Synopsis
Treat rapid cognitive decline as an urgent syndrome, identify reversible inflammatory, infectious and toxic causes, and investigate possible prion disease with national specialist and infection-control support.
- Rapidly progressive dementia evolves over weeks or months rather than years and is a diagnostic emergency because autoimmune, infectious, metabolic, toxic and neoplastic causes may be reversible.
- First distinguish delirium, depression and non-convulsive status from a true progressive cognitive syndrome using attention, arousal, collateral timing and EEG where indicated.
- Sporadic CJD commonly combines rapidly progressive cognitive decline with myoclonus, gait or limb ataxia, visual symptoms, pyramidal or extrapyramidal signs and later akinetic mutism.
- MRI diffusion-weighted and ADC sequences may show cortical ribboning or caudate and putaminal diffusion restriction; the pattern must be reviewed by experienced neuroradiology.
- CSF real-time quaking-induced conversion supports prion diagnosis with high specificity, while 14-3-3 and total tau reflect rapid neuronal injury and are less specific.
- Periodic sharp-wave complexes on EEG can support sporadic CJD, but a normal or non-specific early EEG does not exclude disease and EEG is crucial for status epilepticus.
- Autoimmune encephalitis, vasculitis, lymphoma, HIV or syphilis, Whipple disease, thyroid or B12 disease, drug toxicity and cancer-associated syndromes require history-led testing.
- Contact the National Prion Clinic or National CJD Research and Surveillance Unit early rather than waiting for every result, and involve local infection prevention before biopsy or surgery.
- There is no disease-modifying treatment for CJD; care prioritises clear communication, myoclonus and distress relief, nutrition, mobility, anticipatory planning and family support.
Key red flags
Rapid cognitive decline with myoclonus, cerebellar or visual dysfunction and pyramidal or extrapyramidal signs is characteristic of sporadic CJD but not pathognomonic.
Subacute memory loss, psychiatric change, new seizures, faciobrachial or other abnormal movements, dysautonomia or hyponatraemia should prompt urgent specialist autoimmune assessment.
Fluctuating responsiveness, subtle twitching, gaze deviation or unexplained persistent confusion can represent ongoing seizure activity and requires urgent EEG-led treatment.
Medicine change, organ failure, electrolyte disturbance, malnutrition or exposure with diffuse neurological dysfunction can produce a rapidly reversible encephalopathy.
Restricted diffusion involving cerebral cortex or caudate and putamen in the appropriate pattern raises prion concern, while hypoxia, seizures and metabolic disease are imaging mimics.
Investigation priorities
Identify prion-associated cortical or striatal restriction and structural, inflammatory, vascular or neoplastic alternatives.
Management branches
Cognition and function have deteriorated substantially over weeks or a few months.
- Stabilise physiology, assess attention and consciousness, review medicines and toxins, obtain collateral chronology and treat seizures, sepsis, hypoglycaemia or suspected encephalitis without avoidable delay.
- Perform detailed neurological examination and urgent blood, MRI and EEG assessment, selecting lumbar puncture after structural and procedural safety review.
- Send CSF for routine, infectious, inflammatory, cytological and antibody tests shaped by phenotype while preserving samples for specialist additions.
- Engage neurology early because empirical antimicrobial or immunotherapy decisions and rapidly changing airway or autonomic risk exceed routine outpatient assessment.