Creutzfeldt-Jakob disease: updated diagnostic criteria, treatment algorithm, and the utility of brain biopsy

Abstract

<jats:p>Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition with a rapid disease course and a mortality rate of 100%. Several forms of the disease have been described, and the most common is the sporadic type. The most challenging aspect of this disease is its diagnosis—the gold standard for definitive diagnosis is considered to be histopatho-logical confirmation—but newer tests are providing means for an antemortem diagnosis in ways less invasive than brain biopsy. Imaging studies, electroencephalography, and biomarkers are used in conjunction with the clinical picture to try to make the diagnosis of CJD without brain tissue samples, and all of these are reviewed in this article. The current diagnostic criteria are limited; test sensitivity and specificity varies with the genetics of the disease as well as the clinical stage. Physicians may be unsure of all diagnostic testing available, and may order outdated tests or prematurely request a brain biopsy when the diagnostic workup is incomplete. The authors review CJD, discuss the role of brain biopsy in this patient population, provide a diagnostic pathway for the patient presenting with rapidly progressive dementia, and propose newer diagnostic criteria.</jats:p>

Developments in auxiliary examination of Creutzfeldt-Jakob disease

“…Furthermore, GSS and FFI are nearly negative for 14-3-3 protein testing. [5] With the progress of the research, some other biomarkers of CSF are found. Total tau (t-tau) and phosphorylated tau (p-tau) proteins in CSF are considered as useful biomarkers of CJD.…”

“…[9] Some other forms of fCJD with the phenotype different from sCJD have been classified as distinct types such as Gerstmann Sträussler-Scheinker disease (GSS) and fatal familial insomnia (FFI). [5] GSS even could have a much longer disease duration lasting 5 years. The first iCJD case (a person who was infected by corneal transplant from a CJD patient) was reported in 1974.…”

“…[12][13][14] vCJD has different manifestations from sCJD such as younger age at onset (28-29 years, mean), longer disease course (14 months, mean), prominence of psychiatric and sensory symptoms, and negative of PSWCs. [5] The clinical manifestations of CJD lack specificity, thus it is difficult to distinguish from other dementia diseases such as Alzheimer disease, autoimmune encephalitis, neurologic paraneoplastic syndrome and hepatolenticular degeneration, just depending on clinical symptoms. And the detection of PrP or the genetic diagnosis has not been extensively used clinically.…”

Neurobehavioral Testing in Prion Disease Studies

“…The hereditary form can be further subdivided into three distinct phenotypic subtypes, namely (1) GerstmannStraussler-Scheinker (GSS) disease, (2) fatal familial insomnia (FFI), and familial CJD (fCJD). Although the following section will review the unique clinical features of each of these forms, all variants of CJD are generally characterized by a rapid, progressive onset of dementia of unknown origin [28].…”

New Evidence Suggests Link between Prion Disease and Alzheimer’s Disease

“…Eventually, CJD causes deterioration of cognitive, mental, and physical abilities. There is no treatment available to date and the mean survival time is only 5-14 months after the onset of the illness [4]. On the other hand, Alzheimer's disease is the most prevalent cause of dementia in the world's aging populations [5].…”