Real life data of ONC201 (dordaviprone) in pediatric and adult H3K27-altered recurrent diffuse midline glioma: Results of an international academia-driven compassionate use program.

Introduction: H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.

Patient perspectives on the use of digital medical devices and health data for AI-driven personalised medicine in Parkinson's Disease.

Introduction: Parkinson's Disease (PD) affects around 8.5 million people currently with numbers expected to rise to 12 million by 2040. PD is characterized by fluctuating motor and non-motor symptoms demanding accurate monitoring.

A Machine Learning Model to Harmonize Volumetric Brain MRI Data for Quantitative Neuroradiologic Assessment of Alzheimer Disease.

Purpose To extend a previously developed machine learning algorithm for harmonizing brain volumetric data of individuals undergoing neuroradiologic assessment of Alzheimer disease not encountered during model training. Materials and Methods Neuroharmony is a recently developed method that uses image quality metrics as predictors to remove scanner-related effects in brain-volumetric data using random forest regression. To account for the interactions between Alzheimer disease pathology and image quality metrics during harmonization, the authors developed a multiclass extension of Neuroharmony for individuals with and without cognitive impairment.

Determining Clinical Disease Progression in Symptomatic Patients With CADASIL.

Background And Objectives: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent small artery brain disease caused by pathogenic variants of the NOTCH3 gene. During the disease, we still do not know how the various deficits progress and develop with each other at different stages of the disease. We aim to model disease progression and identify possible progressive subgroups and the effects of different covariates on clinical worsening.

Recognition memory decline is associated with the progression to prodromal Alzheimer's disease in asymptomatic at-risk individuals.

Episodic memory (EM) alterations are a hallmark of Alzheimer's disease (AD). We assessed EM longitudinally in cognitively normal elders at-risk for AD (with subjective memory complaints), as a function of amyloid-β (Aβ) burden, neurodegeneration (N), and progression to prodromal AD. We stratified 264 INSIGHT-preAD study subjects in controls (Aβ-/N-), stable/N- or N + (Aβ +), and progressors/N- or N + (Aβ +) groups (progressors were included only until AD-diagnosis).

Predicting attentional focus: Heartbeat-evoked responses and brain dynamics during interoceptive and exteroceptive processing.

Attention shapes our consciousness content and perception by increasing the probability of becoming aware and/or better encoding a selection of the incoming inner or outer sensory world. Engaging interoceptive and exteroceptive attention should elicit distinctive neural responses to visceral and external stimuli and could be useful in detecting covert command-following in unresponsive patients. We designed a task to engage healthy participants' attention toward their heartbeats or auditory stimuli and investigated whether brain dynamics and the heartbeat-evoked potential (HEP) distinguished covert interoceptive-exteroceptive attention.

Participatory Development of an International Information Brochure on the Multimodal Assessment of Disorders of Consciousness.

Background: Disorders of consciousness (DoC) refers to a group of clinical conditions of altered consciousness. To improve their diagnosis and prognosis, multimodal assessment can be of great importance. Informal caregivers of people with DoC who are confronted with new technologies as such can benefit from interventions to expand their health literacy, i.

IAPRD new consensus classification of myoclonus.

Introduction: Recent new advances in myoclonus characterization and etiology justify an update of the 40-year-old respected classification of myoclonus proposed by Marsden, Hallett, and Fahn. New advances include genetic studies and clinical neurophysiology characterization.

Methods: The IAPRD appointed an expert panel to develop a new myoclonus classification.

Analysis of 1386 epileptogenic brain lesions reveals association with DYRK1A and EGFR.

Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.

Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies.

Background: Persons with schizophrenia are excluded from psychedelic-assisted therapy due to concerns about the risk of triggering or worsening psychosis. However, there is limited meta-analytic data on the risk of psychedelic-induced psychosis in individuals with pre-existing psychotic disorders.

Methods: We conducted a systematic review, meta-analysis, and overview of reviews to assess the incidence of psychedelic-induced psychosis and symptom exacerbation in schizophrenia.

Microstructural Damage and Repair in the Spinal Cord of Patients With Early Multiple Sclerosis and Association With Disability at 5 Years.

Background And Objectives: The dynamics of microstructural spinal cord (SC) damage and repair in people with multiple sclerosis (pwMS) and their clinical relevance have yet to be explored. We set out to describe patient-specific profiles of microstructural SC damage and change during the first year after MS diagnosis and to investigate their associations with disability and SC atrophy at 5 years.

Methods: We performed a longitudinal monocentric cohort study among patients with relapsing-remitting MS: first relapse <1 year, no relapse <1 month, and high initial severity on MRI (>9 T2 lesions on brain MRI and/or initial myelitis).

WONOEP appraisal: Targeted therapy development for early onset epilepsies.

The early onset epilepsies encompass a heterogeneous group of disorders, some of which result in drug-resistant seizures, developmental delay, psychiatric comorbidities, and sudden death. Advancement in the widespread use of targeted gene panels as well as genome and exome sequencing has facilitated the identification of different causative genes in a subset of these patients. The ability to recognize the genetic basis of early onset epilepsies continues to improve, with de novo coding variants accounting for most of the genetic etiologies identified.

Hippocampal neuroinflammation induced by lipopolysaccharide causes sex-specific disruptions in action selection, food approach memories, and neuronal activation.

Hippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt this behaviour is unknown. We investigated this question here using mice. First, the application of an endotoxin to primary cultures containing only hippocampal neurons did not affect their activation.

PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives.

Gliomas are the most common primary malignant brain tumours in adults. Despite decades of research into novel therapeutic approaches, the prognosis remains poor. PARP1-2 are critical for DNA repair, cell survival and genomic stability and PARP inhibition (PARPi) may be a promising therapeutic approach for gliomas.

Serotonergic underpinnings of obsessive-compulsive disorder: A systematic review and meta-analysis of neuroimaging findings.

Obsessive-compulsive disorder (OCD) is a frequent and disabling condition, with many patients being treatment-resistant. Improved understanding of its neurobiology is vital for better therapies. Evidence is still conflicting regarding specific serotonergic-related dysfunctions in OCD.

Typology of sexual disorders in idiopathic Parkinson's disease, a systematic review.

Parkinson's disease is a neurodegenerative disorder primarily characterized by motor impairments. However, non-motor symptoms are increasingly recognized and studied. Among these, sexual dysfunctions are common yet remain underexplored.