Suspected case pathway

What should be arranged first?

The 2021 international review sets out a work-up of clinical investigation, blood sampling and lumbar puncture, with MRI and EEG as a minimum. MRI should include T1 with contrast, FLAIR and diffusion-weighted sequences with ADC maps, since diffusion-weighted imaging is needed to confirm the restricted diffusion pattern. Where RT-QuIC is available it should be performed in every suspected case. CSF 14-3-3 remains the primary surrogate marker, with total tau and the phosphorylated to total tau ratio as supportive markers. Genetic analysis of PRNP should be considered in all suspected cases. Routine blood, CSF and imaging tests are used to rule out common mimics, and brain biopsy is reserved for cases where non-invasive testing is inconclusive and a treatable alternative is suspected.

Blood taken and stored at this stage keeps the genetic question open for the family later without requiring tissue after death.

United Kingdom

Clinicians are asked to refer suspected cases to both the National CJD Diagnostic Advisory Service, based at the University of Edinburgh and led by Professor Richard Knight, and the National Prion Clinic at UCLH, with each unit making sure the other knows about the notification and coordinating advice. This arrangement followed the closure of the National CJD Research and Surveillance Unit on 31 March 2025, when the National Institute for Health and Care Research declined to renew its funding.

The CSF RT-QuIC laboratory continues with NHS funding, the test is provided without cost to the referring hospital, and results go directly to the referring clinician. The Edinburgh services page asks clinicians who want CSF RT-QuIC to contact the laboratory directly, directs clinical advice for suspected cases to the National Prion Clinic, and names pathology contacts for neuropathological enquiries. Specialist nursing continues through the National Prion Clinic and a national service based in NHS Lothian, with details given to referring clinicians. The CJD Support Network notes that national arrangements for collecting data on case numbers and types were still under discussion with UK regional bodies when it published its update in April 2025.

Canada

All human prion diseases are provincially reportable and nationally notifiable. A health care professional must inform their local public health authority, and is strongly encouraged to notify the Creutzfeldt-Jakob Disease Surveillance System as well, by phone on 1-888-489-2999 or email to cjdsurveillance@phac-aspc.gc.ca. The system supports clinicians with consultation, laboratory investigation, logistic support and education, provides specialised laboratory tests through the National Microbiology Laboratory, and coordinates case investigations. With consent from the patient or a representative it completes a detailed medical chart review and a family interview, which feed the epidemiological analysis.

France

Prion disease has been notifiable in France since 19 September 1996. Most suspected cases reach the surveillance network through biochemistry laboratories, which routinely forward their CSF 14-3-3 results, and physicians also notify cases directly to the network’s expert neurologists. Neuropathology laboratories rarely act as the point of entry. Treating physicians complete questionnaires, and all registered cases are investigated until a final diagnosis is obtained. The neuropathology department of the Salpetriere hospital coordinates the neuropathological network, alongside the national reference centre for prion diseases and a national unit for CJD care.

Of 25,676 suspected cases notified between 1992 and 2016, 2,907 were diagnosed as prion disease, of which 2,510 were sporadic CJD, 240 genetic and 157 infectious. The reported sensitivity and specificity in that series were 82 and 58 percent for CSF 14-3-3, 52 and 85 percent for EEG, and 46 and 93 percent for MRI, which gives some sense of how much a single supportive test carries.

Germany

Notification of sporadic CJD is required, and clinics are advised to contact the National Reference Center for Human Transmissible Spongiform Encephalopathies at the University Medical Center Goettingen for case classification. The centre advises clinicians on differential diagnosis and infection control and records clinical data. Until 2006 its physicians visited patients and carers and interviewed them with a standardised questionnaire; the proportion of cases visited fell afterwards, with about 27 percent of sporadic CJD patients examined in the later period. Between June 1993 and December 2016 the centre received 4,645 suspected cases, classifying 1,543 as probable and 1,211 as definite sporadic CJD, 156 as possible, 197 as genetic prion disease and 12 as iatrogenic CJD, with 1,188 classified as non-CJD and 338 left unclassified for want of clinical information.

That non-CJD figure, roughly a quarter of referrals, is the practical argument for keeping the alternative diagnoses in play. They are set out in conditions that can look similar.

Denmark

CJD has been notifiable since 1 May 1997. Physicians report suspected cases on Form 1515, and the Department of Infectious Disease Epidemiology at Statens Serum Institut then sends a CJD questionnaire covering the clinical course and supplementary tests, which can also be downloaded and returned with the form. Neuropathological examination involves the Department of Neuropathology at Copenhagen University Hospital. Between 1997 and 2011 notifications averaged seven sporadic cases a year with a range of four to twelve, 54 percent were autopsied and classified as confirmed, and no hereditary, iatrogenic or variant cases were notified.

United States

The CDC states that confirming CJD requires neuropathologic or immunodiagnostic testing of brain tissue obtained by biopsy or autopsy, and that its criteria repeatedly require alternative diagnoses to be excluded through routine investigations. CSF samples go to the National Prion Disease Pathology Surveillance Center, which also runs the autopsy coordination programme and asks for a call to its autopsy coordinator on 216-368-0587, with staff confirming that prion disease is clinically suspected before agreeing to help. The centre notes that no state is known to require an autopsy for suspected CJD, while several require reporting and strongly recommend one. State and local reporting requirements should be checked locally.

What happens alongside the diagnostic work?

Infection control questions usually arrive at the same time as the first suspicion, particularly if surgery, endoscopy or a dental procedure is planned or has recently happened. The precautions, and the instrument decisions that follow from the risk classification, are in hospitals and care homes. The laboratory destinations are in testing labs by country, the collection rules in samples and shipping, and the plain-language page for families is care settings. The section index is for clinicians.