Creutzfeldt-Jakob disease (CJD) is a rare, slowly degenerating, viral disease that attacks the central nervous system. Originally discovered in 1920, the disease takes the lives of primarily older adults ages 50 to 75 at the rate of approximately one per million each year, worldwide. During the past 5 years, there have been many advances in the assessment and knowledge of this dreadful disease. In 19% a new variant of CJD (nvCJD) emerged. This phenotype, theoretically transmitted by bovine spongiform encephalopathy (BSE) or Mad Cow disease in British cattle, has increased public attention toward the disease. By understanding what has been researched and discovered about CJD, nursing care may be provided to patients more sensitively and efficiently. This article explores the pathophysiology and pathology of CJD. The physical assessment findings and tests used to diagnose the disease are reviewed and evaluated. Finally, nursing care of CJD patients is presented. The article concludes with a synthesis of what is known and unknown about. CJD and the implications for future nursing research and practice.
K.C., a 64-year-old White man, had been well for most of his life. However, in October 1995, after experiencing signs of coronary artery disease, he underwent a coronary artery bypass graft (CABG). What should have been an unremarkable recovery was tainted with severe behavior changes noted by K.C.'s wife, Donna. In March 1996, Donna saw her husband turn. into what she described as "Dr. Jekyll, Mr. Hyde." He became aggressive and paranoid. Accompanying these personality changes were a lack of coordination and vision problems. Eleven months after the CABG, K.C. was placed under the care of a neurologist. One year after the CABG, his wife was aiding his balance and walking, and 1 month later, he became dependent on a walker to ambulate. His neurologist hospitalized him again in December 1996 for plasmophoresis to treat peripheral neuropathy. However, the procedure resulted in no improvement, and K.C.'s ability to ambulate continued to deteriorate. His paranoia and aggressive behavior were magnified by communication and eating problems, incontinence, myoclonus, fearfulness, and a heightened startle reflex. Magnetic resonance imaging and multiple blood tests failed to reveal a cause for his deterioration. K.C. was hospitalized again in January 1997 and was seen by another neurologist who assessed K.C. for the possibility of CJD. Cerebrospinal fluid analysis was positive for proteins 14-3-3, consistent with CJD. A brain biopsy confirmed CJD. K.C. remained in the hospital and died 2 months later.
PATHOPHYSIOLOGY OF A SPONGIFORM ENCEPHALOPATHY
Creutzfeldt-Jakob disease is a member of a large group of spongiform encephalopathies affecting both humans and animals. Related diseases include Gerstmann-Sträussler syndrome in human beings, scrapie in sheep, chronic wasting disease in elk and deer, transmissible mink encephalopathy, and BSE in cows. Although no virus has been isolated in a CJD patient, the disease was labeled as a proteinacious infectious agent or "prion" in 1982 (Prusiner, 1995). Because the disease occurs at a similar incidence rate worldwide, other hypotheses currently are being investigated indicating that the disease may not be merely viral. Spontaneous generation of a selfreplicating host protein, with the virus, may explain the emergence of the disease between family members and in far reaches of the globe.
The disease is termed spongiform (resembling a sponge) because of the physiologic effects the virus has on the tissues of the brain. Encephalopathy implies brain degeneration without inflammation. Although the actual mechanism is not understood entirely, postmortem examination of brain tissue shows three processes that result in neurological deterioration. First, the neurons and glia swell and the nucleus displaces to the side of the cell. The contents of the neuron deteriorate, leaving membranebound nonfunctioning vacuoles containing membranous profiles of cellular structures. This process is called vacuolation.
The second process that impairs neurological function results when amyloid plaques block the transmission of messages across the membrane. These plaques are proteins composed of linear nonbranched grouped fibrils occurring in both the traditional and nvCJD phenotypes. Researchers have postulated three theories of the formation of such plaques. The first theory postulates that the plaques form as the circulating virus attaches to the macrophages of the immune system (Karp & Mirra, 1990). The second theory is that local, intrinsic, and physiochemical factors in the brain of the diseased patient may provoke amyloid formation and deposition (Brown, 1989, Wood & Anderson, 1988). The third theory is that the scrapie-associated fibrils found in CJD patients' brains are neurofilament-like atypical viruses that may interfere with the transport of neurofilaments down the axon and occasionally lead to amyloid accumulations (Gajdusek, 1974).
Astrocytosis coincides with the clinical course of the disease and is the third cause for neurological deterioration in CJD patients. Astrocytes are star-shaped, neuroglial cells with many branches. These cells partially compose the tissue that forms the supporting cells and fibers of the nervous system. The astrocytes become infected by the virus and proliferate, branching out and interfering with neuronal transmission.
The range of neuron deterioration and plaque formation reportedly is distributed throughout the nervous system. Some cases have shown spongiform changes primarily in the cortex. However, other cases have shown such changes deep in the nuclei of primarily the occipital, temporal, and parietal lobes of the brain and in the cerebellum. The location of involvement has been used to further classify the disease and to help identify the symptoms. When the disease is concentrated primarily in the occipital lobe it is known as the Heidenheim variation. The ataxic form is called cerebellar disease. Primarily spinal cord involvement is labeled the amyotrophic disease form (Wallace, 1993).
SYMPTOMS OF OD ACCORDING TO STAGES
PATHOLOGY OF TRADITIONAL AND NEW VARIANT OD
Traditional and nvCJD affects both men and women worldwide. Higher incidences of CJD have been found among Libyan Jewish immigrants to Israel, residents of Czechoslovakia, and Northern African immigrants to France Steelman, 1994). Onset ranges from ages 50 to 75 for traditional CJD but is younger for the new variant form. The officially stated mortality rate is one to two deaths per one million individuals per year (Brown, 1997). However, this statistic may be inaccurate related to difficulty in diagnosing the disease. Although much has been studied and written about the disease in the past 5 years, the route of transmission of CJD is unknown. Transmission is classified as sporadic (no known cause), acquired from iatrogenic, environmental, or familial sources (Brown, 1997). Although approximately 85% of the cases are classified as sporadic (Harries-Jones et al, 1988), this is most likely because of a failure to establish a link between the risk factor and the disease.
Iatrogenic transmission of CJD is of great concern to health care workers and the public. Higher incidences of CJD have been found in individuals who received corneal transplants. For example, a 45-year-old woman who died of respiratory complications related to CJD had undergone a corneal transplantation for keratonoconus 30 years earlier (Heckmann et al., 1997). A correlation between CJD and the transfer of infected cadaveric dura mater (Defebvre, Destee, & Caron, 1997) also has been shown. The association detected as early as the 1970s between CJD and the use of human growth hormone, tonometry measurement for intraocular pressure, and implantation of intracerebral electrodes further indicates the possibility of iatrogenic transmission (Steelman, 1994). More recently, pericardial homograft used to patch the tympanic membrane was viewed as the possible cause of CJD in a 51year-old woman (Tange, Troost, & Limburg, 1990).
The possibility of the causative organism's transmission in the blood supply has the potential to cause increased panic related to fear of an emerging epidemic. However transmission of the causative agent through the blood supply has not been documented (Nguyen & Rickman, 1 997). As continued awareness of CJD transmission is achieved, the risk of iatrogenic transmission likely will diminish and more precautions will be taken. For example, The Centers for Disease Control and Prevention (CDC) recently issued a memorandum stating that individuals who received high-risk medical treatments should not donate blood or organs (United States Department of Health and Human Services, 1996).
Although, research has shown that 5% to 15% of cases of CJD are familial (Brown, 1989), it is not known whether the familial relationship is genetic. It is possible that family members share a culturally related common source of infection (Wood & Anderson, 1988), such as the consumption of beef infected with BSE. The presence of abnormal prion-protein (PrP) has been confirmed in some individuals with the disease, possibly resulting from genetic mutations in a gene that encodes a protein on chromosome 20 (Nguyen & Rickman, 1997). The emergence of the genetic mutation lends support to the possibility of a self-replicating host protein, working in isolation or with an infectious agent. In the future, PrP may help differentiate between sporadic and familial cases of CJD based on genetic analysis.
Much literature has appeared recently about nvCJD, consistent with a different single strain of the infectious organism that causes CJD. A study of 14 patients diagnosed with nvCJD in the United Kingdom and France (Zeidler et al., 1997) showed that the age range for the new variant form was from ages 16 to 48. The disease has a longer course and different morphology and symptomatology than traditional CJD. Although 22 residents of the United Kingdom and France (Zeidler et al., 1997) potentially were infected with CJD from BSEinfected cattle, the relationship has not been established conclusively (Schonberger, 1998).
The CJD prion is not destroyed easily. The infectious organism has been found to remain infectious even after extensive boiling in water and exposure to commonly used disinfective agents (Wood & Anderson, 1988). Steelman (1994) recommends that in addition to universal precautions, instruments used on actual or potential sufferers of CJD should be wiped and steam-sterilized pre vacuum for 1 8 minutes and standard gravity for 60 minutes at 1340C. When this is not possible, Steelman (1994) suggests soaking items for 1 hour in 1 Eq/L sodium hydroxide. Further, all trash, sharps, tissue remnants including liquid waste, and wash water should be contained and incinerated*.
PROTOCOL FOR ASSESSMENT AND MANAGEMENT OF PATIENTS WITH CJD AND nvCJD
PROTOCOL FOR ASSESSMENT AND MANAGEMENT OF PATIENTS WITH CJD AND nvCJD
ONSET AND SYMPTOMS
The time span from onset of symptoms to inevitable death from CJD is 6 to 12 months in traditional CJD. However, nvCJD has an average duration of 14 months (Will et al., 1996). There is evidence suggesting an incubation period between 10 and 15 years (Brown, 1996). The disease generally is divided in three stages (Table 1). The disease may progress from Stage 1 to Stage 2 in a matter of several weeks. However, the transition from Stage 2 to Stage 3 usually is more gradual, lasting from 6 to 18 months. Because of the rapid onset and duration of the disease, symptoms from all stages may occur simultaneously. It often is thought that the psychiatric and behavioral symptoms of the disease are similar to Alzheimer's disease (AD). The acronym PALS describes four early symptoms of the CJD: paranoia, agitation, lassitude, and startle reaction. These symptoms usually are more pronounced in CJD and may help to distinguish CJD from AD.' Zeidler et al. (1997) suggest the psychiatric symptoms are more pronounced in nvCJD. One noticeable difference between AD and CJD is that CJD dementia occurs over 4 to 7 months, while AD progresses over 4 to 7 years.
Neurological examination remains the most effective tool in diagnosing CJD. Because the cerebellum often is infected in both traditional and nvCJD, difficulty with rapid alternating movements and point-to-point examinations often are evident early in the disease. Patients may have marked difficulty in tandem, heel-totoe, and normal walking movement. A Romberg's sign (i.e., inability to maintain balance when eyes are shut and feet are close together) most likely will be positive as early as Stage 1 . Altered muscular tonicity also has been noted.
Cranial nerve examination reveals loss of sensation in CJD sufferers. In nvCJD, painful sensory disturbance early in the disease is more common (Ziedler et al., 1997). Responses to pain, temperature, and touch may be decreased or take the form of a startled response. Losses of olfactory and gustatory sensation, hemiopia (i.e., blindness in half of the visual field), and dissociation of eye movements, suggest dysfunction of the cranial nerve pathway. Apparent imperceptibility and neglect of a limb or of one side of the body shows parietal lobe dysfunction. Optic agnosia indicates occipital lobe disease, although overt sensory loss rarely is observed.
Examination of the reflexes may reveal exaggerated deep tendon reflexes of the arms and legs, nonelicitable ankle reflexes, and negative abdominal reflexes. Babinskys reflex generally will be present. There is no agreement on the presence of pupillary reflexes. Electroencephalogram (EEG) readings always will be abnormal in CJD patients and remain an effective diagnostic tool. Slow wave activity is observed, spreading as the condition worsens. Rhythmic, periodic bursts of high voltage, diphasic, or triphasic sharp wave complexes intervening with periods of electrical silence are evident The frequency of spikes wiU be 20 to 40 per minute in the early stages of the disease, slowing to 3 to 5 spikes per minute in the later stages. The EEG readings in nvCJD are not consistently abnormal (Zeidler et al., 1997).
In the past, the most effective method of diagnosing CJD was through a biopsy of the brain. Although this continues to be an effective method of diagnosing the disease, there is risk of spread of infection and a high rate of false negative results when the part of the brain biopsied is free of the CJD virus. Intracerebral inoculation of the brain tissue from a CJD-infected human brain to the brain of a primate yielded growth of the virus in the infected primate in 90% of experimental cases during a 2-year period (Brown, 1989).
Although brain biopsies still are conducted currently, "research has provided several new, more efficacious methods of diagnosing the disease. In conjunction with the physical findings, a 14-3-3 cerebrospinal fluid (CSF) test often is effective in diagnosing CJD. Bahn, Kido, Lin, and Pearlman (1997) found that diffusion magnetic resonance imaging (MRI) of the brain has joined computed tomography scanning as a sensitive means of imaging the abnormalities in the CJD-infected brain. Mild to moderate ventricular dilation and cortical atrophy may be seen on MRI. Prionprotein gene analysis also has been suggested as a possible way in which to detect the disease (Goldfarb, Brown, Cervenakova, & Gajdusek, 1994). Genetic mutations in a gene that encodes a protein on chromosome 20 changes normal PrP into a PrP isoform that allows for the growth of the viral agent (Nguyen & Rickman, 1997). The presence of the abnormal PrP has been confirmed in some individuals with traditional and nvCJD. Prion-protein gene analysis may become an effective method of diagnosing CJD prior to the onset of symptoms in family members of CJD patients.
TREATMENT AND PROGNOSIS
Despite the advances in public awareness and diagnoses of CJD, there remains no treatment for the disease. Furthermore, nothing has been found to slow oí the progression of the CJD virus. Because the symptoms of CJD are similar to other treatable neurological disorders and no common tests reveal CJD, it is very difficult to diagnose. Thus, many patients are diagnosed incorrectly as having other neurological abnormalities such as peripheral vascular disease, AD, or other long-term illnesses. This presents a double tragedy to families because they may postpone end-of-life decisions, arrangements, and emotional adjustment only to have their loved ones die within 6 to 12 months.
Nursing care for CJD remains palliative. Among individuals with CJD, death from intercurrent infections such as pneumonia, or from effects of seizures, usually occurs within 6 to 12 months of diagnosis (Wood & Anderson, 1988).
NURSING ASSESSMENT AND CARE
All aspects of the nursing process are used for the care of older individuals with CJD and are summarized in the protocol (Table 2). The first critical role of nurses is assessment. Information and knowledge regarding the risk of the disease are essential in helping early diagnosis. Nurses initially may encounter an individual before the diagnosis of CJD. Sudden onset of movement, psychiatric, and behavior disorders may trigger a further assessment of CJD. In addition, the presence of a family history or high-risk iatrogenic exposure, such as the use of human growth hormone or cadaver transplants, suggest the possibility of the disease. Because the disease has been detected only in recent years, death of family members from questionable neurological diseases, in conjunction with physical findings, possibly may indicate a family history of CJD.
Although symptoms of CJD are similar to those of AD, PALS may help to differentiate the two diseases. Dementia should be diagnosed only following a full physical and mental status examination. The MiniMental Status Examination (Folstein, Folstein, & McHugh, 1975) is an effective method to determine the cognitive status of the individual and track future deterioration. A full neurological examination including cerebellar assessment for movement disorders, reflexes, and cranial nerves should be undertaken. If physical findings suggest CJD, the patient should be referred for EEG, CSF analysis, and MRI to confirm the presence of abnormal wave appearance, 14-3-3 proteins, and ventricular and cortical changes in the brain. A brain biopsy may be undertaken if further diagnostic information is needed.
Although definitive diagnosis may not be made until autopsy, if CJD is diagnosed with reasonable certainty, nurses should provide palliative care to the patients. In the case of K.C, an efficient diagnosis would have provided the family both the ability to avoid invasive diagnostic procedures and increased time for anticipatory grieving. Because the disease progresses quickly, frequent evaluations of the patient's mental and neurologic status should be made. The death of CJD patients generally is caused by intercurrent problems such as injuries, epileptic seizures, malnutrition, pneumonia, and sepsis. The functional status will decline to the point at which patients are no longer able to care for themselves or recognize when they are in environmental or physical danger. Nurses must implement interventions to protect patients from further physical deterioration, injury, and infection. These interventions are included in the protocol (Table 2). It is important to note that CJD patients may have a heightened startle response to stimuli. A low-stimulus environment may help decrease hallucinations and delusions.
The short time span from diagnosis until death provides little time for family members to progress through the grieving process. Early diagnosis of the disease is helpful in assisting families to adjust as early as possible. Patients and their families will require education about the disease. Although little written information is available for family members, the World Wide Web may provide appropriate resources for information and support. Patients and thenfamilies should be allowed to express their feelings and questions so therapeutic communication can ensue. It is important to remember that CJD patients, although often cognitively impaired, can hear what is being said in the room. Sensitivity should be displayed to patients and their families at all times while they attempt to cope with the disease. Information and support with decision-making regarding life- sustaining interventions and where and how their relative is treated, is essential.
Although risk of transmission of CJD from patients to health care workers has not been established (Nguyen & Rickman, 1997), disease precautions should be implemented. There is no need to isolate CJD patients in private rooms. However, universal precautions should be practiced. In addition, disease precautions for disposal and sterilization of equipment listed earlier should be used while caring for CJD patients.
There have been many advances in the assessment and knowledge regarding this dreadful disease during the past several years. The emergence of nvCJD has increased public attention toward the disease. In addition, several new diagnostic instruments including CSF analysis, MRI, and the isolation of PrP have increased the ability to diagnose the disease at an earlier stage. However, little is known about this fatal neurological disease. Individuals are not always diagnosed or are diagnosed too late for their families to begin the grieving process. Nursing care provided to CJD patients reflects the current knowledge base. However, nursing research into the care of CJD patients will increase the ability to provide more clinically efficient and sensitive care.
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SYMPTOMS OF OD ACCORDING TO STAGES
PROTOCOL FOR ASSESSMENT AND MANAGEMENT OF PATIENTS WITH CJD AND nvCJD
PROTOCOL FOR ASSESSMENT AND MANAGEMENT OF PATIENTS WITH CJD AND nvCJD