Cerebrospinal Fluid (CSF) Test Panel
<<Return to LaboratoryAccredited by the Standards Council of Canada to Laboratory no. 594 (ISO/IEC 17025)
Requisition Forms
Prion Diseases Section Requisition - CSF
06-PDP-CSF-requisition-ENG.pdf
CSF Shipping Instructions
CSF Shipping Protocol - Bilingual.pdf
Reference Details
End Point Quaking Induced Conversion (EP-QuIC) Assay
14-3-3 gamma (γ) ELISA
Total Tau ELISA
- Creutzfeldt-Jakob Disease (CJD) – sporadic and genetic forms
CSF. Minimum volume of specimen required is 1.0 mL. To avoid false results, specimens must not be xanthochromic or have visible blood.
CSF specimen should be collected in a series of containers until it is clear.
Freeze specimen as soon as possible after collection. Ship frozen on dry ice Monday to Wednesday to ensure receipt by Friday. Shipments of CSF specimens 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.
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 specimen to be processed and reported. Please note we use the unique reference number of the specimen, date of draw and patient initials (Given name, Last name) to identify the patient on the report while maintaining patient privacy.
Specimens are batched and run twice a week. Results are sent by FAX to the sending laboratory as listed on the requisition. Please include the appropriate FAX number in the space provided. Should a second centre require a copy of the report, please include their contact information at the bottom of the requisition.
Quaking Induced Conversion (EP-QuIC) Assay:
The diagnostic value of the EP-QuIC assay, which 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, has been shown in our recent prospective study (1). In EP-QuIC, the CSF samples of patients with suspected CJD are added to wells containing a recombinant PrP (rPrP) substrate that is manufactured at the NML. Patient CSF containing PrPd will convert this substrate rPrP into a misfolded form. The insoluble rPrP aggregates generated by this process will interact with a specific dye, causing a measurable change in the dye’s fluorescence emission spectrum (2,3). Specimens for which the signal ratio between the initial and final readings represent a ≥4 fold increase in signal intensity are classified as positive (4). Our most recent prospective study of Canadian patients with suspected CJD obtained a sensitivity of 96% and specificity of 99%, (PPV of 96%)
14-3-3 gamma (¿) ELISA:
The 14-3-3¿ protein assay is conducted using a commercial CircuLex 14-3-3¿ enzyme-linked immunosorbent assay (ELISA) platform provided with internal standards and used by multiple CJD reference laboratories internationally (5). The CircuLex 14-3-3¿ ELISA measures the amount of 14-3-3¿ in arbitrary units per mL (AU/mL). Our recent prospective study of Canadian patients with suspected CJD, using an optimum 20,000 AU/ mL cut off, obtained a sensitivity of 84% and specificity of 90%. (PPV of 68%)(1)
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. A recent prospective study of Canadian patients with suspected CJD, using an optimum cut off of 976 pg/ mL, obtained a sensitivity of 92% and specificity of 88%, (PPV of 66%) (1)
15 calendar days
- Simon SLR, Peterson A, Phillipson C, Walker J, Richmond M, Jansen G, Knox JD (2020). Prospective study demonstrates utility of EP-QuIC in Creutzfeldt-Jakob Disease diagnoses. Canadian Journal of Neurological Sciences 1-10. 10.1017/cjn.2020.139.
- 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.