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First US BSE Case Since 2006 Underscores Need for Vigilance

Samson, Kurt

doi: 10.1097/01.NT.0000415806.16403.37
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THE FOURTH CASE of bovine spongiform encephalopathy in the US was identified in April

THE FOURTH CASE of bovine spongiform encephalopathy in the US was identified in April

A case of bovine spongiform encephalopathy was identified in a dairy cow in California, prompting new calls for strict ongoing monitoring of cattle, and heightened awareness of variant Creutzfeldt-Jakob disease symptoms by neurologists.

US health officials confirmed a case of bovine spongiform encephalopathy (BSE), or mad cow disease, in April — the first in six years — in a ten-year-old cow on a California dairy farm. It is the fourth confirmed case of BSE in the US since surveillance began, but according to the US Department of Agriculture, no products from the cow entered the human food supply.

The US Department of Agriculture (USDA) stressed that the cow was never presented for slaughter for human consumption, and therefore presented no risk to human health in the United States. In 2011, there were only 29 worldwide cases of BSE, a dramatic decline and 99 percent reduction since the peak in 1992 of 37,311 cases.

At press time, the USDA stated that one progeny born to the positive cow in California in the last two years was stillborn, and another was identified in another state; that animal was euthanized and its tissue was sampled and tested negative for BSE. Dairies in California and at the site where the second calf were found remain under quarantine.

If transmitted to humans, BSE, which is caused by misfolded prion proteins, causes a rare but fatal neurodegenerative condition called variant Creutzfeldt-Jakob disease (vCJD). The disease is transmitted by eating contaminated cow brain, spinal cord, or digestive tract tissue.

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Since an outbreak of BSE in Europe in the late 1980s, after which stringent animal and human surveillance systems were put in place around the globe, more than 200 cases of vCJD in humans have been linked to contaminated cattle; 22 cases were identified in North America, and three in the US.

In all three US cases of vCJD, the affected individuals were believed to have contracted the disease outside the US, according to Pierluigi Gambetti, MD, professor of neurology and pathology and director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland. The center, which was established by the Centers for Disease Control and Prevention (CDC) in collaboration with the American Association of Neuropathologists in 1997, performs diagnostic tests for prion diseases, including postmortem tests for vCJD.

All three brains were examined at the surveillance center, Dr. Gambetti explained, and the evidence suggests that two of the people with vCJD were exposed to the BSE agent in the United Kingdom and the third while living in Saudi Arabia.

“There is no evidence of any case of vCJD being acquired in the US, and this is very comforting news,” he said.



But Dr. Gambetti said the discovery of the latest case of BSE in the California animal points to the need for strict ongoing monitoring of cattle — he noted that only one head of cattle for every thousand or more is currently screened for the disease.

Dr. Gambetti also stressed the need for heightened awareness of vCJD symptoms by neurologists and other health practitioners.

Increasing the number of autopsies on patients with suspected prion disease, including classic CJD — which is not linked to BSE and distinctly different in clinical and pathologic presentation — will enhance efforts to identify cases of vCJD, he said.

The origin of these diseases [in animals] is unclear, said Dr. Gambetti. “We don't know how atypical prion diseases form in animals — if they are spontaneous or related to exposure — and we don't know where they came from,” he said. “We need to find the weak point in the transition of normal to abnormal protein. Without it, treatment will be hard to find.”



The good news is that once found, treatments or treatment principles for one form of disease may work for others as well because the same mechanisms are involved, Dr. Gambetti said.

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The CDC has asked for increased vigilance in monitoring and detecting other possible prion diseases, including classic CJD, by increasing the number of postmortem exams. And the hope is that with increased surveillance there will be better detection of vCJD. But Michael D. Geschwind, MD, PhD, associate professor of clinical neurology at the University of California, San Francisco, stressed there are several important differences between classic CJD and variant CJD.

For the median age of death for classic CJD patients is 68 years, with very few cases in persons under 30 years of age. In contrast, the median age of death of patients with vCJD is 28 years.

vCJD also has atypical clinical features, he said. These include prominent progressive psychiatric and/or sensory symptoms, usually at the time of clinical presentation, and delayed onset of neurologic abnormalities. For example, ataxia may appear within weeks or months, and dementia and myoclonus in later stages of the illness.

For a diagnosis, patients must have four of the following symptoms: ataxia, depression, dementia, persistent painful sensations, and a movement disorder, such as chorea, dystonia, or myoclonus.

The most important differences appear on fluid attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences, said Dr. Geschwind. Most patients have an abnormal MRI, such as a symmetrical high signal in the posterior thalamus. The pattern of FLAIR/DWI hyperintensity and restricted diffusion can differentiate CJD from other nonprion causes of rapidly progressive dementia, he noted.

Cortical gyral grey matter hyperintensity (cortical ribboning) and other gray matter hyperintensities are the most critical sign of CJD on FLAIR, according to Dr. Geschwind. This is never restricted to just the limbic regions, and is rarely seen in the precentral gyrus. With CJD cases with basal ganglia or thalamic DWI hyperintensities, there is associated restricted diffusion not seen in nonprion causes of rapidly progressive dementia, where isolated limbic hyperintensities are common.

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 in other areas.

Unfortunately, many radiologists may not be aware of these differences. In a study published last year Neurology, Dr. Geschwind and colleagues found that one reader's sensitivity and specificity for CJD was 94 percent and 100 percent while another's was 92 percent and 72 percent.

A more definitive diagnosis, he said, can be made by tonsil or brain biopsy if there is evidence of prion protein.

Thomas Wisniewski, MD, professor of neurology, pathology, and psychiatry at New York University School of Medicine, said he believes sporadic cases of BSE will continue, and while the risk to humans “is very low,” health officials and neurologists also need to be on guard for novel and unfamiliar prion diseases.

In a telephone interview with Neurology Today, he said that while BSE and vCJD are a concern that demands vigilance, similar new diseases have the potential to emerge in the near future that might well carry greater risk to humans.

“I think that the neurological community needs to be aware that other infectious CJD-like diseases may start appearing in patients,” he said.

Of special concern is the risk of chronic wasting disease (CWD) jumping the species barrier from wild deer and elk into the human reservoir, he noted. Chronic wasting disease has yet to be reported in humans, but several factors make it potentially more dangerous than BSE, Dr. Wisniewski said.

“In these animal populations it can be more prevalent than BSE, affecting up to 80 percent of a herd population. Furthermore, CWD appears to be more easily transmissible, including by an aerosol route, in the [deer] population. We also know that it can be transmitted to non-human primates such as squirrel monkeys.”

—Kurt Samson

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• Geschwind MD, Vitali P, Maccagnano E, et al. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology 2011;76:1711–1719.
    • Belay ED, Schonberger LB.Variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Clin Lab Med 2002;22(4):849–862.
      • The National Prion Disease Pathology Surveillance Center:
        ©2012 American Academy of Neurology