PubMed Health⌕ Search

Biomedical subjects

I Zerr

Publications and source records attributed to I Zerr.

At least 55 records · Page 3Linked to original sources
PubMed1999

The effect of stress on the onset and progression of Creutzfeldt-Jakob disease: results of a German pilot case-control study.

The association between Creutzfeldt-Jakob disease (CJD) and stressful life events was examined in a pilot case-control study in Germany. The study sample consisted of 37 CJD cases and 37 controls, both groups were frequency-matched for age and sex. In standardised interviews of close relatives of the cases and the controls, all stressful life events were assessed and subsequently grouped into one of the following three subgroups: psychosocial stress events, medical operations with hospitalisation, and other serious medical examinations. A significantly higher proportion of CJD cases experienced stressful life events during the last six months before disease onset than controls (65% vs. 32%, p = 0.01), yielding an odds ratio (OR) of 3.85 (95% confidence interval (CI): 1.33-11.30). We found the clearest distinction between cases and controls for the subgroup of medical operations where an OR of 6.97 (95% CI: 0.76-329.20) was observed. Further data indicated that stressful events seem to influence not only the onset of CJD but also the progression of the disease. Although based on a rather small study sample, this pilot case-control investigation suggests evidence that stressful life events in the last six months before disease onset may influence CJD occurrence and may modify the course of disease. This 'stress hypothesis', which is in line with findings from other epidemiological and experimental studies in CJD, is thus a promising direction for future CJD research as it could enlighten the pathophysiological mechanisms and point towards strategies for the prevention and therapy of CJD.

Age Distribution↗
PubMed1999

Isoform pattern of 14-3-3 proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

Two-dimensional polyacrylamide gel electrophoresis of CSF has been used in the diagnosis of Creutzfeldt-Jakob disease (CJD). One of the two diagnostic protein spots was identified as isoform(s) of the 14-3-3 family of abundant brain proteins. This has led to the development of one-dimensional 14-3-3 sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblot, which is currently used to support the diagnosis of CJD. In the present study employing western blot analysis, we have identified the panel of 14-3-3 isoforms that appear in the CSF of 10 patients with CJD compared with 10 patients with other dementias. The results clearly show that the 14-3-3 isoforms beta, gamma, epsilon, and eta are present in the CSF of patients with CJD and can be used to differentiate other dementias. 14-3-3eta also gave a baseline signal in all patients with other dementias, including six patients with Alzheimer's disease. The presence of 14-3-3eta in the CSF of a patient with herpes simplex encephalitis was particularly noteworthy. This study has determined that isoform-specific 14-3-3 antibodies against beta, gamma, and epsilon should be considered for the neurochemical differentiation of CJD from other neurodegenerative diseases.

14-3-3 Proteins↗
PubMed1999

How to improve the clinical diagnosis of Creutzfeldt-Jakob disease.

This paper describes a prospective follow-up of 364 patients initially notified as suspected Creutzfeldt-Jakob disease to a Surveillance Unit in Göttingen, Germany. Six patients were diagnosed as having genetic prion disease by blood analysis and were excluded from the study. After examination and review of the remaining 358, 193 were classified as probable Creutzfeldt-Jakob disease. However, autopsy revealed that five of the 193 did not have Creutzfeldt-Jakob disease (four cases, Alzheimer's disease; one case, cerebral lymphoma). Of the 54 patients classified as possible Creutzfeldt-Jakob disease, 10 had another diagnosis made at autopsy. Two of the 111 cases originally classified as having other diseases were found to have Creutzfeldt-Jakob disease on autopsy. Autopsy evidence, together with follow-up of the patients still living and those who died without autopsy, revealed a broad range of other diagnoses. In the younger age groups, the commonest were chronic inflammatory diseases including Hashimoto encephalitis, whilst rapidly progressive Alzheimer's disease was most common in the older age groups. The presence of 14-3-3 protein in the CSF discriminated better between Creutzfeldt-Jakob disease and other rapidly progressive dementias than did the EEG pattern or the MRI. The inclusion of this CSF protein in the criteria of Masters and colleagues (Ann Neurol 1979; 5: 177-88) improves the accuracy and confidence in the clinical diagnosis of Creutzfeldt-Jakob disease.

14-3-3 Proteins↗
PubMed1999

Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: During an epidemiological study of Creutzfeldt-Jakob disease in Germany, Hashimoto's encephalitis was encountered as a differential diagnosis, which has not yet been described in this context. METHODS: The symptoms and findings of seven patients who fulfilled the criteria for "possible" Creutzfeldt-Jakob disease are presented. RESULTS: A Hashimoto's thyroiditis with antibodies against thyroglobulin or thyroid peroxidase, or both and a hypoechoic thyroid ultrasonogram were found in all cases. Analysis of CSF disclosed an increased leucocyte count in three patients, and a raised CSF:serum concentration ratio of albumin (QA1b) in four patients. The 14-3-3 protein, typical of Creutzfeldt-Jakob disease, could not be detected in any of our patients. No periodic sharp wave complexes, which are typical of Creutzfeldt-Jakob disease, were detected on EEG in any of the cases. By contrast with Creutzfeldt-Jakob disease, which leads to death within a few months, the patients with Hashimoto's encephalitis often recover quickly when treated adequately. All the patients improved after administration of corticosteroids. CONCLUSION: The clinical symptomatology of both diseases may be very similar: dementia, myoclonus, ataxia, and personality change or psychotic phenomena are characteristic symptoms.

Adult↗
PubMed1999

Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.

Adult↗
PubMed1999

[Brain SPECT using Tc-99m-bicisate (ECD) in rapidly progressive dementia syndrome].

We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeldt-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias.

Brain↗
PubMed1999

Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene

The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion protein (PrP) gene are described. Genetic analysis of the mutated allele revealed a sequence of five extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the documented subjects. Neuropathological evaluation showed neuronal loss and gliosis in the neocortex of the 3 examined cases; spongiform degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology and distinct distribution was present in the cerebellum and neocortex ("blurred staining") of 2 examined cases. One subject showed features usually found in sporadic Creutzfeldt-Jakob disease with a punctate type of PrP deposition in the cerebellum. In addition, there were some plaque-like PrP aggregates morphologically similar to the other 2 cases in the molecular layer of the cerebellum, and unusual PrP immunoreactivity ("fleecy staining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.

Journal Article↗
PubMed1999

Familial Creutzfeldt-Jakob disease with a novel 120-bp insertion in the prion protein gene.

The clinical course, neuropathological features, and genetic findings in 3 members of a German family carrying a novel 120-bp insertion in the prion protein (PrP) gene are described. Genetic analysis of the mutated allele revealed a sequence of five extra octapeptide repeats, distinct from those of the two previously reported families with an insertion of this size. There was distinctive variation in the clinical course and the onset and duration of the illness in the documented subjects. Neuopathological evaluation showed neuronal loss and gliosis in the neocortex of the 3 examined cases; spongiform degeneration was found in 2 of them. PrP immunoreactivity of unusual morphology and distinct distribution was present in the cerebellem and neocortex ("blurred staining") of 2 examined cases. One subject showed features usually found in sporadic Creutzfeldt-Jacob disease with a punctate type of PrP deposition in the cerebellum. In addition, there were some plaque-like PrP aggregates morophologically similar to the other 2 cases in the molecular layer of the cerebellum, and unusual Prp immunoreactivity ("fleecy staining") was found in the neocortex. The clinicopathological heterogeneity in the documented family is in accordance with the phenotypic variability associated with previously reported insertions.

Adult↗
PubMed1998

Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD).

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. Genetic and iatrogenic forms have been recognised but most are sporadic and of unknown cause. We have studied risk factors for CJD as part of the 1993-95 European Union collaborative studies of CJD in Europe. METHODS: The 405 patients with definite or probable CJD who took part in our study had taken part in population-based studies done between 1993 and 1995 in Belgium, France, Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from these patients were compared with data from 405 controls. FINDINGS: We found evidence for familial aggregation of CJD with dementia due to causes other than CJD (relative risk [RR] 2.26, 95% CI 1.31-3.90). No significant increased risk of CJD in relation to a history of surgery and blood transfusion was shown. There was no evidence for an association between the risk of CJD and the consumption of beef, veal, lamb, cheese, or milk. No association was found with occupational exposure to animals or leather. The few positive findings of the study include increased risk in relation to consumption of raw meat (RR 1.63 [95% CI 1.18-2.23]) and brain (1.68 [1.18-2.39]), frequent exposure to leather products (1.94 [1.13-3.33]), and exposure to fertiliser consisting of hoofs and horns (2.32 [1.38-2.91]). Additional analyses, for example stratification by country and of exposures pre-1985 and post-1985, suggest that these results should be interpreted with great caution. INTERPRETATION: Within the limits of the retrospective design of the study, our findings suggest that genetic factors other than the known CJD mutations may play an important part in CJD. Iatrogenic transmission of disease seems rare in this large population-based sample of patients with CJD. There is little evidence for an association between the risk of CJD and either animal exposure, or consumption of processed bovine meat or milk products for the period studied.

Adult↗
PubMed1998

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study.

OBJECTIVE: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. DESIGN: Prospective case-control study. SETTING: National Creutzfeldt-Jakob disease surveillance unit. SUBJECTS: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. MAIN OUTCOME MEASURE: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. RESULTS: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P = 0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P = 0.023). CONCLUSION: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy.

Biomarkers↗
PubMed1998

Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease.

The analysis of 14-3-3 protein in cerebrospinal fluid (CSF) was shown to be highly sensitive and specific for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, the predictive value of this test in the clinical diagnosis of, and its relation to, sporadic, genetic, and iatrogenic CJD cases have yet to be established. CSF samples of suspect CJD cases seen in the prospective German surveillance study were tested for the presence of 14-3-3 protein by using a modified western blot (WB) technique. WB detected 14-3-3 protein in 95.4% of definite and 92.8% of probable cases. In two patients classified initially as not having CJD the test was positive, and both were later proved to have definite CJD. The positive predictive value is 94.7% and the negative predictive value is 92.4%. False-positive results in a single CSF analysis were seen in patients with herpes simplex encephalitis, hypoxic brain damage, atypical encephalitis, intracerebral metastases of a bronchial carcinoma, metabolic encephalopathy, and progressive dementia of unknown cause. WB analysis for 14-3-3 protein was positive in only 5 of 10 cases of familial forms of spongiform encephalopathies. CSF analysis for 14-3-3 protein should thus be performed in any case suspect for CJD.

14-3-3 Proteins↗
PubMed1998

Descriptive epidemiology of Creutzfeldt-Jakob disease in six European countries, 1993-1995. EU Collaborative Study Group for CJD.

After the occurrence of bovine spongiform encephalopathy (BSE), there has been concern that transmission of BSE to the human population might result in a change in the epidemiological characteristics of Creutzfeldt-Jakob disease (CJD). A collaborative study of CJD in the European Union was performed from 1993 to 1995, to compare data from national registries for CJD in France, Germany, Italy, The Netherlands, Slovakia, and the United Kingdom. Five hundred seventy-five patients with definite or probable CJD died in the study period with an overall annual mortality rate of 0.71 cases per million. The incidence rates for CJD were similar in all participating countries despite variations in postmortem rates, and age-specific incidence rates were also relatively consistent, with the exception of an increased incidence of CJD in patients younger than 39 years of age in the United Kingdom. In relation to etiological subtypes of CJD, 87% of cases were sporadic, 8% genetic, and 5% iatrogenic. Genetic forms of CJD comprised 80% of all cases in Slovakia, and iatrogenic forms of CJD occurred most frequently in France and the United Kingdom. The statistical data reported here do not provide evidence of a causal link between BSE and CJD in Europe as a whole. However, the study has established baseline epidemiological parameters for CJD in participating European countries, which may be important in the assessment of any future change in the characteristics of CJD as a result of the epidemic of BSE.

Adult↗
PubMed1998

Akinetic mutism as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: Among the classification criteria for the diagnosis of Creutzfeldt-Jakob disease, akinetic mutism is described as a symptom which helps to establish the diagnosis as possible or probable. Akinetic mutism has been anatomically divided into two forms--the mesencephalic form and the frontal form. The aim of this study was to delimit the symptom of akinetic mutism in patients with Creutzfeldt-Jakob disease from the complex of symptoms of an apallic syndrome and to assign it to the individual forms. METHODS: Between April and December 1996, 25 akinetic and mute patients with Creutzfeldt-Jakob disease were consecutively examined. The patients were classified according to the definition of akinetic mutism by Cairns and secondly in accordance with the features constituting the complete picture of an appalic syndrome (defined by Gerstenbrand). RESULTS: From 25 patients with definite Creutzfeldt-Jakob disease, 24 patients showed impoverishment of speech and, after a mean duration of four (range 1.1-11.2) months, almost complete absence of voluntary movements and speech. Seven patients were classified as being mute and akinetic and assigned to the mesencephalic form whereas 13 patients were classified as apallic. One patient was mute without being akinetic and four patients were comatose. CONCLUSION: Diffuse brain damage underlies akinetic mutism in patients with Creutzfeldt-Jakob disease. The term can be used as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease; however, it should be applied very carefully and delimited clearly from the apallic syndrome.

Adult↗
PubMed1998

Phenotypic variability in fatal familial insomnia (D178N-129M) genotype.

OBJECTIVE: To report the clinical and pathologic features of patients with the D178N-129M mutation living in Germany. METHODS: Patients with clinically suspected Creutzfeldt-Jakob disease (CJD) were seen in an ongoing, prospective epidemiologic study from June 1993 to August 1997 throughout Germany. Suspect patients were referred to the CJD unit by the participating hospitals or physicians. Patients were seen by a physician, and each patient underwent a detailed neurologic examination. Prion protein gene (PRNP) analysis was performed to distinguish patients with familial forms of CJD. RESULTS: The constellation D178N-129M was identified in eight individuals; in one patient, the diagnosis was made by neuropathologic examination. Four affected men and five women belong to eight unrelated families. A family history of a neurodegenerative disorder was recalled in only five patients. In contrast to the first reported fatal familial insomnia (FFI) patient, none of our patients complained of severe, untreatable insomnia in the early stages. Dysautonomia was observed in varying degrees in most patients. The clinical course of these patients resembled sporadic CJD. In six patients, brain tissue was available for neuropathologic study. In one patient, the neuropathologic examination showed changes that were more reminiscent of forms of sporadic CJD; in the remaining five, the histopathology was typical of FFI. CONCLUSIONS: The clinical presentation in patients with FFI may vary to a great extent. Genotyping of the patients was crucial in providing laboratory confirmation of the diagnosis of FFI, even when there was no family history of a prion disease.

Adult↗
PubMed1997

[The Creutzfeld-Jakob disease. A sphinx of current neurobiology].

BACKGROUND: Prospective epidemiological studies are being employed to determine the incidence and possible risk factors of Creutzfeldt-Jakob disease (CJD) in five European countries in which bovine spongiform encephalopathy (BSE) occurs at different rates of incidence. PATIENTS AND METHODS: Using a voluntary reporting system throughout the Federal Republic of Germany, suspected cases of CJD were investigated and the incidence calculated. Possible risk factors in patients and control groups were obtained by questionnaire. Serum and cerebrospinal fluid samples served to delineate genetic forms and distinguish the disease from other major dementias. RESULTS: A total of 544 patients with suspected CJD, reported in Germany between 1993 and 1997, were examined. 232 (plus 27 investigated only neuropathologically) were confirmed as definite or probable, an annual incidence per million population of between 0.76 (for 1994) and 0.98 (for 1995), similar to figures from other European countries. In Great Britain, the cases of "new variant" CJD, not yet observed in Germany, were excluded from the calculation of incidence. So far, dementia in the family and handling of horn shavings have been identified as risk factors. A rise in the concentrations of neurone-specific enolase and of S100 protein as well as the demonstration of certain proteins in cerebrospinal fluid (p130/ 131 and 14-3-3, respectively) have been shown as being diagnostically superior to EEG changes. INTERPRETATION: There has so far been no increase in the incidence of CJD within Europe. However, the occurrence of the new variant in Great Britain requires long-term monitoring. The diagnostic criteria used for this can be improved by biochemical methods.

Animals↗