Hereditary spastic paraplegia with thin corpus callosum and SPG11 mutation: A neuropathological evaluation.

Hereditary spastic paraplegia (HSP) with thin corpus callosum can be due to a variety of genetic causes, the most common of which are biallelic variants in SPG11 (HSP11). Only six cases of neuropathologic examination of HSP11 have been reported. Here we present neuropathological findings in another case of HSP11 with novel mutation (homozygous c.

Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.

Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.

Biallelic loss of SPG11 function constitutes the most frequent cause of complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While the impact of neuroinflammation is an emerging and potentially treatable aspect in neurodegenerative diseases and leukodystrophies, the role of immune cells in SPG11-HSP patients is unknown. Here, we performed a comprehensive immunological characterization of SPG11-HSP, including examination of three human postmortem brain donations, immunophenotyping of patients' peripheral blood cells and patient-specific induced pluripotent stem cell-derived microglia-like cells (iMGL).

Performance of a condensed protocol to assess limbic-predominant age-related TDP-43 encephalopathy neuropathologic change.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a dementia-related proteinopathy common in the elderly population. LATE-NC stages 2 or 3 are consistently associated with cognitive impairment. A condensed protocol (CP) for the assessment of Alzheimer disease neuropathologic change and other disorders associated with cognitive impairment, recommended sampling of small brain portions from specific neuroanatomic regions that were consolidated, resulting in significant cost reduction.

Two cases of pineal anlage tumor with molecular analysis.

Pineal anlage tumor is a rare pediatric tumor with clinical and histological features overlapping with pineoblastoma. Two patients with pineal anlage tumor, a 13-month-old female and an 11-month-old male, underwent subtotal resection, high-dose chemotherapy with autologous stem cell rescue, and radiation. Neither had tumor progression 50 months after diagnosis.

Uveal melanoma incidentally diagnosed with neuroimaging, a case series of 3 patients.

Uveal melanoma is the most common primary intraocular malignancy and can occur in the choroid, the ciliary body, or the iris. It is most often diagnosed based on clinical examination by an ophthalmologist. Nearly all patients present with visual symptoms.

Sensitivity-Enhanced Solid-State NMR Detection of Structural Differences and Unique Polymorphs in Pico- to Nanomolar Amounts of Brain-Derived and Synthetic 42-Residue Amyloid-β Fibrils.

Amyloid-β (Aβ) fibrils in neuritic plaques are a hallmark of Alzheimer's disease (AD). Since the 42-residue Aβ (Aβ42) fibril is the most pathogenic among different Aβ species, its structural characterization is crucial to our understanding of AD. While several polymorphs have been reported for Aβ40, previous studies of Aβ42 fibrils prepared at neutral pH detected essentially only one structure, with an S-shaped β-sheet arrangement (, Xiao et al.

Occult primary breast cancer presenting with brachial plexopathy: A case report.

Breast cancer affects about one in eight women over the course of her lifetime. Occult breast cancer, in which primary breast cancer is detected without evidence of disease in the breast itself, comprises up to 1% of new diagnoses; this is typically detected from abnormal axillary lymph nodes, and distant metastases are rare. Here, we present an unusual case of occult breast cancer presenting as upper extremity pain, edema, and weakness, with a metastatic mass to the brachial plexus being the only site of disease.

Atomic-level differences between brain parenchymal- and cerebrovascular-seeded Aβ fibrils.

Alzheimer's disease is characterized by neuritic plaques, the main protein components of which are β-amyloid (Aβ) peptides deposited as β-sheet-rich amyloid fibrils. Cerebral Amyloid Angiopathy (CAA) consists of cerebrovascular deposits of Aβ peptides; it usually accompanies Alzheimer's disease, though it sometimes occurs in the absence of neuritic plaques, as AD also occurs without accompanying CAA. Although neuritic plaques and vascular deposits have similar protein compositions, one of the characteristic features of amyloids is polymorphism, i.

Rapid Validation of Telepathology by an Academic Neuropathology Practice During the COVID-19 Pandemic.

Context.—: The coronavirus disease 19 (COVID-19) pandemic is placing unparalleled burdens on regional and institutional resources in medical facilities across the globe. This disruption is causing unprecedented downstream effects to traditionally established channels of patient care delivery, including those of essential anatomic pathology services.

Metastatic Renal Cell Carcinoma Masquerading as a Sphenoid Wing Meningioma.

A 47-year-old man who presented with subacute binocular diplopia and a left head turn was found to have a right sixth nerve palsy and right optic disc edema. Radiologic imaging revealed a non-lytic right greater sphenoid wing mass with a dural tail, suggestive of a sphenoid wing meningioma. The patient underwent an orbitotomy with lesion biopsy; histopathologic analysis and subsequent imaging revealed the diagnosis of metastatic clear cell renal cell carcinoma.

Alternative splicing in a presenilin 2 variant associated with Alzheimer disease.

Objective: Autosomal-dominant familial Alzheimer disease (AD) is caused by by variants in presenilin 1 (), presenilin 2 (), and amyloid precursor protein (). Previously, we reported a rare frameshift variant in an early-onset AD case (PSEN2 p.K115Efs*11).

Rapidly Growing Pancreatic Adenocarcinoma Presenting as an Irreducible Umbilical Hernia.

Hernia sacs are a common anatomic pathology specimen, which rarely contain malignancy. We present a case of rapidly growing pancreatic adenocarcinoma, which initially presented as metastasis to an umbilical hernia sac. The patient was a 55-year-old male with a two-year history of umbilical hernia.

Preparation of Amyloid Fibrils Seeded from Brain and Meninges.

Seeding of amyloid fibrils into fresh solutions of the same peptide or protein in disaggregated form leads to the formation of replicate fibrils, with close structural similarity or identity to the original fibrillar seeds. Here we describe procedures for isolating fibrils composed mainly of β-amyloid (Aβ) from human brain and from leptomeninges, a source of cerebral blood vessels, for investigating Alzheimer's disease and cerebral amyloid angiopathy. We also describe methods for seeding isotopically labeled, disaggregated Aβ peptide solutions for study using solid-state NMR and other techniques.

Molecular basis of substrate recognition and degradation by human presequence protease.

Human presequence protease (hPreP) is an M16 metalloprotease localized in mitochondria. There, hPreP facilitates proteostasis by utilizing an ∼13,300-Å(3) catalytic chamber to degrade a diverse array of potentially toxic peptides, including mitochondrial presequences and β-amyloid (Aβ), the latter of which contributes to Alzheimer disease pathogenesis. Here, we report crystal structures for hPreP alone and in complex with Aβ, which show that hPreP uses size exclusion and charge complementation for substrate recognition.

A concise, biomimetic total synthesis of (+)-davanone.

A concise, biomimetic synthesis of the antifungal and antispasmodic natural product (+)-davanone is described. The key stereoselective reactions are a Sharpless asymmetric epoxidation, a thiazolium-catalyzed esterification, and a palladium-mediated cyclization. All carbons are derived from isoprene units and no protecting groups are used, permitting an atom- and redox-economical synthesis.