CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathies.

Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/microl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/microl and one of 20 cells/microl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/microl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests.

CSF tests in the differential diagnosis of Creutzfeldt-Jakob disease.

OBJECTIVES: To analyze the diagnostic sensitivity and specificity of various brain-derived proteins (14-3-3, Tau, neuron specific enolase [NSE], and S100b) in the CSF of patients with Creutzfeldt-Jakob disease (CJD) and to analyze biologic factors that modify these parameters. METHODS: CSF was tested for 14-3-3, Tau, NSE, and S100b in 1,859 patients with sporadic, genetic, iatrogenic, and variant CJD, and in 1,117 controls. RESULTS: The highest sensitivity was achieved for 14-3-3 and Tau in sporadic CJD (85% and 86%), and a combined determination of 14-3-3 and Tau, S100b, or NSE increased the sensitivity to over 93%. A multivariate analysis showed that the sensitivity of all tests was highest in patients with the shortest disease duration, age at onset >40 years, and homozygosity at codon 129 of the prion protein gene. In a group of patients with repeated lumbar punctures, a second test also increased the diagnostic sensitivity. CONCLUSIONS: The detection of elevated levels of brain-derived proteins in the CSF in patients with suspected Creutzfeldt-Jakob disease is a valuable diagnostic test. A second lumbar puncture may be of value in patients with atypical clinical course in whom the first test was negative.

Codon 129 polymorphism of the PRNP gene in normal Polish population and in Creutzfeldt-Jakob disease, and the search for new mutations in PRNP gene.

Polymorphism at codon 129 of the prion protein gene (PRNP) is implicated both in susceptibility and phenotype of human prion diseases. We characterized the valine and methionine allele frequency at codon 129 in 109 individuals representing the normal Polish population and in 15 Polish CJD cases. The distribution of the genotype was 45% Met/Met, 39% Met/Val, and 16% Val/Val in the control group whereas, of the CJD cases, 73.3% were homozygous for methionine, 13.3% homozygous for valine and 13.3% were heterozygous. The novel missense mutation (ATG-->ACG) at codon 232 was identified in one of the samples with a GSS phenotype.

[Familial Alzheimer's disease connected with mutation in presenilin gene 1 (P117L)]. / Rodzinna choroba Alzheimera zwiazana z mutacja w genie preseniliny 1 (P117L).

We describe a Polish family with Alzheimer's disease in some of its members. Two sisters were observed and examined--also neuropathologically in the Institute of Psychiatry and Neurology in Warsaw. The disease onset was in our patients at 32 and 33 years. The first symptoms were memory loss and disorientation. Later on myoclonus and extrapyramidal stiffness were noted in both cases. Neurovisualizing examinations performed in both sisters showed diffuse brain atrophy. The symptoms increased rapidly and in short time (several months) the patients became mute and bedbound. They died at age 35 and 37 years. We were informed that the father of the patients suffered from very similar illness and died at age of 37 years and their older brother had the some symptoms and died at the age of 28 years. Post-mortem brain examination disclosed in the both hospitalized cases diffuse atrophy of the cerebral hemispheres, particularly severe in the temporal lobes. Microscopically senile plaques of various types were found in the cortex. The density of the plaques was very high but Alzheimer's fibrillary degeneration was found occasionally only. The amyloid burden in cortex of the examined brains, estimated as the measure of parenchymal amyloidosis beta, was two to six-fold higher in most areas compared with changes in sporadic AD and Down-syndrome cases. DNA was isolated from blood and tissue of both cases and from blood of their 8 children as well. In both patients mutation in presenilin 1 (PS1) gene of Prol 117 Leu was found and it was discovered that 4 persons of their progeniture were carriers of this mutation. The described mutation causes one of the earliest so far reported onset and death in FAD kindreds. Presenilin isolated from both cases and transfected into cultures of murine neuroblastoma and human kidneys provoked production of beta amyloid with increased A-beta 42/40 ratio.

Report on the first polish case of the Gerstmann-Sträussler-Scheinker syndrome.

In the course of epidemiological studies on Creutzfeldt-Jakob Disease in Poland, the authors found a male patient aged 54 years with dementia rapidly progressing for a year and ataxia of the extremities. EEG tracings were abnormal but without features typical of CJD. About six months after hospitalisation the patient died. Neuropathological examination of his brain demonstrated spongiform lesions of medium intensity present mainly in the cortex of frontal and occipital lobes, with slight proliferation of astroglia. In the cerebellar cortex numerous deposits of PAS-positive substance amorphous or in the shape of kuru plaques were disclosed. A smaller number of these plaques were found in the cortex of occipital and temporal lobes, and in the putamen. All deposits stained strongly with monoclonal 3F4 antibody to human prion protein (PrP). Genetic studies disclosed in the 20th chromosome, in the PrP gene, mutation at codon 102 (P102L). Codon 129 was homozygous for methionine (M129M). It was established, moreover, that patient's father had at the same age a similar disease and died after one year and patient's sister died after a six-year-long neurological disease diagnosed as multiple sclerosis. On the basis of clinical, genetic and neuropathological findings the authors diagnosed the Gerstmann-Sträussler-Scheinker syndrome, a familial prion disease with autosomal dominant character. This is the first report on this syndrome in Poland.

[Creutzfeldt-Jakob disease: the most frequent spongiform encephalopathy in humans]. / Choroba Creutzfeldta-Jakoba--najszerzej wystepujaca u ludzi encefalopatia gabczasta.

Creutzfeldt-Jakob disease (CJD) which for many years was interpreted as one of degenerative brain processes is the most frequent spongiform encephalopathy caused by prions--molecules of erroneously conformed protein. In only few percent ill people occurrence of this pathogenic factor occurs as a result of mutation in gene PrP. Because transmissibility of prions was proved it should be supposed that in other cases CJD is a result of "infection" Susceptibility to prions depends in large part on specificity of host proteins. It creates certain individual and species specific barriers. At the present time we witness, fortunately only in single cases, occurrence in people variant CJD caused by prions originated from animals affected by "mad cow disease". Prognosis for human population is dependent on the effectiveness of between species barrier for prions.

Epidemiological studies on Creutzfeldt-Jakob disease in Poland.

The epidemiological, clinical and neuropathological study of Creutzfeldt-Jakob disease (CJD) in Poland was established in 1996. It was preceded by wide, repeated informative action among neurologists and psychiatrists in the whole country. The investigations were partially sponsored by the European Commission (E.C.) as part of the programme Biomed 1. The results obtained by us during the first three years of the study are presented in this paper. In 1996-1998 over 60 probable or possible cases of CJD (or information about them) were referred to our Institute. Neuropathologically typical changes for spongiform encephalopathy were found in 28 cases (among them four cases in laboratories of Medical Schools in Szczecin and Poznan). Neuropathological evaluation was based on paraffin slices stained by H-E, PAS, Bielschowsky, Kanzler-Arendt and Klüver-Barrera methods. In certain cases antibody 3F4 was used. In three patients only clinically probable CJD were diagnosed, since neuropathology was not done. In twenty-five persons, a detailed inquiry form was filled in after the model indicated by the E.C. As the result of processing the whole material, we diagnosed in twenty-four patients a sporadic form of CJD. The remaining case belonged to a family with Gerstmann-Sträussler-Scheinker syndrome. In sporadic CJD cases examined and observed by us no exogenic risk factors for the disease could be detected.

[Considerations of biopsy in neurological diagnosis]. / Uwagi w sprawie stosowania biopsji w diagnostyce neurologicznej.

The evolution is described in the views of neurologists on the indications to brain biopsy in clinical practice. In the 1960 and 1970s the main indication were diffuse progressing processes in brain associated with dementia. Presently, this biopsy is done mainly in cases of focal lesions of unclear aetiology. Technical advances in neurovisual examinations and the development of stereotactic methods sparing the patients open presently extensive possibilities of neuropathological diagnosis of lesions, even those situated deeply in the brain. The ethical and legal principles of the use of biopsies in neurological practice have not changed over years.

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.

[Subacute sclerosing panencephalitis (SSPE) in Poland in 1996-1999. Phase VII of epidemiologic studies]. / Podostre stwardniajace zapalenie mózgu (SSPE) w Polsce w latach 1996-1999. VII etap badan epidemiologicznych.

In the seventh phase of epidemiological studies of SSPE data were gathered on patients who developed the disease in 1996-1999. In this time period the diagnosis was confirmed in only 10 cases (4 in 1996, 4 in 1997, 0 in 1998 and 2 in 1999). This is a significant reduction of incidence in relation to the preceding stages, in particular to the years 1993-1995 in which 49 new cases were still reported. This is not ruling out the possibility that at the beginning of the years 2,000 cases would be diagnosed in which the first symptoms developed several or more months earlier.

Amyotrophic form of Creutzfeldt-Jakob disease with rapid course in 82-year-old man.

The authors present a case of Creutzfeldt-Jakob disease in 82-year-old man. Besides the onset of the disease in the elderly and short survival time (8 weeks), other uncommon clinical and morphological features also characterized our case. An evident amyotrophic syndrome, confirmed in morphological findings, developed soon after the CJD onset. The spongiform change also observed within the white matter of cerebral hemispheres allowed us to diagnose the 'panencephalopathic' form of CJD.

[Prospects of measles and subacute sclerosing panencephalitis (SSPE) elimination in Poland]. / Perspektywy eliminacji odry i podostrego stwardniajacego zapalenia mózgu (SSPE) w Polsce.

Following the introduction of vaccinations against measles in 1975 supplemented in recent years with booster vaccinations at the age of 6 years the epidemiological situation with respect to measles and SSPE has been gradually improving, particularly recently. In the paper discussion is presented on the question in what degree the present epidemiological situation of measles, the epidemiological supervision and vaccinations against measles in Poland meet the operative aim of measles and, consequently, SSPE elimination, as recommended by the WHO Regional Bureau. Attention is called to incomplete reliability of measles diagnosis based on clinical manifestations, economic difficulties in conducting serological investigations (detection of IgM antibodies to measles) necessary for measles confirmation, and shortcomings in vaccination organization.

[A sporadic case of Creutzfeldt-Jakob disease with peculiar neuropathological lesions]. / Sporadyczny przypadek choroby Creutzfeldta-Jakoba o szczególnym obrazie neuropatologicznym.

The authors report a case of Creutzfeldt-Jakob disease in a man aged 60 years from a family without a history of similar disease. The disease extended over 11 months. In the clinical picture initially equilibrium disturbances and dementia with psychotic symptoms predominated, EEG pattern was not typical of CJD. Neuropathological examination revealed extensive spongiform lesions in the cortex of all cerebral lobes, in striatum and substantia nigra, moreover a considerable number of kuru plaques was found in cerebellar cortex. The authors consider that the case meets the criteria accepted for the sporadic form of CJD but believe that the final differentiation from the Gerstmann-Streussler-Scheinker syndrome should be based on genetic studies.

[Neurological status improvement in central pontine myelinolysis in alcohol-dependent patient]. / Poprawa stanu neurologicznego u osoby z mielinoliza mostu uzaleznionej od alkoholu.

The authors report a case of central pontine myelinolysis in a woman aged 30 years addicted to alcohol since at least 30 years. In the diagnosis the principal role was played by MRI. Attention is called to the disproportion between massive brainstem lesion and relatively low extent of neurological symptoms and signs. The patient had a several-weeks alcohol detoxication treatment and general supportive treatment. During that tine the neurological signs regressed nearly completely which suggests considerable reversibility or compensation of brainstem lesions in this syndrome.

[Early diagnosis of Alzheimer's disease by neuroimaging methods]. / Wczesne rozpoznawanie choroby Alzheimera za pomoca metod neuroobrazowania.

Visual examinations of the brain, MRI in particular, are very important but always only auxiliary methods in the diagnosis of Alzheimer's disease. Since several years the results obtained in them could have been confirmed objectively by introduction of various methods for measurement of cerebral structures undergoing atrophy. The development of functional MRI programmes, particularly those of regional blood flow in capillaries, has helped in detection of early Alzheimer lesions. The main difficulty in these diagnostic methods is the continuum of lesions resulting from physiological senescence and those being pathological atrophy of Alzheimer type.

Central nervous system infection caused by Borrelia burgdorferi. Clinico-pathological correlation of three post-mortem cases.

The spirochete Borrelia burgdorferi (B. burgdorferi) may cause severe meningoencephalomyelitis as the sole manifestation of Lyme borreliosis. We would like to present three such cases, where definite neuroborreliosis was clinically diagnosed in two cases and possible neuroborreliosis was recognized in one case. Alive spirochetes were isolated and cultured from blood and cerebrospinal fluid (CSF) in both definite cases. B. burgdorferi as the causative agent of the infection was confirmed in CSF by polymerase chain reaction (PCR) in one definite case. In the possible case spirochetes were cultured from blood and CSF. Alive spirochetes were not isolated, however anti-B. burgdorferi antibody value in serum was significantly elevated. On necropsy gross examination brain edema without focal changes was detected in two cases. Cerebral atrophy was seen in Case 3. Microscopically, lymphocytic infiltrates, microglial diffuse and nodular activation, spongiform changes, diffuse demyelination of the cerebral and cerebellar white matter, and diffuse astrocytosis, were characteristic pathological features in all presented cases. Multifocal, perivascular degenerative changes in the cerebral and cerebellar white matter were observed in the first case. Inflammatory changes in the nuclei and roots of cranial nerves were present in the third case.

[Juvenile form of Huntington's disease--diagnostic problems]. / Dziecieca i mlodziencza postac choroby Huntingtona--problemy diagnostyczne.

Variability of clinical manifestation is an important feature of Huntington's disease (HD). It is due to the high instability of CAG sequences within a coding region of IT15 gene. We present five pedigrees in which apart from the adult form of HD the juvenile form of the disease affected some of the patients--as a result of genetic anticipation. Molecular analysis confirmed the well known fact that anticipation, which manifests itself by earlier onset of the disease in the subsequent generations, is strongly correlated with the degree of amplification of (CAG)n repeats in IT15 gene. An interesting feature of the presented data is the fact, that expansion of CAG repeats occurred not only at the paternal but also at the maternal transmission of the mutation. Some children in the presented HD pedigrees presented other neurological disturbances which could be suspected of HD; a molecular analysis revealing normal number of CAG repeats, enabled us to avoid misdiagnosis. The presented data provide evidence that clinical diagnosis of HD, particularly in cases with not very characteristic clinical picture--is not possible without DNA analysis--even in the families undoubtfully affected with the disease.

[The usefulness of MRI of the central nervous system in certain diseases of blood and hemopoietic system with neurological symptoms]. / Przydatnosc badan MR osrodkowego ukladu nerwowego w niektórych chorobach krwi i ukladu krwiotwórczego przebiegajacych z symptomatologia neurologiczna.

The results are presented of MRI studies of the brain and spinal cord in patients with neurological symptoms in the course of certain diseases of the haemopoietic system (leukaemias, lymphomas). The analysis showed that MR images, although not specific, can be very useful for the evaluation of the intensity and topography of haematological lesions in the central nervous system. However, the diagnosis of these processes is not easy. In the differential diagnosis focal lesions of vasogenic origin, infections and radiation-induced lesions should be considered, and in cases of lymphoma--metastases are a possibility.

[Sequence of clinical changes and evolution of MR images in a case of chronic SSPE]. / Sekwencja zmian klinicznych a ewolucja obrazów MR mózgowia w przewleklym przypadku podostrego stwardniajacego zapalenia mózgu (SSPE).

Slow course case of subacute sclerosing panencephalitis is reported. The onset was at the age of 16 years and death followed after 5 years. He was observed during nine successive hospitalizations and the authors describe the changing clinical symptomatology parallelly with successive EEG records and brain MR imaging evolution. Successive phases of the disease were associated with hyperintense changes in T2-weighted.images, and were situated initially in occipital lobes, and involved later on periventricular areas and finally the whole white matter of both cerebral hemispheres. Subcortical brain atrophy developed parallelly.