What are the indications for RDP?

Indications for RDP (Rapidly Progressive Dementia)

RDP refers to Rapidly Progressive Dementia, a clinical syndrome requiring urgent neuroimaging evaluation to identify treatable structural abnormalities and diverse etiologies including prion diseases, infections, inflammatory processes, neoplasms, and metabolic disorders. 1

Primary Clinical Indication

MRI brain without and with IV contrast is the recommended initial imaging test for adult patients presenting with rapidly progressive cognitive decline to detect:

• Prion-related diseases (Creutzfeldt-Jakob disease and variants) 1
• Infectious/inflammatory processes (viral encephalitides, HIV-related conditions, Lyme disease, neurosyphilis) 1
• Neoplastic and paraneoplastic processes (lymphoma, metastases, paraneoplastic limbic encephalitis) 1
• Demyelinating diseases (multiple sclerosis, progressive multifocal leukoencephalopathy) 1
• Toxic/metabolic disorders (Wernicke encephalopathy, osmotic demyelination syndrome, Wilson disease) 1
• Vasculitis/vasculopathies (CNS vasculitis, dural arteriovenous fistulae) 1

Critical Diagnostic Features

The hallmark of RPD is cognitive decline developing over weeks to months (median survival approximately 5 months in sporadic CJD), distinguishing it from typical neurodegenerative dementias that progress over years. 2

Mandatory Exclusions Before RPD Diagnosis

Before considering RPD, immediately exclude acute reversible causes 3:

• Delirium from infections (urinary tract infections, pneumonia, sepsis—the most common cause in elderly patients) 3
• Metabolic derangements (hypoglycemia, hyponatremia, hypercalcemia, hepatic/renal failure) 3
• Medication toxicity (anticholinergics, benzodiazepines, opioids) 3
• Acute cerebrovascular events (stroke involving thalamus, hippocampus, frontal lobes) 3
• Structural lesions (subdural hematoma, brain tumors) 3

Imaging Protocol Specifics

MRI brain without and with IV contrast provides superior sensitivity and specificity compared to CT for detecting the diverse etiologies of RPD. 1 The addition of contrast specifically increases detection of infectious, inflammatory, and neoplastic/paraneoplastic causes. 1

Key MRI Findings by Etiology

For prion diseases: Hyperintense signal on T2/FLAIR and diffusion-weighted imaging (DWI) with cortical and deep gray matter involvement; the "hockey stick" or "pulvinar" sign (confluent high signal in dorsomedial/posterior thalami) is more sensitive than CSF 14-3-3 protein or EEG findings. 1 Negative DWI effectively excludes prion disease. 1

CT head without IV contrast is acceptable as an alternative initial test but has lower sensitivity; it can demonstrate subdural hematomas, large mass lesions, hydrocephalus, and parenchymal changes. 1

Non-Recommended Initial Imaging

The following modalities are not recommended for initial RPD evaluation 1:

• MR spectroscopy
• Functional MRI (fMRI)
• Brain amyloid PET/CT
• Brain FDG-PET/CT
• Brain perfusion SPECT/CT
• Brain striatal SPECT/CT
• Brain tau PET/CT

These advanced techniques may be considered later if clinical suspicion suggests an atypical presentation of a specific neurodegenerative disease. 1

Clinical Pitfalls to Avoid

Never attribute acute cognitive decline to progression of pre-existing dementia without excluding reversible causes. 3 This is the most critical error in RPD evaluation.

Do not delay neuroimaging while pursuing extensive laboratory workup—structural lesions require immediate identification. 3

Sudden decline over days is atypical for primary neurodegenerative diseases and mandates aggressive search for acute causes. 3

Diagnostic Algorithm Priority

1. Detailed history: Exact onset timing, new medications, head trauma, infectious symptoms, vascular risk factors 3
2. Physical examination: Temperature, infection signs, focal neurological deficits, trauma evidence 3
3. Immediate neuroimaging: MRI brain with and without contrast (preferred) or CT head without contrast 1
4. Laboratory evaluation: Complete blood count, comprehensive metabolic panel, thyroid function, vitamin B12, urinalysis 3
5. Specialized testing if indicated: CSF analysis with RT-QuIC for prion disease (>90% sensitivity/specificity), PRNP genetic testing 2

Genetic counseling should be offered to all families with confirmed prion disease, regardless of apparent family history, due to possible de novo mutations and incomplete penetrance. 2