Autopsy-Proven "Pure" Parkinson's Disease with Rapidly Progressive Dementia and Cognitive Fluctuations in a Patient with GBA Mutation.

Background: Parkinson's disease (PD) progresses at highly variable rates in different individuals but, in general, has a fairly stable rate of progression in each patient. In cases where the decline in cognition and behavior suddenly accelerates, we usually think of co-existent Alzheimer pathology, as most demented PD patients also have Alzheimer disease (AD) changes, although not necessarily meeting criteria for a distinct pathological diagnosis of AD.

Methods: Clinico-pathological case Results: A 75-year-old woman presented with a typical PD course including a good response to L-Dopa.

Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue.

Androgen Receptor, Although Not a Specific Marker For, Is a Novel Target to Suppress Glioma Stem Cells as a Therapeutic Strategy for Glioblastoma.

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood-brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders.

Pathologic Characteristics Associated With Local Recurrence of Atypical Meningiomas Following Surgical Resection.

Background: Optimal management of grade II meningiomas following resection remains controversial, owing mostly to the heterogeneity of post-operative (post-op) recurrence patterns across studies. Improved risk stratification of these patients would ensure that only those most at risk of recurrence would undergo appropriate post-op radiation therapy (RT).

Methods: Medical records from patients who underwent resection for grade II meningiomas were retrospectively reviewed.

Intracranial mesenchymal tumor with FET-CREB fusion-A unifying diagnosis for the spectrum of intracranial myxoid mesenchymal tumors and angiomatoid fibrous histiocytoma-like neoplasms.

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here, we studied 20 patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS).

SIRT1-NOX4 signaling axis regulates cancer cachexia.

Approximately one third of cancer patients die due to complexities related to cachexia. However, the mechanisms of cachexia and the potential therapeutic interventions remain poorly studied. We observed a significant positive correlation between SIRT1 expression and muscle fiber cross-sectional area in pancreatic cancer patients.

MiR-1253 exerts tumor-suppressive effects in medulloblastoma via inhibition of CDK6 and CD276 (B7-H3).

Of the four primary subgroups of medulloblastoma, the most frequent cytogenetic abnormality, i17q, distinguishes Groups 3 and 4 which carry the highest mortality; haploinsufficiency of 17p13.3 is a marker for particularly poor prognosis. At the terminal end of this locus lies miR-1253, a brain-enriched microRNA that regulates bone morphogenic proteins during cerebellar development.

Combined Treatment with Insulin-Like Growth Factor 1 and AMD3100 Improves Motor Outcome in a Murine Model of Neonatal Hypoxic-Ischemic Encephalopathy.

Stem cell transplantation is a promising intervention for neonatal hypoxic-ischemic encephalopathy (HIE); however, universal feasibility and safety have not been thoroughly evaluated. AMD3100 and insulin-like growth factor 1 (IGF1) mobilize progenitor cells into peripheral circulation. The objective of this study was to assess the short-term efficacy of inducing endogenous stem cell mobilization after injury in a model of neonatal HIE.

Enteric Pathologic Manifestations of Alpha-Synucleinopathies.

Background: Gastrointestinal (GI) symptoms are common in Parkinson disease (PD), often preceding neurological manifestations; however, early diagnostic utility of GI biopsies remains controversial. Studies suggest aberrant deposition of alpha-synuclein (α-syn) follows step-wise progression in central nervous system though histologic interpretation of normal and aberrant staining patterns have shown variable results. This study examines whether GI α-syn mRNA expression combined with standard α-syn immunohistochemical staining enhance the role of GI biopsy in PD.

Minimally invasive endoscopic spinal cord untethering: case report.

Tethered cord syndrome is a constellation of symptoms and signs that include back and leg pain, bowel and bladder dysfunction, scoliosis and lower extremity weakness and deformity. Tethering may be due to a tight filum terminale or a form of spinal dysraphism. The authors present a case of a 40-year-old man who presented with symptoms of back pain, bilateral lower extremity radicular pain, and bowel and bladder dysfunction.

Succinate Dehydrogenase B (SDHB) Immunohistochemistry for the Evaluation of Muscle Biopsies.

Succinate dehydrogenase (SDH) is a key mitochondrial enzyme complex composed of 4 subunits. SDH histochemistry is routinely utilized in the assessment of muscle biopsies to reveal underlying pathology such as subsarcolemmal mitochondrial aggregates. In this study, we evaluated the utility of succinate dehydrogenase B (SDHB) immunohistochemistry (IHC) in 27 muscle biopsies, including 13 mitochondrial myopathies (MMs), 9 inflammatory myopathies, and 5 controls.

Updates in Molecular Pathology of Central Nervous System Gliomas in Adults.

Central nervous system (CNS) tumors are a heterogeneous group of neoplasms divided into two broad categories, glial and non-glial. Non-glial tumors are derived from such diverse structures as the pineal gland, meninges, germ cells, and hematopoietic cells, as well as metastases. Primary glial neoplasms, or those which originate from astrocytes, oligodendrocytes, or ependymal cells, include astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas.

Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations.

Introduction: The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves.

Methods: Sciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment.

Morphological and molecular changes in aging rat prelimbic prefrontal cortical synapses.

Age-related impairments of executive functions appear to be related to reductions of the number and plasticity of dendritic spine synapses in the prefrontal cortex (PFC). Experimental evidence suggests that synaptic plasticity is mediated by the spine actin cytoskeleton, and a major pathway regulating actin-based plasticity is controlled by phosphorylated LIM kinase (pLIMK). We asked whether aging resulted in altered synaptic density, morphology, and pLIMK expression in the rat prelimbic region of the PFC.

Synaptic distributions of GluA2 and PKMζ in the monkey dentate gyrus and their relationships with aging and memory.

Rhesus monkeys provide a valuable model for studying the neurobiological basis of cognitive aging, because they are vulnerable to age-related memory decline in a manner similar to humans. In this study, young and aged monkeys were first tested on a well characterized recognition memory test (delayed nonmatching-to-sample; DNMS). Then, electron microscopic immunocytochemistry was performed to determine the subcellular localization of two proteins in the hippocampal dentate gyrus (DG): the GluA2 subunit of the glutamate AMPA receptor and the atypical protein kinase C ζ isoform (PKMζ).

Radiology-pathology conference: primary adrenal lymphoma.

We present a case of a 62-year-old man with a history of type II diabetes mellitus who presented to our emergency department with back pain and right upper quadrant abdominal pain associated with vomiting and weight loss. A computed tomographic scan of the abdomen and pelvis demonstrated a large adrenal mass, and subsequent biopsy showed primary adrenal lymphoma.

Synaptic characteristics of dentate gyrus axonal boutons and their relationships with aging, menopause, and memory in female rhesus monkeys.

Age-related memory impairment occurs in many mammalian species, including humans. Moreover, women undergoing the menopausal transition often complain of problems with memory. We recently reported that rhesus monkeys display age- and menopause-related recognition memory impairment on a hippocampus-reliant test [delayed nonmatching-to-sample (DNMS)].

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats.

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, i.p.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7-35.

Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology.