Creutzfeldt-Jakob Disease

A form of neurodegenerative human prion (acronym for “proteinaceous infectious particles”) disorder, which belongs to a group of diseases known as transmissible spongiform encephalopathies.

Worldwide, the incidence of Creutzfeldt-Jakob disease (CJD) in the general population is approximately 1:1,000,000 per year. A variant of CJD (vCJD) has been associated with bovine spongiform encephalopathy (BSE) and has the highest occurrence in the United Kingdom. As of November 2005, the total number of definite or probable vCJD cases (dead and alive) in the United Kingdom was 158 (in 108 cases with neuropathologic confirmation). A causal association between vCJD and BSE is supported by epidemiologic and laboratory evidence in areas with high prevalence of BSE and the lack thereof in basically BSE-free regions.

The occurrence of CJD, like other forms of prion diseases, is familial (5-10% of cases, with autosomal dominant inheritance caused by mutations in the PRNP [prion protein] gene, which has been mapped to 20pter-p12), sporadic (approximately 90% of patients with noninherited mutation of the prion protein), or infectious (iatrogenic with the first reported case of vCJD in 1974). The infectious agent in prion disease consists almost entirely of a host-encoded protease-resistant, neuronal cell surface sialoglycoprotein termed prion protein.

The cause is not fully understood but is believed to be related to misfolding of the normal endogenous cellular prion protein PrPC into a new pathogenic conformation PrPSc encoded by PRNP. Prion protein is necessary for normal synaptic function. Iatrogenic and infectious transmission has occurred via tissue transplants (e.g., corneal transplants and no longer used dura mater grafts), cadaveric pituitary gland extracts (e.g., for human growth hormone [hGH] and gonadotropin production, now replaced by synthetic hormones), and contamination by neurosurgical instruments and stereotactic electroencephalography electrodes. Currently, blood is considered to pose a theoretical risk only, and no cases related to blood transmission have been reported. Accumulation of PrPSc in the central nervous system of affected individuals is responsible for the typical degenerative changes, such as loss of neurons, vacuolization, and finally death.

There is no definitive clinical diagnostic test apart from the neuropathologic investigation. Patients have variable clinical and pathologic pictures. Pathology findings include diffuse nerve cell degeneration, status spongiosus, and glial proliferation. The electroencephalogram may show characteristic periodic complex changes.

The vast majority of patients are between 50 and 70 years old at the onset of the disease, although significantly younger affected patients have been reported. The onset of familial cases is significantly earlier than in other forms. The course of the illness may last from a few weeks to several years, although in general it is rapidly progressive. It is uniformly fatal, with the average length of survival from onset of the disease being approximately 6 months. Affected patients present with signs of dementia that often are accompanied by behavioral changes and psychiatric anomalies. Characteristic electroencephalographic changes can be detected (a slow background rhythm with superimposed periodic biphasic or triphasic synchronous sharp-wave complexes), which are clinically often accompanied by myoclonus and progressive motor dysfunction. Numerous other neurologic symptoms such as pyramidal and extrapyramidal signs (muscular rigidity), seizures, nystagmus, autonomic dysfunction, and signs of cerebellar dysfunction (unsteady or atactic gait), may occur. Forgetfulness or nervousness, supranuclear gaze paralysis, and loss of facial expression may occur. Some neurologic features may subside in the terminal phase of the disease. Autopsy reveals generalized brain atrophy; however, if the course of the disease is rapid (i.e., death in less than 6 months), the macroscopic changes may only be subtle. CJD is a spongiform encephalopathy resulting in diffuse loss of neurons, reactive astrocytosis, and widespread vacuolization of the neuropil. Electron microscopy locates the round vacuoles within the neuroplasma and neuropil of the cortical gray matter. The vacuoles vary in diameter from 1 to 50 μm and appear to contain membranous particles.

In contrast to the classic form of CJD, vCJD predominantly affects young persons and presents initially with atypical features such as prominent psychiatric and sensory symptoms, whereas onset of neurologic symptoms is delayed and the electroencephalogram is unspecific. The course of the disease lasts longer than in the classic form (at least 6 months), and the median age at death is approximately 30 years. Spongiform encephalopathy is more pronounced and a higher number of Kuru-type amyloid plaques surrounded by prion protein accumulations and vacuoles can be detected, which may be, at least in part, a reflection of the prolonged course of vCJD.

Except for the cerebral changes, these patients are otherwise healthy. However, in advanced stages of the disease, a chest radiograph may be necessary because recurrent aspirations may occur. Cooperation may be limited secondary to dementia. Sedative premedication may be helpful.

Not different from other forms of dementia. The main issue is preventing infections among staff. Special attention must be paid to the sterilization of medical equipment. Extensive prion infection of lymphoreticular tissues has been detected during the asymptomatic incubation period of vCJD. Medical instruments exposed to these infected tissues (e.g., Waldeyer ring of lymphoid tissue in the pharynx for the laryngoscope blade) of preclinically infected individuals might represent a potential risk of iatrogenic transmission of vCJD if reused after routine sterilization. In a recent study, lymphocytes were detected on 30% of used (and uncleaned) laryngoscope blades. Since prions are resistant to routine sterilization processes, it was concluded, that this might pose a potential risk of transmission of vCJD from patient to patient. Although the blades in that study were not sterilized before sampling them, it seems wise to use disposable equipment whenever possible in patients with known or suspected infection.

These patients may be taking antiseizure medications, which may interact with the metabolism and elimination of anesthetic drugs.