Probable Variant Creutzfeldt-Jakob Disease in a U.S. Resident --- Florida, 2002

On April 18, 2002, the Florida Department of Health and CDC announced the occurrence of a likely case of variant Creutzfeldt-Jakob disease (vCJD) in a Florida resident aged 22 years. This report documents the investigation of this case and underscores the importance of physicians increasing their suspicion for vCJD in patients presenting with clinical features described in this report who have spent time in areas in which bovine spongiform encephalopathy (BSE) is endemic.

In early November 2001, the patient sought medical care for depression and memory loss that adversely affected the patient's work performance. The primary-care physician referred the patient to a psychologist. In early December 2001, the patient received a traffic ticket for failing to yield the right of way. In mid-December 2001, the patient had involuntary muscular movements, gait changes, difficulty dressing, and incontinence. In January 2002, the patient was evaluated in a local emergency department for these symptoms. A computerized tomography scan of the head revealed no abnormalities; a panic attack was diagnosed, and the patient was treated with an anti-anxiety medication.

In late January 2002, the patient's mother, a resident of the United Kingdom, took the patient to England, where medical evaluations were conducted during the next 3 months. During this period, the patient's memory loss and other neurologic symptoms worsened. The patient experienced falls with minor injuries, had difficulty taking a shower and dressing, and was unable to remember a home telephone number or to make accurate mathematical calculations. The patient subsequently became confused, hallucinated, and had speech abnormalities with lack of content, bradykinesia, and spasticity. The patient was referred to a neurologist, who suspected vCJD and subsequently referred the patient to the National Prion Clinic in the United Kingdom.

Medical evaluations at the National Prion Clinic included an electroencephalogram (EEG), which revealed a normal alpharhythm, and magnetic resonance imaging (MRI) studies, which revealed signal abnormalities in the pulvinar and metathalamus region that were suggestive of vCJD. The patient had a tonsil biopsy, and a Western blot analysis of the biopsy tissue demonstrated the presence of protease-resistant prion protein (PrP-res) with the characteristic pattern of vCJD; an immunohistochemical test for PrP-res also supported a diagnosis of vCJD. Analysis of the prion protein gene detected no mutation and showed methionine homozygosity at codon 129, consistent with all 105 vCJD patients tested in the United Kingdom (R. Will, Western General Hospital, Edinburgh, Scotland, personal communication, 2002).

The patient received experimental treatment with quinacrine for 3 months. As of late September 2002, the patient had become bedridden, experienced considerable weight loss requiring surgical insertion of a feeding tube, and was no longer communicating with family members. On the basis of a case definition developed in the United Kingdom, the patient's illness met criteria for a probable case of vCJD (1).

The patient was born in the United Kingdom in 1979 and moved to Florida in 1992. The patient never had donated or received blood, plasma, or organs and never had received human growth hormone. There was no family history of CJD. In October 2001, before the onset of the illness, the patient's wisdom teeth were extracted, but there was no history of major surgery.

Reported by: S Wiersma, MD, State Epidemiologist, Florida Dept of Health. S Cooper, MRCP, R Knight, FRCP, National Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh, Scotland; AM Kennedy, MD, National Prion Clinic, Dept of Neurology, St. Mary's Hospital, London; S Joiner, MSc, Medical Research Council Prion Unit, Dept of Neurodegenerative Disease, Institute of Neurology, London, United Kingdom. E Belay, MD, LB Schonberger, MD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note:

Variant CJD was first reported in 1996 in the United Kingdom, where an outbreak of BSE had been occurring among cattle since the early 1980s (2). Strong laboratory and epidemiologic evidence indicates that vCJD is linked causally with BSE (3). Although specific foods that transmit the BSE agent to humans have not been identified, transmission is believed to occur primarily by processed food items that contain infectious bovine tissues such as the brain or spinal cord. As of early October 2002, a total of 138 vCJD cases were reported worldwide, including the case described in this report. Consistent with the conclusion that the agent of BSE is also the agent responsible for vCJD, most vCJD cases (n=128) were reported in the United Kingdom, where most BSE cases in cattle have occurred (1).

The patient described in this report represents the first probable vCJD case in a U.S. resident. The patient had grown up in the United Kingdom when the BSE outbreak was increasing and when the risk for human exposures to BSE was probably at its peak. Therefore, it is likely that this patient was exposed to the BSE agent one or more times during 1980--1992 before moving to the United States and that the interval between the patient's exposure to BSE and onset of illness was 9--21 years. Such an incubation period would be consistent with known incubation periods for other similar diseases in humans, such as kuru and CJD related to exposures to pituitary-derived human growth hormone (4).

The patient is unlikely to have transmitted the disease to others because the patient did not have surgical procedures that involved manipulation of known infectious tissues. In addition, the disease is not communicable by usual personal contact. Appropriate infection-control procedures should be followed while performing invasive procedures in patients with vCJD (5). Although concerns exist about possible trans-mission of vCJD by transfusion of blood, this risk remains theoretical. The patient never had donated blood or organs. In 1999, because of the theoretical possibility of vCJD transmissions from infected blood donors, blood collection agencies in the United States began implementing a donor-deferral policy to exclude donors who might be at increased risk for infection because of a history of >6 months (later changed to >3 months) residence or travel to the United Kingdom during 1980--1996. In 2001, this donor-deferral policy was expanded to exclude donors who have traveled to other European countries for an extended period of time since 1980 (6).

Compared with the classic form of CJD endemic in the United States (7), vCJD patients typically have illness onset at an unusually young age (median age: 26 years versus approximately 68 years for classic CJD). All but one of the reported vCJD decedents had illness onset and died before age 55 years, compared with approximately 10% of classic CJD cases (7,8). Early in the course of the disease, vCJD patients usually have early and persistent psychiatric symptoms, including anxiety, depression, and social withdrawal; persistent painful sensory symptoms with dysesthesia and/or parasthesia also have been reported (8). Evaluation of the clinical manifestations of the first 100 vCJD patients in the United Kingdom indicated that onset of frank neurologic signs (e.g., gait disturbances, slurring of speech, and tremor) was usually delayed by several months after illness onset. Other neurologic signs (e.g., chorea, dystonia, and myoclonus) frequently developed late in the course of the illness (8). A prominent, symmetrical pulvinar high signal on T2-weighted and/or proton-density--weighted MRI has been reported in most vCJD patients (9). In the absence of any other more plausible explanation, patients showing these clinical and radiologic features should be investigated for vCJD. In such patients, a history of travel to a BSE-endemic area increases the clinical suspicion for vCJD. In vCJD, but not other forms of CJD, there is prominent involvement of the lymphoreticular tissues (10). A tonsil biopsy with demonstration of a characteristic abnormal prion protein by Western blot and immunohistochemistry can help establish a diagnosis of vCJD. The EEG in vCJD patients is typically normal or shows nonspecific abnormalities. All 105 vCJD patients tested in the United Kingdom were homozygous for methionine at the polymorphic codon 129 of the prion protein gene (R. Will, Western General Hospital, Edinburgh, Scotland, personal communication, 2002). The possible benefits of treating classic CJD and vCJD patients with quinacrine are under evaluation.

Physicians should report suspected vCJD cases to their local and state health departments. Because the clinical manifestations and age distribution of vCJD patients can overlap with those of classic CJD patients, a brain autopsy should be conducted in all such cases to distinguish suspected or diagnosed vCJD from classic CJD. A neuropathologic evaluation, in addition to helping to confirm the diagnosis, would help identify other potentially emerging prion diseases in humans. To facilitate neuropathologic studies of suspected or diagnosed prion diseases in humans, CDC, in collaboration with the American Association of Neuropathologists, established the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to use the free services of this pathology center to confirm the diagnosis in suspected vCJD or classic CJD patients. Information about the center is available at http://www.cjdsurveillance.com.

References

1. Department of Health, United Kingdom. Monthly Creutzfeldt-Jakob disease statistics, October 2002. Available at: http://www.doh.gov.uk/cjd/stats/oct02.htm.
2. Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347:921--5.
3. Belay ED, Potter ME, Schonberger LB. Relationship between transmissible spongiform encephalopathies in animals and humans. In: Task Force Report of the Council for Agricultural Science and Technology. Washington, DC: Council for Agricultural Science and Technology, October 2000;No. 136.
4. Will RG, Alpers MP, Dormont D, Schonberger LB, Tateishi J. Infectious and sporadic prion diseases. In: Prusiner SB, ed. Prion Biology and Diseases. Cold Spring, New York: Cold Spring Laboratory Press, 1999.
5. World Health Organization. World Health Organization infection control guidelines for transmissible spongiform encephalopathies: report of a World Health Organization consultation. Geneva, Switzerland: World Health Organization, March 1999. Available at http://www.who.int/emc-documents/tse/whocdscsraph2003c.html.
6. U.S. Food and Drug Administration. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease by blood and blood products. Rockville, Maryland: U.S. Department of Health and Human Services, January 2002. Available at http://www.fda.gov/cber/gdlns/cjdvcjd.htm.
7. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979--1998. JAMA 2000;284:2322--3.
8. Spencer MD, Knight RSG, Will RG. First hundred cases of variant Creutzfeldt-Jakob disease: retrospective case note review of early psychiatric and neurological features. BMJ 2002;324:1479--82.
9. Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000;355:1412--8.
10. Hill AF, Butterworth RJ, Joiner S, et al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999;353:183--9.

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