Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.

Utility of Cerebrospinal Fluid Transferrin Receptor per Ferritin Ratio in Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a major atypical parkinsonism. Because diagnosis based on the cardinal clinical features is often difficult, misdiagnosis with Parkinson's disease (PD) and multiple system atrophy (MSA) is common in PSP patients. Iron metabolism genes are reportedly involved in tau-accumulating neuronal cell death and ferroptosis in PSP, which is more severe than PD and MSA.

Probing the diagnostic values of plasma cf-nDNA and cf-mtDNA for Parkinson's disease and multiple system atrophy.

Background: Cell loss and mitochondrial dysfunction are key pathological features of idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). It remains unclear whether disease-specific changes in plasma circulating cell-free nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) occur in patients with PD and MSA. In this study, we investigated whether plasma cf-nDNA, cf-mtDNA levels, as well as cf-mtDNA integrity, are altered in patients with PD and MSA.

The Role of Hypothalamic Microglia in the Onset of Insulin Resistance and Type 2 Diabetes: A Neuro-Immune Perspective.

Historically, microglial activation has been associated with diseases of a neurodegenerative and neuroinflammatory nature. Some, like Alzheimer's disease, Parkinson's disease, and multiple system atrophy, have been explored extensively, while others pertaining to metabolism not so much. However, emerging evidence points to hypothalamic inflammation mediated by microglia as a driver of metabolic dysregulations, particularly insulin resistance and type 2 diabetes mellitus.

Serum neurofilament light chain as a diagnostic and prognostic biomarker in multiple system atrophy: a prospective cohort study.

Background: Neurofilament light chain (NFL) in blood has been identified as a valuable biomarker in multiple system atrophy (MSA), but data regarding its utility in the early diagnosis and prognosis of MSA remain limited.

Objective: To investigate serum NFL's diagnostic and prognostic value in patients with MSA in a prospective clinical cohort.

Methods: Two hundred twenty-eight participants were enrolled, including ninety-eight with MSA, seventeen with uncertain MSA at inclusion, fifty-nine with Parkinson's disease (PD), and fifty-four healthy controls (HCs).

Reviewing the Diagnostic Performance of 99mTc-TRODAT-1 Imaging in Distinguishing Idiopathic Parkinson's Disease from Parkinson-Plus Syndromes.

 Diagnosing movement disorders can be challenging owing to their similar clinical presentations with other neurodegenerative and basal ganglia disorders, like idiopathic Parkinson's disease (IPD), essential tremors (ET), vascular parkinsonism, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Technetium-99m labeled tropane derivative (99mTc-TRODAT-1) imaging can help in diagnosing Parkinson's disease at an early stage to help early initiation of the treatment. The current study aimed to evaluate the role of 99mTc-TRODAT-1 imaging in differentiating IPD and Parkinson-plus syndromes (PPS).

The Inferior Cerebellar Peduncle Sign: A Novel Imaging Marker for Differentiating Multiple System Atrophy Cerebellar Type from Spinocerebellar Ataxia.

Background And Purpose: The hot cross bun (HCB) sign is a hallmark feature of multiple system atrophy with predominant cerebellar ataxia (MSA-C), typically observed in advanced stages of the disease; however, it can also present in other conditions such as spinocerebellar ataxia (SCA), making the differentiation challenging. The middle cerebellar peduncle (MCP) sign may be observed in various medical conditions and in healthy individuals. We hypothesized that the inferior cerebellar peduncle (ICP), known to be affected in MSA-C, may exhibit hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging, potentially aiding in differentiating MSA-C from SCA.

Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.

Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway.

From onset to advancement: the temporal spectrum of α-synuclein in synucleinopathies.

This review provides an in-depth analysis of the complex role of alpha-synuclein (α-Syn) in the development of α-synucleinopathies, with a particular focus on its structural diversity and the resulting clinical variability. The ability of α-Syn to form different strains or polymorphs and undergo various post-translational modifications significantly contributes to the wide range of symptoms observed in disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), as well as in lesser-known non-classical α-synucleinopathies. The interaction between genetic predispositions and environmental factors further complicates α-synucleinopathic disease pathogenesis, influencing the disease-specific onset and progression.

Myelin basic protein and TREM2 quantification in the CSF of patients with Multiple System Atrophy and other Parkinsonian conditions.

Background: It is well known that myelin disruption and neuroinflammation are early and distinct pathological hallmarks in multiple system atrophy (MSA) as well as in idiopathic Parkinson's disease and in other atypical Parkinsonian syndromes. The objective of this study was to assess the value of non-neuronal biomarker candidates that reflect myelin disruption and neuroinflammation.

Methods: Myelin basic protein (MBP) and the soluble form of TREM2 were quantified in a comprehensive movement disorder cohort from two different neurological centers, comprising a total of 171 CSF samples.

How to distinguish spinocerebellar ataxia 27B from late onset cerebellar ataxia: insights from a case-control study.

Background: Spinocerebellar ataxia 27B is the most common genetic late onset cerebellar ataxia (LOCA). However, it commonly overlaps with other genetic LOCA as with the cerebellar form of multiple system atrophy (MSA-C).

Objectives: To pinpoint which clinical signs and symptoms best discriminate between FGF14 + from FGF14 - patients at symptoms' onset.

Plasma circulating cell-free DNA integrity and relative telomere length as diagnostic biomarkers for Parkinson's disease and multiple system atrophy: a cross-sectional study.

In clinical specialties focusing on neurological disorders, there is a need for comprehensive and integrated non-invasive, sensitive, and specific testing methods. Both Parkinson's disease and multiple system atrophy are classified as α-synucleinopathies, characterized by abnormal accumulation of α-synuclein protein, which provides a shared pathological background for their comparative study. In addition, both Parkinson's disease and multiple system atrophy involve neuronal death, a process that may release circulating cell-free DNA (cfDNA) into the bloodstream, leading to specific alterations.

Blood-brain barrier dysfunction in multiple system atrophy: A human postmortem study.

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by an accumulation of phosphorylated α-synuclein (p-αsyn) in oligodendrocytes in the form of glial cytoplasmic inclusions (GCIs). In MSA, not only mature oligodendrocytes but also oligodendrocyte precursor cells (OPCs) are affected. The latter play an important role in remyelination by differentiating into mature oligodendrocytes, as well as maintaining the blood-brain barrier (BBB) by promoting the expression of tight junction proteins.

Treatment advances of sepsis‑induced myopathy (Review).

Sepsis-induced myopathy (SIM) is a muscle disease caused by multiple pathological and physiological mechanisms associated with sepsis. The pathogenesis of SIM is extremely complex and still unclear, making treatment challenging. At present, clinical treatment includes early functional exercise, respiratory muscle strength training, regulation of nutritional structure and functional electrical stimulation.

Effectiveness of Lee Silverman Voice Treatment (LSVT-LOUD) in Parkinsonian-Type Multiple System Atrophy (MSA-P): A Case Report.

We describe a case of Parkinsonian-type multiple system atrophy (MSA-P) treated with Lee Silverman Voice Treatment (LSVT-LOUD; LSVT Global, Inc., Phoenix, AZ, USA). At age 73, the patient developed motor symptoms, including gait disturbances with a tendency to fall, as well as swallowing difficulties and impaired dexterity in his right hand, prompting a visit to our hospital.

Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

A-synuclein prion strains differentially adapt after passage in mice.

In patients with synucleinopathies, the protein α-synuclein misfolds into multiple conformations, each of which determines whether a patient develops multiple system atrophy (MSA) or one of three Lewy body diseases (LBDs). However, patients may also first present with pure autonomic failure, which strictly impacts autonomic nerves in the periphery, which can then phenoconvert into MSA or a LBD. When neuroinvasion happens, it remains unknown if strain properties are retained or if strain adaptation occurs, even though neuroinvasion of some prion protein (PrP) strains is known to result in the emergence of novel PrP strain variants.

A lipid nanoparticle-based oligodendrocyte-specific mRNA therapy.

Despite the wide range of applications of mRNA therapies, major difficulties exist in the efficient delivery of mRNA into oligodendrocytes, a type of glial cell in the brain. Commonly used viral vectors are not efficient in transforming oligodendrocytes. In this study, we introduced mRNAs into oligodendrocytes with high efficiency and specificity using LUNAR lipid nanoparticles.

Examination of the autonomic nervous system at the bedside.

Autonomic function is an integral part of the assessment of neurological disorders. However, pragmatically, it is often the most neglected part of neurological examination and is often limited to testing for orthostatic hypotension. Testing the autonomic nervous system may aid in the early diagnosis of neurodegenerative disorders, thereby enabling the initiation of neuroprotective strategies and resulting in improved quality of life in this group of patients.

Combined quantitative analysis of the nigro-striata system in multiple system atrophy and Parkinson's disease.

Degeneration of the nigrostriatal system occurs in multiple system atrophy (MSA) and Parkinson's disease (PD) via distinct pathological mechanisms. Here, we investigated nigrostriatal degeneration in MSA and PD by combining a newly developed method for evaluating the regional accumulation of dopamine transporter single-photon emission computed tomography (DAT SPECT) and individual voxel-based morphometry adjusting covariates (iVAC). We recruited 17 MSA patients and 13 PD patients, and compared their clinical and imaging indices.

Gray matter reserve modulates the association between glymphatic system function and cognition in patients with T2DM.

Introduction: We aims to explore the relationship between the glymphatic function and cognitive function in patients with T2DM and whether this relationship is modulated by gray matter (GM) integrity.

Methods: In total, 65 patients with T2DM and 65 healthy controls (HCs) were recruited. All participants underwent evaluation using a comprehensive cognitive assessment scale.