1,001 results match your criteria Olivopontocerebellar Atrophy


[Early onset epileptic encephalopathy caused by mitochondrial arginyl-tRNA synthetase gene deficiency: report of two cases and literature review].

Zhonghua Er Ke Za Zhi 2020 Nov;58(11):893-899

Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

To summarize the clinical features of two early onset epileptic encephalopathy (EOEE) patients with arginyl-tRNA synthetase (RARS2) gene variations and to review related literature. The clinical data and genetic features of two pontocerebellar hypoplasia type 6 (PCH6) patients with RARS2 variation diagnosed by the Department of Neurology, Beijing Children's Hospital from January 2017 to December 2018 were analyzed retrospectively. A literature search with "RARS2" "pontocerebellar hypoplasia type 6" and "early onset epileptic encephalopathy" as key words was conducted at China national knowledge infrastructure (CNKI), Wanfang Data Knowledge Service Platform and PubMed (up to May 2020), literature about RARS2 gene variation patients and their complete clinical data were chosen and reviewed. Read More

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November 2020

Shared Genetics of Multiple System Atrophy and Inflammatory Bowel Disease.

Mov Disord 2021 02 27;36(2):449-459. Epub 2020 Oct 27.

Rita Lila Weston Institute, University College London, London, UK.

Background: Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by intracellular accumulations of α-synuclein and nerve cell loss in striatonigral and olivopontocerebellar structures. Epidemiological and clinical studies have reported potential involvement of autoimmune mechanisms in MSA pathogenesis. However, genetic etiology of this interaction remains unknown. Read More

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February 2021

Early decrease in intermediate monocytes in peripheral blood is characteristic of multiple system atrophy-cerebellar type.

J Neuroimmunol 2020 12 20;349:577395. Epub 2020 Sep 20.

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Translational Neuroscience Center, Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, 137-1 Enokizu, Ookawa, Fukuoka 831-8501, Japan; Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, 2-6-11 Yakuin, Chuou-ku, Fukuoka 810-0022, Japan. Electronic address:

To identify biomarkers for multiple system atrophy-cerebellar type (MSA-C), we used flow cytometry to measure surface marker expression of peripheral blood monocytes from patients with MSA-C or hereditary spinocerebellar degeneration (hSCD) and from healthy controls (HCs). The percentage of intermediate monocytes was significantly lower in MSA-C patients than in hSCD patients and HCs and showed significant positive correlations with disease duration and unified MSA rating scale scores. The percentage of CD62L intermediate monocytes was significantly lower in MSA-C patients than in hSCD patients and HCs. Read More

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December 2020

A clinical report of the massive CAG repeat expansion in spinocerebellar ataxia type 2: Severe onset in a Mexican child and review previous cases.

Genet Mol Biol 2020 08 21;43(3):e20190325. Epub 2020 Aug 21.

Universidad de Guadalajara, Centro Universitario de Ciencias de la Salud - CUCS, Instituto de Genética Humana "Enrique Corona Rivera", Jalisco, Mexico.

The spinocerebellar ataxia type 2 is a neurodegenerative disease with autosomal dominant inheritance; clinically characterized by progressive cerebellar ataxia, slow ocular saccades, nystagmus, ophthalmoplegia, dysarthria, dysphagia, cognitive deterioration, mild dementia, peripheral neuropathy. Infantile onset is a rare presentation that only has been reported in four instances in the literature. In the present work a boy aged 5 years 7 months was studied due to horizontal gaze-evoked nystagmus, without saccades, ataxic gait, dysarthria, dysphagia, dysmetria, generalized spasticity mainly pelvic, bilateral Babinsky. Read More

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The Use of FDG PET Parametric Imaging in the Diagnosis of Olivopontocerebellar Atrophy.

Clin Nucl Med 2020 Sep;45(9):e419-e421

From the Staten Island University Hospital, Northwell Health, Staten Island, NY.

Olivopontocerebellar atrophy is a rare neurodegenerative syndrome associated with 2 distinct disorders: multiple system atrophy and spinocerebellar ataxia. We present a case involving a 66-year-old man with adult-onset progressing cerebellar signs reflective of a cerebellar syndrome with no significant family history and unremarkable genetic testing for spinocerebellar ataxia. This case was found to be most consistent with sporadic olivopontocerebellar atrophy, which falls under the multiple system atrophy category. Read More

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September 2020

Hippocampal α-synuclein pathology correlates with memory impairment in multiple system atrophy.

Brain 2020 06;143(6):1798-1810

Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK.

Recent post-mortem studies reported 22-37% of patients with multiple system atrophy can develop cognitive impairment. With the aim of identifying associations between cognitive impairment including memory impairment and α-synuclein pathology, 148 consecutive patients with pathologically proven multiple system atrophy were reviewed. Among them, 118 (79. Read More

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Teaching Video NeuroImages: Palatal tremor associated with variants.

Neurology 2020 05 21;94(19):e2074-e2075. Epub 2020 Apr 21.

From the UOC Neurofisiopatologia (G.P., S.S.), Fondazione Policlinico Universitario A. Gemelli IRCCS; Istituto di Neurologia (G.P., S.S.), Università Cattolica del Sacro Cuore; and Unit of Neuromuscular and Neurodegenerative Disorders (G.Z., M.N.), Department of Neurosciences, IRCCS, Bambino Gesù Research Hospital, Rome, Italy.

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Supratentorial and Infratentorial Lesions in Spinocerebellar Ataxia Type 3.

Front Neurol 2020 3;11:124. Epub 2020 Mar 3.

Brain Research Center, National Yang-Ming University, Taipei, Taiwan.

Spinocerebellar ataxia type 3 (SCA) is a cerebellum-dominant degenerative disorder that is characterized primarily by infratentorial damage, although less severe supratentorial involvement may contribute to the clinical manifestation. These impairments may result from the efferent loss of the cerebellar cortex and degeneration of the cerebral cortex. We used the three-dimensional fractal dimension (3D-FD) method to quantify the morphological changes in the supratentorial regions and assessed atrophy in the relatively focal regions in patients with SCA3. Read More

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Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes.

J Neurosci 2020 04 2;40(14):2943-2959. Epub 2020 Mar 2.

German Center for Neurodegenerative Diseases, Charité Medical University, 10117 Berlin, Germany,

Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3). We have characterized recently generated Piccolo KO ( ) rats. Read More

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Genes to treat excitotoxicity ameliorate the symptoms of the disease in mice models of multiple system atrophy.

J Neural Transm (Vienna) 2020 02 17;127(2):205-212. Epub 2020 Feb 17.

Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder characterized by striatonigral degeneration and olivopontocerebellar atrophy. The main hallmark of MSA is the aggregation of alpha-synuclein in oligodendrocytes, which contributes to the dysfunction and death of the oligodendrocytes, followed by neurodegeneration. Studies suggested that oxidative-excitatory pathway is associated with the progression of the disease. Read More

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February 2020

Neuroimaging Biomarkers in SCA2 Gene Carriers.

Int J Mol Sci 2020 Feb 4;21(3). Epub 2020 Feb 4.

Nuclear Medicine at University Hospital, 53100 Siena, Italy.

A variety of Magnetic Resonance (MR) and nuclear medicine (NM) techniques have been used in symptomatic and presymptomatic SCA2 gene carriers to explore,in vivo, the physiopathological biomarkers of the neurological dysfunctions characterizing the associated progressive disease that presents with a cerebellar syndrome, or less frequently, with a levodopa-responsive parkinsonian syndrome. Morphometry performed on T1-weighted images and diffusion MR imaging enable structural and microstructural evaluation of the brain in presymptomatic and symptomatic SCA2 gene carriers, in whom they show the typical pattern of olivopontocerebellar atrophy observed at neuropathological examination. Proton MR spectroscopy reveals, in the pons and cerebellum of SCA2 gene carriers,a more pronounced degree of abnormal neurochemical profile compared to other spinocerebellar ataxias with decreased NAA/Cr and Cho/Cr, increased mi/Cr ratios, and decreased NAA and increased mI concentrations. Read More

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February 2020

MSA: From basic mechanisms to experimental therapeutics.

Parkinsonism Relat Disord 2020 04 23;73:94-104. Epub 2020 Jan 23.

Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Austria. Electronic address:

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by rapidly progressive autonomic and motor dysfunction. Pathologically, MSA is mainly characterized by the abnormal accumulation of misfolded α-synuclein in the cytoplasm of oligodendrocytes, which plays a major role in the pathogenesis of the disease. Striatonigral degeneration and olivopontecerebellar atrophy underlie the motor syndrome, while degeneration of autonomic centers defines the autonomic failure in MSA. Read More

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Multiple system atrophy.

Int Rev Neurobiol 2019 21;149:137-192. Epub 2019 Nov 21.

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

Multiple system atrophy (MSA) is a sporadic, adult-onset, relentlessly progressive neurodegenerative disorder, clinically characterized by various combinations of autonomic failure, parkinsonism and ataxia. The neuropathological hallmark of MSA are glial cytoplasmic inclusions consisting of misfolded α-synuclein. Selective atrophy and neuronal loss in striatonigral and olivopontocerebellar systems underlie the division into two main motor phenotypes of MSA-parkinsonian type and MSA-cerebellar type. Read More

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Pathological changes in the cerebellum of patients with multiple system atrophy and Parkinson's disease-a stereological study.

Brain Pathol 2020 05 6;30(3):576-588. Epub 2020 Jan 6.

Research Laboratory for Stereology and Neuroscience, Department of Neurology, Bispebjerg-Frederiksberg Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, Denmark.

Multiple system atrophy (MSA) and Parkinson's disease (PD) are synucleinopathies characterized by aggregation of α-synuclein in brain cells. Recent studies have shown that morphological changes in terms of cerebral nerve cell loss and increase in glia cell numbers, the degree of brain atrophy and molecular and epidemiological findings are more severe in MSA than PD. In the present study, we performed a stereological comparison of cerebellar volumes, granule and Purkinje cells in 13 patients diagnosed with MSA [8 MSA-P (striatonigral subtype) and 5 MSA-C (olivopontocerebellar subtype)], 12 PD patients, and 15 age-matched control subjects. Read More

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Multiple System Atrophy With Predominant Striatonigral Degeneration and TAR DNA-Binding Protein of 43 kDa Pathology: An Unusual Variant of Multiple System Atrophy.

Mov Disord Clin Pract 2019 Nov 6;6(8):661-666. Epub 2019 Sep 6.

Department of Pathology Columbia University Medical Center New York New York USA.

Background: The pathological hallmark in MSA is oligodendrocytic glial cytoplasmic inclusions (GCIs) containing α-synuclein, in addition to neuronal loss and astrogliosis especially involving the striatonigral and olivopontocerebellar systems. Rarely, TAR DNA-binding protein of 43 kDa (TDP-43), a component of ubiquitinated inclusions observed mainly in amyotrophic lateral sclerosis and frontotemporal lobar degeneration has been demonstrated in cases of MSA and, more recently, was shown to colocalize with α-synuclein pathology in GCIs in 2 patients.

Methods: A 66-year-old woman presented with a syndrome characterized by spasticity, dysautonomia, bulbar dysfunction, and parkinsonism. Read More

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November 2019

Neuroradiological Findings in the Spinocerebellar Ataxias.

Tremor Other Hyperkinet Mov (N Y) 2019 26;9. Epub 2019 Sep 26.

Movement Disorders Unit, Neurology Service, Internal Medicine Department, Hospital de Clínicas, Federal University of Paraná, Curitiba, BR.

Background: The spinocerebellar ataxias (SCAs) are a group of autosomal dominant degenerative diseases characterized by cerebellar ataxia. Classified according to gene discovery, specific features of the SCAs - clinical, laboratorial, and neuroradiological (NR) - can facilitate establishing the diagnosis. The purpose of this study was to review the particular NR abnormalities in the main SCAs. Read More

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A patient with pontocerebellar hypoplasia type 6: Novel RARS2 mutations, comparison to previously published patients and clinical distinction from PEHO syndrome.

Eur J Med Genet 2020 Mar 16;63(3):103766. Epub 2019 Sep 16.

Folkhälsan Research Center, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Finland. Electronic address:

Pontocerebellar hypoplasia type 6 (PCH6) is a rare infantile-onset progressive encephalopathy caused by biallelic mutations in RARS2 that encodes the mitochondrial arginine-tRNA synthetase enzyme (mtArgRS). The clinical presentation overlaps that of PEHO syndrome (Progressive Encephalopathy with edema, Hypsarrhythmia and Optic atrophy). The proband presented with severe intellectual disability, epilepsy with varying seizure types, optic atrophy, axial hypotonia, acquired microcephaly, dysmorphic features and progressive cerebral and cerebellar atrophy and delayed myelination on MRI. Read More

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White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy.

Acta Neuropathol 2020 01 18;139(1):135-156. Epub 2019 Sep 18.

The Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London, UK.

Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson's disease are α-synucleinopathies. Pathologically, MSA can be categorized into striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) or mixed subtypes. Read More

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January 2020

Cross-examining candidate genes implicated in multiple system atrophy.

Acta Neuropathol Commun 2019 07 24;7(1):117. Epub 2019 Jul 24.

Brain and Mind Centre & Central Clinical School, The University of Sydney, Sydney, NSW, Australia.

Multiple system atrophy (MSA) is a devastating neurodegenerative disease characterized by the clinical triad of parkinsonism, cerebellar ataxia and autonomic failure, impacting on striatonigral, olivopontocerebellar and autonomic systems. At early stage of the disease, the clinical symptoms of MSA can overlap with those of Parkinson's disease (PD). The key pathological hallmark of MSA is the presence of glial cytoplasmic inclusions (GCI) in oligodendrocytes. Read More

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Young-onset multiple system atrophy: Its rarity and heterogeneity.

Mov Disord 2019 07;34(7):1085-1086

Department of Neurology and Movement Disorder Center, College of Medicine, Seoul National University, Seoul, Korea.

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Expanded PCH1D phenotype linked to EXOSC9 mutation.

Eur J Med Genet 2020 Jan 25;63(1):103622. Epub 2019 Jan 25.

Pediatric Department, Latifa Hospital, Dubai Health Authority, P.O.Box 4115, Dubai, United Arab Emirates.

Pontocerebellar Hypoplasia type 1 is a rare heterogeneous neurodegenerative disorder with multiple subtypes linked to dysfunction of the exosome complex. Patients with mutations in exosome subunits exhibit a generally lethal phenotype characterized by cerebellar and pontine hypoplasia in association with spinal motor neuropathy and multiple systemic and neurologic features. Recently, two variants in the novel PCH1 associated protein EXOSC9 p. Read More

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January 2020

The 'Hot Cross Bun' Sign Is Not Always Multiple System Atrophy: Etiologies of 11 Cases.

J Mov Disord 2019 01 19;12(1):27-30. Epub 2018 Dec 19.

Department of Neurology, Movement Disorders, Portland Veterans Administration, Parkinson’s Disease Research, Education and Clinical Center, Portland, OR, USA

Objective: To clarify the specificity of the 'hot cross bun' sign (HCBS) for multiple system atrophy (MSA) in adult cerebellar ataxia or parkinsonism.

Methods: The radiologic information systems at an academic center and affiliated veterans' hospital were queried using the keywords 'hot cross bun,' 'pontocerebellar,' 'cruciate,' 'cruciform,' 'MSA,' 'multiple system atrophy,' and 'multisystem atrophy.' Scans were reviewed by a neurologist and neuroradiologist to identify the HCBS. Read More

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January 2019

New Radiologic Findings of Hypertrophic Olivary Degeneration in 2 Patients with Brainstem Lymphoma.

World Neurosurg 2019 Mar 26;123:464-468.e1. Epub 2018 Nov 26.

Department of Neurosurgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.

Background: Hypertrophic olivary degeneration (HOD) is a rare neurological condition of trans-synaptic degeneration caused by disruption of the dentatorubro-olivary pathway. We present new radiologic findings of HOD in 2 cases of brainstem lymphoma.

Case Description: A 35-year-old woman (Case 1) and a 69-year-old man (Case 2) presented with remarkably similar clinical courses. Read More

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Neuroimaging Applications in Chronic Ataxias.

Int Rev Neurobiol 2018 29;143:109-162. Epub 2018 Oct 29.

Nuclear Medicine, "Le Scotte" University Hospital, Siena, Italy.

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET) are the main instruments for neuroimaging investigation of patients with chronic ataxia. MRI has a predominant diagnostic role in the single patient, based on the visual detection of three patterns of atrophy, namely, spinal atrophy, cortical cerebellar atrophy and olivopontocerebellar atrophy, which correlate with the aetiologies of inherited or sporadic ataxia. In fact spinal atrophy is observed in Friedreich ataxia, cortical cerebellar atrophy in Ataxia Telangectasia, gluten ataxia and Sporadic Adult Onset Ataxia and olivopontocerebellar atrophy in Multiple System Atrophy cerebellar type. Read More

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Clinics in diagnostic imaging (191). Multiple system atrophy-cerebellar type (MSA-C).

Singapore Med J 2018 Oct;59(10):550-554

Department of Diagnostic Radiology, Singapore General Hospital, Singapore.

A 49-year-old Chinese man was evaluated for progressive uncoordinated movements, dysphagia and urinary symptoms. Magnetic resonance imaging demonstrated a cruciform pattern of T2-weighted hyperintensity within the pons and selective atrophy of the cerebellar hemispheres and pons. The clinical history and radiological findings were consistent with a diagnosis of multiple system atrophy-cerebellar type. Read More

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October 2018

Converging Patterns of α-Synuclein Pathology in Multiple System Atrophy.

J Neuropathol Exp Neurol 2018 11;77(11):1005-1016

Center for Neurodegenerative Disease Research (CNDR), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

We aimed to determine patterns of α-synuclein (α-syn) pathology in multiple system atrophy (MSA) using 70-µm-thick sections of 20 regions of the central nervous system of 37 cases with striato-nigral degeneration (SND) and 10 cases with olivo-ponto-cerebellar atrophy (OPCA). In SND cases with the shortest disease duration (phase 1), α-syn pathology was observed in striatum, lentiform nucleus, substantia nigra, brainstem white matter tracts, cerebellar subcortical white matter as well as motor cortex, midfrontal cortex, and sensory cortex. SND with increasing duration of disease (phase 2) was characterized by involvement of spinal cord and thalamus, while phase 3 was characterized by involvement of hippocampus and amygdala. Read More

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November 2018

Young-onset multiple system atrophy: Clinical and pathological features.

Mov Disord 2018 07;33(7):1099-1107

University College London (UCL) Institute of Neurology, London, UK.

Background: The onset of multiple system atrophy (MSA) before age 40 years is referred to as "young-onset MSA." We identified clinical and pathological characteristics that might help with its early diagnosis and distinction from young-onset Parkinson's disease and late-onset MSA.

Methods: We reviewed the available clinical and pathological features in cases that fulfilled consensus criteria for diagnosis of probable MSA or had autopsy confirmed MSA with an onset before age 40 years and compared the clinical features with 16 autopsy confirmed cases with young-onset Parkinson's disease and a large published series of late-onset MSA from the European MSA Study Group. Read More

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De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.

Am J Med Genet A 2018 12 27;176(12):2623-2629. Epub 2018 Aug 27.

Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects of embryogenesis, including the development of the nervous system, though its function is incompletely understood. We describe an infant with progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to the involvement of anterior horn cells and ventral (motor) nerves. We performed whole exome sequencing on the trio and identified a de novo KIF26B missense variant, p. Read More

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December 2018