease. Rather, part of the brain (probably the trigeminovascular reflex) is hyperactive resulting in triggerable episodes of headache, nausea, and the other symptoms of migraine. Migraine, however, can also be considered a syndrome, since it is a collection of symptoms with many underlying causes (for example, there is at least one genetic mutation that causes migraines).

These definitions are not clean or totally objective, although they are still very useful. For example, is obesity a disease or a disorder? Is alcoholism a disease or a disorder, or perhaps a syndrome? Many patients have chronic fatigue. Chronic fatigue is a symptom – a symptom of many diseases and disorders. When this symptom of fatigue occurs and no underlying cause can be found, it is labeled as chronic fatigue syndrome. Some patients with this syndrome have been found to have chronic Ebstein Barre virus (EBV) infection – a specific disease. Further, as a clinician I find it very useful to consider the following questions: it is more useful to label someone as having chronic fatigue syndrome, or that they have the symptom of chronic fatigue from an as yet unidentified underlying disease? I think these two approaches are not mutually exclusive, as long as the former does not prevent the latter. In other words – as long as the label of “chronic fatigue syndrome” is not confused with the diagnosis of a specific disease.

Tomorrow I will apply all of this to the question of “motor neuron disease.”