Prevalence of Surgical Procedures at Symptomatic Onset of Prion Disease

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive fatal prion disease. Although most cases are sporadic or inherited, prions may be transmitted via contaminated tissues or durable medical equipment. 1,2 The risk of iatrogenic transmission is highest following procedures involving the central nervous system, where prion burden is highest. 2,3 However, experimental models suggest that transmission may occur following contact with other tissues (eg, nasal mucosa, lung, lymph nodes, and spleen). 4 If these models are accurate, surgical procedures involving these tissues may pose a risk to future patients. To evaluate the potential scope of this problem, we determined the frequency of invasive procedures performed in patients with CJD at multiple tertiary care centers. following


Introduction
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive fatal prion disease. Although most cases are sporadic or inherited, prions may be transmitted via contaminated tissues or durable medical equipment. 1,2 The risk of iatrogenic transmission is highest following procedures involving the central nervous system, where prion burden is highest. 2,3 However, experimental models suggest that transmission may occur following contact with other tissues (eg, nasal mucosa, lung, lymph nodes, and spleen). 4 If these models are accurate, surgical procedures involving these tissues may pose a risk to future patients. To evaluate the potential scope of this problem, we determined the frequency of invasive procedures performed in patients with CJD at multiple tertiary care centers.

Methods
Protocols for this case-control study were approved by the Mayo Clinic institutional review board. A waiver of consent was granted for the use of retrospective, deidentified data. This study follows the assays; or rapidly progressive dementia with 1 or more of the following signs and symptoms: myoclonus, visual or cerebellar signs, pyramidal or extrapyramidal signs, akinetic mutism, and consistent brain magnetic resonance imaging; 71 patients) or definite CJD (pathologically or genetically confirmed, 50 patients) 5 and to capture surgical procedures. Procedures performed within 1 year of the onset of symptoms attributed to CJD were counted to include the presymptomatic period associated with latent prion accumulation. Procedures were stratified by risk of prion contamination of instruments. 3,4 Statistical analysis was performed using SPSS statistical software version 28.0 (IBM), using Pearson χ 2 tests for categorical variables and Mann-Whitney U tests for continuous variables to evaluate the association between patient-specific factors and procedures. Significance was set at P < .10 due to the exploratory nature of this analysis.
Data were analyzed from March 2021 to June 2021.

+ Invited Commentary
Author affiliations and article information are listed at the end of this article. behavioral symptoms or signs at presentation (odds ratio [CI] 0.43 [0.16-1.17]. P = .093) ( Table 2).
Median times from symptom onset to brain magnetic resonance imaging and electroencephalogram were greater in patients who underwent procedures, suggesting that diagnostic delays were associated with procedures. Seventeen of 32 procedures (53%) were performed in the months prior to symptomatic onset (median [range,] −5.4 [−0.2 to −10.8] months). Appropriate procedural precautions were observed in 1 patient.

Discussion
Invasive procedures were frequently performed in patients with CJD included in this case-control study. Actual numbers of procedures may have been even greater, recognizing that procedures performed at outside hospitals may have been overlooked or excluded from records. Replication of study methods within additional hospitals-including community-based centers-is required to confirm these findings and establish the generalizability of results.
Features of sporadic CJD typically manifest in the sixth through eighth decades of life (median age, 68 years), 5 a time when gait abnormalities, sensorimotor complaints and visual changes may be mistaken for common age-related surgically responsive conditions, leading to surgical procedures in this cohort and others. 6 Thus, it is essential to accurately decipher the cause of symptoms and signs in clinical practice (eg, distinguishing between difficulty walking due to joint pain vs ataxia due to CJD). Preoperative risk assessment tools may identify patients at risk of CJD, for whom elective surgical procedures should be deferred and emergent procedures completed under precautions. 2 However, prescreening cannot prevent invasive procedures in presymptomatic patients. National registries may address this problem. In the US, The National Prion Disease Pathology and Surveillance Center systematically collects data from patients with suspected CJD. Incorporating questions on recent invasive procedures would allow early notification of surgeons or facilities when a diagnosis of CJD is confirmed, permitting quarantine, decontamination, or decommissioning of affected instruments. This would also allow for prospective surveillance in larger numbers of patients,