Discovery
Creutzfeldt-Jakob Disease (CJD) is not related to food consumption and has been found in vegetarians and meat eaters world-wide. CJD was first characterized in the 1920s by German neuroscientists Hans Gerhard Creutzfeldt and Alphons Maria Jakob. Creutzfeldt had described a case of progressive fatal dementia in a female patient that was accompanied by multiple neurological abnormalities. Jakob described five similar cases. For many years, there was debate about the clinical and pathological features of such diseases, but by 1960, spongiform changes in brain tissue was accepted as the major pathological criteria for diagnosing CJD. 13
Incidence
CJD is estimated to affect approximately one person per million each year worldwide and usually strikes those over the age of 55 (median age of death is 68 in the U.S.11). It is important to note that this incidence rate represents an average over time. Because age is a key factor in evaluating CJD distribution, and because the disease tends to strike people over the age of 55, the actual rate is higher for older people.16
The global incidence of sporadic CJD cases has remained reasonably consistent throughout the world in those countries where it is being monitored, generally ranging between 0.5 and 1.5 cases per million population annually. CJD affects men and women of diverse ethnic backgrounds and is always fatal.4
Recently an unexplained rise in the incidence of CJD has been reported in Switzerland (greater than or equal to 2.7 cases per million in 2001 and early 2002). 25
Transmission
CJD can occur in one of three forms:1-4
- a familial, or genetically inherited form
- a sporadic form, which is of an unknown origin and accounts for roughly 85 percent of all CJD cases
- an acquired form that includes the iatrogenic form. CJD has been acquired through inadvertent exposure to CJD-contaminated equipment or material as a result of brain surgery, corneal grafts, dura mater grafts and through the use of human pituitary-derived growth hormones or gonadotrophin.
Other prion diseases include variant CJD, believed to be acquired from the consumption of BSE-contaminated beef, and Kuru,acquired through cannibalism.
CJD and variant CJD are different TSE diseases, each with its own unique clinical and histopathological features.
Symptoms
The typical early symptoms of sporadic CJD include poor concentration, lethargy, visual disturbance and unsteadiness when standing or walking. As the disease advances, agitation, dementia and muscle twitching (myoclonus) characteristically occurs. The median survival period of CJD patients is less than six months, and almost ninety percent (90%) of sporadic CJD patients die within the first year after the onset of symptoms. No cure is available for CJD. 4, 5, 8
Five subtypes of sporadic CJD and the sporadic form of Fatal Familial Insomnia have been identified.They have distinct clinical and pathological features as well as PrPScSctypes.37
Diagnosis
The preliminary diagnosis of CJD is made following a neurological evaluation and analysis of brain waves through an EEG (electroencephalograph).4, 6
A more reliable and often definitive diagnosis in a living patient can be obtained through a brain biopsy and subsequent examination of brain tissue. In advanced cases, infected brains will appear spongy when viewed under a microscope due to a change in cells’ structures.
Disease-associated PrPRes can also be sought in the biopsied tissue.
However, conducting brain biopsies on living patients solely to confirm a clinical diagnosis of CJD is difficult to justify given the risks, such as extradural hematoma or brain abscesses, the possibility of sampling unaffected tissue and the low chance that the procedure will result in any benefit to the patient.8
Definite diagnosis of CJD and other human TSEs is generally established by analysis of brain tissue obtained after death or autopsy. Neuropathological features of CJD include spongiform change, neuronal loss, and astrocytosis. Additional methodologies used to confirm the diagnosis include immunohistochemistry, and immunoblot techniques that detect the disease-associated PrPRes protein. 4, 7, 12, 13
CJD in the United States
The occurrence of CJD in the United States remains consistent with the rate of CJD cases in many other countries, which is approximately one case per million each year. It’s important to note that this incidence rate represents an average over time. Because age is a key factor in evaluating CJD distribution, and because the disease tends to strike people over the age of 55, the actual rate is higher for older people. The Centers for Disease Control and Prevention (CDC) monitors annual death rates for CJD cases in the U.S., and has found that the national incidence rate has remained relatively stable, particularly between 1985 and 2001.11
|
Table. Creutzfeldt-Jakob disease deaths rates and deaths in the United States, 1979-2000.*
|
|
Characteristics |
Death Rate+ |
RR
(95% Cl) |
Number of
Deaths‡ (%) |
|
Age Group |
|
|
|
|
> 55 years |
4.08 |
33.4 (30.5-36.5) |
4707 (89.9) |
|
< 55 years |
0.12 |
reference |
531 (10.1) |
|
Sex§ |
|
|
|
|
Male |
1.16 |
1.13 (1.07-1.19) |
2471 (47.2) |
|
Female |
1.00 |
reference |
2767 (52.8) |
|
Race§ |
|
|
|
|
White |
1.14 |
reference |
4961 (94.7) |
|
Black |
0.45 |
0.38 (0.33-0.44) |
194 (3.7) |
|
Other |
0.78 |
0.60 (0.48-0.74) |
82 (1.6) |
|
Region§ |
|
|
|
|
Northeast |
1.22 |
1.31 (1.22-1.41) |
1307 (25.0) |
|
Midwest |
1.15 |
1.25 (1.16-1.34) |
1389 (26.5) |
|
West |
1.04 |
1.11 (1.03-1.21) |
966 (18.5) |
|
South |
0.93 |
reference |
1575 (30.1) |
|
Period§ |
|
|
|
|
1999-2000 |
.97 |
0.85 (0.76-0.94) |
487 |
|
1995-1998 |
1.14 |
reference |
1108 |
|
1991-1994 |
1.11 |
0.96 (0.89-1.05) |
1027 |
|
1987-1990 |
1.10 |
0.95 (0.87-1.04) |
964 |
|
1983-1986 |
1.07 |
0.92 (0.84-1.00) |
886 |
|
1979-1982 |
0.96 |
0.83 (0.76-0.91) |
766 |
|
U.S.§ |
1.07 |
|
5238 |
* CJD deaths, 1979-2000, reported primarily in the US multiple cause-of-death data as of 2003.
+ Death rates expressed per million persons using US standard 2000 project population.
Risk ratios (RRs) with 95% confidence intervals (CIs) calculated using Poisson regression analysis.
‡ One death with unknown race and region.
§ Death rates and RRs are age-adjusted.
Source: Division of Viral and Rickettsial Diseases, NationalCenter for Infectious Diseases, Centers for Disease Control and Prevention (CDC) and the Division of Vital Statistics, NationalCenter for Health Statistics, CDC.
With heightened concern about vCJD in the United Kingdom, the CDC enhanced its CJD surveillance since 1996. The CDC team has not seen an increase in the CJD death rate in recent data despite the recent extensive attention to the diseases.From 1979 through 2000, the average annual age-adjusted (adjusted to the year 2000 age distribution) death rate was 1.07 deaths per million persons, ranging from .86 in 1980 to 1.25 in 1987. In the year 2000, this death rate (0.88) declined to a level closer to that reported for 1980.The median age at death was 68 years, while the median age at death of patients with vCJD was 27.5 years.11
An analysis by the University of California at San Francisco also found no sign of the variant CJD in brain specimens from 67 CJD cases researchers collected between 1991 and 1996.2
The CDC continues to conduct national surveillance to identify CJD cases in patients under the age of 55 through mortality data and in collaboration with state health departments.11 It also reviews the available clinical and pathological records of these patients. In addition, the CDC worked with the American Association of Neuropathologists to alert its members about the neurological characteristics of vCJD and request they report any suspected cases of vCJD regardless of age or original clinical diagnosis.
To further improve surveillance and facilitate neuropathological study of suspected CJD cases, the American Association of Neuropathologists, with the support of the CDC, has established a NationalPrionDiseasePathologySurveillanceCenter. 2, 15
The Internet address of the center is http://www.cjdsurveillance.com. Since 1997 the NationalPrionPathologySurveillanceCenter has examined tissues from 732 cases of prion disease, without detecting a single case of vCJD.
In 2002, vCJD was reported for the first time in the United States in a Florida resident who was born in the United Kingdom and grew up there during the height of human exposure to the BSE agent. 26
** CJD affects approximately one person per million each year worldwide and usually strikes those over the age of 55 (median age of death is 68 in the U.S.11). It’s important to note that this incidence rate represents an average over time. Because age is a key factor in evaluating CJD distribution, and because the disease tends to strike people over the age of 55, the actual rate is higher for ages 55 or older. 16
| Classifying Sporadic CJD Cases |
|
Definite = |
cases in which the abnormal prion protein has been detected in brain tissue (Prion proteins may be detected using immunohistochemistry or immunoblot, or histology may illustrate spongiform changes.3,4) |
|
Probable = |
patients with rapidly progressive dementia lasting less than two years, periodic sharp-wave complexes in EEG results and any two of the following neurological symptoms: myoclonus, visual and/or cerebral symptoms, pyramidal and/or extrapyramidal signs or akinetic mutism. |
|
Possible = |
those fulfilling the above criteria without typical EEG abnormalities. |
Source: Global Surveillance, Diagnosis and Therapy of Human Transmissible Spongiform Encephalopathies: Report of a WHO Consultation. World Health Organization, Geneva, Switzerland, 9-11 February 1998.