Neuroaxonal Degeneration as a Converging Mechanism in Motor Neuron Diseases (MNDs): Molecular Insights into RNA Dysregulation and Emerging Therapeutic Targets.

Motor Neuron Diseases (MNDs) such as Amyotrophic Lateral Sclerosis (ALS), Primary Lateral Sclerosis (PLS), Hereditary Spastic Paraplegia (HSP), Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1), Multisystem Proteinopathy (MSP), Spinal and Bulbar Muscular Atrophy (SBMA), and ALS associated to Frontotemporal Dementia (ALS-FTD), have traditionally been studied as distinct entities, each one with unique genetic and clinical characteristics. However, emerging research reveals that these seemingly disparate conditions converge on shared molecular mechanisms that drive progressive neuroaxonal degeneration. This narrative review addresses a critical gap in the field by synthesizing the most recent findings into a comprehensive, cross-disease mechanisms framework.

Quantitative susceptibility mapping for investigating brain iron deposits in amyotrophic lateral sclerosis: correlations with clinical phenotype and disease progression.

: Perturbation of iron homeostasis is a potential key mechanism involved in neurodegeneration across many neurological disorders, including amyotrophic lateral sclerosis (ALS). We hypothesized that changes in quantitative susceptibility mapping (QSM) could capture perturbations in brain iron concentration in subgroups of ALS patients stratified by clinical phenotype and disease progression. : We enrolled 38 ALS patients (23 males - mean age: 58.

Digital Health in Diabetes Care: A Narrative Review from Monitoring to the Management of Systemic and Neurologic Complications.

: Despite the recent advances in glucose-lowering therapy, achieving diabetes control remains challenging. With the advancing progress of innovative digital health technologies, management of diabetes is taking advantage from telehealth and telemedicine, which allow for remote assistance, virtual visits, and monitoring of diabetes-related parameters, and facilitate the exchange of documents and reports to support clinical decisions. We aim to provide an overview of the impact of telehealth and digital technologies on the care of people with diabetes, from therapeutic management to the assessment of complications.

No additional benefit with detoxification strategies: A real world experience in 200 patients with chronic migraine and either simple or complex MOH treated with CGRP monoclonal antibodies.

BackgroundAlthough withdrawal from analgesics with or without detoxification strategy represented a mainstay in medication overuse headache (MOH) management, recent evidence supports that it is no longer beneficial when CGRP-targeting monoclonal antibodies (CGRP-mAbs) are employed. However, MOH could be stratified into simple and complex MOH phenotypes according to different clinical parameters (i.e.

In newly diagnosed diabetes, hyperglycemia is associated with increased brain iron deposition, measured by MRI-based Quantitative Susceptibility Mapping (QSM).

Background: Long-term Type 2 diabetes mellitus (T2DM) affects multiple organs and systems throughout the body, including the cardiovascular, renal, and nervous systems. In the brain, T2DM impacts brain function, leading to cognitive impairment. Due to the faster progression of cognitive decline in diabetic patients, we aim to investigate the relationship between newly diagnosed T2DM and iron deposition by brain MRI technique.

Neurodegenerative and neuroinflammatory changes in SOD1-ALS patients receiving tofersen.

The initiation of tofersen, a new specific antisense oligonucleotide (ASO) for SOD1 pathology, marked a significant turning point for SOD1-ALS patients. While clinical trials and early access program studies reported a significant reduction in plasma and cerebrospinal fluid (CSF) neurofilament levels, neuroinflammation following prolonged treatment was never assessed. In this multicenter study, we evaluated a cohort of 18 SOD1-ALS patients treated with tofersen, analyzing correlations between biomarkers of neurodegeneration/neuroinflammation and clinical variables indicative of disease progression.

Screening of visuospatial abilities in amyotrophic lateral sclerosis (ALS): a pilot study using the battery for visuospatial abilities (BVA).

Background: Cognitive deficits related to frontotemporal dysfunction are common in Amyotrophic Lateral Sclerosis (ALS). Visuospatial deficits, related to posterior cerebral regions, are often underestimated in ALS, though they play a crucial role in attending daily living activities. Our pilot study aims at assessing visuospatial abilities using a domain-specific tool in ALS patients compared to healthy controls (HC).

Harnessing Brain Plasticity: The Therapeutic Power of Repetitive Transcranial Magnetic Stimulation (rTMS) and Theta Burst Stimulation (TBS) in Neurotransmitter Modulation, Receptor Dynamics, and Neuroimaging for Neurological Innovations.

Transcranial magnetic stimulation (TMS) methods have become exciting techniques for altering brain activity and improving synaptic plasticity, earning recognition as valuable non-medicine treatments for a wide range of neurological disorders. Among these methods, repetitive TMS (rTMS) and theta-burst stimulation (TBS) show significant promise in improving outcomes for adults with complex neurological and neurodegenerative conditions, such as Alzheimer's disease, stroke, Parkinson's disease, etc. However, optimizing their effects remains a challenge due to variability in how patients respond and a limited understanding of how these techniques interact with crucial neurotransmitter systems.

Brain neurovascular coupling in amyotrophic lateral sclerosis: Correlations with disease progression and cognitive impairment.

Background And Purpose: 'Neurovascular coupling' (NVC) alterations, assessing the interplay between local cerebral perfusion and neural activity within a given brain region or network, may reflect neurovascular unit impairment in amyotrophic lateral sclerosis (ALS). The aim was to explore NVC as a correlation between the functional connectivity and cerebral blood flow within the large-scale resting-state functional magnetic resonance imaging brain networks in a sample of ALS patients compared to healthy controls (HCs).

Methods: Forty-eight ALS patients (30 males; mean age 60.

Functional Connectome Controllability in Patients with Mild Cognitive Impairment after Repetitive Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex.

: Repetitive transcranial magnetic stimulation (rTMS) has shown therapeutic effects in neurological patients by inducing neural plasticity. In this pilot study, we analyzed the modifying effects of high-frequency (HF-)rTMS applied to the dorsolateral prefrontal cortex (DLPFC) of patients with mild cognitive impairment (MCI) using an advanced approach of functional connectome analysis based on network control theory (NCT). : Using local-to-global functional parcellation, average and modal controllability (AC/MC) were estimated for DLPFC nodes of prefrontal-lateral control networks (R/LH_Cont_PFCl_3/4) from a resting-state fMRI series acquired at three time points (T0 = baseline, T1 = T0 + 4 weeks, T2 = T1 + 20 weeks) in MCI patients receiving regular daily sessions of 10 Hz HF-rTMS ( = 10, 68.

Colchicine treatment in amyotrophic lateral sclerosis: safety, biological and clinical effects in a randomized clinical trial.

In preclinical studies, the anti-inflammatory drug colchicine, which has never been tested in amyotrophic lateral sclerosis, enhanced the expression of autophagy factors and inhibited accumulation of transactive response DNA-binding protein 43 kDa, a known histopathological marker of amyotrophic lateral sclerosis. This multicentre, randomized, double-blind trial enrolled patients with probable or definite amyotrophic lateral sclerosis who experienced symptom onset within the past 18 months. Patients were randomly assigned in a 1:1:1 ratio to receive colchicine at a dose of 0.

Reliability of quantitative magnetic susceptibility imaging metrics for cerebral cortex and major subcortical structures.

Background And Purpose: Susceptibility estimates derived from quantitative susceptibility mapping (QSM) images for the cerebral cortex and major subcortical structures are variably reported in brain magnetic resonance imaging (MRI) studies, as average of all ( ), absolute ( ), or positive- ( ) and negative-only ( ) susceptibility values using a region of interest (ROI) approach. This pilot study presents a reliability analysis of currently used ROI-QSM metrics and an alternative ROI-based approach to obtain voxel-weighted ROI-QSM metrics ( and ).

Methods: Ten healthy subjects underwent repeated (test-retest) 3-dimensional multi-echo gradient-echo (3DMEGE) 3 Tesla MRI measurements.

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

Introduction/aims: Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3.

Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis.

Objective: To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture.

Methods: We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches.

Dihydroergotamine mesylate nasal spray: an acute treatment option for migraine in adults.

Introduction: Although the landscape of migraine symptomatic treatment has been enriched by novel effective drugs, it is mandatory to critically reappraise older molecules to ascertain whether they could still represent reliable alternatives in specific endophenotypes of patients or migraine attacks. Among these, dihydroergotamine (DHE) nasal spray has been shown to be effective and is characterized by greater tolerability and manageability than the parenteral DHE formulation.

Areas Covered: In this narrative review, the authors describe the pharmacodynamic and pharmacokinetic properties of DHE nasal spray and explore the results of the trials which explored its efficacy, safety and tolerability as migraine symptomatic treatment.

Repetitive Transcranial Magnetic Stimulation (rTMS) in Mild Cognitive Impairment: Effects on Cognitive Functions-A Systematic Review.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique also used as a non-pharmacological intervention against cognitive impairment. The purpose of the present review was to summarize what is currently known about the effectiveness of rTMS intervention on different cognitive domains in patients with mild cognitive impairment (MCI) and to address potential neuromodulation approaches in combination with electroencephalography (EEG) and neuroimaging, especially functional magnetic resonance imaging (fMRI). In this systematic review, we consulted three main databases (PubMed, Science Direct, and Scopus), and Google Scholar was selected for the gray literature search.

Retrospective observational study on the use of acetyl-L-carnitine in ALS.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC.

Cognitive, behavioral, and brain functional connectivity correlates of fatigue in amyotrophic lateral sclerosis.

Introduction: Fatigue is defined as a symptom of exhaustion unexplained by drug effects or psychiatric disorders and comprises two main components (i.e., central or "mental" and peripheral or "physical" components), both influencing global disability in amyotrophic lateral sclerosis (ALS).

Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.

Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders.