Symptoms Of Creutzfeldt-Jakob Disease Research Articles

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.

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

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

Vertigo as unspecific debut of Creutzfeldt-Jakob disease: Case series

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder, rapidly progressive and universally fatal, caused by misfolded infectious proteins, called prions. The symptoms of CJD are progressive dementia, myoclonus, depression, psychosis, ataxia, etc. However, it is not clearly reported in the literature what symptom predominates in the debut of the disease.

The Braak hypothesis in prion disease with a focus on Creutzfeldt-Jakob disease.

This review considers whether the Braak hypothesis on protein propagation could account for prion disease, particularly Creutzfeldt-Jakob disease (CJD). In CJD, we can speculate on the pathological onset region to some degree in reference to the clinical symptoms and magnetic resonance imaging findings. Although relating the Braak hypothesis to prion disease is not straightforward, the following could be proposed based on experimental and previously reported case observations. Pathogenic abnormal prion protein (PrP) deposition in the central nervous system (CNS) probably begins several months or years before clinical symptom onset, signifying the potentiality of a preclinical stage, similar to α-synuclein deposition in Parkinson's disease (PD) and amyloid-β/tau deposition in Alzheimer's disease (AD). Unlike in PD and AD, the initial clinical symptoms of CJD vary by case, and thus the onset lesions must also be various and multiple in the CNS. Based on the pathological findings, particularly of PrP deposition extensively observed in the CNS gray matter of autopsy cases, it could be speculated that in the early disease stage, including the preclinical stage, abnormal PrP spreads from the onset region without directionality or hierarchy. Because each CNS region shows either vulnerability to or resistance against PrP deposition and pathological progression in prion disease, the lesion distribution shows system degeneration. Although pathologically combined cases of type 1 and type 2 PrP patterns are often recognized, type 1 and type 2 PrP patterns must never shift toward each other during the disease course; in other words, the original type of PrP deposition in each region presumably remains unchanged in each case. According to the several observations and corresponding speculations, there are at least partial similarities between prion disease and protein propagation, as explained by the Braak hypothesis, in terms of pathological lesion progression, but several noted contradictions preclude the hypothesis from comprehensively accounting for prion disease.

Metal homeostasis disturbances in neurodegenerative disorders, with special emphasis on Creutzfeldt-Jakob disease - Potential pathogenetic mechanism and therapeutic implications.

Creutzfeldt-Jakob disease (CJD) is characterized by a rapidly progressive dementia often accompanied by myoclonus and other signs of brain dysfunction, relying on the conversion of the normal cellular form of the prion protein (PrPC) to a misfolded form (PrPSc). The neuropathological changes include spongiform degeneration, neuronal loss, astrogliosis, and deposition of PrPSc. It is still unclear how these pathological changes correlate with the development of CJD symptoms because few patients survive beyond 2years after diagnosis. Inasmuch as the symptoms of CJD overlap some of those observed in Alzheimer's, Parkinson's, and Huntington's diseases, there may be some underlying pathologic mechanisms associated with CJD that may contribute to the symptoms of non-prion neurodegenerative diseases as well. Data suggest that imbalance of metals, including copper, zinc, iron, and manganese, induces abnormalities in processing and degradation of prion proteins that are accompanied by self-propagation of PrPSc. These events appear to be responsible for glutamatergic synaptic dysfunctions, neuronal death, and PrPSc aggregation. Given that the prodromal symptoms of CJD such as sleep disturbances and mood disorders are associated with brain stem and limbic system dysfunction, the pathological changes may initially occur in these brain regions, then spread throughout the entire brain. Alterations in cerebrospinal fluid homeostasis, which may be linked to imbalance of these metals, seem to be more important than neuroinflammation in causing the cell death. It is proposed that metal dyshomeostasis could be responsible for the initiation and progression of the pathological changes associated with symptoms of CJD and other neurodegenerative disorders.

A Crertzfeldt-jakob disease case presenting with psychiatric symptoms

Creutzfeldt Jakob Disease is an incurable and invariably fatal degenerative brain disease. Sporadic and variant forms of the disease can be observed among patients. We report on a patient for calling attention to clinical features and laboratory findings of Creutzfeldt-Jakob Disease and the psychiatric prodromal symptoms. This case demonstrates that manic symptoms may also be a presenting symptom of Creutzfeldt-Jakob Disease and this diagnosis should be considered when there is rapid deterioration in cognition is observed with presence of psychiatric and neurological symptoms

The alien limb phenomenon and Creutzfeldt–Jakob disease

IntroductionAlien limb phenomenon (ALP) has been rarely reported as a presenting feature of Creutzfeldt–Jakob disease (CJD), though neurologists may not recognize it as a prompt to search for CJD. ObjectiveThis report demonstrates the clinical features of patients with ALP and CJD. MethodsAll patients with the ALP between 1/1/1996 – 7/28/2011 were identified by the Mayo Clinic Medical Record Linkage system and cross-referenced with a diagnosis of CJD in that same time span. This yielded 13 patients, including six women. ResultsThe median age at onset of CJD symptoms was 69 years. Two patients were classified as possible CJD, five as probable CJD, and six as definite CJD based on research diagnostic criteria for CJD. The median time to onset of ALP symptoms was 0.5 weeks. The ALP afflicted the left side in nine patients. The median time to death from CJD symptom onset was 10.5 weeks. In four patients ALP was the initial and sole neurologic sign. In four others it was the initial manifestation coexisting with other deficits. ALP related symptoms initially prompted three other patients to seek medical evaluation. ALP was either initially or eventually accompanied by ipsilateral hemineglect, ideomotor apraxia and/or cortical sensory loss in nine patients. Imaging of the contralateral parietal lobe demonstrated cortical T2 hyperintensity and/or restricted diffusion in all eight patients who had abnormal MRI neuroimaging. ConclusionsALP should trigger suspicion of CJD. The neuroanatomic correlate of ALP in CJD appears to be the contralateral parietal lobe.

The Alien Limb Phenomenon & Creutzfeldt-Jakob Disease (P03.257)

Objective: To report clinical features of patients with alien limb phenomenon (ALP) associated with Creutzfeldt-Jakob disease (CJD). Background CJD is a rare prion disease that destroys cortical and subcortical neurons. The classic clinical signs of CJD are rapidly progressing dementia, ataxia, and myoclonus. Although ALP has been described in a few patients with CJD, there are no large case series assessing ALP caused by CJD. The neuroanatomic correlate of ALP in CJD is unknown. Design/Methods: Using the Mayo Clinic Medical Records Linkage system and the authors9 personal case series, we identified all patients evaluated at our institution between 1/1/1996-7/28/2011 with concomitant ALP and CJD. Only patients meeting strict clinical criteria for ALP and CJD were included. Results: We identified 13 patients, including six women. The median age at onset of CJD symptoms was 69 years (range 39-73). Two patients were classified as possible CJD, five as probable CJD, and six as definite CJD (with pathologic confirmation). The median time to onset of ALP symptoms was 0.5 weeks (range 0-16 weeks). The ALP afflicted the left side in nine patients and only one patient in that group was left hand dominant. The median time to death from CJD symptom onset was 10.5 weeks (range 8-64 weeks). In four patients ALP was the sole presenting neurologic sign. In four others it was the initial manifestation coexisting with other deficits. ALP prompted three other patients to seek initial evaluation. ALP was either initially or eventually accompanied by ipsilateral hemineglect, ideomotor apraxia and/or cortical sensory loss in nine patients. The contralateral parietal lobe demonstrated T2 hyperintensity and/or restricted diffusion in all eight patients who had abnormal MRI neuroimaging. Conclusions: ALP can be a feature of CJD. Isolated or early ALP should trigger suspicion of CJD. The neuroanatomic correlate of ALP in CJD appears to be the contralateral parietal lobe. Disclosure: Dr. Rubin has nothing to disclose. Dr. Graff-Radford has nothing to disclose. Dr. Boeve has nothing to disclose. Dr. Josephs has nothing to disclose. Dr. Aksamit has nothing to disclose.

Clinical aspects of common genetic Creutzfeldt-Jakob disease

Clinical aspects of common genetic Creutzfeldt-Jakob disease

A Case of Familial Creutzfeldt-Jacob Disease (V180I) Initially Presenting with Depression

Creutzfeldt-Jakob disease (CJD) is a degenerative neurological disorder that is incurable and invariably fatal. It is characterized by rapidly progressive dementia presenting with memory loss, personality changes and hallucinations. The symptoms of CJD are caused by progressive death of neurons in the central nervous system, which is associated with build-up of the abnormal prion proteins forming amyloids. In human, CJD can be acquired genetically through a mutation of the gene encoding for the prion protein (PRNP). This occurs in only 5-10% of all CJD cases. We report a 64-year old woman with CJD carrying a V180I mutation that features late onset, rapid progression, no periodic sharp wave complexes on electroencephalography, and cortical signal change and edema in bilateral frontotemporoparietal lobes and basal ganglia on MRI.

Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report

Event Abstract Back to Event Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report Eero Pekkonen1*, Juha Wilenius2, Jukka Lyytinen1, Anders Paetau3, Maarit Palomäki4 and Jyrki Mäkelä5 1 University of Helsinki, Department of Neurology, Finland 2 University of Helsinki, BioMag laboratory, Finland 3 University of Helsinki, Department of Pathology, Finland 4 University of Helsinki, Department of Radiology, Finland 5 Helsinki University Central Hospital, BioMag laboratory, Finland Creutzfeldt-Jakob Disease (CJD) is a rare neurodegenerative disease, which belongs to a group of spongiform encephalopathies termed prion diseases.Main symptoms of CJD are progressive dementia, py-ramidal and extrapyramidal symptoms, and myoclonus. Currently there is no effective therapy for CJD. Definite diagnosis is based on autopsy findings.Here we report a male patient with a rapidly progres-sive memory disorder, ataxia and myoclonus. EEG showed slow wave activity, and head MRI revealed in-creased basal ganglia and left-dominant increase in cor-tical signal intensity. In cerebrospinal fluid (CSF) 14-3-3 test was positive. The autopsy confirmed the sporadic CJD.A 306-channel MEG measurement was performed to the patient. Spontaneous brain activity and auditory evoked fields (AEF) were recorded.Both hemispheres had slow wave activity and periodic sharp waves, activity being more pronounced in the left, more damaged, hemisphere. The source of auditory N100m were more lateral in the left than in the right hemisphere. P200m was larger and more posterior in the left hemisphere compared with the right hemisphere. This is the first MEG-recording of a patient with spo-radic CJD. The more damaged left hemisphere in MRI had more pronounced slow and sharp waves in MEG. The sources of auditory responses and amplitude of later 200m deflection were different between the more and less damaged hemispheres. MEG appears to be suitable to investigate and locate brain activity in prion diseases. Conference: Biomag 2010 - 17th International Conference on Biomagnetism , Dubrovnik, Croatia, 28 Mar - 1 Apr, 2010. Presentation Type: Poster Presentation Topic: MEG: Clinical applications Citation: Pekkonen E, Wilenius J, Lyytinen J, Paetau A, Palomäki M and Mäkelä J (2010). Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report. Front. Neurosci. Conference Abstract: Biomag 2010 - 17th International Conference on Biomagnetism . doi: 10.3389/conf.fnins.2010.06.00286 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Apr 2010; Published Online: 05 Apr 2010. * Correspondence: Eero Pekkonen, University of Helsinki, Department of Neurology, Helsinki, Finland, eero_pekkonen@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Google Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Google Scholar Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä PubMed Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Electroretinograms in three cases of Creutzfeldt-Jakob disease with visual disturbances

To report three cases of idiopathic Creutzfeldt-Jakob disease (CJD) with visual symptoms. Patient 1 initially visited our ophthalmology department complaining of blurred vision. Electro-retinography (ERG) showed a selective reduction of the b wave before she was diagnosed with CJD. Patient 2 had normal ERG results even with severely advanced CJD. However, a reduction of the b wave on ERG was observed 1 month before the patient died. Patient 3 had visual disturbances at the initial visit, but the ERG result was normal even after the CJD had advanced. Atrophy of the visual cortex was later observed. CJD can alter the vision in various ways. The selective reduction of the b wave on ERG indicates the retinal involvement. However, visual disturbances may occur without the retinal implications. Ophthalmologists should be aware that the visual impairment can be the first symptom of CJD.

Creutzfeldt-Jakob Disease in Recipients of Corneal Transplants

Creutzfeldt-Jakob disease (CJD) transmission has been documented to occur from the use of corneal grafts. We report 4 cases of CJD with a history of corneal transplantation and assess the frequency of coincidental CJD among corneal transplant recipients. Medical records and eye bank documents were reviewed. Genetic and neuropathologic tests on available specimens were performed at the National Prion Disease Pathology Surveillance Center. Statistical analyses were used to determine the expected number of coincidental CJD cases among the US population with a history of corneal transplantation. Four CJD decedents with histories of corneal transplantation were identified: 3 from the United States and 1 from Japan. The time from transplant to onset of CJD symptoms ranged from 2 years, 11 months to 18 years. Available eye bank records did not suggest evidence of neurologic illness in the donors. Using corneal transplantation and CJD death data from 1990 through 2006, statistical analyses suggest that a case of coincidental sporadic CJD will occur among the population of corneal transplant recipients approximately every 1.5 years. It is likely that these 4 recipients of transplanted corneas had sporadic CJD. Because of the many corneal transplantations performed each year in the United States, occasional cases of sporadic CJD in this population are expected.

Does the Presentation of Creutzfeldt-Jakob Disease Vary by Age or Presumed Etiology? A Meta-Analysis of the Past 10 Years

Does the Presentation of Creutzfeldt-Jakob Disease Vary by Age or Presumed Etiology? A Meta-Analysis of the Past 10 Years

Novel mutation of the PRNPgene of a clinical CJD case

BackgroundTransmissible spongiform encephalopathies (TSEs), a group of neurodegenerative diseases, are thought to be caused by an abnormal isoform of a naturally occurring protein known as cellular prion protein, PrPC. The abnormal form of prion protein, PrPSc accumulates in the brain of affected individuals. Both isoforms are encoded by the same prion protein gene (PRNP), and the structural changes occur post-translationally. Certain mutations in the PRNP gene result in genetic TSEs or increased susceptibility to TSEs.Case presentationA 70 year old woman was admitted to the hospital with severe confusion and inability to walk. Relatives recognized memory loss, gait and behavioral disturbances over a six month period prior to hospitalization. Neurological examination revealed Creutzfeldt-Jakob disease (CJD) related symptoms such as incontinence, Babinski sign and myoclonus. EEG showed periodic sharp waves typical of sporadic CJD and cerebrospinal fluid analysis (CSF) was positive for the presence of the 14-3-3-protein. As the disease progressed the patient developed akinetic mutism and died in the tenth month after onset of the disease symptoms. Unfortunately, no autopsy material was available. PRNP sequencing showed the occurrence of a point mutation on one allele at codon 193, which is altered from ACC, coding for a threonine, to ATC, encoding an isoleucine (T193I).ConclusionHere we report a novel mutation of the PRNP gene found in an elderly female patient resulting in heterozygosity for isoleucine and threonine at codon 193, in which normally homozygosity for threonine is expected (T193). The patient presented typical clinical symptoms of CJD. EEG findings and the presence of the 14-3-3 protein in the CSF, contributed to CJD diagnosis, allowing the classification of this case as a probable CJD according to the World Health Organization (WHO) accepted criteria.

Serial Diffusion-Weighted MRI of Creutzfeldt-Jakob Disease

The objective of our study was to evaluate the clinical usefulness of MRI findings, including diffusion-weighted imaging, in relation to the clinical signs and symptoms of Creutzfeldt-Jakob disease (CJD). We reviewed nine cases of CJD in which MRI was performed from the early to terminal phase of the disease. MRI findings were correlated before (early phase) and after (intermediate phase) the onset of the characteristic clinical findings of myoclonus and periodic synchronous discharges on electroencephalograms. The chronologic changes in imaging findings were followed from the akinetic mutism to the terminal phase of the disease (terminal phase). T2-weighted images had been obtained in all the patients, and diffusion-weighted images and FLAIR images had been obtained in six patients. We evaluated the images for the presence and location of abnormal signal intensities. During the early phase, the T2-weighted images showed no abnormal findings. The diffusion-weighted images, however, revealed abnormal high signal intensities in the cortex in all patients and in the basal ganglia in five patients. In two cases, there were abnormal signals on FLAIR images that corresponded to diffusion-weighted imaging abnormalities. During the intermediate phase, the area of the high signal intensities on the diffusion-weighted images had expanded and progressive cerebral atrophy had become apparent. During the terminal phase, abnormal high signal intensities in the cerebral cortex and basal ganglia on the diffusion-weighted images in one patient disappeared. Diffusion-weighted imaging is extremely useful in detecting CJD during the very early phase-even before the onset of characteristic clinical findings.

Eye banking and screening for Creutzfeldt-Jakob disease.

To quantify the risk of Creutzfeldt-Jakob disease (CJD) among cornea donors, evaluate supplemental screening strategies, and address concerns about the adequacy of current methods of screening tissue donors in the United States. Reported data on deaths due to CJD and from all causes were used to estimate the rate of CJD among cornea donors. The impact of increased screening on risk of CJD and donor supply was evaluated. Only 1.3 of the approximately 45 000 cornea donors in the United States each year might be expected to have CJD. Most of the estimated risk (91%) is due to preclinical (asymptomatic) disease and therefore could not be eliminated by screening for signs or symptoms. If only the highest-risk age group (60 to 69 years) were screened and specificity were 90%, more than 21 000 otherwise acceptable donors would incorrectly be excluded over a period of 17.5 years to correctly exclude a single donor with symptomatic CJD. Currently, the risk of CJD transmission following cornea transplantation is remarkably low. Screening for symptoms of CJD would have minimal impact on safety, but would reduce donor supply and likely result in many patients not receiving needed treatment.

Motor evoked potential studies in Creutzfeldt–Jakob disease

Objectives: Motor evoked potentials (MEPs) were recorded in 7 cases of Creutzfeldt–Jakob disease (CJD) to asses the involvement of pyramidal motor pathways in these cases. The diagnosis of CJD was confirmed by autopsy in 5 cases and based on clinical data in two cases. Methods: Transcranial (MEP-cortex), root magnetic (MEP-root) and electrical stimulation of peripheral nerves (F-wave, direct M-response) were performed. The cortical excitability threshold, F-wave frequency, MEP amplitudes, peripheral motor conduction velocity, standardized distal latencies and central, root, and F-wave conduction times were evaluated. Results: The results of MEP testing were markedly abnormal. Cortical excitability thresholds were elevated, MEP amplitudes were reduced while the conduction function was rather preserved. The features of functional disturbances and/or loss of upper and lower motor neurons were revealed. They correlated with the advancement of key clinical CJD symptoms (progressive dementia, extrapyramidal and cerebellar signs, myoclonic jerks, mutism and typical periodic EEG changes), while motor lesion signs might only be slight or absent. Conclusions: Conduction slowing, if present, seemed to be secondary to axonal lesion.

Cerebellar basket cells of Creutzfeldt-Jakob disease: immunohistochemical and ultrastructural study.

To elucidate possible abnormalities of cerebellar basket cells of Creutzfeldt-Jakob disease (CJD), seven sporadic cases were examined neuropathologically. Recently, parvalbumin-positive, GABAergic cerebral interneurons have been demonstrated to show early, selective loss in CJD, and the phenomenon is postulated as a cause of characteristic neurological symptoms of CJD. In this study, however, we demonstrated that the basket cells, cerebellar counterparts, were resistant even in patients with severe brain atrophy, and their processes showed intense argyrophilia and immunopositivity to phosphorylated neurofilament. They can newly be listed as CJD-resistant neurons similar to those of the hippocampus and brainstem nuclei. The mechanism to escape cell loss is of great interest, and there might be unknown factors modulating susceptibility within parvalbumin-positive neuronal subgroups. Furthermore, one case showed abnormal positivity with hematoxylin, crystal violet and pyronin in the basket cells. The pyronin positivity was reduced after ribonuclease digestion, suggesting that the causative substance was composed of RNA. Ultrastructurally, the fibers contained free ribosomes and amorphous electron-dense deposits. To our knowledge, such a finding has also not been previously reported.

Molecular analysis of prion protein gene (PRNP) in Korean patients with Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD), a relatively uncommon human dementia, is caused by an unconventional slow infectious agent. Several cases of CJD, clinically or histopathologically diagnosed, have been reported in Korea. In order to confirm the diagnosis of CJD and also differential diagnosis of sporadic and familial types of CJD in Korea, we studied two patients who had symptoms of CJD. The histopathological and immunohistochemical studies showed spongiform neurodegeneration and expression of abnormal isoform of prion protein (PrPSc) in astrocytes. Thus, these two patients were diagnosed CJD. To investigate whether these patients were sporadic or familial type of CJD, the molecular analyses of the prion protein gene (PRNP) were done by restriction fragment length polymorphism (RFLP) and DNA sequencing. In the cases of a healthy Korean and two CJD patients, no point mutation was detected in the known hot spots (178, 180, 200, 210, and 232) and they exhibited wild type PRNP sequences. We concluded that both patients have a sporadic type of CJD, but not familial type.