News Release

Columbia University Medical Center/NY-Presbyterian experts at AAN

Peer-Reviewed Publication

Columbia University Irving Medical Center

The following research from Columbia University Medical Center and NewYork-Presbyterian Hospital is being presented at the 65th annual meeting of the American Academy of Neurology (AAN), March 16-23, 2013, in San Diego.

For additional information, or to arrange an interview, please contact Karin Eskenazi at 212-342-0508 or, or Christina Stolfo at 212-305-5587 or


Deoxypyrimidine Monophosphates Treatment for Thymidine Kinase 2 Deficiency

Authors: Caterina Garone, Beatriz Garcia-Diaz, Valentina Emmanuele, Saba Tadesse, Orhan Akman, Kurenai Tanji, Catarina Quinzii, Michio Hirano

Background/Significance: Autosomal recessive thymidine kinase 2 (TK2) mutations have been associated with severe depletion of mitochondrial DNA (mtDNA) and devastating neuromuscular diseases in infants and children, and with mtDNA multiple deletions and progressive external ophtalmoplegia in adults. Only supportive treatments are available for TK2 deficiency. Using a mouse model of TK2 deficiency, with a phenotype similar to human infantile encephalomyopathy, the researchers demonstrated that oral supplementation with deoxypyrimidine monophosphates is an effective and safe treatment for this disorder. The treatment can potentially be applied to humans.

Session Information: IN1-2.003, Integrated Neuroscience Session: Pediatric Neuromuscular Disease, Data Blitz Session

Presentation Time: Sunday, March 17, 11:40 am

Session Information: S05.005, Muscular Dystrophy and Inherited Myopathy

Presentation Time: Tuesday, March 19, 2:00 pm

Clinical Overview of Parkinson Pathophysiology

Speaker:Stanley Fahn

Background/Significance: Dr. Fahn will review the clinical, pathological, biochemical, imaging, and genetic background of Parkinson disease, as an introductory talk in a session on new basic science developments in Parkinson's. He will also address both motor and nonmotor features of the disease, available therapeutics, and the unmet needs of patients.

Session Information: IN2,Integrated Neuroscience Session:New Insights into Molecular Mechanisms in Parkinson's Disease

Presentation Time: Sunday, March 17,2:00 pm:30 pm

Mitochondrial Encephalomyopathies: 50 Years On

Speaker: Salvatore DiMauro

Background/Significance: On the 50th anniversary of the description of the first patient with a bona fide mitochondrial myopathy, Dr. Mauro will take stock of the extraordinary and ongoing progress in mitochondrial neurology. After briefly reviewing the pre-molecular era and offering a restrictive definition of mitochondrial diseases as those involving the respiratory chain and oxidative phosphorylation, he will discuss where we stand, and what the challenges are, in six areas: mitochondrial DNA (mtDNA)-related diseases; nuclear DNA (nDNA)-related diseases (including "direct" and "indirect" hits); disorders due to faulty intergenomic communication; disorders of the respiratory chain lipid milieu; mitochondrial dynamics; and therapeutic achievements and challenges.

Presentation Time: Tuesday, March 19, 9:00 am:00 pm

Session Information: Robert Wartenberg Lecture, Presidential Plenary Session

LRRK2 G2019S Impairs Chaperone-Mediated Autophagy in Neurons

Authors: Sheng-Han Kuo, Samantha Orenstein, Hiroshi Koga, Guomei Tang, Ellen Kanter, Roy Alcalay, Ana Maria Cuervo, David Sulzer

Background/Significance: This study was designed to explore whether leucine-rich repeat kinase 2 (LRRK2) mutation causes dysfunctional chaperone-mediated autophagy (CMA) in neuronal culture models and post-mortem Parkinson's disease (PD) brains. LRRK2 mutation is the major genetic cause of PD, and most LRRK2 PD cases exhibit α-synuclein containing Lewy body pathology. The researchers found that LRRK2 can interfere with CMA in neurons and that this interference appears to cause α-synuclein accumulation. This mechanism may underlie the α-synuclein pathology in LRRK2 PD cases.

Session Information: S13.003, Parkinson's Disease Genetics and Pathogenesis

Presentation Time: Tuesday March 19, 3:30 pm

Session Information: IN2-1.001, Integrated Neuroscience Session, Poster Rounds: New Insights into Molecular Mechanisms in Parkinson's Disease

Presentation Time: Sunday, March 17, 4:30 pm:30 pm

Parkinson Disease Phenotype in Ashkenazi Jews with and without LRRK2 Mutations

Authors: Roy Alcalay, Anat Mirelman, Rachel Saunders-Pullman, Mingxin Tang, Helen Mejia-Santana, Deborah Raymond, Ernerst Roos, Martha Orbe-Reilly, Llency Rosado, Tanya Gurevich, Ziv Gan-Or, Maayan Zelis, Avi Orr-Urtreger, Laurie Ozelius, Lorraine Clark, Nir Giladi, Susan Bressman, Karen Marder

Background/Significance: The phenotype of Parkinson's disease (PD) patients with LRRK2 mutations is often similar to that of non-carriers. The purpose of this study was to compare PD phenotype of LRRK2 carriers and non-carriers in a large Ashkenazi Jewish PD cohort. The researchers found that LRRK2 PD in Ashkenazi Jews is characterized by earlier age-at-onset, frequent lower extremity involvement at onset, persistent response to levodopa, and dyskinesia.

Session Information: S13.004, Parkinson's Disease: Genetics and Pathogenesis

Presentation Time: Tuesday, March 19, 3:45 pm

Session Information: IN2-2.001, Integrated Neuroscience Session: New Insights into Molecular Mechanisms in Parkinson's Disease, Data Blitz Session

Presentation Time: Sunday, March 17, 5:30 pm:00 pm

Results of an Open-Label, Escalating Dose Study To Assess the Safety, Tolerability, and Dose Range Finding of a Single Intrathecal Dose of ISIS-SMNRX in Patients with Spinal Muscular Atrophy

Authors: Claudia Chiriboga, Kathryn Swoboda, Basil Darras, Susan Iannaccone, Jacqueline Montes, Heather Allen, Rebecca Parad, Shanda Johnson, Darryl De Vivo, Daniel Norris, Katie Alexander, Frank Bennett, Kathie Bishop

Background/Significance: This first-in-human study was conducted to evaluate the safety, tolerability, and pharmacokinetics of escalating single intrathecal doses of ISIS-SMNRx in patients with SMA. ISIS-SMNRx is an antisense oligonucleotide molecule designed to alter splicing of SMN2 mRNA to increase production of functional SMN protein. The drug was found to be safe and well tolerated when given as a single dose. The results support continued development and further examination of ISIS-SMNRx in a longer, multiple-dose clinical study.

Session Information: S36.002, Anterior Horn: Clinical Trials

Presentation Time: Wednesday, March 20, 4:13 pm

Use of Oral Aprepitant for the Management of Nausea with Inpatient Intravenous Dihydroergotamine (DHE) Use

Authors: Denise E. Chou, Peter J. Goadsby

Background/Significance: This study assessed the efficacy and tolerability of oral aprepitant in controlling nausea associated with intravenous administration of dihydroergotamine (DHE) for medically refractory migraine. Oral aprepitant is used in the prevention of postoperative and chemotherapy-induced nausea and vomiting, but had not been studied in the prevention of DHE-related nausea. Oral aprepitant appears to be a novel, effective, and well-tolerated treatment for controlling nausea and vomiting related to intravenous DHE administration. Confirmation of these findings through further prospective studies would improve current intravenous DHE protocols for the treatment of refractory headache.

Session Information: S40.006, Headache: Clinical

Presentation Time: Wednesday, March 20, 5:05 pm


Weakness Is Independent of Fatigue in Diverse Neuromuscular Diseases

Authors: Michelle Blumenschine, Jacqueline Montes, Sally Dunaway, Ashwini Rao, Claudia Chiriboga, Douglas Sproule, Darryl De Vivo

Background/Significance: The 6-minute walk test (6MWT) is a primary end-point in many clinical trials involving neuromuscular disease. Weakness and fatigue are captured by the 6MWT, but it is unclear whether fatigue accompanies weakness in these conditions. Comparison across neuromuscular diseases has not been made. In this study, all patients with neuromuscular disease demonstrated weakness. Only the spinal muscular atrophy (SMA) group demonstrated fatigue, inversely related to walking ability. In contrast, weakness progressed in Duchenne muscular dystrophy without fatigue. Previous studies showed that functional worsening in SMA is absent over 12 months and subtle over longer periods. Conversely, fatigue increased significantly over 12 months. These findings suggest independent mechanisms underlying weakness and fatigue in SMA.

Session Information: N1-1.008, Integrated Neuroscience Session: Pediatric Neuromuscular Diseases, Poster Rounds

Presentation Time: Sunday, March 17, 10:30 am:30 am

Session Information: P03.049, Anterior Horn: Spinal Muscular Atrophy and Other Motor Neuropathies

Presentation Time: Tuesday, March 19, 2:00 pm:30 pm

Case Series: Eosinophilic Vasculitis Isolated to the Central Nervous System

Authors: Brenton Wright, Linda Lewis, James Noble, Jean Paul Vonsattel, Alexander Khandji, R. Sommerville, Clinton Wright

Background/Significance: Eosinophilic vasculitis has been described as part of the Churg-Strauss syndrome, but affects the CNS in only 6 to 7 percent of cases. Presentation in an isolated CNS distribution is rare, with only one case previously reported in the literature. No etiology for the vasculitic process has yet been identified. Here, the researchers present a new case of isolated CNS eosinophilic vasculitis and exhibit it alongside the original case. Spontaneous resolution without recurrence with corticosteroid therapy may suggest an environmental epitope with immune reaction as the cause.

Session Information: P02.053, Cerebrovascular Disease II

Presentation Time: Tuesday, March 19, 7:30 am:00pm

Melatonin, Light & Noise Reduction to Improve Sleep in the Neurological Intensive Care Unit

Authors: Brandon Foreman, Jan Claassen, Carl Bazil

Background/Significance: Sleep in the ICU is often abnormal, because of deficient melatonin production and ambient light and sound levels. Given the cognitive, autonomic, and metabolic impact of sleep deprivation, both supplemental melatonin and mitigation of environmental disruption in the ICU have been tried, with varying results. Sleep has not been studied in neurological ICU patients. This study sought to determine whether total sleep time in 12 brain-injured ICU patients could be increased through the use of melatonin and mitigating environmental disruptions. No difference in sleep time was observed between test and control subjects. However, most patients could not be scored using standard criteria. A larger patient sample size or alternative methods of scoring sleep are needed to better evaluate the use of sleep interventions in brain-injured patients.

Session Information: P01.025, Neurocritical Care: Clinical Neurophysiology/Therapeutics

Presentation Time: Monday, March 18, 2:00 pm:30 pm

A Novel Mutation in the Mitochondrial DNA Cytochrome b Gene (MTCYB) in a Patient with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes Syndrome

Authors: Valentina Emmanuele, Evangelia Sotiriou, Purificacion Gutierrez Rios, Jaya Ganesh, Rebecca Ichord, A. Reghan Foley, H. Orhan Akman, Salvatore DiMauro.

Background/Significance: This study describes a novel mutation in the mitochondrial DNA cytochrome b (MTCYB) gene in a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, or MELAS syndrome — a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. This case demonstrates that MTCYB must be included in the already long list of mitochondrial DNA genes that have been associated with the MELAS phenotype.

Session Information: P02.088, Child Neurology I

Presentation Time: Tuesday, March 19, 7:00 am:00 pm

A Decade of Racial and Ethnic Stroke Disparity: An Insight from Nhanes

Author: Jose Gutierrez

Background/Significance: In the US, stroke is more prevalent in African Americans and Hispanics than in non-Hispanic whites. The difference in prevalence can be explained by variables that reflect the diagnosis and control of important vascular risk factors. These results identify targets for interventions to reduce this disparity.

Session Information: IN6-1.001, Integrated Neuroscience Session, Poster Rounds: Global Impact of Non-Communicable Neurological Diseases

Presentation Time: Tuesday, March 19, 3:30 pm:30 pm

Session Information: P03.151, Cerebrovascular Disease III

Presentation Time: Tuesday, March 19, 2:00 pm:30 pm

A Description of Physical Therapy Services Received by Patients Diagnosed with Spinal Muscular Atrophy (SMA)

Authors: Sally Dunaway, Annie Neisen, Jacqueline Montes, Allan Glanzman, Amy Pasternak, Susan Riley, William Martens, Nicole Holuba LaMarca, Rebecca Parad, Elizabeth Shriber, Douglas Sproule, Claudia Chiriboga, Richard Finkel, Gihan Tennekoon, Basil Darras, Darryl De Vivo, Shree Pandya

Background/Significance: While physical therapy is recommended for patients with SMA, there is no known literature discussing the type and frequency of therapy services given to such patients or its impact on the natural history of SMA. This study is the first to provide information on the setting, frequency, duration, and type of physical therapy services received by SMA patients. One finding was that 36 percent of SNA patients receive no therapy services, although such services are the standard of care. The authors plan to continue to collect longitudinal data to better understand the impact of physical therapy services on the natural history of SMA. This data could contribute to standardization of clinical trial planning.

Session Information: P03.050, Anterior Horn: Spinal Muscular Atrophy and Other Motor Neuropathies

Presentation Time: Tuesday, March 19, 2:00 pm:30 pm

Factors Associated with Phobic and Obsessive Compulsive Symptoms in Epilepsy

Authors: Heidi Munger Clary, Marla Hamberger

Background/Significance: Although generalized anxiety symptoms are a major determinant of quality of life in epilepsy, little is known about other anxiety types, including phobic and obsessive compulsive symptoms. A study of 761 adult epilepsy patients with self-reported phobic and obsessive compulsive symptoms found that epilepsy patients who are nonwhite, have lower education, and receive anti-epileptic drug polytherapy may be at increased risk for phobic symptoms.

Session Information: P03.136, Epilepsy: Comorbidities and Cardiovascular Risk

Presentation Time: Tuesday, March 19, 2:00 pm:30 pm

Infantile Mitochondrial Encephalomyopathy Due to a Novel Mutation in ACAD9

Authors: Caterina Garone, Maria Alice Donati, Michele Sacchini, Sarah Calvo, Beatriz Garcia-Diaz, Vamsi Mootha, Salvatore DiMauro

Background/Significance: The aim of this study was to identify causative gene variants of early-onset complex I deficiency, the most common respiratory chain defect with early-onset fatal encephalomyopathy. Although many molecular defects have been described both in structural subunits and in assembly factors, the genetic diagnosis remains unknown in a large cohort of patients. Testing revealed a new homozygous mutation in the ACAD9 gene. The case adds to the clinical heterogeneity of ACAD9 deficiency and confirms the importance of assembly factors in causing complex I deficiency.

Session Information: P03.017, Child Neurology II

Presentation Time: Tuesday, March 19, 2:00 pm:30 pm

Digitized Spiral Drawing Analysis Discriminates Parkinson Disease from Control

Authors: Marta San Luciano, Cuiling Wang, Qiping Yu, Sarah Boschung, Kaili Stanley, Susan Bressman, Richard Lipton, Seth Pullman, Rachel Saunders-Pullman

Background/Significance: This study examined the discriminative value of digitized spiral analysis in distinguishing Parkinson's disease (PD) from controls. Spiral analysis is a non-invasive clinical test that objectively characterizes kinematic and physiologic features using calculated indices derived from hand-drawn spiral shape and motor execution. While it correlates with Unified Parkinson's Disease Rating Scale motor scores in PD, and may be more sensitive in detecting early changes in motor performance, its ability to discriminate PD from controls has not been established. The researchers concluded that spiral analysis accurately discriminates PD and early PD from controls and may be useful as a biomarker. Further assessment is needed to determine its discriminatory abilities in differentiating tremor disorders such as essential tremor from PD.

Session Information: P04.191, Evaluation of Parkinson's Disease

Presentation Time: Wednesday, March 20, 7:30 am:00pm

Classic Parkinson's Disease and Lewy Body Pathology Associated with a Heterozygous PARKIN Dosage Mutation

Authors: Madeleine Sharp, Karen Marder, Lucien Cote, Lorraine Clark, Jean Paul Vonsattel, Roy Alcalay

Background/Significance: The objective of this study was to describe the clinical and pathological data of a PARKIN heterozygote mutation carrier with early-onset Parkinson's disease (PD). Only a single autopsy from a heterozygote PARKIN carrier with PD has been described, and no autopsy from a carrier of a heterozygote deletion has been reported in the English literature. The pathogenicity of heterozygous PARKIN mutations remains unclear but some evidence supports causality. The patient was found to have a PARKIN exon 3-4 heterozygous deletion with Lewy body pathology and late-onset dementia. The deletion was unlikely to be an incidental finding, considering family history and age at onset.

Session Information: P05.055, Movement Disorders: Parkinson's Disease Genetics

Presentation Time: Wednesday, March 20, 2013 2:00 pm:00pm

Brainstem Venous Congestion Due to Dural Arterio-Venous Fistula Mimicking a Brainstem Tumor

Authors: Michelle Bell, Andrew Lassman, Fabio Iwamoto

Background/Significance: Dural brainstem arterio-venous fistulas are exceedingly rare and not readily apparent with routine imaging studies. These vascular malformations, therefore, pose a formidable diagnostic challenge. A case study of a 54-year-old man who presented to the emergency room with subacute headache and vertigo illustrates the importance of considering these malformations in the differential diagnosis of steroid-responsive brainstem expansile lesions.

Session Information: P06.144, Neuro-Oncology: Imaging

Presentation Time: Thursday, March 21, 7:30 am:00 pm

Clinical Characteristics of Pathologically Confirmed Parkinson Disease Patients with Freezing of Gait

Authors: Tuhin Virmani, Jean Paul Vonsattel, Stanley Fahn

Background/Significance: This study aimed to evaluate the characteristics of patients with Parkinson disease (PD) with or without freezing of gait (FOG) with autopsy-proven presence of Lewy bodies. The researchers found that FOG may be more common in PD with autopsy-proven PD than previously reported. Early FOG was associated with earlier onset of postural instability, memory impairment, and hallucinations, of which the latter two are potential clinical markers of cortical Lewy bodies. Detailed pathologic evaluation of this cohort may help to provide insight into anatomical regions of interest in the pathogenesis of FOG.

Session Information: P06.099, Movement Disorders: Parkinson's Disease

Presentation Time: Thursday, March 21, 7:30 am:00 pm


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