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P Cras

Publications and source records attributed to P Cras.

At least 19 recordsLinked to original sources
PubMed2006

Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium.

From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion protein gene and brain neuropathology was collected. From 1-1-1998 to 31-12-2004, 188 patients were referred to the surveillance system. In 85 patients a 'definite' diagnosis of sporadic CJD (sCJD) could be made, whereas 26 patients remained 'probable'. We further identified two unrelated patients with an E200K mutation, and two patients with a seven octapeptide repeat insertion in one family. In one patient a familial history was noted but genetic analysis was not performed. In 72 patients different final diagnoses were made, Alzheimer's disease being the most frequent (N = 20). The demographic parameters of the Belgian population were similar to those observed in the rest of Europe. We did notice a significantly increased age-specific incidence (> 6/10(6)/year) of sCJD patients between 70 and 90 years old in the period 2002-2004 compared to 1998-2001 and retrospectively obtained data (1990-1997, p < 0.01). We undertook a detailed clinical and biochemical analysis to investigate this increase but could not identify any reason other than an increased vigilance for the diagnosis. In conclusion, our study identified that in the past sCJD may have been underestimated in patients over age 70 although these patients are both clinically and neurobiochemically similar to the general sCJD phenotype.

Age Distribution↗
PubMed2006

Posterior reversible encephalopathy and Guillain-Barré syndrome in a single patient: coincidence or causative relation?

We report 62-year-old female patient with coincident posterior reversible encephalopathy syndrome (PRES) and Guillain-Barré syndrome (GBS). The first presentation of PRES was a generalised tonic-clonic seizure. A risk factor for PRES was acute arterial hypertension. The diagnosis of PRES was established by MRI (magnetic resonance imaging) and hypertension was treated with labetalol 800mg daily followed by regression of symptoms of PRES. Two days after the seizure the first motor signs of GBS presented with a weakness in both upper arms. The diagnosis of GBS was finally established 6 days after the seizure by clinical evolution, lumbar puncture and electrophysiological findings. After treatment of GBS with intravenous immunoglobulins (IVIg), antihypertensive therapy could be phased out and finally stopped. The patient was discharged after 25 days without any medication. At that time she was completely recovered from PRES and recovering well from GBS. The acute arterial hypertension, the provoking factor of PRES, was probably caused by an autonomic dysfunction in the context of GBS before motor signs of GBS were present but we speculate also that there are other GBS related factors playing a role in PRES. This hypothesis is based on the relatively high coincidence of these two rare syndromes which appears from a review of the literature. One other possible mechanism can be the influence of cytokines, produced in the context of a GBS, on the permeability of blood brain barrier.

Brain Diseases↗
PubMed2006

Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.

Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We investigated whether these proteins also accumulate at an early stage of neuropathogenesis in young DS individuals without neuropathology and in early-onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported. In older DS patients (>37 years), a mixed pattern of APP(+1) immunoreactivity was observed in healthy looking neurons and neurites, dystrophic neurites, in association with neuritic plaques, as well as neurofibrillary tangles. UBB(+1) immunoreactivity was exclusively present in AD type of neuropathology. A similar pattern of APP(+1) and UBB(+1) immunoreactivity was also observed for FAD and much less explicit in nondemented controls after the age of 51 years. Furthermore, we observed accumulation of +1 proteins in other types of tauopathies, such as PiD, frontotemporal dementia, PSP and argyrophylic grain disease. These data suggest that accumulation of +1 proteins contributes to the early stages of dementia and plays a pathogenic role in a number of diseases that involve the accumulation of tau.

Adult↗
PubMed2006

Opsoclonus-myoclonus syndrome: a clinicopathological confrontation.

Opsoclonus-myoclonus syndrome (OMS), a movement disorder characterised by chaotic eye movements and myoclonus, is a rare clinical entity. We present two cases of opsoclonus-myoclonus syndrome of paraneoplastic origin. In the first patient the syndrome was associated with a breast carcinoma and in the second patient with a non small cell lung carcinoma. However none of the commonly associated antibodies were found in these cases. From the neuropathological findings from the first patient we find arguments that support the current hypothesis on the pathophysiology of OMS namely a dysfunction in brainstem and cerebellum. We conclude that in adults with OMS one has to be very suspicious of a possible neoplastic origin of the syndrome. The antibodies associated with some cases of OMS are thought to play a role in the pathophysiology of the syndrome although the exact immunologic mechanism remains unknown. Research into the neuropathological substrate of OMS yields a broad range of abnormalities in brain stem and cerebellum. However none of these findings seem to be pathognomonic. As for the possible therapy of OMS, several immunomodulating strategies can be used with varying success. At present there is no established standard therapy.

Brain↗
PubMed2005

Cerebrospinal fluid biomarkers in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder. Since the emergence of variant CJD (vCJD) vigilance concerning the disease's incidence has increased and the interest in accurate in vivo diagnosis has augmented. So far, a large number of biomarkers has been investigated as aid in the differential diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) and vCJD. These include, among others, neuron-specific enolase (NSE), microtubuli associated protein Tau, S-100beta, amyloid-beta (Abeta(1-42)) and the 14-3-3 protein. Multiple studies have confirmed that CSF detection of 14-3-3 protein by Western blot was the best single biomarker for sCJD with an average sensitivity and specificity of 92%. Also, in genetic and iatrogenic CJD (iCJD) patients with an average disease duration of less than 1 year, 14-3-3 is the best differential biomarker. Unfortunately, the 14-3-3 protein has a lower sensitivity if the disease duration exceeds beyond 1 year in both sporadic CJD and other CJD types (vCJD, and specific genetic or iatrogenic CJD types).

14-3-3 Proteins↗
PubMed2005

14-3-3 {gamma}-isoform detection distinguishes sporadic Creutzfeldt-Jakob disease from other dementias.

We developed a polyclonal antiserum directed to the gamma-isoform of the human 14-3-3 protein and compared the immunoreactivity with a commercially available antibody (CG31). We analysed 14-3-3 in 253 cerebrospinal fluid samples blinded for the diagnosis by western blot and ELISA, with a commonly used polyclonal antiserum (Sc-731) and the gamma specific antibodies. Our patient population consisted of 52 patients with definite sporadic Creutzfeldt-Jakob disease (sCJD) and 201 patients with a different final diagnosis. We obtained similar sensitivity, ranging from 96% to 98% with all antibodies. Of all the samples that were false positive with Sc-731, 50% were negative with both gamma-isoform specific antibodies resulting in a significantly higher specificity (85% v 93%, respectively). If only sCJD and patients with dementia differing from sCJD were analysed we found that 64% of false positives were negative which also resulted in significantly increased specificity and positive predictive value. The gamma-isoform specific antibodies strongly improve the specificity of the immunoblot and might improve worldwide acceptance of the use of the 14-3-3 assay in the differential diagnosis of sCJD.

14-3-3 Proteins↗
PubMed2005

Central neurocytoma presenting with intraventricular hemorrhage: case report and review of literature.

We report a case of a 25 year old man presenting with acute headache, vomiting and nuchal rigidity. Computed Tomography (CT) scan and MRI without contrast showed a right ventricular hemorrhage surrounding a mass lesion. The tumor and hematoma were completely removed by neurosurgical transcortical-transventricular approach. Anatomopathological analysis revealed a central neurocytoma. Central neurocytoma seldom present with hemorrhage. We review 16 cases of neurocytoma with hemorrhage. It is important to recognize central neurocytoma as a cause of intraventricular hemorrhage, especially in adolescents and young adults. Outcome is often favorable when the tumor is completely removed. In some patients the clinical course is more aggressive and additional treatment such as radiotherapy, radiosurgery or chemotherapy is needed.

Adult↗
PubMed2003

Contrast enhancement in Lhermitte-Duclos disease of the cerebellum: correlation of imaging with neuropathology in two cases.

Lhermitte-Duclos disease (LDD), also known as dysplastic gangliocytoma, is a rare cerebellar lesion. It has long been regarded as avascular. We report two patients with surgically proven LDD in whom contrast enhancement was observed on MRI. Neuropathological examination revealed proliferation of veins. We suggest that peripheral enhancement of LDD probably reflects vascular proliferation of the cerebellar venous draining system, and should be considered part of the imaging features of LDD.

Adult↗
PubMed2003

A prospective study of CSF markers in 250 patients with possible Creutzfeldt-Jakob disease.

OBJECTIVE: To investigate various cerebrospinal fluid (CSF) markers that could assist in the clinical diagnosis of Creutzfeldt-Jakob disease (CJD). METHODS: CSF samples were analysed for the presence of 14-3-3 protein, microtubule associated protein tau, and beta amyloid in 250 patients with possible CJD. Densitometric analysis was used to quantify the level of 14-3-3 in all patients. RESULTS: Analysis of the clinical data showed that cerebellar signs or myoclonus combined with progressive dementia were the main features leading to a clinical suspicion of CJD. While 14-3-3 detection had a sensitivity of 100% and a specificity of 92%, tau determination using a threshold of 1300 pg/ml had a sensitivity of 87% and a specificity of 97%. If the protocol for the analysis of 14-3-3 was modified (using densitometric analysis) a higher specificity (97%) could be obtained, but with a lower sensitivity (96%). Maximum sensitivity, specificity, and positive predictive value were obtained with a combination of 14-3-3 and beta amyloid determinations. The concentrations of 14-3-3 and tau in the CSF were reduced in CJD patients with a long duration of disease (more than one year; p < 0.05). The concentrations of 14-3-3 or tau were lowest at the onset or at the end stage of the disease, while the beta amyloid concentration remained low throughout the course of the disease. CONCLUSIONS: Both 14-3-3 and tau protein are sensitive and specific biomarkers for CJD. The combination of 14-3-3 and beta amyloid analysis resulted in the maximum sensitivity, specificity, and positive predictive value. When these biomarkers are used in the diagnosis of CJD, the phase of the disease in which the CSF sample was obtained should be taken into account. Disease duration, dependent on the PrP genotype, also has a significant influence on the level of 14-3-3 and tau in the CSF.

14-3-3 Proteins↗
PubMed2002

Inadvertent intrathecal use of ionic contrast agent.

Intrathecal administration of ionic contrast media may cause severe and fatal neurotoxic reactions due to their hyperosmolarity and ionic nature. They are therefore strictly contraindicated for all radiologic applications involving the central nervous system (e.g., myelography). We present a case in which ioxitalamate was accidentally injected intrathecally. The patient recovered completely due to a combination of the different therapeutic options reported in the literature, including early mechanical ventilation and neuromuscular paralysis, aggressive control of seizures, elevation of head and trunk to prevent cephalad migration of contrast, steroids, cerebrospinal fluid drainage and lavage and prophylactic antibiotics.

Contrast Media↗
PubMed2002

Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt-Jakob disease.

OBJECTIVE: To determine the concentrations of microtubule associated protein tau and multiple phosphorylated tau epitopes in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease (sCJD), dementias, and controls, in order to evaluate their diagnostic use and clinical relevance. METHODS: The CSF concentrations of total tau and phosphorylated tau at epitope 181 were determined by enzyme linked immunosorbent assay in 66 definite and nine probable sCJD patients, and in 97 controls. Other phosphorylated tau epitopes were investigated by western blot. RESULTS: In the sCJD population, determination of 14-3-3 protein and total tau protein concentrations was of the highest diagnostic value, with a sensitivity of 96% and 92%, respectively, and a specificity of 94% and 97%. Two distinct subgroups could be identified among the 75 sCJD patients based on the detection of phosphorylated tau at threonine 181 and serines 199, 202, and 404. A high phosphorylated tau concentration was clinically correlated with a significantly shorter disease duration, early onset of akinetic mutism, and a higher rate of typical EEGs (p < 0.05). CONCLUSIONS: Although the determination of phosphorylated tau levels cannot be used as a diagnostic biomarker, it may prove useful for estimating the prognosis of an sCJD patient. These experiments reconfirm that sCJD is a disease with a complex pathology.

Aged↗
PubMed2001

Early diagnosis of cerebral fat embolism syndrome by diffusion-weighted MRI (starfield pattern).

BACKGROUND: Cerebral fat embolism syndrome is a rare, but potentially lethal, complication of long bone fractures. Neurological symptoms are variable, and the clinical diagnosis is difficult. The purpose of this case study is to demonstrate the value of diffusion-weighted MRI of the brain for early diagnosis of fat embolism syndrome. Case Description- A non-head-injured 18-year-old woman suffered acute mental status changes 21 hours after an uncomplicated fracture of the left tibia. MRI of the brain was performed 48 hours after injury. T2-weighted images showed multiple nonconfluent areas of high signal intensity, which, on the diffusion-weighted scans, were revealed as bright spots on a dark background ("starfield" pattern). We suggest that this indicates areas of restricted diffusion that are due to cytotoxic edema, resulting from multiple microemboli. CONCLUSIONS: High-intensity lesions in the brain on diffusion-weighted images may serve as an early-appearing and more sensitive indicator of the diagnosis of fat embolism in the clinical context of long bone injury without head trauma.

Accidents, Traffic↗
PubMed2001

Influence of the prion protein and the apolipoprotein E genotype on the Creutzfeldt-Jakob Disease phenotype.

We investigated the risk associated with the codon 129 polymorphism in the prion protein gene (PRNP) and apolipoprotein E gene (APOE) isoforms for development of Creutzfeldt-Jakob disease (CJD) (n=126) and the possible influences on the disease pathology and its most important clinical characteristics. The PRNP M129V (PRNP129) polymorphism was determined using both DNA extracted from formalin fixed and paraffin embedded brain tissue (n=59) and leukocyte extracted DNA (n=67). In the latter group also the PRNP open reading frame and the APOE genotype were analysed and compared to a neurologically unaffected, age and sex matched control group (n=79). We found that methionine homozygosity of the PRNP129 increases the risk for developing CJD. PRNP129 also influenced the prion accumulation patterns in brain. The APOE 4 allele was an independent risk factor for developing CJD. We further observed a significant dose dependent APOE 4 effect on the number and type of amyloid-beta plaques in the brain of CJD patients.

Aged↗
PubMed2001

Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination.

Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. Qualitative examination of human brain autopsy material has shown that fragile-X patients exhibit abnormal dendritic spine lengths and shapes on parieto-occipital neocortical pyramidal cells. Similar quantitative results have been obtained in fragile-X knockout mice, that have been engineered to lack the fragile-X mental retardation protein. Dendritic spines on layer V pyramidal cells of human temporal and visual cortices stained using the Golgi-Kopsch method were investigated. Quantitative analysis of dendritic spine length, morphology, and number was carried out on patients with fragile-X syndrome and normal age-matched controls. Fragile-X patients exhibited significantly more long dendritic spines and fewer short dendritic spines than did control subjects in both temporal and visual cortical areas. Similarly, fragile-X patients exhibited significantly more dendritic spines with an immature morphology and fewer with a more mature type morphology in both cortical areas. In addition, fragile-X patients had a higher density of dendritic spines than did controls on distal segments of apical and basilar dendrites in both cortical areas. Long dendritic spines with immature morphologies and elevated spine numbers are characteristic of early development or a lack of sensory experience. The fact that these characteristics are found in fragile-X patients throughout multiple cortical areas may suggest a global failure of normal dendritic spine maturation and or pruning during development that persists throughout adulthood.

Adult↗
PubMed2001

Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease due to a novel presenilin 1 mutation.

The dense-cored plaques are considered the pathogenic type of amyloid deposition in Alzheimer's disease brains because of their predominant association with dystrophic neurites. Nevertheless, in > 90% of cases of Alzheimer's disease amyloid is also deposited in cerebral blood vessel walls (congophilic amyloid angiopathy; CAA) but its role in Alzheimer's disease pathogenesis remains enigmatic. Here, we report a family (family GB) in which early-onset Alzheimer's disease was caused by a novel presenilin 1 mutation (L282V). This was unusually severe CAA reminiscent of the Flemish amyloid precursor protein (A692G) mutation we reported previously, which causes Alzheimer's disease and/or cerebral haemorrhages. In family GB, however, the disease presented as typical progressive Alzheimer's disease in the absence of strokes or stroke-like episodes. Similarly, neuroimaging studies and neuropathological examination favoured a degenerative over a vascular dementia. Interestingly, an immunohistochemical study revealed that, similar to causing dense-cored amyloid plaques, CAA also appeared capable of instigating a strong local dystrophic and inflammatory reaction. This was suggested by the observed neuronal loss, the presence of tau- and ubiquitin-positive neurites, micro- and astrogliosis, and complement activation. Together, these data suggest that, like the dense-cored neuritic plaques, CAA might represent a pathogenic lesion that contributes significantly to the progressive neurodegeneration that occurs in Alzheimer's disease.

Adult↗
PubMed2001

The many faces of human prion diseases in Belgium and the world.

Prion diseases are rare neurodegenerative disorders that always lead to death and that can be transmissible under certain conditions. Although sporadic Creutzfeldt-Jakob's disease (CJD) is the best known human variant of these transmissible spongiform encephalopathies with an incidence of about 1 in 106 inhabitants, several other types of human prion disease have been described (e.g. Familial CJD, Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia,...). In 1996, a variant of CJD has been linked to the epidemic of bovine spongiform encephalopathy (BSE). Therefore, vigilance concerning prion diseases was increased throughout the whole of Europe. In Belgium, a comprehensive, nation-wide study has been conducted both retrospectively (1960-1997) and prospectively (1998-...) to identify prion disease patients. In 1998, a surveillance system has also been created to monitor the incidence of CJD and other prion diseases. Using data from both studies and the surveillance program, the occurrence and phenotype of all types of prion diseases in Belgium was investigated. The sporadic type of CJD was identified in 116 patients, while 4 suffered from a hereditary form. In our series, we could find no evidence for variant or iatrogenic CJD, neither for the more rare types of prion diseases.

Belgium↗