Diagnosis Of Creutzfeldt-Jakob Disease Research Articles

Sporadic Creutzfeldt Jakob disease: Case series in Peru.

A series of 6 cases with a probable diagnosis of sporadic CJD, treated in a Peruvian national reference hospital, are presented. The relevant clinical signs were rapidly progressive dementia and myoclonus, followed by akinetic mutism and pyramidal signs. Of the cases presented, 80% were men, with an average age of presentation of 65 years and duration from diagnosis to death of 6.5 months. Laboratory tests, images (Brain Resonance) and protein dosage 14.3.3 were performed to support the clinical suspicion. There is no effective treatment at the moment for said pathology. Creutzfeldt-Jakob disease (CJD) is a progressive, fatal, neurodegenerative disease of low prevalence and incidence. Great clinical suspicion and the exclusion of other etiologies are required. Currently there is no treatment for this entity and there is a high probability of death before one year.

Characterization of Laboratory-Confirmed Creutzfeldt-Jakob Disease From 3 Ontario Tertiary Care Centers Between 2012 and 2022: A Retrospective Cohort Study.

Globally, Creutzfeldt-Jakob disease (CJD) affects one in one million people annually, but there is a paucity of recent Canadian data. This study summarizes epidemiology trends and diagnostic timelines of laboratory-confirmed CJD cases in three tertiary Ontario hospitals. Using laboratory information systems, we identified 30 patients with a laboratory-confirmed CJD diagnosis between 2012 and 2022 at three major tertiary hospitals in Ontario. Retrospective chart reviews were then completed. Patients had a mean of 2.2 hospital visits (SD, 1.2) prior to being admitted for testing. The most common symptom presentations included loss of coordination (63.3%), behavioral changes (60%), progressive mobility loss (53.4%), memory loss (50.0%), and involuntary movements (50.0%). Magnetic resonance imaging findings showed potential CJD in 76.7% of cases, and 56.7% exhibited periodic sharp wave complexes characteristic of CJD on electroencephalogram. The mean duration from symptom onset to microbiologic testing was 91 days (SD, 90.7). End-point quaking-induced conversion (EP-QuIC) testing of cerebrospinal fluid was positive in 90.0% of patients, while 83.3% tested positive for 14-3-3 on enzyme-linked immunosorbent assay. Elevated cerebrospinal fluid 14-3-3 levels significantly correlated with shorter duration from symptom onset to death (R 2 = 0.71, F = 19.55, P = .0022). Post-diagnosis, 46.7% of patients were discharged home, 16.6% were transferred to external palliative care or hospice facilities, and 36.7% died during admission. The mean time from symptom onset to death was 121 days (SD, 120.7), and from diagnosis to death 35 days (SD, 83.9). This study highlights the importance of early CJD consideration and laboratory testing when appropriate neurologic symptoms are present.

Correlating Histopathological Microscopic Images of Creutzfeldt–Jakob Disease with Clinical Typology Using Graph Theory and Artificial Intelligence

Creutzfeldt–Jakob disease (CJD) is a rare, degenerative, and fatal brain disorder caused by abnormal proteins called prions. This research introduces a novel approach combining AI and graph theory to analyze histopathological microscopic images of brain tissues affected by CJD. The detection and quantification of spongiosis, characterized by the presence of vacuoles in the brain tissue, plays a crucial role in aiding the accurate diagnosis of CJD. The proposed methodology employs image processing techniques to identify these pathological features in high-resolution medical images. By developing an automatic pipeline for the detection of spongiosis, we aim to overcome some limitations of manual feature extraction. The results demonstrate that our method correctly identifies and characterize spongiosis and allows the extraction of features that will help to better understand the spongiosis patterns in different CJD patients.

Understanding Creutzfeldt-Jakob disease in Iran: a systematic review of case reports.

To systematically review the reported cases of Creutzfeldt-Jakob disease (CJD) in Iran. A comprehensive literature review of CJD cases in Iran was undertaken using the PubMed®, Scopus® and Google Scholar databases. In addition, the Iranian database MagIran was searched for Persian language reports. Case selection used the following criteria: (i) patients of Iranian origin; (ii) publication in peer-reviewed journals or reputable medical databases; (iii) a definitive diagnosis of CJD based on established diagnostic criteria. Thirteen cases from twelve reports were included in this systematic review. The majority of the cases were female (11 of 13; 84.6%). The mean ± SD age of patients at hospital admission was 59.38 ± 7.44 years. The findings of the case review suggested that the prevalence of CJD in Iran is not fully established. CJD may be misdiagnosed alongside other clinical signs. The most prevalent early indications of the disease were psychiatric and neurological in nature. A considerable delay in diagnosis was observed in some cases and there was a shortage of brain autopsy records. Efforts to improve diagnostic capabilities, promote awareness and establish monitoring systems are necessary for managing the challenges of providing an early diagnosis of CJD in Iran.

Creutzfeldt-Jakob disease presenting as psychiatric disorder: case presentation and systematic review.

Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy caused by misfolded human prion proteins (PrP)s. Due to variability in presentation, the diagnosis may be missed in lieu of various psychiatric disorders. Our study reports on a prototypical case and psychiatric mimic for CJD, and the workup used to establish the correct diagnosis. A 54-year-old male with a past medical history of traumatic brain injury and major depressive disorder presented with chest pain. During the hospital stay, he was found to be increasingly aggressive, and behaved out of character. Further review of clinical history revealed that the patient was diagnosed with cognitive impairment and depression one year prior. The patient was agitated, poorly redirectable, and had unstable gait on neurological examination. Magnetic resonance imaging (MRI) of the brain demonstrated restricted diffusion (DWI) along the parietooccipital and temporal regions (L > R) and in the subcortical structures, including the basal ganglia and thalami, with accompanying subtle fluid attenuation inversion recovery (FLAIR) hyperintense signal abnormality in these regions, deemed as artifactual at the time. Repeat MRI brain two months later demonstrated progression of the DWI signal with ADC correlate and FLAIR findings. Cerebrospinal fluid 14-3-3 and RT-QuIC samples were positive. Upon passing a few months later, brain autopsy and Western Blot confirmed the CJD diagnosis. Literature review was conducted on PubMed to identify CJD cases initially diagnosed as psychiatric disorder. Search terms included "CJD" or "Creutzfeldt-Jakob disease" with three common psychiatric diagnoses, "Depression," "Psychosis," and "Mania." Positive EEG, MRI, PET, and CSF (including protein 14-3-3 and tau) findings for CJD were found in 66.7, 81.1, 50, and 72.7% of cases, respectively. Overall, CJD can present as a psychiatric mimic. In suspicious cases, EEG, imaging, and CSF studies should be promptly utilized to arrive at the correct diagnosis. Repeated MRI imaging is often required to help in the diagnostic process. Brain biopsy should be considered in selected cases.

A rare case of rapidly progressive dementia- Creutfeldt Jakob disease: Case report

Background: Creutzfeldt Jakob disease is a rare and usually fatal neurodegenerative disorder characterized by rapidly progressive dementia with other neuropsychiatric manifestations like pyramidal, extrapyramidal, cerebellar, visual and behavioral abnormalities. Here we report a case of clinically probable Creutzfeldt Jakob disease in a 55 years old service holder lady presented with rapidly progressive dementia. Objective: The aim was to report a rare case of rapidly progressive dementia caused by Creutzfeldt Jakob disease. Methods: The case was thoroughly evaluated clinically then probable diagnosis was made by characteristic generalized periodic discharges on EEG and cortical and basal ganglia hyperintensity on FLAIR and DWI sequences of MRI of brain in addition to the clinical features of rapidly progressive dementia, rigidity, myoclonus, akinetic mutism and behavioral abnormalities. Other causes of dementia were excluded. Result: Finally probable diagnosis of Creutzfeldt Jakob disease was done according to CDC diagnostic criteria. The case could not be confirmed due to lack of available newer investigations in our country and refusal of autopsy by the patient’s guardian. Conclusion: Though rare, a suspicion of Creutzfeldt Jakob disease should be considered in patients with rapidly progressive dementia with complex neurological manifestations. Variable clinical presentation and rarity of the disease always delay the diagnosis. The disease is always fatal and no accepted treatment is available till date. So if early and accurate diagnosis is possible then the prognosis and plan of management could be explained to the caregiver properly. Bangladesh Med Res Counc Bull 2023; 49: 190-194

Hyperintensity on Diffusion‐Weighted MRI and Clinical Correlations in Probable Creutzfeldt‐Jakob Disease

AbstractBackgroundAlthough definite diagnosis for Creutzfeldt‐Jakob disease(CJD) requires tissue confirmation, diffusion‐weighted imaging (DWI) of the brain has an important role in the diagnosis of CJD. Also elevated CSF total tau (t‐tau) is considered as an useful CJD biomarker revealing neuro‐axonal damage although it is not specific for CJD. In this study, we attempted to find out the association between DWI abnormality and CSF t‐tau in CJD patients.MethodWe retrospectively analyzed the medical records reported as human prion disease.The patients who had been diagnosed and reported as human prion disease to Korea Disease Control and Prevention Agency (KDCA) by medical institutions in South Korea during the period of January 1, 2019 to December 31, 2019 were included in this study. The clinical information of the reported patients had been reviewed by a clinical review committee of KDCA for CJD and the patients who had fulfilled the criteria for probable CJD were evaluated for clinical, radiological, and laboratory findings.ResultA total of 186 patients had been reported as suspected human prion disease during the one‐year period and 53 patients who satisfied the criteria for human prion disease were included in the analysis. The most common clinical presentation was cognitive change, followed by cerebellar dysfunction and extrapyramidal symptoms. Hyperintense lesions on DWI were observed in 52 patients (98%). The involvement of neocortex was observed in almost all patients (98%) and asymmetrical and bilateral hyperintensities on DWI were common. Among neocortex, the most commonly involved region was parietal lobe, followed by frontal lobe, temporal lobe, and occipital lobe. DWI abnormality in striatum and/or thalamus was observed in 65.3% of patients. CSF t‐tau was elevated in sporadic CJD patients (8998.3±11903.7 pg/ml) There was no significant association between the extent of the lesions on DWI and CSF t‐tau.ConclusionIn this study,most of the patients with probable CJD showed DWI abnormality mainly on neocortex (parietal > frontal > temporal > occipital) but the association between the pattern of DWI abnormality and the level of CSF t‐tau was not observed.

Magnetic resonance imaging arterial spin labeling hypoperfusion with diffusion-weighted image hyperintensity is useful for diagnostic imaging of Creutzfeldt-Jakob disease.

Magnetic resonance imaging with arterial spin labeling (ASL) perfusion imaging is a noninvasive method for quantifying cerebral blood flow (CBF). We aimed to evaluate the clinical utility of ASL perfusion imaging to aid in the diagnosis of Creutzfeldt-Jakob disease (CJD). This retrospective study enrolled 10 clinically diagnosed with probable sporadic CJD (sCJD) based on the National CJD Research & Surveillance Unit and EuroCJD criteria and 18 healthy controls (HCs). Diffusion-weighted images (DWIs), CBF images obtained from ASL, N-isopropyl-(123I)-p-iodoamphetamine (123IMP)-single-photon emission computed tomography (SPECT) images, and 18F-fluorodeoxyglucose (18FDG)-positron emission tomography (PET) images were analyzed. First, the cortical values obtained using volume-of-interest (VOI) analysis were normalized using the global mean in each modality. The cortical regions were classified into DWI-High (≥ +1 SD) and DWI-Normal (< +1 SD) regions according to the DWI-intensity values. The normalized cortical values were compared between the two regions for each modality. Second, each modality value was defined as ASL hypoperfusion (< -1 SD), SPECT hypoperfusion (< -1 SD), and PET low accumulation (< -1 SD). The overall agreement rate of DWIs with ASL-CBF, SPECT, and PET was calculated. Third, regression analyses between the normalized ASL-CBF values and normalized SPECT or PET values derived from the VOIs were performed using a scatter plot. The mean values of ASL-CBF (N = 10), 123IMP-SPECT (N = 8), and 18FDG-PET (N = 3) in DWI-High regions were significantly lower than those in the DWI-Normal regions (p < 0.001 for all); however, HCs (N = 18) showed no significant differences in ASL-CBF between the two regions. The overall agreement rate of DWI (high or normal) with ASL-CBF (hypoperfusion or normal) (81.8%) was similar to that of SPECT (85.2%) and PET (78.5%) in CJD. The regression analysis showed that the normalized ASL-CBF values significantly correlated with the normalized SPECT (r = 0.44, p < 0.001) and PET values (r = 0.46, p < 0.001) in CJD. Patients with CJD showed ASL hypoperfusion in lesions with DWI hyperintensity, suggesting that ASL-CBF could be beneficial for the diagnostic aid of CJD.

MRI abnormalities in Creutzfeldt–Jakob disease and other rapidly progressive dementia

ObjectiveTo investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt–Jakob disease (CJD).MethodsOne hundred and seven patients with diagnosis of prion disease (60 with definite sCJD, 33 with probable sCJD and 14 with genetic prion disease) and 40 non-prion related RPD patients (npRPD) underwent brain MRI including DWI and FLAIR. MRIs were evaluated with a semiquantitative rating score, which separately considered abnormal signal extent and intensity in 22 brain regions. Clinical findings at onset, disease duration, cerebrospinal-fluid 14-3-3 and t-tau protein levels, and EEG data were recorded.ResultsAmong patients with definite/probable diagnosis of CJD or genetic prion disease, 2/107 had normal DWI-MRI: in one patient a 2-months follow-up DWI-MRI showed CJD-related changes while the other had autopsy-proven CJD despite no DWI abnormalities 282 days after clinical onset. CJD-related cortical changes were detected in all lobes and involvement of thalamus was common. In the npRPD groups, 6/40 patients showed DWI alterations that clustered in three different patterns: (1) minimal/doubtful signal alterations (limbic encephalitis, dementia with Lewy bodies); (2) clearly suggestive of alternative diagnoses (status epilepticus, Wernicke or metabolic encephalopathy); (3) highly suggestive of CJD (mitochondrial disease), though cortical swelling let exclude CJD.ConclusionsIn the diagnostic work-up of RPD, negative/doubtful DWI makes CJD diagnosis rather unlikely, while specific DWI patterns help differentiating CJD from alternative diagnoses. The pulvinar sign is not exclusive of the variant form.

A Case Series of RT-QuIC Positive Sporadic Creutzfeldt-Jakob Disease-First Two Cases from Malaysia

Creutzfeldt-Jakob disease (CJD) is invariably a fatal neurodegenerative disorder that presents rapidly progressive dementia with multifaceted involvement of the nervous system. In this case series, we present case reports of two elderly patients diagnosed with sporadic CJD who presented with rapid progression of cognitive decline and myoclonus. Supportive findings on further investigations included cortical ribboning on diffusion-weighted MRI brain; generalised periodic complexes on electroencephalogram with positive cerebrospinal fluid 14-3-3 and pathogenic prion protein (PrPSc) detection on RT QuIC confirming the diagnosis of sporadic CJD in both cases to a great extent.

Creutzfeldt‐Jakob Disease (CJD): Time from Symptom Onset Until Subnormal Magnetic Resonance Imaging (MRI) of brain

AbstractBackgroundAbnormal MRI of brain is one out of three supportive diagnostic criteria for CJD along with abnormal EEG and positive 14‐3‐3 protein when there is rapidly progressive dementia (RPD), myoclonus, visual or cerebellar disturbance, pyramidal or extrapyramidal dysfunction, akinetic mutism. MRI can be normal in CJD even when the symptoms are advanced posing a diagnostic challenge. The goal of this study was to review cases of RPD suspected to be due to CJD and correlate with the diagnostic findings.MethodsCohort of patients with RPD and/or neuropsychiatric presentation suspicious for CJD over the 10 years at our institution was identified using EPIC Slicer Dicer tool to search electronic medical records. Clinical presentation and diagnostic markers including CSF (protein 14‐3‐3, RT‐QuIC, total‐tau), MRI and EEG findings were analyzed to determine the sensitivity of each at early disease state.ResultsTotal of 25 cases suspected of CJD were identified. 4 patients were confirmed to have probable CJD based on positive RT‐QuIC, protein 14‐3‐3 and elevated total‐tau. Initial suspicion for CJD was later not considered high enough to pursue CSF analysis in 4 patients. 1 patient didn’t have CSF study done due to technical error. 16 patients were tested negative for RT‐QuIC. Out of the 16 patients 4 had elevated protein 14‐3‐3, out of which 3 had elevated total‐tau. Out of 25 patients 24 had MRI, 1 couldn’t undergo MRI due to MRI incompatible cardiac pacemaker. Out of 24 patients 4 had findings suggestive of CJD on the initial MRI, 2 of them confirmed to have CJD based on CSF studies. 2 patients had normal initial MRI despite multiple symptoms of CJD. The first patient developed classic findings for CJD on repeat MRI 8 months from symptom onset and the 2nd had such MRI changes 4 months from symptom onset. These 2 patients had diagnosis confirmed by positive RT‐QuIC, 14‐3‐3 protein and elevated total‐tau.ConclusionWhile abnormal MRI findings support the diagnosis of probable CJD in the correct clinical setting, negative test results don’t exclude diagnosis of CJD. CSF markers and a repeated brain MRI are instrumental for correct CJD diagnosis.

Real-time quaking-induced conversion assay using a small-scale substrate production workflow for the diagnosis of Creutzfeldt-Jakob disease.

The lack of a dedicated surveillance program for prion disease, particularly in low- and middle-income countries (LMICs), has hindered the global effort to address this public health threat. Although cerebrospinal fluid (CSF) Real-time quaking-induced conversion (RT-QuIC) is considered the most reliable test for sporadic Creutzfeldt-Jakob disease (sCJD), its availability in LMICs is limited due to its cost and technical difficulty in generating the recombinant prion protein substrate (recPrP). This study aimed to evaluate the performance of RT-QuIC with recPrP produced in-house through a small-scale method - i.e. the application of reusable pre-packed chromatography columns and subsequent dialysis. Here, CSF specimens from patients suspected of having prion disease were consecutively collected and stored between October 2015 and January 2023. Electronic medical record data were reviewed to clinically classified participants as probable sCJD or non-sCJD. CSF RT-QuIC was performed using in-house recPrP. Its specificity and sensitivity for diagnosing probable sCJD were reported, along with details of other clinical data and investigations. We found that among 39 eligible participants, with a median (interquartile range) age of 64 (56-70) years and 16 (41%) female, 13 had probable sCJD and the remaining 26 unequivocally suffered from non-prion disorders. Magnetic resonance imaging and electroencephalogram were suggestive of sCJD in 100% (13/13) and 46.2% (6/13) of sCJD participants, respectively. RT-QuIC was positive in 12/13 sCJD participants (sensitivity 0.92, 95% confidence interval (CI) 0.67-0.99) and negative in all non-sCJD participants (specificity 1.00, 95%CI 0.87-1.00). CSF tau/p-tau ratio showed sensitivity and specificity of 0.62-1.0 and 0.85-1.0, respectively. In summary, RT-QuIC using recPrP generated through a small-scale workflow demonstrated great performance in detecting sCJD. Given its performance results along with its low cost, this technique could feasibly be implemented in LMICs and potentially be the first step towards establishing local prion disease surveillance programs.

Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) as a differential diagnosis of Creutzfeldt-Jakob disease.

Steroid-responsive encephalopathy in autoimmune thyroiditis (SREAT) is characterised by a wide range of neuropsychiatric symptoms and elevated thyroid antibodies. SREAT can mimic sporadic Creutzfeldt-Jakob disease (sCJD) and distinguishing between both entities is important because SREAT responds to corticosteroids. Data of patients reported to the National Reference Centre for the Surveillance of CJD in Göttingen, Germany between August 1994 and October 2008 was retrospectively reviewed. In the case and control groups, 49 patients had SREAT and 48 had sCJD with elevated thyroid antibodies. Antibodies against thyroid peroxidase were the most common antibodies in both SREAT (86%) and sCJD (88%), followed by antibodies against thyroglobulin (SREAT, 63.3%; sCJD, 39.6%; p = 0.020) and TSH-receptor-antibodies (SREAT, 14.3%; sCJD, 2.1%; p = 0.059). Epileptic seizures were observed more frequently in the SREAT group (SREAT, 44.9%; sCJD, 12.5%; p < 0.001). Dementia (SREAT, 61.2%; sCJD, 100%; p < 0.001), ataxia (SREAT, 44.9%; sCJD, 89.6%; p < 0.001), visual impairment (SREAT, 22.4%; sCJD, 50%; p = 0.005), extrapyramidal disorder (SREAT, 32.7%; sCJD, 60.4%; p = 0.006), myoclonus (SREAT, 38.8%; sCJD, 81.3%; p < 0.001) and akinetic mutism (SREAT, 6.1%; sCJD, 37.5%; p < 0.001) were observed more frequently in sCJD. Cerebrospinal fluid (CSF) pleocytosis was observed more frequently in SREAT patients (SREAT, 33.3%; sCJD, 6.4%; p = 0.001), as was a pathological increase in protein concentration (SREAT, 68.8%; sCJD, 36.2%; p = 0.001). In a case of encephalopathy, the diagnosis of SREAT should also be considered in suspected cases of CJD so as to be able to start corticosteroid treatment quickly.

Total Tau Level in Cerebrospinal Fluid as a Predictor of Survival in Creutzfeldt-Jakob Disease: A Retrospective Analysis.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and universally fatal neurodegenerative disorder with highly variable survival times, ranging from weeks to years. However, there are currently no tools for prognosticating a patient's survival time. This study aims to fill this gap by examining the relationship between CSF total tau (t-tau) levels and time to death in patients with CJD. We use cases with CJD recorded in the electronic health record of a tertiary academic medical center from 2010 to 2022. We identified 29 cases with diagnosis of CJD. Using a Cox proportional hazards model, we find that elevated t-tau levels (>4,000 pg/mL) are associated with 9.62 (95% confidence interval: 1.93-47.92) times the hazard of death compared with CJD patients with t-tau less than 4,000 pg/mL. This finding supports the use of CSF t-tau as a prognostic biomarker for CJD.

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.

Unusual Presentations Accentuating the Diagnostic Confusion of CJD (P2-6.010)

<h3>Objective:</h3> To report an unusual case of Creutzfeldt-Jakob Disease (CJD) presenting with worsening extrapyramidal symptoms preceding the onset of cognitive dysfunction. <h3>Background:</h3> CJD is a fatal progressive neurodegenerative disease mediated by misfolded proteins or prions. While definitive diagnosis requires histopathological confirmation, diagnostic criteria exist to predict the disease antemortem. However, only a few patients with CJD meet all components of this criteria. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 71-year-old healthy female presented with 2-months of recurrent falls and intermittent jerking of left arm and leg that started 5 days after her COVID-19 vaccine booster. At baseline she lives by herself and can manage her 10-acre property. On exam, she has appropriate mood, intact cognition, and orientation. Speech was dysarthric and was rigid in all muscle groups associated with hyperreflexia. The intermittent left hemibody jerking was consistent with focal myoclonus associated with spike and wave discharges on EEG. Brain magnetic resonance imaging (MRI) showed increased signal in the bilateral caudate, putamen, medial thalami, and right cerebral cortex on diffusion-weighted imaging. Cerebrospinal fluid (CSF) analysis showed normal cell count, protein and negative for autoimmune/paraneoplastic antibodies. While in the hospital over a few weeks her symptoms progressed to akinetic mutism, and she developed cognitive dysfunction. Real-time Quaking Induced Conversion (RT-QuIC), T-tau protein, and 14-3-3 protein ultimately resulted positive on CSF confirming diagnosis of CJD. She was discharged home with palliative care. <h3>Conclusions:</h3> Unusual presentations in a rare fatal condition like CJD can mimic many other neurological conditions at presentation. This can pose challenges in diagnosis and providing the prognosis to the caregivers. <b>Disclosure:</b> Mrs. Weeks has nothing to disclose. Dr. Mannyam has nothing to disclose. Dr. Bhatti has nothing to disclose. Dr. Gunturu has nothing to disclose.

Clinical Correlates of Cerebrospinal Fluid 14-3-3 Protein in Non-Prion Rapid Progressive Dementia.

The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable biomarker for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, it has also been detected in various non-prion-related rapidly progressive dementia (RPD), which affected its diagnostic performance and clinical utilization. To investigate the general disease distribution with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features in patients with non-prion RPD. A total of 150 patients with non-prion RPD were enrolled. The clinical data were collected and CSF 14-3-3 test was performed for all patients. The distribution of various diseases with a positive 14-3-3 result was analyzed and the association of CSF 14-3-3 with clinical features was tested. The CSF 14-3-3 protein was detected in 23.3% of non-prion RPD patients, and the most frequent diagnoses were autoimmune encephalitis (22.9%) and neurodegenerative disease (22.9%). CSF 14-3-3 protein was more common in older patients (p = 0.028) and those presenting myoclonus (p = 0.008). In subgroup analysis, the positive 14-3-3 test was more common in neurodegenerative disease with a long time from the symptom onset to CSF 14-3-3 test (p = 0.014). CSF 14-3-3 protein could be detected in a broad spectrum of non-prion RPD. In particular, patients with autoimmune encephalitis and rapidly progressive neurodegenerative diseases and those with myoclonus have a greater likelihood of a positive 14-3-3 result. These results could help clinicians interpret the results of CSF 14-3-3 protein more reasonably.

Biomarkers and clinical presentations in Creutzfeldt‐Jakob Disease

AbstractBackgroundThe ability to detect malformed prion proteins using real‐time quaking‐induced conversion (RT‐QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt‐Jakob disease (CJD), facilitating earlier recognition of affected patients. Recognizing this, we evaluated the frequency of clinical features and biomarker results at initial evaluation in patients with CJD and determined the relationship between these early features and CJD diagnosis and prognosis.MethodClinical data were extracted from the electronic medical records of patients with probable or definite (pathologically confirmed) CJD assessed at Mayo Clinic from 2014‐2021. Diagnoses of probable CJD were established by clinical consensus, referencing the Centers for Disease Control and Prevention diagnostic criteria. Clinical features and biomarkers results were evaluated at presentation, and associations with CJD diagnosis and symptomatic disease duration determined.ResultOne‐hundred fifteen patients were included (40, [35%] with definite CJD). Mean age‐at‐symptom onset was 64.8±9.4 years; 68 patients were female (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD (e.g., stereotyped EEG abnormalities (16%), CSF 14‐3‐3 (60%)) was poor. Biomarkers with good diagnostic sensitivity included RT‐QuIC (93%), t‐tau levels &gt;1149 pg/mL (88%), and characteristic signal abnormalities on MRI (77%). Multivariable linear regression confirmed shorter survival for patients with myoclonus (125.9 days, 95%CI 23.3‐15.5, p=0.026), visual/cerebellar signs (180.19 days, 95%CI 282.2‐78.2, p&lt;0.001), positive 14‐3‐3 (193 days, 95%CI 304.9‐82.9; p&lt;0.001), and elevated t‐tau levels (each 1000 pg/ml increase was associated with a nine‐day shorter time‐to‐death, 95%CI 1‐18; p=0.041).ConclusionCSF RT‐QuIC and elevated t‐tau levels, and stereotyped MRI abnormalities continue to be strongly associated with the diagnosis in the modern era, while other clinical findings (myoclonus) and biomarkers results traditionally ascribed to CJD (e.g., PSWC on EEG, 14‐3‐3) offered less value in the diagnostic evaluation. Detection of visual or cerebellar features, myoclonus, CSF 14‐3‐3, and t‐tau levels may predict disease duration, justifying inclusion in the evaluation of CJD‐suspected patients.

Evaluation of the impact of CSF prion RT-QuIC and amended criteria on the clinical diagnosis of Creutzfeldt-Jakob disease: a 10-year study in Italy

BackgroundThe introduction of the prion Real-Time Quaking-Induced Conversion assay (RT-QuIC) has led to a revision of the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD).Validation studies are needed for the amended...

Analysis of Clinical Features, Diagnostic Tests, and Biomarkers in Patients With Suspected Creutzfeldt-Jakob Disease, 2014-2021

Detection of prion proteins in cerebrospinal fluid (CSF) using real-time quaking-induced conversion (RT-QuIC) assays has transformed the diagnostic approach to sporadic Creutzfeldt-Jakob disease (CJD), facilitating earlier and more complete recognition of affected patients. It is unclear how expanded recognition of affected patients may affect the diagnostic and prognostic relevance of clinical features and diagnostic tests historically associated with CJD. To evaluate clinical features and diagnostic testing in patients presenting with CJD and determine the associations of these features with prognosis. This cohort study incorporated data from electronic medical records of patients with CJD treated at Mayo Clinic Enterprise tertiary care centers in Rochester, Minnesota; Jacksonville, Florida; and Scottsdale, Arizona. Participants included patients with definite or probable CJD assessed from 2014 to 2021. Data were analyzed October 2021 to January 2022. Dominant presentation, clinical features, and diagnostic tests associated with CJD. The outcomes of interest were the sensitivity and prognostic value of clinical features and accessible diagnostic tests at presentation with possible CJD. A total of 115 patients were identified, including 40 patients (35%) with definite CJD. Mean (SD) age at symptom onset was 64.8 (9.4) years, and 68 patients were women (59%). The sensitivity of clinical markers (myoclonus) and tests historically considered in patients with suspected CJD was poor (eg, stereotyped electroencephalography anomalies: 17 of 105 patients [16%]; elevated CSF protein 14-3-3 levels: 54 of 90 patients [60%]). By comparison, biomarkers with good diagnostic sensitivity at presentation included RT-QuIC (66 of 71 patients [93%]), CSF total tau (T-tau) level greater than 1149 pg/mL (81 of 92 patients [88%]), and characteristic signal anomalies on magnetic resonance imaging (88 of 115 patients [77%]). Multivariable linear regression confirmed shorter survival in patients with myoclonus (difference, -125.9 [95% CI, -236.3 to -15.5] days; P = .03), visual or cerebellar signs (difference, -180.2 [95% CI, -282.2 to -78.2] days; P < .001), elevated CSF protein 14-3-3 levels (difference, -193 [95% CI, -304.9 to -82.9] days; P < .001), and elevated T-tau level (difference for every 1000 pg/mL elevation, -9.1 [95% CI, -17.7 to -1.0] days; P = .04). These findings suggest that CSF RT-QuIC, elevated CSF T-tau level, and stereotyped magnetic resonance imaging anomalies were associated with the diagnosis of CJD, while other clinical findings (eg, myoclonus), stereotyped electroencephalography anomalies, and CSF protein 14-3-3 levels offered less diagnostic value. Visual or cerebellar features, myoclonus, and CSF 14-3-3 and T-tau levels may be associated with disease duration, justifying continued inclusion in the evaluation of patients suspected to have CJD.