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This paper examines key CJD diagnostic challenges, especially differential diagnosis and diagnostic delays. 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Due to its heterogenous clinical presentation diagnosis uncertainties are common. In this paper we explore CJD diagnostic challenges focusing on differential diagnosis and diagnostic delays.  \nMethods  \nWe report a case of a patient who was misclassified and evaluated by several medical specialties before the CJD suspicion. A systematic review of the literature of the CJD case reports focused on the timely and differential diagnosis was carried out in Medline and Embase until May 2023.  \nOpen Peer Review  \n\n| Approval Status  |  |\n| --- | --- |\n| 1 | 2 |\n| version 2\u003Cbr>(revision)\u003Cbr>09 Dec 2025\u003Cbr>version 1  \u003Cbr>view view\u003Cbr>11 Apr 2025 |  |\n\n1. Anna Ladogana , Istituto Superiore di Sanità, Rome, Italy  \n2. Shi-Lin Yang, Fudan University, Shanghai, China  \nAny reports and responses or comments on the  \narticle can be found at the end of the article.  \nResults  \nPatient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In  \nsystematic review, fifteen articles were selected, who reported 31 cases of CJD with problems in the timely diagnosis and incorrect initial diagnosis, the main initial differential diagnoses were psychiatry exacerbation, myelopathy, epilepsy, stroke, parkinsonism, cerebellarataxia and autoimmune encephalitis. The most common clinical onset was psychobehavioral disturbances (apathy, confusion and sleep disturbance), extrapyramidal signs and cognitive impairment. The diagnosis delay was from one to eighteen months.  \nConclusion  \nA discussion of the case report and the diagnostic challenges reported in the literature was made. Patients can present a wide range of symptoms. It is recommended to consider CJD for the differential diagnosis in patients with behavioral symptoms, and cognitive impairment.  \nKeywords  \nCreutzfeldt-Jakob syndrome; Prion diseases; differential diagnosis; behavioral symptoms; 14-3-3 Proteins; Peru  \nCorresponding author: Kevin Pacheco-Barrios ([kevin.pacheco.barrios@gmail.com](kevin.pacheco.barrios@gmail.com))  \nAuthor roles: Failoc Rojas VE: Conceptualization, Data Curation, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing; Yazawa-Ballena Y: Conceptualization, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing; Alvarado-Moreno G: Conceptualization, Inve","cbCair0OLqSNkQqg","https://ap.wps.com/l/cbCair0OLqSNkQqg","pdf",644411,18,"English","# Introduction\n# Methods\n# Results\n# Conclusion\n# Keywords","[{\"question\":\"What makes Creutzfeldt-Jakob disease diagnosis difficult in practice?\",\"answer\":\"CJD shows heterogeneous clinical presentations, so early findings can lead to uncertainty and misclassification. The paper emphasizes frequent differential-diagnosis problems and diagnostic delays.\"},{\"question\":\"How was the evidence synthesized for diagnostic challenges?\",\"answer\":\"The study reports a misclassified clinical case and conducts a systematic review of CJD case reports in Medline and Embase up to May 2023, focusing on timely and differential diagnosis.\"},{\"question\":\"What differential diagnoses were commonly mistaken for CJD?\",\"answer\":\"The main initial differential diagnoses included psychiatric exacerbation, myelopathy, epilepsy, stroke, parkinsonism, cerebellar ataxia, and autoimmune encephalitis.\"}]","Case Report: Creutzfeldt-Jakob disease and diagnosis challenges - case report and evidence synthesis | PDF",1790739047,45]