An autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion assay

Abstract

We report an autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion (RT-QUIC) assay. A 61-year-old Japanese man presented with acute onset of consciousness disturbance, and convulsions, but without a past medical or family history of progressive dementia, epilepsy, or prion disease. Brain diffusion and fluid-attenuated inverted recovery MR images revealed edematous cortical hyper-intensity, which diminished after the acute phase. Steroid pulse therapy was partially effective, although he continued to have dementia with myoclonus and psychiatric symptoms, despite resolution of the consciousness disturbance. Cerebrospinal fluid (CSF) analysis revealed a normal cell count, with significantly elevated levels of 14-3-3 protein and total tau protein. In addition, prion protein in the CSF was slowly amplified by the RT-QUIC assay. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. The patient died of sudden cardiac arrest at 3 months after the onset of symptoms. The positive result from the RT-QUIC assay led us to suspect involvement of prion disease, although a postmortem assessment revealed that he had pathological changes after convulsion, and no prion disease. This case indicates that convulsion may cause false-positive RT-QUIC results, and that a postmortem evaluation remains the gold standard for diagnosing similar cases.

Second-Generation RT-QuIC Assay for the Diagnosis of Creutzfeldt-Jakob Disease Patients in Brazil

“…Despite having an extremely high specificity, IQ-CSF RT-QuIC false-positive results have been reported in the literature. Hayashi et al (2017) reported the case of a 61-year-old man who presented with rapid cognitive impairment, myoclonus and recurrent seizures. A brain MRI revealed cortical hyperintensities, and the CSF analysis showed elevated 14-3-3 and tau levels, with a positive RT-QuIC.…”

Steroid-responsive encephalopathy with a peculiar CSF biomarker profile in an 89-year-old man

“…However, it has been reported to be positive in many other neurological disorders such as acute stroke, encephalitis and other forms of dementia and disturbingly often even in patients with treatable conditions [ 6 ]. These include SREAT, although then often associated with epileptic activity [ 7 ]. Our patient, however, presented no evidence of epileptic activity yet he was found positive for CSF protein 14-3-3, which proved to be transient following corticosteroid therapy.…”

Towards an improved early diagnosis of neurodegenerative diseases: the emerging role of in vitro conversion assays for protein amyloids

“…Western blot analysis of the pellet revealed low but above-threshold levels of PK-resistant PrP Sc , which led to the conclusion that this might have been a case of subclinical prion disease, who died from DLB comorbidity. In other recent reports [ 38 , 72 ], an autopsy-verified case of steroid-responsive encephalopathy with status epilepticus and one with dementia of mixed type (AD and vascular) also received a false-positive result, respectively, by PQ and IQ-CSF RT-QuIC. Thus, although false readouts by prion RT-QuIC seem to be extremely rare and some of them may even represent real prion cases, the test does not seem to provide yet a level of diagnostic certainty comparable to a neuropathological examination.…”