Variant Creutzfeldt-Jakob Disease Research Articles

Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2022.

Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2022. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2022, a total of 599 domestic CSF specimens were referred for diagnostic testing and 79 persons with suspected human prion disease were formally added to the national register. As of 31 December 2022, just under half of the 79 suspect case notifications (36/79) remain classified as 'incomplete'; 15 cases were classified as 'definite' and 23 as 'probable' prion disease; five cases were excluded through neuropathological examination. For 2022, fifty-five percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia during 2022.

Unexpected decrease of full-length prion protein in macaques inoculated with prion-contaminated blood products.

The presence of prion infectivity in the blood of patients affected by variant Creutzfeldt-Jakob disease (v-CJD), the human prion disease linked to the bovine spongiform encephalopathy (BSE), poses the risk of inter-human transmission of this fatal prion disease through transfusion. In the frame of various experiments, we have previously described that several cynomolgus macaques experimentally exposed to prion-contaminated blood products developed c-BSE/v-CJD, but the vast majority of them developed an unexpected, fatal disease phenotype focused on spinal cord involvement, which does not fulfill the classical diagnostic criteria of v-CJD. Here, we show that extensive analyses with current conventional techniques failed to detect any accumulation of abnormal prion protein (PrPv-CJD) in the CNS of these myelopathic animals, i.e., the biomarker considered responsible for neuronal death and subsequent clinical signs in prion diseases. Conversely, in the spinal cord of these myelopathic primates, we observed an alteration of their physiological cellular PrP pattern: PrP was not detectable under its full-length classical expression but mainly under its physiological terminal-truncated C1 fragment. This observed disappearance of the N-terminal fragment of cellular PrP at the level of the lesions may provide the first experimental evidence of a link between loss of function of the cellular prion protein and disease onset. This original prion-induced myelopathic syndrome suggests an unexpected wide extension in the field of prion diseases that is so far limited to pathologies associated with abnormal changes of the cellular PrP to highly structured conformations.

When vision loss is beyond cataract: a case of fatal neurodegenerative disease (P1-9.010)

<h3>Objective:</h3> NA <h3>Background:</h3> Creutzfeldt Jakob disease (CJD) is a rare and fatal neurodegenerative disorder of unclear etiology. Presentation include myoclonic jerks, visual disturbances, pyramidal/extrapyramidal signs and rapidly progressive cognitive decline. Visual symptoms are a common manifestation of CJD. Here we present a case of progressive vision loss initially attributed to cataract with eventual diagnosis of CJD. <h3>Design/Methods:</h3> Patient is a 75-year-old woman with history of osteoporosis, dyslipidemia, and arthritis presented to the emergency (ED) with bilateral vision loss and cognitive decline. Symptoms started 8 weeks prior presentation with progressive vision loss and difficulty recognizing color and shapes. She also had intermittent horizontal diplopia. Patient was initially evaluated by an ophthalmologist where vision loss was attributed to cataract and underwent bilateral cataract extraction with no improvement in vision. Vision loss worsened and she became unable to recognize familiar faces or identify objects, and had recurrent falls. She suffered visual hallucination, progressive abnormal body posturing, memory loss, dysphagia and severe dysarthria. On her exam she was noted to be mute, unable to follow commands, and had stimulus induced myoclonic jerks of limbs. CXR, urine analysis, urine and blood cultures, and urine drug screen were all unrevealing. Serum and CSF paraneoplastic panel were negative. EEG showed absence of the posterior dominant rhythm. Brain MRI demonstrated cortical ribbon sign and hyperintensities of basal ganglia (image 1). CSF Rt-Quic was indeterminate. Given the history, exam and MRI findings, she was diagnosed with Heidenhain variant of CJD and passed away shortly after transfer to inpatient hospice. <h3>Results:</h3> NA <h3>Conclusions:</h3> CJD can present with isolated visual symptoms that precede cognitive decline by weeks. Detailed history and careful exam are essential for early diagnosis as this will allow patients and their families to prepare for the expected disease course, consider goals of care, and possibly have palliative care if desired. <b>Disclosure:</b> Dr. Abusamra has nothing to disclose. Dr. Ali has nothing to disclose. Dr. Sudhakar has nothing to disclose.

Teaching Neuro Images : Extensive cortical involvement in Creutzfeldt-Jakob disease

A 53-year-old alcoholic man presented with a 2-day history of worsening confusion. Initial examination showed appendicular hypertonia with multifocal arrhythmic asynchronous myoclonic jerks suggestive of cortical myoclonus occurring spontaneously intermittently and stimulus sensitive, with exaggerated deep tendon reflexes and extensor plantars. MRI brain demonstrated low-grade restricted diffusion affecting the entire cerebral cortex (figure 1), sparing the subcortical gray matter and cerebellum.1 T1-weighted imaging and fluid-attenuated inversion recovery sequences showed mild cerebral atrophy. 14-3-3 protein testing was positive and generalized slowing was demonstrated on EEG.2 Changes consistent with Creutzfeldt-Jakob disease (CJD) were found on histopathology (figure 2). The patient had no risk factors for familial, new variant, or iatrogenic CJD. Sporadic CJD was the final diagnosis.

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variantCreutzfeldt–Jakobdisease

Plasma-derived medicinal products (PDMPs) are life-saving and life-improving therapies, but the raw material is in short supply: Europe depends on importation from countries including the United States. Plasma from donors resident in the United Kingdom has not been fractionated since 1999 when a precautionary measure was introduced in response to the outbreak of variant Creutzfeldt-Jakob disease (vCJD). Cases of vCJD have been far fewer than originally predicted in the 1990s. Since the introduction of leucodepletion in 1999, and accounting for the incubation period, more than 40 million UK-derived blood components have been issued with no reports of TT vCJD. In February 2021, the UK Government authorized manufacture of immunoglobulin from UK plasma. Following separate reviews concluding no significant difference in the risk posed, the United States, Australia, Ireland and Hong Kong also lifted their deferrals of blood donors with a history of living in the United Kingdom. Other countries are actively reviewing their position. Demand is rising for PDMPs, and Europe faces a threat of supply shortages. Industry and patient groups are clear that using UK plasma would bring significant immediate benefits to patients and to the resilience of the European supply chain. From this scientific review, we conclude that UK plasma is safe for fractionation and urge blood regulators and operators to take account of this safety profile when considering fractionation of UK plasma, and to revise their guidelines on the deferral of donors who have lived in, or received a transfusion in, the United Kingdom.

The Zoonotic Potential of Chronic Wasting Disease—A Review

Prion diseases are transmissible neurodegenerative disorders that affect humans and ruminant species consumed by humans. Ruminant prion diseases include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. In 1996, prions causing BSE were identified as the cause of a new prion disease in humans; variant Creutzfeldt-Jakob disease (vCJD). This sparked a food safety crisis and unprecedented protective measures to reduce human exposure to livestock prions. CWD continues to spread in North America, and now affects free-ranging and/or farmed cervids in 30 US states and four Canadian provinces. The recent discovery in Europe of previously unrecognized CWD strains has further heightened concerns about CWD as a food pathogen. The escalating CWD prevalence in enzootic areas and its appearance in a new species (reindeer) and new geographical locations, increase human exposure and the risk of CWD strain adaptation to humans. No cases of human prion disease caused by CWD have been recorded, and most experimental data suggest that the zoonotic risk of CWD is very low. However, the understanding of these diseases is still incomplete (e.g., origin, transmission properties and ecology), suggesting that precautionary measures should be implemented to minimize human exposure.

Prions: a threat to health security and the need for effective medical countermeasures

Prions are infectious conformations of certain naturally occurring proteins. These misfolded proteins can structurally alter healthy protein, creating misfolded copies that repeat the process and form protein aggregates that lead to neuronal cell death. Although years can pass from initial prion infection to clinical presentation of symptoms, onset of symptoms is typically followed by rapid neurological decline resulting in death. Prion diseases have been characterized in animals ranging from sheep and cattle to cervids and humans, with notable cross-species infections such as the variant Creutzfeldt-Jakob disease. Thus, prions present a health risk with the potential to disrupt major food sources as well affect human health through animal to human and human to human transmission events. While human to human prion transmission is rare and the immediate risks for a prion-facilitated pandemic are low, prions are a class of pathogens for which we are underprepared. In addition, prions, and prion disease-like approaches, have also been discussed in the context of biological weapons and toxins, adding another layer of complexity surrounding biosecurity and biodefense. These threats underscore the need for increased scrutiny and research on prions. Here, pharmaceutical and nonpharmaceutical prion-specific interventions are discussed. Recent advances in prion therapeutic development are also briefly highlighted, and a set of policy recommendations are given that aims to provide high level suggestions for the prevention and mitigation of prion diseases.

Addition of clobazam successfully treating drug resistant seizures in Heidenhain variant Creutzfeldt Jakob disease: A case report

Creutzfeldt Jakob Disease (CJD) is a rapidly progressive and fatal neurodegenerative disease that is uncommonly accompanied with seizures. In this case report, we describe a 63-year-old male patient who presented with a 3-week history of visual disturbances and clonic movement of his left arm. Additionally, the patient was reported to have developed erratic behaviors along with insomnia during this period. An EEG showed 4 electrographic seizures of bilateral temporo-occipital onset characterized by 1.5Hz periodic discharges, lasting 2-13min. Levetiracetam was started and titrated to the maximal dose however seizures continued so lacosamide and clonazepam were initiated. Despite these aggressive treatments, seizures continued, and oral clobazam 5mg BID replaced clonazepam. Continued electrographic seizures warranted an increase in clobazam to 10mg BID after which the seizures stopped; of note, lateralized periodic discharges (LPDs) remained. The patient's symptoms were consistent with the Heidenhain variant, along with probable CJD due to positive RT-QuIC assay, positive 14-3-3 protein, MRI FLAIR hyperintensities, and EEG findings. Although the patient passed away 3weeks following admission as a result of CJD, we propose that there may be clinical benefit in the use of clobazam in suspected CJD patients presenting with seizures, and its use merits further investigation.

Public Action for Prevention of Iatrogenic Transmission Of CJD

Creutzfeldt-Jakob Disease (CJD) is a rare and a rapidly progressive, invariably fatal neurodegenerative disorder believed to be caused by an abnormal isoform of a cellular glycoprotein known as the prion protein. The disease develops in very different ways, such as sporadic, familial, and iatrogenic. Although there is no means to prevent sporadic and familial CJD outbreaks, iatrogenic CJD can be prevented since the iatrogenic transmission pathway to human is mostly identified. However, despite its public health importance, there is no practical laboratory method for diagnosing this disease in an asymptomatic state. Therefore, it is very important to track the infection route one by one and act public preventive measure. However, there are no manual for prevention of iatrogenic transmission of this disease in Korea. Accordingly, this review summarizes on how to evaluate and act on surgical incidents that occurred in patients with CJD or high-risk patients. However, this is not an easy task for public health management teams as this field continues to require new scientific or specialized clinical knowledge. Therefore, a group or organization of expert panels is needed to manage and make decisions in general. Finally, this review was made with reference to the management regulations of countries with widespread exposure to CJD, including variant CJD. In other words, it is a very conservative and strict safety-oriented guideline. However, since the surveillance of diseases must take into each national medical situation and economic burden, some readjustments are necessary to the situation of the Republic of Korea.

Glycans are not necessary to maintain the pathobiological features of bovine spongiform encephalopathy.

The role of the glycosylation status of PrPC in the conversion to its pathological counterpart and on cross-species transmission of prion strains has been widely discussed. Here, we assessed the effect on strain characteristics of bovine spongiform encephalopathy (BSE) isolates with different transmission histories upon propagation on a model expressing a non-glycosylated human PrPC. Bovine, ovine and porcine-passaged BSE, and variant Creutzfeldt-Jakob disease (vCJD) isolates were used as seeds/inocula in both in vitro and in vivo propagation assays using the non-glycosylated human PrPC-expressing mouse model (TgNN6h). After protein misfolding cyclic amplification (PMCA), all isolates maintained the biochemical characteristics of BSE. On bioassay, all PMCA-propagated BSE prions were readily transmitted to TgNN6h mice, in agreement with our previous in vitro results. TgNN6h mice reproduced the characteristic neuropathological and biochemical hallmarks of BSE, suggesting that the absence of glycans did not alter the pathobiological features of BSE prions. Moreover, back-passage of TgNN6h-adapted BSE prions to BoTg110 mice recovered the full BSE phenotype, confirming that the glycosylation of human PrPC is not essential for the preservation of the human transmission barrier for BSE prions or for the maintenance of BSE strain properties.

Kinetics of the reduction of Creutzfeldt–Jakob disease prion seeding activity by steam sterilization support the use of validated 134°C programmes

Prions are renowned for their distinct resistance to chemical or physical inactivation, including steam sterilization. Impaired efficacy of inactivation poses a risk to patients for iatrogenic transmission of Creutzfeldt-Jakob disease (CJD) via contaminated surgical instruments. Most established prion inactivation methods were validated against scrapie agents, although those were found to be generally less thermostable than human prions. Thus, knowledge gaps regarding steam-sterilization kinetics of CJD prions should be filled and current guidelines reviewed accordingly. Prion inactivation through widely recommended steam sterilization at 134°C was assessed for several holding times by analysing the residual prion seeding activity using protein misfolding cyclic amplification (PMCA). Scrapie 263K was found to be the least thermoresistant prion strain showing no seeding activity after 1.5min at 134°C, while variant CJD was the most stable one demonstrating some seeding activity even after 18min of steam sterilization. Sporadic CJD subtype VV2 exhibited residual seeding activity after 3min, but no detectable activity after 5min at 134°C. Validated steam sterilization for 5min at 134°C as previously recommended for the routine reprocessing of surgical instruments in contact with high-risk tissues is able to substantially reduce the seeding activity of CJD agents, provided that no fixating chemical disinfection has been performed prior to sterilization and that thorough cleaning has reduced the protein load on the surface to less than 100μg per instrument.

Abstract 27 Limitations of Current Human Cell, Tissue, and Cellular-based Product Donor Eligibility Guidance: Analyzing the Impact on a Large Public Cord Blood Bank

IntroductionCord blood (CB) is considered a human cell, tissue, and cellular-based product (HCT/P) by the U.S. Food and Drug Administration (FDA) and is licensed through a Biological Licensing Application (BLA). Cord blood units (CBUs) require less precise donor tissue matching than other stem cell sources, which increases their availability for racial/ethnic minorities. However, a small percentage of banked CBUs are used for transplants. Updating FDA donor eligibility guidance may expand licensed CBU supply and cord blood bank (CBB) sustainability.ObjectiveThe objectives of this study were to analyze the impact of Zika virus (ZIKV) donor screening recommendations on the licensing status of banked CBUs and to propose updated policy recommendations.MethodsA retrospective analysis of Carolinas Cord Blood Bank (CCBB) data (from January 2016 to May 2022) was performed to describe CBU eligibility and shipment status. Qualitative comparisons of FDA guidance to reduce the risk of relevant communicable diseases were completed for blood versus HCT/P.Results CCBB: 8,877 banked CBUs from 2016-2022 (85.3% licensed; 14.7% unlicensed) (Table 1). 4,361 (49.1%) of CBUs were from Caucasian donors and 1,349 (15.2%) were from African American donors. 689 (52.7%) CBUs were unlicensed due to ZIKV risk. The number of CBUs with ZIKV risk banked annually has decreased significantly since 2020, with 174 ZIKV-risk CBUs in 2020 versus 63 in 2021. 26 unlicensed CBUs collected in 2016 or later have been infused versus 210 licensed CBUs. 7 unlicensed, infused CBUs had identified ZIKV risk. No ZIKV transmission was reported from these transplants. FDA Guidance: HCT/P ZIKV recommendations have not been updated since 2018 despite FDA removal of ZIKV from the relevant transfusion-transmitted infections in 2021. Recommendations for minimizing transfusion-transmission risk of human immunodeficiency virus (HIV) and variant Creutzfeldt-Jakob disease (vCJD) were updated in 2020 and 2022, respectively, to increase blood supply. New vCJD guidance eliminated geographic risk-related donor restrictions.Table 1.Characteristics of CBUs banked at CCBB January 2016 to May 2022CBU StatusNumber of Units (%)Banked8,877 (100%) Banked, licensed7,569 (85.3%) Banked, unlicensed1,308 (14.7%) Banked with ZIKV risk (travel-related donor deferral)689 (7.8%) Banked with Hepatitis B core antibody positive82 (<1.0%)Infused236/8,877 (2.7%) Infused, licensed210 (89.0 %) Infused, unlicensed26 (11.0%) Infused, Caucasian donor134 (56.8%) Infused, African American donor28 (11.9%) Infused, unlicensed with ZIKV risk7/26 (26.9%) Infused, unlicensed with Hepatitis B core antibody positive3/26 (11.5%)DiscussionGuidance for reducing disease transmission for blood and blood components have recently been updated to increase blood supply. The FDA must consider new data to revise the HCT/P donor screening recommendations. Adopting these changes will increase the number of HCT/P donors, the quantity of licensed CBUs, and potentially improve access to cellular therapies for a more diverse patient population.

Creutzfeldt-Jakob Disease and Lyodura:A Special Reference to Prion Disease Control in the Field of Neurosurgery

In Japan, 156 cases of dura mater-transplanted Creutzfeldt-Jakob disease(dCJD)with a history of Lyodura transplantation have been confirmed until February 2022, with only a few new cases still being identified. The history of Lyodura transplantation is one involving a neurosurgical procedure. The cumulative global number of cases of bovine spongiform encephalopathy-related variant CJD(BSE-related vCJD), which has shaken societies around the world, is 232 as of 2019. Thus, the impact of dCJD on the society in Japan needs no explanation. Thanks to the world's concerted efforts in research and countermeasures, medically induced prion diseases are finally becoming a thing of the past. However, due to the extremely long incubation period of CJD and the difficulty of tracing the source of infection, immediate action in the event of an outbreak is not possible, and efforts must focus on preventing disease outbreaks. Independent of this, approximately 200 cases of solitary and hereditary prion diseases occur annually in Japan. If neurosurgery must be performed on such patients, secondary transmission of prion disease by neurosurgical instruments must be prevented. Therefore, sterilization methods for neurosurgical instruments are critical, and various measures including sterilization methods have been determined and published by a research group designated by the Japanese Ministry of Health, Labour and Welfare. The sterilization of neurosurgical instruments should comply with the latest guidelines that are published by this study group.

Characteristics of Different Types of Prion Diseases - China's Surveillance.

This report briefly described the establishment and implementation of national surveillance for human prion disease (PrD) in China. Reported cases came from Chinese surveillance network for PrD. Immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA), Polymerase Chain Reaction (PCR), and real-time quaking-induced conversion (RT-QuIC) tests were used for the samples of brain, cerebrospinal fluid (CSF), and blood. Diagnosis standard for the PrDs is based on the National Commission of Health (WS/T 562-2017). The study summarized major epidemiological, clinical and laboratory features of more than 2,100 diagnosed different types of Chinese PrD cases. Sporadic Creutzfeldt-Jacob disease (sCJD) is the predominant type of PrD (88.7%). 19 different genotypes of genetic PrDs (gPrDs) were identified, accounting for about 11.3% of all PrDs, revealing ethno-relationships. No iatrogenic CJD (iCJD) and variant CJD (vCJD) was identified. The characteristics of different types of sCJD in China showed similar features as those reported globally, but gPrDs showed an obvious ethno-relationship.

Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2021.

Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2021. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2021, a total of 548 domestic CSF specimens were referred for 14-3-3 protein testing; 73 persons with suspected human prion disease were formally added to the national register. As of 31 December 2021, just over half of the 73 suspect case notifications (37/73) remain classified as 'incomplete'; 17 cases were classified as 'definite' and 13 as 'probable' prion disease; six cases were excluded through either detailed clinical follow-up (two cases) or neuropathological examination (four cases). For 2021, sixty-four percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia.

The First Evaluation of Proteinase K-Resistant Prion Protein (PrPSc) in Korean Appendix Specimens.

Background and Objectives: Prion diseases are fatal neurodegenerative disorders caused by the abnormal proteinase K-resistant prion protein (PrPSc). Since variant Creutzfeldt–Jakob disease (CJD) was first reported in the United Kingdom (UK) in 1996, the occurrence of variant CJD has been reported in over 10 countries. To date, variant CJD has not been reported in Korea. However, the E211K somatic mutation in the prion protein gene (PRNP), which is related to bovine spongiform encephalopathy (BSE), was reported in Korean Holstein cattle, and atypical BSE, which is supposed to be sporadic BSE, has been occurring in many countries, including Japan and the USA. These results suggest that BSE may occur naturally in Korea. Thus, we performed a preemptive PrPSc test in appendix specimens to diagnose variant CJD in a Korean population. Materials and Methods: In the present study, we investigated CJD-related mutations and polymorphisms of the PRNP gene and carried out an examination on PrPSc in appendix specimens of Korean patients after appendectomy. Results: In all Korean appendix specimens tested, PrPSc bands were not detected. Conclusion: To the best of our knowledge, this was the first evaluation of PrPSc in Korean appendix specimens.

Abnormal prion protein, infectivity and neurofilament light-chain in blood of macaques with experimental variant Creutzfeldt-Jakob disease.

Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative infections. Variant Creutzfeldt-Jakob disease (vCJD) and sporadic CJD (sCJD) are human TSEs that, in rare cases, have been transmitted by human-derived therapeutic products. There is a need for a blood test to detect infected donors, identify infected individuals in families with TSEs and monitor progression of disease in patients, especially during clinical trials. We prepared panels of blood from cynomolgus and rhesus macaques experimentally infected with vCJD, as a surrogate for human blood, to support assay development. We detected abnormal prion protein (PrPTSE) in those blood samples using the protein misfolding cyclic amplification (PMCA) assay. PrPTSE first appeared in the blood of pre-symptomatic cynomolgus macaques as early as 2 months post-inoculation (mpi). In contrast, PMCA detected PrPTSE much later in the blood of two pre-symptomatic rhesus macaques, starting at 19 and 20 mpi, and in one rhesus macaque only when symptomatic, at 38 mpi. Once blood of either species of macaque became PMCA-positive, PrPTSE persisted through terminal illness at relatively constant concentrations. Infectivity in buffy coat samples from terminally ill cynomolgus macaques as well as a sample collected 9 months before clinical onset of disease in one of the macaques was assayed in vCJD-susceptible transgenic mice. The infectivity titres varied from 2.7 to 4.3 infectious doses ml-1. We also screened macaque blood using a four-member panel of biomarkers for neurodegenerative diseases to identify potential non-PrPTSE pre-symptomatic diagnostic markers. Neurofilament light-chain protein (NfL) increased in blood before the onset of clinical vCJD. Cumulatively, these data confirmed that, while PrPTSE is the first marker to appear in blood of vCJD-infected cynomolgus and rhesus macaques, NfL might offer a useful, though less specific, marker for forthcoming neurodegeneration. These studies support the use of macaque blood panels to investigate PrPTSE and other biomarkers to predict onset of CJD in humans.

Blood donor notification of variant Creutzfeldt-Jakob disease risk: Lessons in communicating donor deferral and risk.

In 2005, the blood service in England notified 101 donors by letter that they may be at risk of variant Creutzfeldt-Jakob disease (vCJD) because a recipient of their blood later developed vCJD. Donor experience of the notification was studied in a 2009 survey. Fifteen questions focused on satisfaction, emotional response and understanding of the notification letter. An average Likert score was calculated: 1 and 2= dissatisfied, 3= equivocal and 4 and 5= satisfied; the per cent satisfied and dissatisfied were calculated and characteristics compared using the Fisher and Chi-squared tests. The questionnaire was completed by 56 of 90 notified donors, mostly repeat, U.K.-born donors over 45 years of age. Four years after notification, many individuals still felt surprise (44%), upset (44%) or worry (50%) about the letter, with 10 feeling depressed. Thirty per cent were uncertain if they had vCJD or not. For future notifications, 57% would still favour a detailed letter and 36% would prefer a discussion in person. It was notable how many individuals, 4 years later, still felt continuing anxiety about the vCJD notification letter, not noted in earlier interviews. This highlights a need for on-going support required in donor notifications where outcome for the individual is highly uncertain.

The Various Faces of Creutzfeldt-Jakob Disease (CJD); a Case of CJD Presenting as Psychosis in a Middle-Aged Woman

AimsCreutzfeldt-Jakob disease (CJD) is a rare, progressive, fatal neurodegenerative disorder caused by an abnormal glycoprotein known as the prion protein. The core features include progressive cognitive decline, cerebellar dysfunction, personality changes, and visual disturbances. Although psychiatric symptoms are rare, they can be the primary symptom of CJD, and such presentations can pose diagnostic difficulties. In this paper, we describe the case of Ms. R, who manifested psychotic symptoms as the first signs of CJD.MethodsMs. R, was a 49-year-old white British female not previously known to psychiatric services, who presented with acute onset of florid psychotic symptoms. Her symptoms included auditory hallucinations, paranoia, and thought disorder. She was treated with antipsychotics for over four weeks, following her admission, but no improvement was seen. Instead, her psychosis worsened with cognitive decline, mutism, and the appearance of neurological symptoms such as jerky body movement, ataxia, and falls. All screening blood tests, chest X-ray, and CT abdomen were normal. The MRI, however revealed few patches of high T2/FLAIR signal in the deep white matter. Cerebrospinal fluid showed increased protein. Neurologist reviews suggested the possibility of sporadic CJD (sCJD) as a probable diagnosis. As her condition deteriorated, she became comatose and died four months after the appearance of the first psychiatric symptoms.ResultsIt can be challenging to diagnose CJD since the clinical picture overlaps with other neuropsychiatric and neurodegenerative conditions. It requires the presence of relevant clinical findings along with positive CSF, EEG, or MRI findings to make a probable diagnosis. Regarding our case, some noteworthy observations were psychosis as the initial symptom, relatively delayed onset of neurological signs, rapid deterioration with brief duration of illness. The MRI findings were typical of those seen in sCJD, although the EEG did not suggest sCJD. A differential of variant CJD was considered because of her age, prominent psychiatric symptoms, and delayed neurological signs.ConclusionCreutzfeldt-Jakob disease course is rapidly progressive, and majority of patients die within one year. Therefore, awareness of early clinical features is of great significance. Among other things, this would enable patients and their families time to understand the nature of CJD, prognosis and prepare advanced directives. This case adds to the growing number of atypical presentation of CJD as well as pointing to an expanding spectrum of the disease. Therefore, clinicians should consider CJD in the differential diagnosis of new-onset psychosis, particularly if symptoms persist and worsen despite standard psychiatric treatment.

Risk of variant Creutzfeldt-Jakob disease transmission by blood transfusion in Australia.

Background and ObjectivesMost of the 233 worldwide cases of variant Creutzfeldt–Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion‐transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980–1996. We have modified a previously published methodology to estimate the transfusion‐transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed.Materials and MethodsThe prevalence of current pre‐symptomatic vCJD infection in the United Kingdom by age at infection and genotype was estimated based on risk of exposure to the bovine spongiform encephalopathy agent for the period 1980–1996. These results were used to estimate the age‐specific prevalence of undiagnosed, pre‐symptomatic vCJD in the Australian population in the current year due to prior UK residency or travel. The primary model outputs were the 2020 vCJD risks/unit of vCJD contamination, transfusion‐transmission (infections) and clinical cases.ResultsThe overall (prior UK residency in and travel to United Kingdom, 1980–1996) mean risk of contamination per unit was 1 in 29,900,000. The risks of resulting vCJD transmission (infection) and clinical case were 1 in 389,000,000 and 1 in 1,450,000,000, respectively.ConclusionOur modelling suggests that removing the Lifeblood donation deferral for travel to, or UK residence, would result in virtually no increased risk of vCJD transfusion‐transmission and would be a safe and effective strategy for increasing the donor base.