1,137 results match your criteria: "Olivopontocerebellar Atrophy"

Article Synopsis
  • The inferior olive (IO) is a key brainstem region affected by spinocerebellar ataxias (SCAs), impacting motor learning, but its degeneration mechanisms remain unclear.
  • Researchers studied SCA1 using a genetically modified mouse model (SCA1-KI) and found that these mice show olivary hypertrophy similar to hypertrophic olivary degeneration (HOD), with early neuronal changes but no loss of cells.
  • The SCA1-KI IO neurons are hyperexcitable and have reduced expression of ion channels that typically regulate their activity, indicating a dysregulation linked to mutant ataxin-1 expression in these neurons.
View Article and Find Full Text PDF

Olivopontocerebellar degeneration (OPCD) primarily affects individuals in their mid to late adulthood, making its early onset in young adults, particularly postpartum women, a notable rarity. This case report describes OPCD in a 24-year-old female, underscoring the importance of considering neurodegenerative disorders in differential diagnoses even in younger patients. The unique presentation post childbirth adds to the sparse literature on the timing and triggers of neurodegenerative diseases in younger populations, especially in scenarios that might involve hormonal, vascular, or autoimmune shifts such as those occurring postpartum.

View Article and Find Full Text PDF

Atypical Parkinsonian Syndromes: Structural, Functional, and Molecular Imaging Features.

AJNR Am J Neuroradiol

December 2024

Neuroradiology Division (F.M., S.S., A.M.F.), Department of Radiology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lenox Hill Hospital, New York, New York

Atypical parkinsonian syndromes, also known as Parkinson-plus syndromes, are a heterogeneous group of movement disorders, including dementia with Lewy bodies (DLB), progressive supranuclear palsy (PSP), multisystem atrophy (MSA), and corticobasal degeneration (CBD). This review highlights the characteristic structural, functional, and molecular imaging features of these complex disorders. DLB typically demonstrates parieto-occipital hypometabolism with involvement of the cuneus on FDG-PET, whereas dopaminergic imaging, such as [I]-FP-CIT SPECT (DaTscan) or fluorodopa (FDOPA)-PET, can be utilized as an adjunct for diagnosis.

View Article and Find Full Text PDF
Article Synopsis
  • Pontocerebellar hypoplasia type 2a (PCH2a) is a rare genetic disorder affecting children, characterized by underdeveloped brain regions (cerebellum and pons) and progressive small head size (microcephaly).
  • The disorder is caused by a specific genetic variant in the TSEN54 gene, which impacts a key protein involved in RNA processing, but the underlying mechanisms of the disease are not well understood.
  • Researchers created human models of PCH2a using stem cells to study the disease, finding that cerebellar organoids from affected individuals were smaller and showed altered cell growth patterns, suggesting a developmental issue in the brain as part of the disease's
View Article and Find Full Text PDF

A rapidly progressive multiple system atrophy-cerebellar variant model presenting marked glial reactions with inflammation and spreading of α-synuclein oligomers and phosphorylated α-synuclein aggregates.

Brain Behav Immun

October 2024

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Translational Neuroscience Research Center, Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan; Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka, Japan. Electronic address:

Multiple system atrophy (MSA) is a severe α-synucleinopathy facilitated by glial reactions; the cerebellar variant (MSA-C) preferentially involves olivopontocerebellar fibres with conspicuous demyelination. A lack of aggressive models that preferentially involve olivopontocerebellar tracts in adulthood has hindered our understanding of the mechanisms of demyelination and neuroaxonal loss, and thus the development of effective treatments for MSA. We therefore aimed to develop a rapidly progressive mouse model that recaptures MSA-C pathology.

View Article and Find Full Text PDF

Long-Term Disease Course of Pontocerebellar Hypoplasia Type 10.

Pediatr Neurol

September 2024

Istanbul Medical Faculty, Department of Medical Genetics, Istanbul University, Istanbul, Turkey.

Background: Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and physical disabilities, and spasticity. In this follow-up study, evolution of phenotypic and neurological characteristics of patients with PCH10 is discussed.

Methods: Phenotype, growth parameters, motor functions, developmental tests, spasticity assessments, functional independence assessments, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) of 10 patients with PCH10 were monitored on separate examinations.

View Article and Find Full Text PDF

Multiple system atrophy is a neurodegenerative disease with α-synuclein pathology predominating in the striatonigral and olivopontocerebellar systems. Mixed pathologies are considered to be of low frequency and mostly comprise primary age-related tauopathy or low levels of Alzheimer's disease-related neuropathologic change. Therefore, the concomitant presence of different misfolded proteins in the same brain region is less likely in multiple system atrophy.

View Article and Find Full Text PDF

Mitofusin 2 Variant Presenting With a Phenotype of Multiple System Atrophy of Cerebellar Subtype.

Neurol Genet

February 2024

From the Department of Medical Genetics (A.E., K.D., C.F.B., S.J.J.), University of British Columbia; Provincial Medical Genetics Program (A.E., S.H., C.B.), B.C. Women's Hospital and Health Centre; Canada's Michael Smith Genome Sciences Centre (K.D., Y.S., S.J.J.), BC Cancer; Fraser Health Movement Disorders Clinic (A.K.K.), Jim Pattison Outpatient Care and Surgery Centre, Surrey; and Department of Medicine (A.K.K.), Division of Neurology, University of British Columbia, Vancouver, Canada.

Objectives: To investigate the etiology of cerebellar ataxia in an adult male patient.

Methods: We performed standard neurologic assessment and genome sequencing of a 62-year-old man with rapidly progressive balance and gait abnormalities.

Results: The propositus exhibited cognitive dysfunction, mild appendicular bradykinesia, prominent appendicular ataxia, dysarthria, and hypomimia with minimal dysautonomic symptoms.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • RARS2 gene defects are linked to cerebellopontine hypoplasia type 6 (PCH6), a rare mitochondrial disease, as demonstrated in two male patients with unique family histories.
  • The study utilized clinical presentations, MRI scans, and whole-exome sequencing to identify specific genetic mutations in both patients, revealing novel RARS2 variants that were not previously reported.
  • The findings suggest a broader spectrum of RARS2 mutations and highlight new phenotypes, including early infantile developmental and epileptic encephalopathies, which strengthen the connection between PCH6 and the RARS2 gene.
View Article and Find Full Text PDF

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that presents with variable combinations of autonomic dysfunction, cerebellar ataxia, parkinsonism, and pyramidal signs. The inferior olivary nucleus is targeted in MSA, with a phenotype of olivopontocerebellar atrophy in particular, and involvement of the olivocerebellar tract is well known. However, degeneration of the olivospinal tract has not been studied in MSA.

View Article and Find Full Text PDF

Quantitative cellular changes in multiple system atrophy brains.

Neuropathol Appl Neurobiol

December 2023

Centre for Neuroscience and Stereology, Department of Neurology, Bispebjerg-Frederiksberg Hospital, Copenhagen, Denmark.

Multiple system atrophy (MSA) is a neurodegenerative disorder characterised by a combined symptomatology of parkinsonism, cerebellar ataxia, autonomic failure and corticospinal dysfunction. In brains of MSA patients, the hallmark lesion is the aggregation of misfolded alpha-synuclein in oligodendrocytes. Even though the underlying pathological mechanisms remain poorly understood, the evidence suggests that alpha-synuclein aggregation in oligodendrocytes may contribute to the neurodegeneration seen in MSA.

View Article and Find Full Text PDF

The spinocerebellar ataxias (SCAs) are a group of dominantly inherited neurodegenerative diseases, several of which are caused by CAG expansion mutations (SCAs 1, 2, 3, 6, 7 and 12) and more broadly belong to the large family of over 40 microsatellite expansion diseases. While dysregulation of alternative splicing is a well defined driver of disease pathogenesis across several microsatellite diseases, the contribution of alternative splicing in CAG expansion SCAs is poorly understood. Furthermore, despite extensive studies on differential gene expression, there remains a gap in our understanding of presymptomatic transcriptomic drivers of disease.

View Article and Find Full Text PDF

Application of the Yamanaka Transcription Factors , , , and from the Laboratory to the Clinic.

Genes (Basel)

August 2023

Faculty of Medicine, Universidad de La Sabana, Km 7, Autopista Norte de Bogotá, Chía 250001, Colombia.

The transcription factors , , , and enable the reprogramming of somatic cells into induced pluripotent cells. Reprogramming generates newly differentiated cells for potential therapies in cancer, neurodegenerative diseases, and rejuvenation processes. In cancer therapies, these transcription factors lead to a reduction in the size and aggressiveness of certain tumors, such as sarcomas, and in neurodegenerative diseases, they enable the production of dopaminergic cells in Parkinson's disease, the replacement of affected neuronal cells in olivopontocerebellar atrophy, and the regeneration of the optic nerve.

View Article and Find Full Text PDF

It is well established that extreme prematurity can be associated with cerebellar lesions potentially affecting the neurologic prognosis. One of the commonly observed lesions in these cases is pontocerebellar hypoplasia resulting from prematurity, which can pose challenges in distinguishing it from genetically caused pontocerebellar hypoplasia. This confusion leads to unacceptable and prolonged diagnostic ambiguity for families as well as difficulties in genetic counseling.

View Article and Find Full Text PDF

Polyglutamine (polyQ) diseases are neurodegenerative disorders caused by abnormally expanded Cytosine, Adenine, Guanine (CAG) triplet repeat sequences in the coding region of otherwise unrelated genes. Until now, nine different polyQ diseases have been described: Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy and six types of spinocerebellar ataxias-1, 2, 3, 6, 7 and 17. The pathogenic expansion translates into an aberrant tract of glutamines in the encoded proteins, compromising several cellular functions and biological processes.

View Article and Find Full Text PDF

Bi-allelic variants in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene have been involved in early-onset encephalopathies classified as pontocerebellar hypoplasia (PCH) type 6 and in epileptic encephalopathy. A variant (NM_020320.3:c.

View Article and Find Full Text PDF

Objective: To describe the features of the clinical presentation and evaluate the incidence of HIV-associated cerebellar degeneration in patients with progressive cerebellar ataxia.

Material And Methods: Three hundred and seventy-seven patients with progressive cerebellar ataxia were studied. Brain MRI study, assessment by the Scale for the Assessment and Rating of Ataxia (SARA), screening for cognitive impairment by the Montreal Cognitive Assessment Scale (MoCA) were performed.

View Article and Find Full Text PDF

Background: Amplitude-based exercise training has been shown to be effective in the motor performance of individuals with idiopathic Parkinson's disease, with limited research investigating its effects on Parkinson plus syndromes such as olivopontocerebellar atrophy (OPCA). The purpose of this clinical case report is to examine the effects of amplitude-based training exercises on an individual with OPCA.

Case Description: A 68-year-old man with a 14-month history of OPCA presented to physical therapy with bradykinesia, rigidity, and postural instability.

View Article and Find Full Text PDF

Multiple system atrophy: at the crossroads of cellular, molecular and genetic mechanisms.

Nat Rev Neurosci

June 2023

Division of Neurobiology, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Multiple system atrophy (MSA) is a rare oligodendroglial α-synucleinopathy characterized by neurodegeneration in striatonigral and olivopontocerebellar regions and autonomic brain centres. It causes complex cumulative motor and non-motor disability with fast progression and effective therapy is currently lacking. The difficulties in the diagnosis and treatment of MSA are largely related to the incomplete understanding of the pathogenesis of the disease.

View Article and Find Full Text PDF

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders characterized by a wide phenotypic range including severe motor and cognitive impairments, microcephaly, distinctive facial features, and other features according to the type. Several classes of PCH1 have been linked to mutations in the evolutionarily conserved RNA exosome complex that consists of nine subunits (EXOSC1 to EXOSC9) and facilitates the degradation and processing of cytoplasmic and nuclear RNA from the 3' end. Only a single individual with an EXOSC1 mutation was reported with clinical features of PCH type 1 (PCH1F).

View Article and Find Full Text PDF

Role of Oligodendrocyte Lineage Cells in Multiple System Atrophy.

Cells

February 2023

Brain and Mind Centre, Faculty of Medicine and Health, School of Medical Sciences, The University of Sydney, Sydney, NSW 2050, Australia.

Article Synopsis
  • Multiple system atrophy (MSA) is a serious movement disorder characterized by symptoms like parkinsonism and cerebellar dysfunction, caused by degeneration in specific brain regions.
  • The early stages of the disease involve a prodromal phase, making it crucial to understand initial pathological changes to help develop future treatments.
  • Recent findings confirm MSA as an oligodendrogliopathy linked to α-synuclein, highlighting potential origins of toxic proteins and their impact on neuron loss, which could shape future research on MSA.
View Article and Find Full Text PDF

A novel INPP4A mutation with pontocerebellar hypoplasia, myoclonic epilepsy, microcephaly, and severe developmental delay.

Brain Dev

May 2023

Faculty of Medicine, Department of Pediatric Neurology, Farabi Hospital, Karadeniz Technical University, Trabzon, Türkiye. Electronic address:

Background: The inositol polyphosphate 4-phosphatase intracellular signaling pathway is susceptible to genetic or epigenetic alterations that may result in major neurological illnesses with clinically significant pons and cerebellum involvement.

Case Reports: A seven-year-old girl with pontocerebellar hypoplasia, resistant myoclonic epilepsy with axial hypotonia, microcephaly, atypical facial appearance, nystagmus, ophthalmoplegia, hyperactive tendon reflexes, spasticity, clonus, extensor plantar response, contractures in wrists and ankles and growth retardation, whole-exome sequencing was performed and a homozygous "NM_001134225.2:c.

View Article and Find Full Text PDF