Is It Really ALS?

by Margaret Wahl on Tue, 2003-04-01 11:56
Dr. Miller Tim Miller

"How do you really know I have ALS? Couldn’t this be something else?"

It’s a question that neurologist Tim Miller, neuromuscular disease specialist at Arizona Health Sciences Center in Tucson, where he sees patients at the MDA/ALS Center, often hears.

"When patients come in very early, the chance for misdiagnosis is greater," Miller says. "But as patients progress, there’s a significantly reduced chance of misdiagnosis."

He cites an Irish study published in Archives of Neurology in January 2000 that found that 32 out of 437 people (7.3 percent) between 1993 and 1997 were mistakenly told they had ALS.

Still, doctors admit that most ALS (with the exception of those few cases that are clearly genetic) is still diagnosed largely by excluding other conditions. There’s no specific blood test, scan or any other procedure that definitively says: "This is ALS and nothing else."

Diagnostic criteria

To help clarify things, in 1990, at a World Federation of Neurology meeting in El Escorial, Spain, experts decided on a set of criteria for ALS diagnosis. These guidelines, which were revised in 1998, are known as the El Escorial criteria, and remain the standard in the United States and Europe.

You can read these guidelines at, but they can be boiled down to a fairly simple statement: A definite diagnosis of ALS can be made when there are clear signs of damage to both the upper (brain) and the lower (brainstem and spinal cord) motor neurons; and when the neuron damage can’t be explained by the presence of any other abnormalities.

Those other abnormalities must be sought with extensive testing — physical examinations, blood tests, electrodiagnostic studies and sometimes muscle biopsies.

Both kinds of motor (muscle-influencing) neuron damage can be demonstrated by physical exam and by electrodiagnostic testing. The latter involves reading the electrical signals from muscle and nerve cells and looking for patterns indicating damage.

"A fair number of patients never reach the definite [El Escorial] criteria, at least on presentation," Miller says. But most people with ALS, he says, eventually do show signs of both upper and lower motor neuron degeneration.

Because signs aren’t always present immediately, El Escorial criteria say that patients should be re-examined about every six months when ALS is under consideration.

If, after extensive testing, only upper motor neuron damage is noted, the patient is said to have primary lateral sclerosis — and may or may not develop full-blown ALS.

If, after equally extensive testing and time, only lower motor neuron damage is found, the diagnosis is progressive muscular atrophy, which can but won’t necessarily eventually meet ALS criteria.

Other neuromuscular diseases

But what about those "other abnormalities" that doctors search for in the patient suspected of having ALS?

Miller assures his patients, "We would love to be able to tell you that you don’t have ALS." And that does happen sometimes.

Almost all patients suspected of having ALS undergo imaging studies, such as MRI or CAT scans, he says. "We’re looking for signs of local [nonsystemic] problems." These problems include compressions of the nerves as they leave the spinal cord, caused by tumors, bony malformations or vertebral disks that have slipped out of place. Such compressions cause "local" or "regional" anatomical problems, and they usually can be readily seen on an MRI scan.

Disorders of muscle, such as some late-onset muscular dystrophies, inclusion-body myositis and some metabolic muscle diseases, can overlap with ALS in some of their symptoms. But weakness is generally where the similarity ends. Muscle biopsy studies, DNA tests and electrodiagnostic testing reveal important differences.

Some nervous system disorders, such as spinal-bulbar muscular atrophy (SBMA, or Kennedy’s disease) can sometimes look like ALS, but SBMA doesn’t cause upper motor neuron damage, and it can be tested for in a blood DNA test.

Infectious, autoimmune or other disorders

Infectious diseases like AIDS, Lyme disease and the late stages of syphilis can sometimes affect the nervous system in ways that resemble ALS, but these have other signs. They generally behave like infections, and blood tests for them are usually clearly positive. They have a variety of systemic symptoms not seen in ALS.

Miller says lead and mercury poisoning can also, on occasion, mimic ALS. If the patient gives an occupational history that suggests exposure to these heavy metals, he certainly checks their levels. But, he notes, mercury intoxication usually causes behavioral changes and incoordination, while lead poisoning decreases the number of red blood cells — none of which is characteristic of ALS.

Some autoimmune diseases, in which the immune system mistakenly attacks the body’s own tissues, can be confused with ALS, at least early in the diagnostic workup. The most common source of such confusion, Miller says, is a disease called "multifocal motor neuropathy." In this disorder, the immune system attacks the nerve fibers that run from the spinal cord to the muscles. Specific proteins called anti-GM1 antibodies, made by the immune system to attack the nerve fibers, show up in the blood of MMN patients. They’re almost never seen in ALS.

Miller says there are many disorders that can look like ALS superficially, but they have features that make them different from ALS. It’s important to look for those features, which may not be obvious at first.

On the other hand, says Miller, if a competent neuromuscular specialist has ruled out all likely causes of motor neuron degeneration except ALS, then that’s most likely the right diagnosis. These days, Miller says, he doesn’t see too many mistakes.

"It’s actually more common for patients to be told they have something else when they really have ALS," he says. "Occasionally patients are referred for other problems when they really have ALS. That happens more often than patients who are referred for ALS who turn out not to have it."

A caveat is that the doctor should be "well trained in the diagnosis and treatment of motor neuron disorders," Miller says, adding, "MDA has made it certain that every patient can visit [such a doctor], even if their insurance doesn’t cover it. There are a lot of us that can be sought."

Additional reading

For detailed discussions of ALS compared to Lyme disease, see "ALS Doesn’t Masquerade as Lyme Disease" (March 2003). For a discussion of SBMA and ALS, see "Mistaken Diagnosis?" (August 1997).

Margaret Wahl
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