Cerebrospinal fluid (CSF) and Genetics

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Cerebrospinal fluid (CSF) and Genetics

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 CSF Laboratory

The cerebrospinal fluid (CSF) laboratory in the NCJDRSU provides a national and international diagnostic service for the analysis of CSF 14-3-3, RT-QuiC and other brain-specific proteins.  The laboratory has been recognised as a centre of excellence by the World Health Organisation since 2002.  In addition to our analytical and interpretative services, we also offer specialised training to scientists and clinicians across the world in the techniques used for the analysis of these proteins.  The CSF laboratory also provides information to healthcare professionals regarding health and safety issues concerning CSF analysis.

Changes to the diagnostic CSF service from the 1st April 2022

From the 1st April 2022 we will no longer provide CSF 14-3-3 and S-100b analysis, but will continue to provide CSF RT-QuIC analysis. CSF RT-QuIC has a superior sensitivity and specificity for the diagnosis of sporadic CJD when compared to other CSF biomarkers including CSF 14-3-3.  In our hands the sensitivity and specificity of CSF RT-QuIC is 94% and 100% respectively, compared to a sensitivity of 52% and a specificity of 96% for CSF 14-3-3.[1]  This high degree of sensitivity and specificity agrees with results obtained by other international centres[2-7].   This diagnostic accuracy has led to CSF RT-QuIC being introduced into revised European CJD surveillance Network diagnostic criteria for sCJD in 2017[8].

There are a small number of sCJD cases that may be negative for CSF RT-QuIC and in those cases we may proceed to analyse CSF 14-3-3 and these will be considered on a case by case basis after consultation with local clinicians.  It is important to understand that not all prion diseases are positive for RT-QuIC and that some cases may only be identified at post-mortem. 

In addition, the NCJDRSU will no longer be arranging the shipment of the CSF samples to our laboratories.  The CSF RT-QuIC samples will still need to be transported to us on dry-ice.  Instructions regarding CSF sample requirements and how to send the CSF samples to us are given below.

If you are a clinician and have a patient you suspect may have CJD and want to send us a CSF sample please consult our clinical team on 0131 537 1980 prior to performing the lumbar puncture.

If you are working within a laboratory in the United Kingdom and have received a CSF sample for RT-QuIC analysis, please freeze an aliquot of at least 0.5ml of CSF and ask the requesting clinician to contact us on 0131 537 1980 to discuss the case with our clinical team.

Unfortunately we CANNOT proceed with CSF analysis without prior consultation with our clinical team.  Guidance for the collection and storage of CSF prior to analysis is given below.

CSF samples should be sent to the following address:

Mary Andrews/Kim Burns (tel no. 0131 465 9558)
Room GU312, Ground Floor
Chancellor's Building
Little France Crescent
Edinburgh EH16 4SB
United Kingdom

For all international requests please contact Dr Marcelo Barria (marcelo.barriamatus@nhs.scot)

Useful information:

  1. CSF RT-QuIC request form, sample requirements and information regarding sending CSF samples to us (please do not email this form if you do not have an nhs.net email account) 

  2. New updated ACDP TSE subgroup Laboratory containment and control measures (November 2021)


[1] The National CJD Research & Surveillance Unit, Annual Report 2020

[2] Hermann P, Appleby B, Brandel J-P, Caughey B, Collins S, Geschwind M, Green A, Haik, S, Kovacs GG, Ladagana A, Llorens F, Mead S, Nishida N, Pal S, Parchi P, Pocchiari M, Satoh K, Zanusso G, Zerr I. Sporadic Creutzfeldt-Jakob disease: advanced biomarkers and diagnostic guidelines.  The Lancet Neurology 2021;20:235-246, doi.org/10.1016/S1474-4422(20)30477-4

[3] McGuire LI, Peden AH, Orrú CD et al. RT-QuIC analysis of cerebrospinal fluid in sporadic Creutzfeldt-Jakob disease. Ann Neurol 2012;72: 278–285, doi: 10.1002/ana.23589.

[4] Park JH, Choi YG, Lee YJ et al. Real-Time Quaking-Induced Conversion Analysis for the Diagnosis of Sporadic Creutzfeldt-Jakob Disease in Korea. J Clin Neurol 2016;12:101-6, doi: 10.3988/jcn.2016

[5] Foutz A, Appleby BS, Hamlin C et al. Diagnostic and prognostic value of human prion detection in cerebrospinal fluid. Ann Neurol. 2017;81:79-92, doi: 10.1002/ana.24833.

[6] Lattanzio F, Abu-Rumeileh S, Franceschini A et al. (2017). Prion-specific and surrogate CSF biomarkers in Creutzfeldt-Jakob disease: diagnostic accuracy in relation to molecular subtypes and analysis of neuropathological correlates of p-tau and Aβ42 levels. Acta Neuropathol 2017;133:559-578, doi: 10.1007/s00401-017-1683-0

[7] High diagnostic value of second generation CSF RT-QuIC across the wide spectrum of CJD prions.  Sci Rep 2017;7(1):10655. doi: 10.1038/s41598-017-10922-w, doi: 10.1038/s41598-017-10922-w.

[8] European Centre for Disease Prevention and Control EU case definition (europa.eu)

 Genetics (Blood Samples)

Blood Samples for Genetic Testing:

- Only samples referred through our clinical team should be sent to the NCJDRSU.

- Sample requirements: Citrate / EDTA Blood Collection Vacutainer, Minimum 7ml Fresh Blood

- Testing of samples out with these conditions may still be possible but it is the responsibility of the referring site to provide a sample that will not compromise the integrity of the results.

Sample Transport Requirements:

- A brief overview of the requirements can be found here Blood Sample Guidance

- Blood samples should be packaged in line with UK Health & Safety Executive (HSE) and Transport of Dangerous Goods Regulations. Find out more on the HSE website about Transporting Dangerous Goods

- We recommend the use of a Royal Mail Safebox™  - Find out more about on the Royal Mail website, Safebox

- The safe and correct transport arrangements are the responsibility of the sender.

Where to send blood samples for testing:

Ms Helen Yull
National CJD Research and Surveillance Unit
University of Edinburgh
Bryan Matthews Building
Western General Hospital
Crewe Road, Edinburgh, EH4 2XU

Updated ACDP TSE Subgroup Health and Safety Guidance

The Advisory Committee for Dangerous Pathogens (ACDP) TSE subgroup has revised the laboratory guidelines for handling TSE tissues which was published on the 18th November 2021.  Under this guidance no additional precautions are needed for the analysis, storage and disposal of cerebrospinal fluid (CSF), blood, saliva, and urine samples from patients with suspected Creutzfeldt-Jakob disease (CJD) patients, over and above those taken for other CSF, blood, saliva and urine samples. The guidance for handling, analysis and storage of high risk materials such as brain and other nervous tissue has NOT changed.

Advisory Committee on Dangerous Pathogens' Transmissible Spongiform Encephalopathy (ACDP TSE) subgroup, Minimise transmission risk of CJD and vCJD in healthcare settings, Part 3 Laboratory containment and control measures. https://www.gov.uk/government/publications/guidance-from-the-acdp-tse-risk-management-subgroup-formerly-tse-working-group