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I Zerr

Publications and source records attributed to I Zerr.

66 records · Page 4Linked to original sources
PubMed1997

Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for CJD, tau-protein concentrations in CSF were significantly higher than in two control-groups of patients with other diseases (median 13,153 pg/ml, range 1,533-27,648 pg/ml; P = 0.0001). One group comprised 19 patients who were seen in the same study and were diagnosed as having other dementing diseases (tau concentration: median 558 pg/ml, range 233-1,769 pg/ml). The second control group comprised 13 patients from our hospital with no dementing disease (tau concentration: median 296 pg/ml, range 109-640 pg/ml). We conclude that determination of tau protein levels in CSF is a useful marker for laboratory diagnosis of CJD.

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PubMed1997

[Expanded illness spectrum of human spongiform encephalopathies or prion diseases].

Since its first description by H.G. Creutzfeldt and A. Jakob, six forms of human spongiform encephalopathies have been described. Besides Creutzfeldt-Jakob disease (CJD), a new variant CJD (nvCJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and potentially familial progressive subcortical gliosis have been reported. The most likely causative agent of these and at least six animal-transmissible spongiform encephalopathies (TSE) is a structurally altered form of a regular cellular protein, designated prion. The best known animal forms are bovine spongiform encephalopathy (BSE) and scrapie. The clinical spectrum of human spongiform encephalopathies has been expanded in recent years by the discovery of new, partially genetically determined forms. The currently available clinical, neurophysiological, neuroradiological, biochemical and molecular-biological methods permit only a probable diagnosis of CJD. A definite diagnosis can only be achieved by the neuropathological demonstration of the pathological prion protein (PrPSc). The transmission of BSE to humans has neither been shown nor definitely excluded.

Animals↗
PubMed1997

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Adult↗
PubMed1997

Diagnosis of Creutzfeldt-Jakob disease and related human spongiform encephalopathies.

Spongiform encephalopathies are transmissible diseases (TSE) of animals and humans. With the appearance of bovine spongiform encephalopathy (BSE) in 1986 and in 1996 with the identification of an apparently new variant of the human spongiform encephalopathy Creutzfeldt-Jakob disease (CJD), great concerns of a potential transmission of BSE to humans have been voiced. The agent known to transmit CJD and other human and animal spongiform encephalopathies is designated as prion, i.e., proteinaceous infectious agent, due to the absence of evidence for the involvement of a nucleic acid in disease transmission. In humans the clinical diagnosis of typical CJD cases can now be supported by paraclinical parameters. Electroencephalographic changes, so called periodic sharp wave complexes, are pathognomonic for CJD but by no means specific. The detection of neuronal enzymes in the cerebrospinal fluid (CSF) such as neuron specific enolase (NSE) or glial proteins such as S-100 aids greatly in the diagnosis of a human spongiform encephalopathy. By far the most specific marker in CSF are a group of proteins designated 14-3-3. Current evidence suggests that by including elevated levels of NSE (> or = 35 ng/mL), S-100 (> or = 8 ng/mL) and tau protein in the CSF and the presence of 14-3-3, a laboratory supported diagnosis of CJD can be achieved which in the appropriate clinical setting has a better diagnostic accuracy than the currently used clinical and paraclinical diagnostic criteria alone.

Animals↗
PubMed1996

Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid.

BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on clinical and electroencephalographic criteria which do not allow a reliable diagnosis to be made during life. METHODS: Serum and cerebrospinal fluid (CSF) samples were obtained after informed consent from relatives of suspected cases of CJD referred to the German CJD surveillance unit. CSF samples from 58 definite (neuropathologically verified), 46 probable, and 34 possible CJD cases, and from 44 patients without CJD were analysed by two-dimensional gel electrophoresis (2-DE). Two investigators blinded to clinical findings recorded the presence of two proteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared with the determination of neuron-specific enolase (NSE) in CSF. NSE concentrations of more than 35 ng/mL were considered indicative of CJD. FINDINGS: p130/131 was detected in 81% of definite (47/58), 80% of probable (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases. NSE concentrations of more than 35 ng/mL were seen in 79% of definite (46/58), 80% of probable (37/46), 59% of possible (20/34) CJD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% CI 0.86-0.99). Of 13 cases initially classified as possible and later reclassified as definite, ten cases were identified correctly by the 2-DE analysis, indicating a better diagnostic accuracy of this test compared with the current clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE. INTERPRETATION: 2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG.

Adult↗
PubMed1996

Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

OBJECTIVE: To assess the sensitivity, specificity, and interobserver reliability of periodic sharp wave complexes in the electroencephalograms of patients with Creutzfeldt-Jakob disease. DESIGN: Sixty-eight electroencephalograms in 29 patients who had been suspected of having Creutzfeldt-Jakob disease were reanalyzed by an investigator who was unaware of the clinical data. The incidence of periodic sharp wave complexes in neuropathologically confirmed Creutzfeldt-Jakob disease vs progressive dementia other than Creutzfeldt-Jakob disease was assessed. Blinded electroencephalogram analysis was performed by a second investigator. The interobserver reliability was assessed by the kappa value. SETTING: University hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. PATIENTS: Fifteen patients with neuropathologically confirmed Creutzfeldt-Jakob disease and 14 patients who had been suspected of having Creutzfeldt-Jakob disease because of rapidly progressive dementia but in whom other dementias were diagnosed by unblinded investigators based on clinical and electroencephalographic criteria. MAIN OUTCOME MEASURE: Sensitivity and specificity of periodic sharp wave complexes assessed by their incidence in Creutzfeldt-Jakob disease vs other dementias. Interobserver reliability of periodic sharp wave complexes was expressed by the kappa value. RESULTS: For periodic sharp wave complexes, blinded electroencephalographic analysis resulted in a sensitivity and a specificity of 67% and 86%, respectively. Interobserver reliability was excellent (kappa = 0.95). CONCLUSION: This blinded electroencephalographic study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.

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PubMed1996

Apolipoprotein E phenotype frequency and cerebrospinal fluid concentration are not associated with Creutzfeldt-Jakob disease.

OBJECTIVE: To analyze the distribution of apolipoprotein E (Apo E) phenotypes between patients with Creutzfeldt-Jakob disease (CJD) and control subjects. SETTING: University hospital, base of the German National CJD Surveillance Study. DESIGN: Prospective case-control study. SUBJECTS: Sixty-two patients with definite or probable CJD, 90 patients with initial suspected CJO, and 51 controls matched for age, sex, and place of residence. MAIN OUTCOME MEASURES: Phenotyping of Apo E in serum by isoelectric focusing, assessment of the gels by 3 independent investigators, measurement of of Apo E in cerebrospinal fluid using an enzyme-linked immunosorbent assay, and calculation of Kaplan-Meier cumulative survival plots. RESULTS: The most frequent phenotype was E 3-3 with 56% in patients and 59% in controls, followed by E 3-4 with a frequency of 29% vs 25%, respectively. The phenotype E 3-2 was much rarer (13% vs 16%, respectively). Patients with definite CJD had a mean (SD) Apo E concentration of 3.4 (2.0) mg/L; patients with probable CJD, 3.1 (1.6) mg/L; patients with possible CJD, 3.8 (2.2) mg/L; and subjects with other diseases, 3.0 (1.7) mg/L. Mean (SD) disease duration for patients with E 3-2 was 11.8 (9.8) months; for patients with E 3-3, 12.0 (9.02) months; and for patients with E 3-4, 14.2 (12.3) months. CONCLUSIONS: We found no significant difference in the distribution of Apo E phenotypes between patients with CJD and controls. The concentration of Apo E in cerebrospinal fluid cannot be taken as a biochemical marker for the disease. The Apo E phenotype had no influence on the duration of CJD. Our data do not support an association of Apo E4 with either the duration or time at onset of CJD.

Adult↗
PubMed1996

MR imaging of Creutzfeldt-Jakob disease.

PURPOSE: To describe the magnetic resonance (MR) imaging appearance of Creutzfeldt-Jakob disease (CJD). MATERIALS AND METHODS: MR images obtained in 29 patients who died of CJD (aged 53-77 years at death) were retrospectively reviewed by three neuroradiologists blinded to the diagnosis. RESULTS: Moderate to marked bilateral, symmetrically increased signal intensity was demonstrated in the putamen and caudate nucleus on T2- and proton-density-weighted MR images in 23 patients (79%). In six patients (21%), images showed no major signal intensity abnormalities. T1-weighted images revealed no signal intensity abnormalities and no contrast material enhancement. The degree of atrophy in the cortex and basal ganglia corresponded to the time between onset of symptoms and MR imaging. All patients with a disease duration of longer than 4 months had substantial volume loss. CONCLUSION: Although approximately 20% of the patients did not have MR imaging abnormalities, MR imaging did show signal intensity alterations due to gliosis and spongiform changes early in the course of CJD in the remaining 80%. The demonstration of bilateral areas of increased signal intensity that predominantly affected the caudate nuclei and the putamina on long-repetition-time MR images in an elderly patient with rapidly progressive dementia represents a specific finding and clearly should suggest the diagnosis of CJD.

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PubMed1995

Prion disease associated with a novel nine octapeptide repeat insertion in the PRNP gene.

Some cases of spongiform encephalopathies are linked to mutations within the prion protein gene (PRNP). Repetitive octapeptide insertions of variable length in the PRNP gene are also associated with spongiform encephalopathies, mostly familial Creutzfeldt-Jakob disease (CJD). In this study we report on a novel insertion mutation comprising nine extra octapeptide repeats between codons 51 and 91 of the PRNP gene. The affected patient showed a slowly progressive dementia of at least 6 years duration and ataxia.

Adult↗
PubMed1995

Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease.

Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94.0, interquartile range 256 ng/mL) were significantly higher (p < 0.001) than in 26 control patients (9.5, 15.5 ng/mL). At a cut-off of 35 ng/mL an optimum sensitivity of 80% with a specificity of 92% for the diagnosis of Creutzfeldt-Jakob disease by NSE in cerebrospinal fluid was obtained.

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