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J Neural Transm (Vienna) 2020 Feb 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

Parkinsonism Relat Disord 2020 Jan 23. 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

Mol Genet Genomic Med 2020 Feb 26;8(2):e1101. Epub 2019 Dec 26.

Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing, China.

Background: VAC14 is a component of a trimolecular complex that tightly regulates the level of phosphatidylinositol 3,5-bisphosphate [PI (3,5) P2]. VAC14 pathogenic variants cause prominent vacuolation of neurons in basal ganglia of patients with childhood-onset striatonigral degeneration (SNDC).

Methods: We identified two siblings with SNDC. Read More

Acta Neuropathol Commun 2019 12 23;7(1):219. Epub 2019 Dec 23.

Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.

Synucleinopathies are mostly sporadic neurodegenerative disorders of partly unexplained aetiology, and include Parkinson's disease (PD) and multiple system atrophy (MSA). We have further investigated our recent finding of somatic SNCA (α-synuclein) copy number variants (CNVs, specifically gains) in synucleinopathies, using Fluorescent in-situ Hybridisation for SNCA, and single-cell whole genome sequencing for the first time in a synucleinopathy. In the cingulate cortex, mosaicism levels for SNCA gains were higher in MSA and PD than controls in neurons (> 2% in both diseases), and for MSA also in non-neurons. Read More

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

J Parkinsons Dis 2020 ;10(1):123-130

Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Both Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative disorder affecting striatonigral system. Although various lines of evidence demonstrate that dopaminergic neuron degeneration emerges before the onset of motor symptoms in PD, preclinical/prodromal progression of neurodegeneration is far less understood in MSA.

Objective: The aim of this study was to clarify the difference in the progression of dopaminergic degeneration in MSA and PD using dopamine transporter single-photon emission computed tomography (DAT SPECT). Read More

Br J Pharmacol 2020 Jan 3;177(1):28-47. Epub 2020 Jan 3.

Department of Medical Sciences, Section of Pharmacology, University of Ferrara and National Institute of Neuroscience, Ferrara, Italy.

The opioid-like neuropeptide nociceptin/orphanin FQ (N/OFQ) and its receptor (NOP receptor) contribute to Parkinson's disease (PD) and motor complications associated with levodopa therapy. The N/OFQ-NOP receptor system is expressed in cortical and subcortical motor areas and, notably, in dopaminergic neurons of the substantia nigra compacta. Dopamine depletion, as in rodent models of PD results in up-regulation of N/OFQ transmission in the substantia nigra and down-regulation of N/OFQ transmission in the striatum. Read More

J Hum Genet 2019 Dec 8;64(12):1237-1242. Epub 2019 Oct 8.

Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India.

VAC14-related disorders include two distinct phenotypes, striatonigral degeneration [MIM# 617054] and Yunis-Varon syndrome. Striatonigral degeneration is a recently described childhood onset dystonia caused by pathogenic variants in VAC14. It is characterized by a period of apparent normalcy followed by abrupt onset neuroregression, dystonia, involuntary movements and degenerative brain lesions involving caudate nucleus, putamen and substantia nigra. Read More

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

Cold Spring Harb Mol Case Stud 2019 12 13;5(6). Epub 2019 Dec 13.

NYS Institute for Basic Research in Developmental Disabilities (IBR), Staten Island, New York 10314, USA.

Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressing neurological disease present in two of six siblings with early childhood onset of severe progressive spastic paraparesis and learning disabilities. A homozygous mutation (c.2005G>T, p, V669L) was found in , and the clinical phenotype is consistent with the recently described -related striatonigral degeneration, childhood-onset syndrome (SNDC) (MIM#617054). Read More

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

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

Front Neurosci 2019 11;13:590. Epub 2019 Jun 11.

Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.

Cerebral dopamine neurotrophic factor (CDNF) has shown therapeutic potential in rodent and non-human primate models of Parkinson's disease by protecting the dopamine neurons from degeneration and even restoring their phenotype and function. Previously, neurorestorative efficacy of CDNF in the 6-hydroxydopamine (6-OHDA) model of Parkinson's disease as well as diffusion of the protein in the striatum (STR) has been demonstrated and studied. Here, experiments were performed to characterize the diffusion and transport of supra-nigral CDNF in non-lesioned rats. Read More

PLoS One 2019 10;14(6):e0218130. Epub 2019 Jun 10.

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

Background: Unresponsiveness to dopaminergic therapies is a key feature in the diagnosis of multiple system atrophy (MSA) and a major unmet need in the treatment of MSA patients caused by combined striatonigral degeneration (SND). Transgenic, alpha-synuclein animal models do not recapitulate this lack of levodopa responsiveness. In order to preclinically study interventions including striatal cell grafts, models that feature SND are required. Read More

Br J Pharmacol 2019 07 21;176(13):2146-2161. Epub 2019 May 21.

Instituto Cajal, Consejo Superior de Investigaciones Científicas, CSIC, Madrid, Spain.

Background And Purpose: L-DOPA-induced dyskinesia (LID) remains a major complication of L-DOPA therapy in Parkinson's disease. LID is believed to result from inhibition of substantia nigra reticulata (SNr) neurons by GABAergic striatal projection neurons that become supersensitive to dopamine receptor stimulation after severe nigrostriatal degeneration. Here, we asked if stimulation of direct medium spiny neuron (dMSN) GABAergic terminals at the SNr can produce a full dyskinetic state similar to that induced by L-DOPA. Read More

Mol Genet Metab 2019 03 5;126(3):250-258. Epub 2019 Jan 5.

Department of Child Neurology, Hospital Vall d'Hebron - Institut de Recerca (VHIR), Barcelona, Spain; CIBERER, Centro de Investigaciones Biomédicas en Red de Enfermedades Raras, Madrid, Spain; Faculty of Medicine, Universitat Autónoma de Barcelona, Unitat Docent Vall d'Hebrón, Spain. Electronic address:

Aim: To perform a deep phenotype characterisation in a pedigree of 3 siblings with Leigh syndrome and compound heterozygous NDUFAF6 mutations.

Method: A multi-gene panel of childhood-onset basal ganglia neurodegeneration inherited conditions was analysed followed by functional studies in fibroblasts.

Results: Three siblings developed gait dystonia in infancy followed by rapid progression to generalised dystonia and psychomotor regression. Read More

Mol Genet Genomic Med 2019 03 8;7(3):e541. Epub 2019 Jan 8.

Department of Neurology, Peking University People's Hospital, Beijing, China.

Background: Heteroplasmic mitochondrial 3697G>A mutation has been associated with leber hereditary optic neuropathy (LHON), mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and LHON/MELAS overlap syndrome. However, homoplasmic m.3697G>A mutation was only found in a family with Leigh syndrome, and the phenotype and pathogenicity of this homoplasmic mutation still need to be investigated in new patients. Read More

Gene Ther 2019 02 7;26(1-2):57-64. Epub 2018 Dec 7.

CNS Gene Therapy, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Glial cell-line derived neurotrophic factor (GDNF) is a promising therapeutic molecule to treat Parkinson's disease. Despite an excellent profile in experimental settings, clinical trials testing GDNF have failed. One of the theories to explain these negative outcomes is that the clinical trials were done in late-stage patients that have advanced nigrostriatal degeneration and may therefore not respond to a neurotrophic factor therapy. Read More

Parkinsonism Relat Disord 2019 04 15;61:170-178. Epub 2018 Oct 15.

Department of Neurology, University of Luebeck, Luebeck, Germany. Electronic address:

Background: X-linked dystonia-parkinsonism (XDP) is characterized by the unique transition of dystonia to parkinsonism and striatal degeneration. Slowing of saccades on clinical examination has been taken as suggestive of a progressive supranuclear palsy (PSP) phenotype.

Objectives: To elucidate whether eye movement abnormalities in XDP patients reflect striatonigral impairment or deficits in the brainstem saccade generator as present in PSP. Read More

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

J Neuroinflammation 2018 Aug 13;15(1):227. Epub 2018 Aug 13.

Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Background: The first pathology observed in Parkinson's disease (PD) is 'dying back' of striatal dopaminergic (DA) terminals. Connexin (Cx)30, an astrocytic gap junction protein, is upregulated in the striatum in PD, but its roles in neurodegeneration remain elusive. We investigated Cx30 function in an acute PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to wild-type (WT) and Cx30 knockout (KO) mice. Read More

Sci Rep 2018 07 3;8(1):10068. Epub 2018 Jul 3.

Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.

Dendritic regression of striatal spiny projection neurons (SPNs) is a pathological hallmark of Parkinson's disease (PD). Here we investigate how chronic dopamine denervation and dopamine replacement with L-DOPA affect the morphology and physiology of direct pathway SPNs (dSPNS) in the rat striatum. We used a lentiviral vector optimized for retrograde labeling (FuG-B-GFP) to identify dSPNs in rats with 6-hydroxydopamine (6-OHDA) lesions. Read More

J Neuropathol Exp Neurol 2018 07;77(7):598-607

Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterized by aggregation of α-synuclein in oligodendrocytes to form glial cytoplasmic inclusions. According to the distribution of neurodegeneration, MSA is subtyped as striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), or as combination of these 2 (mixed MSA). In the current study, we aimed to investigate regional microglial populations and gene expression in the 3 different MSA subtypes. Read More

J Neurol 2018 Jul 25;265(7):1540-1547. Epub 2018 Apr 25.

Department of Neurology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomo-ri, Mulgum-eup, Yangsan, Gyeongsangnam-do, 626-770, Republic of Korea.

Objective: The variability of the severity and regional distribution of pathological process in basal ganglia (BG) and brainstem-cerebellar systems results in clinical heterogeneity and represents the motor subtype of multiple system atrophy (MSA). This study aimed to quantify spatial patterns of multimodal MRI abnormalities in BG and stem-CB regions and define structural MRI findings that correlate with clinical characteristics.

Methods: We simultaneously measured R2*, mean diffusivity (MD), and volume in the subcortical structures (BG, thalamus, brainstem-cerebellar regions) of 39 probable MSA and 22 control subjects. Read More

Br J Dermatol 2018 08 29;179(2):509-511. Epub 2018 May 29.

Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Acta Neurol Scand 2018 Aug 24;138(2):170-176. Epub 2018 Mar 24.

Department of Neurology & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Objectives: To investigate the differences in the pattern of striatal (caudate and putamen) dopamine transporter (DAT) loss in a multiple system atrophy (MSA) cohort, based on the clinical variants parkinsonian subtype (MSA-P) and cerebellar subtype (MSA-C) via (11)C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ( C-CFT) positron emission tomography (PET) imaging.

Materials And Methods: One hundred and six subjects (forty-one patients with probable MSA-P; forty patients with probable MSA-C; twenty-five healthy controls) underwent C-CFT PET. Subregional C-CFT uptake of bilateral caudate, anterior putamen, and posterior putamen was calculated respectively to measure the striatal dopaminergic function. Read More

Neuroimmunomodulation 2017 6;24(4-5):276-281. Epub 2018 Mar 6.

Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Prompted by findings suggesting immune instability in infantile bilateral striatal necrosis (IBSN), we evaluated levels of proinflammatory (tumor necrosis factor α, interleukin [IL]-1β, IL-6, interferon [IFN]γ) and anti-inflammatory (IL-10 and IL-1ra) cytokines produced by peripheral blood mononuclear cells (PBMC) from 6 children with IBSN and 11 age-matched controls. Compared to controls, non-stimulated PBMC from the IBSN group produced a significantly lower level of IL-1ra (by 38%; p < 0.001) and significantly lower levels of TNFα, IL-1β, and IFNγ (by 36% [p < 0. Read More

J Parkinsons Dis 2018 ;8(1):93-100

Parkinson's Institute and Clinical Center, Sunnyvale, CA, USA.

Background: Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are among the most common genetic causes of Lewy body Parkinson's disease (PD). However, LRRK2 mutations can also lead to a variety of pathological phenotypes other than typical PD, including relatively pure nigrostriatal cell loss without alpha-synuclein-positive Lewy bodies or Lewy neurites, progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). The mechanisms behind this remarkable pleomorphic pathology are currently unclear. Read More

J Alzheimers Dis 2018 ;61(4):1253-1273

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

Iron is essential for cellular development and maintenance of multiple physiological processes in the central nervous system. The disturbance of its homeostasis leads to abnormal iron deposition in the brain and causes neurotoxicity via generation of free radicals and oxidative stress. Iron toxicity has been established in the pathogenesis of Parkinson's disease; however, its contribution to multiple system atrophy (MSA) remains elusive. Read More

Acta Neuropathol Commun 2018 01 3;6(1). Epub 2018 Jan 3.

Division of Neurobiology, Department of Neurology, Medical University of Innsbruck, Innrain 66 / G2, 6020, Innsbruck, Austria.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA. Read More

Ann Clin Transl Neurol 2017 12 7;4(12):859-864. Epub 2017 Nov 7.

Bruce Lefroy Centre for Genetic Health Research Murdoch Childrens Research Institute Parkville Victoria 3052 Australia.

Objective: To characterize the clinical features and neuropathology associated with recessive mutations.

Methods: Whole-exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination.

Results: We identified compound heterozygous variants in in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration. Read More

Auton Neurosci 2018 05 16;211:39-42. Epub 2017 Dec 16.

The Multiple System Atrophy Coalition, Inc., 9935-D Rea Rd, #212, Charlotte, NC 28277, USA. Electronic address:

Multiple system atrophy (MSA) is a rare, progressive and ultimately fatal neurodegenerative disease with no known cause and no available disease modifying treatment. Known previously by various names including Shy-Drager Syndrome, olivopontocerebellar atrophy (OPCA) and striatonigral degeneration, MSA can be classified simultaneously as a movement disorder, an autonomic disorder, a cerebellar ataxia and an atypical parkinsonian disorder. Despite scholarly attempts to better describe the disease, awareness among medical practitioners about multiple system atrophy as a diagnostic possibility has been slow to catch on. Read More

Front Cell Neurosci 2017 21;11:364. Epub 2017 Nov 21.

Department of Neurodegenerative Disorders Research, Institute of Biomedical Sciences, Graduate School of Medical Sciences, Tokushima University, Tokushima, Japan.

The motor symptoms of Parkinson's disease (PD) result from striatal dopamine (DA) deficiency due to a progressive degeneration of nigral dopaminergic cells. Although DA replacement therapy is the mainstay to treat parkinsonian symptoms, a long-term daily administration of levodopa often develops levodopa-induced dyskinesia (LID). LID is closely linked to the dysregulation of cyclic adenosine monophosphate (cAMP) signaling cascades in the medium spiny neurons (MSNs), the principal neurons of the striatum, which are roughly halved with striatonigral MSNs by striatopallidal MSNs. Read More

Expert Rev Neurother 2017 Dec 23;17(12):1189-1208. Epub 2017 Oct 23.

a Institute of Clinical Neurobiology , Vienna , Austria.

Introduction: Multiple system atrophy (MSA), an adult-onset, fatal disorder of uncertain etiology, characterized by parkinsonism, cerebellar, autonomic and motor dysfunctions, is an α-synucleinopathy with glioneuronal degeneration involving multiple parts of the nervous system. The clinical variants correlate with the morphological phenotypes of striatonigral degeneration (MSA-P), olivoponto-cerebellar atrophy (MSA-C), and mixed type MSA. Neuropathological hallmark is the deposition of aberrant α-synuclein in glia and neurons forming cytoplasmic inclusions that cause cell dysfunction/demise. Read More

J Alzheimers Dis 2018 ;62(3):1141-1179

Institute of Clinical Neurobiology, Vienna, Austria.

Multiple system atrophy (MSA) is an orphan, fatal, adult-onset neurodegenerative disorder of uncertain etiology that is clinically characterized by various combinations of parkinsonism, cerebellar, autonomic, and motor dysfunction. MSA is an α-synucleinopathy with specific glioneuronal degeneration involving striatonigral, olivopontocerebellar, and autonomic nervous systems but also other parts of the central and peripheral nervous systems. The major clinical variants correlate with the morphologic phenotypes of striatonigral degeneration (MSA-P) and olivopontocerebellar atrophy (MSA-C). Read More

Neuroimage Clin 2017 9;16:557-563. Epub 2017 Sep 9.

William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

The cardinal movement abnormalities of Parkinson's disease (PD), including tremor, muscle rigidity, and reduced speed and frequency of movements, are caused by degeneration of dopaminergic neurons in the substantia nigra that project to the putamen, compromising information flow through frontal-subcortical circuits. Typically, the nigrostriatal pathway is more severely affected on the side of the brain opposite (contralateral) to the side of the body that manifests initial symptoms. Several studies have suggested that PD is also associated with changes in white matter microstructural integrity. Read More

J Neurol Neurosurg Psychiatry 2018 02 31;89(2):175-184. Epub 2017 Aug 31.

Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively. Read More

Sci Rep 2017 08 8;7(1):7495. Epub 2017 Aug 8.

Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom.

Alpha-synuclein (α-syn) is involved in both familial and sporadic Parkinson's disease (PD). One of the proposed pathogenic mechanisms of α-syn mutations is mitochondrial dysfunction. However, it is not entirely clear the impact of impaired mitochondrial dynamics induced by α-syn on neurodegeneration and whether targeting this pathway has therapeutic potential. Read More

J Neurol Sci 2017 Jul 10;378:177-181. Epub 2017 May 10.

Department of Neurology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Electronic address:

Bilateral striatal necrosis (BSN) has many causes and is characterized by unique clinical and neuroradiological features. Herein, we report a clinical and genetic analysis of three BSN cases from two independent Japanese families harboring a mitochondrial DNA (mtDNA) 14459G>A mutation located in a coding region of the NADH dehydrogenase subunit 6 gene. In the first family, two male siblings from non-consanguineous parents exhibited similar phenotypes, with infantile-onset generalized dystonia. Read More

Proc Jpn Acad Ser B Phys Biol Sci 2017 ;93(5):251-258

Department of Neurology, Brain Research Institute, Niigata University.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disorder that has both clinical and pathological variants. Clinical examples include MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P), whereas olivopontocerebellar atrophy and striatonigral degeneration represent pathological variants. We performed systematic reviews of studies that addressed the relative frequencies of clinical or pathological variants of MSA in various populations to determine the clinicopathological characteristics in Japanese MSA. Read More

Neuropathology 2017 Oct 16;37(5):431-440. Epub 2017 Apr 16.

Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

We report the case of a 79-year-old Japanese woman who developed cerebellar ataxia followed by rigidity, dysautonomia and cognitive disorders, and was thus clinically diagnosed as having possible MSA with dementia. Neuropathological findings demonstrated not only olivopontocerebellar and striatonigral degeneration with frequent glial cytoplasmic inclusions (GCIs), but also degenerative changes in the parahippocampal region, accentuated in the anterior portion of perirhinal cortex, where neuronal cytoplasmic inclusions (NCIs) and NFTs were numerous while GCIs were limited. NCIs were frequent in the deep layer, whereas NFTs were more frequent in superficial cortical layers. Read More

Folia Neuropathol 2016 ;54(4):405-409

Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. Read More

Case Rep Neurol 2016 Sep-Dec;8(3):243-250. Epub 2016 Dec 13.

Department of Neurology, Tokai University Oiso Hospital, Oiso, Japan.

We report a 44-year-old female with striatonigral degeneration (SND) who showed wearing-off oscillations after 4 months of levodopa treatment. The patient presented with asymmetric left-side dominant rigidity, and levodopa was effective at first. However, she began to show wearing-off oscillations of motor symptoms, which gradually worsened thereafter. Read More

Mol Genet Metab 2016 11 3;119(3):214-222. Epub 2016 Sep 3.

Medical Genetics, University of Siena, Siena, Italy.

We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome analysis using autosomal/X-linked recessive or de novo models. Read More

Neurosci Res 2017 Jan 22;114:62-69. Epub 2016 Sep 22.

College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. Electronic address:

Accumulating evidence suggests that chronic inflammation plays a role in the progressive dopaminergic neurodegeneration that occurs in Parkinson's disease. It has been hypothesized that inflammation mediates neuronal damage via exacerbation of a vicious cycle of oxidative stress and mitochondrial dysfunction. The bacterial endotoxin, lipopolysaccharide (LPS), induces microglial activation and inflammation driven dopaminergic neurodegeneration. Read More

Parkinsonism Relat Disord 2016 10 26;31:91-97. Epub 2016 Jul 26.

Department of Neurology, University of Lübeck, Lübeck, Germany.

Background: X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset basal ganglia model disease associated with severe striatal atrophy. Anatomical changes exceeding striatal pathology were not yet described in XDP. The present study aimed to assess the microstructure of white matter tracts in XDP using magnetic resonance tomography. Read More

Toxicol Lett 2016 Sep 14;258:36-45. Epub 2016 Jun 14.

Department of Pharmacology, College of Medicine, Hanyang University, Seoul, Republic of Korea; Hanyang Biomedical Research Institute, Seoul, Republic of Korea; Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address:

Inflammatory responses are involved in mechanisms of neuronal cell damage in the pathogenesis of neurodegenerative diseases such as Parkinson's disease (PD). We investigated the mechanisms whereby inflammatory responses contribute to loss of dopaminergic neurons in fipronil (FPN)-treated rats. After stereotaxic injection of FPN in the substantia nigra (SN), the number of tyrosine hydroxylase (TH)-positive neurons and the levels of TH expression in the SN decreased at 7days, and a significant decrease was observed at 14days with a subsequent reduction in striatal TH expression. Read More

Neuropathology 2016 Oct 11;36(5):421-431. Epub 2016 Mar 11.

Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo Metropolitan Neurological Hospital, Fuchu-shi, Tokyo, Japan.

Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease, which is characterized clinically by parkinsonism, cerebellar ataxia and/or autonomic dysfunction, and pathologically by alpha-synuclein-related multisystem neurodegeneration, so-called alpha-synucleinopathy, which particularly involves the striatonigral and olivopontocerebellar systems, with glial cytoplasmic inclusions and neuronal cytoplasmic/nuclear inclusions (NCIs/NNIs). In the recent consensus criteria for the diagnosis of MSA, dementia is described as one of the features not supporting a diagnosis of MSA. However, MSA with dementia has been reported, although the location of the lesion responsible for the dementia remains unclear. Read More

PLoS One 2016 19;11(2):e0149557. Epub 2016 Feb 19.

Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom.

Background: The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases.

Methods: Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. Read More

Neurol Med Chir (Tokyo) 2016 20;56(3):125-31. Epub 2016 Jan 20.

Departments of Neurosurgery, University of Toyama.

(123)I-ioflupane SPECT (DaTscan) is an examination that detects presynaptic dopamine neuronal dysfunction, and has been used as a diagnostic tool to identify degenerative parkinsonism. Additionally, myocardial (123)I-metaiodobenzyl guanidine (MIBG) scintigraphy measures the concentration of cardiac sympathetic nerve fibers and is used to diagnose Parkinson's disease (PD). These exams are used as adjuncts in the diagnosis of parkinsonism, however, the relationship of these two examinations are not well-known. Read More