A case in California suggests the degree to which patients and neurologists alike have become hyper-vigilant for the human form of mad cow disease in the months since the first cow in the US was diagnosed with the malady.
No longer eating or able to walk, a young woman was transferred to the University of California-San Francisco's (UCSF) Memory and Aging Center with a tentative diagnosis of variant Creutzfeldt-Jakob Disease (vCJD), the form of the disorder which can be transmitted from cows infected with bovine spongiform encephalopathy (BSE).
She had been transferred to our center for end-of-stage management issues, recalled Michael D. Geschwind, MD, PhD, Assistant Professor of Neurology at UCSF. They wanted to put a feeding tube into her stomach.
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His neurological exam, however, did not confirm the standard criteria for diagnosing the disease. In talking with the young woman, Dr. Geschwind soon learned that her symptoms had begun immediately following a psychologically traumatic event.
It was a personal event that had been brushed over, he said. I quickly saw that her condition was psychosomatic. Within an hour we had her running up and down the halls. Through appropriate psychiatric care she recovered.
While extreme, the case was not unusual in one respect, he said. At least once every week or two, Dr. Geschwind gets a referral from a doctor, often a neurologist, convinced that a patient has variant CJD. Many neurologists don't know what the criteria are for variant CJD, he said. What that tells me is we need better education.
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But, he emphasized, he prefers to see neurologists being too quick to tentatively diagnose the disease than too slow. I have little doubt that eventually variant CJD will be found in the US, Dr. Geschwind said. The only way we're going to be able to detect it is if we look. We have to be very vigilant. In order to improve surveillance for vCJD in the US, the CDC, through state health departments, is now trying to ensure that every vCJD case in the country under the age of 55 is investigated, as most cases of the disease have occurred in this age range.
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PUBLIC FEAR OUTPACES RISK
Right now, though, public fear of the disease clearly outpaces the actual risk, he said. People are worried about it, absolutely, Dr. Geschwind said. A lot of people are scared.
Richard T. Johnson, MD, Professor of Neurology, Microbiology, and Neuroscience at the Johns Hopkins University School of Medicine in Baltimore, MD, said that even his neighbors ask him about the disorder, often inquiring whether he still eats meat.
Of course I'm still eating meat, he said. It's a matter of assessing risk. I drive a car to work - that's a real risk. But the number of people who have died of mad cow in the United States is zero. There may be one case this year, but I would be surprised if there were more than one.
Last December, one week after the first case of BSE was diagnosed in a US cow, the US Department of Agriculture voted to ban all downer cows - those too sick to walk - from the food supply, and to test 38,000 cows for the disease in 2004, up from 20,000 last year.
But when Dr. Johnson met with fellow members of the Transmissible Spongiform Encephalopathies Advisory Committee of the US Food and Drug Administration (FDA) in February, the consensus was that more had to be done.
The Agriculture Department took heed. In late March, the Agriculture Department announced that it would expand testing to more than 221,000 animals - including 201,000 considered at high risk for bovine spongiform encephalopathy, because they show signs of nervous system disorder, and 20,000 animals - to be tested at random - that are old enough to have eaten feed produced before 1997, when the FDA banned the use of cattle tissue in feed for other cattle. The surveillance program will begin in June and will last 12 to 18 months.
According to a statement from the FDA, While there wasn't an official charge or requested vote, several members [of the committee] requested more inspection and better compliance of the US Feed Ban, including compliance on farms, along with more testing of cattle, including apparently healthy animals. Some members suggested routine testing of all cattle over 30 months of age. Several committee members requested prohibition of high-risk bovine materials in medicinals, foods, and dietary supplements.
At one point at the FDA committee meeting, Dr. Johnson held up a bottle of capsules labeled Body Fortress, which he said he had bought at a Baltimore health food store.
It contains raw brains, he said to his fellow committee members. Anybody want to try it?
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NEW REGULATIONS ARE LACKING
In an interview with Neurology Today, Dr. Johnson said that any dietary supplement containing animal brains is far riskier than beef. I wouldn't take one on a bet, he said, pointing out that the FDA has little regulatory authority over dietary supplements.
A researcher at the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, OH, agreed with Dr. Johnson that the new regulations do not go far enough. When the cow is down, it's already quite sick, said Man-Sun Sy, PhD, who runs a laboratory at the prion center and is a Professor of Pathology and Neurosciences at Case Western. In Japan and Italy, where they screen every single cow, they have identified BSE in animals that appear to be normal.
In February, the advocacy group Public Citizen released a statistical analysis which, they said, showed that by removing all downer cows from the food system, the USDA had cut only 12 percent of the total BSE risk. Downer cows do carry a much higher risk of BSE than seemingly healthy cows, the group conceded. But because there are so many more normal-appearing cattle than downers, there is more overall BSE risk among normal cattle than among downer cattle.
The United Kingdom tests all cows older than 30 months, and found 425 cases there in 2003. But following that policy in the US would require the testing of over six million cow brains per year, at a cost of $50 each.
The Agriculture Department's new testing program will cost an estimated $70 million, according to Agriculture Secretary Ann M. Veneman. But several leading consumer groups say the program does not go far enough in guaranteeing - and reassuring consumer confidence in - the safety of the nation's beef supply. Only a program that tests all cattle, regardless of age, will do that.
ARTICLE IN BRIEF
✓ With mad cow disease in the news, neurologists are seeing increasing referrals for possible cases of variant Creutzfeldt-Jakob disease (CJD). But, experts in transmissible spongiform encephalopathies say, greater efforts must be made to educate neurologists about the criteria for diagnosing variant CJD.
CRITERIA FOR DIAGNOSING VARIANT CJD
Because only about 300 cases of Creutzfeldt-Jakob Disease (CJD) are diagnosed in the US each year, many neurologists have never seen the disease, according to Michael D. Geschwind, MD, PhD, Assistant Professor of Neurology at the University of California-San Francisco Memory and Aging Center.
Not surprisingly, then, only 30 to 40 percent of the postmortem brain tissue samples sent to the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, OH, receive a positive diagnosis, said Man-Sun Sy, PhD, Professor of Pathology and Neurosciences there.
About 85 percent of cases worldwide are sporadic or spontaneous, Dr. Geschwind said. About 15 percent are genetic, and less than 1 percent are believed to be infectious, including iatrogenic cases in which neurosurgical instruments were unwittingly infected.
Worldwide, only 154 cases of variant CJD, the infectious type transmitted from cows, have been reported, said Dr. Sy. And not a single patient has yet to be infected with variant CJD in the Western hemisphere. Two cases - one in Florida and one in Canada - involved patients who had become infected while living in Great Britain between 1980 and 1996.
Rare as it is, All of the cases identified so far of variant CJD fulfill certain criteria, said Dr. Geschwind.
First, he said, the patient must have a progressive psychiatric disorder going on for at least six months.
Next, the patient must have four of the five following symptoms: ataxia, depression, dementia, persistent painful sensations, and a movement disorder (chorea, dystonia, or myoclonus).
Their EEGs, in all cases, have not shown the typical changes seen in sporadic forms of the disease, Dr. Geschwind said. And in most cases, there is an abnormal signal on the MRI: a high signal in the thalamus, particularly on fluid attenuated inversion recovery (FLAIR) diffusion-weighted sequences. Other areas of the brain, such as the neocortex and the basal ganglia, may also have a high signal, but what distinguishes vCJD is that on MRI the thalamus is brighter than those other areas.
Patients with the variant form of the disease are also more likely to be younger than those with the spontaneous form. A more definitive diagnosis, he said, can be made by tonsil or brain biopsy.
One likely indication that a patient is not suffering from the CJD, however, is when he or she is the only one reporting it. In my experience, if patients are the only ones saying it, said Dr. Geschwind, chances are they don't even have anything neurologically wrong. Many of these cases have been purely psychiatric disorders, often depression or anxiety. If the family or friends are saying something is wrong, though, then I have found that it is much more likely that something neurological is going on.
While keeping in mind the rarity of the disease, he said, It needs to be on the differential if we're ever going to find it.
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