Background (1-6):  Creutzfeldt-Jakob Disease (CJD) is a transmissible, neurodegenerative disease. Though it is relatively rare, affecting about one person per million each year, it is the most common of five recognized human prion diseases and it is devastating for patients, families, and caregivers considering its rapid progression and incurable nature. Sporadic is the most common form of CJD (85% of cases), followed by hereditary (10-15%), and acquired/iatrogenic (<1%).  This Fast Fact addresses the clinical presentation, diagnosis, prognosis, symptom management, and after-death care for patients with CJD.

Clinical Presentation (1,3-6):  Symptom onset follows an undetermined incubation period, estimated at 10-12 years. Initially, patients present with difficulty walking, impaired concentration, emotional lability, depression, disordered sleep, diplopia, and hallucinations.  This is followed by ataxia, startle-induced myoclonus, and a rapidly progressive dementia (RPD) developing over weeks to months. 

Diagnosis (1,3,5-8):  Development of any non-reversible dementia over days to months should trigger clinical consideration for CJD.  The mean age of onset is 62 years.  White populations, notably those of North African, Israeli, Italian, and Slovakian ancestry have a higher incidence (1). No gender difference exists. Brain biopsy with neuropathological examination provides definitive diagnosis; however, in most cases it is not required nor pursued. More commonly, CJD is a clinical diagnosis made by neurologists based on a constellation of key diagnostic criteria: a) lumbar puncture findings (e.g. 14-3-3 protein and/or Tau protein which may take several days to weeks to result), b) relevant clinical signs, c) a lack of an alternative diagnosis, d) suggestive imaging findings such as periodic sharp-wave complexes on EEG and high signals in the caudate/putamen or at least two cortical regions on diffusion-weighted imaging (5).  

Prognosis (1,3-6): CJD is incurable and ultimately fatal.  Clinical progression leads to akinetic mutism, pronounced myoclonus, and a moribund functional status.  Death often occurs within one year of symptom onset, though many die within 6 months. Hereditary CJD may have a slightly longer course.

Symptom Management:  There are no available treatments to cure or slow CJD progression. Palliative care consultation at CJD diagnosis can benefit advance care planning, anticipatory guidance, and symptom management. Hospice referral at the onset of RPD should be considered.  

Nonpharmacologic Management (1,3-5,9-11)

• Involve an interdisciplinary team: elicit help from social workers to expedite advance directive completion and pursuit of disability and other benefits. Chaplaincy support can help with anticipatory grief and spiritual support (see Fast Fact #32). Reflective listening and/or psychological counseling can help caregivers cope with the rapid personality and functional changes associated with CJD. Music therapists and aromatherapy can foster a more therapeutic care environment. 
  • Family education:  prepare families for the progressive feeding difficulties which prompt difficult feeding decisions. Providing a consistent daily routine, including consistent sleep hygiene practices as well as a calming environment can alleviate behavioral manifestations. Genetic counseling is advised in hereditary cases.  

Pharmacologic Management – There are no specific guidelines nor evidence to base the pharmacologic management of CJD-related symptoms.  The following empirical advice has been extrapolated from published evidence of delirium and myoclonus for patients nearing the end of life.  Clinicians should routinely reassess risks, benefits, and response to pharmacotherapies and adjust as appropriate.

• Delirium and/or Agitation (see Fast Facts #1, #60 and #315)
  • Atypical antipsychotics – olanzapine (starting dose 2.5 mg PO daily), risperidone (starting dose 1.0 PO nightly), quetiapine (starting dose 25.0 mg PO daily, divided dosing) (9-13).
  • Typical antipsychotics – haloperidol (starting dose 0.5 mg PO/IV daily) (9-13).
  • For severe cases of agitation, coadministration of lorazepam 1-2 mg po/SQ/IV may be needed.
  • Myoclonus (14-20) (see Fast Fact #114)
    • Antiepileptics – levetiracetam (starting dose 500 mg PO BID) or valproate (starting dose 15 mg/kg PO daily, divided dosing)
    • Benzodiazepines – clonazepam (starting dose 0.5 mg PO daily)

After-death Care (21-23):  Those involved in the care and after-death care of a CJD patient are not at increased risk of prion infection if the following precautions are pursued. Compassion and empathy are paramount when discussing autopsy, funeral arrangements, and burial/cremation preferences. 

• Autopsy:  there are a lot of clinical unknowns about CJD. Experts hope autopsy can help fill in these gaps of knowledge as well as offer diagnostic closure. Therefore, autopsy is recommended when in suspected cases. The CJD Foundation offers financial assistance for autopsies. Autopsy is typically free in suspected and/or confirmed cases of CJD in the United States and should not delay a funeral.
• Funeral Arrangements: funeral homes should be notified when CJD is suspected. In addition to standard precautions, the following after-death practices can minimize prion contamination:
  • Transportation – a leak proof bag lined with absorbent material.
  • Preparation (embalming) – use plastic sheets to collect fluids; pack the cranial cavity with bleach-soaked material if leaking; close incision sites with glue; use disposable instruments.
  • Dressing – wash entire body with bleach and sanitize before dressing
  • Casket and viewing – avoid superficial contact with body.
• Cremation and burial: neither cremation nor burial poses any infection or environmental risk.  

Resources for Patients and Families (4,24,25):  CJD Foundation, CJD Support Group Network, CJD Support Network, National Institute of Neurological Disorders and Stroke, and the WHO Infection Control Guidelines all have freely available patient and family educational resources about CJD.

References

1. Creutzfeldt-Jakob disease. UpToDate. (Accessed September 20, 2019.)
2. Diseases of the central nervous system caused by prions. UpToDate. (Accessed October 9, 2019.)
3. National Institute of Health. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov. Accessed October 9, 2019. 
4. Creutzfeldt-Jakob Disease Foundation, Inc: Supporting Families Affected by Prion Disease. https://cjdfoundation.org. Accessed October 9, 2019.
5. Centers for Disease Control and Prevention. Creutzfeldt-Jakob Disease, Classic. https://www.cdc.gov/prions.cjd/. Accessed October 9, 2019. 
6. World Health Organization. Transmissable Spongiform Encephalopathies (TSE). https://www.who.int/bloodproducts/tse/en/. Accessed October 9, 2019.
7. Biology and genetics of prions. UpToDate. (Accessed October 9, 2019.)
8. Case Western Reserve University. National Prion Disease Pathology Surveillance Center. https://www.djdsurveillance.com. 2019. Accessed October 9, 2019. 
9. Care of patients with advanced dementia. UpToDate. (Accessed October 9, 2019.)
10. Management of neuropsychiatric symptoms of dementia. UpToDate. (Accessed September 20, 2019.) 
11. Kranitz FJ, Simpson DM. Using non-pharmacological approaches for CJD patient and family support as provided by the CJD foundation and CJD insight. CNS Neurol Disord Drug Targets. 2009;8(5):372-9.
12. Antipsychotic drugs for dementia: a balancing act. Lancet Neurol. 2009;8(2):125.
13. Grassi L, et al. Management of delirium in palliative care: a review. Curr Psychiatry Rep. 2015;17(3):550.
14. Crest C, et al. Levetiracetam in progressive myoclonic epilepsy: an exploratory study in 9 patients. Neurology. 2004;62(4):640.
15. Striano P, et al. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord.2005;20(12):1610.
16. Nevitt SJ, et al. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Dyst Rev. 2017;6:CD011412. Epub 2017 Jun 29.
17. Caviness JN. Treatment of myoclonus. Neurotherapeutics. 2014;11(1):188.
18. Obeso JA, et al. The treatment of severe action myoclonus. Brain. 1989;112(Pt 3):765.
19. Obeso JA. Therapy of myoclonus. Clin Neurosci. 1995-1996;3(4):253.
20. Treatment of myoclonus. UpToDate. (Accessed September 20, 2019.)
21. Crain B. Creutzfeldt-Jakob disease: Safety tips for anatomic studies of possible CJD. College of American Pathologists Today, January 1996.
22. WHO CJD Infection Control Guidelines for Transmissable Spongiform Encephalopathies. Report of a WHO consultation, Geneva, Switzerland, 23-26 March 1999.
23. Medscape. Universal Precautions and High-Risk Autopsies. https://emedicine.medscape.com/article/1711526-overview. 2019. Accessed October 20, 2019.
24. CJD Support Group Network. https://www.cjdsupport.org.au. 2019. Accessed October 9, 2019. 
25. CJD Support Network. https://www.cjdsupport.net. 2019. Accessed October 20, 2019.

Author’s Affiliations: Eastern Virginia Medical School

Conflicts of Interest: none

Version History:  first electronically published in December 2019; originally edited by Sean Marks MD.