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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

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

Mov Disord 2018 Jul;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 Neuropathol Exp Neurol 2018 Jul;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

Wiad Lek 2018;71(3 pt 1):603-606

The Higher State Educational Institution Of Ukraine "Ukrainian Medical Stomatological Academy", Poltava, Ukraina.

Features of the onset, the course of the disease causes difficulties in the early diagnosis and formulation of the correct diagnosis. Olivopontocerebellar atrophy is characterized by a broad polymorphism of clinical manifestations. There is a need to develop new methods of symptomatic and neuroprotective treatment, as well as the optimization of non-drug therapy. 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

Eur J Paediatr Neurol 2018 Jul 3;22(4):674-681. Epub 2018 Apr 3.

VIB Center for Molecular Neurology, University of Antwerp, Belgium; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University-Sofia, Sofia, Bulgaria. Electronic address:

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases. 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

Auton Neurosci 2018 May 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

World Neurosurg 2018 Feb 20;110:294-300. Epub 2017 Oct 20.

Department of Neurosurgery, Drexel Neurosciences Institute, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Background: Hypertrophic olivary degeneration (HOD) is a rare phenomenon in the dento-rubro-olivary pathway caused by lesion or disruption of the fibers of the Guillain-Mollaret triangle. Hemorrhage of pontine and midbrain cavernous angiomas can rarely lead to HOD portending neurologic deterioration and possible concomitant life-threatening complications; for this reason, it may define a poignant consideration in planning intervention.

Case Description: The patient was a 57-year-old woman with known midbrain-pontine cavernous angioma. 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

J Neurol Neurosurg Psychiatry 2018 Feb 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

Curr Biol 2017 Sep 24;27(17):2661-2669.e5. Epub 2017 Aug 24.

State Key Laboratory of Pharmaceutical Biotechnology and Department of Biological Science and Technology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China. Electronic address:

Cerebellar ataxia, characterized by motor incoordination, postural instability, and gait abnormality [1-3], greatly affects daily activities and quality of life. Although accumulating genetic and non-genetic etiological factors have been revealed [4-7], effective therapies for cerebellar ataxia are still lacking. Intriguingly, corticotropin-releasing factor (CRF), a peptide hormone and neurotransmitter [8, 9], is considered a putative neurotransmitter in the olivo-cerebellar system [10-14]. Read More

Mitochondrion 2017 11 4;37:46-54. Epub 2017 Jul 4.

NeuroCure Clinical Research Center (NCRC), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Department of Neuropediatrics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany. Electronic address:

Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial complex I and pyruvate dehydrogenase complex (PDHc) deficiency. Read More

Pediatr Neurol 2017 Sep 1;74:87-91.e2. Epub 2017 Jun 1.

Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario Canada; Institute of Medical Sciences, University of Toronto, Toronto, Ontario Canada. Electronic address:

Background: Likely pathogenic variants in SLC17A5 results in allelic disorders of free sialic acid metabolism including (1) infantile free sialic acid storage disease with severe global developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; (2) intermediate severe Salla disease with moderate to severe global developmental delay, hypotonia, and hypomyelination with or without coarse facial features, and (3) Salla disease with normal appearance, mild cognitive dysfunction, and spasticity.

Patient Description: This five-year-old girl presented with infantile-onset severe global developmental delay, truncal hypotonia, and generalized dystonia following normal development during her first six months of life. Brain magnetic resonance imaging showed marked hypomyelination and a thin corpus callosum at age 19 months, both unchanged on follow-up at age 28 months. 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

RNA 2017 04 4;23(4):466-472. Epub 2017 Jan 4.

Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, California 90095-1569, USA.

The RNA exosome is a conserved multiprotein complex that achieves a large number of processive and degradative functions in eukaryotic cells. Recently, mutations have been mapped to the gene encoding one of the subunits of the exosome, EXOSC3 (yeast Rrp40p), which results in pontocerebellar hypoplasia with motor neuron degeneration in human patients. However, the molecular impact of these mutations in the pathology of these diseases is not well understood. Read More

Mov Disord 2017 02 10;32(2):264-273. Epub 2016 Nov 10.

Department of Nuclear Medicine and Molecular Imaging Group, University Hospital of Santiago de Compostela (CHUS), IDIS Health Research Institute, Santiago de Compostela, Spain.

Background: The spinocerebellar ataxias (SCAs) form a clinically, genetically, and pathological heterogeneous group of autosomal-dominant degenerative diseases. In particular, SCA36 is characterized by a late-onset, slowly progressive cerebellar syndrome typically associated with sensorineural hearing loss. This study was aimed at analyzing the neurodegenerative process underlying SCA36 through fluorodeoxyglucose positron emission tomography (FDG-PET) and MRI scans. Read More

Curr Neurol Neurosci Rep 2016 12;16(12):105

Department of Surgery and Translational Medicine, Università of Milano-Bicocca, Milan, Italy.

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by a combination of autonomic failure, parkinsonism, and/or cerebellar ataxia. The cause of MSA is unknown, but neuropathologically the disease is characterized by widespread α-synuclein-positive glial cytoplasmic inclusions and striatonigral and/or olivopontocerebellar neurodegeneration. Two motor phenotypes have been clinically identified: parkinsonian (MSA-P) and cerebellar (MSA-C). Read More

Orphanet J Rare Dis 2016 10 21;11(1):140. Epub 2016 Oct 21.

Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.

Background: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Read More

Mov Disord 2016 11 22;31(11):1752-1753. Epub 2016 Sep 22.

Program in Neuroscience, Arizona State University, Tempe, Arizona, USA.

Orphanet J Rare Dis 2016 07 19;11(1):100. Epub 2016 Jul 19.

Department of Child Neurology, Children's Hospital, University of Tübingen, Hoppe-Seyler-Str. 1, 72072, Tübingen, Germany.

Background: Pontocerebellar hypoplasia type 2 (PCH2) is caused by a defect in the TSEN54-gene and leads to severe and early disruption of brain development, especially of cerebellum and pons. The aim of this work was to quantify the infra- and supratentorial brain growth during postnatal brain development in children with PCH2.

Methods: MRI data of 24 children with PCH2 (age 0. Read More

Neurol Genet 2016 Apr 3;2(2):e54. Epub 2016 Mar 3.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.

Objective: The aim of this study was to analyze the association between the variations of coenzyme Q2 4-hydroxybenzoate polyprenyltransferase gene (COQ2) and Japanese patients with multiple system atrophy (MSA).

Methods: We investigated the genetic variations in exons 1, 2, 6, and 7 of the COQ2 gene in 133 Japanese patients with MSA and 200 controls and analyzed the association between the variations and MSA.

Results: Six DNA variations (G21S, L25V, V66L, P157S, V393A, and X422K) were found in the 133 patients with MSA, and G21S and X422K were new variations that had never been reported. 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

J Hum Genet 2016 Jun 18;61(6):527-31. Epub 2016 Feb 18.

Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.

Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. Read More

Masui 2015 Dec;64(12):1258-60

There are only a few reports on anesthetic management for olivopontocerebellar atrophy (OPCA), a type of multiple system atrophy (MSA). We experienced anesthetic management for a surgical repair of cervical spondylotic myelopathy (CSM), a complication of OPCA. We used minimal doses of anesthetics, considering the specific perioperative complications of OPCA patients, such as hypotension, respiratory failure and prolonged effect of muscle relaxants. Read More

Turk J Pediatr 2015 May-Jun;57(3):286-9

Division of Child Neurology, Department of Pediatrics, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.

The pontocerebellar hypoplasias (PCHs) are a heterogeneous group of autosomal recessive disorders characterized by hypoplasia of the ventral pons and cerebellum, with variable cerebral involvement and severe psychomotor retardation. Eight different subtypes (PCH1-8) have been reported up to now. PCH2 is the most common type, generally caused by homozygous mutations in the TSEN54 gene and characterized by cerebellar hypoplasia that affects the hemispheres more severely than the vermis, progressive cerebral atrophy, microcephaly, dyskinesia, seizures and death in early childhood. Read More

BMC Neurosci 2015 Dec 2;16:86. Epub 2015 Dec 2.

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

Background: Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease characterized by α-synuclein (α-syn) positive oligodendroglial cytoplasmic inclusions. The latter are associated with a neuronal multisystem neurodegeneration targeting central autonomic, olivopontocerebellar and striatonigral pathways, however the underlying mechanisms of neuronal cell death are poorly understood. Previous experiments have shown that oligodendroglial α-syn pathology increases the susceptibility to mitochondrial stress and proteasomal dysfunction leading to enhanced MSA-like neurodegeneration. Read More

J Neurol 2016 Jan;263(1):61-7

The objective of this study is to determine whether diffusion tensor imaging (DTI) tractography analysis is a potential method for differentiating cerebellar ataxia patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) and cortical cerebellar atrophy (CCA). Forty-one MSA-C patients (62.7 ± 8. Read More

Ugeskr Laeger 2015 Sep;177(40):V05150380

The hypotone neonate, floppy infant, often proves to be a diagnostic challenge, as the causes of floppy infant syndrome are many and often rare. In this case story a floppy girl was diagnosed with the rare, autosomal recessive disease pontocerebellar hypoplasia type I. The tests for the most common causes of floppy infant syndrome showed nothing abnormal, but an array comparative genomic hybridization test gave information of loss of heterozygosity. Read More

J Neurol Sci 2015 Nov 18;358(1-2):501-2. Epub 2015 Sep 18.

Department of Neurology, Greater Manchester Neurosciences Centre, Salford, U.K.; Centre for Clinical and Cognitive Neurosciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, U.K.. Electronic address:

Curr Pharm Des 2015 ;21(34):4989-95

C/ Luis Vives 6, esc dcha, 7º B, 50006 Zaragoza, Spain.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system, and diseases that associate a deficiency in GABA might benefit from GABAergic drugs. Cerebellar Purkinje cells employ GABA as a neurotransmitter. Cortical cerebellar atrophy (CCA) shows Purkinje cell loss, and ataxia caused by it was alleviated by gabapentin and pregabalin. Read More

Clin Neurophysiol 2016 Feb 22;127(2):1491-1502. Epub 2015 Aug 22.

Department of Neurology, School of Medicine, Fukushima Medical University, Japan.

Objective: Patients with multiple system atrophy (MSA) are classified into those mainly manifesting cerebellar ataxia (MSA-C) and those mainly manifesting parkinsonism (MSA-P). Pathophysiological bases of these subtypes remain unclear. We hypothesized that MSA-C patients would resemble spinocerebellar degeneration patients and MSA-P patients would resemble Parkinson's disease (PD) patients in saccade abnormalities. Read More

Arq Neuropsiquiatr 2015 Oct 18;73(10):823-7. Epub 2015 Aug 18.

Departamento de Neurologia e Neurocirurgia, Divisão de Neurologia Geral e Unidade de Ataxia, Universidade Federal de São Paulo, Sao Paulo, SP, BR.

Cerebellar ataxias represent a wide group of neurological diseases secondary to dysfunctions of cerebellum or its associated pathways, rarely coursing with acute-onset acquired etiologies and chronic non-progressive presentation. We evaluated patients with acquired non-progressive cerebellar ataxia that presented previous acute or subacute onset. Clinical and neuroimaging characterization of adult patients with acquired non-progressive ataxia were performed. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2015 Aug;32(4):601

Department of Oncology, Fuling Central Hospiter of Chongqing City, Chongqing 408000, P. R. China.

Neuropathology 2016 Feb 31;36(1):64-76. Epub 2015 Jul 31.

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

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by ABCD1 mutations. A cerebello-brainstem dominant form that mainly involves the cerebellum and brainstem is summarized in a review of the literature, with autopsy-confirmed cases exceedingly rare. We report a 69-year-old White man who was diagnosed with this rare disorder and describe neuropathologic, ultrastructural and genetic analyses. Read More

Neurotox Res 2015 Oct 21;28(3):185-94. Epub 2015 Jul 21.

Department of Neurology, Innsbruck Medical University, Anichstraße 35, 6020, Innsbruck, Austria.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease. Post-mortem hallmarks of MSA neuropathology include oligodendroglial α-synuclein (αSYN) inclusions, striatonigral degeneration, olivopontocerebellar atrophy, and increased microglial activation that accompanies the wide spread neurodegeneration. Recently, we demonstrated upregulation of myeloperoxidase (MPO) in activated microglia and provided evidence for the role of microglial MPO in the mediation of MSA-like neurodegeneration (Stefanova et al. Read More

J Neuropathol Exp Neurol 2015 Jul;74(7):688-703

From the Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, UK (NZL, CLA, LH, GF, RM, RWT); East Anglian Medical Genetics Service, Cambridge University Hospital NHS foundations Trust, Cambridge Biomedical Campus, Cambridge, UK (KS, SP); Department of Paediatric Neurology, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge UK (DK); Neonatal Unit, The Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK (AO); The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, Du Cane Road, London, UK (CL); Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK (RHK); Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK (IPH); Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Trust, Oxford, UK (GKB); and Department of Histopathology, Cambridge University Hospital NHS foundations Trust, Cambridge, UK (AFD).

Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Read More

Neuroophthalmology 2015 Jun 17;39(3):147-151. Epub 2015 Jun 17.

Pacific University College of Optometry Forest Grove, Oregon USA and.

Acquired involuntary eye movement disorders, including noncomitant strabismus, nystagmus, and saccadic dyskinesia, are common ocular manifestations of many neurodegenerative diseases. These patients may experience visual symptoms, such as blurred vision, diplopia, and oscillopsia, which can significantly impact their use of vision. The goal of the management for these patients is to reduce the visual symptoms using any combination of available management strategies. Read More

J Neurol 2015 Aug 28;262(8):1876-82. Epub 2015 May 28.

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, South Korea,

Magnetic resonance imaging (MRI) can be useful not only for the diagnosis of multiple system atrophy (MSA) itself, but also to distinguish between different clinical subtypes. This study aimed to investigate whether there are differences in the progression of subcortical atrophy and iron deposition between two variants of MSA. Two serial MRIs at baseline and follow-up were analyzed in eight patients with the parkinsonian variant MSA (MSA-P), nine patients with cerebellar variant MSA (MSA-C), and fifteen patients with Parkinson's disease (PD). Read More

Acta Neuropathol 2015 Jul 12;130(1):93-105. Epub 2015 May 12.

Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease clinically characterized by cerebellar signs, parkinsonism, and autonomic dysfunction. Pathologically, MSA is an α-synucleinopathy affecting striatonigral and olivopontocerebellar systems, while neocortical and limbic involvement is usually minimal. In this study, we describe four patients with atypical MSA with clinical features consistent with frontotemporal dementia (FTD), including two with corticobasal syndrome, one with progressive non-fluent aphasia, and one with behavioral variant FTD. Read More

PLoS One 2015 21;10(4):e0118828. Epub 2015 Apr 21.

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ROC; Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan, ROC.

Patients with spinocerebellar ataxia type 3 (SCA3) have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE) and electroencephalography (EEG), are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD) method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. Read More

Acta Neurol Belg 2015 Dec 3;115(4):783-5. Epub 2015 Apr 3.

Department of Neurology, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Slot # 500, Little Rock, AR, 72205, USA.

Clin Auton Res 2015 Feb 17;25(1):19-36. Epub 2015 Feb 17.

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.

Classically defined phenotypically by a triad of cerebellar ataxia, parkinsonism, and autonomic dysfunction in conjunction with pyramidal signs, multiple system atrophy (MSA) is a rare and progressive neurodegenerative disease affecting an estimated 3-4 per every 100,000 individuals among adults 50-99 years of age. With a pathological hallmark of alpha-synuclein-immunoreactive glial cytoplasmic inclusions (GCIs; Papp-Lantos inclusions), MSA patients exhibit marked neurodegenerative changes in the striatonigral and/or olivopontocerebellar structures of the brain. As a member of the alpha-synucleinopathy family, which is defined by its well-demarcated alpha-synuclein-immunoreactive inclusions and aggregation, MSA's clinical presentation exhibits several overlapping features with other members including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Read More

Eur J Med Genet 2015 Mar 30;58(3):123-8. Epub 2015 Jan 30.

Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.

In a genetically isolated community in the Netherlands four severe recessive genetic disorders occur at relatively high frequency (pontocerebellar hypoplasia type 2 (PCH2), fetal akinesia deformation sequence (FADS), rhizomelic chondrodysplasia punctata type 1 (RCDP1), and osteogenesis imperfecta (OI) type IIB/III. Over the past decades multiple patients with these disorders have been identified. This warranted the start of a preconception outpatient clinic, in 2012, aimed at couples planning a pregnancy. Read More

J Neurol 2015 Jan 30;262(1):154-64. Epub 2014 Oct 30.

Pediatric Neurology Policlinico, University of Catania, Via Santa Sofia, 78, 95123, Catania, Italy,

PMM2-CDG (PMM2 gene mutations) is the most common congenital disorder of N-glycosylation. We conducted a nationwide survey to characterize the frequency, clinical features, glycosylation and genetic correlates in Italian patients with PMM2-CDG. Clinical information was obtained through a questionnaire filled in by the referral physicians including demographics, neurological and systemic features, neuroimaging data and genotype. Read More