Neuropathological spectrum of anti-IgLON5 disease and stages of brainstem tau pathology: updated neuropathological research criteria of the disease-related tauopathy.

Anti-IgLON5 disease is a unique condition that bridges autoimmunity and neurodegeneration. Since its initial description 10 years ago, an increasing number of autopsies has led to the observation of a broader spectrum of neuropathologies underlying a particular constellation of clinical symptoms. In this study, we describe the neuropathological findings in 22 patients with anti-IgLON5 disease from 9 different European centers.

Brain aggregoma with clonal B-cell perivascular proliferation detected by next-generation sequencing. A case report and review of the literature.

Light-chain deposition disease (LCDD), a rare type of monoclonal immunoglobulin deposition disease, can be presented as systemic or localized, very rarely affecting central nervous system (CNS). Only 10 cases of CNS-LCDD have been described so far. We present an eleventh case of cerebral tumour-like LCDD, called aggregoma, and compare it with previously reported cases.

Latent brain infection with as a possible cause of cerebral gliomatosis type 2: A case report.

Background: The gram-negative aerobic bacterium is an opportunistic pathogen in brain tissues.

Case Summary: The gram-negative aerobic bacterium was isolated from a patient's brain tissue during a stereotactic biopsy.

Conclusion: This is the first report of a brain tissue infection with possibly causing brain gliomatosis.

Atypical clinical presentation of pathologically proven Parkinson's disease: The role of Parkinson's disease related metabolic pattern.

Regional changes in brain metabolism upgraded with measurements of specific metabolic brain patterns and automated diagnostic algorithms can help to differentiate among neurodegenerative parkinsonisms, but with few reports on pathological confirmation. Here we describe a parkinsonian patient with atypical presentation and F-FDG-PET imaging consistent with idiopathic Parkinson's disease. The latter was confirmed at the pathohistological examination.

A case of MV2K subtype of sporadic Creutzfeldt-Jakob disease with florid-like plaques: Similarities and differences to variant Creutzfeldt-Jakob disease.

Variant Creutzfeldt-Jakob disease (vCJD) is traditionally regarded as having a distinct clinical course, imaging study findings and neuropathological features, which in combination should allow a clear distinction from the six currently well-defined subtypes of sporadic Creutzfeldt-Jakob disease (sCJD). This is of major importance, especially from the standpoint of epidemiology. As we would like to demonstrate through this case report, the MV2K subtype of sCJD, being rare and heterogeneous in both clinical and neuropathological presentations, might challenge this concept by virtue of partial overlapping, both clinically and neuropathologically, with the characteristic phenotype of vCJD.

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population.

Advances in the management of craniopharyngioma in children and adults.

Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient's quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas.

A novel PTPRZ1-ETV1 fusion in gliomas.

The aggressive nature of malignant gliomas and their genetic and clinical heterogeneity present a major challenge in their diagnosis and treatment. Development of targeted therapy brought attention on detecting novel gene fusions, since they represent promising therapeutic targets (eg, TRK inhibitors in NTRK fusion-positive tumors). Using targeted next-generation sequencing, we prospectively analyzed 205 primary brain tumors and detected a novel PTPRZ1-ETV1 fusion transcript in 11 of 191 (5.

Corticosteroid-induced immunodeficiency in a patient with gliomatosis cerebri: Are corticosteroids indicated in all brain tumors?

An elderly male was admitted to the Department of Neurology for slowly progressive dysarthria and right-sided atactic hemiparesis. Magnetic resonance imaging (MRI) revealed a small contrast-enhanced focus of malignant glioma in the left parietal lobe - with the growth pattern of cerebral gliomatosis - involving the whole left cerebral hemisphere, the corpus callosum, and spreading into the right frontal hemisphere. Diagnostic biopsy was deferred until the exclusion of other possible causes of the brain lesion.

Dynamic expression of 11 miRNAs in 83 consecutive primary and corresponding recurrent glioblastoma: correlation to treatment, time to recurrence, overall survival and MGMT methylation status.

Background Glioblastoma (GBM) is the most common and the most malignant glioma subtype. Among numerous genetic alterations, miRNAs contribute to pathogenesis of GBM and it is suggested that also to GBM recurrence and resistance to therapy. Based on publications, we have selected 11 miRNAs and analyzed their expression in GBM.

Analysis of 22 Years of Surveillance for Prion Diseases in Slovenia, 1996 to 2017.

Introduction: The objective was to present the results of surveillance of prion diseases in Slovenia that was established in 1996 and then to assess the interdisciplinary approach according to the algorithm of case management and reporting data to the National Register at the National Institute of Public Health.

Methods: A descriptive study of Creutzfeldt-Jakob disease (CJD) recorded in the period from 1996 to 2017 was carried out.

Results: A total of 123 cases of prion disease were notified between 1996 and 2017.

Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.

Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models.

High Incidence of Sporadic Creutzfeldt-Jakob Disease in Slovenia in 2015: A Case Series.

Background: Creutzfeldt-Jakob disease (CJD) is a rare fatal neurodegenerative disorder presenting with rapid cognitive decline and additional signs. The clinical characteristics of an increasing number of sporadic CJD (sCJD) patients admitted to the Ljubljana University Medical Centre are presented as well as the incidence of sCJD in Slovenia in 2015 compared to previous years.

Methods: We investigated patients presenting with rapidly progressive dementia and at least one additional sign.

Identifying Novel Glioma-Associated Noncoding RNAs by Their Expression Profiles.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play a significant role in cancer development as regulators of protein-coding genes. Their dysregulation was in some extent already associated with glioma, the most aggressive primary brain tumours in adults. The correct diagnosis and treatment selection due to high tumour heterogeneity might be difficult and inadequate, resulting in poor prognosis.

Expression of LOC285758, a Potential Long Non-coding Biomarker, is Methylation-dependent and Correlates with Glioma Malignancy Grade.

Background: Identifying the early genetic drivers can help diagnose glioma tumours in their early stages, before becoming malignant. However, there is emerging evidence that disturbance of epigenetic mechanisms also contributes to cell's malignant transformation and cancer progression. Long non-coding RNAs are one of key epigenetic modulators of signalling pathways, since gene expression regulation is one of their canonical mechanisms.

Long-term survival in glioblastoma: methyl guanine methyl transferase (MGMT) promoter methylation as independent favourable prognostic factor.

Background: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma.

Zika Virus-Associated Micrencephaly: A Thorough Description of Neuropathologic Findings in the Fetal Central Nervous System.

Context: -The 2015 outbreak of Zika virus in Brazil resulted in a 20-times increased prevalence of congenital microcephaly in stillborns and neonates and was instrumental in raising the suspicion of a causal association between Zika virus and microcephaly.

Objective: -To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection.

Design: -Autopsy evaluation of the brain from a fetus of 32 weeks and 6 days of gestation, with a prenatal diagnosis of microcephaly associated with polymerase chain reaction-confirmed, fetal, Zika virus infection.

Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia.

The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation and characterization, including single-cell RNA-seq, of neocortical and spinal cord neuroepithelial stem (NES) cells to model early human neurodevelopment and ZIKV-related neuropathogenesis. By analyzing human NES cells, organotypic fetal brain slices, and a ZIKV-infected micrencephalic brain, we show that ZIKV infects both neocortical and spinal NES cells as well as their fetal homolog, radial glial cells (RGCs), causing disrupted mitoses, supernumerary centrosomes, structural disorganization, and cell death.

Neuropathological criteria of anti-IgLON5-related tauopathy.

We recently reported a novel neurological syndrome characterized by a unique NREM and REM parasomnia with sleep apnea and stridor, accompanied by bulbar dysfunction and specific association with antibodies against the neuronal cell-adhesion protein IgLON5. All patients had the HLA-DRB1*1001 and HLA-DQB1*0501 alleles. Neuropathological findings in two patients revealed a novel tauopathy restricted to neurons and predominantly involving the hypothalamus and tegmentum of the brainstem.

Zika Virus Associated with Microcephaly.

A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil.

Fatal recurrent dermatoneuro syndrome associated with systemic AL amyloidosis.

A male patient is presented with long-lasting paraproteinemia of monoclonal IgG λ, who suffered from recurrent, and until the last one, mostly reversible episodes of dermatoneuro syndrome, described exclusively in scleromyxedema. The skin biopsy revealed λ-light chain amyloid deposition instead of changes typical for scleromyxedema. Systemic AL amyloidosis was diagnosed post mortem since the patient had no clinical signs of any other organ impairment except skin and brain.

Possible pitfalls in the diagnostic of progressive multifocal leukoencephalopathy.

The most accurate diagnosis of clinically suspected progressive multifocal leukoencephalopathy (PML) is made by neuronavigated needle brain biopsy and microscopic examination of the specimen confirming typical morphological features of the disease and, additionally, using immunohistochemistry (IHC) for detection of early viral proteins of the etiologic agent - polyoma virus JC (JCV). Due to the small biopsy volume, this approach can sometimes fail to confirm the clinical diagnosis of PML, as demonstrated by the presented clinical case. To check the reliability of using only IHC, we additionally tested 6 archival cases from our institute using IHC, in-situ hybridization (ISH) and real-time polymerase chain reaction (PCR).