Prusinski, Christian

AbstractBackgroundDiagnostic criteria emphasize the use of real‐time quaking‐induced conversion (RT‐QuIC) assays in cerebrospinal fluid (CSF) to identify patients with rapidly progressive dementia (RPD) due to for Creutzfeldt‐Jakob disease (CJD; CDC Diagnostic Criteria; Oct‐2018). Yet, this test is often performed in specialized centers, leading to delays in return of results. There is a need to leverage clinical features and the results of readily available tests to distinguish patients with CJD from those with other causes (‘CJD mimics’), including patients with potentially treatment‐responsive RPD.MethodPatients with definite (pathology‐confirmed) or probable CJD (clinical features with positive RT‐QuIC) were identified through retrospective review of Mayo Clinic Enterprise (n=91) and Washington University in St. Louis records (n=14; Jan‐2014 to Dec‐2020). Demographic, clinical details and results of common investigations (e.g., neuroimaging, CSF analyses and electroencephalogram) were compared between CJD cases and ‘mimics’ who met clinical criteria for probable CJD but did not have CJD.ResultCJD mimics were diagnosed with autoimmune encephalitis (n=8), neurosarcoidosis (n=1), FTLD/MND (n=1) and unknown dementia (n=1), comprising 11/155 (7%) patients enrolled with RPD at study sites. Median [range] ages‐at‐presentation (65.6 [21.9‐81.5] vs 62.4 [32.8‐76.4] years; p=0.09), % females (51% vs 46%; p>0.99) and symptoms/signs were similar between groups, with the exception of motor complaints (e.g., spasms, focal weakness), which were more common in mimics (11/11 vs 55/105; p<0.01). Electroencephalogram findings did not differ between groups. MRI findings compatible with CJD (i.e., restricted diffusion within deep nuclei/cortical ribbon) predominated in cases (80/105 vs 4/11; p<0.01), while elevations in CSF leukocytes (>5 cells/hpf: 6/11 vs 5/103; p<0.01) and protein >45 mg/dL (10/11 vs 43/103; p<0.01) were more common in mimics. Total‐tau levels >1150 pg/mL (76/84 vs 2/10; p<0.01) and ‘positive’ 14‐3‐3 (67/98 vs 3/10; p=0.03) were frequent in cases. Autoantibodies associated with autoimmune encephalitis were detected in 5/10 mimics but 0/87 cases (p<0.01). Immunosuppressant therapies were provided to 10 mimics and 24 cases, with response limited to mimics.ConclusionsAutoimmune encephalitis, neurosarcoidosis and select neurodegenerative diseases may mimic CJD at presentation. Findings from brain MRI and commonly available CSF tests may facilitate early recognition of mimics, providing an opportunity for early treatment.

AbstractBackgroundPatients with prion disease commonly present with visual, sensorimotor or gait complaints that may prompt surgical interventions for related disorders (e.g., cataracts, carpal tunnel syndrome and joint disease). To prevent iatrogenic transmission of prion disease, surgical instruments used on patients with possible prion disease must be decontaminated or decommissioned. This is only done when the diagnosis of possible prion disease is recognized by the healthcare team. We considered the frequency with which patients with definite or probable prion disease underwent surgeries within one year of the symptomatic onset of prion disease diagnosed.MethodThe Mayo Clinic’s Advanced Cohort Explorer was used to identify patients with prion disease diagnostic codes assessed since 1/1/2014 (n=296). Patients with prion disease enrolled in prospective studies of rapidly progressive dementia beginning 2/14/2015 at Washington University School of Medicine (St. Louis, MO) were also included (n=14). Charts were independently reviewed by two team members, and demographic and clinical details extracted.Result108 patients with probable or definite prion disease were identified, including 62 (57%) with autopsy‐ or genetically‐proven prion disease (57 sporadic, 4 familial, 1 fatal familial insomnia). The majority of patients experienced a rapidly progressive course (mean symptom‐duration 10.0±9.7 months). Twenty‐nine patients (26.9%) underwent 36 surgeries or invasive procedures using durable instruments, including 3 high‐risk procedures directly involving the central nervous system, and 13 intermediate‐ (e.g., joint replacement) and 20 low‐risk procedures (e.g., endoscopy). Surgeries were performed a median of 10.2 months before death (range: 0.8‐62.3), with 16 (44%) performed after symptom onset. Surgical operators were unaware of the diagnosis of possible prion disease in all but one case (diagnostic brain biopsy).ConclusionSurgeries were common in patients with prion disease in this series and were commonly performed by operators who were unaware of the diagnosis. Coordinated approaches to screening and reporting may be needed to reduce the risk of iatrogenic spread of prion disease.