A 13-Year-Old Girl Affected by Melanocytic Tumors of the Central Nervous System-The Case.

Primary intracranial melanoma is a very rare brain tumor, especially when accompanied by benign intramedullary melanocytoma. Distinguishing between a primary central nervous system (CNS) lesion and metastatic melanoma is extremely difficult, especially when the primary cutaneous lesion is not visible. Here we report a 13-year-old girl admitted to the Neurosurgery Department of the Institute of Polish Mother's Health Centre in Lodz due to upper limb paresis.

Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases.

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons. Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP.

Neuropathological consensus criteria for the evaluation of Lewy pathology in post-mortem brains: a multi-centre study.

Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and colleagues (Beach). All of these systems use semi-quantitative scoring (4- or 5-tier scales) of Lewy pathology (LP; i.e.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms.

Sensitive detection of FGFR1 N546K mosaic mutation in patient with encephalocraniocutaneous lipomatosis and pilocytic astrocytoma.

Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous disorder, with only about 100 cases reported worldwide. It is characterized by congenital lesions of the eye, skin, and central nervous system. Only recently, potential causative FGFR1 point mutations have been identified in brain tumors and cultured skin biopsies from patients with this condition.

Kuru, the First Human Prion Disease.

Kuru, the first human prion disease was transmitted to chimpanzees by D. Carleton Gajdusek (1923⁻2008). In this review, we summarize the history of this seminal discovery, its anthropological background, epidemiology, clinical picture, neuropathology, and molecular genetics.

Light and electron microscopic studies of the 139A-H strain of scrapie passaged in hamsters.

We report here the light and electron microscopic neuropathology of the 139A-H strain of scrapie passaged in Syrian golden hamsters. The general neuropathological picture consisted of the spongiform change and severe astrocytic gliosis. The topography of prion protein (PrP) was variable, the highest signal was observed in the CA2-molecular layer, CA1-pyramidal and entorhinal cortex.

Dystrophic neurites accumulating autophagic vacuoles show early stages of neuritic destruction.

We re-examined the database of some 20,000 electron micrographs from the Echigo-1, the 263K-strain or the 22C-H of scrapie-infected hamsters to look for the cytoplasmic clearance. We reevaluated the largest database in the world of photographed dystrophic neurites for the presence of cytoplasmic clearance as shown in transgenic fruit flies transfected with A-42. In several neurites, we found electron-lucent areas not bound by any membranes or only partially bound; thus, they were not autophagic vacuoles as the latter are membrane-bound and contain cargo.

Cerebrospinal fluid neurofilament light in suspected sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease. It is invariably fatal and displays a short clinical disease stage. The key event in sCJD is the propagation of a beta-sheet rich conformer of the physiological PrP protein, known as PrP.

Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases.

Introduction: Neurofilament light (NFL) levels in the cerebrospinal fluid are increased in several neurodegenerative dementias. However, their diagnostic accuracy in the differential diagnostic context is unknown.

Methods: Cerebrospinal fluid NFL levels were quantified in nonprimarily neurodegenerative neurological and psychiatric diseases (n = 122), mild cognitive impairment (n = 48), Alzheimer's disease (n = 108), dementia with Lewy bodies/Parkinson's disease dementia (n = 53), vascular dementia (n = 46), frontotemporal dementia (n = 41), sporadic Creutzfeldt-Jakob disease (sCJD, n = 132), and genetic prion diseases (n = 182).

Electron microscopic and confocal laser microscopy analysis of amyloid plaques in chronic wasting disease transmitted to transgenic mice.

We report here on the ultrastructure of amyloid plaques in chronic wasting disease (CWD) transmitted to Tg20 transgenic mice overexpressing prion protein (PrP). We identified three main types of amyloid deposits in mCWD: large amyloid deposits, unicentric plaques similar to kuru plaques in human prion diseases and multicentric plaques reminiscent of plaques typical of GSS. The most unique type of plaques were large subpial amyloid deposits.

Glioblastoma-derived cells unveil the spectrum of drug resistance capability - comparative study of tumour chemosensitivity in different culture systems.

Resistance to cancer drugs is a complex phenomenon which could be influenced by conditions. However, tumour-derived cell cultures are routinely used for studies related to mechanisms of drug responsiveness or the search for new therapeutic approaches. The purpose of our work was to identify the potential differences in drug resistance and response to treatment of glioblastoma with the use of three models: traditional adherent culture, serum-free spheroid culture and novel adherent serum-free culture.

Altered Ca homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrP). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca responsive genes in sCJD brain tissue, accompanied by two Ca-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2.

Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range.

Cerebrospinal Fluid Biomarker-Based Diagnosis of Sporadic Creutzfeldt-Jakob Disease: A Validation Study for Previously Established Cutoffs.

Background: Several biomarkers have been proposed to discriminate sporadic Creutzfeldt-Jakob disease (sCJD) from other dementias and control cases. However, their clinical accuracy depends on the PRNP codon 129 genotype, leaving it unclear how well established markers behave in untested conditions.

Methods: We analyzed 14-3-3, tau, p-tau levels, and the p-tau/tau ratio in a population sample collected from Polish hospitals including nondementia, dementia, and definite sCJD cases and validated their parameters according to previously established cutoffs.

Evaluation of α-synuclein as a novel cerebrospinal fluid biomarker in different forms of prion diseases.

Introduction: Accurate diagnosis of prion diseases and discrimination from alternative dementias gain importance in the clinical routine, but partial overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination in the differential diagnostic context.

Methods: We established the clinical parameters for prion disease diagnosis for the quantification of CSF α-synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion diseases, in cases with cognitive impairment/dementia or neurodegenerative disease (n = 278), and in the neurologic control group (n = 111).

Results: An optimal cutoff value of 680 pg/mL α-synuclein results in 94% sensitivity and 96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD).

Recurrence-associated chromosomal anomalies in meningiomas: Single-institution study and a systematic review with meta-analysis.

Complete removal of a meningioma (MG) does not guarantee relapse-free survival. Alterations on several chromosomes responsible for MG recurrence were suggested, although their role was not validated by a systematic review. Following the analysis of own 161 cases, all previously published data has been collected for evidence synthesis.

The correlation of clinical and chromosomal alterations of benign meningiomas and their recurrences.

Meningiomas (MGs) are the frequent benign intracranial tumors. Their complete removal does not always guarantee relapse-free survival. Recurrence-associated chromosomal anomalies in MGs haves been proposed as prognostic factors in addition to the World Health Organisation (WHO) grading, tumor size and resection rate.

Altered MicroRNA Expression Is Associated with Tumor Grade, Molecular Background and Outcome in Childhood Infratentorial Ependymoma.

Background: Ependymal tumors are the third most common group of brain tumors in children, accounting for about 10% of all primary brain neoplasms. According to the current WHO classification, they comprise four entities with the most frequent ependymoma and anaplastic ependymoma. The most of pediatric tumors are located within the posterior fossa, with a tendency to infiltrate the vital brain structures.

Tau pathology in Creutzfeldt-Jakob disease revisited.

Creutzfeldt-Jakob disease (CJD) is a human prion disease with different etiologies. To determine the spectrum of tau pathologies in CJD, we assessed phospho-Tau (pTau) immunoreactivities in 75 sporadic CJD cases including an evaluation of the entorhinal cortex and six hippocampal subregions. Twelve cases (16%) showed only small tau-immunoreactive neuritic profiles.

The molecular pattern of histopathological progression to anaplastic meningioma - A case report.

Meningiomas (MGs) are the most frequent primary tumours of the central nervous system (CNS) and exhibit a large spectrum of histological types and clinical phenotypes. The WHO classification of CNS tumours established strict diagnostic criteria of the benign (Grade 1), atypical (Grade 2) and anaplastic (Grade 3) subtypes. Combined with the resection rate, WHO grading has the most crucial role as the prognostic factor.

Isolation and partial characterization of a highly divergent lineage of hantavirus from the European mole (Talpa europaea).

Genetically distinct hantaviruses have been identified in five species of fossorial moles (order Eulipotyphla, family Talpidae) from Eurasia and North America. Here, we report the isolation and partial characterization of a highly divergent hantavirus, named Nova virus (NVAV), from lung tissue of a European mole (Talpa europaea), captured in central Poland in August 2013. Typical hantavirus-like particles, measuring 80-120 nm in diameter, were found in NVAV-infected Vero E6 cells by transmission electron microscopy.

Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease.

Introduction: Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown.

Methods: CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia.

Results: Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias.