Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis

Case Report: Creutzfeldt-Jakob disease and... | F1000Research "use strict";function _typeof(t){return(_typeof="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(t){return typeof t}:function(t){return t&&"function"==typeof Symbol&&t.constructor===Symbol&&t!==Symbol.prototype?"symbol":typeof t})(t)}!function(){var t=function(){var t,e,o=[],n=window,r=n;for(;r;){try{if(r.frames.__tcfapiLocator){t=r;break}}catch(t){}if(r===n.top)break;r=r.parent}t||(!function t(){var e=n.document,o=!!n.frames.__tcfapiLocator;if(!o)if(e.body){var r=e.createElement("iframe");r.style.cssText="display:none",r.name="__tcfapiLocator",e.body.appendChild(r)}else setTimeout(t,5);return!o}(),n.__tcfapi=function(){for(var t=arguments.length,n=new Array(t),r=0;r 3&&2===parseInt(n[1],10)&&"boolean"==typeof n[3]&&(e=n[3],"function"==typeof n[2]&&n[2]("set",!0)):"ping"===n[0]?"function"==typeof n[2]&&n[2]({gdprApplies:e,cmpLoaded:!1,cmpStatus:"stub"}):o.push(n)},n.addEventListener("message",(function(t){var e="string"==typeof t.data,o={};if(e)try{o=JSON.parse(t.data)}catch(t){}else o=t.data;var n="object"===_typeof(o)&&null!==o?o.__tcfapiCall:null;n&&window.__tcfapi(n.command,n.version,(function(o,r){var a={__tcfapiReturn:{returnValue:o,success:r,callId:n.callId}};t&&t.source&&t.source.postMessage&&t.source.postMessage(e?JSON.stringify(a):a,"*")}),n.parameter)}),!1))};"undefined"!=typeof module?module.exports=t:t()}(); dataLayer = dataLayer || []; // Standard GTM initialization - Google Consent Mode handles consent automatically (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start': new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0], j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src= 'https://www.googletagmanager.com/gtm.js?id='+i+dl+ '>m_auth=hzk0Vc3qFsQYhCrIoHz68A>m_preview=env-1>m_cookies_win=x';f.parentNode.insertBefore(j,f); })(window,document,'script','dataLayer','GTM-MWFK8L5J'); ;window.NREUM||(NREUM={});NREUM.init={distributed_tracing:{enabled:true},privacy:{cookies_enabled:true},ajax:{deny_list:["bam.nr-data.net"]}}; ;NREUM.loader_config={accountID:"438030",trustKey:"438030",agentID:"772317073",licenseKey:"97f8f67f26",applicationID:"772317073"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"97f8f67f26",applicationID:"772317073",sa:1} ;/*! For license information please see nr-loader-spa-1.236.0.min.js.LICENSE.txt */ (()=>{"use strict";var e,t,r={5763:(e,t,r)=>{r.d(t,{P_:()=>l,Mt:()=>g,C5:()=>s,DL:()=>v,OP:()=>T,lF:()=>D,Yu:()=>y,Dg:()=>h,CX:()=>c,GE:()=>b,sU:()=>_});var n=r(8632),i=r(9567);const o={beacon:n.ce.beacon,errorBeacon:n.ce.errorBeacon,licenseKey:void 0,applicationID:void 0,sa:void 0,queueTime:void 0,applicationTime:void 0,ttGuid:void 0,user:void 0,account:void 0,product:void 0,extra:void 0,jsAttributes:{},userAttributes:void 0,atts:void 0,transactionName:void 0,tNamePlain:void 0},a={};function s(e){if(!e)throw new Error("All info objects require an agent identifier!");if(!a[e])throw new Error("Info for ".concat(e," was never set"));return a[e]}function c(e,t){if(!e)throw new Error("All info objects require an agent identifier!");a[e]=(0,i.D)(t,o),(0,n.Qy)(e,a[e],"info")}var u=r(7056);const d=()=>{const e={blockSelector:"[data-nr-block]",maskInputOptions:{password:!0}};return{allow_bfcache:!0,privacy:{cookies_enabled:!0},ajax:{deny_list:void 0,enabled:!0,harvestTimeSeconds:10},distributed_tracing:{enabled:void 0,exclude_newrelic_header:void 0,cors_use_newrelic_header:void 0,cors_use_tracecontext_headers:void 0,allowed_origins:void 0},session:{domain:void 0,expiresMs:u.oD,inactiveMs:u.Hb},ssl:void 0,obfuscate:void 0,jserrors:{enabled:!0,harvestTimeSeconds:10},metrics:{enabled:!0},page_action:{enabled:!0,harvestTimeSeconds:30},page_view_event:{enabled:!0},page_view_timing:{enabled:!0,harvestTimeSeconds:30,long_task:!1},session_trace:{enabled:!0,harvestTimeSeconds:10},harvest:{tooManyRequestsDelay:60},session_replay:{enabled:!1,harvestTimeSeconds:60,sampleRate:.1,errorSampleRate:.1,maskTextSelector:"*",maskAllInputs:!0,get blockClass(){return"nr-block"},get ignoreClass(){return"nr-ignore"},get maskTextClass(){return"nr-mask"},get blockSelector(){return e.blockSelector},set blockSelector(t){e.blockSelector+=",".concat(t)},get maskInputOptions(){return e.maskInputOptions},set maskInputOptions(t){e.maskInputOptions={...t,password:!0}}},spa:{enabled:!0,harvestTimeSeconds:10}}},f={};function l(e){if(!e)throw new Error("All configuration objects require an agent identifier!");if(!f[e])throw new Error("Configuration for ".concat(e," was never set"));return f[e]}function h(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");f[e]=(0,i.D)(t,d()),(0,n.Qy)(e,f[e],"config")}function g(e,t){if(!e)throw new Error("All configuration objects require an agent identifier!");var r=l(e);if(r){for(var n=t.split("."),i=0;i {r.d(t,{D:()=>i});var n=r(50);function i(e,t){try{if(!e||"object"!=typeof e)return(0,n.Z)("Setting a Configurable requires an object as input");if(!t||"object"!=typeof t)return(0,n.Z)("Setting a Configurable requires a model to set its initial properties");const r=Object.create(Object.getPrototypeOf(t),Object.getOwnPropertyDescriptors(t)),o=0===Object.keys(r).length?e:r;for(let a in o)if(void 0!==e[a])try{"object"==typeof e[a]&&"object"==typeof t[a]?r[a]=i(e[a],t[a]):r[a]=e[a]}catch(e){(0,n.Z)("An error occurred while setting a property of a Configurable",e)}return r}catch(e){(0,n.Z)("An error occured while setting a Configurable",e)}}},6818:(e,t,r)=>{r.d(t,{Re:()=>i,gF:()=>o,q4:()=>n});const n="1.236.0",i="PROD",o="CDN"},385:(e,t,r)=>{r.d(t,{FN:()=>a,IF:()=>u,Nk:()=>f,Tt:()=>s,_A:()=>o,il:()=>n,pL:()=>c,v6:()=>i,w1:()=>d});const n="undefined"!=typeof window&&!!window.document,i="undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self.navigator instanceof WorkerNavigator||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis.navigator instanceof WorkerNavigator),o=n?window:"undefined"!=typeof WorkerGlobalScope&&("undefined"!=typeof self&&self instanceof WorkerGlobalScope&&self||"undefined"!=typeof globalThis&&globalThis instanceof WorkerGlobalScope&&globalThis),a=""+o?.location,s=/iPad|iPhone|iPod/.test(navigator.userAgent),c=s&&"undefined"==typeof SharedWorker,u=(()=>{const e=navigator.userAgent.match(/Firefox[/\s](\d+\.\d+)/);return Array.isArray(e)&&e.length>=2?+e[1]:0})(),d=Boolean(n&&window.document.documentMode),f=!!navigator.sendBeacon},1117:(e,t,r)=>{r.d(t,{w:()=>o});var n=r(50);const i={agentIdentifier:"",ee:void 0};class o{constructor(e){try{if("object"!=typeof e)return(0,n.Z)("shared context requires an object as input");this.sharedContext={},Object.assign(this.sharedContext,i),Object.entries(e).forEach((e=>{let[t,r]=e;Object.keys(i).includes(t)&&(this.sharedContext[t]=r)}))}catch(e){(0,n.Z)("An error occured while setting SharedContext",e)}}}},8e3:(e,t,r)=>{r.d(t,{L:()=>d,R:()=>c});var n=r(2177),i=r(1284),o=r(4322),a=r(3325);const s={};function c(e,t){const r={staged:!1,priority:a.p[t]||0};u(e),s[e].get(t)||s[e].set(t,r)}function u(e){e&&(s[e]||(s[e]=new Map))}function d(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:"",t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"feature";if(u(e),!e||!s[e].get(t))return a(t);s[e].get(t).staged=!0;const r=[...s[e]];function a(t){const r=e?n.ee.get(e):n.ee,a=o.X.handlers;if(r.backlog&&a){var s=r.backlog[t],c=a[t];if(c){for(var u=0;s&&u {let[t,r]=e;return r.staged}))&&(r.sort(((e,t)=>e[1].priority-t[1].priority)),r.forEach((e=>{let[t]=e;a(t)})))}function f(e,t){var r=e[1];(0,i.D)(t[r],(function(t,r){var n=e[0];if(r[0]===n){var i=r[1],o=e[3],a=e[2];i.apply(o,a)}}))}},2177:(e,t,r)=>{r.d(t,{c:()=>f,ee:()=>u});var n=r(8632),i=r(2210),o=r(1284),a=r(5763),s="nr@context";let c=(0,n.fP)();var u;function d(){}function f(e){return(0,i.X)(e,s,l)}function l(){return new d}function h(){u.aborted=!0,u.backlog={}}c.ee?u=c.ee:(u=function e(t,r){var n={},c={},f={},g=!1;try{g=16===r.length&&(0,a.OP)(r).isolatedBacklog}catch(e){}var p={on:b,addEventListener:b,removeEventListener:y,emit:v,get:x,listeners:w,context:m,buffer:A,abort:h,aborted:!1,isBuffering:E,debugId:r,backlog:g?{}:t&&"object"==typeof t.backlog?t.backlog:{}};return p;function m(e){return e&&e instanceof d?e:e?(0,i.X)(e,s,l):l()}function v(e,r,n,i,o){if(!1!==o&&(o=!0),!u.aborted||i){t&&o&&t.emit(e,r,n);for(var a=m(n),s=w(e),d=s.length,f=0;fn,p:()=>i});var n=r(2177).ee.get("handle");function i(e,t,r,i,o){o?(o.buffer([e],i),o.emit(e,t,r)):(n.buffer([e],i),n.emit(e,t,r))}},4322:(e,t,r)=>{r.d(t,{X:()=>o});var n=r(5546);o.on=a;var i=o.handlers={};function o(e,t,r,o){a(o||n.E,i,e,t,r)}function a(e,t,r,i,o){o||(o="feature"),e||(e=n.E);var a=t[o]=t[o]||{};(a[r]=a[r]||[]).push([e,i])}},3239:(e,t,r)=>{r.d(t,{bP:()=>s,iz:()=>c,m$:()=>a});var n=r(385);let i=!1,o=!1;try{const e={get passive(){return i=!0,!1},get signal(){return o=!0,!1}};n._A.addEventListener("test",null,e),n._A.removeEventListener("test",null,e)}catch(e){}function a(e,t){return i||o?{capture:!!e,passive:i,signal:t}:!!e}function s(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;window.addEventListener(e,t,a(r,n))}function c(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2],n=arguments.length>3?arguments[3]:void 0;document.addEventListener(e,t,a(r,n))}},4402:(e,t,r)=>{r.d(t,{Ht:()=>u,M:()=>c,Rl:()=>a,ky:()=>s});var n=r(385);const i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx";function o(e,t){return e?15&e[t]:16*Math.random()|0}function a(){const e=n._A?.crypto||n._A?.msCrypto;let t,r=0;return e&&e.getRandomValues&&(t=e.getRandomValues(new Uint8Array(31))),i.split("").map((e=>"x"===e?o(t,++r).toString(16):"y"===e?(3&o()|8).toString(16):e)).join("")}function s(e){const t=n._A?.crypto||n._A?.msCrypto;let r,i=0;t&&t.getRandomValues&&(r=t.getRandomValues(new Uint8Array(31)));const a=[];for(var s=0;s {r.d(t,{Bq:()=>n,Hb:()=>o,oD:()=>i});const n="NRBA",i=144e5,o=18e5},7894:(e,t,r)=>{function n(){return Math.round(performance.now())}r.d(t,{z:()=>n})},7243:(e,t,r)=>{r.d(t,{e:()=>o});var n=r(385),i={};function o(e){if(e in i)return i[e];if(0===(e||"").indexOf("data:"))return{protocol:"data"};let t;var r=n._A?.location,o={};if(n.il)t=document.createElement("a"),t.href=e;else try{t=new URL(e,r.href)}catch(e){return o}o.port=t.port;var a=t.href.split("://");!o.port&&a[1]&&(o.port=a[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===a[0]?"443":"80"),o.hostname=t.hostname||r.hostname,o.pathname=t.pathname,o.protocol=a[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var s=!t.protocol||":"===t.protocol||t.protocol===r.protocol,c=t.hostname===r.hostname&&t.port===r.port;return o.sameOrigin=s&&(!t.hostname||c),"/"===o.pathname&&(i[e]=o),o}},50:(e,t,r)=>{function n(e,t){"function"==typeof console.warn&&(console.warn("New Relic: ".concat(e)),t&&console.warn(t))}r.d(t,{Z:()=>n})},2587:(e,t,r)=>{r.d(t,{N:()=>c,T:()=>u});var n=r(2177),i=r(5546),o=r(8e3),a=r(3325);const s={stn:[a.D.sessionTrace],err:[a.D.jserrors,a.D.metrics],ins:[a.D.pageAction],spa:[a.D.spa],sr:[a.D.sessionReplay,a.D.sessionTrace]};function c(e,t){const r=n.ee.get(t);e&&"object"==typeof e&&(Object.entries(e).forEach((e=>{let[t,n]=e;void 0===u[t]&&(s[t]?s[t].forEach((e=>{n?(0,i.p)("feat-"+t,[],void 0,e,r):(0,i.p)("block-"+t,[],void 0,e,r),(0,i.p)("rumresp-"+t,[Boolean(n)],void 0,e,r)})):n&&(0,i.p)("feat-"+t,[],void 0,void 0,r),u[t]=Boolean(n))})),Object.keys(s).forEach((e=>{void 0===u[e]&&(s[e]?.forEach((t=>(0,i.p)("rumresp-"+e,[!1],void 0,t,r))),u[e]=!1)})),(0,o.L)(t,a.D.pageViewEvent))}const u={}},2210:(e,t,r)=>{r.d(t,{X:()=>i});var n=Object.prototype.hasOwnProperty;function i(e,t,r){if(n.call(e,t))return e[t];var i=r();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(e,t,{value:i,writable:!0,enumerable:!1}),i}catch(e){}return e[t]=i,i}},1284:(e,t,r)=>{r.d(t,{D:()=>n});const n=(e,t)=>Object.entries(e||{}).map((e=>{let[r,n]=e;return t(r,n)}))},4351:(e,t,r)=>{r.d(t,{P:()=>o});var n=r(2177);const i=()=>{const e=new WeakSet;return(t,r)=>{if("object"==typeof r&&null!==r){if(e.has(r))return;e.add(r)}return r}};function o(e){try{return JSON.stringify(e,i())}catch(e){try{n.ee.emit("internal-error",[e])}catch(e){}}}},3960:(e,t,r)=>{r.d(t,{K:()=>a,b:()=>o});var n=r(3239);function i(){return"undefined"==typeof document||"complete"===document.readyState}function o(e,t){if(i())return e();(0,n.bP)("load",e,t)}function a(e){if(i())return e();(0,n.iz)("DOMContentLoaded",e)}},8632:(e,t,r)=>{r.d(t,{EZ:()=>u,Qy:()=>c,ce:()=>o,fP:()=>a,gG:()=>d,mF:()=>s});var n=r(7894),i=r(385);const o={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net"};function a(){return i._A.NREUM||(i._A.NREUM={}),void 0===i._A.newrelic&&(i._A.newrelic=i._A.NREUM),i._A.NREUM}function s(){let e=a();return e.o||(e.o={ST:i._A.setTimeout,SI:i._A.setImmediate,CT:i._A.clearTimeout,XHR:i._A.XMLHttpRequest,REQ:i._A.Request,EV:i._A.Event,PR:i._A.Promise,MO:i._A.MutationObserver,FETCH:i._A.fetch}),e}function c(e,t,r){let i=a();const o=i.initializedAgents||{},s=o[e]||{};return Object.keys(s).length||(s.initializedAt={ms:(0,n.z)(),date:new Date}),i.initializedAgents={...o,[e]:{...s,[r]:t}},i}function u(e,t){a()[e]=t}function d(){return function(){let e=a();const t=e.info||{};e.info={beacon:o.beacon,errorBeacon:o.errorBeacon,...t}}(),function(){let e=a();const t=e.init||{};e.init={...t}}(),s(),function(){let e=a();const t=e.loader_config||{};e.loader_config={...t}}(),a()}},7956:(e,t,r)=>{r.d(t,{N:()=>i});var n=r(3239);function i(e){let t=arguments.length>1&&void 0!==arguments[1]&&arguments[1],r=arguments.length>2?arguments[2]:void 0,i=arguments.length>3?arguments[3]:void 0;return void(0,n.iz)("visibilitychange",(function(){if(t)return void("hidden"==document.visibilityState&&e());e(document.visibilityState)}),r,i)}},1214:(e,t,r)=>{r.d(t,{em:()=>v,u5:()=>N,QU:()=>S,_L:()=>I,Gm:()=>L,Lg:()=>M,gy:()=>U,BV:()=>Q,Kf:()=>ee});var n=r(2177);const i="nr@original";var o=Object.prototype.hasOwnProperty,a=!1;function s(e,t){return e||(e=n.ee),r.inPlace=function(e,t,n,i,o){n||(n="");var a,s,c,u="-"===n.charAt(0);for(c=0;c 2?n-2:0),o=2;o {r(A[T],e,w),r(E[T],e,w)})),r(l._A,"fetch",y),t.on(y+"end",(function(e,r){var n=this;if(r){var i=r.headers.get("content-length");null!==i&&(n.rxSize=i),t.emit(y+"done",[null,r],n)}else t.emit(y+"done",[e],n)})),t}const O={},j=["pushState","replaceState"];function S(e){const t=function(e){return(e||n.ee).get("history")}(e);return!l.il||O[t.debugId]++||(O[t.debugId]=1,s(t).inPlace(window.history,j,"-")),t}var P=r(3239);const C={},R=["appendChild","insertBefore","replaceChild"];function I(e){const t=function(e){return(e||n.ee).get("jsonp")}(e);if(!l.il||C[t.debugId])return t;C[t.debugId]=!0;var r=s(t),i=/[?&](?:callback|cb)=([^&#]+)/,o=/(.*)\.([^.]+)/,a=/^(\w+)(\.|$)(.*)$/;function c(e,t){var r=e.match(a),n=r[1],i=r[3];return i?c(i,t[n]):t[n]}return r.inPlace(Node.prototype,R,"dom-"),t.on("dom-start",(function(e){!function(e){if(!e||"string"!=typeof e.nodeName||"script"!==e.nodeName.toLowerCase())return;if("function"!=typeof e.addEventListener)return;var n=(a=e.src,s=a.match(i),s?s[1]:null);var a,s;if(!n)return;var u=function(e){var t=e.match(o);if(t&&t.length>=3)return{key:t[2],parent:c(t[1],window)};return{key:e,parent:window}}(n);if("function"!=typeof u.parent[u.key])return;var d={};function f(){t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}function l(){t.emit("jsonp-error",[],d),t.emit("jsonp-end",[],d),e.removeEventListener("load",f,(0,P.m$)(!1)),e.removeEventListener("error",l,(0,P.m$)(!1))}r.inPlace(u.parent,[u.key],"cb-",d),e.addEventListener("load",f,(0,P.m$)(!1)),e.addEventListener("error",l,(0,P.m$)(!1)),t.emit("new-jsonp",[e.src],d)}(e[0])})),t}var k=r(5763);const H={};function L(e){const t=function(e){return(e||n.ee).get("mutation")}(e);if(!l.il||H[t.debugId])return t;H[t.debugId]=!0;var r=s(t),i=k.Yu.MO;return i&&(window.MutationObserver=function(e){return this instanceof i?new i(r(e,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype),t}const z={};function M(e){const t=function(e){return(e||n.ee).get("promise")}(e);if(z[t.debugId])return t;z[t.debugId]=!0;var r=n.c,o=s(t),a=k.Yu.PR;return a&&function(){function e(r){var n=t.context(),i=o(r,"executor-",n,null,!1);const s=Reflect.construct(a,[i],e);return t.context(s).getCtx=function(){return n},s}l._A.Promise=e,Object.defineProperty(e,"name",{value:"Promise"}),e.toString=function(){return a.toString()},Object.setPrototypeOf(e,a),["all","race"].forEach((function(r){const n=a[r];e[r]=function(e){let i=!1;[...e||[]].forEach((e=>{this.resolve(e).then(a("all"===r),a(!1))}));const o=n.apply(this,arguments);return o;function a(e){return function(){t.emit("propagate",[null,!i],o,!1,!1),i=i||!e}}}})),["resolve","reject"].forEach((function(r){const n=a[r];e[r]=function(e){const r=n.apply(this,arguments);return e!==r&&t.emit("propagate",[e,!0],r,!1,!1),r}})),e.prototype=a.prototype;const n=a.prototype.then;a.prototype.then=function(){var e=this,i=r(e);i.promise=e;for(var a=arguments.length,s=new Array(a),c=0;c e())),t};function m(e,t){i.inPlace(t,["onreadystatechange"],"fn-",E)}function b(){var e=this,t=r.context(e);e.readyState>3&&!t.resolved&&(t.resolved=!0,r.emit("xhr-resolved",[],e)),i.inPlace(e,f,"fn-",E)}if(function(e,t){for(var r in e)t[r]=e[r]}(o,p),p.prototype=o.prototype,i.inPlace(p.prototype,J,"-xhr-",E),r.on("send-xhr-start",(function(e,t){m(e,t),function(e){h.push(e),a&&(y?y.then(A):u?u(A):(w=-w,x.data=w))}(t)})),r.on("open-xhr-start",m),a){var y=c&&c.resolve();if(!u&&!c){var w=1,x=document.createTextNode(w);new a(A).observe(x,{characterData:!0})}}else t.on("fn-end",(function(e){e[0]&&e[0].type===d||A()}));function A(){for(var e=0;e {r.d(t,{t:()=>n});const n=r(3325).D.ajax},6660:(e,t,r)=>{r.d(t,{A:()=>i,t:()=>n});const n=r(3325).D.jserrors,i="nr@seenError"},3081:(e,t,r)=>{r.d(t,{gF:()=>o,mY:()=>i,t9:()=>n,vz:()=>s,xS:()=>a});const n=r(3325).D.metrics,i="sm",o="cm",a="storeSupportabilityMetrics",s="storeEventMetrics"},4649:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageAction},7633:(e,t,r)=>{r.d(t,{Dz:()=>i,OJ:()=>a,qw:()=>o,t9:()=>n});const n=r(3325).D.pageViewEvent,i="firstbyte",o="domcontent",a="windowload"},9251:(e,t,r)=>{r.d(t,{t:()=>n});const n=r(3325).D.pageViewTiming},3614:(e,t,r)=>{r.d(t,{BST_RESOURCE:()=>i,END:()=>s,FEATURE_NAME:()=>n,FN_END:()=>u,FN_START:()=>c,PUSH_STATE:()=>d,RESOURCE:()=>o,START:()=>a});const n=r(3325).D.sessionTrace,i="bstResource",o="resource",a="-start",s="-end",c="fn"+a,u="fn"+s,d="pushState"},7836:(e,t,r)=>{r.d(t,{BODY:()=>A,CB_END:()=>E,CB_START:()=>u,END:()=>x,FEATURE_NAME:()=>i,FETCH:()=>_,FETCH_BODY:()=>v,FETCH_DONE:()=>m,FETCH_START:()=>p,FN_END:()=>c,FN_START:()=>s,INTERACTION:()=>l,INTERACTION_API:()=>d,INTERACTION_EVENTS:()=>o,JSONP_END:()=>b,JSONP_NODE:()=>g,JS_TIME:()=>T,MAX_TIMER_BUDGET:()=>a,REMAINING:()=>f,SPA_NODE:()=>h,START:()=>w,originalSetTimeout:()=>y});var n=r(5763);const i=r(3325).D.spa,o=["click","submit","keypress","keydown","keyup","change"],a=999,s="fn-start",c="fn-end",u="cb-start",d="api-ixn-",f="remaining",l="interaction",h="spaNode",g="jsonpNode",p="fetch-start",m="fetch-done",v="fetch-body-",b="jsonp-end",y=n.Yu.ST,w="-start",x="-end",A="-body",E="cb"+x,T="jsTime",_="fetch"},5938:(e,t,r)=>{r.d(t,{W:()=>o});var n=r(5763),i=r(2177);class o{constructor(e,t,r){this.agentIdentifier=e,this.aggregator=t,this.ee=i.ee.get(e,(0,n.OP)(this.agentIdentifier).isolatedBacklog),this.featureName=r,this.blocked=!1}}},9144:(e,t,r)=>{r.d(t,{j:()=>m});var n=r(3325),i=r(5763),o=r(5546),a=r(2177),s=r(7894),c=r(8e3),u=r(3960),d=r(385),f=r(50),l=r(3081),h=r(8632);function g(){const e=(0,h.gG)();["setErrorHandler","finished","addToTrace","inlineHit","addRelease","addPageAction","setCurrentRouteName","setPageViewName","setCustomAttribute","interaction","noticeError","setUserId"].forEach((t=>{e[t]=function(){for(var r=arguments.length,n=new Array(r),i=0;i 1?r-1:0),i=1;i {e.exposed&&e.api[t]&&o.push(e.api[t](...n))})),o.length>1?o:o[0]}(t,...n)}}))}var p=r(2587);function m(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{},m=arguments.length>2?arguments[2]:void 0,v=arguments.length>3?arguments[3]:void 0,{init:b,info:y,loader_config:w,runtime:x={loaderType:m},exposed:A=!0}=t;const E=(0,h.gG)();y||(b=E.init,y=E.info,w=E.loader_config),(0,i.Dg)(e,b||{}),(0,i.GE)(e,w||{}),(0,i.sU)(e,x),y.jsAttributes??={},d.v6&&(y.jsAttributes.isWorker=!0),(0,i.CX)(e,y),g();const T=function(e,t){t||(0,c.R)(e,"api");const h={};var g=a.ee.get(e),p=g.get("tracer"),m="api-",v=m+"ixn-";function b(t,r,n,o){const a=(0,i.C5)(e);return null===r?delete a.jsAttributes[t]:(0,i.CX)(e,{...a,jsAttributes:{...a.jsAttributes,[t]:r}}),x(m,n,!0,o||null===r?"session":void 0)(t,r)}function y(){}["setErrorHandler","finished","addToTrace","inlineHit","addRelease"].forEach((e=>h[e]=x(m,e,!0,"api"))),h.addPageAction=x(m,"addPageAction",!0,n.D.pageAction),h.setCurrentRouteName=x(m,"routeName",!0,n.D.spa),h.setPageViewName=function(t,r){if("string"==typeof t)return"/"!==t.charAt(0)&&(t="/"+t),(0,i.OP)(e).customTransaction=(r||"http://custom.transaction")+t,x(m,"setPageViewName",!0)()},h.setCustomAttribute=function(e,t){let r=arguments.length>2&&void 0!==arguments[2]&&arguments[2];if("string"==typeof e){if(["string","number"].includes(typeof t)||null===t)return b(e,t,"setCustomAttribute",r);(0,f.Z)("Failed to execute setCustomAttribute.\nNon-null value must be a string or number type, but a type of was provided."))}else(0,f.Z)("Failed to execute setCustomAttribute.\nName must be a string type, but a type of was provided."))},h.setUserId=function(e){if("string"==typeof e||null===e)return b("enduser.id",e,"setUserId",!0);(0,f.Z)("Failed to execute setUserId.\nNon-null value must be a string type, but a type of was provided."))},h.interaction=function(){return(new y).get()};var w=y.prototype={createTracer:function(e,t){var r={},i=this,a="function"==typeof t;return(0,o.p)(v+"tracer",[(0,s.z)(),e,r],i,n.D.spa,g),function(){if(p.emit((a?"":"no-")+"fn-start",[(0,s.z)(),i,a],r),a)try{return t.apply(this,arguments)}catch(e){throw p.emit("fn-err",[arguments,this,"string"==typeof e?new Error(e):e],r),e}finally{p.emit("fn-end",[(0,s.z)()],r)}}}};function x(e,t,r,i){return function(){return(0,o.p)(l.xS,["API/"+t+"/called"],void 0,n.D.metrics,g),i&&(0,o.p)(e+t,[(0,s.z)(),...arguments],r?null:this,i,g),r?void 0:this}}function A(){r.e(439).then(r.bind(r,7438)).then((t=>{let{setAPI:r}=t;r(e),(0,c.L)(e,"api")})).catch((()=>(0,f.Z)("Downloading runtime APIs failed...")))}return["actionText","setName","setAttribute","save","ignore","onEnd","getContext","end","get"].forEach((e=>{w[e]=x(v,e,void 0,n.D.spa)})),h.noticeError=function(e,t){"string"==typeof e&&(e=new Error(e)),(0,o.p)(l.xS,["API/noticeError/called"],void 0,n.D.metrics,g),(0,o.p)("err",[e,(0,s.z)(),!1,t],void 0,n.D.jserrors,g)},d.il?(0,u.b)((()=>A()),!0):A(),h}(e,v);return(0,h.Qy)(e,T,"api"),(0,h.Qy)(e,A,"exposed"),(0,h.EZ)("activatedFeatures",p.T),T}},3325:(e,t,r)=>{r.d(t,{D:()=>n,p:()=>i});const n={ajax:"ajax",jserrors:"jserrors",metrics:"metrics",pageAction:"page_action",pageViewEvent:"page_view_event",pageViewTiming:"page_view_timing",sessionReplay:"session_replay",sessionTrace:"session_trace",spa:"spa"},i={[n.pageViewEvent]:1,[n.pageViewTiming]:2,[n.metrics]:3,[n.jserrors]:4,[n.ajax]:5,[n.sessionTrace]:6,[n.pageAction]:7,[n.spa]:8,[n.sessionReplay]:9}}},n={};function i(e){var t=n[e];if(void 0!==t)return t.exports;var o=n[e]={exports:{}};return r[e](o,o.exports,i),o.exports}i.m=r,i.d=(e,t)=>{for(var r in t)i.o(t,r)&&!i.o(e,r)&&Object.defineProperty(e,r,{enumerable:!0,get:t[r]})},i.f={},i.e=e=>Promise.all(Object.keys(i.f).reduce(((t,r)=>(i.f[r](e,t),t)),[])),i.u=e=>(({78:"page_action-aggregate",147:"metrics-aggregate",242:"session-manager",317:"jserrors-aggregate",348:"page_view_timing-aggregate",412:"lazy-feature-loader",439:"async-api",538:"recorder",590:"session_replay-aggregate",675:"compressor",733:"session_trace-aggregate",786:"page_view_event-aggregate",873:"spa-aggregate",898:"ajax-aggregate"}[e]||e)+"."+{78:"ac76d497",147:"3dc53903",148:"1a20d5fe",242:"2a64278a",317:"49e41428",348:"bd6de33a",412:"2f55ce66",439:"30bd804e",538:"1b18459f",590:"cf0efb30",675:"ae9f91a8",733:"83105561",786:"06482edd",860:"03a8b7a5",873:"e6b09d52",898:"998ef92b"}[e]+"-1.236.0.min.js"),i.o=(e,t)=>Object.prototype.hasOwnProperty.call(e,t),e={},t="NRBA:",i.l=(r,n,o,a)=>{if(e[r])e[r].push(n);else{var s,c;if(void 0!==o)for(var u=document.getElementsByTagName("script"),d=0;d {s.onerror=s.onload=null,clearTimeout(h);var i=e[r];if(delete e[r],s.parentNode&&s.parentNode.removeChild(s),i&&i.forEach((e=>e(n))),t)return t(n)},h=setTimeout(l.bind(null,void 0,{type:"timeout",target:s}),12e4);s.onerror=l.bind(null,s.onerror),s.onload=l.bind(null,s.onload),c&&document.head.appendChild(s)}},i.r=e=>{"undefined"!=typeof Symbol&&Symbol.toStringTag&&Object.defineProperty(e,Symbol.toStringTag,{value:"Module"}),Object.defineProperty(e,"__esModule",{value:!0})},i.j=364,i.p="https://js-agent.newrelic.com/",(()=>{var e={364:0,953:0};i.f.j=(t,r)=>{var n=i.o(e,t)?e[t]:void 0;if(0!==n)if(n)r.push(n[2]);else{var o=new Promise(((r,i)=>n=e[t]=[r,i]));r.push(n[2]=o);var a=i.p+i.u(t),s=new Error;i.l(a,(r=>{if(i.o(e,t)&&(0!==(n=e[t])&&(e[t]=void 0),n)){var o=r&&("load"===r.type?"missing":r.type),a=r&&r.target&&r.target.src;s.message="Loading chunk "+t+" failed.\n("+o+": "+a+")",s.name="ChunkLoadError",s.type=o,s.request=a,n[1](s)}}),"chunk-"+t,t)}};var t=(t,r)=>{var n,o,[a,s,c]=r,u=0;if(a.some((t=>0!==e[t]))){for(n in s)i.o(s,n)&&(i.m[n]=s[n]);if(c)c(i)}for(t&&t(r);u {i.r(o);var e=i(3325),t=i(5763);const r=Object.values(e.D);function n(e){const n={};return r.forEach((r=>{n[r]=function(e,r){return!1!==(0,t.Mt)(r,"".concat(e,".enabled"))}(r,e)})),n}var a=i(9144);var s=i(5546),c=i(385),u=i(8e3),d=i(5938),f=i(3960),l=i(50);class h extends d.W{constructor(e,t,r){let n=!(arguments.length>3&&void 0!==arguments[3])||arguments[3];super(e,t,r),this.auto=n,this.abortHandler,this.featAggregate,this.onAggregateImported,n&&(0,u.R)(e,r)}importAggregator(){let e=arguments.length>0&&void 0!==arguments[0]?arguments[0]:{};if(this.featAggregate||!this.auto)return;const r=c.il&&!0===(0,t.Mt)(this.agentIdentifier,"privacy.cookies_enabled");let n;this.onAggregateImported=new Promise((e=>{n=e}));const o=async()=>{let t;try{if(r){const{setupAgentSession:e}=await Promise.all([i.e(860),i.e(242)]).then(i.bind(i,3228));t=e(this.agentIdentifier)}}catch(e){(0,l.Z)("A problem occurred when starting up session manager. This page will not start or extend any session.",e)}try{if(!this.shouldImportAgg(this.featureName,t))return void(0,u.L)(this.agentIdentifier,this.featureName);const{lazyFeatureLoader:r}=await i.e(412).then(i.bind(i,8582)),{Aggregate:o}=await r(this.featureName,"aggregate");this.featAggregate=new o(this.agentIdentifier,this.aggregator,e),n(!0)}catch(e){(0,l.Z)("Downloading and initializing ".concat(this.featureName," failed..."),e),this.abortHandler?.(),n(!1)}};c.il?(0,f.b)((()=>o()),!0):o()}shouldImportAgg(r,n){return r!==e.D.sessionReplay||!1!==(0,t.Mt)(this.agentIdentifier,"session_trace.enabled")&&(!!n?.isNew||!!n?.state.sessionReplay)}}var g=i(7633),p=i(7894);class m extends h{static featureName=g.t9;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];if(super(r,n,g.t9,i),("undefined"==typeof PerformanceNavigationTiming||c.Tt)&&"undefined"!=typeof PerformanceTiming){const n=(0,t.OP)(r);n[g.Dz]=Math.max(Date.now()-n.offset,0),(0,f.K)((()=>n[g.qw]=Math.max((0,p.z)()-n[g.Dz],0))),(0,f.b)((()=>{const t=(0,p.z)();n[g.OJ]=Math.max(t-n[g.Dz],0),(0,s.p)("timing",["load",t],void 0,e.D.pageViewTiming,this.ee)}))}this.importAggregator()}}var v=i(1117),b=i(1284);class y extends v.w{constructor(e){super(e),this.aggregatedData={}}store(e,t,r,n,i){var o=this.getBucket(e,t,r,i);return o.metrics=function(e,t){t||(t={count:0});return t.count+=1,(0,b.D)(e,(function(e,r){t[e]=w(r,t[e])})),t}(n,o.metrics),o}merge(e,t,r,n,i){var o=this.getBucket(e,t,n,i);if(o.metrics){var a=o.metrics;a.count+=r.count,(0,b.D)(r,(function(e,t){if("count"!==e){var n=a[e],i=r[e];i&&!i.c?a[e]=w(i.t,n):a[e]=function(e,t){if(!t)return e;t.c||(t=x(t.t));return t.min=Math.min(e.min,t.min),t.max=Math.max(e.max,t.max),t.t+=e.t,t.sos+=e.sos,t.c+=e.c,t}(i,a[e])}}))}else o.metrics=r}storeMetric(e,t,r,n){var i=this.getBucket(e,t,r);return i.stats=w(n,i.stats),i}getBucket(e,t,r,n){this.aggregatedData[e]||(this.aggregatedData[e]={});var i=this.aggregatedData[e][t];return i||(i=this.aggregatedData[e][t]={params:r||{}},n&&(i.custom=n)),i}get(e,t){return t?this.aggregatedData[e]&&this.aggregatedData[e][t]:this.aggregatedData[e]}take(e){for(var t={},r="",n=!1,i=0;i t.max&&(t.max=e),e 2&&void 0!==arguments[2])||arguments[2];super(e,r,j.t,n),c.il&&((0,t.OP)(e).initHidden=Boolean("hidden"===document.visibilityState),(0,N.N)((()=>(0,s.p)("docHidden",[(0,p.z)()],void 0,j.t,this.ee)),!0),(0,O.bP)("pagehide",(()=>(0,s.p)("winPagehide",[(0,p.z)()],void 0,j.t,this.ee))),this.importAggregator())}}var P=i(3081);class C extends h{static featureName=P.t9;constructor(e,t){let r=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(e,t,P.t9,r),this.importAggregator()}}var R,I=i(2210),k=i(1214),H=i(2177),L={};try{R=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(L.console=!0,-1!==R.indexOf("dev")&&(L.dev=!0),-1!==R.indexOf("nr_dev")&&(L.nrDev=!0))}catch(e){}function z(e){try{L.console&&z(e)}catch(e){}}L.nrDev&&H.ee.on("internal-error",(function(e){z(e.stack)})),L.dev&&H.ee.on("fn-err",(function(e,t,r){z(r.stack)})),L.dev&&(z("NR AGENT IN DEVELOPMENT MODE"),z("flags: "+(0,b.D)(L,(function(e,t){return e})).join(", ")));var M=i(6660);class B extends h{static featureName=M.t;constructor(r,n){let i=!(arguments.length>2&&void 0!==arguments[2])||arguments[2];super(r,n,M.t,i),this.skipNext=0;try{this.removeOnAbort=new AbortController}catch(e){}const o=this;o.ee.on("fn-start",(function(e,t,r){o.abortHandler&&(o.skipNext+=1)})),o.ee.on("fn-err",(function(t,r,n){o.abortHandler&&!n[M.A]&&((0,I.X)(n,M.A,(function(){return!0})),this.thrown=!0,(0,s.p)("err",[n,(0,p.z)()],void 0,e.D.jserrors,o.ee))})),o.ee.on("fn-end",(function(){o.abortHandler&&!this.thrown&&o.skipNext>0&&(o.skipNext-=1)})),o.ee.on("internal-error",(function(t){(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,o.ee)})),this.origOnerror=c._A.onerror,c._A.onerror=this.onerrorHandler.bind(this),c._A.addEventListener("unhandledrejection",(t=>{const r=function(e){let t="Unhandled Promise Rejection: ";if(e instanceof Error)try{return e.message=t+e.message,e}catch(t){return e}if(void 0===e)return new Error(t);try{return new Error(t+(0,D.P)(e))}catch(e){return new Error(t)}}(t.reason);(0,s.p)("err",[r,(0,p.z)(),!1,{unhandledPromiseRejection:1}],void 0,e.D.jserrors,this.ee)}),(0,O.m$)(!1,this.removeOnAbort?.signal)),(0,k.gy)(this.ee),(0,k.BV)(this.ee),(0,k.em)(this.ee),(0,t.OP)(r).xhrWrappable&&(0,k.Kf)(this.ee),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}onerrorHandler(t,r,n,i,o){"function"==typeof this.origOnerror&&this.origOnerror(...arguments);try{this.skipNext?this.skipNext-=1:(0,s.p)("err",[o||new F(t,r,n),(0,p.z)()],void 0,e.D.jserrors,this.ee)}catch(t){try{(0,s.p)("ierr",[t,(0,p.z)(),!0],void 0,e.D.jserrors,this.ee)}catch(e){}}return!1}}function F(e,t,r){this.message=e||"Uncaught error with no additional information",this.sourceURL=t,this.line=r}let U=1;const q="nr@id";function G(e){const t=typeof e;return!e||"object"!==t&&"function"!==t?-1:e===c._A?0:(0,I.X)(e,q,(function(){return U++}))}function V(e){if("string"==typeof e&&e.length)return e.length;if("object"==typeof e){if("undefined"!=typeof ArrayBuffer&&e instanceof ArrayBuffer&&e.byteLength)return e.byteLength;if("undefined"!=typeof Blob&&e instanceof Blob&&e.size)return e.size;if(!("undefined"!=typeof FormData&&e instanceof FormData))try{return(0,D.P)(e).length}catch(e){return}}}var X=i(7243);class W{constructor(e){this.agentIdentifier=e,this.generateTracePayload=this.generateTracePayload.bind(this),this.shouldGenerateTrace=this.shouldGenerateTrace.bind(this)}generateTracePayload(e){if(!this.shouldGenerateTrace(e))return null;var r=(0,t.DL)(this.agentIdentifier);if(!r)return null;var n=(r.accountID||"").toString()||null,i=(r.agentID||"").toString()||null,o=(r.trustKey||"").toString()||null;if(!n||!i)return null;var a=(0,_.M)(),s=(0,_.Ht)(),c=Date.now(),u={spanId:a,traceId:s,timestamp:c};return(e.sameOrigin||this.isAllowedOrigin(e)&&this.useTraceContextHeadersForCors())&&(u.traceContextParentHeader=this.generateTraceContextParentHeader(a,s),u.traceContextStateHeader=this.generateTraceContextStateHeader(a,c,n,i,o)),(e.sameOrigin&&!this.excludeNewrelicHeader()||!e.sameOrigin&&this.isAllowedOrigin(e)&&this.useNewrelicHeaderForCors())&&(u.newrelicHeader=this.generateTraceHeader(a,s,c,n,i,o)),u}generateTraceContextParentHeader(e,t){return"00-"+t+"-"+e+"-01"}generateTraceContextStateHeader(e,t,r,n,i){return i+"@nr=0-1-"+r+"-"+n+"-"+e+"----"+t}generateTraceHeader(e,t,r,n,i,o){if(!("function"==typeof c._A?.btoa))return null;var a={v:[0,1],d:{ty:"Browser",ac:n,ap:i,id:e,tr:t,ti:r}};return o&&n!==o&&(a.d.tk=o),btoa((0,D.P)(a))}shouldGenerateTrace(e){return this.isDtEnabled()&&this.isAllowedOrigin(e)}isAllowedOrigin(e){var r=!1,n={};if((0,t.Mt)(this.agentIdentifier,"distributed_tracing")&&(n=(0,t.P_)(this.agentIdentifier).distributed_tracing),e.sameOrigin)r=!0;else if(n.allowed_origins instanceof Array)for(var i=0;i 2&&void 0!==arguments[2])||arguments[2];super(r,n,Z.t,i),(0,t.OP)(r).xhrWrappable&&(this.dt=new W(r),this.handler=(e,t,r,n)=>(0,s.p)(e,t,r,n,this.ee),(0,k.u5)(this.ee),(0,k.Kf)(this.ee),function(r,n,i,o){function a(e){var t=this;t.totalCbs=0,t.called=0,t.cbTime=0,t.end=E,t.ended=!1,t.xhrGuids={},t.lastSize=null,t.loadCaptureCalled=!1,t.params=this.params||{},t.metrics=this.metrics||{},e.addEventListener("load",(function(r){_(t,e)}),(0,O.m$)(!1)),c.IF||e.addEventListener("progress",(function(e){t.lastSize=e.loaded}),(0,O.m$)(!1))}function s(e){this.params={method:e[0]},T(this,e[1]),this.metrics={}}function u(e,n){var i=(0,t.DL)(r);i.xpid&&this.sameOrigin&&n.setRequestHeader("X-NewRelic-ID",i.xpid);var a=o.generateTracePayload(this.parsedOrigin);if(a){var s=!1;a.newrelicHeader&&(n.setRequestHeader("newrelic",a.newrelicHeader),s=!0),a.traceContextParentHeader&&(n.setRequestHeader("traceparent",a.traceContextParentHeader),a.traceContextStateHeader&&n.setRequestHeader("tracestate",a.traceContextStateHeader),s=!0),s&&(this.dt=a)}}function d(e,t){var r=this.metrics,i=e[0],o=this;if(r&&i){var a=V(i);a&&(r.txSize=a)}this.startTime=(0,p.z)(),this.listener=function(e){try{"abort"!==e.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==e.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof t.onload)&&"function"==typeof o.end)&&o.end(t)}catch(e){try{n.emit("internal-error",[e])}catch(e){}}};for(var s=0;s 1?e[1]=i:e.push(i)}else e[0]&&e[0].headers&&s(e[0].headers,n)&&(this.dt=n);function s(e,t){var r=!1;return t.newrelicHeader&&(e.set("newrelic",t.newrelicHeader),r=!0),t.traceContextParentHeader&&(e.set("traceparent",t.traceContextParentHeader),t.traceContextStateHeader&&e.set("tracestate",t.traceContextStateHeader),r=!0),r}}function x(e,t){this.params={},this.metrics={},this.startTime=(0,p.z)(),this.dt=t,e.length>=1&&(this.target=e[0]),e.length>=2&&(this.opts=e[1]);var r,n=this.opts||{},i=this.target;"string"==typeof i?r=i:"object"==typeof i&&i instanceof Y?r=i.url:c._A?.URL&&"object"==typeof i&&i instanceof URL&&(r=i.href),T(this,r);var o=(""+(i&&i instanceof Y&&i.method||n.method||"GET")).toUpperCase();this.params.method=o,this.txSize=V(n.body)||0}function A(t,r){var n;this.endTime=(0,p.z)(),this.params||(this.params={}),this.params.status=r?r.status:0,"string"==typeof this.rxSize&&this.rxSize.length>0&&(n=+this.rxSize);var o={txSize:this.txSize,rxSize:n,duration:(0,p.z)()-this.startTime};i("xhr",[this.params,o,this.startTime,this.endTime,"fetch"],this,e.D.ajax)}function E(t){var r=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var o=0;o 2&&void 0!==arguments[2])||arguments[2];super(e,t,we.t,r),this.importAggregator()}}new class{constructor(e){let t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:(0,_.ky)(16);c._A?(this.agentIdentifier=t,this.sharedAggregator=new y({agentIdentifier:this.agentIdentifier}),this.features={},this.desiredFeatures=new Set(e.features||[]),this.desiredFeatures.add(m),Object.assign(this,(0,a.j)(this.agentIdentifier,e,e.loaderType||"agent")),this.start()):(0,l.Z)("Failed to initial the agent. Could not determine the runtime environment.")}get config(){return{info:(0,t.C5)(this.agentIdentifier),init:(0,t.P_)(this.agentIdentifier),loader_config:(0,t.DL)(this.agentIdentifier),runtime:(0,t.OP)(this.agentIdentifier)}}start(){const t="features";try{const r=n(this.agentIdentifier),i=[...this.desiredFeatures];i.sort(((t,r)=>e.p[t.featureName]-e.p[r.featureName])),i.forEach((t=>{if(r[t.featureName]||t.featureName===e.D.pageViewEvent){const n=function(t){switch(t){case e.D.ajax:return[e.D.jserrors];case e.D.sessionTrace:return[e.D.ajax,e.D.pageViewEvent];case e.D.sessionReplay:return[e.D.sessionTrace];case e.D.pageViewTiming:return[e.D.pageViewEvent];default:return[]}}(t.featureName);n.every((e=>r[e]))||(0,l.Z)("".concat(t.featureName," is enabled but one or more dependent features has been disabled (").concat((0,D.P)(n),"). This may cause unintended consequences or missing data...")),this.features[t.featureName]=new t(this.agentIdentifier,this.sharedAggregator)}})),(0,T.Qy)(this.agentIdentifier,this.features,t)}catch(e){(0,l.Z)("Failed to initialize all enabled instrument classes (agent aborted) -",e);for(const e in this.features)this.features[e].abortHandler?.();const r=(0,T.fP)();return delete r.initializedAgents[this.agentIdentifier]?.api,delete r.initializedAgents[this.agentIdentifier]?.[t],delete this.sharedAggregator,r.ee?.abort(),delete r.ee?.get(this.agentIdentifier),!1}}}({features:[J,m,S,class extends h{static featureName=oe;constructor(t,r){if(super(t,r,oe,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;const n=this.ee;let i;(0,k.QU)(n),this.eventsEE=(0,k.em)(n),this.eventsEE.on(se,(function(e,t){this.bstStart=(0,p.z)()})),this.eventsEE.on(ae,(function(t,r){(0,s.p)("bst",[t[0],r,this.bstStart,(0,p.z)()],void 0,e.D.sessionTrace,n)})),n.on(ce+ne,(function(e){this.time=(0,p.z)(),this.startPath=location.pathname+location.hash})),n.on(ce+ie,(function(t){(0,s.p)("bstHist",[location.pathname+location.hash,this.startPath,this.time],void 0,e.D.sessionTrace,n)}));try{i=new PerformanceObserver((t=>{const r=t.getEntries();(0,s.p)(te,[r],void 0,e.D.sessionTrace,n)})),i.observe({type:re,buffered:!0})}catch(e){}this.importAggregator({resourceObserver:i})}},C,xe,B,class extends h{static featureName=de;constructor(e,r){if(super(e,r,de,!(arguments.length>2&&void 0!==arguments[2])||arguments[2]),!c.il)return;if(!(0,t.OP)(e).xhrWrappable)return;try{this.removeOnAbort=new AbortController}catch(e){}let n,i=0;const o=this.ee.get("tracer"),a=(0,k._L)(this.ee),s=(0,k.Lg)(this.ee),u=(0,k.BV)(this.ee),d=(0,k.Kf)(this.ee),f=this.ee.get("events"),l=(0,k.u5)(this.ee),h=(0,k.QU)(this.ee),g=(0,k.Gm)(this.ee);function m(e,t){h.emit("newURL",[""+window.location,t])}function v(){i++,n=window.location.hash,this[ve]=(0,p.z)()}function b(){i--,window.location.hash!==n&&m(0,!0);var e=(0,p.z)();this[pe]=~~this[pe]+e-this[ve],this[ye]=e}function y(e,t){e.on(t,(function(){this[t]=(0,p.z)()}))}this.ee.on(ve,v),s.on(be,v),a.on(be,v),this.ee.on(ye,b),s.on(ge,b),a.on(ge,b),this.ee.buffer([ve,ye,"xhr-resolved"],this.featureName),f.buffer([ve],this.featureName),u.buffer(["setTimeout"+le,"clearTimeout"+fe,ve],this.featureName),d.buffer([ve,"new-xhr","send-xhr"+fe],this.featureName),l.buffer([me+fe,me+"-done",me+he+fe,me+he+le],this.featureName),h.buffer(["newURL"],this.featureName),g.buffer([ve],this.featureName),s.buffer(["propagate",be,ge,"executor-err","resolve"+fe],this.featureName),o.buffer([ve,"no-"+ve],this.featureName),a.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"],this.featureName),y(l,me+fe),y(l,me+"-done"),y(a,"new-jsonp"),y(a,"jsonp-end"),y(a,"cb-start"),h.on("pushState-end",m),h.on("replaceState-end",m),window.addEventListener("hashchange",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("load",m,(0,O.m$)(!0,this.removeOnAbort?.signal)),window.addEventListener("popstate",(function(){m(0,i>1)}),(0,O.m$)(!0,this.removeOnAbort?.signal)),this.abortHandler=this.#e,this.importAggregator()}#e(){this.removeOnAbort?.abort(),this.abortHandler=void 0}}],loaderType:"spa"})})(),window.NRBA=o})(); window.jQuery || document.write(' ') CKEDITOR_BASEPATH='https://f1000research.com/js/vendor/ckeditor/' window.reactTheme = 'research'; window.MathJax = { CommonHTML: { linebreaks: { automatic: true } }, 'HTML-CSS': { linebreaks: { automatic: true } }, SVG: { linebreaks: { automatic: true } }, AuthorInit: function() { MathJax.Hub.Register.MessageHook('End Process', function () { let timeout = false; // holder for timeout id const delay = 250; // delay after event is "complete" to run callback const reflowMath = function() { const dispFormulas = document.querySelectorAll('.disp-formula.panel'); if (!dispFormulas) { return; } for (const dispFormula of dispFormulas) { const child = dispFormula.querySelector('.MathJax_Preview').nextSibling.firstChild; const isMultiline = MathJax.Hub.getAllJax(dispFormula)[0].root.isMultiline; if (dispFormula.offsetWidth < child.offsetWidth || isMultiline) { MathJax.Hub.Queue(['Rerender', MathJax.Hub, dispFormula]); } } }; window.addEventListener('resize', function() { clearTimeout(timeout); // clear the timeout timeout = setTimeout(reflowMath, delay); // start timing for event "completion" }); }); }, }; if (window.location.hash == '#_=_'){ window.location = window.location.href.split('#')[0] } !function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function() {n.callMethod? n.callMethod.apply(n,arguments):n.queue.push(arguments)} ;if(!f._fbq)f._fbq=n; n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0; t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js'); fbq('init', '1641728616063202'); fbq('track', "PixelInitialized", {}); (function(h,o,t,j,a,r){ h.hj=h.hj||function(){(h.hj.q=h.hj.q||[]).push(arguments)}; h._hjSettings={hjid:2318163,hjsv:6}; a=o.getElementsByTagName('head')[0]; r=o.createElement('script');r.async=1; r.src=t+h._hjSettings.hjid+j+h._hjSettings.hjsv; a.appendChild(r); })(window,document,'https://static.hotjar.com/c/hotjar-','.js?sv='); search file_upload Submit your research search menu close search Browse Gateways & Collections How to Publish Submit your Research My Submissions Article Guidelines Article Guidelines (New Versions) Open Data, Software and Code Guidelines Open Data and Accessible Source Materials Guidelines (HSS) Open Data, Software and Code Guidelines (PSE) Prepublication Checks Production Process Posters and Slides Guidelines Document Guidelines Article Processing Charges Peer Review Finding Article Reviewers About How it Works For Reviewers Our Advisors Policies Glossary FAQs For Developers Newsroom Contact My Research Submissions Content and Tracking Alerts My Details Sign In file_upload Submit your research { "@context": "https://schema.org", "@type": "ScholarlyArticle", "mainEntityOfPage": { "@type": "WebPage", "@id": "https://f1000research.com/articles/14-425" }, "headline": "Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis", "datePublished": "2025-04-11T11:43:01", "dateModified": "2025-12-09T07:19:02", "author": [ { "@type": "Person", "name": "Virgilio E Failoc Rojas" }, { "@type": "Person", "name": "Yiro Yazawa-Ballena" }, { "@type": "Person", "name": "Gustavo Alvarado-Moreno" }, { "@type": "Person", "name": "Alba Navarro-Flores" }, { "@type": "Person", "name": "Carlos Alva-Diaz" }, { "@type": "Person", "name": "Kevin Pacheco-Barrios" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Introduction Prion diseases are mortal neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD). 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. Methods We 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. Results Patient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In systematic 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, cerebellar ataxia 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. Conclusion A 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. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-425/v1", "name": "Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case..." } } ] } Home Browse Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Failoc Rojas VE, Yazawa-Ballena Y, Alvarado-Moreno G et al. Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.12688/f1000research.150498.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] Virgilio E Failoc Rojas https://orcid.org/0000-0003-2992-9342 1 , Yiro Yazawa-Ballena 2 , Gustavo Alvarado-Moreno 2 , Alba Navarro-Flores 3,4 , Carlos Alva-Diaz 5-7 , Kevin Pacheco-Barrios https://orcid.org/0000-0002-7166-2816 8 Virgilio E Failoc Rojas https://orcid.org/0000-0003-2992-9342 1 , Yiro Yazawa-Ballena 2 , [...] Gustavo Alvarado-Moreno 2 , Alba Navarro-Flores 3,4 , Carlos Alva-Diaz 5-7 , Kevin Pacheco-Barrios https://orcid.org/0000-0002-7166-2816 8 PUBLISHED 11 Apr 2025 Author details Author details 1 Universidad Cesar Vallejo, Piura, Piura, 20001, Peru 2 Internal medicine, Hospital Regional Lambayeque, Lambayeque, Lambayeque, 14011, Peru 3 International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany, 80804, Germany 4 Institute of Psychiatric Phenomics and Genomics (IPPG), LMU University Hospital, LMU Munich, Munich, Germany 5 Servicio de Neurología, Departamento de Medicina y Oficina de Apoyo a la Docencia e Investigación (OADI), Hospital Daniel Alcides Carrión, Callao, Peru 6 Grupo de Investigación NEMECS: Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria, Universidad Cientifica del Sur, Lima, Peru 7 Universidad Cientifica del Sur, Miraflores, Lima, 15067, Peru 8 Universidad San Ignacio de Loyola, Lima District, Lima Region, 150114, Peru Virgilio E Failoc Rojas Roles: Conceptualization, Data Curation, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Yiro Yazawa-Ballena Roles: Conceptualization, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Gustavo Alvarado-Moreno Roles: Conceptualization, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Alba Navarro-Flores Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Carlos Alva-Diaz Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Kevin Pacheco-Barrios Roles: Conceptualization, Data Curation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Introduction Prion diseases are mortal neurodegenerative disorders, which include Creutzfeldt-Jakob disease (CJD). 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. Methods We 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. Results Patient with diagnosis was made due to the form of presentation and clinical evolution, neuroimaging and the presence of protein 14-3-3. In systematic 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, cerebellar ataxia 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. Conclusion A 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. READ ALL READ LESS Keywords Creutzfeldt-Jakob syndrome; Prion diseases; differential diagnosis; behavioral symptoms; 14-3-3 Proteins; Peru Corresponding Author(s) Kevin Pacheco-Barrios ( [email protected] ) Close Corresponding author: Kevin Pacheco-Barrios Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Failoc Rojas VE et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Failoc Rojas VE, Yazawa-Ballena Y, Alvarado-Moreno G et al. Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.12688/f1000research.150498.1 ) First published: 11 Apr 2025, 14 :425 ( https://doi.org/10.12688/f1000research.150498.1 ) Latest published: 09 Dec 2025, 14 :425 ( https://doi.org/10.12688/f1000research.150498.2 )  There is a newer version of this article available. Suppress this message for one day. Introduction Creutzfeldt-Jakob disease (CJD) is one of the main prion diseases, a neurodegenerative disorder with high mortality. 1 The common pathological process is characterized by the conversion of the normal cellular prion protein (PrPc) to an insoluble anomalous form (PrPSc) that accumulates progressively in the brain, forming extracellular amyloid plaques. 2 CJD is classified, according to the etiology, into sporadic (idiopathic or classic) (85%), acquired (or exogenous) (5%), genetic (or hereditary) (10%), and other variants such as Gerstmann-Sträussler-Scheinker disease (GSSD), fatal familial insomnia (FFI) and kuru. 1 , 3 , 4 The probable diagnosis is based on progressive dementia and other clinical criteria (myoclonus, visual disorders, cerebellar signs, pyramidal or extrapyramidal signs, and akinetic mutism), as well as a compatible electroencephalogram (EEG) (periodic epileptiform discharges) and/or detection of neuronal protein related to neuronal destructions that accumulates in cerebrospinal fluid (CSF), called protein 14-3-3. 1 , 3 , 5 The definitive diagnosis requires a post-mortem study. 6 Due to these clinical complexities and the variable initial onset, it presents a common delayed detection with issues during the differential diagnosis. In this paper, we include a representative case from our institution and discuss the common challenges during the course of the disease. We present a case report from the “Hospital Regional Lambayeque”, in Lambayeque, Peru. This report followed the CARE guidelines. 7 Consent Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. Case report We present the case of a 47-year-old male from the Amazon region of Peru, unemployed, with no pathological or surgical history. His symptoms start with oppressive non-located headache 80-weeks before, which were treated with analgesic medication without response. It was associated with a hands rest tremor, perceptual alteration of time, difficulty in recognizing relatives, aggressiveness, agitation, and mild memory impairment. 24-weeks before, symptomatology persists and progress until presenting alterations of sphincter control and difficulty for walking, and upper limb rest and intention tremor generating partial dependence for their daily activities. He had a hospital admission for presenting focal to bilateral tonic-clonic seizures for which he received antiepileptic drugs with an incomplete response. Subsequently, due to the persistence of symptomatology and the development of epileptic status, he was hospitalized again. The blood studies showed anemia (10.2 g/dl), with any other abnormalities. The CSF analysis found a clear fluid without alterations. Brain magnetic resonance imaging (MRI) showed moderate to severe cortico-subcortical atrophic changes and subcortical hyperintensities ( Figure 1 ). Additionally, an EEG was performed, without any alteration. The progressive neurological compromise with the development of early and progressive dementia in the next months, and the MRI suggestive of prion disease, CJD diagnostic was suspected. We performed a 14-3-3 protein western blot test in CSF, finding elevated titles, indicative results of CJD. The patient was classified as spongiform encephalopathy, probable CDJ. Symptomatic treatment and palliative care were indicated to the patient. Figure 1. Axial brain-MRI of the patient with probable sporadic CJD. Axial section in a fluid attenuated inversion recovery (FLAIR) sequence showing hippocampal volume decreased in both temporal lobes with increase of temporal horns predominantly on right side; mild hyperintensity in right caudate nucleus and moderate in periventricular regions with confluent zones in the right parietal region; and moderate to severe atrophic cortical-subcortical with frontotemporal predominance. All these tests were performed during the hospitalization of the patient. The Western blot test of the protein 14-3-3 was performed two weeks after his hospitalization. The patient was evaluated one month after discharge, but he did not return for his next consultation, and it was not possible to follow up on his case. Discussion The case reported a progressive neurological condition (headache that progress to dementia) with early onset of cognitive impairment and behavioral symptoms at the age of 47 years, a Brain-MRI showing moderate to severe cortico-subcortical trophic changes, and basal nuclei hyperintensity, added to a positive Western-Blot quantification of CSF 14-3-3 protein (sensitivity of 94% and specificity of 84%), 5 , 8 hence the condition was classified as spongiform encephalopathy, probable CJD. It was not possible to make the definitive diagnosis with brain biopsy confirmation, where neuronal loss, gliosis, and intracytoplasmic vacuolization are observed in the brain parenchyma. 6 , 9 CJD is a rare and fatal neurodegenerative disease, due to the high mortality, an early and timely diagnosis must be made. 10 , 11 However, currently the diagnostic criteria are controversial and there are several variances of the onset symptoms, thus, the diagnosis is usually made in the terminal phases of the disease. We search the available literature to compare with our experience and found ten articles reporting diagnostic challenges in CJD ( Table 1 ). 12 – 21 The age range of the patients reported was 30 to 86 years [median 64 years]. The main initial clinical manifestation was psycho-behavioral symptoms (50% of the cases), predominantly: apathy, confusion, aggressiveness, irritability, and sleep disturbance. The initial differential diagnoses were psychiatry exacerbation (depression and schizophrenia), myelopathy, epilepsy, stroke and parkinsonism. Our patient is 47-years old, male, with an initial presentation of headache, extrapyramidal signs, and behavioral symptoms. In another case series, 22 they found that the presentation was nonspecific, from headache to ataxias. The extrapyramidal and cerebellar signs onset is presented as a frequent initial manifestation. 23 These data coincide with our systematic review results, indicating a common non-specific initial symptomatology in these cases. Table 1. Description of previously reported cases with diagnostic challenges. Author (year) Patient information Clinical manifestations Initial diagnosis Neuroimaging EEG Differential diagnosis Time until final diagnosis Final diagnosis Ziso, B. et al (2017) 57-years-old woman, no previous diseases history. 1-month history of sensorial disturbances in left arm and walk difficulties. Hypertonia and hyperreflexia. 5 weeks after worsening of mobility, quadriparesis, and sphincter dysfunction. Myelopathy Restricted diffusion in the right frontal cortical region. Theta range with slower delta rhythms. Cervical radiculopathy 6 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Roest et al. (2016) 51-years-old woman, depression history. Suicide ideation, memory impairment and sleep disturbances. 14 weeks after worsening cognitive impairment and confusion. Depression exacerbation Normal Initial: w/o alterations. After 14 weeks: generalized, synchronous triphasic complexes. Depression and posttraumatic stress disorder. 14 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Ghadiri-Sani et al. (2015) 56-years old woman, with history of stroke 10 years ago. Left homonymous hemianopia, dysarthria, mild left-sided weakness, hyperreflexia with bilateral Babinski. After 4 weeks: progressive episodes of confusion and apparent blindness, cognitive deterioration. Multiple territory strokes Initial: w/o alterations. After 4 weeks: mild global brain atrophy was noted. Triphasic waves Vertebral artery dissection with showers of emboli or cerebral vasculitis. 5 weeks Sporadic CJD (Biopsy) Chauvin et al. (2014) 78-years-old man, no previous diseases history. Tonic-clonic seizures. 3-months after: muscular weakness. 4-months after: progressive cognitive impairment (apraxia and akinetic mutism). Epilepsy Initial: w/o alteration. After 3 months: Fronto-temporal hypersignal. Normal Myelopathy 15 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Damato et al. (2014) 78 years-old man, hypertension history. Right hemiparesis, Babinski sign present and dysarthria. After 4 weeks: intermittent myoclonic jerks in both arms and legs and a rapidly progressive cognitive decline and abnormal behavior, confusion and agitation. Stroke Showed hyperintensity of left frontal gyri on T2-weighted FLAIR. Diffuse theta -delta activity. Stroke mimics 5 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Jacquin et al. (2014) 64-years-old man, no previous diseases history. Language disorders, apathy and behavioral disorders. Progressive primary aphasia Not reported Not reported CJD Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) 68-years-old man, no previous diseases history. Aphasia, apraxia and ataxia of right upper limb with parkinsonian syndrome. Corticobasal degeneration Not reported Not reported Parkinsonism Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) 2 Case reports, females, 58 and 61 years-old, no previous diseases history. Anxiety and depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome and fluctuating cognitive decline. Lewy body dementia Not reported Not reported CJD Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Chuang et al. (2012) 61 years-old man, history of schizophrenia. Initial: visual hallucinations, hyperreflexia and parkinsonism. After 4 days: multifocal myoclonus. After 1 month: cognitive decline and behavior change. Exacerbation of schizophrenia After 8 days: Hyperintensities on diffusion weighted imaging in the occipital lobes bilaterally. After 6 days: left periodic lateralizing epileptiform discharges (PLEDs), generalized disorganization, and slowing. Parkinsonism 4 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Mahmoudi et al. (2010) 74-year-old man, no previous diseases history. Psychobehavioral disturbances including verbal aggressiveness, anxiety, and irritability. After 18 months: cognitive and psychobehavioral symptoms increased, and gait disorders appeared. Alzheimer disease Cortico-subcortical atrophy Not reported Atypical AD 72 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Chadenat et al. (2009) 79-years-old woman, no previous diseases history. Subacute dementia associated with gait disorder. Serum calcium elevated. CJD Not reported Not reported Metabolic-originated cognitive impairment Not reported Creutzfeldt-Jakob like syndrome due to parathyroid Adenoma duPlessis et al. (2008) 74-year-old man, no previous diseases history. Cognitive impairment and visual hallucination and parkinsonism. After 18 months: rapid cognitive decline and orthostatic hypotension Dementia with Lewy bodies Not reported Not reported CJD 72 weeks Sporadic CJD (Biopsy) Hamaguchi et al. (2005) Case 1: 65-year-old woman Dementia, pyramidal signs, insomnia. CJD Not reported Not reported Dementia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 2: 75-year-old woman Psychiatric symptoms, dementia, myoclonus CJD Not reported Not reported Major depression Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 3: 65-year-old man Dementia, myoclonus, cerebellar ataxia, akinetic mutism CJD Not reported Not reported Cerebellar ataxia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 4: 49-year-old woman Insomnia, dementia, psychiatric symptoms, pyramidal signs, extrapyramidal signs, autonomic symptoms, myoclonus, akinetic mutism Progressive supranuclear palsy Not reported Not reported Dementia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 5: 64-year-old man Visual symptoms, extrapyramidal signs, dementia, autonomic symptoms, psychiatric symptoms, myoclonus, akinetic mutism Progressive supranuclear palsy Not reported Not reported Dementia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 6: 30-year-old woman Visual symptoms, psychiatric symptoms, cerebellar ataxia, dementia, pyramidal signs, extrapyramidal signs, myoclonus, akinetic mutism Spinocerebellar degeneration Not reported Not reported Dementia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 7: 71-year-old man Cerebellar ataxia, autonomic symptoms, dementia Spinocerebellar degeneration Not reported Not reported Cerebellar ataxia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Case 8: 58-year-old man Dementia, cerebellar ataxia, myoclonus, pyramidal signs, psychiatric symptoms Alzheimer disease Not reported Not reported Dementia Not reported Sporadic CJD (clinical + 14-3-3 protein in CSF) Pereira et al. (2002) 63-year-old man, no previous diseases history. Progressive memory loss and word finding difficulty Alzheimer disease Large areas of increased signal in the frontal, temporoparietal and occipital lobes in DWI. Normal CJD 32 weeks Sporadic CJD (Biopsy) Walsh et al. (2001) 76-year-old woman, history of multiple stroke. Memory impairment and behavioral changes Vascular dementia Brain Atrophy, older stroke lesions. Not reported CJD 4 weeks Sporadic CJD (clinical + 14-3-3 protein in CSF) Seipelt et al. (1999) 7 Case reports, females, 44-86 years-old, history of Hashimoto’s thyroiditis Progressive cognitive impairment, myoclonus, ataxia, and personality change or psychotic phenomena CJD Not reported Not reported autoimmune encephalitis Not reported Autoimmune encephalitis (Hashimoto’s encephalitis) Wilhelm-gling et al. (1998) 58-year-old woman, history of Hashimoto’s thyroiditis Unconsciousness, progressive severe dementia and generalized myoclonus. Increased thyroid antibodies titles. CJD Not reported Slowing activity and episodes of triphasic waves. Infectious encephalitis, autoimmune encephalitis Not reported Autoimmune encephalitis (Hashimoto’s encephalitis) The initial neuroimaging evaluations were reported in nine of the cases, 12 – 14 , 16 – 21 mainly, they found hyperintensity in frontotemporal lobes and cortico-subcortical atrophy. EEG evaluations reporting theta range with slower delta rhythms. The broad clinical findings spectrum included a progressive neuropsychiatric syndrome –whose initial symptoms could be depression, insomnia, anxiety, apathy, and hallucinations. Besides, movement disorders– cerebellar ataxia, involuntary movements, myoclonus, chorea, and dystonia- and persistent pain or paresthesia, could be associated. Finally, dementia and akinetic mutism could be presented at the end of this disease. In general, psychiatric symptoms precede neurological manifestations. 9 , 22 , 24 We found that 65% of cases start clinical manifestation with psychobehavioral symptoms; it is according to our case report. Timely diagnosis of CJD is often difficult, in part because of the frequency of unusual variants, with potential modifications due to early interventions. The available literature on this topic shows a wide diagnosis delay range from four to 80 weeks [median 14 (5-72 weeks)]. The best approach is to add CJD as our differential diagnosis options, not only in the classical rapid-progressive dementia diagnosis, but also in front of patients with suspicious of psychiatry exacerbation, myelopathy, epilepsy, stroke, and Parkinsonism. The reports show that autoimmune encephalitis due to Hashimoto’s thyroiditis and a CJD-like syndrome due to parathyroid adenoma could simulate the CJD clinical manifestations even meeting partially the diagnostic criteria. 25 Thus, it is important to evaluate carefully the autoimmune disease history in patients with CJD suspicious. Current reviews indicate that the changes in brain-MRI are bilateral, symmetric, and predominant in basal ganglia and cortical regions, 6 , 26 in addition, 85% show signs of atrophy in the MRI. 6 Our case findings are according to this literature, however, in most of the cases with difficult timely diagnosis, the MRI results were inconclusive or normal until the end-stage of the disease, and the most common finding was cortical-subcortical atrophy and basal nuclei hyperintensity. The patient presented unspecific characteristics of onset, in addition to a delay of 80-weeks before CJD diagnosis, with broad clinical manifestations, alterations in the MRI and the presence of protein 14-3-3 in CSF. In conclusion, not all the CJD symptoms are at the beginning of the disease, and not all the classical symptoms and signs indicate CJD. In addition, as seen in the review, the delay to a proper diagnosis of this disease is large, so this is a significant diagnostic challenge for physicians and neurologists. CJD should be included as a differential diagnosis at the beginning of behavioral symptoms or rapid cognitive impairment, even if it is a remote possibility. Authors’ contributions Conceptualization: VEFR, YKYB, GAM, CAD, KPB; Data curation: VEFR, KPB; Investigation: VEFR, YKYB, GAM; Methodology: VEFR, ANF, CAD, KPB; Supervision: KPB; Writing – Original Draft Preparation: All authors; Writing – Review & Editing: All authors. Ethics and consent This study was conducted according to the ethical standards of the Declaration of Helsinki. Informed consent was obtained from the patient and this case study was approved by the ethical board of Hospital de Lambayeque. Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. Data availability statement No data are associated with this article. Acknowledgements None. References 1. Appleby BS, Appleby KK, Crain BJ, et al. : Characteristics of established and proposed sporadic Creutzfeldt-Jakob disease variants. Arch. Neurol. 2009; 66 (2): 208–215. PubMed Abstract | Publisher Full Text 2. Kanata E, Thüne K, Xanthopoulos K, et al. : MicroRNA alterations in the brain and body fluids of humans and animal prion disease models: current status and perspectives. Front. Aging Neurosci. 2018; 10 : 10. Publisher Full Text 3. Carrillo Robles D, García Maldonado G: Manifestaciones psiquiátricas por priones. Una revisión narrativa. Rev. Colomb. Psiquiatr. 2016; 45 (2): 118–123. 4. Imran M, Mahmood S: An overview of human prion diseases. Virol. J. 2011; 8 (1): 559. PubMed Abstract | Publisher Full Text | Free Full Text 5. Torres M, Cartier L, Matamala JM, et al. : Altered prion protein expression pattern in CSF as a biomarker for Creutzfeldt-Jakob disease. PLoS One. 2012; 7 (4): e36159. PubMed Abstract | Publisher Full Text | Free Full Text 6. Gibson LM, Chappell FM, Summers D, et al. : Post-mortem magnetic resonance imaging in patients with suspected prion disease: Pathological confirmation, sensitivity, specificity and observer reliability. A national registry. PLoS One. 2018; 13 (8): e0201434. PubMed Abstract | Publisher Full Text | Free Full Text 7. Gagnier JJ, Kienle G, Altman DG, et al. : The CARE guidelines: consensus-based clinical case reporting guideline development. Glob. Adv. Health Med. 2013; 2 (5): 38–43. PubMed Abstract | Publisher Full Text | Free Full Text 8. Muayqil T, Gronseth G, Camicioli R: Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012; 79 (14): 1499–1506. PubMed Abstract | Publisher Full Text | Free Full Text 9. Torres-Ramirez L, Ramirez-Quinones J, Cosentino-Esquerre C, et al. : Creutzfeldt-Jakob disease in Peru: report of eleven cases. Rev. Peru Med. Exp. Salud Publica. 2014; 31 (2): 364–369. PubMed Abstract 10. Johnson RT: Prion diseases. Lancet Neurol. 2005; 4 (10): 635–642. Publisher Full Text 11. Taşkapilioğlu Ö, Seferoğlu M, Yurtoğullari Ş, et al. : Sporadic Creutzfeldt-Jacob Disease: An 8-Year Experience from a Single Center in Turkey. Nöro Psikiyatri Arşivi. 2013; 50 (4): 306–311. PubMed Abstract | Publisher Full Text | Free Full Text 12. Chauvin A, Dubost JL, Cleophax C, et al. : Differential diagnosis of status epilepticus in intensive care: about one case of sporadic Creutzfeldt-Jakob. Ann. Fr. Anesth. Reanim. 2014; 33 (4): 279–281. PubMed Abstract | Publisher Full Text 13. Chuang DT, O'Dowd MA, Frieder A, et al. : Delayed diagnosis of sporadic Creutzfeldt-Jakob disease in a patient with schizophrenia. Psychosomatics. 2012; 53 (4): 392–396. PubMed Abstract | Publisher Full Text 14. Damato V, Cuccagna C, Costantini EM, et al. : Creutzfeldt-Jakob disease manifesting as stroke mimic in a 78-year-old patient: pitfalls and tips in the diagnosis. J. Neurol. Sci. 2014; 346 (1-2): 343–344. PubMed Abstract | Publisher Full Text 15. Du Plessis D, Larner A: Phenotypic similarities causing clinical misdiagnosis of pathologically-confirmed sporadic Creutzfeldt-Jakob disease as dementia with Lewy bodies. Clin. Neurol. Neurosurg. 2008; 110 (2): 194–197. PubMed Abstract | Publisher Full Text 16. Ghadiri-Sani M, Sekhar A, Larner AJ: A stroke of ill-fortune: an unexpected diagnosis following a stroke-like event. Br. J. Hosp. Med. (Lond.). 2015; 76 (1): 54–55. PubMed Abstract | Publisher Full Text 17. Mahmoudi R, Manckoundia P, Morrone I, et al. : Atypical case of Alzheimer's disease mimicking Creutzfeldt-Jakob disease: interest of cerebrospinal fluid biomarkers in the differential diagnosis. J. Am. Geriatr. Soc. 2010; 58 (9): 1821–1823. PubMed Abstract | Publisher Full Text 18. Pereira E: Diffusion-weighted sequence on MRI for the diagnosis of Creutzfeldt-Jakob disease. Arq. Neuropsiquiatr. 2002; 60 (4): 906–908. Publisher Full Text 19. Roest S, Mestdagh I, de Grave C , et al. : Delayed diagnosis in a patient with Creutzfeldt-Jakob disease in a psychiatric hospital. Tijdschr. Psychiatr. 2016; 58 (12): 891–894. PubMed Abstract 20. Walsh ET, Bishop-Miller J, Coles RJ: Creutzfeldt-Jakob disease: the need to widen the differential diagnosis. Scott. Med. J. 2001; 46 (6): 186–188. PubMed Abstract | Publisher Full Text 21. Ziso B, Larner AJ, Aji BM: Suspected cervical myelopathy: an unexpected diagnosis. Br. J. Hosp. Med. (Lond.). 2017; 78 (1): 50–51. PubMed Abstract | Publisher Full Text 22. Herrán GET, Herrera ADO, Burbano BM, et al. : Case series of Creutzfeldt-Jakob disease in a third-level hospital in Quito. BMC Neurol. 2018; 18 (1): 55. PubMed Abstract | Publisher Full Text | Free Full Text 23. Setti SA, Meoli JE, Jacob HR, et al. : Enfermedad de Creutzfeldt-Jakob: presentación atáxica. Neurol. Arg. 2016; 8 (3): 196–200. Publisher Full Text 24. Peckeu L, Delasnerie-Lauprètre N, Brandel J-P, et al. : Accuracy of diagnosis criteria in patients with suspected diagnosis of sporadic Creutzfeldt-Jakob disease and detection of 14-3-3 protein, France, 1992 to 2009. Euro Surveill. 2017; 22 (41). PubMed Abstract | Publisher Full Text | Free Full Text 25. Muramatsu T, Hamano T, Shirafuji N, et al. : Hashimoto's encephalopathy presenting periodic synchronous discharge, as a differential diagnosis for Creutzfeldt-Jakob disease. Rinsho Shinkeigaku. 2013; 53 (9): 716–720. PubMed Abstract | Publisher Full Text 26. Macfarlane RG, Wroe SJ, Collinge J, et al. : Neuroimaging findings in human prion disease. J. Neurol. Neurosurg. Psychiatry. 2007; 78 (7): 664–670. PubMed Abstract Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 11 Apr 2025 ADD YOUR COMMENT Comment Author details Author details 1 Universidad Cesar Vallejo, Piura, Piura, 20001, Peru 2 Internal medicine, Hospital Regional Lambayeque, Lambayeque, Lambayeque, 14011, Peru 3 International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany, 80804, Germany 4 Institute of Psychiatric Phenomics and Genomics (IPPG), LMU University Hospital, LMU Munich, Munich, Germany 5 Servicio de Neurología, Departamento de Medicina y Oficina de Apoyo a la Docencia e Investigación (OADI), Hospital Daniel Alcides Carrión, Callao, Peru 6 Grupo de Investigación NEMECS: Neurociencias, Metabolismo, Efectividad Clínica y Sanitaria, Universidad Cientifica del Sur, Lima, Peru 7 Universidad Cientifica del Sur, Miraflores, Lima, 15067, Peru 8 Universidad San Ignacio de Loyola, Lima District, Lima Region, 150114, Peru Virgilio E Failoc Rojas Roles: Conceptualization, Data Curation, Investigation, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Yiro Yazawa-Ballena Roles: Conceptualization, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Gustavo Alvarado-Moreno Roles: Conceptualization, Investigation, Writing – Original Draft Preparation, Writing – Review & Editing Alba Navarro-Flores Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Carlos Alva-Diaz Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Kevin Pacheco-Barrios Roles: Conceptualization, Data Curation, Methodology, Supervision, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 09 Dec 2025, 14:425 https://doi.org/10.12688/f1000research.150498.2 version 1 Published: 11 Apr 2025, 14:425 https://doi.org/10.12688/f1000research.150498.1 Copyright © 2025 Failoc Rojas VE et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Failoc Rojas VE, Yazawa-Ballena Y, Alvarado-Moreno G et al. Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.12688/f1000research.150498.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 11 Apr 2025 Views 0 Cite How to cite this report: Yang SL. Reviewer Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r390131 ) The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-390131 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Jun 2025 Shi-Lin Yang , Fudan University, Shanghai, China Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.165074.r390131 This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the ... Continue reading READ ALL This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: My major is cerebrovascular diseases and neuroophthalmology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Yang SL. Reviewer Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r390131 ) The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-390131 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Dec 2025 Kevin Pacheco-Barrios , Universidad San Ignacio de Loyola, Lima District, 150114, Peru 09 Dec 2025 Author Response Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD ... Continue reading Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Response. Thank you for your appraisal. The manuscript has been updated based on the comments from the other reviewer. All changes can be observed in the new version with tracked changes. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Response. Thank you for your appraisal. The manuscript has been updated based on the comments from the other reviewer. All changes can be observed in the new version with tracked changes. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Dec 2025 Kevin Pacheco-Barrios , Universidad San Ignacio de Loyola, Lima District, 150114, Peru 09 Dec 2025 Author Response Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD ... Continue reading Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Response. Thank you for your appraisal. The manuscript has been updated based on the comments from the other reviewer. All changes can be observed in the new version with tracked changes. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Response. Thank you for your appraisal. The manuscript has been updated based on the comments from the other reviewer. All changes can be observed in the new version with tracked changes. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Ladogana A. Reviewer Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r384616 ) The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-384616 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Jun 2025 Anna Ladogana , Istituto Superiore di Sanità, Rome, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.165074.r384616 The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following ... Continue reading READ ALL The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. Minor I suggest First sentence: always fatal instead of " high mortality". Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Third sentence: Add Zerr et al 2024 in the references and delete references 3. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? The term of the search in Medline and Embase should be reported. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: prion diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Ladogana A. Reviewer Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r384616 ) The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-384616 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Dec 2025 Kevin Pacheco-Barrios , Universidad San Ignacio de Loyola, Lima District, 150114, Peru 09 Dec 2025 Author Response Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of ... Continue reading Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following: Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. R. Thank you for your suggestions. The two references were added while the other three references were removed from the manuscript as suggested. Minor I suggest First sentence: always fatal instead of " high mortality". Response. Thank you for your suggestion. The sentences was rephrased. Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Response. Thank you for your suggestion. We have rephrased the sentence accordingly. Third sentence: Add Zerr et al 2024 in the references and delete references 3. Response. Thank you for your suggestion. This reference was added to the text. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Response. We appreciate the reviewer’s important clarification regarding the diagnostic criteria for probable CJD. In our case, several neurological features consistent with pyramidal and extrapyramidal involvement were present, but we recognize that they were not described explicitly enough in the manuscript. As documented in the case narrative, the patient exhibited: Extrapyramidal signs — including rest tremor, intention tremor, and parkinsonian-like motor slowing; Pyramidal signs — such as hyperreflexia and bilateral Babinski sign noted during hospitalization (we added these details); Cerebellar involvement — suggested by intention tremor and progressive gait impairment; Episodes compatible with myoclonus — reported during clinical deterioration but not explicitly labeled as myoclonus in the original text. To address the reviewer’s point, we have revised the clinical description to clearly and systematically report these neurological signs. This ensures alignment with the diagnostic criteria that require at least two of the following: myoclonus, visual/cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? Response. We thank the reviewer for this question and agree that the description of the 14-3-3 Western blot method and the definition of a “high titre” (titer) should be clearer. In our case, the 14-3-3 protein was measured in CSF by a semi-quantitative Western blot assay performed in an external reference laboratory. The laboratory runs patient CSF samples alongside positive and negative controls. Band intensity corresponding to 14-3-3 is then densitometrically compared with these controls, and the result is reported using their internal semi-quantitative scale (e.g. negative, low, moderate, or high). In our patient, the sample was reported as “strongly positive / high titre”, meaning that the 14-3-3 band intensity was clearly above the laboratory’s predefined positivity threshold and comparable to or higher than their positive control. We have now clarified in the case description. As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. R. Thank you, we have added the arrows in the figure as suggested. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? Response. We appreciate the reviewer’s important observation regarding early-onset cases and the possibility of hereditary prion disease. In our patient, no family history of neurodegenerative disorders, rapidly progressive dementia, psychiatric disease, or movement disorders was reported by relatives during the clinical assessment. Because the clinical presentation, evolution, MRI pattern, and 14-3-3 positivity were all compatible with sporadic CJD, and due to limited diagnostic resources at our institution, genetic testing for PRNP mutations was not performed. We agree that in younger patients genetic testing may be informative, and we have now acknowledged this point in the manuscript as a limitation. We specify that although no family history was identified, the absence of PRNP testing prevents us from fully excluding a genetic form of prion disease. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Response. Thank you for your comment. The sentence was corrected. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following: Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. R. Thank you for your suggestions. The two references were added while the other three references were removed from the manuscript as suggested. Minor I suggest First sentence: always fatal instead of " high mortality". Response. Thank you for your suggestion. The sentences was rephrased. Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Response. Thank you for your suggestion. We have rephrased the sentence accordingly. Third sentence: Add Zerr et al 2024 in the references and delete references 3. Response. Thank you for your suggestion. This reference was added to the text. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Response. We appreciate the reviewer’s important clarification regarding the diagnostic criteria for probable CJD. In our case, several neurological features consistent with pyramidal and extrapyramidal involvement were present, but we recognize that they were not described explicitly enough in the manuscript. As documented in the case narrative, the patient exhibited: Extrapyramidal signs — including rest tremor, intention tremor, and parkinsonian-like motor slowing; Pyramidal signs — such as hyperreflexia and bilateral Babinski sign noted during hospitalization (we added these details); Cerebellar involvement — suggested by intention tremor and progressive gait impairment; Episodes compatible with myoclonus — reported during clinical deterioration but not explicitly labeled as myoclonus in the original text. To address the reviewer’s point, we have revised the clinical description to clearly and systematically report these neurological signs. This ensures alignment with the diagnostic criteria that require at least two of the following: myoclonus, visual/cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? Response. We thank the reviewer for this question and agree that the description of the 14-3-3 Western blot method and the definition of a “high titre” (titer) should be clearer. In our case, the 14-3-3 protein was measured in CSF by a semi-quantitative Western blot assay performed in an external reference laboratory. The laboratory runs patient CSF samples alongside positive and negative controls. Band intensity corresponding to 14-3-3 is then densitometrically compared with these controls, and the result is reported using their internal semi-quantitative scale (e.g. negative, low, moderate, or high). In our patient, the sample was reported as “strongly positive / high titre”, meaning that the 14-3-3 band intensity was clearly above the laboratory’s predefined positivity threshold and comparable to or higher than their positive control. We have now clarified in the case description. As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. R. Thank you, we have added the arrows in the figure as suggested. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? Response. We appreciate the reviewer’s important observation regarding early-onset cases and the possibility of hereditary prion disease. In our patient, no family history of neurodegenerative disorders, rapidly progressive dementia, psychiatric disease, or movement disorders was reported by relatives during the clinical assessment. Because the clinical presentation, evolution, MRI pattern, and 14-3-3 positivity were all compatible with sporadic CJD, and due to limited diagnostic resources at our institution, genetic testing for PRNP mutations was not performed. We agree that in younger patients genetic testing may be informative, and we have now acknowledged this point in the manuscript as a limitation. We specify that although no family history was identified, the absence of PRNP testing prevents us from fully excluding a genetic form of prion disease. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Response. Thank you for your comment. The sentence was corrected. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Dec 2025 Kevin Pacheco-Barrios , Universidad San Ignacio de Loyola, Lima District, 150114, Peru 09 Dec 2025 Author Response Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of ... Continue reading Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following: Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. R. Thank you for your suggestions. The two references were added while the other three references were removed from the manuscript as suggested. Minor I suggest First sentence: always fatal instead of " high mortality". Response. Thank you for your suggestion. The sentences was rephrased. Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Response. Thank you for your suggestion. We have rephrased the sentence accordingly. Third sentence: Add Zerr et al 2024 in the references and delete references 3. Response. Thank you for your suggestion. This reference was added to the text. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Response. We appreciate the reviewer’s important clarification regarding the diagnostic criteria for probable CJD. In our case, several neurological features consistent with pyramidal and extrapyramidal involvement were present, but we recognize that they were not described explicitly enough in the manuscript. As documented in the case narrative, the patient exhibited: Extrapyramidal signs — including rest tremor, intention tremor, and parkinsonian-like motor slowing; Pyramidal signs — such as hyperreflexia and bilateral Babinski sign noted during hospitalization (we added these details); Cerebellar involvement — suggested by intention tremor and progressive gait impairment; Episodes compatible with myoclonus — reported during clinical deterioration but not explicitly labeled as myoclonus in the original text. To address the reviewer’s point, we have revised the clinical description to clearly and systematically report these neurological signs. This ensures alignment with the diagnostic criteria that require at least two of the following: myoclonus, visual/cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? Response. We thank the reviewer for this question and agree that the description of the 14-3-3 Western blot method and the definition of a “high titre” (titer) should be clearer. In our case, the 14-3-3 protein was measured in CSF by a semi-quantitative Western blot assay performed in an external reference laboratory. The laboratory runs patient CSF samples alongside positive and negative controls. Band intensity corresponding to 14-3-3 is then densitometrically compared with these controls, and the result is reported using their internal semi-quantitative scale (e.g. negative, low, moderate, or high). In our patient, the sample was reported as “strongly positive / high titre”, meaning that the 14-3-3 band intensity was clearly above the laboratory’s predefined positivity threshold and comparable to or higher than their positive control. We have now clarified in the case description. As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. R. Thank you, we have added the arrows in the figure as suggested. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? Response. We appreciate the reviewer’s important observation regarding early-onset cases and the possibility of hereditary prion disease. In our patient, no family history of neurodegenerative disorders, rapidly progressive dementia, psychiatric disease, or movement disorders was reported by relatives during the clinical assessment. Because the clinical presentation, evolution, MRI pattern, and 14-3-3 positivity were all compatible with sporadic CJD, and due to limited diagnostic resources at our institution, genetic testing for PRNP mutations was not performed. We agree that in younger patients genetic testing may be informative, and we have now acknowledged this point in the manuscript as a limitation. We specify that although no family history was identified, the absence of PRNP testing prevents us from fully excluding a genetic form of prion disease. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Response. Thank you for your comment. The sentence was corrected. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following: Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. R. Thank you for your suggestions. The two references were added while the other three references were removed from the manuscript as suggested. Minor I suggest First sentence: always fatal instead of " high mortality". Response. Thank you for your suggestion. The sentences was rephrased. Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Response. Thank you for your suggestion. We have rephrased the sentence accordingly. Third sentence: Add Zerr et al 2024 in the references and delete references 3. Response. Thank you for your suggestion. This reference was added to the text. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Response. We appreciate the reviewer’s important clarification regarding the diagnostic criteria for probable CJD. In our case, several neurological features consistent with pyramidal and extrapyramidal involvement were present, but we recognize that they were not described explicitly enough in the manuscript. As documented in the case narrative, the patient exhibited: Extrapyramidal signs — including rest tremor, intention tremor, and parkinsonian-like motor slowing; Pyramidal signs — such as hyperreflexia and bilateral Babinski sign noted during hospitalization (we added these details); Cerebellar involvement — suggested by intention tremor and progressive gait impairment; Episodes compatible with myoclonus — reported during clinical deterioration but not explicitly labeled as myoclonus in the original text. To address the reviewer’s point, we have revised the clinical description to clearly and systematically report these neurological signs. This ensures alignment with the diagnostic criteria that require at least two of the following: myoclonus, visual/cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? Response. We thank the reviewer for this question and agree that the description of the 14-3-3 Western blot method and the definition of a “high titre” (titer) should be clearer. In our case, the 14-3-3 protein was measured in CSF by a semi-quantitative Western blot assay performed in an external reference laboratory. The laboratory runs patient CSF samples alongside positive and negative controls. Band intensity corresponding to 14-3-3 is then densitometrically compared with these controls, and the result is reported using their internal semi-quantitative scale (e.g. negative, low, moderate, or high). In our patient, the sample was reported as “strongly positive / high titre”, meaning that the 14-3-3 band intensity was clearly above the laboratory’s predefined positivity threshold and comparable to or higher than their positive control. We have now clarified in the case description. As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. R. Thank you, we have added the arrows in the figure as suggested. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? Response. We appreciate the reviewer’s important observation regarding early-onset cases and the possibility of hereditary prion disease. In our patient, no family history of neurodegenerative disorders, rapidly progressive dementia, psychiatric disease, or movement disorders was reported by relatives during the clinical assessment. Because the clinical presentation, evolution, MRI pattern, and 14-3-3 positivity were all compatible with sporadic CJD, and due to limited diagnostic resources at our institution, genetic testing for PRNP mutations was not performed. We agree that in younger patients genetic testing may be informative, and we have now acknowledged this point in the manuscript as a limitation. We specify that although no family history was identified, the absence of PRNP testing prevents us from fully excluding a genetic form of prion disease. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Response. Thank you for your comment. The sentence was corrected. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 11 Apr 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 09 Dec 25 read read Version 1 11 Apr 25 read read Anna Ladogana , Istituto Superiore di Sanità, Rome, Italy Shi-Lin Yang , Fudan University, Shanghai, China Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Yang S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Jan 2026 | for Version 2 Shi-Lin Yang , Fudan University, Shanghai, China 0 Views copyright © 2026 Yang S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I have no further comments to make. Competing Interests No competing interests were disclosed. Reviewer Expertise My major is cerebrovascular diseases and neuroophthalmology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Yang SL. Peer Review Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.192648.r439926) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-425/v2#referee-response-439926 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Ladogana A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Dec 2025 | for Version 2 Anna Ladogana , Istituto Superiore di Sanità, Rome, Italy 0 Views copyright © 2026 Ladogana A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The manuscript has been comprehensively revised by the authors in accordance with our comments. All issues highlighted in the reviewer’s report have been duly addressed. The manuscript is hereby approved. Competing Interests No competing interests were disclosed. Reviewer Expertise prion diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Ladogana A. Peer Review Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.192648.r439927) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-425/v2#referee-response-439927 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Yang S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Jun 2025 | for Version 1 Shi-Lin Yang , Fudan University, Shanghai, China 0 Views copyright © 2025 Yang S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise My major is cerebrovascular diseases and neuroophthalmology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 09 Dec 2025 Kevin Pacheco-Barrios, Universidad San Ignacio de Loyola, Lima District, 150114, Peru Reviewer 2: Shi-Lin Yang This article made a detailed review and summary of the previous literature, which is helpful to improve understanding of the CJD. The clinical manifestations of CJD are heterogeneous. Multiple case analyses have been reported. This article focused on reviewing the characteristics of the disease rather than more novel clinical manifestations. Response. Thank you for your appraisal. The manuscript has been updated based on the comments from the other reviewer. All changes can be observed in the new version with tracked changes. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes View more View less Competing Interests None reply Respond Report a concern Yang SL. Peer Review Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r390131) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-390131 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Ladogana A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Jun 2025 | for Version 1 Anna Ladogana , Istituto Superiore di Sanità, Rome, Italy 0 Views copyright © 2025 Ladogana A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. Minor I suggest First sentence: always fatal instead of " high mortality". Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Third sentence: Add Zerr et al 2024 in the references and delete references 3. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? The term of the search in Medline and Embase should be reported. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise prion diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 09 Dec 2025 Kevin Pacheco-Barrios, Universidad San Ignacio de Loyola, Lima District, 150114, Peru Reviewer 1: Ana Ladogana The authors report a case of CJD with an atypical onset that initially made the diagnosis challenging. They also present a systematic review of the literature on published CJD case reports. My suggestions are the following: Introduction Main issue The background does not include the most recent diagnostic criteria for CJD, In the 4th sentence "The probable diagnosis…" eliminate ref 1,3 and 5 and add see CDC diagnostic criteria and Hermann 2021 ECDC diagnostic criteria. R. Thank you for your suggestions. The two references were added while the other three references were removed from the manuscript as suggested. Minor I suggest First sentence: always fatal instead of " high mortality". Response. Thank you for your suggestion. The sentences was rephrased. Second sentence: Sometime forming extracellular amyloid plaques instead of "forming extracellular amyloid plaques" and change the ref 2 with Baiardi et al 2019 . Response. Thank you for your suggestion. We have rephrased the sentence accordingly. Third sentence: Add Zerr et al 2024 in the references and delete references 3. Response. Thank you for your suggestion. This reference was added to the text. Are enough details provided of any physical examination and diagnostic tests Although the clinical picture and some test results are suggestive, extrapyramidal, pyramidal, cerebellar signs, or myoclonus are not clearly reported. In the absence of at least two of these symptoms, a diagnosis of probable CJD cannot be made. Response. We appreciate the reviewer’s important clarification regarding the diagnostic criteria for probable CJD. In our case, several neurological features consistent with pyramidal and extrapyramidal involvement were present, but we recognize that they were not described explicitly enough in the manuscript. As documented in the case narrative, the patient exhibited: Extrapyramidal signs — including rest tremor, intention tremor, and parkinsonian-like motor slowing; Pyramidal signs — such as hyperreflexia and bilateral Babinski sign noted during hospitalization (we added these details); Cerebellar involvement — suggested by intention tremor and progressive gait impairment; Episodes compatible with myoclonus — reported during clinical deterioration but not explicitly labeled as myoclonus in the original text. To address the reviewer’s point, we have revised the clinical description to clearly and systematically report these neurological signs. This ensures alignment with the diagnostic criteria that require at least two of the following: myoclonus, visual/cerebellar signs, pyramidal/extrapyramidal signs, or akinetic mutism. Regarding the diagnostic test for 14-3-3 protein using the Western blot method: how is a high titre measured? Response. We thank the reviewer for this question and agree that the description of the 14-3-3 Western blot method and the definition of a “high titre” (titer) should be clearer. In our case, the 14-3-3 protein was measured in CSF by a semi-quantitative Western blot assay performed in an external reference laboratory. The laboratory runs patient CSF samples alongside positive and negative controls. Band intensity corresponding to 14-3-3 is then densitometrically compared with these controls, and the result is reported using their internal semi-quantitative scale (e.g. negative, low, moderate, or high). In our patient, the sample was reported as “strongly positive / high titre”, meaning that the 14-3-3 band intensity was clearly above the laboratory’s predefined positivity threshold and comparable to or higher than their positive control. We have now clarified in the case description. As for the brain MRI, the figure is not very clear—possibly due to motion artifacts. Please consider adding arrows to indicate the areas of high signal intensity. R. Thank you, we have added the arrows in the figure as suggested. Given the relatively young age at onset, was family history investigated or genetic test for PRNP gene mutations done? Response. We appreciate the reviewer’s important observation regarding early-onset cases and the possibility of hereditary prion disease. In our patient, no family history of neurodegenerative disorders, rapidly progressive dementia, psychiatric disease, or movement disorders was reported by relatives during the clinical assessment. Because the clinical presentation, evolution, MRI pattern, and 14-3-3 positivity were all compatible with sporadic CJD, and due to limited diagnostic resources at our institution, genetic testing for PRNP mutations was not performed. We agree that in younger patients genetic testing may be informative, and we have now acknowledged this point in the manuscript as a limitation. We specify that although no family history was identified, the absence of PRNP testing prevents us from fully excluding a genetic form of prion disease. Minor This sentence should be checked, something seems missed: "The progressive neurological compromise with the development of early and progressive dementia in the next months…... CJD diagnostic was suspected" Response. Thank you for your comment. The sentence was corrected. Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment Again, there is a problem with the case classification if the authors did not report on other neurologic symptoms/signs as reported in the diagnostic criteria. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? Partly References 1. Zerr I, Ladogana A, Mead S, Hermann P, et al.: Creutzfeldt–Jakob disease and other prion diseases. Nature Reviews Disease Primers . 2024; 10 (1). Publisher Full Text 2. Baiardi S, Rossi M, Capellari S, Parchi P: Recent advances in the histo‐molecular pathology of human prion disease. Brain Pathology . 2019; 29 (2): 278-300 Publisher Full Text 3. Hermann P, Appleby B, Brandel J, Caughey B, et al.: Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease. The Lancet Neurology . 2021; 20 (3): 235-246 Publisher Full Text View more View less Competing Interests None reply Respond Report a concern Ladogana A. Peer Review Report For: Case Report: Creutzfeldt-Jakob disease and diagnosis challenges: case report and evidence synthesis [version 1; peer review: 2 approved with reservations] . F1000Research 2025, 14 :425 ( https://doi.org/10.5256/f1000research.165074.r384616) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-425/v1#referee-response-384616 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Stay Updated Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with F1000Research Already registered? Sign in Not now, thanks close PLEASE NOTE If you are an AUTHOR of this article, please check that you signed in with the account associated with this article otherwise we cannot automatically identify your role as an author and your comment will be labelled as a “User Comment”. If you are a REVIEWER of this article, please check that you have signed in with the account associated with this article and then go to your account to submit your report, please do not post your review here. If you do not have access to your original account, please contact us . All commenters must hold a formal affiliation as per our Policies . The information that you give us will be displayed next to your comment. User comments must be in English, comprehensible and relevant to the article under discussion. We reserve the right to remove any comments that we consider to be inappropriate, offensive or otherwise in breach of the User Comment Terms and Conditions . Commenters must not use a comment for personal attacks. When criticisms of the article are based on unpublished data, the data should be made available. I accept the User Comment Terms and Conditions Please confirm that you accept the User Comment Terms and Conditions. Affiliation ✕ refresh Please enter your institution. Note: To add your institution or organisation, start typing the name and then select the correct name from the list. Where applicable, the name will appear in both the original language and in English. Do not paste in the name. If the name does not appear in the drop-down list, we will display the information you have entered. ✕ refresh Country/Region * USA UK Canada China France Germany Afghanistan Aland Islands Albania Algeria American Samoa Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory British Virgin Islands Brunei Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Cook Islands Costa Rica Cote d'Ivoire Croatia Cuba Cyprus Czech Republic Democratic Republic of the Congo Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands Faroe Islands Federated States of Micronesia Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and Mcdonald Islands Holy See (Vatican City State) Honduras Hong Kong Hungary Iceland India Indonesia Iran Iraq Ireland Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Kosovo (Serbia and Montenegro) Kuwait Kyrgyzstan Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macao Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mayotte Mexico Minor Outlying Islands of the United States Moldova Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Antilles New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island North Korea North Macedonia Northern Mariana Islands Norway Oman Pakistan Palau Palestinian Territory Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Reunion Romania Russian Federation Rwanda Saint Helena Saint Kitts and Nevis Saint Lucia Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Is South Korea South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syria Taiwan Tajikistan Tanzania Thailand The Gambia The Netherlands Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu UK USA Uganda Ukraine United Arab Emirates United States Virgin Islands Uruguay Uzbekistan Vanuatu Venezuela Vietnam Wallis and Futuna West Bank and Gaza Strip Western Sahara Yemen Zambia Zimbabwe Please select your country/region. You must enter a comment. Competing Interests Please disclose any competing interests that might be construed to influence your judgment of the article's or peer review report's validity or importance. Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). You work at the same institute as any of the authors. You hope/expect to benefit (e.g. favour or employment) as a result of your submission. You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Please state your competing interests The comment has been saved. An error has occurred. Please try again. Cancel Post var lTitle = "Case Report: Creutzfeldt-Jakob disease and...".replace("'", ''); var linkedInUrl = "http://www.linkedin.com/shareArticle?url=https://f1000research.com/articles/14-425/v1" + "&title=" + encodeURIComponent(lTitle) + "&summary=" + encodeURIComponent('Read the article by '); var deliciousUrl = "https://del.icio.us/post?url=https://f1000research.com/articles/14-425/v1&title=" + encodeURIComponent(lTitle); var redditUrl = "http://reddit.com/submit?url=https://f1000research.com/articles/14-425/v1" + "&title=" + encodeURIComponent(lTitle); linkedInUrl += encodeURIComponent('Failoc Rojas VE et al.'); var offsetTop = /chrome/i.test( navigator.userAgent ) ? 4 : -10; var addthis_config = { ui_offset_top: offsetTop, services_compact : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_expanded : "facebook,twitter,www.linkedin.com,www.mendeley.com,reddit.com", services_custom : [ { name: "LinkedIn", url: linkedInUrl, icon:"/img/icon/at_linkedin.svg" }, { name: "Mendeley", url: "http://www.mendeley.com/import/?url=https://f1000research.com/articles/14-425/v1/mendeley", icon:"/img/icon/at_mendeley.svg" }, { name: "Reddit", url: redditUrl, icon:"/img/icon/at_reddit.svg" }, ] }; var addthis_share = { url: "https://f1000research.com/articles/14-425", templates : { twitter : "Case Report: Creutzfeldt-Jakob disease and diagnosis challenges:.... Failoc Rojas VE et al., published by " + "@F1000Research" + ", https://f1000research.com/articles/14-425/v1" } }; if (typeof(addthis) != "undefined"){ addthis.addEventListener('addthis.ready', checkCount); addthis.addEventListener('addthis.menu.share', checkCount); } $(".f1r-shares-twitter").attr("href", "https://twitter.com/intent/tweet?text=" + addthis_share.templates.twitter); $(".f1r-shares-facebook").attr("href", "https://www.facebook.com/sharer/sharer.php?u=" + addthis_share.url); $(".f1r-shares-linkedin").attr("href", addthis_config.services_custom[0].url); $(".f1r-shares-reddit").attr("href", addthis_config.services_custom[2].url); $(".f1r-shares-mendelay").attr("href", addthis_config.services_custom[1].url); function checkCount(){ setTimeout(function(){ $(".addthis_button_expanded").each(function(){ var count = $(this).text(); if (count !== "" && count != "0") $(this).removeClass("is-hidden"); else $(this).addClass("is-hidden"); }); }, 1000); } close How to cite this report {{reportCitation}} Cancel Copy Citation Details $(function(){R.ui.buttonDropdowns('.dropdown-for-downloads');}); $(function(){R.ui.toolbarDropdowns('.toolbar-dropdown-for-downloads');}); $.get("/articles/acj/150498/165074") new F1000.Clipboard(); new F1000.ThesaurusTermsDisplay("articles", "article", "165074"); $(document).ready(function() { $( "#frame1" ).on('load', function() { var mydiv = $(this).contents().find("div"); var h = mydiv.height(); console.log(h) }); var tooltipLivingFigure = jQuery(".interactive-living-figure-label .icon-more-info"), titleLivingFigure = tooltipLivingFigure.attr("title"); tooltipLivingFigure.simpletip({ fixed: true, position: ["-115", "30"], baseClass: 'small-tooltip', content:titleLivingFigure + " " }); tooltipLivingFigure.removeAttr("title"); $("body").on("click", ".cite-living-figure", function(e) { e.preventDefault(); var ref = $(this).attr("data-ref"); $(this).closest(".living-figure-list-container").find("#" + ref).fadeIn(200); }); $("body").on("click", ".close-cite-living-figure", function(e) { e.preventDefault(); $(this).closest(".popup-window-wrapper").fadeOut(200); }); $(document).on("mouseup", function(e) { var metricsContainer = $(".article-metrics-popover-wrapper"); if (!metricsContainer.is(e.target) && metricsContainer.has(e.target).length === 0) { $(".article-metrics-close-button").click(); } }); var articleId = $('#articleId').val(); if($("#main-article-count-box").attachArticleMetrics) { $("#main-article-count-box").attachArticleMetrics(articleId, { articleMetricsView: true }); } }); var figshareWidget = $(".new_figshare_widget"); if (figshareWidget.length > 0) { window.figshare.load("f1000", function(Widget) { // Select a tag/tags defined in your page. In this tag we will place the widget. _.map(figshareWidget, function(el){ var widget = new Widget({ articleId: $(el).attr("figshare_articleId") //height:300 // this is the height of the viewer part. [Default: 550] }); widget.initialize(); // initialize the widget widget.mount(el); // mount it in a tag that's on your page // this will save the widget on the global scope for later use from // your JS scripts. This line is optional. //window.widget = widget; }); }); } close Error Close Add Reset F1000.MICROSERVICES.AFFILIATION = ''; $(document).ready(function () { $('.js-affiliations-form').each((index, form) => { new AffiliationForm({ formId: form.id, institutionErrorSelector: '.comment-enter-institution', departmentErrorSelector: '.comment-enter-department', placeSelector: '.js-add-comment-place', stateSelector: '.js-add-comment-state', zipCodeSelector: '.js-add-comment-zipcode', countrySelector: '.js-add-comment-country', countryErrorSelector: '.comment-enter-country', }); }); }); $(document).ready(function () { var reportIds = { "382479": 0, "382485": 0, "382484": 0, "382487": 0, "382486": 0, "382481": 0, "382480": 0, "382483": 0, "382482": 0, "382488": 0, "378149": 0, "378148": 0, "378151": 0, "378150": 0, "378145": 0, "378144": 0, "378147": 0, "378146": 0, "378153": 0, "378152": 0, "386357": 0, "386356": 0, "386359": 0, "386358": 0, "386355": 0, "386364": 0, "386361": 0, "386360": 0, "386363": 0, "386362": 0, "443462": 0, "446022": 0, "443463": 0, "446023": 0, "443460": 0, "443461": 0, "443459": 0, "446030": 0, "443468": 0, "446028": 0, "388559": 0, "446029": 0, "443466": 0, "446026": 0, "443467": 0, "446027": 0, "443464": 0, "446024": 0, "443465": 0, "446025": 0, "388565": 0, "388564": 0, "388567": 0, "388566": 0, "388561": 0, "388560": 0, "388563": 0, "388562": 0, "388568": 0, "390117": 0, "384613": 0, "384612": 0, "384615": 0, "390118": 0, "384614": 0, "384609": 0, "384611": 0, "384610": 0, "380653": 0, "380652": 0, "380655": 0, "380654": 0, "384617": 0, "384616": 17, "384618": 0, "439926": 6, "390133": 0, "380661": 0, "439927": 4, "390132": 0, "380660": 0, "390135": 0, "390134": 0, "380657": 0, "390128": 0, "380656": 0, "390131": 15, "380659": 0, "390130": 0, "380658": 0, }; $(".referee-response-container,.js-referee-report").each(function(index, el) { var reportId = $(el).attr("data-reportid"), reportCount = reportIds[reportId] || 0; $(el).find(".comments-count-container,.js-referee-report-views").html(reportCount); }); var uuidInput = $("#article_uuid"), oldUUId = uuidInput.val(), newUUId = "7e3e0c1c-d4cc-4301-b0d4-a37832b763b1"; uuidInput.val(newUUId); $("a[href*='article_uuid=']").each(function(index, el) { var newHref = $(el).attr("href").replace(oldUUId, newUUId); $(el).attr("href", newHref); }); }); An innovative open access publishing platform offering rapid publication and open peer review, whilst supporting data deposition and sharing. Browse Gateways Collections How it Works Contact For Developers Cookie Notice Privacy Notice RSS Submit Your Research Follow us © 2012-2026 F1000 Research Ltd. ISSN 2046-1402 | Legal | Partner of Research4Life • CrossRef • ORCID • FAIRSharing R.templateTests.simpleTemplate = R.template(' $text $text $text $text $text '); R.templateTests.runTests(); var F1000platform = new F1000.Platform({ name: "f1000research", displayName: "F1000Research", hostName: "f1000research.com", id: "1", editorialEmail: "[email protected]", infoEmail: "[email protected]", usePmcStats: true }); $(function(){R.ui.dropdowns('.dropdown-for-authors, .dropdown-for-about, .dropdown-for-myresearch');}); // $(function(){R.ui.dropdowns('.dropdown-for-referees');}); $(document).ready(function () { if ($(".cookie-warning").is(":visible")) { $(".sticky").css("margin-bottom", "35px"); $(".devices").addClass("devices-and-cookie-warning"); } $(".cookie-warning .close-button").click(function (e) { $(".devices").removeClass("devices-and-cookie-warning"); $(".sticky").css("margin-bottom", "0"); }); $("#tweeter-feed .tweet-message").each(function (i, message) { var self = $(message); self.html(linkify(self.html())); }); $(".partner").on("mouseenter mouseleave", function() { $(this).find(".gray-scale, .colour").toggleClass("is-hidden"); }); }); Sign In Remember me Forgotten your password? Sign In Cancel Email or password not correct. Please try again Please wait... $(function(){ // Note: All the setup needs to run against a name attribute and *not* the id due the clonish // nature of facebox... $("a[id=googleSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("GOOGLE"); $("form[id=oAuthForm]").submit(); }); $("a[id=facebookSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("FACEBOOK"); $("form[id=oAuthForm]").submit(); }); $("a[id=orcidSignInButton]").click(function(event){ event.preventDefault(); $("input[id=oAuthSystem]").val("ORCID"); $("form[id=oAuthForm]").submit(); }); }); If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here . If you still need help with your Google account password, please click here . You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here . If you still need help with your Facebook account password, please click here . Code not correct, please try again Reset password Cancel Email us for further assistance. Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait... Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });