Impact of Duration of Parkinsonism and Antiparkinsonian Drugs on Coagulation Parameters in Patients with Parkinson's Disease.

Background And Objectives: Parkinson's disease (PD) is a neurodegenerative disorder involving depletion of dopaminergic neurons. Pathogenetic mechanisms leading to striatonigral degeneration are debatable. Chronic inflammation is proposed as one of the mechanisms.

Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson's disease model.

The differential vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies in mice show diverse susceptibility of subpopulations of nigral dopaminergic neurons to various toxic agents. In the primate midbrain, the molecular phenotypes of dopaminergic neurons and their differential vulnerability are poorly characterized.

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks.

Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions.

Pain in Multiple System Atrophy a Systematic Review and Meta-Analysis.

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA.

Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA.

Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism.

Secondary neurodegeneration of ipsilateral substantia nigra in acute ischemic stroke.

Introduction: Secondary neurodegeneration after stroke is a complex phenomenon affecting remote and synaptically linked cerebral areas. The involvement of the substantia nigra in this process has been rarely described in infarcts involving the striatum.

Methods: We are presenting a case of ischemic stroke involving the right striatum due to atrial fibrillation and associated in a few days with the neuroimaging finding of hyperintensity of the ipsilateral substantia nigra and striatonigral tract on T2-fluid attenuated inversion recovery and diffusion-weighted imaging sequences of brain magnetic resonance imaging.

Deep learning segmentation results in precise delineation of the putamen in multiple system atrophy.

Objectives: The precise segmentation of atrophic structures remains challenging in neurodegenerative diseases. We determined the performance of a Deep Neural Patchwork (DNP) in comparison to established segmentation algorithms regarding the ability to delineate the putamen in multiple system atrophy (MSA), Parkinson's disease (PD), and healthy controls.

Methods: We retrospectively included patients with MSA and PD as well as healthy controls.

Somatic SNCA Copy Number Variants in Multiple System Atrophy are Related to Pathology and Inclusions.

Background: Somatic α-synuclein (SNCA) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains.

Objective: The aim was to compare somatic SNCA CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions.

Methods: We combined fluorescent in situ hybridization with immunofluorescence for α-synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP).

Recessive NUP54 Variants Underlie Early-Onset Dystonia with Striatal Lesions.

Infantile striatonigral degeneration is caused by a homozygous variant of the nuclear-pore complex (NPC) gene NUP62, involved in nucleo-cytoplasmic trafficking. By querying sequencing-datasets of patients with dystonia and/or Leigh(-like) syndromes, we identified 3 unrelated individuals with biallelic variants in NUP54. All variants clustered in the C-terminal protein region that interacts with NUP62.

Improving the Accuracy of Diagnosis for Multiple-System Atrophy Using Deep Learning-Based Method.

Multiple-system atrophy (MSA) is primarily an autonomic disorder with parkinsonism or cerebellar ataxia. Clinical diagnosis of MSA at an early stage is challenging because the symptoms change over the course of the disease. Recently, various artificial intelligence-based programs have been developed to improve the diagnostic accuracy of neurodegenerative diseases, but most are limited to the evaluation of diagnostic imaging.

A Mouse Model of Multiple System Atrophy: Bench to Bedside.

Multiple system atrophy (MSA) is a rare neurodegenerative disorder with unclear etiology, currently difficult and delayed diagnosis, and rapid progression, leading to disability and lethality within 6 to 9 years after symptom onset. The neuropathology of MSA classifies the disease in the group of a-synucleinopathies together with Parkinson's disease and other Lewy body disorders, but features specific oligodendroglial inclusions, which are pathognomonic for MSA. MSA has no efficient therapy to date.

An autopsy case of amyotrophic lateral sclerosis with striatonigral and pallidoluysian degeneration and cat's-eye-shaped neuronal nuclear inclusions.

We report the case of a Japanese woman with sporadic amyotrophic lateral sclerosis (ALS) of 28 months' duration who died at the age of 66 years. Postmortem examination revealed moderate loss of neurons and phosphorylated TDP-43 (p-TDP-43)-immunoreactive neuronal and glial cytoplasmic inclusions in the upper and lower motor neurons. Additionally, marked neuronal loss was observed in the neostriatum, globus pallidum, subthalamic nucleus, and substantia nigra.

Heterogeneity of Multiple System Atrophy: An Update.

Multiple system atrophy (MSA) is a fatal, rapidly progressing neurodegenerative disease of uncertain etiology, clinically characterized by various combinations of Levodopa unresponsive parkinsonism, cerebellar, autonomic and motor dysfunctions. The morphological hallmark of this α-synucleinopathy is the deposition of aberrant α-synuclein in both glia, mainly oligodendroglia (glial cytoplasmic inclusions /GCIs/) and neurons, associated with glioneuronal degeneration of the striatonigral, olivopontocerebellar and many other neuronal systems. Typical phenotypes are MSA with predominant parkinsonism (MSA-P) and a cerebellar variant (MSA-C) with olivocerebellar atrophy.

Interleukin-4 Aggravates LPS-Induced Striatal Neurodegeneration In Vivo via Oxidative Stress and Polarization of Microglia/Macrophages.

The present study investigated the effects of interleukin (IL)-4 on striatal neurons in lipopolysaccharide (LPS)-injected rat striatum in vivo. Either LPS or PBS as a control was unilaterally injected into the striatum, and brain tissues were processed for immunohistochemical and Nissl staining or for hydroethidine histochemistry at the indicated time points after LPS injection. Analysis by NeuN and Nissl immunohistochemical staining showed a significant loss of striatal neurons at 1, 3, and 7 days post LPS.

History of Ataxias and Paraplegias with an Annotation on the First Description of Striatonigral Degeneration.

The aim of this paper is to carry out a historical overview of the evolution of the knowledge on degenerative cerebellar disorders and hereditary spastic paraplegias, over the last century and a half. Original descriptions of the main pathological subtypes, including Friedreich's ataxia, hereditary spastic paraplegia, olivopontocerebellar atrophy and cortical cerebellar atrophy, are revised. Special attention is given to the first accurate description of striatonigral degeneration by Hans Joachim Scherer, his personal and scientific trajectory being clarified.

A historical review of multiple system atrophy with a critical appraisal of cellular and animal models.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), and dysautonomia with cerebellar ataxia or parkinsonian motor features. Isolated autonomic dysfunction with predominant genitourinary dysfunction and orthostatic hypotension and REM sleep behavior disorder are common characteristics of a prodromal phase, which may occur years prior to motor-symptom onset. MSA is a unique synucleinopathy, in which alpha-synuclein (aSyn) accumulates and forms insoluble inclusions in the cytoplasm of oligodendrocytes, termed glial cytoplasmic inclusions (GCIs).

Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients.

Background: Impaired bioenergetics are partially involved in the pathogenesis of Parkinson's disease (PD). Phosphoglycerate kinase (PGK), an essential enzyme for glycolysis, has recently attracted attention due to its pathogenic role in PD and as a target for disease-modifying therapies. This study is aimed to evaluate the profiles of PGK activity in red blood cells (RBCs) of PD patients and controls.

Neuropathology of multiple system atrophy: Kurt Jellinger`s legacy.

Multiple System Atrophy (MSA) is a rare, fatal neurodegenerative disorder. Its etiology and exact pathogenesis still remain poorly understood and currently no disease-modifying therapy is available to halt or slow down this detrimental neurodegenerative process. Hallmarks of the disease are α-synuclein rich glial cytoplasmic inclusions (GCIs).

ATH434 Reduces α-Synuclein-Related Neurodegeneration in a Murine Model of Multiple System Atrophy.

Background: Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by aggregated α-synuclein (α-syn) in oligodendrocytes and accompanied by striatonigral and olivopontocerebellar degeneration and motor symptoms. Key features of MSA are replicated in the PLP-α-syn transgenic mouse, including progressive striatonigral degeneration and motor deterioration. There are currently no approved treatments for MSA.

Expanding the spectrum of VAC14 related pediatric-onset neurological disease; striatonigral degeneration with brainstem involvement.

VAC14 related childhood-onset striatonigral degeneration was first defined in 2016 in two unrelated children with sudden onset neurological disease and regression of developmental milestones. Up to now, 11 cases have been reported. VAC14 is a component of a trimolecular complex that tightly regulates the level of phosphatidylinositol 3,5-bisphosphate (PI (3, 5)P2) and PI (3, 5)P2 is critical for the survival of neural cells.

A Clinicopathologic Study of Movement Disorders in Frontotemporal Lobar Degeneration.

Background: Despite the considerable overlap with atypical parkinsonism, a systematic characterization of the movement disorders associated with frontotemporal lobar degeneration (FTLD) is lacking.

Objective: The aim of this study is to provide a detailed description of the phenomenology and neuropathologic correlations of movement disorders in FTLD.

Methods: In this cohort study, movement disorder clinical data were retrospectively collected from medical records of consecutive patients with a postmortem diagnosis of FTLD from the Queen Square Brain Bank between January 2010 and December 2018.

Altered homodimer formation and increased iron accumulation in VAC14-related disease: Case report and review of the literature.

Background: Pathogenic variants in the VAC14 component of PIKFYVE complex (VAC14) gene have been identified as a cause of a childhood-onset complex dystonia with striato-nigral degeneration. VAC14 is a scaffold protein relevant for the regulation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P) and is known to form homodimers.

Methods: Whole exome sequencing was performed in a 32-year-old patient with adolescence-onset complex dystonia and his unaffected mother.