Congenital Titinopathy: Comprehensive Characterization of the Most Severe End of the Disease Spectrum.

Unlabelled: Congenital titinopathy has recently emerged as one of the most common congenital muscle disorders.

Objective: To better understand the presentation and clinical needs of the under-characterized extreme end of the congenital titinopathy severity spectrum.

Methods: We comprehensively analyzed the clinical, imaging, pathology, autopsy, and genetic findings in 15 severely affected individuals from 11 families.

The schizophrenia risk gene C4 induces pathological synaptic loss by impairing AMPAR trafficking.

Neuroimmune interactions play a significant role in regulating synaptic plasticity in both the healthy and diseased brain. The complement pathway, an extracellular proteolytic cascade, exemplifies these interactions. Its activation triggers microglia-dependent synaptic elimination via the complement receptor 3 (CR3).

Perfusion MRI in Cerebral Venous and Sinus Thrombosis.

Background And Purpose: Cerebral venous and sinus thrombosis (CVST) leads to perfusion abnormality in the brain. Our aim was to assess perfusion abnormalities in the center and periphery of the parenchymal lesion in CVST patients and correlate with the clinical outcome.

Materials And Methods: Dynamic susceptibility contrast (DSC) perfusion imaging was performed in patients with CVST.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.

Fast-spiking parvalbumin (PV)-positive cells are key players in orchestrating pyramidal neuron activity, and their dysfunction is consistently observed in myriad brain diseases. To understand how immune complement dysregulation - a prevalent locus of brain disease etiology - in PV cells may drive disease pathogenesis, we have developed a transgenic mouse line that permits cell-type specific overexpression of the schizophrenia-associated complement component 4 () gene. We found that overexpression of mouse () in PV cells causes sex-specific behavioral alterations and concomitant deficits in synaptic connectivity and excitability of PV cells of the prefrontal cortex.

Melanoma skin cancer detection using mask-RCNN with modified GRU model.

Melanoma Skin Cancer (MSC) is a type of cancer in the human body; therefore, early disease diagnosis is essential for reducing the mortality rate. However, dermoscopic image analysis poses challenges due to factors such as color illumination, light reflections, and the varying sizes and shapes of lesions. To overcome these challenges, an automated framework is proposed in this manuscript.

C4 induces pathological synaptic loss by impairing AMPAR trafficking.

During development, activation of the complement pathway, an extracellular proteolytic cascade, results in microglia-dependent synaptic elimination via complement receptor 3 (CR3). Here, we report that decreased connectivity caused by overexpression of (C4-OE), a schizophrenia-associated gene, is CR3 independent. Instead, C4-OE triggers GluR1 degradation through an intracellular mechanism involving endosomal trafficking protein SNX27, resulting in pathological synaptic loss.

A pipeline for STED super-resolution imaging and Imaris analysis of nanoscale synapse organization in mouse cortical brain slices.

Advances in super-resolution imaging enable us to delve into its intricate structural and functional complexities with unprecedented detail. Here, we present a pipeline to visualize and analyze the nanoscale organization of cortical layer 1 apical dendritic spines in the mouse prefrontal cortex. We describe steps for brain slice preparation, immunostaining, stimulated emission depletion super-resolution microscopy, and data analysis using the Imaris software package.

REVEALS: An Open Source Multi Camera GUI For Rodent Behavior Acquisition.

Understanding the rich behavioral data generated by mice is essential for deciphering the function of the healthy and diseased brain. However, the current landscape lacks effective, affordable, and accessible methods for acquiring such data, especially when employing multiple cameras simultaneously. We have developed REVEALS (odent Bhaior Multi-camraboratory Acquiition), a graphical user interface (GUI) written in python for acquiring rodent behavioral data via commonly used USB3 cameras.

Long-term Natural History of Pediatric Dominant and Recessive -Related Myopathy.

Background And Objectives: -related myopathies are the most common congenital myopathies, but long-term natural history data are still scarce. We aim to describe the natural history of dominant and recessive -related myopathies.

Methods: A cross-sectional and longitudinal retrospective data analysis of pediatric cases with -related myopathies seen between 1992-2019 in 2 large UK centers.

Glycogen storage disease type IV without detectable polyglucosan bodies: importance of broad gene panels.

Glycogen storage disease type IV (GSD IV) is caused by mutations in the glycogen branching enzyme 1 (GBE1) gene and is characterized by accumulation of polyglucosan bodies in liver, muscle and other tissues. We report three cases with neuromuscular forms of GSD IV, none of whom had polyglucosan bodies on muscle biopsy. The first case had no neonatal problems and presented with delayed walking.

Management of scalp arteriovenous malformations: a rising trend towards percutaneous direct puncture embolization technique-our experience.

Background: Scalp arteriovenous malformations (AVMs), or cirsoid aneurysms of the scalp, usually present with troublesome symptoms and cosmetic disfigurement. Endovascular/percutaneous embolization has evolved as a sole treatment method or adjunct to surgical excision in the management of scalp AVMs with an excellent outcome.

Purpose: To discuss minimally invasive techniques for treating scalp AVMs as well as to highlight the role of embolization before surgery.

Blood in the Brain on Susceptibility-Weighted Imaging.

Intraparenchymal brain hemorrhage is not uncommon and results from a wide variety of causes ranging from trauma to tumor. Many a time, it is not possible to determine the exact cause of non-traumatic hemorrhage on conventional magnetic resonance imaging (MRI). Susceptibility-weighted imaging (SWI) is a high-resolution (3D) gradient-echo sequence.

Expanding the phenotype of children presenting with hypoventilation with biallelic TBCK pathogenic variants and literature review.

Individuals with biallelic TBCK pathogenic variants present in infancy with distinctive facial features, profound hypotonia, severe intellectual impairment and epilepsy. Although rare, it may mimic other neurogenetic disorders leading to extensive investigations. Improved understanding of the clinical phenotype can support early monitoring of complications due to respiratory insufficiency.

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.

Endovascular management of pulmonary arteriovenous malformations presenting as multiple brain abscesses.

Pulmonary arteriovenous malformations (PAVMs) are rare vascular lesions characterised by abnormal connections between the pulmonary artery and vein bypassing the pulmonary capillary bed and causing right-to-left shunt. Paradoxical embolism is known to occur in these cases, leading to inoculation of septic focus in the systemic circulation. We report a case of multiple PAVMs who presented clinically with seizures and altered sensorium.

Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing.

Diagnostic whole genome sequencing (WGS) is increasingly used in rare diseases. However, standard, semi-automated WGS analysis may overlook diagnoses in complex disorders. Here, we show that specialist multidisciplinary analysis of WGS, following an initial 'no primary findings' (NPF) report, improves diagnostic rates and alters management.

Cytokine Storm and Neuropathological Alterations in Patients with Neurological Manifestations of COVID-19.

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6 IL-8, IL- 10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients may persist even after apparent recovery from infection.

Neurology and the histiocytoses: a case of Rosai-Dorfman-Destombes disease.

The histiocytoses are a group of rare disorders characterised by the accumulation of neoplastic or non-neoplastic activated histiocytes in various tissues. Phenotypes vary widely from cutaneous lesions or lymphadenopathy that regress spontaneously to disseminated disease with poor prognosis. Neurological symptoms can be a presenting feature or appear during the course of disease.

Balloon-Assisted Coiling of Intracranial Aneurysms: Technical Details and Evaluation of Local Complications.

Background: Wide-neck intracranial aneurysms need additional devices like balloons or stent for management. Balloon-assisted coiling has evolved both with interventionalist experience and device modifications.

Objective: We discussed our experience, evolution, and complications with this novel technique.

Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence.