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Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative condition. This report presents the largest published case series on the condition. The palliative care symptom burden and management of these patients is considered. Early advanced care planning and goals of care discussions are necessary. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (sCJD) is a frequent differential diagnostic consideration in patients with rapidly progressive dementia (RPD). Fortunately, in the last 2 decades there has been substantial cumulative improvements in sCJD biomarkers, particularly those based on imaging and cerebrospinal fluid (CSF) interrogation. Brain MRI is a very frequently employed investigation in patients with RPD, often utilized quite early in the evaluation and thereby offering a potentially key role in prompting initial concerns for sCJD. Extant conventional MRI criteria for sCJD diagnosis are relatively stringent, requiring fluid attenuated inversion recovery (FLAIR) or diffusion weighted imaging (DWI) high signal changes in 2 or more cortical regions (excluding frontal) or in both the caudate and putamen. Challenging these conventional criteria, a recent publication described improved sensitivity and unchanged specificity if MRI criteria were arguably less rigorous, requiring DWI high signal changes in only 1 or more of 7 discrete brain regions: frontal, parietal, occipital or temporal cortices, as well as the caudate, putamen or thalamus. The aim of the current study was to test the diagnostic performance of this proposed change in MRI criteria in the Australian context and compare it with conventional criteria, as well as 2 other stringent sets of criteria, predicting that a similar improved sensitivity with unchanged specificity would be observed when the proposed criteria were utilized. Sixty-five definite sCJD cases were compared with 63 age- and sex-matched controls. Radiological review of all MRIs applying the different sets of MRI criteria was undertaken by a blinded neuroradiologist, very experienced in CJD interpretation, with independent assessment of 71 MRIs performed by a second blinded neuroradiologist less experienced in sCJD imaging findings. Our study found the sensitivity of the recently proposed MRI criteria (92.3%) to be comparable to that originally reported (90–95%) and also equivalent to the conventional MRI diagnostic criteria (92.3%), while the specificities were also quite similar between the conventional MRI criteria (87.3%) and proposed criteria (85.7%), with the latter lower than previously reported. Negative predictive values and positive predictive values were also very similar between the conventional and proposed MRI criteria. Other MRI criteria assessed were associated with unacceptably low sensitivity for clinical use. Inter-rater reliability as assessed by intra-class correlation coefficients (ICC) revealed moderate reliability for the conventional and proposed MRI criteria, modestly better in the former and when the frontal lobe was retained versus excluded in comparisons. [ABSTRACT FROM AUTHOR]

The Heidenhain variant of Creutzfeld-Jakob disease (CJD) is a rare form that initially presents with visual disturbances. In early stages, the presentation can mimic neuromyelitis optica spectrum disorders (NMOSD) and lead to unnecessary treatment modalities. Herein, we describe a case of a 66-year-old man who presented with bilateral vision loss and retro-orbital discomfort. In addition to immunosuppressive therapy, he received 4 rounds of therapeutic plasma exchange after his preliminary diagnosis of NMOSD. We were surprised to note that his condition did not show improvement but deteriorated, with severe neurocognitive symptoms. Eventually, CJD was suspected, and real-time quaking-induced conversion (RT-QuIC) was performed. By the time the diagnosis of Heidenhain variant of CJD was confirmed, the patient was discharged to hospice care and died shortly after. [ABSTRACT FROM AUTHOR]

Introduction Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years. Age-specific incidence declines after 80 years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations and improving ascertainment for public health purposes. Objective To phenotype the clinical features and investigation profile of sCJD in adults >80 years. Methods We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011–2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared. Results 10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3 months; P  < 0.001). Pyramidal signs (48.3% vs 34.2%; P  = 0.008) and akinetic mutism (55.1% vs 33.2%; P  < 0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; P  = 0.01) and cerebellar signs (65.4% vs 78.6%, P  = 0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of cerebrospinal fluid real-time quaking-induced conversion (CSF RT-QuIC) (92.9% vs 91.9%, P  = 0.74) was comparable, electroencephalography was superior (41.5% vs 25.4%; P  = 0.006) and MRI was inferior (67.8% vs 91.4%; P  < 0.001). Conclusions Late-onset sCJD has distinct clinical features, shorter survival and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive. [ABSTRACT FROM AUTHOR]

Background: As a rare neurodegenerative disease, sporadic Creutzfeldt-Jakob disease (sCJD) is poorly understood in the elderly populace. This study aims to enunciate the multidimensional features of sCJD in this group. Methods: A case of probable sCJD was reported in a 90-year-old Chinese man with initial dizziness. Then, available English literature of the elderly sCJD cases (aged 80 years and over) was reviewed and analyzed. Patients (15 cases) were subdivided and compared geographically. Results: In the elderly sCJD cohort, the onset age was 84.9 ± 4.5 years and the median disease duration was 6.8 months, with respiratory infection/failure as the commonest death cause. Various clinical symptoms were identified, with cognitive disorder (86.7%) as the commonest typical symptom and speech impairment (66.7%) as the most atypical one. Restricted hyperintensities were reported in 60.0% cases on DWI, periodic sharp wave complexes in 73.3% cases on electroencephalogram, and cerebral hypoperfusion/hypometabolism in 26.7% cases on molecular imaging. The sensitive cerebrospinal fluid biomarkers were total tau (83.3%), 14-3-3 protein (75.0%), and PrP RT-QuIC (75.0%). Neuropathological profiles in the cerebral cortex revealed vacuolar spongiosis, neuronal loss, gliosis, and aging-related markers, with synaptic deposit as the commonest PrP pattern (60.0%). The polymorphic PRNP analysis at codon 129 was M/M (90.9%), with MM1 and MM2C as the primary molecular phenotypes. Latency to first clinic visit, hyperintense signals on DWI, and disease duration were significantly different between the patient subgroups. Conclusion: The characteristics of sCJD are multidimensional in the elderly, deepening our understanding of the disease and facilitating an earlier recognition and better care for this group. [ABSTRACT FROM AUTHOR]

Purpose: This study sought to investigate the diagnostic sensitivity of diffusion-weighted imaging (DWI) in variant Creutzfeldt-Jakob disease (vCJD), a prion disease with significant public health implications on account of its transmissibility. The importance of this research stemmed from the first neuropathologically confirmed vCJD case in a PRNP heterozygous individual in 2016, which displayed DWI features typical of sporadic CJD (sCJD). The case was classified as 'probable' sCJD in life, predominantly based on these imaging findings. While DWI has proven valuable in diagnosing sCJD, its utility in vCJD diagnosis remains unclear. Methods: DWI and Fluid-attenuated inversion recovery (FLAIR) images from probable and definite vCJD cases referred to the National CJD Research and Surveillance Unit (NCJDRSU) were independently analysed by an expert neuroradiologist. Scans were reviewed within a mixed cohort of CJD cases including definite sCJD and non-CJD controls. Results: FLAIR sequences demonstrated greater sensitivity in identifying the pulvinar sign in vCJD compared to DWI (73% vs 41%, p-value <0.001). Basal ganglia hyperintensities were more prevalent in DWI (84%) than FLAIR (64%), and cortical hyperintensities were exclusive to DWI (24%). The pulvinar sign showed a specificity of 98% for vCJD and was rare in sCJD. Conclusion: DWI showed reduced sensitivity compared to FLAIR imaging in detecting the pulvinar sign in vCJD. Conversely, DWI can more distinctively identify basal ganglia and cortical hyperintensities, thus leading to imaging patterns more characteristic of sCJD. Therefore, DWI should be cautiously interpreted in vCJD diagnosis, with axial FLAIR potentially providing a more precise evaluation of the pulvinar sign. [ABSTRACT FROM AUTHOR]

Prion disease is a rare entity, with an estimated prevalence ranging from 0.32 to 1.73 cases per million individuals. The familial form corresponds to 10% of all cases, with an age of onset between 40 and 50 years. To date, over forty germline mutations have been described, with the most frequent being the c.598G>Ap.Glu200Lys (E200K) mutation. Case presentation: A 41-year-old male presented in November 2021 with progressive memory impairment. By April 2022, he developed tremors and balance disturbances. Neurological examination revealed features consistent with dementia, pancerebellar and parkinsonian syndromes. Magnetic resonance imaging showed symmetrical and bilateral hyperintensities in the basal ganglia. Given these findings and familial factors, genetic sequencing of the PrP gene was performed, revealing a mutation in the PrPSc gene (c.532G>A, p. Asp178sn), compatible with a familial variant of Creutzfeldt Jacob Disease. Conclusions: Prionopathy should be considered as a diagnosis possibility in individuals with rapidly progressing dementia. Although there are both clinical and paraclinical diagnostic criteria, DNA sequencing is essential for identifying de novo or autosomal dominant hereditary mutations. [ABSTRACT FROM AUTHOR]

Creutzfeldt–Jakob disease (CJD) belongs to the group of fatal neurodegenerative disorders known as prion diseases. We are going to describe the case of a 54-year-old married man who initially presented with rapidly progressive cognitive decline along with behavioral symptoms and was subsequently diagnosed with probable CJD. He presented with 1½ months history of disinhibited behavior, decreased social interaction, persecutory ideas, food refusal, and decreased sleep along with cognitive decline. On examination, the patient had myoclonus and ataxia. Routine blood investigations, serological tests, and autoimmune and paraneoplastic profiles were normal. Injection haloperidol 2.5 mg intramuscular for behavioral symptoms was given with no improvement. The cerebrospinal fluid study revealed positive results for 14-3-3 protein. The patient was diagnosed with probable CJD and subsequently passed away within 1 month of presentation. Thus, CJD should be kept in the differential diagnosis of patients with cognitive decline and persistent behavioral symptoms despite standard psychiatric treatment. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease (CJD) is a group of clinically rare neurodegenerative diseases caused by misfolding of prion proteins, and is the most common type of human prion diseases. Since the prion characteristics were recognized in the 1970s, the diagnostic detection technology has made great progress, especially the real-time quaking-induced conversion (RT-QuIC). This paper describes the pathogenesis of CJD, the mechanism of action of RT-QuIC and its application in the diagnosis of CJD in order to promote the application and development of RT-QuIC technology in the field of CJD. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob disease (CJD) can be difficult to distinguish clinically from some non-prion neurological diseases. Previous studies have reported markedly increased levels of α-synuclein in cerebrospinal fluid (CSF) of CJD patients, indicating that it is a potential diagnostic biomarker.Objective: The aim of this study was to assess the diagnostic power of CSF α-synuclein in discriminating CJD from non-prion disorders.Methods: The Ovid MEDLINE, Cochrane, and Embase databases were searched for articles published on or before February 25, 2022, using the search term (prion diseases OR Creutzfeldt-Jakob syndrome) AND (synuclein OR α-synuclein). The difference in CSF α-synuclein levels between CJD and non-prion diseases was calculated using random-effects models (I2 > 50%) or fixed-effects models (I2 < 50%) in terms of standardized mean difference (SMD) and 95% confidence interval (CI). The publication bias was estimated using funnel plots and the Egger's test.Results: Ten studies were included in this study. The concentrations of CSF α-synuclein were significantly higher in CJD patients compared to total non-prion controls (SMD = 1.98, 95% CI 1.60 to 2.36, p < 0.00001), tauopathies (SMD = 1.34, 95% CI 0.99 to 1.68, p < 0.00001), synucleinopathies (SMD = 1.78, 95% CI 1.11 to 2.44, p < 0.00001), or Alzheimer's (SMD = 1.14, 95% CI 0.95 to 1.33, p < 0.00001). CSF α-synuclein could distinguish CJD from non-prion diseases with overall sensitivity of 89% (95% CI 80-95%), specificity of 92% (95% CI 86-95%), and AUC of 0.96 (95% CI: 0.94-0.97).Conclusion: CSF α-synuclein has excellent diagnostic value in discriminating CJD from non-prion neurological diseases. Given the high heterogeneity among the included studies, further studies are needed to confirm its clinical utility. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jacob disease (CJD) is a fatal neuro-degenerative disease, characterized by rapid and intense deterioration, mainly cognitive, leading to death. The typical onset of the disease is around the age of 67.Purpose: To characterize the demographic and clinical features of the population of CJD patients with late-onset disease.Methods: In this retrospective study, the Israeli national database of prion diseases was screened for CJD patients with disease age of onset > 80 years between 1960 and 2016. Patient's demographic and clinical data were collected including sex, type of disease (sporadic/ genetic), clinical presentation, lab results including tau protein level, imaging, and EEG characteristics. Then, the clinical and demographic data of patients with late onset (> 80 years) (L) and patients with usual age of onset (< 80 years) (U) were compared.Results: The study included 728 patients, 23 patients (3.3%) with late-onset disease (82.2.4±4 years, range 80-88) and 705 with usual disease onset (61.31 ± 9.47 years, range 34-80). Sporadic CJD was more common in the late-onset group (18/23 patients (78.2%) (L) vs. 256/705 patients (36.3%) (U)) (p = 0.0001, chi-square test). Classical EEG finding of periodic sharp wave activity were seen more often in the late-onset patients (55% (L) vs. 32.5% (U)) (p = 0.05, chi-square test). The rest of the demographic and clinical features were similar in both groups.Conclusion: Late- and usual-onset diseases are similar in most of demographic and clinical features suggesting a common disease type with normal distribution of age of onset. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeld Jakob Disease is a rare disease with diagnostic challenges. While there is very little human data regarding this disease, some studies have indicated that certain medications may be useful in slowing its progression. Case study data implies psychiatric and cognitive symptoms preceding the diagnosis. This single case report presents a 68-year-old male with suspected late-onset bipolar disorder, later found to have sporadic Creutzfeld Jakob Disease. The patient was treated with lithium for this purported bipolar disorder. Approximately 2 years later, the patient met the Center for Disease Control (CDC) diagnostic criteria for prion disease following a rapid decline in cognition. This case provides an example of a medical mimic of bipolar disorder in the geriatric population. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Creutzfeldt-Jakob Disease. Topics include underlying the pathogenesis of prion diseases being conformational change of the normal neuronal host prion protein; and characterizing genetic forms of prion disease or contact with infectious tissue accounting for transmitted and iatrogenic forms.

Creutzfeldt‐Jakob disease (CJD) is a rare, progressive neurological condition of which the sporadic form is most common. It can present with a wide variety of symptoms that make its recognition difficult. In this case there was a rapid progression of neurological symptoms that presented as catatonia. The presence of a history of depression contributed to diagnostic overshadowing, delaying medical investigation of catatonia. While not included in the Euro CJD or WHO criteria, psychiatric symptoms are common in sporadic CJD and their presence therefore should not preclude thorough medical investigation. [ABSTRACT FROM AUTHOR]

Background: Human prion diseases, including Creutzfeldt-Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrPC) into self-propagating multimeric assemblies or prions. Preclinical studies have firmly validated the targeting of PrPC as a therapeutic strategy. We aimed to evaluate a first-in-human treatment programme using an anti-PrPC monoclonal antibody under a Specials Licence.Methods: We generated a fully humanised anti-PrPC monoclonal antibody (an IgG4κ isotype; PRN100) for human use. We offered treatment with PRN100 to six patients with a clinical diagnosis of probable CJD who were not in the terminal disease stages at the point of first assessment and who were able to readily travel to the University College London Hospital (UCLH) Clinical Research Facility, London, UK, for treatment. After titration (1 mg/kg and 10 mg/kg at 48-h intervals), patients were treated with 80-120 mg/kg of intravenous PRN100 every 2 weeks until death or withdrawal from the programme, or until the supply of PRN100 was exhausted, and closely monitored for evidence of adverse effects. Disease progression was assessed by use of the Medical Research Council (MRC) Prion Disease Rating Scale, Motor Scale, and Cognitive Scale, and compared with that of untreated natural history controls (matched for disease severity, subtype, and PRNP codon 129 genotype) recruited between Oct 1, 2008, and July 31, 2018, from the National Prion Monitoring Cohort study. Autopsies were done in two patients and findings were compared with those from untreated natural history controls.Findings: We treated six patients (two men; four women) with CJD for 7-260 days at UCLH between Oct 9, 2018, and July 31, 2019. Repeated intravenous dosing of PRN100 was well tolerated and reached the target CSF drug concentration (50 nM) in four patients after 22-70 days; no clinically significant adverse reactions were seen. All patients showed progressive neurological decline on serial assessments with the MRC Scales. Neuropathological examination was done in two patients (patients 2 and 3) and showed no evidence of cytotoxicity. Patient 2, who was treated for 140 days, had the longest clinical duration we have yet documented for iatrogenic CJD and showed patterns of disease-associated PrP that differed from untreated patients with CJD, consistent with drug effects. Patient 3, who had sporadic CJD and only received one therapeutic dose of 80 mg/kg, had weak PrP synaptic labelling in the periventricular regions, which was not a feature of untreated patients with sporadic CJD. Brain tissue-bound drug concentrations across multiple regions in patient 2 ranged from 9·9 μg per g of tissue (SD 0·3) in the thalamus to 27·4 μg per g of tissue (1·5) in the basal ganglia (equivalent to 66-182 nM).Interpretation: Our academic-led programme delivered what is, to our knowledge, the first rationally designed experimental treatment for human prion disease to a small number of patients with CJD. The treatment appeared to be safe and reached encouraging CSF and brain tissue concentrations. These findings justify the need for formal efficacy trials in patients with CJD at the earliest possible clinical stages and as prophylaxis in those at risk of prion disease due to PRNP mutations or prion exposure.Funding: The Cure CJD Campaign, the National Institute for Health Research UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust, and the UK MRC. [ABSTRACT FROM AUTHOR]

Objective: To use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.Methods: Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008-December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.Results: The Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.Conclusions: These two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up. [ABSTRACT FROM AUTHOR]

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons. Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP. CSF samples were assessed for the surrogate markers of neurodegeneration, 14-3-3 protein (14-3-3), total-tau protein (t-tau) and α-synuclein and for prion seeding activity through the real-time quaking-induced conversion assay. Biomarker results were compared with those obtained in healthy and neurological controls. For the most prevalent PRNP pathogenic sequence variations, biomarker accuracy and associations between biomarkers, demographic and genetic determinants were assessed. Additionally, the prognostic value of biomarkers for predicting total disease duration from symptom onset to death was investigated. High sensitivity of the four biomarkers was detected for genetic Creutzfeldt-Jakob disease associated with the E200K and V210I mutations, but low sensitivity was observed for mutations associated with Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. All biomarkers showed good to excellent specificity using the standard cut-offs often used for sporadic Creutzfeldt-Jakob disease. In genetic prion diseases related to octapeptide repeat insertions, the biomarker sensitivity correlated with the number of repeats. New genetic prion disease-specific cut-offs for 14-3-3, t-tau and α-synuclein were calculated. Disease duration in genetic Creutzfeldt-Jakob disease-E200K, Gerstmann-Sträussler-Scheinker-P102L and fatal familial insomnia was highly dependent on PRNP codon 129 MV polymorphism and was significantly associated with biomarker levels. In a large cohort of genetic prion diseases, the simultaneous analysis of CSF prion disease biomarkers allowed the determination of new mutation-specific cut-offs improving the discrimination of genetic prion disease cases and unveiled genetic prion disease-specific associations with disease duration. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrPSc). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. Development and clinical application of disease-specific protein aggregation and amplification assays, such as real-time quaking induced conversion (RT-QuIC), have constituted major breakthroughs for the confident pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrPSc seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation. [ABSTRACT FROM AUTHOR]

Introduction: 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. Method: A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

The article discusses Creutzfeldt–Jakob disease has a fatal neurodegenerative brain disorder caused by a prion protein. Topics include clinical symptoms overlap with of dementia with Lewy bodies and require careful attention in making a diagnosis; and vital signs, chest radiographs, electrocardiograms, and blood tests have all within normal limits.

Introduction: Creutzfeldt-Jakob disease (CJD) as a prion disease is an untreatable type of progressive neurodegenerative encephalopathy. Although no definitive case has been reported yet, here we report a case that given the history, course of symptoms, and recent dental practice, it is highly probable that it was caused by dental procedures. Case Report: The patient was a 52-year-old woman who has had memory problems gradually with forgetting the names of family members since 6 weeks prior to the visit and shortly after the dental procedure. She experienced progressive visual hallucinations accompanied by a sharp decline in cognitive, verbal, and motor abilities in just a few weeks. Finally, the diagnosis of Creutzfeldt-Jakob was made for her based on the clinical history and typical brain MRI. Discussion: Clinical evidence of this patient, along with positive brain MRI results, indicates the risk of prion transfer through dental procedures. Paying attention to the neurological aspects of psychiatric manifestations and increasing the awareness of dentists about how to deal with and act on the potential dangers of prion transfer is of paramount importance. [ABSTRACT FROM AUTHOR]

Introduction: Sporadic Creutzfeldt Jakob Disease, the most common reported prion disease, is a fatal neurodegenerative disease caused by the misfolding of protein PrPC to PrPSC. EEG is the first in vivo test to support the clinical diagnosis of sporadic CJD (sCJD). This study is carried out to describe the comprehensive electroencephalography changes in a cohort of patients with probable sCJD from south India. Methodology: This retrospective observational study is conducted by reviewing case records from 2013–2020. Demographic, clinical, imaging details were noted. Electroencephalogram (EEG) recordings were retrieved and reviewed independently by two qualified epileptologists and the findings were visually analyzed and correlated with clinical and imaging abnormalities. Results: Fifty patients with probable sCJD with the availability of artefact-free EEG were included in the study. The mean age was 59.76 ± 8.17 years and M: F was 31:19. Magnetic resonance imaging (MRI) brain showed abnormality defining CJD in 48/50, i.e., 96%patients. EEG showed specific and or nonspecific abnormalities in 88%. The specific abnormalities, i.e., periodic sharp wave complexes (PSWC), were noted 66%. PSWC were mostly asymmetric (90%) and more frequently seen in the right hemisphere (57.6%). Amplitude maximum in the occipital region was noted in 42.4% and in frontal region in 36.4%. The sensitivity of EEG specific abnormalities to diagnose probable sCJD according to CDC 2018 criteria with positive MRI findings was 68.75%. Conclusion: This study showed that EEG is a relatively inexpensive and sensitive tool and assists in the diagnosis of sCJD. However, it can be normal or show nonspecific abnormalities in the early stages of the disease. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic accuracy and the prognostic value of blood and cerebrospinal fluid (CSF) tests across prion disease subtypes.Methods: We used a single-molecule immunoassay to measure tau and neurofilament light chain (NfL) protein levels in the plasma and assessed CSF total(t)-tau, NfL and protein 14-3-3 levels in patients with prion disease (n=336), non-prion rapidly progressive dementias (n=106) and non-neurodegenerative controls (n=37). We then evaluated each plasma and CSF marker for diagnosis and their association with survival, taking into account the disease subtype, which is a strong independent prognostic factor in prion disease.Results: Plasma tau and NfL concentrations were higher in patients with prion disease than in non-neurodegenerative controls and non-prion rapidly progressive dementias. Plasma tau showed higher diagnostic value than plasma NfL, but a lower accuracy than the CSF proteins t-tau and 14-3-3. In the whole prion cohort, both plasma (tau and NfL) and CSF (t-tau, 14-3-3 and NfL) markers were significantly associated with survival and showed similar prognostic values. However, the intrasubtype analysis revealed that only CSF t-tau in sporadic Creutzfeldt-Jakob disease (sCJD) MM(V)1, plasma tau and CSF t-tau in sCJD VV2, and plasma NfL in slowly progressive prion diseases were significantly associated with survival after accounting for covariates.Conclusions: Plasma markers have lower diagnostic accuracy than CSF biomarkers. Plasma tau and NfL and CSF t-tau are significantly associated with survival in prion disease in a subtype-specific manner and can be used to improve clinical trial stratification and clinical care. [ABSTRACT FROM AUTHOR]

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.Methods: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country.Findings: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions.Interpretation: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders.Funding: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust. [ABSTRACT FROM AUTHOR]

Objectives: Creutzfeldt- Jakob Disease (CJD) is a neurodegenerative disease characterized by abnormally-shaped proteins. CJD is the most common type of prion diseases with incidence of 1/100000 per year. In this study, we aimed to review clinical, laboratory, electrophysiological and radiological findings and prognosis of 21 cases with the diagnosis of CJD. Methods: A retrospective review of patient records in a single institution was performed to identify patients with sporadic CJD from 2010 to 2018. January 2017 diagnostic criteria were used for inclusion. In this study, 21 patients were included for analysis. Demographic features, symptoms, clinical findings of neurological examination, disease duration, laboratory findings, electrophysiological test results, findings of magnetic resonance imaging and prognosis were documented. Results: Twelve of the patients included in this study were male and nine were female. The mean age was 64.1 (49-79). All the patients had dementia and changes in personality at admission to the hospital. The duration of complaints was 5.4±4 months. Periodic sharp wave complexes were observed in the electroencephalogram at baseline or follow-up. Twenty patients had undergone lumbar puncture to identify 14.3.3 protein tests in cerebrospinal fluid. In six of twelve patients whose results were received, 14.3.3 protein level was positive, whereas four of them were negative and two were at borderline. Seven patients died of the disease during the follow-up in our hospital within 2.8 (1-6) months from the symptom onset. Conclusion: In patients with rapidly progressive dementia, behavioral changes, hallucinations and myoclonus, CJD should be kept in mind for earlier diagnosis. [ABSTRACT FROM AUTHOR]

We investigated a clinical case of variant Creutzfeldt-Jakob Disease in a person heterozygous for methionine/valine at codon 129 of the prion protein gene and identified the same strain properties in variant Creutzfeldt-Jakob disease in methionine homozygous persons and in bovine spongiform encephalopathy. These results indicate no adaptation of the agent in a different genetic background. [ABSTRACT FROM AUTHOR]

Introduction Creutzfeldt-Jakob disease (CJD) is an extremely rare and invariably fatal neurodegenerative disease caused by a conformationally misfolded infectious protein (prion) which is resistant to degradation by proteases and acts as a template to induce further pathological changes in normal prion proteins. This causes the exponential accumulation of pathogenic prions, disrupting the neuronal cell architecture and resulting in neural cell death and neurodegeneration in affected regions.1 As the multi-organ pathologies of coronavirus disease 2019 (COVID-19) become increasingly recognised, so too does its role in the brain and nervous system. Materials and methods We present a case of CJD with consent gained from next of kin. A literature review was conducted with search terms pertaining to 'CJD' and 'COVID-19' in the databases EMBASE, MEDLINE and PubMed. Results and discussion A previously healthy man in his 80s was admitted to the hospital with rapid progression of neuropsychiatric symptoms including personality change, gait abnormalities and myoclonus alongside COVID-19 infection. Blood tests showed mild elevation of CRP and neutrophils, CT head was unremarkable and CSF analysis showed only mildly raised protein. Brain MRI revealed bilateral cortical and striatal diffusion restriction (Fig 1) and EEG findings included diffuse activity slowing with high amplitude sharp/slow-wave complexes (Fig 2). He was diagnosed with probable sporadic CJD. Management prioritised comfort and care. Shortly thereafter he passed away, a mere 8 weeks after the first onset of symptoms. A review of the literature found only seven case reports of CJD with concomitant COVID-19 infection, with our case representing the first documented case in the UK.3-9 These reports contribute to a growing body of evidence that COVID-19 may play a role in accelerating neurodegeneration. Several proposed models exist to explain the impact of COVID-19 upon the central nervous system, including its pro-inflammatory effects and subsequent implication in neuroinflammation and pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's disease. Conclusion We present the first documented case of CJD with concomitant COVID-19 infection in the UK, joining only seven other cases worldwide. We provide learning points for the diagnosis of CJD as a rare differential of rapidly progressing dementia, and we provide further evidence that COVID-19 may aggravate the progression of CJD, as seen in other neurodegenerative diseases like Alzheimer's disease. [ABSTRACT FROM AUTHOR]

A case study of a 98‑year‑old retired farmer, non‑smoker, non‑alcoholic, and enjoying his daily routine activities with his family was referred to our hospital for evaluation of rapidly progressive dementia for last 10 weeks. Topics include patient had progressive short‑term memory loss and it was associated with emotional liability; and focal intermittent myoclonus emerging spontaneously and response to auditory or tactile stimuli were observed.

Variant Creutzfeldt-Jakob disease (vCJD) is caused by prion infection with bovine spongiform encephalopathy and can be transmitted by blood transfusion. Protein misfolding cyclic amplification (PMCA) can detect prions in blood from vCJD patients with 100% sensitivity and specificity. To determine whether PMCA enables prion detection in blood during the preclinical stage of infection, we performed a blind study using blood samples longitudinally collected from 28 control macaques and 3 macaques peripherally infected with vCJD. Our results demonstrate that PMCA consistently detected prions in blood during the entire preclinical stage in all infected macaques, without false positives from noninfected animals, when using the optimized conditions for amplification of macaque prions. Strikingly, prions were detected as early as 2 months postinoculation (>750 days before disease onset). These findings suggest that PMCA has the potential to detect vCJD prions in blood from asymptomatic carriers during the preclinical phase of the disease. [ABSTRACT FROM AUTHOR]

Background In Ireland, there are approximately 55,000 cases of dementia. One of the rare causes of dementia is Creutzfeldt-Jakob disease (CJD), affecting one person per million each year worldwide. It is a rapidly progressive degenerative fatal disorder with an estimated mortality of 70% within one year. In this case report we present a rare case of possible familial-CJD which presented initially as a stroke mimic. Methods A 64-year old female referred via GP with abnormal left arm athetoid movements and in-coordination. MRI brain demonstrated a small sub-acute hyper-intense lesion in the right basal ganglia on diffusion weighted imaging. Her symptoms were atypical for acute stroke, however an alternative cause was not evident. She was monitored closely with early supported discharge. However the left sided athetoid movements worsened and were associated with intermittent myoclonic jerks and dystonic posturing. She was reassessed with a wider differential including focal impaired seizures, Rasmussen's encephalitis, and CJD. EEG showed periodic lateralizing epileptic discharges, however patient failed to show any response to anti-epileptic treatment and her clinical course was one of rapid deterioration. Clinical findings and subsequent MRI findings showed new areas of hyperintensity supporting CJD. Results Ultimately our patient deteriorated rapidly resulting in an akinetic and abulic state, resulting in death. A final diagnosis of sporadic-CJD was made based on rapid progressive deterioration and findings on MRI as well as confirmation on post-mortem brain pathology. A deeper review of family history revealed a sister who had passed away years prior with rapid progressive neurological illness. Her work-up showed clinical signs and EEG findings supporting CJD, however there was no post mortem to confirm her diagnosis. Conclusion This case highlights the importance of genetics shaping phenotypes and that consideration should always be given to a full relevant family history. It also shows a rare case of rapidly progressive dementia confirmed due to CJD with a likely underlying familial predisposition. [ABSTRACT FROM AUTHOR]

We present two historic cases of severe encephalopathy associated with antithyroid antibodies. The first was published by Lord Brain of Eynsham, and the second was from our department's archives. Although both cases are from archival sources, they continue to inform current clinical care. We briefly review the poorly defined entity, Hashimoto's encephalopathy, and discuss diagnostic advances for autoimmune encephalopathy and for Creutzfeldt-Jakob disease. We advocate for giving a trial of corticosteroids to patients with 'encephalopathy, not otherwise specified' while awaiting antibody results or more definitive testing. Our case, initially diagnosed as having Creutzfeldt-Jakob disease, responded remarkably (with video evidence) to a trial of corticosteroids. [ABSTRACT FROM AUTHOR]

Heroin-induced spongiform leukoencephalopathy (HSLE) is a rare condition that is strongly associated with heroin vapor inhalation which has become a popular method among heroin addicts because it poses a less immediate danger to the user and makes the drug much easier to use. We present a case of a 22-year-old male who presented with dysarthria and cerebellar symptoms starting, after 3 months of heroin inhalation. Diagnosis was confirmed to be HSLE after extensive diagnostic testing. HSLE is a rare complication of which the pathogenesis is poorly understood. Clinical history and characteristic findings on magnetic resonance imaging (diffuse, symmetric T2-hyperintensity, and diffusion restriction in frontal, parietal, occipital lobs, basal ganglia, and superior cerebellum) are diagnostic; however, care should be taken to exclude other etiologies. Treatment is primarily supportive; however, there is anecdotal evidence that coenzyme Q10 may be of benefit. The growing number of victims of the opioid crisis requires that physicians be aware of and counsel patients on the devastating neurological complications that can occur with abuse of these drugs. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeld-Jakob disease (CJD) is a rare neurodegenerative disorder. It is uniformly fatal. Clinical signs include myoclonus, visual disturbances, cerebellar ataxia, akinetic mutism and pyramidal/extrapyramidal signs in addition to a rapidly progressive dementia. Premortem diagnosis is challenging due to the rarity of the condition and the subsequent low index of suspicion held for it. On literature review, isolated language impairment as the first neurological symptom occurs in only about 1% of patients with sporadic CJD (El Tawil et al. (2017, Acta Neurol Scand, 135: 316–23)). We present this patient's case, marked for the unusual presentation and the rapidity of decline, to emphasise the need for awareness of CJD as an important differential diagnosis on stroke units. In our case, magnetic resonance imaging findings drove the suspicion of sporadic CJD as the diagnosis. This seems to correlate with other case reports recognising CJD presenting with progressive aphasic disorders (Terrin et al. (2017, Neurol Sci, 38: 1535–7); Mandell et al. (1989, Neurology, 39: 55–8); Martory et al. (2012, Eur Neurol, 67: 360–2)). [ABSTRACT FROM AUTHOR]

The diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) can be difficult, but the real-time quaking-induced conversion (RT-QuIC) assays have made a considerable impact on its clinical diagnosis. This technique exploits the ability of the misfolded pathological form of prion protein (PrPSc) found in cerebrospinal fluid (CSF) to induce conversion of normal PrP to the misfolded form, which subsequently aggregates. The formation of these aggregates of misfolded PrP is monitored in real time using fluorescent dyes. The current sensitivity of CSF RT-QuIC undertaken at the UK National CJD Research & Surveillance Unit is 92% and the specificity is 100%. The interpretation of the RT-QuIC traces is affected by the presence of raised CSF red and white cells counts and elevated total protein concentrations. We recommend that CSF samples for RT-QuIC analysis are clear and colourless with a white cell count of <10 x10^6/L and have a total protein concentration of <1 g/L. [ABSTRACT FROM AUTHOR]

Objectives: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters.Methods: The database set in the project was the source for epidemiological and clinical analysis of CJD cases.Results: The incidence of CJD in ES (2004-2016) was 1.7/million person-years (95% CI 1-2.4); the incidence increase in the last five years (2012-2016) was comparable to the whole country. Twenty seven of 29 reported CJD cases were available for analysis (mean age 59 years, F/M 15/12). The proportion of gCJD (E200K mutation) cases remained dominant (78%), with 9 familiar cases originating in 4 families. Analysis of the clinical features revealed shorter duration of the symptomatic phase in sporadic CJD (sCJD) (3.4 months) versus gCJD (5.15 months). Cognitive/behavioural changes, insomnia, and sensory disturbance were more pronounced in the early symptoms of gCJD. Periodic EEG discharges were more frequent in sCJD (83%) than gCJD (56%), all 19 available MR findings were CJD specific and localisation of abnormalities varied amongst the CJD forms.Conclusions: The surveillance of CJD in ES (2004-2016) showed an increased incidence of CJD in ES, reaching the incidence rate of the whole country, with a permanent proportion of 70% gCJD cases based on the E200K mutation. Clinical, electrophysiological and MR features of sCJD and gCJD cases were in conformity with already published data. Epidemiological analysis of CJD in ES shows increasing detection of CJD but also suggests that current routine surveillance systems for CJD may underestimate the true burden of disease, especially sporadic cases in Slovakia. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease is themost common human prion disorder. Although associated with heterogeneous clinical phenotypes, its distinctive feature is the presence of a rapidly progressive multidomain cognitive impairment. We describe the atypical case of a patient affected by sporadic Methionine/Methionine type 1 Creutzfeldt-Jakob disease (typically associated with early cognitive decline) who presented with an isolated hemiballic syndrome and no signs of cognitive involvement until death. We review sporadic Creutzfeldt-Jakob disease diagnostic criteria and their updates since their first formulation, highlighting their limitations in clinical diagnostic work-up. Finally, we discuss the recently introduced National Creutzfeldt-Jakob Disease Research and Surveillance Unit diagnostic criteria, suggesting how their application could support an early clinical diagnosis, even in atypical cases, such as the one presented. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease (CJD) is a prion disease manifesting with signs of impaired conscious and mental state, cerebellar ataxia, myoclonus, and loss of vision. Since the disease progresses rapidly to death, it is important to distinguish it from other diseases. The exact diagnosis is made by postmortem histopathological analysis of the brain. The diagnosis of CJD is difficult because the clinical presentation varies between cases. In this paper, we present two cases of CJD. The first case was a 50-year-old male who was admitted with agitation, impaired consciousness and involuntary movements for three months. The second case was a 70-year-old male presented with forgetfulness, total loss of vision in the form of conversion disorder and ataxia. Diagnostic support was provided by magnetic resonance imaging (MRI) and electroencephalography (EEG). Increased cerebrospinal fluid concentration of 14.3.3 protein was determined. As a result, prion disease was considered in these cases due to rapid progression of the neuropsychiatric symptoms. Repeated EEG and MRI are useful for diagnosis in these patients. Although there is not effective treatment, diagnosis of the condition is very important in terms of preventive measures. [ABSTRACT FROM AUTHOR]

Objectives: A blood-based biomarker of neuronal damage in sporadic Creutzfeldt-Jakob disease (sCJD) will be extremely valuable for both clinical practice and research aiming to develop effective therapies.Methods: We used an ultrasensitive immunoassay to measure two candidate biomarkers, tau and neurofilament light (NfL), in serum from patients with sCJD and healthy controls. We tested longitudinal sample sets from six patients to investigate changes over time, and examined correlations with rate of disease progression and associations with known phenotype modifiers.Results: Serum concentrations of both tau and NfL were increased in patients with sCJD. NfL distinguished patients from controls with 100% sensitivity and 100% specificity. Tau did so with 91% sensitivity and 83% specificity. Both tau and NfL appeared to increase over time in individual patients, particularly in those with several samples tested late in their disease. Tau, but not NfL, was positively correlated with rate of disease progression, and was particularly increased in patients homozygous for methionine at codon 129 of PRNP.Conclusions: These findings independently replicate other recent studies using similar methods and offer novel insights. They show clear promise for these blood-based biomarkers in prion disease. Future work should aim to fully establish their potential roles for monitoring disease progression and response to therapies. [ABSTRACT FROM AUTHOR]

The introduction of prion RT-QuIC, an ultrasensitive specific assay for the in vivo detection of the abnormal prion protein, has significantly increased the potential for an early and accurate clinical diagnosis of Creutzfeldt-Jakob disease (CJD). However, in the clinical setting, the early identification of patients with possible CJD is often challenging. Indeed, CJD patients may present with isolated symptoms that remain the only clinical manifestation for some time, or with neurological syndromes atypical for CJD. To enhance awareness of unusual disease presentations and promote earlier diagnosis, we reviewed the entire spectrum of atypical early manifestations of CJD, mainly reported to date as case descriptions or small case series. They included sensory either visual or auditory disturbances, seizures, isolated psychiatric manifestations, atypical parkinsonian syndromes (corticobasal syndrome, progressive supranuclear palsy-like), pseudobulbar syndrome, isolated involuntary movements (dystonia, myoclonus, chorea, blepharospasm), acute or subacute onsets mimicking a stroke, isolated aphasia, and neuropathy. Since CJD is a rare disease and its clinical course rapidly progressive, an in-depth understanding and awareness of early clinical features are mandatory to enhance the overall diagnostic accuracy in its very early stages and to recruit optimal candidates for future therapeutic trials. [ABSTRACT FROM AUTHOR]

Objective: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis.Methods: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics).Results: Patients with an alternative diagnosis and those with sCJD were of similar age, sex and frequency of dementia but CJD mimics had a longer clinical history. Myoclonus, rigidity and hallucinations were more frequent in patients with sCJD but these features were not helpful in classifying individual patients. Alzheimer's disease, dementia with Lewy bodies and genetic neurodegenerative disorders were alternative diagnoses in more than half of the CJD mimic cases, and 10% had an immune-mediated encephalopathy; lymphoma, hepatic encephalopathy and progressive multifocal leukoencephalopathy were seen more than once. Diffusion-weighted MRI was the most useful readily available test to classify cases correctly (92% CJD, 2% CJD mimics). The CSF cell count, 14-3-3 protein detection and S100B were of limited value. A positive CSF RT-QuIC test, introduced during the course of the study, was found in 89% of tested CJD cases and 0% CJD mimics.Conclusion: The combination of diffusion-weighted MRI analysis and CSF RT-QuIC allowed a perfect classification of sCJD versus its mimics in this study. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, is a fatal condition with a mortality rate reaching 85% within one year of clinical presentation. CJD is characterized by rapidly progressive neurological deterioration in combination with typical electroencephalography (EEG) and magnetic resonance imaging (MRI) findings and positive cerebrospinal spinal fluid (CSF) analysis for 14-3-3 proteins. Unfortunately, CJD can have atypical clinical and radiological presentation in approximately 10% of cases, thus making the diagnosis often challenging. We report a rare clinical presentation of sporadic CJD (sCJD) with combination of both expressive aphasia and nonconvulsive status epilepticus. This patient presented with slurred speech, confusion, myoclonus, headaches, and vertigo and succumbed to his disease within ten weeks of initial onset of his symptoms. He had a normal initial diagnostic workup, but subsequent workup initiated due to persistent clinical deterioration revealed CJD with typical MRI, EEG, and CSF findings. Other causes of rapidly progressive dementia and encephalopathy were ruled out. Though a rare condition, we recommend consideration of CJD on patients with expressive aphasia, progressive unexplained neurocognitive decline, and refractory epileptiform activity seen on EEG. Frequent reimaging (MRI, video EEGs) and CSF examination might help diagnose this fatal condition earlier. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob disease (CJD) is a rare fatal neurodegenerative disorder presenting with rapid cognitive decline and additional signs. The clinical characteristics of an increasing number of sporadic CJD (sCJD) patients admitted to the Ljubljana University Medical Centre are presented as well as the incidence of sCJD in Slovenia in 2015 compared to previous years. Methods: We investigated patients presenting with rapidly progressive dementia and at least one additional sign. The diagnosis was made based on clinical diagnostic criteria and an autopsy was performed in all cases. Data on definite sCJD cases in Slovenia since 1999 were obtained and its incidence was calculated. Results: Eight patients with definite sCJD died in 2015 in Slovenia (incidence: 3.89 cases per million). The long-term incidence 1999 was 1.67 per million. Conclusions: The incidence of sCJD was considerably higher in 2015. It reflects fluctuations in sporadic cases of this rare disease. The rising trend might indicate a previous underestimation and better recognition of the disease. [ABSTRACT FROM AUTHOR]

The present study described the characteristics of three cases of Creutzfeldt-Jakob disease (CJD) in China and analyzed their clinical presentations. The clinical information of the three cases was collected and analyzed. Blood and cerebrospinal fluid (CSF) specimens of the patients were collected for detection of the prion protein (PRNP) gene and 14-3-3 protein levels. Dynamic changes of electroencephalograms (EEGs) and brain magnetic resonance images (MRIs) were also observed. All the three cases were sporadic CJD cases. They presented with symptoms including hyposthenia, progressive memory loss, truncal and limb ataxia, dysarthria, lowered vision acuity, bucking, language disorders, myoclonia and akinetic mutism state. One of the three cases was associated with a prolonged duration of >6 years. The EEG of two cases showed slow biphasic waves. The diffusion-weighted MRI sequence revealed abnormal hyperintensity and bilateral ribboning in the cortex. Two patients tested positive for the 14-3-3 protein in the CSF. All patients were of methionine homozygosity at codon 129 in the gene encoding PRNP protein and one patient had a mutation. The CJD cases showed differences in terms of symptoms and disease duration. Subacute onset was common and with attentive nursing and supportive treatments, one of the patients had a prolonged survival time of >6 years. [ABSTRACT FROM AUTHOR]

Introduction: Sporadic Creutzfeldt-Jakob disease (sCJD) includes a broad spectrum of clinical-pathological subtypes, which complicates the clinical differential diagnosis with other rapidly progressive neurological syndromes.Aim: To provide a better characterisation of clinical features and results of diagnostic investigations, especially at an early disease stage, in patients with sCJDVV2, the second most common sCJD subtype.Methods: We evaluated neurological symptoms/signs, and results of brain diffusion-weighted resonance imaging (DW-MRI), electroencephalographic recordings (EEG) and cerebrospinal fluid (CSF) biomarker studies in 120 patients with a definite (n=93) or probable (n=27) diagnosis of sCJDVV2.Results: All patients presented with prominent cerebellar signs, which were often associated with memory loss and/or oculomotor, visual or peripheral/spinal cord signs. In contrast, dementia was invariably a late finding. All CSF samples were positive for the 14-3-3 protein assay and had total-tau protein levels above 1250 pg/mL. Brain DW-MRI showed hyperintensity of basal ganglia, thalamus and cerebral cortex, respectively in 91.5%, 57.4% and 19.1% of cases. EEG revealed periodic sharp-wave complexes in only 17.8% of cases.Conclusions: sCJDVV2 should be considered in any patient presenting with a rapidly progressive ataxia, especially when associated with oculomotor, visual or peripheral/spinal cord signs, even in the absence of dementia or myoclonus. CSF assays and brain DW-MRI represent sensitive diagnostic tests, even at an early stage. These data strongly suggest that sCJDVV2 can be clinically diagnosed early and accurately based on clinical data, DW-MRI, CSF assays and codon 129 genotyping and provide the basis for improved and subtype-specific diagnostic criteria of sCJD. [ABSTRACT FROM AUTHOR]

Patients can have more than one neurological problem, and sorting out acute from chronic disease can be challenging. The authors report a middle-aged patient who presented with ataxia, right hemiparesis, and abnormal nystagmus. Magnetic resonance imaging (MRI) showed a Chiari and an arachnoid cyst with brainstem compression that appeared to explain his abnormal examination. Shortly after admission, he was noted to have intermittent abnormal behavior and confusion. History from family revealed significant acute and chronic psychiatric problems that appeared to explain his abnormal mental status; this delayed the diagnosis of intermittent complex partial seizures. The multitude of various symptoms resulted in a delay of the final diagnosis of Creutzfeldt-Jakob disease (CJD), which in retrospect explained the entire new physical examination, seizures, and mental status changes. [ABSTRACT FROM PUBLISHER]