Creutzfeldt Jakob Disease Evaluation, CSF (Sendout)

Useful For: Assessment of Creutzfeldt-Jakob disease or other human prion disease in patients with rapidly progressive dementia. This evaluation includes Total-Tau, Phospho-Tau(181P), t-Tau/p-Tau ratio, RT-QuIC (real-time quaking-induced conversion), and medical interpretation by Mayo Clinic Laboratories. RT-QuIC identifies the disease-causing agent.

For patients with sufficient clinical suspicion for CJD to warrant testing, prion testing should be prioritized and performed in the initial set of CSF tests. This ensures appropriate handling of patient samples in the laboratory. Some tests may be delayed pending CJD results. The Lab Medicine Resident on-call can clarify what tests can be performed while CJD testing is pending and can assist with test prioritization.

Note: This test replaces RCCJD, Creutzfeldt Jakob Disease (Sendout), previously sent to National Prion Disease Pathology Surveillance Center.

Ordering Requirements:

• This test requires Laboratory Medicine Resident (LMR) approval. Exception noted in Processing section below.
• Samples must be collected using a Mayo CJD/RPD Evaluation Kit (T966). Contact the laboratory to obtain a kit prior to collection.

Reference Values:

Interpretation:

A positive real-time quaking-induced conversion (RT-QuIC) is supportive of prion disease and, in the correct clinical context, fulfills the Centers of Disease Control and Prevention diagnostic criteria of probable prion disease.¹

An elevated total Tau/p-Tau (threonine 181) ratio (>18) increases the likelihood of prion disease but can be seen in patients with rapidly progressive dementia due to other causes, including autoimmune encephalitis, central nervous system malignancy, seizure disorder, stroke, and other neurodegenerative diseases.

Negative results do not exclude the possibility of prion disease.

RT-QuIC = Real-time quaking-induced conversion

Cautions:

These test results should be interpreted in the appropriate clinical context along with other clinical and paraclinical findings. Only through neuropathological assessment of brain tissue can a definitive diagnosis of sporadic prion disease be established.

Some molecular subtypes of prion protein have been reported to have lower detectability by real-time quaking-induced conversion (RT-QuIC) assays.

Even small quantities of blood in cerebrospinal fluid (CSF) can result in false-negative RT-QuIC results.

The presence of fluorescent substances may interfere with testing and prevent an accurate interpretation of the RT-QuIC assay.

Careful consideration of the differential diagnosis is advised when RT-QuIC test results are unexpectedly negative. Repeat testing with RT-QuIC may be warranted if there is high suspicion of prion disease. A small subset of initially negative cases by RT-QuIC may become positive as the disease progresses. However, a small proportion of patients with definitive prion disease may be persistently negative by RT-QuIC. False-negative RT-QuIC results are most often encountered in cases of genetic prion disease, such as fatal familial insomnia and Gerstmann-Straussler-Scheinker disease, and in atypical sporadic prion disease subtypes that have slower indolent disease progression.

In rare cases, some individuals can develop antibodies to mouse or other animal antibodies (often referred to as human anti-mouse antibodies [HAMA] or heterophile antibodies), which may cause interference in some immunoassays. The presence of antibodies to streptavidin or ruthenium can also rarely occur and may interfere in this assay. Caution should be used in interpretation of results, and the laboratory should be alerted if the result does not correlate with the clinical presentation.

NOTE: A Mayo CJD/RPD Evaluation Kit (T966) is required for collection. Obtain a kit from UW-MT, UW-NW, or HMC Specimen Processing Services. Outside clients may contact Client Support Services to obtain a kit.

• UW-MT: (206) 520-4600
• UW-NW: (206) 668-1344
• HMC: (206) 744-3451

Supplies: CJD/RPD Evaluation Kit (T966) including collection instructions and 2 x 2.5 mL Sarstedt CSF False Bottom Tubes 63.614.625 (also known as CSF AD Biomarker Tubes)

• Also Accepted: CSF collected in Sarstedt 72.703.600 (1.5 mL) or Sarstedt 72.694.600 (2 mL) tubes

Specimen Volume: 2 designated collection tubes, each containing 1.5 mL to 2.5 mL CSF.

Collection Instructions:

1. Perform lumbar puncture and discard the first 1 to 2 mL of cerebrospinal fluid (CSF).
2. Collect two tubes of CSF directly into an acceptable collection tube until the tube is at least 50% full. Minimum: 1.5 mL per tube.
3. Send CSF specimen in original collection tube. Do not aliquot.
4. Mayo Spinal Fluid Specimen Collection Instructions for Creutzfeldt-Jakob Disease

Outside Laboratories: If no concurrent CSF testing is ordered that is to be performed by the UW Department of Laboratory Medicine and Pathology clinical laboratories, clients outside of the University system are encouraged to send samples directly to Mayo Clinical Laboratories.

Failure to follow the guidelines below for submitting CJD samples may result in significant processing delays.

• Approval from the Laboratory Medicine Resident must be obtained prior to sample submission. The ordering provider should contact the paging operator at 206-598-6190 and ask to speak to the General Lab Medicine Resident on-call.
• After approval, contact UW Client Support Services at (206) 520-4600 or 1-800-713-5198 to obtain a Mayo CJD/RPD Evaluation Kit (T966) and notify them of incoming samples. Communicate the name of the approving doctor.
• Clearly label the requisition and all samples as “Suspected Prion.”

Stability: Frozen (preferred): 28 days; Refrigerated: 14 days; Ambient: 12 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, discolored CSF. Samples arriving in unapproved tube types.

LMR Approval Exception for Outside Orders: Outside clients should be discouraged from sending samples for CJD without concurrent CSF orders for in-house testing. However, if the sample has already been shipped to/received by UW from an outside facility, DLMP will accept the order and send to Mayo.

• LMR approval is not required in this case. The order may be accessioned and sample(s) forwarded to Sendouts for transport to Mayo.
• Create an HC1 Task to document the error, assign to CSS, and set the status to "Supervisor Review" so that CSS Management can provide feedback to the client.

Specimen Processing Services (SPS)/Microbiology Set-Up:

• Review HC1 for an existing case associated with CJD testing for this patient. If pre-approval was obtained, the case number should be provided in the Epic order information.
  • Confirm that the case indicates testing is approved and look for any additional instructions from the LMR.
  • Update the case that the sample has been received.
• If there is no HC1 case documenting prior LMR approval:
  • Page the LMR immediately upon receipt of specimen(s) and prior to aliquoting, testing, or freezing. When paging through operator or text paging, include comment: “urgent CSF, call-back within 15 min.,” in addition to your name, lab location, and call-back number.
    • Create a case in HC1 to document approval and any instructions given by the resident.
    • If no response within 15 minutes, contact the LMR again.
• Samples for CJD testing must be received in designated collection tubes.
  • If samples are submitted in any tube type besides the Mayo Sarstedt CSF False Bottom Tubes 63.614.625, Sarstedt 72.703.600 (1.5 mL), or Sarstedt 72.694.600 (2 mL) tubes, notify the LMR.
• Hold all CSF samples at the temperature received.
• Do not setup testing on any CSF from this patient until approved by LMR. Do not send out CJD testing prior to LMR approval.
• If the LMR approves CJD testing:
  • Label all specimens and aliquots of CSF from the same patient as “Suspected Prion Disease.”
  • Freeze the CJD samples in Mayo Sarstedt tubes at -20°C.
• If CJD order is cancelled, other testing may proceed without special precautions or labels.

Sendouts:

• Order Mayo Test: CJDE
• Interfaced: Yes [Interface: 601; Worksheet: MAFZ]
• Label all sendout specimens and aliquots of CSF from the same patient as “Suspected Prion Disease.”

Stability: Frozen (preferred): 28 days; Refrigerated: 14 days; Ambient: 12 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, discolored CSF. Samples arriving in unapproved tube types.