Cases of Early-Onset Sporadic Creutzfeld-Jakob Disease in Michigan
Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,† Michael W. Miller,‡ Pierluigi Gambetti,§ and Lawrence B. Schonberger*
In 2001, two additional CJD patients 26 and 28 years of age were reported from a single state (Table 2) (34). The patients grew up in adjacent counties and had illness onset within several months of each other. As a result of this fact and their unusually young age, a possible environmental source of infection, including exposure to CWD-infected venison, was considered. One of the patients died after an illness lasting 5–6 months that was characterized by progressive aphasia, memory loss, social withdrawal, vision disturbances, and seizure activity leading to status epilepticus and induced coma. Histopathologic, immunohistochemical, and Western blot testing of brain biopsy and autopsy samples confirmed a CJD diagnosis. The patient’s disease phenotype corresponded to the MM2 sporadic CJD subtype reported by Parchi et al. (35). This patient did not hunt, and family members provided no history of regularly eating venison. The patient may have occasionally eaten venison originating from the Upper Peninsula of Michigan while away from home during his college years. However, ongoing surveillance has not detected CWD in Michigan deer (36).
The second patient died from an illness lasting ˜16 months. The patient’s illness began with behavioral changes, including unusual outbursts of anger and depression. Confusion, memory loss, gait disturbances, incontinence, headaches, and photophobia also developed. Western blot analysis of frozen brain biopsy tissue confirmed a prion disease diagnosis. Immunohistochemical analysis of brain tissue obtained after the patient’s death
showed prion deposition consistent with GSS. Aprion protein gene analysis could not be performed because appropriate samples were lacking. However, prion protein gene analysis of a blood sample from one of the patient’s parents indicated a GSS P102L mutation. The patient did not hunt but may have eaten venison from Michigan once when he was 1–2 years old. The GSS diagnosis greatly reduced the likelihood that the two patients reported from adjacent counties had disease with a common origin. Recently, rare neurologic disorders resulting in the deaths of three men who participated in “wild game feasts” in a cabin owned by one of the decedents created concern about the possible relationship of their illnesses with CWD (Table 2) (37). Two of the patients reportedly died of CJD, and the third died from Pick’s disease. More than 50 persons were identified as possibly participating in these feasts; the three patients were the only participants reported to have died of a degenerative neurologic disorder. Reanalysis of autopsy brain tissues from the three patients at the National Prion Disease Pathology Surveillance Center indicated that two of them had no evidence of a prion disease by immunohistochemical analysis. CJD was confirmed in the third patient, who had clinicopathologic, codon 129, and prion characteristics similar to the most common sporadic CJD subtype (MM1/MV1) (35). This patient participated in the feasts only once, perhaps in the mid-1980s. In addition, the investigation found no evidence that the deer and elk meat served during the feasts originated from the known CWD-endemic areas of Colorado and Wyoming.
In 2003, CJD in two deer and elk hunters (54 and 66 years of age) was reported (38). The report implied that the patients had striking neuropathologic similarities and that their illness may represent a new entity in the spectrum of prion diseases. A third patient (63 years of age), who was also purported to have been a big game hunter, was subsequently reported from the same area. However, none of the three patients were reported to have eaten venison from the CWD-endemic areas of the western United States. The 66- year-old patient hunted most of his life in Washington State. Although information about the 54-year-old patient was limited, there was no evidence that he hunted in CWD-endemic areas. The third patient was not a hunter but ate venison harvested from Pennsylvania and Washington. The neuropathologic changes, Western blot profile, and genotype at codon 129 of the three patients each fit the MM1, VV1, or VV2 sporadic CJD subtype, indicating absence of phenotypic similarity among the cases or atypical neuropathologic features (35). To date, only two nonfamilial CJD cases with a positive history of exposure to venison obtained from the known CWD-endemic areas have been reported. One of the patients was a 61-year-old woman who grew up in an area where this disease is known to be endemic, and she ate venison harvested locally. She died in 2000, and analysis of autopsy brain specimens confirmed that the patient’s CJD phenotype fit the MM1 subtype, with no atypical neuropathologic features. The second patient was a 66-yearold man who was reported to have eaten venison from two deer harvested in a CWD-endemic area. Both deer tested negative for CWD, and the patient’s illness was consistent with the MM1 CJD phenotype.
Archive Number 20020430.4061
Published Date 30-APR-2002
Subject PRO/AH/EDR> CJD, sporadic? - USA (Michigan)
CJD, SPORADIC? - USA (MICHIGAN)
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[see also: CJD (new var.), suspected - USA (FL) ex UK 20020419.3989 CJD (new var.) - UK: update Apr 2002 20020404.3877 CJD (new var.) - France: sixth case 20020418.3983 CJD (new var.), suspected case - Italy (Sicily) (03) 20020210.3528 CJD (new var.) - China (Hong Kong): confirmed 20020222.3604 2001 ---- Chronic wasting disease, cervid - USA: human risk? 20010126.0193 CJD (new var.), incidence & trends - UK 20011115.2816 CJD (new var.), incidence & trends - UK (02) 20011124.2875 CJD (new var.) - UK: 9th Annual Report 20010706.1293 CJD (new var.) - UK: regional variation 20010628.1231 CJD (new var.) - UK: regional variation (02) 20010907.2145 1999 ---- CJD (new var.), human - Ireland 19990715.1192]
 Date: Sat, 27 Apr 2002 20:28:05 -0400 From: Terry Allen <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000043/!x-usc:mailto:firstname.lastname@example.org>
Source: Abstract presented at American Academy of Neurology meeting, Denver, 13-20 Apr 2002
Cases of Early-Onset Sporadic Creutzfeld-Jakob Disease in Michigan
Amanda C. Peltier, Patience H. Reading, Karen Kluin, SharinSakurai, Ahmad Beydoun, Jonathan Edwards, Pierluigi Gambetti, Norman L. Foster Ann Arbor , MI; Cleveland, OH
OBJECTIVE: To describe the clinical, pathological and genetic features in 2 young men who developed sporadic Creutzfeldt-Jakob disease (CJD) concurrently in Michigan.
BACKGROUND: Sporadic CJD typically occurs in the 6th and 7th decades of life and is rarely reported in persons younger than 30, except with exposure to bovine spongiform encephalopathy (BSE) or pituitary extract derived human growth hormone (HGH). BSE has not been found in the US.
DESIGN/METHODS: Case Reports.
RESULTS: In our hospital, 2 young men, ages 26 and 28, who were unknown to each other and had lived their entire lives in Michigan, developed rapidly progressive dementia and were simultaneously evaluated. Neither had traveled to countries with known BSE, received HGH, eaten venison or elk, or had a family history of dementia. The first patient had a 2-month history of progressive aphasia, social withdrawal, and memory difficulties. An EEG performed on admission revealed waxing and waning rhythmic spike and wave discharges. He was treated for nonconvulsive status epilepticus, which became convulsive during his hospital course. His seizures were refractory to medical therapy despite multiple anticonvulsants, including midazolam coma. His EEG became more periodic and he never recovered responsiveness even as medication was tapered. A brain biopsy and subsequent postmortem examination following his death 5 months after the onset of symptoms showed spongiform changes. The scrapie prion protein (PrPsc) was distributed in a cluster pattern as revealed by immunohistochemistry. Genetic analysis and immunoblot established that this patient had the MM2 subtype of sporadic CJD. Treatment with quinacrine had no benefit.
The second patient had a 10-month history of progressive memory loss, inappropriate behavior, violent outbursts, and difficulty performing his job. He had bradykinesia and rigidity on examination. There were no periodic discharges on EEG and CSF protein 14-3-3 was negative. Following a brain biopsy showing spongiform changes he developed startle myoclonus. The presence of PrPsc type 1 was confirmed with immunoblot and immunostaining.
Both patients had abnormal MRI scans with increased signal in the basal ganglia and cerebral cortex on T2- and diffusion-weighted images.
CONCLUSIONS: These cases expand the spectrum of sporadic CJD to include younger age of onset than previously suspected and cases presenting as non-convulsive status epilepticus. The appearance of CJD in 2 individuals within a few months of each other in southeastern Michigan may indicate that very early-onset CJD is more common than previously believed. Alternatively, other unrecognized risk factors may exist. It is important to consider CJD in young people with progressive behavioral and cognitive disturbances, even in the absence of typical EEG or CSF abnormalities.
Supported By: This study was supported by NIH grant AG14359 and grant CCU 515004 to the National Prion Disease Pathology Surveillance Center and the Michigan Alzheimers Disease Research Center (NIH grant P50-AG0871).
Kathy Stone Media Relations Manager American Academy of Neurology 1080 Montreal Avenue St. Paul, Minnesota 55116 USA ph: 651-695-2763 fax: 651-695-2791 <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000043/!x-usc:mailto:email@example.com>
-- Terry J. Allen <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000043/!x-usc:mailto:firstname.lastname@example.org>
******  Date: Mon 29 Apr 2002 8:29 PM From: Terry Allen <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000043/!x-usc:mailto:email@example.com> Source: USA Today 29 Apr 2002 Page 7D
Michigan brain-disease deaths 'unusual, disturbing' -
Last fall 2 young men, ages 26 and 28, died in the same Michigan hospital of a rare brain disease that occurs mainly in elderly people. The incident, which raised fears that the human form of mad cow disease, or something similar, had emerged in the USA, prompted a swift investigation by federal health officials, but doctors familiar with the cases say there is no evidence to support that fear. They say autopsies and other tests indicate the victims died from so-called "classic" forms of Creutzfeldt-Jakob disease (CJD).
While the cases are "highly unusual and disturbing," says University of Michigan neurologist Norman Foster, the data show that the forms of CJD suffered by the young men are ones seen previously in older individuals. CJD occurs at the rate of about one person per million per year, almost always in people over age 60. What doctors feared is that a new form of CJD, possibly similar to a variant that emerged in the mid-1990s in the United Kingdom and linked to consumption of mad-cow-infected beef, had struck.
Unlike classic CJD, the new variant, vCJD, strikes mainly young adults. It has killed more than 100 people. The only known case of vCJD in the USA was diagnosed recently in a 22-year-old British woman living in Florida, who is thought to have contracted the disease in England. Mad cow disease has not been detected in cattle in the USA, but a similar disease in deer and elk is spreading in the Midwest. Chronic wasting disease (CWD) is fatal to deer and elk but is not known to cause illness in humans.
Lawrence Schoenberger of the Centers for Disease Control and Prevention in Atlanta says the agency sent investigators to Michigan in late August 2001, when the victims were still alive. "The key thing here is the 2 were right together. We were worried that there was maybe a common exposure, but our investigation revealed that was not the case." The men lived in adjacent counties but did not know each other, he says.
In the rare cases when CJD strikes before age 30, it is often caused by a hereditary form of the disease, says Foster, and "tests are continuing to see if that may be a factor in these cases." But extensive family interviews determined that neither man had a family history of dementia, nor had they eaten venison or elk meat or visited countries where mad cow disease has been detected.
"We feel as comfortable as anyone can that this is not related to either CWD or (mad cow disease)," says Foster, who treated the patients at the University of Michigan Medical Center in Ann Arbor. Not everyone is comfortable. "I discount the statement that these 2 young people, dying at the same time in the same hospital in southeast Michigan, did not eat venison, after living their entire lives in that state," says John Stauber of the Center for Media & Democracy and co-author of Mad Cow USA.
He suspects a new American variant of CJD, perhaps related to chronic wasting disease, may be emerging. "Any attempt to portray these CJD deaths as some sort of 'normal' occurrence that has simply, to date, gone unobserved is absurd," Stauber says. Current estimates of only 5 cases per billion of CJD in people 30 and younger may be incorrect, says Foster, who co-wrote a report on the cases presented this month at a meeting of the American Academy of Neurology.
"The fact that they both occurred at the same time in a relatively small population suggests that (CJD in younger people) may be more common than previously suspected," Foster says. Doctors don't expect to see it in young people, so misdiagnosis may occur. " Any young individual with progressive neurologic disease should be considered for CJD."
He says the cases also underscore the need for a national system to seek out and report all cases of CJD. "There certainly is the possibility that other cases have been seen and not diagnosed, or even if diagnosed, not reported."
[Byline: Anita Manning]
-- Terry j allen <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000043/!x-usc:mailto:firstname.lastname@example.org>
[At present a link between CWD and CJD in the USA or Canada has not been established. Unfortunately, reviewing the UK and European experience, it would not be a surprise if such a link were identified. Clearly we are very early in our understanding of prion disease and early in our identification of the full range and spectrum of the prion disease presently manifested as CWD in cervids in North America. The occurrence of 2 cases of sporadic CJD in unrelated individuals below the age of 30 is unusual and warrants the scrutiny it has been receiving. We await more information as it becomes available.
Some useful reference for our readers:
1: Belay ED, Gambetti P, Schonberger LB, Parchi P, Lyon DR, Capellari S, McQuiston JH, Bradley K, Dowdle G, Crutcher JM, Nichols CR. Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch Neurol. 2001 Oct;58(10):1673-8.
2. Brown P, Will RG, Bradley R, Asher DM, Detwiler L. Perspective: Bovine Spongiform Encephalopathy and Variant Creutzfeldt-Jakob Disease: Background, Evolution, and Current Concerns. EID 7(1) Jan-Feb 2001 <http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm>
3. Holman RC, Khan AS, Belay ED, Schonberger LB. Dispatches: Creutzfeldt-Jakob Disease in the United States, 1979-1994: Using National Mortality Data to Assess the Possible Occurrence of Variant Cases. EID 2(4) Oct-Dec 1996 <http://www.cdc.gov/ncidod/eid/vol2no4/holman2.htm>
4. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Research letter: Creutzfeldt-Jakob Disease in the United States: 1979-1998. JAMA 284(18) 8 Nov 2000 <http://jama.ama-assn.org/issues/v284n18/ffull/jlt1108-6.html>
5. Surveillance for Creutzfeldt-Jakob Disease. MMWR, 45(31):665-668 9 Aug 1996 <http://www.cdc.gov/mmwr/preview/mmwrhtml/00043220.htm> - Mod.MPP] ..................................lm/mpp/pg/lm
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Monday, July 27, 2009
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?
WHY DID THIS VIDEO NOT SHOW ON EVERY NEWS CHANNEL IN THE U.S.A. $$$
IT IS A DAMNING VIDEO !!!
I WATCHED THIS RECENTLY, and had never seen it. i was so mad, i was spitting nails out faster than a framing gun.
WHY DID THE CANADIAN MEDIA ONLY PRESENT THIS TO THE U.S.A. PUBLIC (thank you very much though), and why has the U.S.A. MEDIA FAILED US ???
WHY DID R-CALF NOT SHOW THIS ??? where was r-calf when you needed them back then $$$
Monday, July 27, 2009
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?
Saturday, June 13, 2009
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009
Tuesday, July 14, 2009
U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST
WHERE did we go wrong $$$
Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]
Transmissible mink encephalopathy - review of the etiology
Wednesday, July 1, 2009
Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)
Monday, June 01, 2009 Biochemical typing of pathological prion protein in aging cattle with BSE
SOMETHING TO PONDER ???
O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???
OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$
IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???