Sporadic CJD: more detail

Presentation and course

The dominant feature is a rapidly progressive dementia, usually in someone over 50. Average age at onset is in the late 60s, about 90 percent of diagnoses fall between 45 and 85, and presentation under 30 is very unusual.

Early neurological features include gait ataxia and balance difficulty, dysarthria, vertigo, visual disturbance such as diplopia or cortical visual loss, and paraesthesia. Myoclonus, which is sudden involuntary jerking, often appears within weeks. The NHS description of the sporadic form notes that these features worsen in the space of a few months, and the advanced picture adds incontinence, dysphagia, loss of speech, severe memory loss, agitation and akinetic mutism. Death usually follows an intercurrent infection such as pneumonia, or respiratory failure.

CDC gives a median time from symptom onset to death of 4 to 5 months, while the patient-facing accounts from CDC and the NHS state that people usually die within a year of onset. Both figures are in circulation, and the honest summary for a family is months to about a year, with a minority living longer.

Subtypes and what they predict

Subtype is assigned from the PRNP codon 129 genotype, methionine homozygous, valine homozygous or heterozygous, together with the type of protease-resistant prion protein on Western blot, giving MM1, MV1, VV1, MM2, MV2 and VV2. All six were represented in the 2026 Annals of Neurology diagnostic series by Myskiw and colleagues. Subtype correlates with clinical phenotype, so a VV2 case more often presents with ataxia and may run a longer course than a typical MM1 case.

Two cautions are worth stating to colleagues and families. Subtype is usually established late or at post mortem, so it rarely guides care in real time. And it is a description of a case, with limited power to forecast one person’s course.

Diagnostic criteria

The CDC criteria define three levels.

Definite sporadic CJD requires neuropathology, immunocytochemistry, a Western blot demonstrating protease-resistant prion protein, or the presence of scrapie-associated fibrils. In practice that means brain tissue by biopsy or at autopsy.

Probable sporadic CJD is reached either by a neuropsychiatric disorder with a positive RT-QuIC assay in cerebrospinal fluid or other tissue, or by a rapidly progressive dementia with at least two of myoclonus, visual or cerebellar signs, pyramidal or extrapyramidal signs and akinetic mutism, plus at least one supportive investigation, with no routine investigation indicating an alternative diagnosis.

Possible sporadic CJD covers a progressive dementia with two of those four features, duration under two years and no positive confirmatory test.

The supportive investigations are a positive 14-3-3 assay in cerebrospinal fluid where the illness has lasted less than two years, a typical EEG pattern of periodic sharp wave complexes at any stage, and MRI high signal in caudate and putamen or in at least two cortical regions among temporal, parietal and occipital on diffusion weighted or FLAIR sequences. A negative EEG or an unremarkable early MRI does not exclude the diagnosis, and repeat imaging later in the illness is often more informative.

In the United States the National Prion Disease Pathology Surveillance Center at Case Western Reserve University performs diagnostic neuropathology with CDC support. The sequence of tests from a family’s point of view is on how it is diagnosed.

Where the seeding assays are going

Real-time QuIC changed practice because it detects seeding activity attributable to misfolded prion protein itself, where 14-3-3 and tau report downstream neuronal injury. Work continues on sensitivity for the rarer subtypes, which the standard assays detect less reliably.

Myskiw and colleagues modified end-point QuIC to use a recombinant prion protein substrate from the North American deer mouse. In their retrospective series they reported 96.6 percent sensitivity, 111 of 116 samples, and 100 percent specificity, 35 of 35, compared with 87.1 percent sensitivity for the earlier end-point format and 72.4 percent for a real-time CSF assay in the same work. Their own stated limitations should travel with those numbers: validation in independent laboratories, inter-laboratory reproducibility and protocol harmonisation are outstanding, the deer mouse substrate has to be produced and standardised, and no prospective serial CSF samples were available, so longitudinal performance is untested. This is an assay under validation, and a clinician reviewing the paper should check the sensitivity figures in the tables as well as those in the abstract.

Management

Care is supportive, and the 2026 multidisciplinary recommendations in Age and Ageing give the most specific guidance now available for this illness.

Myoclonus is treated when it interferes with daily function or care or causes distress. Levetiracetam is suggested first line, being well tolerated, easy to titrate and available in several formulations, with clonazepam reserved for the more advanced stages when a person is no longer ambulant.

Neuropsychiatric symptoms are approached on the principle that so-called challenging behaviour is generally the communication of an unmet need, so triggers and the environment come first and medication is kept for distress or risk that has not responded. Because symptoms in prion disease can appear and resolve quickly, the authors state that a watch-and-wait approach to troubling symptoms such as delusional ideas is often justified. They also observe that delirium appears less common here than in other dementias.

Pain is generally not found to be a problematic symptom in sporadic CJD, though it should not be dismissed; assessment uses caregiver history and observational tools, with regular paracetamol as a stepped first line and opioids used cautiously under palliative care guidance. Sleep is managed without medication where possible. Swallowing deteriorates over time, and whether clinically assisted nutrition and hydration serves a person’s best interests is decided individually and reviewed at every care review.

Two process points carry as much weight as the drug choices. Early palliative care involvement is encouraged, and in the United Kingdom all individuals with suspected prion disease should be referred to the National Prion Clinic. Families need disease-specific information about what to expect, training, respite, financial help and mental health support, and peer networks such as the CJD Support Network. The family-facing version of this is what to expect.

The trial record

Human studies completed between roughly 1997 and 2013 were flupirtine in Germany with 28 participants, randomised and double blind, which reported slowed cognitive decline on ADAS-Cog but never entered standard care; pentosan polysulphate in the United Kingdom with 7 and in Japan with 11, neither randomised; quinacrine in France with 32, in the United Kingdom with 107 in an open-label patient-preference design, and in the United States with 54 in a randomised trial that showed no benefit; and doxycycline in France and Italy with 121 participants, randomised, double blind and negative.

The design lessons drawn from that record are directly useful when a family asks why there is still nothing to offer. Compounds that only work before symptoms in animals should be tested in people without symptoms. Diagnosis needs to come earlier if treatment is to start earlier. Trials in asymptomatic carriers will require a predictive biomarker and a registry. Historical controls carry ascertainment bias, so stratification within randomised designs is the safer route to power.

Studies currently recruiting are listed under current trials, with the mechanistic account in our research page on sporadic CJD. The plain version of this page is sporadic CJD.

Surveillance and notification

Sporadic CJD is tracked nationally, which is how iatrogenic clusters have been identified. Incidence is about 1 to 2 cases per million per year. In Canada, health care professionals must notify their local public health authority of a suspected case and are strongly encouraged to notify the national CJD Surveillance System as well, on 1-888-489-2999 or at cjdsurveillance@phac-aspc.gc.ca. Clinicians elsewhere should use the equivalent national unit.