Search

Creutzfeldt–Jakob Disease (CJD) is a rare, fatal neurodegenerative disorder that is caused by prion proteins. Patients often present with rapidly progressive dementia, ataxia, myoclonus, memory impairment, visual problems, and changes in personality. In this case report, we aimed to address the course of a 62 year old female who presented with progressive decline in cognitive function and died within 6 months of presentation. The patient underwent cerebrospinal fluid testing, MRI brain, and electroencephalography during her stay in the hospital. Ultimately, an autopsy was performed, which demonstrated spongiform changes, neuronal loss, and astrogliosis, consistent with CJD.

Abstract Objective The goal of the research presented here is to determine if methods previously developed for the aqueous extraction of PrPSc from formalin-fixed paraffin-embedded tissue (FFPET) are applicable to the detection PrPSc by real-time quaking induced conversion (RT-QuIC). Previous work has utilized aqueous extraction of FFPET for detection of transmissible spongiform encephalopathies (TSEs) utilizing western blot and ELISA. This research extends the range of suitable methods for detection of TSEs in FFPET to RT-QuIC, which is arguably the most sensitive method to detect TSEs. Results We found complete agreement between the TSE status and the results from RT-QuIC seeded with the aqueous extract of FFPET samples. The method affords the diagnostic assessment TSE status by RT-QuIC of FFPET without the use of organic solvents that would otherwise create a mixed chemical-biological waste for disposal.

Objective: The goal of the research presented here is to determine if methods previously developed for the aqueous extraction of PrPSc from formalin-fixed paraffin-embedded tissue (FFPET) are applicable to the detection PrPSc by real-time quaking induced conversion (RT-QuIC). Previous work has utilized aqueous extraction of FFPET for detection of transmissible spongiform encephalopathies (TSEs) utilizing western blot and ELISA. This research extends the range of suitable methods for detection of TSEs in FFPET to RT-QuIC, which is arguably the most sensitive method to detect TSEs. Results: We found complete agreement between the TSE status and the results from RT-QuIC seeded with the aqueous extract of FFPET samples. The method affords the diagnostic assessment TSE status by RT-QuIC of FFPET without the use of organic solvents that would otherwise create a mixed chemical-biological waste for disposal. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Creutzfeldt–Jakob disease is a neurodegenerative disorder caused by brain accumulation of a misfolded form of the cellular prion protein, whose diagnosis is challenging, particularly in early stages, due to the variability and nonspecificity of the clinical and radiological features. 18F‐fluorodeoxyglucose positron‐emitted tomography has the potential to be considered a crucial investigation in these patients, revealing metabolic abnormalities earlier than the conventional neuroimaging analysis. A 59‐year‐old man, the military officer, was referred to our Units for the onset of neurological symptoms rapidly evolving within a month, characterized by akinetic mutism, constructional apraxia, and disorders of spatial orientation. Brain 18F‐fluorodeoxyglucose (18F‐FDG) positron‐emitted tomography (PET)/CT depicted an asymmetric hypometabolism in the left fronto‐temporo‐parietal cortex, as well as in the left thalamus and the right cerebellar hemisphere, while the glucose metabolism appears to be preserved in the somatosensory cortex and the basal ganglia. Laboratory routine analyses, cerebrospinal fluid routine, infective tests, electroencephalography (EEG), and brain magnetic resonance (MR) were all unremarkable. A positive RT‐QuIC result on cerebro‐spinal fluid (CSF) was subsequently shown, without any pathogenic gene mutations and, therefore, the result was consistent with a diagnosis of sporadic Creutzfeld–Jacob disease. The clinical evolution was quickly unfavorable, and the patient died about 4 months after hospital admission. FDG PET/computed tomography (CT) has the potential to be considered a crucial investigation in these patients, documenting metabolic changes long time before other diagnostic investigations such as CSF, EEG, brain CT, and brain MR, thus suggesting a greater sensitivity of glucose metabolic evaluation in the early stage of the disease in question. [ABSTRACT FROM AUTHOR]

Key Clinical Message Creutzfeldt–Jakob disease is a neurodegenerative disorder caused by brain accumulation of a misfolded form of the cellular prion protein, whose diagnosis is challenging, particularly in early stages, due to the variability and nonspecificity of the clinical and radiological features. 18F‐fluorodeoxyglucose positron‐emitted tomography has the potential to be considered a crucial investigation in these patients, revealing metabolic abnormalities earlier than the conventional neuroimaging analysis. Abstract A 59‐year‐old man, the military officer, was referred to our Units for the onset of neurological symptoms rapidly evolving within a month, characterized by akinetic mutism, constructional apraxia, and disorders of spatial orientation. Brain 18F‐fluorodeoxyglucose (18F‐FDG) positron‐emitted tomography (PET)/CT depicted an asymmetric hypometabolism in the left fronto‐temporo‐parietal cortex, as well as in the left thalamus and the right cerebellar hemisphere, while the glucose metabolism appears to be preserved in the somatosensory cortex and the basal ganglia. Laboratory routine analyses, cerebrospinal fluid routine, infective tests, electroencephalography (EEG), and brain magnetic resonance (MR) were all unremarkable. A positive RT‐QuIC result on cerebro‐spinal fluid (CSF) was subsequently shown, without any pathogenic gene mutations and, therefore, the result was consistent with a diagnosis of sporadic Creutzfeld–Jacob disease. The clinical evolution was quickly unfavorable, and the patient died about 4 months after hospital admission. FDG PET/computed tomography (CT) has the potential to be considered a crucial investigation in these patients, documenting metabolic changes long time before other diagnostic investigations such as CSF, EEG, brain CT, and brain MR, thus suggesting a greater sensitivity of glucose metabolic evaluation in the early stage of the disease in question.

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Creutzfeldt-Jakob disease is a rare and incurable form of rapidly progressive neurodegenerative disease. The disease is fatal, and most patients die within 1 year of diagnosis. Clinical features include progressive cognitive dysfunction, delusions or hallucinations, cerebellar ataxia, myoclonus, visual disturbances, extrapyramidal signs and eventually akinetic mutism. Most patients present with varied clinical presentation, hence making it difficult to diagnose at an early stage. We report five cases of sporadic Creutzfeldt-Jakob disease presenting to a Tasmanian hospital in Australia over a period of 52 months. We highlight significant clinical features in all our patients including few atypical presentations, emphasise on relevant clinical biomarkers and illustrate characteristic abnormalities on electroencephalogram and neuroimaging. [ABSTRACT FROM AUTHOR]

Yu Sun,1,2 Chih-Ching Liu,3,* Ling-Yun Fan,4,* Chung-Te Huang,5 Ta-Fu Chen,2 Chien-Jung Lu,1,2 Wan-Yuo Guo,6,7 Yang-Chyuan Chang,2,8 Ming-Jang Chiu2,9– 11 1Department of Neurology, En Chu Kong Hospital, New Taipei City, Taiwan; 2Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan; 4Queensland Brain Institute, University of Queensland, St. Lucia, Brisbane, QLD, Australia; 5Center for Research, Diagnostics and Vaccine Development, Taiwan Centers for Disease Control, Taipei, Taiwan; 6Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan; 7School of Medicine, National Yang-Ming University, Taipei, Taiwan; 8Department of Neurology, Min-Sheng General Hospital, Taoyuan, Taiwan; 9Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan; 10Graduate Institute of Psychology, College of Science, National Taiwan University, Taipei, Taiwan; 11Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ming-Jang Chiu Tel +886-2-23123456 ext 65339Fax +886-2-23418395Email mjchiu@ntu.edu.twIntroduction: Epidemiologic studies of Creutzfeldt-Jakob disease (CJD) have been undertaken worldwide since the new variant CJD outbreak in 1996 in the United Kingdom. A nationwide report system, the Creutzfeldt-Jakob Disease Surveillance Unit (CJDSU), directed by the Centers for Disease Control of Taiwan, was established in 1997 to identify human prion diseases.Methods: From 1998 to 2017, 647 cases were referred to the committee for confirmation. The report to CJDSU included a structured questionnaire recording the clinical, demographic data, and potential iatrogenic exposure, and the results of the clinical and laboratory examination, including tests of blood and cerebrospinal fluid, electroencephalography, and brain magnetic resonance imaging.Results: In total, 356 cases (women, n=178) were ascertained to be human prion diseases, and 97.4% (n=347) were sporadic CJD, including three definite, 314 probable, and 30 possible cases; one probable variant CJD and 8 cases of the genetic form human prion diseases. The age- and gender-specific average annual incidence were also significantly higher in the second decade (0.95/1,000,000) than in the first decade (0.63/1,000,000), with an incidence rate ratio of 1.51. The incidences increased with increasing age, reaching a peak at the age of 70– 79 years. The 10-year survival curve for sCJD patients showed that the 1-, 5-, and 10-year cumulative survival rate were 52%, 5%, and 1%, respectively. PRNP polymorphisms in 170 patients showed that 98.8% were M129M and 97.6% E219E.Discussion: The significant increase in incidence after 2008 suggests the increase in the awareness of this rare disease among physicians. The longer disease duration in patients with sCJD in Taiwan than in other countries indicates that the comprehensive support of the health care system, as well as the end-of-life care culture in Taiwan, may prolong survival time in patients with such a progressive and fatal disease.Keywords: human prion diseases, spongiform encephalopathy, incidence, mortality, disease duration

Abstract Background To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson’s and Creutzfeldt-Jakob disease (CJD), linked through copper. Case presentation A 44-year-old male with a history of inherited Wilson’s disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson’s disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14–3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient’s CSF, using the RT-QuIC method, which has a 99.4–100% specificity for CJD, made the diagnosis of CJD highly probable. Conclusion This is the first report of Wilson’s and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD.

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]

Background: Little is known about the clinical characteristics and significance of Creutzfeldt-Jakob disease (CJD) in Mexico. Objective: This study aimed to conduct a retrospective revision and analysis of the clinical cases of Mexican patients with CJD available in the literature. Methods: We systematically searched electronic databases for studies in English and Spanish conducted in Mexico over the period of 1990-2020 that involved Mexican patients with any of the clinical forms of CJD. Clinical variables were extracted from the selected studies that met eligibility criteria. Descriptive statistics were used to characterize the study population. Results: A total of seven studies were included in the analysis. From these, 29 cases were revised, and their clinical characteristics analyzed. The median age at the time of diagnosis was 54 years (range 23-75 years). CJD was more frequent among females than male patients (male:female ratio 1:1.41). Most patients resided in Mexico City and the State of Mexico, and 93% attended public hospitals. The most frequent form of CJD was sporadic, with only two probable cases of familiar disease. The most common clinical symptoms observed in order or frequency were rapidly progressive dementia (68.9%), cerebellar signs (51.7%), neuropsychiatric symptoms (51.7%), akinetic mutism (51.7%), myoclonus (44,8%), extrapyramidal signs (44.8%), visual disturbances (41.3%), pyramidal signs (31%), and sleep disorders (17.2%). Only 20% of the cases were confirmed by histopathological analysis of brain biopsy or autopsy specimens. Conclusions: Our study provides an overview of the main clinical characteristics of CJD in Mexican patients. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative prion disease potentially transmissible through corneal transplantation. While statistical analyses performed two decades ago estimated the overall prevalence of CJD in the corneal donor pool to be low, the recent significant increase in corneal transplants performed and deaths due to CJD in the U.S. warrants a contemporary risk analysis. Methods: A literature review was conducted to determine the overall number of globally reported cases of CJD transmission through corneal transplantation. U.S. mortality and cornea donation data were utilized to estimate the age-stratified prevalence of undiagnosed, latent CJD in the cornea donor pool in 2018. A historical statistical analysis was performed to estimate the number of corneas from donors with latent CJD entering the U.S. donor pool for each year between 1979 and 2018. From these statistical analyses, risk factors of iatrogenic transmission were identified and summarized. Results: Ten reported cases of iatrogenic transmission of CJD through corneal transplants were identified globally. In 2018, an estimated 3.8 corneas from donors with undiagnosed latent CJD potentially entered the pool of 111,703 transplant-intended corneas harvested from individuals aged 31–80. Between 1979 and 2018, an estimated 47 corneas may have entered the U.S. transplant-intended pool from donors with latent CJD aged 35 to 84. The advanced age of donors and a history of multiple transplants in recipients were both prominent risk factors for iatrogenic transmission. Conclusions: The 10 reported global cases of iatrogenic transmission likely under-represent the number of individuals with a coinciding history of death by CJD and prior corneal transplantation, as supported by our statistical analysis and lack of geographical diversity of reported cases. As effective screening methods develop and globalization of cornea transplantation broadens, it is of utmost importance that cornea transplantation history among victims of CJD should be investigated and reported. [ABSTRACT FROM AUTHOR]

Background: To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson's and Creutzfeldt-Jakob disease (CJD), linked through copper. Case presentation: A 44-year-old male with a history of inherited Wilson's disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson's disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14–3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient's CSF, using the RT-QuIC method, which has a 99.4–100% specificity for CJD, made the diagnosis of CJD highly probable. Conclusion: This is the first report of Wilson's and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD. [ABSTRACT FROM AUTHOR]

Traditional tablet filler combinations, lactose-maize starch were replaced with a new dextrinized maize starch-maize starch filler combination. Dextrinization process under controlled conditions was targeted for this purpose and specifications were determined for the dextrinized product. Granules were prepared by wet granulation method using the new filler combination. Placebo tablets T1 were first prepared with lactose-maize starch filler combination as a model. Based on the properties of resulting tablets, lactose was replaced with dextrinized maize starch, introduced a different binder and the active ingredient furosemide anticipating a tablet of acceptable quality. The flow properties of dextrinized maize starch had improved over maize starch with an angle of repose of 40°. Hausner ratio and Carr's index of dextrinized maize starch and lactose were found to be 1.34, 1.54, and 25.45, 35.24 %, respectively favourable to the former. The placebo tablets (T2) prepared with the new filler combination using 12.0 % w/w maize starch binder resulted in unacceptable hardness and friability. However, furosemide tablets (T3) prepared with the new filler combination and the binder solution of low substituted hydroxypropyl cellulose 3.2 % w/w showed excellent physical properties. The study shows that dextrinized maize starch and maize starch filler combination without lactose could be employed successfully in tablet manufacture. [ABSTRACT FROM AUTHOR]

An autosomal recessive disease of Black Russian Terriers was previously described as a juvenile-onset, laryngeal paralysis and polyneuropathy similar to Charcot Marie Tooth disease in humans. We found that in addition to an axonal neuropathy, affected dogs exhibit microphthalmia, cataracts, and miotic pupils. On histopathology, affected dogs exhibit a spongiform encephalopathy characterized by accumulations of abnormal, membrane-bound vacuoles of various sizes in neuronal cell bodies, axons and adrenal cells. DNA from an individual dog with this polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV) was used to generate a whole genome sequence which contained a homozygous RAB3GAP1:c.743delC mutation that was absent from 73 control canine whole genome sequences. An additional 12 Black Russian Terriers with POANV were RAB3GAP1:c.743delC homozygotes. DNA samples from 249 Black Russian Terriers with no known signs of POANV were either heterozygotes or homozygous for the reference allele. Mutations in human RAB3GAP1 cause Warburg micro syndrome (WARBM), a severe developmental disorder characterized by abnormalities of the eye, genitals and nervous system including a predominantly axonal peripheral neuropathy. RAB3GAP1 encodes the catalytic subunit of a GTPase activator protein and guanine exchange factor for Rab3 and Rab18 respectively. Rab proteins are involved in membrane trafficking in the endoplasmic reticulum, axonal transport, autophagy and synaptic transmission. The neuronal vacuolation and membranous inclusions and vacuoles in axons seen in this canine disorder likely reflect alterations of these processes. Thus, this canine disease could serve as a model for WARBM and provide insight into its pathogenesis and treatment.

Creutzfeldt-Jakob disease (CJD), also known as corticostriate spinal degeneration, subacute spongiform encephalopathy or infectious spongiform encephalopathy, is a type of degenerative disease of the central nervous system caused by prion protein (PrP) infection, which is the most common type of human PrP disease. CJD is genetic and infectious, and is one of the most common causes of rapid progressive dementia with rare clinical occurrence. Herein, we report the clinical conditions of 2 cases of patients with different type of CJD we treated and followed up recently, and a review of relevant literature. The patient in case 1 was admitted due to 'dizziness with hypomnesis, and mental and behavior disorder'. He was considered to suffer from a central nervous system infection - a viral encephalitis, but one month later, a repeated cranial MRI showed lace sign of bilateral frontotemporal parietal lobe in DWI sequence, an AEEG indicated periodic synchronous discharge, and the detection of cerebrospinal fluid 14-3-3 protein was positive. It was suggested to be diagnosed as the sporadic CJD. The patient in case 2 was admitted because of 'progressive hypomnesis'. Cerebrospinal fluid 14-3-3 protein detection was negative, but the V203I-related mutation was found in the PRNP gene detection. The patient was suggested to be diagnosed as genetic CJD. Both patients died in a short time. An earlier diagnosis can provide a time window for treatment, and avoid unnecessary transmission in hospital, as well as doctor-patient dispute. [ABSTRACT FROM AUTHOR]

A 73-year-old woman presented with vision loss and recurrent proptosis with conjunctival chemosis 4 weeks after an uncomplicated fat-only orbital decompression for thyroid eye disease. Her Graves disease was biochemically “burnt out,” and she had diabetes mellitus. Initial neuro-imaging showed a straightened optic nerve and orbital apex fat streaking so a bilateral bony decompression of the orbital apex was performed for presumed compressive optic neuropathy. Vision failed to improve, and she experienced cognitive decline. She described metamorphopsia and insomnia. Examination showed a hemifield loss of red sensitivity, difficulties with higher visual processing, and memory problems. Occipital cortical ribboning was seen on diffusion weighted magnetic resonance imaging, cerebrospinal fluid was positive for 14-3-3, and her electroencephalogram showed periodic complexes. A diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. She became akinetic and mute, dying a few months later. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive neurodegenerative disease that almost always results in death in under a year from onset of symptoms. Here, we report four cases of CJD with different clinical presentations diagnosed at our institution over two-year period. Cases: The first patient is an 82-year-old woman who presented with depression, cognitive decline and word-finding difficulty over 4 weeks. The patient deteriorated neurologically to akinetic mutism and death within 6 weeks of presentation. The second patient is a 54-year-old woman with liver cirrhosis who presented with confusion, ataxia and multiple falls over 4 weeks. She was treated initially for hepatic encephalopathy, but continued to progress to mutism, startle myoclonus and obtundation. Death occurred within 4 weeks of presentation. The third patient is a 58-year-old woman who presented with an 8-week history of confusion, urinary incontinence, Parkinsonism, ataxia and myoclonus. Death occurred within 2 months from presentation. The fourth patient is a 67-year-old man who presented with a 6-week history of headache, blurred vision, ataxia and personality change and progressed to confusion, myoclonus, akinetic mutism and obtundation. Death occurred within 3 weeks from presentation. Conclusion: These 4 cases highlight the varied possible clinical presentations of CJD and demonstrate the importance of considering CJD in patients with atypical presentations of rapidly progressive cognitive decline. To diagnose CJD, brain biopsy remains the gold standard. However, the presence of CSF protein 14-3-3, typical MRI findings and suggestive EEG abnormalities all support the diagnosis.

The first case of spongiform encephalopathy in a zebu (Bos indicus) was identified in a zoo in Switzerland. Although histopathologic and immunohistochemical analyses of the central nervous system indicated a diagnosis of bovine spongiform encephalopathy (BSE), molecular typing showed some features different from those of BSE in cattle (B. taurus).

Background: Creutzfeldt--Jakob disease (CJD) is a rare, rapidly progressive neurodegenerative disease that almost always results in death in under a year from onset of symptoms. Here, we report four cases of CJD with different clinical presentations diagnosed at our institution over a 2-year period. Cases: The first patient is an 82-year-old woman who presented with depression, cognitive decline, and word-finding difficulty over 4 weeks. The patient deteriorated neurologically to akinetic mutism and death within 6 weeks of presentation. The second patient is a 54-year-old woman with liver cirrhosis who presented with confusion, ataxia, and multiple falls over 4 weeks. She was treated initially for hepatic encephalopathy but continued to progress to mutism, startle myoclonus, and obtundation. Death occurred within 4 weeks of presentation. The third patient is a 58-year-old woman who presented with an 8-week history of confusion, urinary incontinence, Parkinsonism, ataxia, and myoclonus. Death occurred within 2 months from presentation. The fourth patient is a 67-year-old man who presented with a 6-week history of headache, blurred vision, ataxia, and personality change and progressed to confusion, myoclonus, akinetic mutism, and obtundation. Death occurred within 3 weeks from presentation. Conclusion: These four cases highlight the varied possible clinical presentations of CJD and demonstrate the importance of considering CJD in patients with atypical presentations of rapidly progressive cognitive decline. To diagnose CJD, brain biopsy remains the gold standard. However, the presence of CSF protein 14-3-3, typical MRI findings and suggestive EEG abnormalities, all support the diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Involvement of the outer membrane protein C (OmpC) of Escherichia coli in neurodegeneration was investigated using a mouse model. Results: OmpC formed protease-resistant fibres that exhibited the diagnostic features of an amyloid. The spectral shift in the Congo Red and the thioflavin T assays produced features similar to neurotoxic peptides. Intramuscular administration of OmpC in mice resulted in spongiform neurodegeneration of the brain through calcium-dependent apoptosis and also showed upregulation of apoptosis related genes. Immunolocalization of OmpC in brain demonstrated the direct involvement of the porin in neurodegeneration and formation of spongiform encephalopathy. Conclusion: We have demonstrated the ability of OmpC of E. coli to induce neurodegeneration in mice. [ABSTRACT FROM AUTHOR]

Background: The presence of Aspergillus in the central nervous system (CNS) is rare in immunocompetent patients but not in immunocompromised patients who may have a more common infection. This article describes a case of an adult immunocompetent patient with a diagnosis of cerebral aspergillosis and with a clinical process of rapidly progressive dementia which simulated a Creutzfeldt -Jakob syndrome. Case Description: A 34-year-old adult was previously healthy and had no medical history of any significance. The patient had suffered only facial trauma 8 months before admission. One month prior to admission, he showed rapidly progressing changes in his behavior and higher mental functions. He was admitted to the emergency room with an occipital headache with 2 months of history. By the time he arrived, he suffered from total disability and was prostrate. He was diagnosed with meningeal and demential syndrome in the process of being studied. After starting the diagnostic approach by investigating cerebrospinal fluid, a magnetic resonance of the skull, an electroencephalogram, a brain biopsy was indicated. The histopathological study reported the presence of the hyphae characteristics of Aspergillus. The patient died 7 days after the diagnosis. Conclusion: Cerebral aspergillosis is a common aggressive disease in immunosuppressed patients. However, the disease is rare in individuals with respected immunity and in individuals with neurological impairment and a rapid and progressive deterioration of mental functions. The suspected diagnosis should always be considered given its poor prognosis and the encouraging efficacy of antifungal treatment administered in a timely manner. [ABSTRACT FROM AUTHOR]

An autosomal recessive disease of Black Russian Terriers was previously described as a juvenile-onset, laryngeal paralysis and polyneuropathy similar to Charcot Marie Tooth disease in humans. We found that in addition to an axonal neuropathy, affected dogs exhibit microphthalmia, cataracts, and miotic pupils. On histopathology, affected dogs exhibit a spongiform encephalopathy characterized by accumulations of abnormal, membrane-bound vacuoles of various sizes in neuronal cell bodies, axons and adrenal cells. DNA from an individual dog with this polyneuropathy with ocular abnormalities and neuronal vacuolation (POANV) was used to generate a whole genome sequence which contained a homozygous RAB3GAP1 : c.743delC mutation that was absent from 73 control canine whole genome sequences. An additional 12 Black Russian Terriers with POANV were RAB3GAP1 : c.743delC homozygotes. DNA samples from 249 Black Russian Terriers with no known signs of POANV were either heterozygotes or homozygous for the reference allele. Mutations in human RAB3GAP1 cause Warburg micro syndrome (WARBM), a severe developmental disorder characterized by abnormalities of the eye, genitals and nervous system including a predominantly axonal peripheral neuropathy. RAB3GAP1 encodes the catalytic subunit of a GTPase activator protein and guanine exchange factor for Rab3 and Rab18 respectively. Rab proteins are involved in membrane trafficking in the endoplasmic reticulum, axonal transport, autophagy and synaptic transmission. The neuronal vacuolation and membranous inclusions and vacuoles in axons seen in this canine disorder likely reflect alterations of these processes. Thus, this canine disease could serve as a model for WARBM and provide insight into its pathogenesis and treatment. [ABSTRACT FROM AUTHOR]

Sporadic Creutzfeldt-Jakob disease (CJD) is the most common prion disease. It is a rare, fatal neurodegenerative disease caused by an infectious protein called prion. The diagnosis can be confirmed only by histological examination of brain tissue. Because of the transmissible nature of the disease, autopsy or brain biopsy cannot be performed at many institutions. Histology shows spongiform changes, neuronal loss, reactive astrocytic proliferation, accumulation of pathologic protein occurring in three general forms: Sporadic, familial, and acquired form, including a variant form of CJD. It clinically presents as predominantly progressive dementia with a rapid onset, myoclonus, cerebellar, pyramidal, extra pyramidal and visual signs. Occurrence of periodical spikes in electro-encephalogram, observation of cortical signal alterations in magnetic resonance imaging (MRI) studies, and detection of protein 14-3-3 in cerebrospinal fluid substantiate diagnosis. Autopsy case is presented of a 50 year old woman with progressive dementia, typical neurological symptoms, MRI findings and confirmation of CJD on histology and immunostaining.

The purpose of our study was to describe the progressive accumulation of the abnormal conformer of the prion protein (PrPCWD) and spongiform degeneration in a single section of brain stem in Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease (CWD). A section of obex from 85 CWD-positive elk was scored using the presence and abundance of PrPCWD immunoreactivity and spongiform degeneration in 10 nuclear regions and the presence and abundance of PrPCWD in 10 axonal tracts, the subependymal area of the fourth ventricle, and the thin subpial astrocytic layer (glial limitans). Data was placed in a formula to generate an overall obex score. Data suggests that PrPCWD immunoreactivity and spongiform degeneration has a unique and relatively consistent pattern of progression throughout a section of obex. This scoring technique utilizing a single section of obex may prove useful in future work for estimating the presence and abundance of PrPCWD in peripheral tissues and the nervous system in elk with CWD. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge–like appearance of brain and are responsible for the typical clinical symptoms. In this report, we present 4 cases referred to the neurology department of Uludağ University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease. Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration. [ABSTRACT FROM AUTHOR]

In order to characterize synaptic involvement in human spongiform encephalopathies, the expression of synaptic vesicle-associated proteins, synaptophysin and synapsin-I, and presynaptic plasma membrane proteins, synaptosomal-associated protein of 25 kDa (SNAP-25) and syntaxin-I, was examined in the brains of four patients who had suffered from sporadic Creutzfeldt–Jakob disease. Nerve cell loss, spongiform degeneration, astrocytosis, and deposition of prion protein (PrP) were observed in the cerebral cortex in every case. Decreased immunoreactivity for synaptophysin, synapsin-I, SNAP-25, and syntaxin-I was observed in the cerebral cortex in every case, thus showing generalized reduction of proteins involved in exocytosis of synaptic vesicles in the brains of patients with spongiform encephalopathy. Upregulation of synaptophysin and SNAP-25, a feature associated with βA4 deposits in Alzheimer's disease (AD), was not observed in association with PrP deposition. The present results indicate that synaptic pathology is a major event in spongiform encephalopathy, and suggest that synaptic loss, together with neuron loss and selective involvement of certain populations of local-circuit neurons, as shown in other studies, may account for the dramatic neurological decay and for the main neurological symptoms in patients with CJD.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most commonly diagnosed human prion disease caused by the abnormal misfolding of the 'cellular' prion protein (PrPC) into the transmissible 'scrapie-type' prion form (PrPSc). Neuropathologic evaluation of brains with sCJD reveals abnormal PrPSc deposits primarily in grey matter structures, often associated with micro-vacuolar spongiform changes in neuropil, neuronal loss, and gliosis. Abnormal PrPSc deposits have also been reported in the retina of patients with sCJD, but few studies have characterized the morphology of these retinal PrPSc deposits or evaluated for any retinal neurodegenerative changes. We performed histopathologic and morphometric analyses of retinal and brain prion deposits in 14 patients with sCJD. Interestingly, we discovered that the morphology of retinal PrPSc deposits generally differs from that of brain PrPSc deposits in terms of size and shape. We found that retinal PrPSc deposits consistently localize to the outer plexiform layer of the retina. Additionally, we observed that the retinal PrPSc deposits are not associated with the spongiform change, neuronal loss, and gliosis often seen in the brain. The stereotypic morphology and location of PrPSc deposits in sCJD retinas may help guide the use of ocular imaging devices in the detection of these deposits for a clinical diagnosis. [ABSTRACT FROM AUTHOR]

Creutzfeldt-Jakob disease (CJD) is a transmissible disease of the nervous system causatively related to the presence of an abnormal prion protein, with dementia, myoclonic jerks, and periodic EEG activity. Fourteen patients (7 females and 7 males) ranging from 26 to 76 years of age (median 59 years) were evaluated between 1974 and 1995 at the Neurologic Clinic of São Paulo University School of Medicine. The average duration of the disease was 12 months (3.5 - 34 months). Early clinical findings were: behaviour changes in 7 patients, dementia in 4, visual disturbances in 4, vertigo in 2, tremor in 9, and dystonia in one. Advanced symptoms were dementia and myoclonus in all patients. Pyramidal tract dysfunction was found in 6, cerebellar ataxia in 2, seizures in 3, nystagmus and vertigo in 4, and peripheral nervous system involvement in 2. Atypical clinical forms were found in 5 patients. Periodic EEG activity was found in 10 patients. Cerebrospinal fluid evaluation showed pleocytosis in 1 patient, higher protein content in 2, and higher gamma globulin level in 2. In 10 patients anatomopathological evidence in the central nervous system confirmed the clinical diagnosis by presenting with status spongiosus. All except one patient presented with the sporadic form of the disease.As encefalopatias espongiformes humanas ou doenças priônicas são um grupo de doenças rapidamente progressivas caracterizadas por déficit cognitivo, ataxia, mioclonia e manifestações visuais, piramidais e extrapiramidais. A doença de Creutzfeldt-Jakob (DCT) pode apresentar forma iatrogênica, genética e esporádica. Os autores apresentam 14 pacientes com DCJ forma esporádica e um com forma familial, acompanhados na Disciplina de Neurologia Clínica da FMUSP, no período de 1974 a 1995. Sete eram do sexo feminino e 7 do sexo masculino, com idade variando de 26 a 76 anos (média de 59 anos). As manifestações neurológicas iniciais foram distúrbio do comportamento em 7, demência em 4, deficiência visual em 4, vertigens em 2, tremor em 9 e distonia em um paciente. Posteriormente, demência e mioclonias ocorreram em todos os pacientes. Foram encontrados: disfunção do trato piramidal em 6, vertigens em 4, convulsões em 3, ataxia cerebelar em 2, distúrbio do sistema nervoso periférico em 2. A forma atípica da doença ocorreu em 5 pacientes. Atividade periódica ao eletroencefalograma ocorreu em 10 pacientes. O líquido cefalorraquidiano mostrou pleocitose em 1, hiperproteinorraquia em 2 e hipergamaglobulinorraquia em 2. O estudo anátomo-patológico do sistema nervoso central, feito em 10, revelou alterações vacuolares do neurópilo em todos os pacientes.

Prionpathies represent a group of neurodegenerative diseases of familiar, sporadic or acquired origin, heterogeneous symptoms and fatal outcome. The psychiatric symptoms can be present at the beginning and/or during the clinical evolution, with the presence or not of neurological disorders. Patients with these sympthoms are referred to psychiatric units, both at hospital level and as outpatients, to study a psychiatric disorder. In the described clinical case, the patieht was admitted several times at emergency units, rated by neurologists and psychiatrists leading to different psychiatric disorders diagnoses. However spongiform encephalopathy was diagnosed only during the last month of the disease. [ABSTRACT FROM AUTHOR]

The article presents four pathomorphologically verified cases of sporadic Creutzfeldt-Jacob disease in the Neurology Department of Vilnius University Hospital Santariskiu Klinikos since 2004. The short case analysis and review of the literature are also included. Two of these cases were already published in the Journal "Neurologijos seminarai" 2004 and 2007. The diagnoses of Creutzfeldt-Jacob disease were initially suspected clinically and verified postmortem by histopathological immunohistochemical assay using monoclonal antibodies against protease resistant prion protein (PrP). The article presents clinical features, course, diagnostic examination, and preventive recommendations of sporadic Creutzfeldt-Jacob disease. [ABSTRACT FROM AUTHOR]

This commentary reports of a deer chronic disease (chronic wasting disease - CWD), which might be transmitted to humans. It is due to a prion infection, similar to the bovine spongiform encephalopathy (BSE). At the moment, it is not known if the disease may be transmitted to humans. That is why all of us should be aware of the disease, and more careful while consuming deer meat. [ABSTRACT FROM AUTHOR]

The article discusses the single nucleotide polymorphisms at prion protein (PrPSC) gene's codons Suffolk sheep affected with scrapie in Brazil. The study discovers polymorphisms at 3 of the 15 codons being analyzed. It finds out that most of the animals had genotypes that correspond to the risk group. It also explains the preventive measures associating positive selection and genotyping for disease control.

The article presents research on the effect of comingling of fallow deer or Dama dama with infected mule deer or Odocoileus hemionus. It references a study on Jack C. Rhyan and colleagues published in the same issue of the journal. It examines evidence of prion infection on fallow deer which have been exposed to the chronic wasting disease (CWD) agent from mule deer through lymphoid tissue immunohistochemistry (IHC).

The article discusses the intraspecies transmission studies of transmissible spongiform encephalopathies (TSE) to cattle. The results show cattle's susceptibility to intracerebrally (IC) inoculation of scrapie, transmissible mink encephalopathy (TME), and chronic wasting disease (CWD). Cattle develop spongiform lesions or clinical disease similar to bovine spongiform encephalopathy (BSE) only when inoculated with TME. Cattle's resistance to oral transmission of scrapie or CWD is also noted.

Abstract: It has been known for many years that the offspring of scrapie affected ewes are at increased risk of developing scrapie but whether this is simply the result of an increased genetic susceptibility or transmission of infection has always been unclear. To contribute to clarify this we analysed the data collected in a detailed study of scrapie occurrence in a number of naturally affected commercial sheep flocks in Great Britain (GB) to investigate the association between PrP genotype and parental scrapie status and the incidence of scrapie. Our analyses confirmed the strong association between PrP genotype and the incidence of scrapie found in previous studies and a low incidence of scrapie in animals carrying the ARR allele and a high risk in homozygous VRQ animals. However, we also demonstrate an increased incidence of scrapie in the offspring of scrapie affected ewes controlling for the confounding effect of PrP genotype, but no increased scrapie incidence in the offspring of scrapie affected sires. Our results suggest that some of the increased incidence of scrapie in the offspring of scrapie affected ewes is the result of transmission of infection from mother to offspring. Our results confirm that a breeding policy aimed at decreasing the genetic susceptibility of the population should decrease the incidence of scrapie and that removing the offspring of scrapie affected animals from affected flocks could contribute to the control of this disease. [Copyright &y& Elsevier]

Eleven years after a brief visit to some European countries, a 48-year-old Japanese man developed writing difficulty, irritability and general fatigue. Then he complained of dysesthetic pains in his legs, for which benzodiazepines were prescribed. However, at the time pulvinar sign was retrospectively confirmed on brain MRI. Eighteen months after the onset, his gait became ataxic with rapid deterioration of mental status over the following several months. Thirty-one months after the onset, he became akinetic and mute with periodic synchronous discharges on EEG, and died at the age of 51. The total clinical course was approximately 43 months. Pathological examination revealed the characteristic alterations of spongiform encephalopathy, severe in the thalamus, moderate but widely spread in the cerebral cortices, and moderate in the cerebellum. Abundant amyloid plaques were easily identified in the cerebral cortex and the cerebellum on HE staining. Immunohistochemistry for abnormal prion protein (PrPsc) confirmed amyloid plaques in several forms, such as florid, uni- and multi-centric plaques as well as perineuronal and periaxonal deposits in the basal ganglia and synaptic patterns in the thalami. A Western blotting study identified type 2B protease-resistant PrP. This is the first Japanese patient who was definitely diagnosed as variant Creutzfeldt-Jakob disease (vCJD). The pathological findings were similar to those of previous reports of vCJD in the UK. However, the changes were much more severe both in degree and distribution, probably due to a longer duration of the illness than those in the UK. [ABSTRACT FROM AUTHOR]

The article reports on aspects of scrapie, a naturally occuring fatal neurodegenerative disease of sheep and goats. It states that the susceptibility to the disease is dependent on the genetic makeup of the host. It notes that the present study documents clinicopathologic findings and the distribution of abnormal prion proteins by immunohistochemical and Western blot techniques in tissues of sheep inoculated with sheep scrapie. The sheep developed clinical disease and were euthanized within 7.7 months.