Standing Tall

By Bruce H. Dobkin|Thursday, September 01, 1994
I was talking with a neurology resident in the hallway when a tall man with a peppery gray beard walked toward us in step with a woman about his age. As they passed, the top of her head was about level with his shoulders, but when I glanced at them a few moments later, she seemed to have shrunk several inches. Her head now barely reached his armpits. When they turned to enter my examination room, I saw why. The woman was leaning so far forward that the strand of large pearls around her neck dangled away from her chest. Eyeing her husband as a plumb line, I guessed that her tilt roughly matched that of the Tower of Pisa.

What’s that about? Parkinson’s? asked the resident.

I shrugged. I guess she’s my next patient. I better get in there before she keels over like a log.

To my surprise, I found her sitting quite upright beside her husband. I introduced myself and asked how I might help them.

Mrs. Toga explained that she had developed a tremor in her right hand about 30 years ago. You know, I always thought it was psychosomatic, she said, because it began when I decided to go back to school after the kids went off to college. I think I was afraid to go back and try to get my degree. She had succeeded in earning a master’s in library science and had served as head librarian at a community college until five years ago, when she turned 68.

Mr. Toga interrupted. The real problem as I see it is that you bend over when you walk.

Yes, she agreed. When I say that this shaking has gotten a little worse over the years and I have trouble standing up, my doctors keep telling me that I have Parkinson’s disease. About eight years ago, a prominent doctor in Beverly Hills--for what that’s worth--watched me walk, heard about the tremor, and told me to take medication for Parkinson’s.

Did it help?

I refused to fill his prescription. He never really listened to what I had to say. And he didn’t examine me or explain his diagnosis. Besides, I read some things about Parkinson’s and decided that I did not have it.

I already liked this woman. She was going to wring out of me answers she could believe. As I talked with Mrs. Toga further, I learned that ten years ago a co-worker at the library had pointed out to her that she stooped when she carried books. This had upset Mrs. Toga, who prided herself on her military bearing. When she was a child, her father had always told her to stand tall like a soldier, so she and her sister had marched around the house like a couple of Prussian militiamen.

She fought off the bent-over posture by throwing back her shoulders. But on long walks with her husband she gradually found the tendency to stoop impossible to resist. At first she began to droop after walking a mile. But a few years ago she was slumping forward after strolling only a block; in the past year, within 100 feet. By the time the leaning set in, she added, she always felt short of breath. Yet she wasn’t aware of having any lung or heart disease that would make her gasp for air after only modest exertion.

Do you feel weak when you stand or walk?

I get tired, she offered, but I don’t think I’m weak. I still go to the gym to bicycle and lift some weights.

Nothing she told me pinpointed a problem in her nerves, muscles, or cardiovascular system. I asked her to walk down the hall. When she started, she walked quite regally for a woman in her early seventies. But after about 50 feet her trunk began to tilt forward, and by 100 feet she had to throw her head back just to be able to see ahead. Then she put her hands in the front pockets of her baggy slacks and straightened up a bit. I asked if that helped.

I push against my thighs . . . and it seems to prop me up, she said breathlessly. Her breathing had become rapid and shallow, and her heart was beating fast. Of course, after a while my arms get tired.

Her coordination and reflexes were normal, and there was no hint of heart or lung disease. I could tell that the tremor in her right hand was the kind that often runs in families and worsens with an activity such as writing. That ruled out Parkinson’s, which causes a tremor that is most noticeable at rest. So far, Parkinson’s was the one disease I was sure Mrs. Toga didn’t have.

I asked Mrs. Toga to clasp her hands in front of her chest and raise her elbows to the side. When I pressed down on them to break her resistance, I couldn’t. So her muscle strength was good. I then asked her to clap her hands overhead 15 times to see if her strength ebbed easily. She began briskly and smoothly, drawing her hands from her sides up over her head, but by the last few tries she had to work to throw her arms up. I immediately retested her shoulder muscles. This time I was able to break her resistance with just two of my fingers pressing down against her raised elbows. I then asked Mrs. Toga to sit down and cross her right leg over her left leg 15 times. I easily broke the strength of the right leg, but I could not budge the same group of hip muscles of her left leg. When I tested her two minutes later, I failed once more to overcome the muscles in her shoulders and, this time, her right hip.

So Mrs. Toga had strength in her muscles, but it waned extremely rapidly. That was the clue I needed. She wasn’t getting tired in the sense of feeling beat and wanting to plop on the sofa. She was probably stooping and getting short of breath because the back muscles that straighten the spine and the muscles that expand the chest wall and work the diaphragm for breathing tired quickly. Somewhere along the pathways for the control of these muscles--indeed, all her muscles--messages were being interrupted.

Perhaps because of damage to nerve cells in the brain there weren’t enough nerve fibers to bear a sustained flow of electric signals to the spinal cord. However, since the rest of Mrs. Toga’s mental functions appeared normal, a brain disease seemed unlikely. I suspected that the problem lay in getting the signal directly to the muscles. Perhaps something was impairing the transmission of signals from nerve cells in the spinal cord to muscles in the chest wall, arms, and legs.

So what provocateur had turned my proud lady into a leaning tower?

Many diseases can damage nerve cells and muscle, causing weakness that increases with exertion. But only one disease classically produces dramatic fatigability. I explained to Mrs. Toga that I was pretty certain that myasthenia gravis was the cause of her obscure symptoms.

In patients with myasthenia, the immune system mistakenly makes antibodies that prevent muscles from contracting properly. Normally muscles contract after nerve cells in the brain and spinal cord signal the release of a fleet of molecules of acetylcholine, or Ach, from nerve endings that run out from the spinal cord. These chemical messengers travel across a tiny cleft and dock at receptors along the surface of a muscle fiber. When Ach molecules attach to the receptors, they activate the muscle fibers. The force with which a muscle contracts is controlled by how many volleys of Ach it receives.

The problem for myasthenics is that their bodies produce antibodies that latch onto Ach receptors on the muscle surface, preventing Ach molecules from docking. If a muscle doesn’t get bursts of Ach, it cannot sustain a contraction. When the eye muscles are affected, the patient sees double. When muscles in the throat are affected, a patient cannot swallow easily and must often be fed through a tube. The disease can weaken some or all of the muscles of the body. In the most severe cases, the patient becomes paralyzed and can breathe only with the aid of a respirator.

Fortunately there are drugs that can help make each fleet of Ach that arrives in the nerve-muscle junction last longer, which gives the Ach molecule a better chance of docking. Although that strategy is no cure, the patient is stronger and tires less easily. I gave Mrs. Toga pyridostigmine, one such medication. When I tested her about 30 minutes later, I could not break her resistance when she repeated the overhead claps and leg crosses. The drug worked.

Yet she still leaned forward and got short of breath after walking just 150 feet. Other diseases sometimes responded to the drug, so I suggested some tests to verify my diagnosis. Delighted that we had identified a disease that matched her symptoms, Mrs. Toga agreed to the tests as well as a drug trial. I prescribed a modest dose of the drug three times a day.

When she returned two weeks later, she said that the drug had not lessened her leaning or her breathlessness very much. She still could not vacuum or mop continuously or go for long walks. A lung specialist had found no other medical reason for her shortness of breath.

I was puzzled. Mrs. Toga’s blood tests showed no sign of antibodies to the Ach receptors. And several high-tech tests of the electrical activity of her nerves and muscles failed to reveal the typical abnormalities that myasthenia gravis produces. Indeed, tiny electrodes popped through the skin to record the electrical activity of resting and contracting muscle hinted that the weakness originated in the nerve cells in the spinal cord. I was going to have to let go of the diagnosis of myasthenia gravis. I explained my new uncertainty.

Mrs. Toga smiled. I feel that we’re making progress. At least I know it isn’t all in my head.

Since the test results didn’t point to a specific diagnosis, I decided to get as close a look at the problem as possible. That meant a muscle biopsy. Over a dozen unusual hereditary and acquired diseases could produce the picture of Mrs. Toga’s illness that was evolving. Muscle was the one tissue we could get at that might provide a clue about what was going wrong in the spinal cord.

A few days later a surgeon cut out a piece of muscle half the size of a pencil eraser from a spot along Mrs. Toga’s back muscles and another from her deltoid, at the shoulder. Under the microscope, normal muscle fiber has a monotonous cobblestone pattern. But Mrs. Toga’s muscle showed bits of dying muscle fiber and clumps of shrunken fibers that looked like trapezoids with sharp corners. Dying muscles meant that the nerve cells nourishing them were dying. But the strange-looking clusters told me that some of the healthy neurons had sprouted new twigs to rescue the starving muscle fibers and arrest their atrophy.

The most likely mechanism for Mrs. Toga’s insidious disease was the gradual degeneration of nerve cells within her spinal cord. From what I saw in my exams, Mrs. Toga’s trunk and the muscles that powered her breathing probably had the fewest surviving nerve cells. Her arms and legs were better off, but if overtaxed by repeated exertion, their nerve cells, too, began to fail. So far, the loss had been slow enough that muscle and nerve regeneration helped protect her. But for how long? I gave the couple my latest best-guess diagnosis.

Well, I just wanted some knowledge about what’s wrong, said Mrs. Toga. That’s most important. If there’s something to do for it, terrific. I’d like to make it to 80 in good health, so tell me what’s going to happen.

The degeneration might have begun more than 10 years ago, when her stooped posture at the library had been noticed. It might even have started 20 years ago and crept along at a glacial pace. Since Mrs. Toga was the type of person who quietly compensated for anything that interfered with her activities, precisely dating the onset was impossible. So what would I call her disease? The all-too-common motor neuron disease known as amyotrophic lateral sclerosis, or Lou Gehrig’s disease, runs its course far more rapidly. Most people watch their muscles wither within two to five years; complete paralysis follows.

Though I couldn’t be certain, Mrs. Toga did not seem to have this form of nerve cell degeneration. She may have inherited a biochemical defect that doomed the spinal neurons. We would never know, because her parents had died in an accident in their fifties, before either might have experienced any symptoms. At some point in the last few years, the supply of nerve cells that fed signals to the muscles in her trunk had dwindled to a critical number. What was left had to work harder and longer, so the muscles tired easily. Even so, making it to 80 seemed within reach.

We decided to stick with the medication for myasthenia gravis for when she had to be active. For short periods of time, the drug prolonged the action of Ach at the nerve-muscle junction, where the disease had altered the muscle’s ability to respond normally. It might give her the reserves she needed to go shopping or enjoy an evening out. She could also continue to exercise to help maintain her strength.

A month later, my wife and I found ourselves standing next to the Togas at the theater during an intermission. As we exchanged critiques of the show, Mrs. Toga stood with both hands in her pockets, imperceptibly pinning herself upright. She coped so gracefully with her dwindling reserves that it was easy to see why she had gone years without being diagnosed accurately. No one would guess that she was struggling against the inexorable erosion of her strength and stamina. It was a masterful performance.
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