Simple question leads to answers in medical mystery What's a Neuropathy?

[Guest guest]

A simple question leads to answers in medical mystery

Humans might like to think we have nothing in common with pigs, but

the facts suggest otherwise in rabies studies and others.

http://www.minnpost.com/stories/2008/02/28/994/a_simple_question_leads

_A simple question leads to answers in medical mystery

to_answers_in_medical_mystery

By Dr. Craig Bowron

In midsummer 2007, health officials at the Quality Pork Processors

plant in Austin, Minn., knew something wasn't right. By then, four or

five workers with symptoms of fatigue, leg weakness and numbness had

been seen at the plant's clinic and referred on to the Austin Medical

Center for further evaluation.

A dialogue was beginning between the two sites. Were the workers,

with varying degrees of somewhat similar symptoms, really complaining

of the same thing? Was this just some odd " bug " moving through the

plant, or was it something job-related?

Here's the story of how a Spanish interpreter helped crack an unusual

medical mystery, and how a pork-processing technology might end up

resurrecting the lessons from Louis Pasteur's seminal work on the

rabies vaccine more than a century ago.

Connecting the dots

For Dr. Schindler, a family practitioner at the Austin

Medical Center, a simple question in mid-September gave the

cryptically scattered dots the beginnings of a recognizable form.

" One of our Spanish interpreters stopped me in the hallway and

asked, 'What's a neuropathy?' " recalled Schindler, " and so we talked

about it for a little bit, and I asked her why she was interested.

She said she had interpreted for several different patients, who all

had similar symptoms but were being seen by different doctors in the

clinic. "

Not only did they have similar symptoms, interpreter Carol Hidalgo

noted, but they also were all working in the same general area at

QPP.

Dr. Schindler Next, Schindler quickly tracked down the nurse

practitioners involved with the cases Hidalgo had interpreted for,

and with their help, he was able to identify several other suspect

cases of nerve damage. " We started sifting through names and charts,

and by noon we had six different cases for sure, " Schindler said.

By week's end the number was 11.

It turns out the first case had been seen in the clinic in December

2006. Nine months might seem like a long stretch for the pattern to

go unnoticed, but neuropathies like these are a rather unusual

illness, and as it happened, the QPP workers were randomly assigned

to different doctors or nurse practitioners.

Though clinic-based health care providers physically appear to be

working shoulder to shoulder, practically speaking they can be

professionally isolated. It took someone like Carol Hidalgo to see a

forest in a few unusual trees. (Hidalgo declined to be interviewed

for this story.)

List in hand, Schindler knew it was time to make some phone calls. He

spoke with the head nurse at QPP, contacted the state epidemiologist

based in Rochester, and emailed several of the Mayo

neurologists who had already seen a few of the six patients while

doing outreach at the clinic. Again, none of the neurologists had

seen more than a case or two — not enough to see a pattern.

One of Schindler's emails went to Dr. Lachance, a Mayo

neurologist in charge of outreach to the Austin Medical Center who

just happened to have a special interest in the area of

neuropathies. " I started reviewing the cases and I realized that yes,

the interpreter was correct, " Lachance said.

Dr. Lachance By mid-October the Minnesota Department of Health

was involved, and after a few weeks of preliminary investigation it

became clear that the illness pattern didn't fit the repetitive

motion injuries that are so common in the meat-packing industry.

Something else was going on.

Sounding the alarm, cautiously

Because of the way our food is produced and distributed, an outbreak

involving any kind of illness at a food-processing plant draws an

aggressive response from state health department officials. The

department began immediately interviewing both affected and non-

affected workers to identify potential exposures. They reviewed

clinical data and obtained diagnostic samples.

A Dec. 3 press release from MDH made some preliminary

conclusions. " All of the information we have to date indicates that

the general public is not at increased risk for developing this type

of illness, " said Dr. Sanne Magnan, state health commissioner. " Also,

there is no evidence that the food supply has been affected. "

As for the cause of the outbreak, the press release said only that

all of the patients had worked in an area where swine heads were

processed, and that at the request of the state, QPP had

implemented " additional precautionary measures " at the plant.

No doubt trying to avoid a consumer panic that would tank the pork

industry, the calming tones of the Dec. 3 press release gave no

indication of the rather startling findings that state epidemiologist

Dr. Ruth Lynfield encountered on a tour of the QPP plant just five

days earlier.

According to a New York Times article, when Dr. Lynfield toured the

epidemiological epicenter of the outbreak — the " head table " — she

saw workers using high-pressure compressed air to liquefy the swine

brains and evacuate the skull, a procedure termed " blowing the

brains. " True to its description, the procedure sent swine brains

splattering across a sizeable area, with some of them being

aerosolized into a fine mist. Lynfield and Wadding, the plant

owner, made the obvious decision: Stop the brain harvesting

immediately.

MDH spokesman Doug Schultz said the unnamed " precautionary measures "

alluded to in the original press release included having workers

harvesting skull meat use a face shield — a clear plastic version of

a welder's mask. " Prior to this, workers had either worn eye goggles

or no particular protection, " noted Schultz. MDH also asked that

workers wear rubberized arm sleeves that extend up to armpit

height. " Previously the workers were wearing gloves and a short

sleeved lab coat, so there was some potential exposure between the

two, " he said.

A review of other pork processors in the country found only two

others that were " blowing brains " : one in Nebraska, the other in

Indiana. Both have stopped the practice. The Indiana plant is being

investigated by the U.S. Centers for Disease Control for several

cases of neuropathy. No other similar cases have been identified.

Putting a name to the symptoms

So, we know the illness started with the head table and a high-

pressure hose. But what was actually causing the neuropathy?

Back at Mayo Clinic, Lachance's team was ready to give the patients'

constellation of symptoms a name: progressive inflammatory

neuropathy.

Magnetic Resonance Imaging of the patients' spinal cords and

electrical testing of the affected nerves showed that the protective

casing of the nerves was being destroyed. Many of the nerves in the

human body are wrapped in a fatty sheath called myelin. This myelin

casing insulates the long tentacle of each neuron, similar to the way

household copper wire is insulated by a plastic sheath. The

protective covering allows the nerve to conduct impulses much more

quickly (five- to 50-fold faster) and much more efficiently (100

times less energy needed).

When this myelin sheath is damaged ( " demyelinated " ), nerve conduction

slows down and begins to malfunction, firing irregularly — a toaster

on the blink, if you will. Sometimes the nerve itself, the copper

wire, can be injured as well. Either way, sensation is altered and

often becomes painful, and the muscles weaken under a barrage of

irregular nervous impulses.

If that answers Carol Hidalgo's original question, " So what's a

neuropathy? " there was still the question of what was triggering the

nerve destruction.

" We are finding evidence of antibody formation and immune system

activation towards nervous tissue, " Lachance said. In other words,

the patients' own immune systems seemed to be attacking their

nerves. " But we're also waiting on final information about whether

there could be a common infective etiology, " he cautioned. In that

scenario, antibodies against some infectious agent — a bacteria or

virus — might be cross-reacting with the workers' nerves.

The link to the rabies virus

When Dr. Marker, a pediatric infectious disease specialist

with Park Nicollet, first heard about the outbreak, he thought he

knew exactly what was going on. Early in his training, Marker spent

three years working in the U.S. Army Medical Research Institute of

Infectious Diseases' virology lab, and he was certain that the answer

could be found, historically speaking, in the rabies virus.

" Pasteur knew about this 110 years ago, " said Marker. " The earliest

version of his rabies vaccine was made up of dried spinal cord from

rabbits who had been infected with the rabies virus. The dried spinal

cord was injected into humans, and though most people did OK with it,

a number of people had an allergic response to the rabbit nerve

tissue and came down with what was eventually termed 'acute

disseminated encephalomyelitis (ADEM).' " That's longhand for a

widespread demyelinating process.

To Marker, the parallels were clear. " It was obvious what they were

doing: using high pressure hoses to spread rabbit, or in this case,

pig brains all around the room. Anyone involved in this knew it

seemed like a really bad idea. I'm sure the investigators understood

it that way right away, but in the press they were taking a more

measured, cautious approach. "

Whether or not this will be the final answer to the QPP outbreak,

Marker is right about the rabies vaccine. Because the rabies virus

replicates best within nerve tissue, for years rabies vaccines were

routinely cultured in animal nerve tissue. Recipients of the vaccine

then took a small risk of developing antibodies to the myelin

surrounding the animal nerves, with the chance that some of those

antibodies would cross-react with their own myelin. (Humans might

like to think that we have nothing in common with pigs or rabbits,

but the facts suggest otherwise).

Eventually, scientists figured out a way to culture a rabies virus in

a human cell line so that any tissue contamination in the vaccine is

strictly human, making today's rabies vaccine very safe.

The market for swine brains

After liquefaction, the swine brains from QPP were pooled into

containers and shipped to Asia or South America, where such things

are stir-fried or scrambled. Eating nerve tissue doesn't seem to

carry a risk for acute disseminated encephalomyelitis, presumably

because the heat of cooking and the digestive process destroys the

proteins that stimulate the immune response. That doesn't happen when

a protein is inhaled into the lungs, or absorbed through the skin, as

it was at the pork plants.

That's also different from Mad Cow disease, where the infective agent

called a " prion " is found in high concentrations in nerve tissue and

can be heat-resistant. That's why, after the Mad Canuck Cow scare of

2003, the U.S. Food and Drug Administration mandated changes in the

meat-processing industry as an extra precaution to keep nerve tissue

out of meat supplies.

In acute disseminated encephalomyelitis (the immune reaction to the

old rabies vaccine), some patients have inflammation not just in the

peripheral nerves, but also in the brain. Thankfully, this has not

been the case in the QPP workers, whose problems involve just the

peripheral nerves as they exit the spinal cord. According to

Lachance, those workers ill enough to require treatment seem to be

responding.

" We've treated a few of the more seriously affected workers with

immune suppressants like steroids, and we've seen some good

responses, " Lachance said. " But it's too early to know whether the

disease could have a chronic relapsing course; that is, will the

syndrome recur once treatment is stopped? "

Nerves are not the most resilient of tissues; they heal slowly, and

the road to recovery could be long or even incomplete.

" None of the workers has completely normalized, but I have a few who

presented with mild illness who are getting close to being back to

doing their normal activities, " he said.

Dr. Craig Bowron is a Twin Cities internist and writer who reports on

medical topics for MinnPost.