Abstract
Background
Creutzfeldt–Jakob Disease (CJD) is a transmissible neurodegenerative disease. Although 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%).1–6 This Fast Fact addresses the clinical presentation, diagnosis, prognosis, symptom management, and after-death care for patients with CJD.
Clinical Presentation
Symptom onset follows an undetermined incubation period, estimated at 10 to 12 years.1,3–6 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
Development of any nonreversible dementia over days to months should trigger clinical consideration for CJD.1,3,5–8 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 neuropathologic 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: (1) lumbar puncture findings (e.g., 14–3–3 protein and/or Tau protein that may take several days to weeks to result), (2) relevant clinical signs, (3) a lack of an alternative diagnosis, and (4) suggestive imaging findings such as periodic sharp-wave complexes on electroencephalography (EEG) and high signals in the caudate/putamen or at least two cortical regions on diffusion-weighted imaging. 5
Prognosis
CJD is incurable and ultimately fatal.1,3–6 Clinical progression leads to akinetic mutism, pronounced myoclonus, and a moribund functional status. Death often occurs within one year of symptom onset, although many die within six 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
Involve an interdisciplinary team: elicit help from social workers to expedite advance directive completion and pursuit of disability and other benefits.1,3–5,9–11 Chaplaincy support can help with anticipatory grief and spiritual support (see Fast Fact #32). Reflective listening and/or psychologic 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 mg 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 to 2 mg PO/SQ/IV may be needed.
○ 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
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.21–23 Compassion and empathy are paramount when discussing autopsy, funeral arrangements, and burial/cremation preferences.
• Autopsy: there are many 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 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
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.4,24,25