Duration of Prion Disease is Longer in Japan Than in Other Countries
Kiwamu Nagoshi1), Atsuko Sadakane1), Yosikazu Nakamura1), Masahito Yamada2) and Hidehiro Mizusawa3)
1) Department of Public Health, Jichi Medical University
2) Department of Neurology & Neurobiology of Aging, Kanazawa University Graduate School of Medical Science
3) Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Graduate School of Medical and Dental Sciences
(Received: June 2, 2010) (Accepted: February 3, 2011)
Background: Prion diseases are untreatable, progressive, and fatal brain disorders that occur worldwide, and the annual incidence rate is approximately 1 case per 1 million people. The duration of these diseases in Japan is unclear.
Methods: Based on data from 1 April 1999 through 4 September 2008 provided by the Japanese Creutzfeldt-Jakob disease (CJD) surveillance program, we analyzed disease duration and its relationship with clinical features. Duration was assumed to be the time from disease onset to death.
Results: Evaluation by the surveillance committee indicated that during the observed period 1128 individuals received a diagnosis of prion disease and were registered in the surveillance program. Mean disease duration in the 855 patients who died was 17.4 months. Overall, 46.0% of patients died within 1 year and 77.2% died in less than 2 years. Among those with sporadic Creutzfeldt-Jakob disease, which represented 77.0% of cases, mean disease duration was 15.7 months, while that of patients surveyed by the European Creutzfeldt Jakob Disease Surveillance Network (EUROCJD) was only 5 months.
Conclusions: Disease duration among Japanese with prion diseases was much longer than that of patients in Western countries conducting surveillance of prion diseases. This finding suggests that the characteristics of the system for providing life-sustaining treatment for patients with fatal, progressive diseases in Japan are related to the longer duration of these illnesses.
Key words: prion disease; Creutzfeldt-Jakob Syndrome; epidemiology; disease duration; Japan
The codon129 polymorphism distribution of sCJD in EUROCJD (MM type: 66.1%, MV: 17.0%, VV: 16.9%)18 was different from that among Japanese (especially the MM type). However, it is specious to attribute the disparity in disease duration to racial differences, as most Asians likely have the MM genotype, which is not associated with longer survival as compared with other subtypes.27,28
A possible reason why patients with prion diseases lived longer in Japan may be that they received much greater attention. In Western countries, due to financial and ethical concerns, intensive life-sustaining treatments like tube feeding and ventilator therapy are not commonly provided to patients with progressive, fatal neurologic condition, such as prion disease.29 In Japan, however, the well-organized health care system (ie, universal health insurance and free access to care) gives patients access to intensive medical treatments that prolong their lives.30–32 In addition, the ethical and social environment in Japan allows patients with end-stage neurologic disease to receive intensive life-sustaining treatments.29,33,34 Even after deterioration to akinetic mutism, many patients continue to receive life-sustaining treatment because Japanese physicians tend to have very negative attitudes toward withdrawal of life-sustaining treatment, as compared with withholding it.35,36
In addition to the robust public medical insurance system in Japan, under the Specific Intractable Diseases Treatment Program, the financial burden on patients and their families is reduced.5–8 In particular, medical treatment is free for patients with certain diseases (including prion diseases) and those in grave stages of other diseases.8 In this situation, many patients with a fatal neurologic disease (including prion diseases) have chosen respirator treatment under strict medical supervision. There are several limitations in the current study. First, the new case definition of prion diseases, published in 2003,26,37 has not been completely incorporated into Japanese surveillance programs. In addition, the much longer disease duration in Japanese patients could cause yet another problem, especially in the diagnosis of sCJD. A new case definition of probable sCJD was introduced to the Japanese surveillance program in 2009, while a definition of possible sCJD was not. According to the new diagnostic criteria, the disease duration of possible sCJD should be shorter than 2 years. The average disease duration of possible sCJD, which constitutes 6.0% of CJD cases in Japan, was longer than 20 months, so many cases may potentially be excluded from the new diagnostic criteria. In the future, the entire Japanese CJD surveillance system will adopt the new case definition, which will result in fewer diagnoses of possible sCJD in Japan. However, the number of such cases will not be large enough to affect trends in the Japanese surveillance data.
Second, far fewer definite cases than probable cases were collected in the Japanese study, probably due to the low autopsy rate, which was only 2.7% according to Japanese Vital Statistics for 2008.38 However, the skill of physicians who diagnose prion disease is thought to be sufficient in Japan because information on diagnosis is disseminated via the nationwide surveillance system6,8,9 and because neuroimaging procedures that are required for diagnosis, such as MRI and CT, are frequently ordered.31 To analyze the relationship between long-term survival and the accuracy of diagnosis, the frequency of autopsies must be increased. In addition, comprehensive analysis of the details of treatment and duration of akinetic mutism is necessary if data for research is to become sufficient.
To investigate the status of prion diseases in Japan, it is necessary to use data from patients registered in the Specific Intractable Diseases Treatment Program, as well as the Japanese CJD surveillance, because most patients are enrolled in these programs.5–8 To receive the benefits of these programs, recipients are required to report their status annually.8,9,39 The data from these programs are based on information contained in the grant application form, which may not include precise clinical records. In addition, the registration system may have overlooked data from patients who died after a brief interval. However, it is useful to examine summaries of patients with intractable diseases in Japan. The mean registration period of recipients with prion diseases in 2003 (n = 122) was 1.5 years.39 This is the same as the average disease duration for fatal cases collected by Japanese CJD surveillance; therefore it is possible that disease duration in Japanese patients with prion diseases may be further extended.
In conclusion, data provided by the Japanese CJD surveillance program indicate that disease duration in patients with prion diseases is much longer in Japan than in Western countries. This suggests that the Japanese practice of providing life-sustaining treatment for patients with fatal, progressive diseases prolongs disease duration.
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