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Indian J Pediatr 2021 06 9;88(6):596. Epub 2021 Apr 9.

Department of Pediatric Medicine, Indira Gandhi Institute of Child Health, Bangalore, Karnataka, India.

Int J Mol Sci 2021 Mar 7;22(5). Epub 2021 Mar 7.

Department of Systems Medicine, Tor Vergata University of Rome, 00133 Rome, Italy.

We aimed to investigate A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia. A2A was studied in control Tor1a+/+ and Tor1a+/- knock-out mice. A2A expression was assessed by anti-A2A antibody immunofluorescence and Western blotting. Read More

J Neurosci 2021 03 19;41(9):2024-2038. Epub 2021 Jan 19.

Department of Molecular Biology, Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390

DYT1 dystonia is a hereditary neurologic movement disorder characterized by uncontrollable muscle contractions. It is caused by a heterozygous mutation in (), a gene encoding a membrane-embedded ATPase. While animal models provide insights into disease mechanisms, significant species-dependent differences exist since animals with the identical heterozygous mutation fail to show pathology. Read More

J Pediatr Orthop 2021 Jan;41(1):33-39

Rady Children's Hospital, San Diego, San Diego, CA.

Background: Low-dose biplanar radiographs (LDBRs) significantly reduce ionizing radiation exposure and may be of use in evaluating lower extremity torsion in children. In this study, we evaluated how well femoral and tibial torsional profiles obtained by LDBR correspond with 3-dimensional (3D) computed tomography (CT) and magnetic resonance axial imaging (MRI) in pediatric patients with suspected rotational abnormalities.

Methods: Patients who had both LDBR and CT/MRI studies performed for suspected lower extremity rotational deformities were included. Read More

Neurology 2021 04 17;96(14):e1887-e1897. Epub 2020 Sep 17.

From the Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (J.F.B., A.E.L.), Toronto Western Hospital and University of Toronto, Ontario, Canada; Department of Neurology (J.F.B.), University of Geneva and University Hospitals of Geneva, Switzerland; Department of Internal Medicine (S.C., F.C.), Universidade Federal de Minas Gerais, Belo Horizonte; Hospital Israelita Albert Einstein (C.O.d.S., R.D.P., P.d.C.A.), Sao Paulo, SP, Brazil; Departments of Neurology (D.S.K., T.L.) and Neurosurgery (D.S.K.), University of Colorado School of Medicine; Aurora; Department of Neurology and Neurosurgery (F.P.d.S.-J., E.R.B., P.d.C.A.), Universidade Federal de Sao Paulo, SP, Brazil; and Department of Neurology (R.Y., L.J.O.), Massachusetts General Hospital, Boston. Dr. Bally is currently at Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland.

Objective: To report 4 novel mutations leading to laryngeal and cervical dystonia with frequent generalization.

Methods: We screened 4 families including a total of 11 definitely affected members with a clinical picture resembling the original description.

Results: Four novel variants in the gene have been identified: D295N, R46M, Q424H, and R121W. Read More

Rinsho Shinkeigaku 2020 Aug 7;60(8):520-526. Epub 2020 Jul 7.

Department of Brain Disease Research, Shinshu University School of Medicine.

A 46 year-old man with schizophrenia had taken several anti-psychotic drugs since 25 years of age. From ~35 years of age, he noticed occasional neck torsion to the left, and later an ataxic gait; both symptoms gradually worsened. On admission, the patient was taking olanzapine (5 mg/day) and biperiden hydrochloride (1 mg/day) because his schizophrenia was well controlled. Read More

Pharmacol Biochem Behav 2020 09 30;196:172977. Epub 2020 Jun 30.

Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, 04103 Leipzig, Germany. Electronic address:

The metabotropic glutamate 5 (mGlu) receptor is critically involved in corticostriatal plasticity which is disturbed in various animal models of dystonia. Recently, the positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) exerted prodyskinetic effects in a phenotypic model of episodic dystonia. In the DYT1 knock-in (KI) mouse, a model for a persistent type of dystonia, previous ex vivo electrophysiological experiments indicated that mGlu receptors are involved in abnormal striatal plasticity. Read More

PLoS One 2020 4;15(5):e0226790. Epub 2020 May 4.

Department of Neurology, Ninewells Hospital & Medical School, Dundee, United Kingdom.

Patients with DYT1 dystonia caused by the mutated TOR1A gene exhibit risk neutral behaviour compared to controls who are risk averse in the same reinforcement learning task. It is unclear whether this behaviour can be linked to changes in cortico-striatal plasticity demonstrated in animal models which share the same TOR1A mutation. We hypothesised that we could reproduce the experimental risk taking behaviour using a model of the basal ganglia under conditions where cortico-striatal plasticity was abnormal. Read More

Zhonghua Er Ke Za Zhi 2020 Feb;58(2):123-128

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

To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children's Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. Read More

Behav Brain Res 2020 03 28;381:112451. Epub 2019 Dec 28.

Department of Neurology and Norman Fixel Institute of Neurological Diseases, College of Medicine, University of Florida, Gainesville, FL, USA. Electronic address:

DYT1 dystonia is an inherited movement disorder without obvious neurodegeneration. Multiple mutant mouse models exhibit motor deficits without overt "dystonic" symptoms and neurodegeneration. However, some mouse models do. Read More

PLoS One 2019 5;14(12):e0226080. Epub 2019 Dec 5.

Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.

In early-onset generalized torsion dystonia, caused by a GAG deletion in TOR1A (DYT1), enhanced striatal cholinergic activity has been suggested to be critically involved. Previous studies have shown increased acetylcholine levels in the striatum of DYT1 knock-in (KI) mice. Ex vivo data indicated that muscarinic receptor antagonists normalize the activity of striatal cholinergic interneurons. Read More

Neurobiol Dis 2020 02 13;134:104638. Epub 2019 Oct 13.

Norman Fixel Institue for Neurological Diseases, Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, United States. Electronic address:

DYT1 early-onset generalized torsion dystonia is a hereditary movement disorder characterized by abnormal postures and repeated movements. It is caused mainly by a heterozygous trinucleotide deletion in DYT1/TOR1A, coding for torsinA. The mutation may lead to a partial loss of torsinA function. Read More

Prog Brain Res 2019 21;249:251-260. Epub 2019 Jun 21.

Motor Control and Movement Disorder Group, Institute of Molecular and Clinical Sciences, St George's University of London, London, United Kingdom.

Clinical movement disorders are classified by an algorithm implemented by a practising movement disorder specialist based on information extracted during the history and clinical examination of a patient. Most simply, dystonia, is a classifier which is reached when a predominant abnormality of posture is noted. In this chapter we summarize studies that have used a variety of techniques to probe beyond the clinical examination and study kinematic features experimentally. Read More

Neurobiol Dis 2019 12 10;132:104529. Epub 2019 Jul 10.

Departments of Molecular Biophysics, Bogomoletz Institute of Physiology, Kyiv, Ukraine; Kyiv Academic University, Ukraine. Electronic address:

A recent report of autosomal-recessive primary isolated dystonia (DYT2 dystonia) identified mutations in HPCA, a gene encoding a neuronal calcium sensor protein, hippocalcin (HPCA), as the cause of this disease. However, how mutant HPCA leads to neuronal dysfunction remains unknown. Using a multidisciplinary approach, we demonstrated the failure of dystonic N75K HPCA mutant to decode short bursts of action potentials and theta rhythms in hippocampal neurons by its Ca-dependent translocation to the plasma membrane. Read More

Neurobiol Dis 2019 05 30;125:115-122. Epub 2019 Jan 30.

Department of Pharmacology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA; Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, WMB 6304, Atlanta, GA 30322, USA. Electronic address:

Trihexyphenidyl, a nonselective muscarinic receptor antagonist, is the small molecule drug of choice for the treatment of DYT1 dystonia, but it is poorly tolerated due to significant side effects. A better understanding of the mechanism of action of trihexyphenidyl is needed for the development of improved treatments. Because DTY1 dystonia is associated with both abnormal cholinergic neurotransmission and abnormal dopamine regulation, we tested the hypothesis that trihexyphenidyl normalizes striatal dopamine release in a mouse model of DYT1 dystonia using ex vivo fast scan cyclic voltammetry and in vivo microdialysis. Read More

AJNR Am J Neuroradiol 2019 01;40(1):178-183

Hospital of the Institute of Neurology (X.-E.Y., R.-M.Y., Y.-Z.H.), Anhui University of Chinese Medicine, Hefei, China.

Background And Purpose: Neurologic Wilson disease is an inherited disease characterized by a copper metabolic disorder that causes damage to many organs, especially the brain. Few studies report the relationships between these neurologic symptoms and MR imaging of the brain. Therefore, we investigated the correlation of brain abnormalities in patients with neurologic Wilson disease with their clinical symptoms, age of onset, and lag time to diagnosis. Read More

Hum Mol Genet 2019 04;28(8):1343-1356

Davee Department of Neurology.

Dystonia is a movement disorder characterized by involuntary and repetitive co-contractions of agonist and antagonist muscles. Dystonia 6 (DYT6) is an autosomal dominant dystonia caused by loss-of-function mutations in the zinc finger transcription factor THAP1. We have generated Thap1 knock-out mice with a view to understanding its transcriptional role. Read More

EMBO Mol Med 2019 01;11(1)

Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy

Dopamine D2 receptor signaling is central for striatal function and movement, while abnormal activity is associated with neurological disorders including the severe early-onset dystonia. Nevertheless, the mechanisms that regulate D2 receptor signaling in health and disease remain poorly understood. Here, we identify a reduced D2 receptor binding, paralleled by an abrupt reduction in receptor protein level, in the striatum of juvenile mice. Read More

JAMA Neurol 2019 02;76(2):211-216

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

Importance: Anecdotal evidence suggests that deep brain stimulation (DBS) of the internal globus pallidus (GPi) is effective in ameliorating dystonia in X-linked dystonia parkinsonism (XDP), a disease that is usually refractive to medical therapy.

Objective: To determine the efficacy of GPi-DBS in a cohort of patients with XDP in a prospective study and identify predictors of postoperative outcomes.

Design, Setting, And Participants: This observational prospective cohort study enrolled patients in February 2013 and was completed in December 2014. Read More

Brain Res 2019 03 23;1706:24-31. Epub 2018 Oct 23.

Raymond G. Perelman Center for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania. Philadelphia, PA 19104, United States. Electronic address:

DYT1 dystonia is a neurological disease caused by a dominant mutation that results in the loss of a glutamic acid in the endoplasmic reticulum-resident protein torsinA. Currently, treatments are symptomatic and only provide partial relief. Multiple reports support the hypothesis that selectively reducing expression of mutant torsinA without affecting levels of the wild type protein should be beneficial. Read More

Parkinsonism Relat Disord 2019 01 31;58:63-69. Epub 2018 Aug 31.

Movement Disorders Program, Atlantic Neuroscience Institute, Overlook Medical Center, AHS, Summit, NJ, USA; The Center for Neurological and Neurodevelopmental Health, NJ, USA. Electronic address:

Objective: To individuate morphometric changes and prevalent types of intraneuronal inclusions in nigral neurons of DYT1 dystonia autopsy-brains.

Methods: Using precise methods of quantification, such as unbiased stereology, we measured cellular and subcellular volumes of neuromelanin-containing (pigmented) neurons in the substantia nigra (SN) of DYT1 carriers with and without manifestation of generalized dystonia (manif-DYT1 and non-manif-DYT1, respectively), non-DYT1 carriers manifesting generalized dystonia (manif-non-DYT1) patients, and age-matched control subjects (controls). A total of four DYT1 carriers (two manif-DYT1 and two non-manif-DYT1), six manif-non-DYT1 carriers, and six controls autopsy-brains were available for these neuropathological-morphometric analyses. Read More

Brain 2018 10;141(10):2995-3008

Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

X-linked dystonia-parkinsonism is a neurodegenerative movement disorder characterized by adult-onset dystonia combined with parkinsonism over the disease course. Previous imaging and pathological findings indicate exclusive striatal atrophy with predominant pathology of the striosomal compartment in the dystonic phase of X-linked dystonia-parkinsonism. The striosome occupies 10-15% of the entire striatal volume and the density of striosomes follows a rostrocaudal gradient with the rostral striatum being considered striosome-rich. Read More

Tremor Other Hyperkinet Mov (N Y) 2018 29;8:568. Epub 2018 May 29.

Laboratory of Experimental and Computational Neuroscience, Department of Biosystems, Federal University of São João del-Rei, São João Del-Rei, Brazil.

In Response To: Giron C, Roze E, Degos, B, Méneret A, Jardel C, Lannuzel A, et al. Adult-onset generalized dystonia as the main manifestation of MEGDEL syndrome. Tremor Other Hyperkinet Mov. Read More

Dev Period Med 2018;22(1):33-38

Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.

Objective: Introduction: Torsion dystonia type 1 is the most common form of early-onset primary dystonia. Previous reports have suggested that torsin 1A, a protein mutated in this disease, might function as a chaperone that prevents the toxic aggregation of misfolded polypeptides. The aim of the study: The aim of this study was to verify the chaperone function of torsin 1A by investigating its ability to prevent the aggregation of huntingtin model peptides. Read More

Sci Rep 2018 02 26;8(1):3653. Epub 2018 Feb 26.

Galea Lab, School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK.

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Read More

Neuroscience 2018 02 28;371:455-468. Epub 2017 Dec 28.

Raymond G. Perelman Center for Cellular & Molecular Therapeutics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address:

DYT1 dystonia is a neurological disease caused by dominant mutations in the TOR1A gene, encoding for the endoplasmic reticulum (ER)-resident protein torsinA. Recent reports linked expression of the DYT1-causing protein with dysregulation of eIF2α, a key component of the cellular response to ER stress known as the unfolded protein response (UPR). However, the response of the DYT1 mammalian brain to acute ER stress inducers has not been evaluated in vivo. Read More

JBJS Case Connect 2017 Jul-Sep;7(3):e47

1Departments of Orthopaedic Surgery (A.K.B. and M.J.S.) and Neurological Surgery (R.N. and D.M.W.), Allegheny General Hospital, Pittsburgh, Pennsylvania.

Case: An adolescent girl presented with an atypical scoliotic curve, pelvic obliquity, back pain, and lower-extremity paresthesias. A workup revealed generalized primary torsion dystonia. The condition was refractory to medical treatment and necessitated implantation of a deep brain stimulator. Read More

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2017 Dec;34(6):870-873

Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Email:

Objective: To explore the feasibility of using PCR-based capillary electrophoresis method to analysis mutation of the TOR1A gene in a family affected with primary torsion dystonia (PTD).

Methods: Peripheral blood sample was collected from proband and amnionic fluid from her fetus for the extraction of DNA. The 5th exon of the TOR1A gene and its flanking sequences were amplified with PCR and analyzed with agarose electrophoresis, fluorescence labeled fragment analysis and Sanger sequencing. Read More

Biochem Biophys Res Commun 2018 01 7;495(1):346-352. Epub 2017 Nov 7.

Laboratory of Molecular Neuroscience and Neurology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; Department of Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan. Electronic address:

Dystonia-1 (DYT1) is an autosomal dominant early-onset torsion form of dystonia, a neurological disease affecting movement. DYT1 is the prototypic hereditary dystonia and is caused by the mutation of the tor1a gene. The gene product has chaperone functions important for the control of protein folding and stability. Read More