Sporadic Creutzfeldt-Jakob Disease: Diagnosing Typical and Atypical Presentations under Limited Circumstances

Abstract

<b><i>Introduction:</i></b> Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible disorder of the central nervous system caused by the transformation of normal prion protein into an abnormal misfolded form. The process begins spontaneously and runs a vicious cycle to cause spongiform encephalopathy, rapidly resulting in death. Amply described in the western literature, CJD is scarcely reported in Asia due to certain limitations including missed diagnosis, under-reporting, and rarity of the disease. Brain MRI, electroencephalogram, cerebrospinal fluid testing, and biopsy of the infected brain tissue support the diagnosis in cases of clinical suspicion. However, the diagnosis can still be made with limited available resources in developing countries. <b><i>Method:</i></b> A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. <b><i>Results:</i></b> Eleven cases labeled as sCJD are identified based on the European MRI-CJD consortium criteria. This is the first study on CJD from Pakistan, which includes both the typical and atypical presentations. <b><i>Conclusion:</i></b> Even with limited testing available, the diagnosis of CJD can be made with confidence in the developing countries, provided the suspicion is kept high in cases of rapid onset dementia and acute behavioral changes.

microRNA-146a-5p, Neurotropic Viral Infection and Prion Disease (PrD)

“…Among the most significant advances in human neuroscience, neurology and molecular neurogenetics over the last fifteen years are: (i) the discovery of a family of small noncoding single-stranded RNAs called microRNAs in the mammalian brain and cen-tral nervous system (CNS) and (ii) the analysis and categorization of their abundance, speciation and complexity in development, aging and in neurological health and CNS disease [2,5,6,9,70,71,93,101,107]. A growing body of evidence indicates that select species of the 2650 member human miRNA gene family are brain-abundant and participate in the initiation, propagation and development of insidious age-related neurological disorders of the mammalian brain and CNS.…”

“…The misfolded, abnormal and insoluble isoform of PrPc known as PrPsc self-associates into pro-inflammatory, protease-resistant aggregates that are insoluble in most detergents and chaotropic agents [59,75,84,[89][90][91]. The molecular mechanisms of PrPsc neurotoxicity that drive the initiation, development and progression of PrD are highly complex and, similar to the case of AD, increased oxidative stress and chronic inflammation appear to be critically involved in the initiation and progression of PrD [5,73,86,[92][93][94][95]. Typically, activated microglia accumulate within the immediate vicinity of abnormal PrPsc aggregates, and they release cytokines such as IL-1β that play important roles in the inflammatory pathogenesis of PrD, including the upregulation of genes that promote pro-inflammatory signaling and innate-immune system deficits [86,90].…”