Nemaline Myopathy Type 6 Caused by Variants in the Gene: A Cross-Sectional Study of 24 Patients.

Background And Objectives: Nemaline myopathy type 6 (NEM6) is the most prevalent type of nemaline myopathy in the Netherlands. Because a detailed clinical characterization is not available yet, we here provide a detailed assessment of 24 patients.

Methods: In this cross-sectional study, we performed a full clinical assessment (medical history and neurologic examination) in patients with NEM6.

Autosomal recessive -related disorder: comprehensive analysis of phenotypic variability and genetic mutations.

A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain-containing 1 (). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through genome or exome sequencing, incorporating neurophysiological, laboratory and imaging data, along with data from previously reported cases across three different studies. Newly reported clinical features include hypermobility/hyperlaxity, axial weakness, dysmorphic signs, asymmetric presentation, dystonic features and, notably, upper motor neuron signs.

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.

Added Value of Histological Evaluation of Muscle Biopsies in Porcine Vascularized Composite Allografts.

: Machine perfusion (MP) offers extended preservation of vascularized complex allografts (VCA), but the diagnostic value of histology using hematoxylin and eosin (H&E) in detecting ischemia-reperfusion injury (IRI) in muscle cells remains unclear. This study aims to document the application of the Histology Injury Severity Score (HISS) and to assess whether additional staining for nicotinamide adenine dinucleotide (NADH) and membrane attack complex (MAC) improves IRI detection in a porcine limb replantation model. : The forelimbs of 16 Dutch Landrace pigs were amputated and preserved for 24 h using hypothermic MP ( = 8) with Histidine-Tryptophan-Ketoglutarate (HTK) or for 4 h with SCS ( = 8) before heterotopic replantation and 7 days of follow-up.

A Likely Pathogenic variant in the KBTBD13 Gene: A Case Series of Three Patients with Nemaline Myopathy Type 6.

Background: Nemaline myopathy type 6 (NEM6) or KBTBD13-related congenital myopathy is the most prevalent type of nemaline myopathy in the Netherlands and is characterised by mild childhood-onset axial, proximal and distal muscle weakness with prominent neck flexor weakness combined with slowness of movements. The most prevalent variant in the Netherlands is the c.1222C > T p.

A cross-sectional study in 18 patients with typical and mild forms of nemaline myopathy in the Netherlands.

Nemaline myopathy (NM) is a congenital myopathy with generalised muscle weakness, most pronounced in neck flexor, bulbar and respiratory muscles. The aim of this cross-sectional study was to assess the Dutch NM patient cohort. We assessed medical history, physical examination, quality of life (QoL), fatigue severity, motor function (MFM), and respiratory muscle function.

Deep learning-based segmentation in MRI-(immuno)histological examination of myelin and axonal damage in normal-appearing white matter and white matter hyperintensities.

The major vascular cause of dementia is cerebral small vessel disease (SVD). Its diagnosis relies on imaging hallmarks, such as white matter hyperintensities (WMH). WMH present a heterogenous pathology, including myelin and axonal loss.

Characterisation of an Adult Zebrafish Model for -Associated Phaeochromocytomas and Paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from chromaffin cells. Pathogenic variants in the gene are associated with malignancy and poor prognosis. When metastases arise, limited treatment options are available.

Altered brain expression and cerebrospinal fluid levels of TIMP4 in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a highly prevalent and progressive pathology, involving amyloid-β (Aβ) deposition in the cerebral blood vessel walls. CAA is associated with an increased risk for intracerebral hemorrhages (ICH). Insight into the molecular mechanisms associated with CAA pathology is urgently needed, to develop additional diagnostic tools to allow for reliable and early diagnosis of CAA and to obtain novel leads for the development of targeted therapies.

The expanding clinical and genetic spectrum of DYNC1H1-related disorders.

Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons.

Decreased microvascular claudin-5 levels in cerebral amyloid angiopathy associated with intracerebral haemorrhage.

Decreased microvascular levels of claudin-5 in the occipital and temporal lobe of patients with cerebral amyloid angiopathy are associated with intracerebral haemorrhage.

Brody Disease, an Early-Onset Myopathy With Delayed Relaxation and Abnormal Gait: A Case Series of 9 Children.

Brody disease is a rare autosomal recessive myopathy, caused by pathogenic variants in the gene. It is characterized by an exercise-induced delay in muscle relaxation, often reported as muscle stiffness. Children may manifest with an abnormal gait and difficulty running.

An up-to-date myopathologic characterisation of facioscapulohumeral muscular dystrophy type 1 muscle biopsies shows sarcolemmal complement membrane attack complex deposits and increased skeletal muscle regeneration.

The aim of this study was to identify key routinely used myopathologic biomarkers of FSHD1. Needle muscle biopsies were taken in 34 affected muscles (m. quadriceps femoris (QF), n = 20, m.

Efficacy and Safety of Panitumumab in Patients With RAF/RAS-Wild-Type Glioblastoma: Results From the Drug Rediscovery Protocol.

Background: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).

Heparin-resistance in AL amyloidosis: a case report.

Background: Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance.

Case Presentation: We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed.

The double homeodomain protein DUX4c is associated with regenerating muscle fibers and RNA-binding proteins.

Background: We have previously demonstrated that double homeobox 4 centromeric (DUX4C) encoded for a functional DUX4c protein upregulated in dystrophic skeletal muscles. Based on gain- and loss-of-function studies we have proposed DUX4c involvement in muscle regeneration. Here, we provide further evidence for such a role in skeletal muscles from patients affected with facioscapulohumeral muscular dystrophy (FSHD).

Association between hypertension and neurovascular inflammation in both normal-appearing white matter and white matter hyperintensities.

The major vascular cause of dementia is cerebral small vessel disease (SVD), including white matter hyperintensities (WMH) amongst others. While the underlying pathology of SVD remains unclear, chronic hypertension and neuroinflammation are recognized as important risk factors for SVD and for the conversion of normal-appearing white matter (NAWM) to WMH. Unfortunately, most studies investigating the role of neuroinflammation in WMH relied on peripheral blood markers, e.

Integrin α7 Mutations Are Associated With Adult-Onset Cardiac Dysfunction in Humans and Mice.

Background Integrin α7β1 is a major laminin receptor in skeletal and cardiac muscle. In skeletal muscle, integrin α7β1 plays an important role during muscle development and has been described as an important modifier of skeletal muscle diseases. The integrin α7β1 is also highly expressed in the heart, but its precise role in cardiac function is unknown.

[F]FDG Uptake and Expression of Immunohistochemical Markers Related to Glycolysis, Hypoxia, and Proliferation in Indeterminate Thyroid Nodules.

Purpose: The current study explored the association between 2-[F]fluoro-2-deoxy-D-glucose ([F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology.

Procedures: Using a case-control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [F]FDG-positive malignant, [F]FDG-positive benign, and [F]FDG-negative benign nodules were included.

Superior preservation of capillaries, myofibrils and mitochondria after long-term extracorporeal perfusion of free muscle flaps - A descriptive electron microscopy study.

Background: Extracorporeal perfusion (ECP) is a promising technique for prolonged tissue preservation, but might have side effects. For instance, increased radical oxygen species or capillary endothelial damage.

Objective: To assess ultra-morphological muscle damage during 36-hour ECP of porcine musculocutaneous flaps, hypothesizing that it would delay the onset of damage compared to static cold storage (SCS).

Changes of the CYP11B2 Expressing Zona Glomerulosa in Human Adrenals From Birth to 40 Years of Age.

Background: Aldosterone synthase (CYP11B2) antibodies for immunohistochemistry, enables to visualize aldosterone-producing zona glomerulosa (ZG), aldosterone-producing micronodules, and aldosterone-producing adenomas. The architecture of the ZG differs in old versus young age but the evolution of the changes is not well known. The pathogenesis of aldosterone-producing micronodules and aldosterone-producing adenomas is still unclear and research on the ZG in young populations is limited.

Early Restrictive Fluid Strategy Impairs the Diaphragm Force in Lambs with Acute Respiratory Distress Syndrome.

Background: The effect of fluid management strategies in critical illness-associated diaphragm weakness are unknown. This study hypothesized that a liberal fluid strategy induces diaphragm muscle fiber edema, leading to reduction in diaphragmatic force generation in the early phase of experimental pediatric acute respiratory distress syndrome in lambs.

Methods: Nineteen mechanically ventilated female lambs (2 to 6 weeks old) with experimental pediatric acute respiratory distress syndrome were randomized to either a strict restrictive fluid strategy with norepinephrine or a liberal fluid strategy.