Real-time quaking-induced conversion assays for prions: Applying a sensitive but imperfect test in clinical practice

Area of Science:

• Neurology
• Biochemistry
• Pathology

Background:

• Real-time quaking-induced conversion (RT-QuIC) assays are sensitive and specific for prion detection.
• False negative results in RT-QuIC assays are a recognized challenge in clinical prion disease diagnosis.

Purpose of the Study:

• To profile clinical, laboratory, and pathologic features associated with false negative RT-QuIC assays.
• To inform the diagnostic approach for patients with suspected prion disease.

Main Methods:

• 113 patients with probable or definite prion disease were assessed.
• Cerebrospinal fluid (CSF) RT-QuIC testing was performed.
• Clinical, laboratory, and pathologic data were collected and analyzed.

Main Results:

• 13 out of 113 patients (11.5%) had initial negative RT-QuIC results (sensitivity 88.5%).
• RT-QuIC negative patients were younger (median 52.0 vs. 66.1 years) and had longer symptomatic duration (710 vs. 148 days).
• Lower CSF 14-3-3 positivity and total tau levels were observed in RT-QuIC negative patients.

Conclusions:

• RT-QuIC is a sensitive but imperfect diagnostic tool for prion disease.
• False negative RT-QuIC results are associated with a more indolent disease course and lower markers of neuronal damage.
• Diagnostic strategies for suspected prion disease should incorporate RT-QuIC results with other clinical and laboratory findings.