Creutzfeldt-Jakob disease overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.
Overview
Creutzfeldt-Jakob disease is a very rare, invariably fatal degenerative neurological disorder of the brain. It is caused by the presence of a prion protein, an abnormal isoform of a cellular glycoprotein.[1] Creutzfeldt-Jakob disease may be classified into either sporadic, familial and iatrogenic forms. The sporadic form may be further categorized into either classic or variant Creutzfeldt-Jakob disease. The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission. Reports on transmission by human growth hormone products, grafting, surgical electrode implantation, and consumption of infected products have been described. Once transmitted, the CJD prion promotes refolding of the native proteins into the diseased state. The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells, resulting in cell death. Risk factors for Creutzfeldt-Jakob disease include advanced age, positive family history, personal history of psychosis, history of surgical procedures, grafts or implants, and history of ingestion of human growth hormones or contaminated meat. Once symptoms develop, Creutzfeldt-Jakob disease is rapidly progressive and almost always fatal. Early symptoms are often non-specific. Patients' relatives usually report rapidly progressive dementia, personality changes, uncontrolled sporadic laughter, and sleep disorders. The majority of patients (85% of patients) die within 1 year of symptom-onset. Common complications of Creutzfeldt-Jakob disease include overwhelming infections, congestive heart failure, or respiratory failure. The diagnosis of Creutzfeldt Jakob disease depends on a combination of positive findings from physical examination and laboratory testing. Based on the findings, the diagnosis of Creutzfeldt Jakob disease may be either probable or possible. There are no definitive criteria for the diagnosis of Creutzfeldt Jakob disease. Typical EEG findings in Creutzfeldt-Jakob disease include periodic biphasic or triphasic sharp wave complexes (PSWCs). Periodic synchronous discharges (PSDs) occur either before or in synchronicity with myoclonus. Biopsy of the brain tissue is the definitive diagnostic test for Creutzfeldt-Jakob disease, but is not usually performed. Management of Creutzfeldt-Jakob disease is directed towards palliative care. There is no effective treatment or vaccine for Creutzfeldt Jakob disease.
Historical Perspective
Creutzfeldt Jakob disease was first described in 1920-1921 by two German neurologists, Hans Gerhard Creutzfeldt and Alfons Maria Jakob.
Classification
Creutzfeldt-Jakob disease may be classified into either sporadic, familial and iatrogenic forms. The sporadic form may be further categorized into either classic or variant Creutzfeldt-Jakob disease.
Pathophysiology
The majority of cases of Creutzfeldt-Jakob disease are thought to occur sporadically from prions by an unknown route of transmission. Reports on transmission by human growth hormone products, grafting, surgical electrode implantation, and consumption of infected products have been described. Once transmitted, the CJD prion promotes refolding of the native proteins into the diseased state. The number of misfolded protein molecules increases exponentially, and the process leads to a large quantity of insoluble prions in the affected cells, resulting in cell death. On gross histopathological analysis, the brain tissue appears "spongy" with areas of perforation within the brain tissue. On microscopic histopathological analysis, spongiform changes, neuronal loss, astrocyte proliferation, and deposition of prion proteins in the brain are characteristic findings.
Causes
Creutzfeldt-Jakob disease (CJD) is caused by the presence of a prion protein, an abnormal isoform of a cellular glycoprotein.[1]
Differential Diagnosis
Creutzfeldt-Jakob disease must be differentiated from other causes of rapidly progressive dementia, such as other neurodegenerative diseases, infections, Alzheimer's disease, vascular dementia, and dementia due to metabolic or toxic etiology.[2]
Epidemiology and Demographics
Creutzfeldt-Jakob disease is a rare disorder with an incidence of approximately 0.1 to 0.3 cases per 100,000 individuals. In the USA, less than 300 cases of Creutzfeldt-Jakob disease have been reported. Individuals > 50 years of age are at higher risk of developing Creutzfeldt-Jakob disease than younger individuals. The most common age at diagnosis is approximately 60-65 years (range 45-90). On the other hand, variant (non-classic) Creutzfeldt-Jakob disease is more common among younger individuals. There is no gender or racial predilection for the development of Creutzfeldt-Jakob disease. Creutzfeldt-Jakob disease is more commonly described in Africa, but this is thought to be attributed to cannibalism practices in certain African tribes in the 1950s and ingestion of infected human brains, rather than true racial variation.
Risk Factors
Risk factors for Creutzfeldt-Jakob disease include advanced age, positive family history, personal history of psychosis, history of surgical procedures, grafts or implants, and history of ingestion of human growth hormones or contaminated meat.
Natural History, Complications and Prognosis
Once symptoms develop, Creutzfeldt-Jakob disease is rapidly progressive and almost always fatal. Early symptoms are often non-specific. Patients' relatives usually report rapidly progressive dementia, personality changes, uncontrolled sporadic laughter, and sleep disorders. The majority of patients (85% of patients) die within 1 year of symptom-onset. Common complications of Creutzfeldt-Jakob disease include overwhelming infections, congestive heart failure, or respiratory failure.
Diagnosis
Diagnostic Criteria
The diagnosis of Creutzfeldt Jakob disease depends on a combination of positive findings from physical examination and laboratory testing. Based on the findings, the diagnosis of Creutzfeldt Jakob disease may be either probable or possible. There are no definitive criteria for the diagnosis of Creutzfeldt Jakob disease.
History and Symptoms
Common symptoms of Creutzfeldt-Jakob disease include progressive dementia, depression, personality changes, uncontrolled sporadic laughter, sleep disorders, and jerky movements (characteristic myoclonus).[3]
Physical Examination
Physical examination is required for the diagnosis of Creutzfeldt-Jakob disease. Physical examination findings of Creutzfeldt-Jakob diseasefindings include myoclonus, extrapyramidal signs, akinetic mutism, and visual or cerebellar signs[4]
Laboratory Findings
Routine laboratory tests are usually normal in Creutzfeldt Jakob disease. Analysis of CSF for 14-3-3 protein may be helpful in the diagnosis of Creutzfeldt-Jakob disease.[5] Other elevated proteins in CSF may include S-100, neuron specific enolase, and Tau protein.
MRI
MRI findings in CJD include high signal abnormalities in caudate nucleus and/or putamen on diffusion-weighted imaging (DWI) or fluid attenuated inversion recovery (FLAIR).[1] Additional findings on diffusion weighted imaging include cortical, subcortical, and thalamic involvement. An abnormal signal in the poster thalami on T2 (pulvinar sign) and diffusion weighted images and fluid-attenuated inversion recovery sequences on brain MRI, in the appropriate clinical context, is highly specific for variant Creutzfeldt-Jakob disease.
CT and PET Scan
CT and PET scans are generally normal in Creutzfeldt-Jakob disease and may be helpful in ruling out other diseases. On CT scan, rapidly progressive ventricular enlargement and cortical atrophy may be present. On PET scan, abnormalities in thalamic regions may be present.
EEG
EEG findings are not diagnostic of CJD, but may help in the diagnosis of CJD. Typical EEG findings in Creutzfeldt-Jakob disease include periodic biphasic or triphasic sharp wave complexes (PSWCs). Periodic synchronous discharges (PSDs) occur either before or in synchronicity with myoclonus.[6]
Biopsy
Biopsy of the brain tissue is the definitive diagnostic test for Creutzfeldt-Jakob disease, but is not usually performed. Deposits of prion protein (scrapie), PrPSc, can be found in the skeletal muscle and/or the spleen (approximately 30% of cases).
Treatment
Medical Therapy
Management of Creutzfeldt-Jakob disease is directed towards palliative care. There is no effective treatment for Creutzfeldt Jakob disease.
Primary Prevention
There is no vaccine against Creutzfeldt-Jakob disease. Preventive measures to reduce Creutzfeldt-Jakob disease have not been studied and may or may not be helpful. Preventive measures may include sterilizing medical equipment before use, avoiding the use of infected patients as cornea donors, managing infected animals (e.g. cows), and not accepting transfusions from individuals with certain travel histories (e.g. travel to UK for > 6 months between 1980-1996).
References
- ↑ 1.0 1.1 1.2 "http://www.cdc.gov/ncidod/dvrd/cjd/qa_cjd_infection_control.htm#what". Retrieved 14 February 2014. External link in
|title=(help) - ↑ Paterson RW, Torres-Chae CC, Kuo AL, Ando T, Nguyen EA, Wong K; et al. (2012). "Differential diagnosis of jakob-creutzfeldt disease". Arch Neurol. 69 (12): 1578–82. doi:10.1001/2013.jamaneurol.79. PMID 23229042.
- ↑ Haywood, AM. (1997). "Transmissible spongiform encephalopathies". N Engl J Med. 337 (25): 1821–8. doi:10.1056/NEJM199712183372508. PMID 9400041. Unknown parameter
|month=ignored (help) - ↑ Rabinovici, GD.; Wang, PN.; Levin, J.; Cook, L.; Pravdin, M.; Davis, J.; DeArmond, SJ.; Barbaro, NM.; Martindale, J. (2006). "First symptom in sporadic Creutzfeldt-Jakob disease". Neurology. 66 (2): 286–7. doi:10.1212/01.wnl.0000196440.00297.67. PMID 16434680. Unknown parameter
|month=ignored (help) - ↑ Muayqil, T.; Gronseth, G.; Camicioli, R. (2012). "Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology". Neurology. 79 (14): 1499–506. doi:10.1212/WNL.0b013e31826d5fc3. PMID 22993290. Unknown parameter
|month=ignored (help) - ↑ Hayashi, R.; Hanyu, N.; Kuwabara, T.; Moriyama, S. (1992). "Serial computed tomographic and electroencephalographic studies in Creutzfeldt-Jakob disease". Acta Neurol Scand. 85 (3): 161–5. PMID 1574996. Unknown parameter
|month=ignored (help)