TEST OF NERVE
Charcot-Marie-Tooth disease is the most common inherited neurological disorder, though most remain unaware of its existence.

by Jon Nalick

 

Kathy Hawthorne* often felt clumsy as a child. Born with knock-knees, small heels and high arches, "I always had some kind of problem running and I sprained my ankles all the time."

Over the years, however, she discovered that her awkward gait and quirky foot structure warned of more troubling problems to come.

At 27 she was diagnosed as having an inherited condition called Charcot-Marie-Tooth-a progressive disorder that ravages the nerves of the feet, legs, hands and arms. Learning that she had a disease for which there is no treatment and no cure, "was the biggest let down," says Hawthorne, now 42.

As time passed, the weakness that gnawed at her feet and calves spread.

"About three years ago, I started losing the muscles in my hand and more muscle mass in my calves. My ankles started turning inward and suddenly, I couldn't walk because I couldn't extend my knee," she says.

"It was very depressing, even though I have a personality of not being depressed," she adds.

W. King Engel, M.D., professor of neurology and pathology and director of the USC Neuromuscular Center, says that Hawthorne's experiences are typical of someone with the disease, especially in that the diagnosis came after years of low-grade symptoms that grew to be unmanageable.

"When it starts in childhood, it can be hard for parents and physicians to recognize and identify the problem. Often, the child always seems to be the slowest runner, or maybe falls down a lot and is merely labeled as being clumsy."

Named after two French and one British scientists who in 1886 first described the syndrome, Charcot-Marie-Tooth (CMT) disease is one of the most
common inherited neurological diseases, Engel says. Even though it affects 150,000 Americans, many people are unaware of CMT's existence and its effects because although the disease can be debilitating, "People don't die from it." Engel says.

"Lou Gehrig's death from ALS [amyotropic lateral sclerosis] was dramatic. And when people die from cancer, or kids suffer muscular dystrophy, it really grabs your attention. But CMT is not dramatic, even though it can have a terrible impact on a person's life," he says.

Technically CMT is not a single disease, but a group of similar hereditary diseases that cause progressive deterioration of the peripheral nerves-those branching out from the spinal cord that control sensory information and muscle function of the feet, legs, hands and arms.

CMT is an inherited condition: if one parent has the disease there is a 50 percent chance of passing it on to each child. The illness targets members of both sexes and of all ethnic groups in about the same proportions.

The most common symptoms include: numbness, tightness, burning sensations, shooting pains, muscle cramps or weakness in the affected limbs. As the illness progresses, it can also spread to the upper legs, hips and shoulders.

People with CMT tend to slowly lose normal use of their limbs as the peripheral nerves degenerate. The muscles in the extremities often become weakened because of the loss of stimulation by the affected nerves. Sensory nerve function may degenerate as well. Unlike muscular dystrophy in which the defect is in the muscles, CMT is a disorder in which the defect is in the nerves that control the muscles.

As the disease advances, structural foot deformities such as the appearance of a high arched foot and hammer toes can occur. Progressive muscle wasting leads to problems with walking, running, and balance. To avoid tripping, patients with foot problems often raise their knees unusually high, resulting in a distinctive gait. Hand function also becomes affected because of progressive muscle atrophy, making fine movements, such as writing, difficult. Loss of nerve function in the extremities can also lead to impairment of the sense of touch as well as the ability to distinguish hot and cold. Aside from pain that can make running, walking or even standing impossible, the disease can also be enough of a distraction that it routinely interferes with sleep, leaving sufferers little respite.

Although symptoms usually grow worse over time, their level of severity can vary dramatically. For example, several members of Hawthorne's extended family have the disease, but most live relatively unimpaired by the condition.

"My grandmother has it. So does my father, uncle, aunt, two younger brothers and some of my cousins-but I have it the worst. They don't have much trouble and are still active," she says.

In many cases, the disease creeps up so slowly and subtly that it may be dismissed as any number of other ailments.

"Symptoms often start out as foot pain that could be caused by numerous problems, so it is not unusual for us to see patients who have unsuccessfully tried to treat their condition with arch supports, or even foot surgery," Engel says.

Onset of symptoms usually occurs by the teens or early adult years-and pinpointing specifically when the symptoms appear can help physicians differentiate the disease from other neuropathies that have no hereditary basis.

"Nearly all hereditary neuropathies begin before age 50, so if a patient first notices clinical symptoms after age 50, it's most likely not hereditary-so we have a fairly good chance of identifying a treatable cause," he says.

Engel says that the speed of the disease progression is usually slow (a fast progression suggests something other than CMT), but regardless of how quickly it progresses, it tends to do so at a constant speed, the pace firmly established within the first several years after onset.

To establish an accurate diagnosis, physicians may perform a clinical exam, nerve conduction tests, muscle biopsies, electromyography (which examines muscle response to nerve stimulation), and draw a sample of spinal fluid.

By definition, all cases of CMT are hereditary. In some cases the cause is a known genetic defect, for example having a damaged peripheral nerve protein 22 gene. In other cases, no specific blood test pinpoints the diagnosis, but a family history of the illness will help confirm it.

Although there is no cure for CMT, physical therapy and moderate activity are often recommended to maintain muscle strength and endurance. Custom shoes or shoe inserts can help to improve gait and leg braces can prevent ankle sprains, improve gait, and reduce the amount of energy needed to walk. Corrective orthopaedic foot surgery can also help maintain mobility when medically indicated. In addition, splinting, specific exercises, adaptive devices and surgery can help maintain hand function.

Engel emphasizes that a correct diagnosis is crucial because there are many peripheral neuropathies that trigger similar symptoms that can be treated successfully. A patient who is misdiagnosed as having CMT can spend years living with unnecessary pain.

Desert Hot Springs resident Lillian Wilson, 80, was diagnosed in 1982 as having CMT and was told that she would simply have to learn to live with it. For the next 17 years, her symptoms, which included difficulty walking, poor balance and hand tremors, grew steadily worse.

"I had such great difficulty eating because of how my hands would shake, I'd be spilling stuff on myself. It was so embarrassing to eat in public and hard on my ego-and my clothes. Even at home eating was such a struggle it hardly seemed worth the effort," she says. "In my feet and legs, I'd get shooting pains like electricity."

In 1999, however, a new physician reexamined Wilson in light of medical knowledge amassed since her original diagnosis. He determined that Wilson actually suffered from a peripheral neuropathy with the tongue-twisting name of chronic inflammatory demylinating polyneuropathy (CIDP) and suggested she see Engel for possible treatment.

Engel treated her with weekly doses of intravenous immunoglobulin, hoping simply to arrest the disease's progress, but within months, it became clear she was experiencing far better results than expected. Her symptoms had begun to evaporate.

"I'm just making a fantastic recovery, well beyond what they said would happen. After six months, I can walk without a cane. I can write again, which is wonderful. I've even regained some movement in my toes, which my doctors had never seen before. It's like getting a new lease on life, it's almost like a miracle," she says.

The Neuropathy Association estimates that as many as 20 million Americans have some form of peripheral neuropathy, resulting from conditions such as CMT, kidney disease, diabetes, alcoholism, chemotherapy drugs, anti-HIV drugs and some herpes infections. Neuropathy treatments-for those conditions that are treatable-focus on either relieving the symptoms, or attacking the cause of the ailment itself. In the first case, standard pain medications can help, as can drugs such as Gabapentin that relieve pain by quieting nerves that fire when they should not.

Alternatively, physicians can sometimes target the underlying cause-specifically, the disease mechanisms responsible for damaging neurons and also the myelin-secreting Schwann cells that surround, insulate and protect neurons.
Sometimes-as in Wilson's case of CIDP for example-the mechanism causing the damage is the body's own immune system, which misidentifies neurons or Schwann cells as foreign bodies to be eliminated.

This is also what happens in Guillain-Barré Syndrome, a potentially life-threatening neuropathy that can interfere with autonomic nerves responsible for breathing. Fortunately, as with many non-hereditary neuropathies, the illness can be treated-in this case, with intravenous immunoglobulin and plasmapheresis, a process in which the fluid part of the blood, called plasma, is removed from the blood cells.

"Despite these treatments that are often successful, new, better and more convenient treatments are needed," Engel says.

In the absence of effective treatments, CMT sufferers such as Hawthorne can try to mitigate the damage with physical therapy.

"Since my knee problems, I found a physical therapist who would work with me, and watch me exercise and spend time to figure out which exercises would help compensate for my weak muscles," Hawthorne says.

She says that a regimen of stretching and workouts that focus on the upper body, abdomen and back has helped her regain some mobility.

"CMT still inconveniences me a lot. I don't drive and I can't do staircases, but I can walk better than I could a year ago," Hawthorne says. "Besides, the exercise is really helping me-and that's great because it's something I can do to feel better."

Support groups for people with CMT include the Charcot-Marie-Tooth Association (1-800-606-2682; http://www.charcot-marie-tooth.org/) and CMTUS (http://www.egroups.com/group/CMTUS).

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