Stroke recurrence and all-causemortality in CPAP-treated sleep-disordered-breathing patients.

Background: Obstructive sleep apnea (OSA) affects about 70 % of stroke patients and is closely linked to stroke development. It is unclear whether treatment with continuous positive airway pressure (CPAP) reduces the risk of stroke recurrence or mortality in post-stroke patients, partly due to limited follow-up time and small sample sizes of previous studies. To close this knowledge gap, this study investigated changes in stroke recurrence and mortality among CPAP-treated post-stroke patients with sleep-disordered breathing.

Hypertension and cerebral blood flow in the development of Alzheimer's disease.

Introduction: We investigated the interactive associations between amyloid and hypertension on the entorhinal cortex (EC) tau and atrophy and the role of cerebral blood flow (CBF) as a shared mechanism by which amyloid and hypertension contribute to EC tau and regional white matter hyperintensities (WMHs).

Methods: We analyzed data from older adults without dementia participating in the Add-Tau study (NCT02958670, n = 138) or Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 523) who had available amyloid-positron emission tomography (PET), tau-PET, fluid-attenuated inversion recovery (FLAIR), and T1-weighted magnetic resonance imaging (MRI). A subsample in both cohorts had available arterial spin labeling (ASL) MRI (Add-Tau: n = 78; ADNI: n = 89).

Recurrent p.H119Y variant in MAP2K1 expands the phenotypic spectrum of MAP2K1 -related RASopathy.

We report three unrelated individuals with atypical clinical findings for cardio-facio-cutaneous (CFC) syndrome, all of whom have the same novel, heterozygous de novo p.H119Y (c.355 C>T) transition variant in MAP2K1, identified by exome sequencing.

Translating multiscale research in rare disease.

This Editorial introduces DMM's new Special Issue on ‘Translating Multiscale Research in Rare Disease’. The Guest Editors reflect on how articles in the issue advance the rare disease research field.

Dermoscopic Features of Melanocytic Nevi in Cardiofaciocutaneous and Costello Syndromes.

Importance: Somatic variants in the RAS/MAPK pathway genes are commonly associated with melanocytic nevi and melanoma, whereas germline variants in these genes are associated with RASopathies, syndromes involving multiple organs, including the skin. Nevi counts may be higher in some RASopathies, but studies on features observed through dermoscopy are limited.

Objective: To determine the distinguishing dermoscopic features of melanocytic nevi and how the RAS pathway influences them by comparing nevi in patients with cardiofaciocutaneous syndrome (CFC) and Costello syndrome (CS).

RASopathies - what they reveal about RAS/MAPK signaling in skeletal muscle development.

RASopathies are rare developmental genetic syndromes caused by germline pathogenic variants in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) signal transduction pathway. Although the incidence of each RASopathy syndrome is rare, collectively, they represent one of the largest groups of multiple congenital anomaly syndromes and have severe developmental consequences. Here, we review our understanding of how RAS/MAPK dysregulation in RASopathies impacts skeletal muscle development and the importance of RAS/MAPK pathway regulation for embryonic myogenesis.

White matter hyperintensity patterns: associations with comorbidities, amyloid, and cognition.

Background: White matter hyperintensities (WMHs) are often measured globally, but spatial patterns of WMHs could underlie different risk factors and neuropathological and clinical correlates. We investigated the spatial heterogeneity of WMHs and their association with comorbidities, Alzheimer's disease (AD) risk factors, and cognition.

Methods: In this cross-sectional study, we studied 171 cognitively unimpaired (CU; median age: 65 years, range: 50 to 89) and 51 mildly cognitively impaired (MCI; median age: 72, range: 53 to 89) individuals with available amyloid (18F-flutementamol) PET and FLAIR-weighted images.

Frequency and predictors of headache in the first 12 months after traumatic brain injury: results from CENTER-TBI.

Background: Headache is a prevalent and debilitating symptom following traumatic brain injury (TBI). Large-scale, prospective cohort studies are needed to establish long-term headache prevalence and associated factors after TBI. This study aimed to assess the frequency and severity of headache after TBI and determine whether sociodemographic factors, injury severity characteristics, and pre- and post-injury comorbidities predicted changes in headache frequency and severity during the first 12 months after injury.

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences.

Introduction: Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges.

Methods: In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal.

Traumatic Encephalopathy Syndrome and Tauopathy in a 19-Year-Old With Child Abuse.

The majority of traumatic encephalopathy syndrome (TES) cases have been reported in former contact sport athletes. This is the first case with TES in a 19-year-old male patient with progressive cognitive decline after daily domestic physical violence through repeated hits to the head for 15 years. The patient presented with a moderate depressive episode and progressive cognitive decline.

Melanocytic neoplasms in neurofibromatosis type 1: a systematic review.

Neurofibromatosis type 1 ( NF1 ) is commonly mutated in melanoma, yet the risk of melanoma in individuals with NF1 is incompletely understood. We performed a systematic review to investigate the risk and characteristics of melanoma and melanocytic nevi in NF1 individuals. PubMed was searched for articles describing NF1 individuals with melanoma, or melanocytic nevi.

Age-, sex-, and pathology-related variability in brain structure and cognition.

This work aimed to investigate potential pathways linking age and imaging measures to early age- and pathology-related changes in cognition. We used [18F]-Flutemetamol (amyloid) and [18F]-Flortaucipir (tau) positron emission tomography (PET), structural MRI, and neuropsychological assessment from 232 elderly individuals aged 50-89 years (46.1% women, 23% APOE-ε4 carrier, 23.

Obstetrical and neonatal outcomes of cardio-facio-cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation.

We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio-facio-cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records.

MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere.

Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation.

Purpose: Neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) are genetically distinct tumor predisposition syndromes with overlapping phenotypes. We sought to update the diagnostic criteria for NF2 and SWN by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging.

Methods: We used a multistep process, beginning with a Delphi method involving global disease experts and subsequently involving non-neurofibromatosis clinical experts, patients, and foundations/patient advocacy groups.

Lifestyle Affects Amyloid Burden and Cognition Differently in Men and Women.

Objective: Evidence on associations of lifestyle factors with Alzheimer's pathology and cognition are ambiguous, potentially because they rarely addressed inter-relationships of factors and sex effects. While considering these aspects, we examined the relationships of lifestyle factors with brain amyloid burden and cognition.

Methods: We studied 178 cognitively normal individuals (women, 49%; 65.

Relationship Between Time of Admission, Help-Seeking Behavior, and Psychiatric Outcomes: "From Dusk Till Dawn".

Introduction: Day and time of admission influence treatment outcomes and prognosis in several medical specialties; this seems related to resources' ability. It is largely unknown whether this also applies to mental health services. We investigate the relationship between time of admission, patients' demographic and clinical profile, and treatment outcomes.

A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder.

Purpose: Diphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).

Methods: Molecular testing was performed using exome or genome sequencing.

Cross-species analysis of LZTR1 loss-of-function mutants demonstrates dependency to RIT1 orthologs.

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of classical RAS GTPases.