Fatal familial insomnia

First identified in the 1920s, Creutzfeldt-Jakob disease (CJD) is a fatal degenerative disease of the central nervous system that is caused by a prion (ie, an infectious particle smaller than a virus). The protein prion PrPSc is an aberrant conformer of a normal membrane protein, PrPC.

The disease is not accompanied by any inflammatory reaction after it finds a host. It can lie dormant for decades before any of its symptoms manifest themselves. After they do, however, their presence is evident and initially is reflected in the infected person's neglect of proper grooming, bathing, or eating. This rapidly progresses to profound apathy or irritability. Sleep disorders, disorientation, and fatigue may supervene, followed by serious intellectual deterioration, such as the inability to speak, recognize objects, read, or write. With the passage of time, muscle spasms, palsies, and rigid paralysis usually occur, together with bizarre visual disturbances. There is no treatment for the disease, and its victims usually die within one year after symptoms develop. Most of those affected are in their later fifties at onset. (1)

Until recently, no method for identifying a carrier of the disease during its incubation period has been available. It rarely occurs in humans (ie, one in one million), so the disease never has been considered critical enough to warrant development of a method that would make it identifiable. What is known is that the highest concentrations of the infectious agent are found in the brain, spinal cord, and eye. The need for biopsies of these types of tissue has been a major detriment to diagnosing the disease before a patient's death.

TRANSMISSION

Eighty-five percent of CJD cases are sporadic (ie, they have no verified source of transmission); familial and iatrogenic cases account for the remainder. (2) It is yet to be determined whether CJD can be transmitted by blood. Historically, the disease has been transmitted by contaminated neurosurgery instruments, transplants (eg, cornea), and injection of tissue extracts (eg, growth hormone). The means of transmission is of particular concern because the protein nature of prions makes them extremely resistant to conventional means of disinfection and sterilization. As a result, it is not uncommon for instruments used on known or prospective carriers of the disease to be discarded in biohazardous trash destined for incineration. (3,4,5,)

A management solution that was developed for one such instance recently was reported in the literature. (6) A 43-year-old woman with a family history of CJD underwent surgery for a herniated disc. Familial cases of CJD involve mutations in the prion protein gene. Although her condition was asymptomatic, mutation test results confirmed her as a carrier of the disease. A $5,900 set of instruments used during her surgical procedure was felt to be near the end of its useful life (ie, with an estimated value of $1,000), so the instruments were discarded. The patient later was scheduled for a repeat lumbar laminectomy. With the understanding that she might require additional laminectomies in the future, the instruments used during the second procedure were set aside and reserved for use on this patient only.

In addition to the legal and financial challenges that might be expected in the event of an outbreak of the disease, two recent reports on the possibility of CJD transmission during surgery highlight the ethical considerations. In both cases, neurosurgery was performed on patients who had not been identified as carriers of the disease. In the first case, it was only after the patient's death that a postmortem brain biopsy revealed that the patient had CJD. It is believed that some of the potentially contaminated instruments used on this patient subsequently might have been used on eight other patients.

In the second case, a patient who had not presented with any CJD symptoms underwent a brain biopsy to rule out vasculitis. Three weeks after surgery, a pathology report indicated that he was a carrier of CJD. In the interim, six other patients had undergone brain biopsies in which the same instruments were used. It should be noted that in both of these situations, all the instruments had been washed and steam sterilized after each use. (7)

In the second case, a manual tracking system helped identify procedures in which the potentially contaminated instruments were used, so hospital authorities made the ethical decision to inform the six patients about their possible exposure. From a thorough analysis of the series of events, the hospital learned three important lessons to share with other health care providers:

* a patient with CJD or prion disease does not always present with symptoms,

* the interval between a biopsy and a pathology report should be monitored and reviewed to ensure the shortest possible time from biopsy to results, and

* instruments used in brain biopsy procedures should not be reused when a patient's diagnosis is uncertain at the time of the procedure. (8)

After this incident, the hospital revised its policies and procedures to follow up on pathology reports within one week and to quarantine instruments used in neurosurgery--including brain biopsies--with unknown or uncertain diagnoses until a diagnosis can be confirmed.

A NEW VARIANT

In the mid to late 1980s, CJD began receiving global attention by making its presence felt in England. Bovine spongiform encephalopathy (BSE), labeled mad cow disease, is a variant of CJD, the neurological disorder that has plagued humans for three quarters of a century. It became a bovine scourge almost without parallel for a single country. More than one-third of British dairy herds were affected and almost 200,000 animals died. New cases still are being reported because of the disease's long incubation period.

This variant of CJD (vCJD) can be acquired by people who have eaten beef contaminated with BSE; therefore, concern arose about a potential epidemic among humans. Some 900,000 cattle were eaten during the disease's incubation period, so literally millions of people may have been exposed to vCJD. It also is possible that because of the disease's long incubation period, the extent of the exposure may not be known for 10 to 20 years. (9)

The symptoms of vCJD differ dramatically from those of sporadic cases. Patients' mean age is 26 years, and many patients present with prominent affective symptoms, including dysphoria, irritability, anxiety, apathy, loss of energy, insomnia, and social withdrawal. The diagnosis usually is not suspected until the neurological symptoms, including cognitive impairment, pain and paresthesias, dysarthria, and gait abnormalities, appear. Myoclonus is a late feature, and startle myoclonus is elicited in rare cases.

Recently, the tonsils have been reported to be a storage site for prion proteins and implicated in the transmission of vCJD. Similarly detectable lymphoreticular reservoirs are not present in sporadic cases of CJD. (2) The recognition that patients with vCJD have PrPSc in extraneural sites, including lymphoreticular tissues, has led to the use of tonsil biopsy as an important diagnostic test. (2) This finding was taken so seriously by England's department of health that, at one point, the department considered recommending that elective tonsillectomies be suspended until single-use disposable instruments became available. The agency went so far as to offer funding to underwrite the cost of developing the instruments. (10)

COPING WITH THE CHALLENGE

The predicted epidemic of vCJD among humans has not yet materialized, and the number of cases in the United Kingdom has declined from a peak of 28 in 2000 to 17 in 2002. (2) The entire clinical community, however, was confronted with the challenge of decreasing occurrences because the disease had the potential to reach epidemic proportions.

Two options were available. Rather than discarding all the expensive instruments used in neurological surgery after use, instruments designed for single-use only could be used and disposed of afterward. The alternative, of course, would be to reprocess the reusable ones. It is known, however, that conventional disinfection and sterilization techniques are not effective against CJD. (3-5) The need for a method that renders them safe for another use is imminent. Actually, three new techniques are required:

* a technique that would effectively disinfect instruments used on known carriers of CJD,

* a technique that would validate the efficacy of the disinfection and sterilization process, and

* a test to identify a CJD carrier before he or she undergoes surgery.

DISINFECTING AND STERILIZING

The World Health Organization (WHO) responded to this issue with a new set of guidelines for rendering instruments suitable for reuse. (11) The recommendations called for instruments to be immersed in a solution of sodium hydroxide, which then would be heated in a gravity displacement sterilizer for 30 minutes. After this disinfection process, the instruments would be cleaned, rinsed in water, and then subjected to routine sterilization. The hazards and problems associated with the use of sodium hydroxide (ie, human exposure, possible damage to both instruments and sterilizer), however, led the group to suggest two alternate methods that use sodium hypochlorite (ie, chlorine bleach).

Currently, not much is known about how the WHO's protocol will affect the integrity of instruments (ie, corrosion, discoloration, damage to hinges) over time. Nevertheless, it is that very uncertainty that may account for the development of a replacement for these methods being identified as the second most intensive issue being researched by industry today. (12)

VERIFYING THE CLEANING PROCESS

To assess the effectiveness of the disinfection method, one must consider the inactivation and removal factor--(ie, the reduction of infectious units during the process). The probability of an instrument or device remaining capable of transmitting disease depends on the initial degree of contamination and the effectiveness of the decontamination procedure. (13) A group of English anesthesiologists conducted a study on how to make that determination. (10) Having taken note that tonsils are known to be a storage site for the prion proteins implicated in the spread of vCJD, they reasoned that if the laryngeal mask airway devices used in these procedures were not satisfactorily clear of proteins, there was a possible risk of transmission of the disease during their reuse. The goal of the study was to determine whether the reusable airway devices were clear of protein material after passing through the routine cleaning efforts in a hospital. Cleaning consisted of scrubbing the devices with a commercial detergent containing chlorhexidine under running tap water, drying, and sterilizing.

Using a dye that turns red when it adheres to bacterial protein remaining on teeth after they are cleaned, researchers found staining on all of the 20 previously used devices tested--90% on the outer surface, 45% on the inner surface, and 70% on the edges. Eighty-two percent of the laryngoscope blades were stained, 11% heavily. Staining was present on many of the other instruments they examined as well, including four of five bougie tips and three of five Magill forceps. Although the findings have not yet been validated, based on their experiences, the team members concluded that

Despite new processing recommendations and new disinfection products being developed, two neurologists have suggested that patients might want to consider asking surgeons if the instruments being used on them are free of prions. (14) The result of any method of disinfecting instruments is contingent upon the effectiveness of that process, so it is reasonable to believe that the need for an adjunct product capable of verifying the efficacy of the process in its entirety is imminent.

IDENTIFYING A CARRIER

Notwithstanding the moral and ethical issues of reusing potentially contaminated instruments, the legal and financial ramifications are infinite. This is compounded by the consideration that the same disinfecting, cleaning, and sterilization techniques are being recommended for use not only on devices and instruments used on known carriers but also on those used on patients who are suspected of being carriers. As of now, a carrier of sporadic CJD only can be identified by either a surgical brain biopsy or an autopsy after death. Not to be overlooked is the possibility that a person may be a carrier of a dormant prion and, therefore, not be aware of his or her infection.

Is there a solution to this perplexing situation? It appears that one is available. A group of researchers at the Hadassah University Hospital in Jerusalem determined that a precipitable and protease-resistant form of the prion protein could be detected in dialyzed urine. Dialyzed urine is considered to be depleted of molecules shorter than the dialysis settings, usually a molecular weight of approximately 8,000 daltons.

The experiments further suggest that the protease-resistant prion protein isoform is excreted in urine parallel to its accumulation in the brain; thus, the researchers concluded that urine testing for protease-resistant protein prion can be used not only to diagnose prion diseases in animals and humans at terminal stages of the disease but also in the subclinical stages of the infection. (15,16) Based on the favorable results of the initial trials by the research group, arrangements have been made for the manufacture of diagnostic test kits for humans and animals that will be used to confirm the efficacy of the method. (17) Pending favorable outcome of experiments being conducted in collaboration with different entities and the completion of blind studies to determine the status of the test, the universal use of this urine test could identify every carrier of this fatal disease--be they human or animal.

CONCLUSION

With the availability of high-tech diagnostic tests and myriad new antibiotics, it is difficult to comprehend how new diseases, about which little is known and for which cures must be developed, emerge as frequently as they do. On the other hand, although CJD has plagued society for three-quarters of a century, a simple way to identify its victims, much less cure them, has not yet been developed. Nevertheless, from the perspective of patient safety, it is incumbent upon the perioperative nurse community to be aware of symptoms of CJD and the importance of nurses' role in preventing the transmission of this fatal disease. As for patients who are suspected of being carriers, the availability of a noninvasive diagnostic test will serve a dual purpose. The results could alert the surgical team to the patient's condition and emphasize the need for special measures to be taken in rendering instruments suitable for reuse. Not to be overlooked is that the results also could make it possible for a patient and his or her family members to be relieved of whatever fears or anxieties they may have had about the quality of their lives.

NOTES

(1.) L M Crawford, "Bovine spongiform encephalopathy," American Journal of Infection Control 26 (February 1998) 5-7.

(2.) K L Tyler, Creutzfeldt-Jakob disease, The New England Journal of Medicine 348 (Feb 20, 2003) 681-682.

(3.) V M Steelman, "Creutzfeldt-Jakob disease: Recommendations for infection control," American Journal of Infection Control 22 (October 1994) 312-318.

(4.) V M Steelman, "Creutzfeldt-Jakob Disease: Decontamination issues," Infection Control and Sterilization Technology 3 (September 1996) 32-39.

(5.) V M Steelman, "Prion diseases--An evidence-based protocol for infection control," AORN Journal 69 (May 1999) 946-967.

(6.) M Fishman, G G Fort, D J Mikolich, "Handling of surgical instruments in a presymptomatic familial carrier of Creutzfeldt-Jakob Disease, American Journal of Infection Control 30 (August 2002) 303-306.

(7.) L F Muscarella, "Assessing the risk of Creutzfeldt-Jakob disease," Infection Control Today 7 (August 2001) 28-30.

(8.) Joint Commission of Accreditation of Healthcare Organizations, "Exposure to Creutzfeldt-Jakob disease," in Sentinel Event Alert, no 20 (June 2001) http://www.jcaho.org /about+us/news+letters/sentinel+event+alert /sea_20.htm (accessed 9 June 2003).

(9.) "Mad cows and Englishmen: Variant CJD emerges in UK," Hospital Infection Control 28 (September 2001) 120-122.

(10.) D M Miller et al, "Presence of protein deposits on 'cleaned' re-usable anaesthetic equipment," Anaesthesia 56 (November 2001) 1069-1072.

(11.) World Health Organization Department of Communicable Disease Surveillance and Response, "WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Report of a WHO Consultation, Geneva, 23-26 March 1999," World Health Organization, http://www.who.int/emc-documents/tse/who cdscsraph2003c.html (accessed 9 June 2003).

(12.) C Werner, "Sterilization market a vibrant, active segment," Healthcare Purchasing News 27 (February 2003) 40-42.

(13.) W A Rutala, D J Weber, "Creutzfeldt-Jakob disease. Recommendations for disinfection and sterilization," Clinical Infectious Diseases 32 (May 1, 2001) 1348-1356.

(14.) J Mastrianni, R P Roos, "'Out, damned spot! out I say!'...: Issues related to prion contamination," Neurology 59 (Aug 27, 2002) 488-89.

(15.) G M Shaked et al, "A protease-resistant prion protein isoform is present in urine of animals and humans affected with prion diseases," Journal of Biological Chemistry 276 (Aug 24, 2001) 31479-31482.

(16.) Y Shaked, R Engelstein, R Gabizon, "The binding of prion proteins to serum components is affected by detergent extraction conditions," Journal of Neurochemistry 82 (July 2002) 1-5.

(17.) A Tzurket, personal communication with the author, Jerusalem, 11 Aug 2002.

Nathan L. Belkin, PhD, is retired and lives in Clearwater, Fla.

COPYRIGHT 2003 Association of Operating Room Nurses, Inc.
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