eMedicine Specialties > Neurology > Neurological Infections

Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy: Follow-up

Author: Chitharanjan Rao, MD, DM, MRCP, DNB, Assistant Professor, Department of Neurology, University of Pittsburgh School of Medicine
Coauthor(s): Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Contributor Information and Disclosures

Updated: Apr 27, 2007

Follow-up

Further Inpatient Care

Patients may be admitted for an expedited workup, including lumbar puncture and biopsies. Some patients may need inpatient psychiatric care.

Further Outpatient Care

As discussed, patients may need treatment for psychiatric and sensory symptoms in addition to the increasing need for supportive care.

Deterrence/Prevention

Variant CJD may spread by iatrogenic means; concern is even more necessary with variant CJD compared with other prion diseases because the titer of the causative agent appears to be high in systemic organs, although not as high as in the neural tissues.

Because the prion agent is highly resistant to inactivation, routine sterilization methods such as autoclaving are not effective. Hence, electromyography and EEG needles, surgical instruments, and other equipment that has been exposed to a patient with variant CJD should not be reused. When such equipment is used in patients with suspected prionoses, it can be quarantined while the definitive studies are pending. If variant CJD is proven, used equipment must be destroyed. If the diagnosis is disproved, equipment can be reused.

Complications

Any part of the CNS can be affected; therefore, a range of CNS complications can be expected. These include gait difficulties due to spasticity and cerebellar ataxia, choreoathetosis, startle responses, myoclonus, dysphagia due to pseudobulbar palsy, incontinence, and akinetic mute state.

Most patients succumb to bronchopneumonia, brought about by their bed-ridden state.

Patient Education

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center and Public Health Center. In addition, see eMedicine's patient education articles Mad Cow Disease and Variant Creutzfeldt-Jakob Disease and FDA Overview.

Miscellaneous

Medicolegal Pitfalls

In the United States and Europe, surveillance of patients with prion diseases is performed. Therefore, reporting any suspected prion disease, in particular suspected variant CJD, to surveillance agencies is necessary.

Autopsies are performed in only an estimated 22% of cases of CJD in California. The autopsy rates of suspected cases of CJD should increased because only a pathologic review of tissue can distinguish between classic and variant forms of CJD.

Two of the surveillance agencies in the United States are the National Prion Disease Pathology Surveillance Center at Case Western Reserve University in Cleveland, Ohio and the California Creutzfeldt-Jakob Disease (CJD) Surveillance Project.

Because the incubation period of variant CJD is long, patients may be infectious during the clinically silent period. Therefore, determine if patients donated blood or other body tissues during that period. This concern is particularly relevant for variant CJD because systemic organs, especially lymphoid tissues, contain a fairly large amount of infectious material.

Special Concerns

Because prions are highly resistant to inactivation, material from patients with variant CJD must be handled with special care. CNS tissue has the highest concentration of prion agent and needs to be handled with greatest caution. Unlike other prion diseases, in variant CJD, other body tissues, especially lymphoid material, have significant concentrations of prion agent and, therefore, merit particular care.

Special disinfection protocols have been developed by the WHO, and they should be meticulously followed (see WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies).

Individuals exposed to BSE might be asymptomatic carriers of the infection.92,93,94 Because of this potential problem, awareness of the need to use adequate sterilization procedures for surgical instruments is increasing. However, the recommended use of high-temperature autoclaving plus sodium hydroxide is difficult to achieve for some types of instruments.95

Concern is widespread that the blood supply might be contaminated with the variant CJD agent. This possibility is supported by evidence that BSE in sheep can be transmitted by blood transfusion.39 This concern progressed to fear with a recent report of a patient who died of variant CJD 6.5 years after receiving a transfusion of red blood cells donated by an individual who subsequently developed variant CJD.45 The authors do not present direct evidence that the disease was transmitted by blood transfusion, but the chance that this case is not transfusion related is very small.

One more case of blood transfusion–related variant CJD has been reported.47 This case is unique and very important in terms of its implications. This patient died from a non-neurologic disorder 5 years after receiving a blood transfusion from a donor who subsequently developed variant CJD, and he had no symptoms suggestive of variant CJD at the time of his death. Protease-resistant prion protein (PrPres) was detected in the spleen and a cervical lymph node but not in the brain. He was heterozygote at codon 129 of PRNP, suggesting that susceptibility to variant CJD infection is not confined to methionine homozygous PRNP genotype.

This possibility, combined with the probable existence of subclinical carriers, raises the specter of an iatrogenic human-to-human wave of variant CJD transmission.96 This again highlights the need for reliable detection methods for prion-tainted blood products.97 In addition, a finding of preclinical infection in a patient heterozygous at codon 129 of PRNP has significant implications regarding the future estimates and surveillance of variant CJD.

Although polymerase chain reaction–based assays have almost eliminated the risk of transmission of many blood-borne viruses, no tools of similar efficacy exist for prion detection.98 However, a novel technique based on protein misfolding cyclic amplification of aggregated PrPSc may enable detection of very small quantities of PrPSc-priming template in the blood; as yet, this method is not suited to high-volume screening of blood donations.99

UK Blood Transfusion Services have taken a number of measures to minimize the transmission of variant CJD by blood, plasma, and tissue products (UK Blood Transfusion & Tissue Transplantation Guidelines):

  • Withdrawal and recall of any blood components, plasma derivatives, or tissue derivatives obtained from any individual who later develops variant CJD
  • Importation of plasma from countries other than the United Kingdom for fractionation to manufacture plasma derivatives 
  • Leukodepletion of all blood components 
  • Deferral of whole blood donors who state that they have received a blood component transfusion, including those with UK-derived plasma; those who have received intravenous immunoglobulin in the United Kingdom since January 1, 1980; or those who have undergone plasma exchange 

Similarly, the US FDA has introduced progressively more stringent recommendations for deferral from blood donation from individuals who have traveled or resided in the United Kingdom and other parts of Europe (Guidance for Industry - Revised Preventative Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease [CJD] and Variant Creutzfeldt-Jakob Disease [vCJD] by Blood and Blood Products). According to these guidelines, blood donations from any individual who has traveled to or resided in the United Kingdom for longer than 3 months from 1980 through 1996, receipt of a blood transfusion in the United Kingdom since 1980, and travel or residence in a European country (including US military bases) for more than 5 years since 1980 are excluded. Implementation of these guidelines would probably result in deferral of 5-9% of donors.
 
Concerns about the prevalence of subclinical prion carriers and human-to-human transmission have caused considerable insecurity among public health authorities as to the potential size of the variant CJD epidemic. Therefore, despite the fact that cross-sectional studies to assess the prevalence of prion carriers pose organizational and ethical problems, no alternative is available for assessing the future of the variant CJD epidemic.100

 


More on Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy

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Differential Diagnoses & Workup: Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy
Treatment & Medication: Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy
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References
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Further Reading

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Keywords

transmissible spongiform encephalopathies, TSE, prion diseases, prionosis, prionoses, PrP diseases, Creutzfeldt-Jakob disease, CJD, sporadic CJD, sCJD, new variant CJD, nvCJD, variant CJD, vCJD, bovine spongiform encephalopathies, BSE, mad cow disease, mad cow, mad cows, scrapie, kuru, Gerstmann-Strãussler-Scheinker disease, GSS, familial fatal insomnia, FFI, sporadic fatal insomnia, SFI, chronic wasting disease, CWD

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Contributor Information and Disclosures

Author

Chitharanjan Rao, MD, DM, MRCP, DNB, Assistant Professor, Department of Neurology, University of Pittsburgh School of Medicine
Chitharanjan Rao, MD, DM, MRCP, DNB is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association, Medical Council of India, and Royal College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

Medical Editor

Amy A Pruitt, MD, Program Director, Assistant Professor, Department of Neurology, University of Pennsylvania
Amy A Pruitt, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, University of Pittsburgh Medical Center - Shadyside, Clinical Associate Professor, Department of Neurology, University of Pittsburgh School of Medicine
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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