Hereditary Transthyretin Amyloidosis in Israel: Genetic Landscape and Clinical Characteristics.

Background: Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset autosomal-dominant disorder caused by pathogenic variants in the transthyretin (TTR) gene. Data about relevant variants in specific populations and typical initial manifestations may facilitate early diagnosis and treatment. We here describe the genetic landscape of ATTRv amyloidosis in Israel.

Refractory Psychosis as a Red Flag for End of Life in Individuals With Dementia With Lewy Bodies: A Case Series and Re-analysis of Prior Qualitative Data.

Objectives: Many individuals with dementia with Lewy bodies (DLB) die of disease-related complications, but predicting the end of life can be challenging. We identified a phenotype associated with approaching end of life.

Methods: We present 4 exemplar cases where individuals with DLB experienced refractory psychosis before death.

Sleep spindles and slow oscillations predict cognition and biomarkers of neurodegeneration in mild to moderate Alzheimer's disease.

Introduction: Changes in sleep physiology can predate cognitive symptoms by decades in persons with Alzheimer's disease (AD), but it remains unclear which sleep characteristics predict cognitive and neurodegenerative changes after AD onset.

Methods: Using data from a prospective cohort of mild to moderate AD (n = 60), we analyzed non-rapid eye movement sleep spindles and slow oscillations (SOs) at baseline and their associations with baseline amyloid beta (Aβ) and tau and with cognition from baseline to 3-year follow-up.

Results: Higher spindle and SO activity predicted significant changes in Aβ and tau at baseline, lower Alzheimer's Disease Assessment Scale Cognitive Subscale (better cognitive performance) score, and higher Mini-Mental State Examination score from baseline to 36 months.

Pattern Separation and Pattern Completion Within the Hippocampal Circuit During Naturalistic Stimuli.

Pattern separation and pattern completion in the hippocampus play a critical role in episodic learning and memory. However, there is limited empirical evidence supporting the role of the hippocampal circuit in these processes during complex continuous experiences. In this study, we analyzed high-resolution fMRI data from the "Forrest Gump" open-access dataset (16 participants) using a sliding-window temporal autocorrelation approach to investigate whether the canonical hippocampal circuit (DG-CA3-CA1-SUB) shows evidence consistent with the occurrence of pattern separation or pattern completion during a naturalistic audio movie task.

Trafficking of Muscarinic 1 Acetylcholine Receptor Regulated by VPS35 in Alzheimer's Disease.

Introduction: Muscarinic 1 acetylcholine receptor (M1AChR) is a member of the Gprotein- coupled receptor superfamily, with the dysfunction being linked to the onset of Alzheimer's Disease (AD).

Aims: Retromer complex with Vacuolar Protein Sorting-35 (VPS35) as the core plays an important role in the transport of biological proteins and has been confirmed to be closely related to the pathogenesis of AD. This study was designed to determine whether VPS35 could affect the trafficking mechanism of M1AChRs.

Predictors for Development of Asphyxiated Neonates Treated With Therapeutic Hypothermia.

Aim: To describe the long-term neurodevelopmental outcomes of asphyxiated neonates treated with hypothermia in association with neonatal magnetic resonance imaging (MRI) findings.

Methods: We evaluated, retrospectively, clinical and radiological single-centre data at 0, 2, and 5 years of age of 53 asphyxiated neonates born between 2005 and 2015. Neonatal cranial MRI was re-evaluated using the Weeke score ranging from 0 (normal finding) to 55 (cerebral devastation) by a single neuroradiologist blinded to patient outcomes.

Learning About Their Condition: The Gradual Path of Young People With Childhood-Onset Motor Disabilities.

Aim: Young people with childhood-onset motor disabilities face unique challenges in understanding and managing their condition. This study explored how they learnt about their condition.

Method: A descriptive qualitative study was conducted in 2023-2024 at a Swiss paediatric neurorehabilitation unit.

Headache in infections.

Purpose Of Review: This review explores the phenomenology, pathogenesis, and nosology of headaches associated with infections, an often-overlooked yet clinically significant symptom. With the increasing recognition of secondary headaches in infections, understanding their clinical patterns, mechanisms, and classifications is crucial for accurate diagnosis and management.

Recent Findings: Headaches in infections are ubiquitous but vary in presentation, severity, and underlying mechanisms depending on the causative pathogen.

Sophoricoside Inhibited Glioblastoma Cell Progression Through Activated AMP-Activated Protein Kinase (AMPK).

Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood-brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L.

Impact of atrial fibrillation on productivity in working-age patients: an analysis of Swiss-AF prospective cohort study data.

Aims: We aimed to explore atrial fibrillation (AF)-induced productivity losses in working-age atrial fibrillation patients and to estimate atrial fibrillation-related indirect costs.

Methods: Between 2014 and 2017, the Swiss Atrial Fibrillation prospective cohort study (Swiss-AF) enrolled 217 working-age patients with documented atrial fibrillation. Self-reported changes in professional activity and the reasons thereof were descriptively analysed over 8 years of follow-up or until patients reached the retirement age.

APP antisense oligonucleotides are effective in rescuing mitochondrial phenotypes in human iPSC-derived trisomy 21 astrocytes.

Introduction: Antisense oligonucleotides (ASOs) have shown promise in reducing amyloid precursor protein (APP) levels in neurons, but their effects in astrocytes, key contributors to neurodegenerative diseases, remain unclear. This study evaluates the efficacy of APP ASOs in astrocytes derived from an individual with Down syndrome (DS), a population at high risk for Alzheimer's disease (AD).

Methods: Human induced pluripotent stem cells (hiPSCs) from a healthy individual and an individual with DS were differentiated into astrocytes.

Cross-cultural validation of plasma p-tau217 and p-tau181 as precision biomarkers for amyloid PET positivity: An East Asian study in Taiwan and Korea.

Introduction: Plasma phosphorylated tau (p-tau) biomarkers have improved Alzheimer's disease (AD) diagnosis, but data from diverse Asian populations are limited. This study evaluated plasma p-tau217 and p-tau181 levels in Korean and Taiwanese populations.

Methods: All participants (n = 270) underwent amyloid positron emission tomography (PET) and blood tests.

Impact of CGRP monoclonal antibody treatment on blood pressure in patients with migraine: A systematic review and potential clinical implications.

Background: Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or the CGRP-receptor have revolutionized the prevention of migraine. Despite their effectiveness, worries have surfaced regarding potential unwanted cardiovascular effects linked to the vasodilation function of CGRP, suggesting a potential influence on blood pressure (BP).

Methods: Studies were systematically retrieved from PubMed, Cochrane Database of Systematic Reviews, Web of Science, MEDLINE and EMBASE up to 1 May 2024.

Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome.

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1).

Noncoding variants and sulcal patterns in congenital heart disease: Machine learning to predict functional impact.

Neurodevelopmental impairments associated with congenital heart disease (CHD) may arise from perturbations in brain developmental pathways, including the formation of sulcal patterns. While genetic factors contribute to sulcal features, the association of noncoding variants (ncDNVs) with sulcal patterns in people with CHD remains poorly understood. Leveraging deep learning models, we examined the predicted impact of ncDNVs on gene regulatory signals.

The impact of temporal distribution on fear extinction learning.

Fear extinction is the foundation of exposure therapy for anxiety and phobias. However, the stability of extinction memory diminishes over time, coinciding with fear recovery. To augment long-term extinction retention, the temporal distribution of extinction learning sessions is critical.

Examining the Time to Diagnosis in Idiopathic Intracranial Hypertension Presentations in a Specialist Eye Emergency Department.

Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by chronic headaches, cognitive difficulties, reduced quality of life, and rarely irreversible visual loss. Community diagnosis is often challenging due to unfamiliarity with current guidelines and a lack of clinical experience, leading to misdiagnosis and treatment delays, which can negatively impact visual recovery and quality of life. Our study examined the time to diagnosis and investigated the barriers to timely diagnosis in adults with newly diagnosed IIH.

Therapeutic manipulation and bypass of the blood-brain barrier: powerful tools in glioma treatment.

The blood-brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms.

AI-guided virtual biopsy: Automated differentiation of cerebral gliomas from other benign and malignant MRI findings using deep learning.

Background: This study aimed to develop an automated algorithm to noninvasively distinguish gliomas from other intracranial pathologies, preventing misdiagnosis and ensuring accurate analysis before further glioma assessment.

Methods: A cohort of 1280 patients with a variety of intracranial pathologies was included. It comprised 218 gliomas (mean age 54.

ALS Motor Observational Telemedicine Objective Rasch-Built Assessment: A Quantitative Scale for the Era of Teleneurology.

Background And Objectives: Telemedicine has become a mainstay of ALS clinical care, but there is currently no standardized approach for assessing and tracking changes to the neurologic examination in this format. The goal of this study was to create a standardized telemedicine-based motor examination scale to objectively and reliably track ALS progression and use Rasch methodology to validate the scale and improve its psychometric properties.

Methods: A draft telemedicine examination scale with 25 items assessing movement in the bulbar muscles, neck, trunk, and extremities was created by an ALS expert panel, incorporating input from patient advisors.

Fingolimod-associated cryptococcal meningitis in a patient with Multiple Sclerosis: A case report and literature review.

A 65-year-old woman with Multiple Sclerosis treated with fingolimod developed headaches and convulsions. Cerebrospinal fluid (CSF) culture indicated . A literature review of 20 cases of cryptococcal meningitis indicated that headache was the most common initial symptom, and all cases were positive for serum and/or CSF cryptococcal antigens.

Effective and Engaging Active Learning in the Medical School Classroom: Lessons from Case-Based Collaborative Learning.

Large group collaborative teaching approaches are rapidly gaining popularity in undergraduate medical education. The case-based collaborative Learning (CBCL) pedagogy was instituted for pre-clerkship teaching at Harvard Medical School in 2015 with subsequent implementation at other medical schools. CBCL emphasizes inductive reasoning, integrates basic and clinical sciences, stimulates curiosity, and fosters teamwork.

The role of intraoperative monitoring in target selection in deep brain stimulation: A single centre study.

Introduction: Intraoperative microelectrode recording (MER) and intraoperative test stimulation may provide vital information for optimal electrode placement and clinical outcome in movement disorders patients treated with deep brain stimulation (DBS). The aims of this retrospective study were to determine (i) how often the planned (imaging based) placements of electrodes were changed due to MER and intraoperative test stimulation in Parkinson's disease (PD), dystonia and essential tremor (ET) patients; (ii) whether the frequency of repositioning changed over time; (iii) whether patients' age or disease duration (in PD) influenced the frequency of repositioning.

Methods: Data on the planned and the final placement of 141 electrodes in 72 consecutive DBS treated patients (52 PD, 11 dystonia, 9 ET) was collected over the first 8 years of DBS implementation in a single center.

Advantages and challenges of using arterial spin labelling MRI to monitor cerebral blood flow in multi-centre clinical trials of neurodegenerative disease: Experience from the RADAR study.

Arterial spin labelling (ASL) enables non-invasive quantification of regional brain perfusion using MRI. ASL was used in the Reducing Pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR) multi-centre trial to pilot the assessment of the effects of the anti-hypertension drug losartan on cerebral blood flow (CBF). In the multi-centre setting, disparities in ASL implementation on scanners from different manufacturers lead to inherent differences in measured CBF and its associated parameters (e.

Inflammatory microglia correlate with impaired oligodendrocyte maturation in multiple sclerosis.

Introduction: Remyelination of demyelinated axons can occur as an endogenous repair mechanism in multiple sclerosis (MS), but its efficacy varies between both MS individuals and lesions. The molecular and cellular mechanisms that drive remyelination remain poorly understood. Here, we studied the relation between microglia activation and remyelination activity in MS.