Clinical use
Investigation of CSF for CJD.
Background
Cruetzfeldt-Jakob Disease (CJD) is part of a group of diseases known as Transmissible Spongiform Encephalopathy (TSE), occurring in both humans and animals and caused by prions. Prions are abnormally folding proteins found in the brain and spinal cord, known as prion proteins (PrP). TSEs are characterised by degeneration of the nervous system and are ultimately fatal. CJD’s classification is based upon its aetiology, described in the table below.
| Aetiology | Description |
|---|---|
| Sporadic (sCJD) | The most common variant. Occurring world-wide in all populations. sCJD causes 1-2 deaths per million population per year; patients are usually over 50. |
| Inherited or familial (genetic) | Very rare and is attributed to a genetic mutation in the prion gene. With most people developing symptoms between ages 30-50 |
| Acquired – Iatrogenic | High risk tissue contamination (cornea, dura mater graft; use of high-risk instrumentation during neurosurgery (rare and before modern sterilisation/disinfection processes); and use of human pituitary growth hormones. |
| Acquired – Variant CJD (vCJD) | Consumption of cattle infected with Bovine Spongiform Encephalitis (BSE) associated prions. The protein has been found in lymphoid tissue. There has also been recorded transmission through blood transfusion. |
| Acquired – Kuru | This was first isolated and confined to natives in Papua New Guinea. Transmission was a result of ritualistic cannibalism. |
Consumption of material containing prion is thought to be the primary method of acquisition of vCJD. This risk of infection with prions via medical/ surgical/laboratory procedures or percutaneous injury results in the requirement for specific health and safety measures to protect patients and staff. Prion diseases are atypical in their resistance to chemical and traditional sterilisation techniques thus requiring specific protocols to ensure inactivation.
Detailed guidelines on the transmission and precautions required for patients with confirmed or suspected TSE are detailed within the Infection prevention control (IPC) Creutzfeldt – Jakob Disease (CJD) policy (HIC13), available for staff on the South Tees intranet. A full categorisation of the infectivity risk from a range of tissues is included in HIC13 and from the GOV.UK guidance page, “Minimise transmission risk of CJD and vCJD in healthcare settings”.
The IPC team may be contacted for advice when any patient is being cared for with suspected CJD
CJD testing is performed by an external laboratory in Edinburgh.
Patient preparation
Warning
The following MUST be done prior to performing the lumbar puncture.
- The requesting clinician must contact The National CJD Research & Surveillance Unit (NCJDRSU), University of Edinburgh, on their contact number, 0131 537 1980, to discuss the case and arrange testing.
- The CSF CANNOT be analysed without prior consultation with the NCJDRSU clinical team.
- The requesting clinician is required to complete the sample request form on the NCJDRSU website and send this with the sample to the local laboratory.
- Importantly, the clinician is also required to inform their local Health Protection Team (HPT) about new suspected cases of all types of CJD. Information on the reporting of CJD to the HPT is detailed on the reporting new cases section on the NCJDRSU website.
If CJD is suspected the laboratory at James Cook MUST also be contacted prior to sending samples and ALL samples must include TSE / CJD in the clinical details to ensure the safety of laboratory staff can be maintained. The James Cook laboratory will arrange for storage of the sample and transport to the NCJDRSU.
Further details are provided on the NCJDRSU website in regard to the transport requirements and further details for the requesting clinician.
Specimen requirements
CSF samples
- NCJDRSU requires 0.5 mL of clear and colourless CSF, if the sample is blood-stained this invalidates the test. The laboratory does NOT accept CSF samples with Red Cell counts greater than 1250 x106 cells/L.
- If the tap is traumatic the reference laboratory advises that the CSF sample is collected in a series of containers until it is clear.
- The CSF should be collected into a routine sterile white topped universal.
- The samples should be sent to the James Cook Microbiology laboratory for storage. The samples must be frozen within 2-3 hours of collection, ideally at -70oC to -80oC.
Limitations and restrictions
- Samples must be received prior to antibiotic treatment if possible.
- Samples must not be visibly blood stained or have an RBC greater than 1250 x106 cells/L.
- Some cases of CJD may not be detected by first line tests, if the case is highly indicative of CJD but the result is negative initially there may be precedent to discuss with NCJDRSU regarding testing using 2nd line tests.
- Elevated CSF total protein concentrations of above 1 g/L and a CSF white cell count >20 may interfere with the assay.
Turnaround time
10 – 15 working days after receipt of the CSF sample
Analysing laboratory
Mary Andrews/Kim Burns (Tel no: 0131 465-9524-office), Room GU312, Ground Floor, Chancellor’s Building, 40 Little France Crescent, Edinburgh, EH16 4SB
Additional information
Cell count, Gram stain and culture will be performed at James Cook University Hospital by the Microbiology department within a containment level 3 facility. Samples will be frozen locally and will be forwarded on to the Edinburgh laboratory for confirmation.