Cerebrospinal Fluid (CSF) Test Panel<<Return to Laboratory
Accredited by the Standards Council of Canada to Laboratory no. 594 - CAN-P-4E (ISO/IEC 17025)
End Point Quaking Induced Conversion (EP-QuIC) Assay
14-3-3 gamma (γ) ELISA
- Creutzfeldt-Jakob Disease (CJD) – sporadic and genetic forms
CSF. Minimum volume of sample required is 1.0 mL. To avoid false results samples must not be xanthochromic or have visible blood.
CSF sample should be collected in a series of containers until it is clear.
Freeze sample as soon as possible after collection. Ship frozen on dry ice Monday to Wednesday to ensure receipt by Friday. Shipments of CSF samples are not received on the weekend. Shipments must contain enough dry ice (>5kg) in a Styrofoam box inside a rigid outer package to withstand weather conditions and warehouse storage for up to four days.
Shipping of specimens shall be done by a TDG certified individual in accordance with TDG regulations. For additional information regarding classification of specimens for the purposes of shipping, consult either Part 2 Appendix 3 of the TDG Regulations or section 3.6.2 of the IATA Dangerous Goods Regulations as applicable.
For additional guidance on the transport of infectious substances in other languages, please click on the link below.
Inclusion of CJD, GSS or FFI in the differential diagnosis of the patient.
Completed Prion Diseases Section requisition found at https://cnphi.canada.ca must be completed for sample to be processed and reported. Please note we use the unique sample number, date of draw and patient initials (First name, Last name) to identify the patient on the report while maintaining patient privacy.
Samples are batched and run weekly each Friday. Results are sent by FAX to the sending laboratory as listed on the requisition. Please include the appropriate secure FAX line in the space provided.
Quaking Induced Conversion (EP-QuIC) Assay:
The EP-QuIC assay exploits the ability of pathogenic prion protein (PrPd) to induce the conversion of the normal cellular form of the prion protein (PrPc) into a misfolded form. In EP-QuIC, the CSF samples of patients with suspected CJD are added to wells containing recombinant PrP (rPrP). Patient CSF containing PrPd will convert the rPrP into a misfolded form. The insoluble rPrP aggregates generated by this process then interact with a specific dye, causing a measurable change in the dye’s fluorescence emission spectrum (1,2). Samples for which the signal ratio between the initial and final readings represent a ≥4 fold increase in signal intensity in at least 2 of 3 assay replicates are classified as positive (3). A prospective study of test performance characteristics conducted in Canadian patients with suspected CJD obtained a sensitivity of 96% and specificity of 99%.
14-3-3 gamma (γ) ELISA:
The 14-3-3γ protein assay is conducted using a commercial CircuLex 14-3-3γ enzyme-linked immunosorbent assay (ELISA) platform provided with internal standards and used by multiple CJD reference laboratories internationally (4). The CircuLex 14-3-3γ ELISA measures the amount of 14-3-3γ in arbitrary units per mL (AU/mL). A prospective study of test performance characteristics conducted in Canadian patients with suspected CJD, using an optimum 20,000 AU/ mL cut off, obtained a sensitivity of 82% and specificity of 90%.
hTau ELISA: The tau protein assay is conducted by sandwich enzyme-linked immunosorbent assay (ELISA), using a commercial kit, Innotest® hTAU Ag (Fujirebio) and colorimetric signal detection. Results are reported quantitatively in units of pg/mL (5). A prospective study of test performance characteristics conducted in Canadian patients with suspected CJD, using an optimum cut off of 976 pg/ mL, obtained a sensitivity of 93% and specificity of 84%.
15 calendar days
- Godal G, Simon SLR, Cheng K, Knox JD: A new test for Creutzfeldt-Jakob disease: real-time quaking induced conversion. CCDR 41-8:192-195. 2015.
- McGuire LI, Poleggi A, Poggiolini I, Suardi S, Grznarova K, Shi S, de Vil B, Sarros S, Satoh K, Cheng K, Cramm M, Fairfoul G, Schmitz M, Zerr I, Cras P, Equestre M, Tagliavini F, Atarashi R, Knox JD, Collins S, Haïk S, Parchi P, Pocchiari M, Green A: CSF RT-QuIC is a robust and reliable test for sporadic CJD: An international study. Ann Neurol. 80(1):160-165. 2016.
- Cheng K, Vendramelli R, Sloan A, Waitt B, Podhorodecki L, Godal D, Knox JD. Endpoint quaking-induced conversion: a sensitive, specific and high throughput method for antemortem diagnosis of Creutzfeldt-Jakob disease. J Clin Microbiol 54(7):1751-1754. 2016.
- Schmitz M, Ebert E, Stoeck K et al : Validation of 14-3-3 Protein as a Marker in Sporadic Creutzfeldt- Jakob Disease Diagnostic. Mol Neurobiol DOI 10.1007/s12035-015-9167-5, 2015.
- Coulthart M, Jansen GH, Olsen E, Godal DL, Connolly T, Choi BCK, Wang Z and Cashman NR: diagnostic accuracy of cerebrospinal fluid markers for sporadic Creutzfeldt-Jakob disease in Canada: a 6-yearprospective study. BMC Neurology 11:213, 2011.