Neurology Commons^™

Lysosomal Abnormalities In Hereditary Spastic Paraplegia Types Spg15 And Spg11, Benoit Renvoise, Jaerak Chang, Rajat Singh, Sayuri Yonekawa, Edmond J. Fitzgibbon, Ami Mankodi, Adeline Vanderver, Alice B. Schindler, Camilo Toro, William A. Gahl, Don J. Mahuran, Craig Blackstone, Tyler Pierson

Neurology Faculty Publications

Objective

Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to early-onset parkinsonism.

Methods

We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes.

Results

Fibroblasts …

Implicit Sequence Learning In People With Parkinson's Disease, Katherine R. Gamble, Thomas J. Cummings, Steven E. Lo, Pritha T. Ghosh, James H. Howard, Darlene V. Howard

Neurology Faculty Publications

Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD) have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these …

Assessing Function And Endurance In Adults With Spinal And Bulbar Muscular Atrophy: Validity Of The Adult Myopathy Assessment Tool., Michael O. Harris-Love, Lindsay Fernandez-Rhodes, Galen Joe, Joseph A. Shrader, Angela Kokkinis, Alison La Pean Kirschner, Sungyoung Auh, Cheunju Chen, Li Li, Ellen Levy, Todd E. Davenport, Nicholas A. Di Prospero, Kenneth H. Fischbeck

Exercise and Nutrition Sciences Faculty Publications

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA).

Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer …

Two-Category Place Representations Persist Over Body Rotations, Hyoun Kyoung Pyoun, Jesse Sargent, Stephen Dopkins, John W. Philbeck

Neurological Surgery Faculty Publications

We explored a system that constructs environment-centered frames of reference and coordinates memory for the azimuth of an object in an enclosed space. For one group, we provided two environmental cues (doors): one in the front, and one in the rear. For a second group, we provided two object cues: a front and a rear cue.For a third group, we provided no external cues; we assumed that for this group, their reference frames would be determined by the orthogonal geometry of the floor-and-wall junction that divides a space in half or into multiple territories along the horizontal …

Analysis Of Lmnb1 Duplications In Autosomal Dominant Leukodystrophy Provides Insights Into Duplication Mechanisms And Allele-Specific Expression, Elisa Giorgio, Harshvardhan Rolyan, Laura Kropp, Anish Baswanth Chakka, Svetlana Yatsenko, Adeline Vanderver, +31 Additional Authors

Neurology Faculty Publications

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications …

Hyper-Arousal Decreases Human Visual Thresholds, Adam J. Woods, John W. Philbeck, Philip Wirtz

Neurological Surgery Faculty Publications

Arousal has long been known to influence behavior and serves as an underlying component of cognition and consciousness. However, the consequences of hyper-arousal for visual perception remain unclear. The present study evaluates the impact of hyper-arousal on two aspects of visual sensitivity: visual stereoacuity and contrast thresholds. Sixty-eight participants participated in two experiments. Thirty-four participants were randomly divided into two groups in each experiment: Arousal Stimulation or Sham Control. The Arousal Stimulation group underwent a 50-second cold pressor stimulation (immersing the foot in 0–2° C water), a technique known to increase arousal. In contrast, the Sham Control group immersed their …

Neurosurgery Concepts: Key Perspectives On Regulatory Proteins, Management Of Ossification Of The Posterior Longitudinal Ligament, And Radiosurgery For Intracranial Lesions, Jonathan H. Sherman, Zachary A. Smith, Jin Mo Cho, Michael Lim, Chaim B. Colen, Chae-Yong Kim, Vincent Yat Wang, Gabriel Zada, Gordon Li, Isaac Yang

Neurological Surgery Faculty Publications

No abstract provided.

Metabolic Causes Of Epileptic Encephalopathy, Joe Yuezhou Yu, Phillip L. Pearl

Neurology Faculty Publications

Epileptic encephalopathy can be induced by inborn metabolic defects that may be rare individually but in aggregate represent a substantial clinical portion of child neurology. These may present with various epilepsy phenotypes including refractory neonatal seizures, early myoclonic encephalopathy, early infantile epileptic encephalopathy, infantile spasms, and generalized epilepsies which in particular include myoclonic seizures. There are varying degrees of treatability, but the outcome if untreated can often be catastrophic. The importance of early recognition cannot be overemphasized. This paper provides an overview of inborn metabolic errors associated with persistent brain disturbances due to highly active clinical or electrographic ictal activity. …

Imaging Findings Associated With Cognitive Performance In Primary Lateral Sclerosis And Amyotrophic Lateral Sclerosis, Avner Meoded, Justin Y. Kwan, Tracy L. Peters, Edward D. Huey, Laura E. Danielian, Edythe Wiggs, Arthur Morrissette, Tianxia Wu, James W. Russell, Elham Bayat, Jordan Grafman, Mary Kay Floeter

Neurology Faculty Publications

Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS), but it has not been well studied in primary lateral sclerosis (PLS). The aims of this study were to (1) compare cognitive function in PLS to that in ALS patients, (2) explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI) metrics of white matter tracts and gray matter volumes, and (3) compare DTI metrics in patients with and without cognitive and behavioral changes.

Methods: The Delis-Kaplan Executive Function System (D-KEFS), the Mattis Dementia Rating Scale (DRS-2), and other behavior and mood scales were …

Middle Ear Myoclonus: Two Informative Cases And A Systematic Discussion Of Myogenic Tinnitus, Aviva Ellenstein, Nadia Yusuf, Mark Hallett

Neurology Faculty Publications

Background: The term middle ear myoclonus (MEM) has been invoked to explain symptoms of tinnitus presumably caused by the dysfunctional movement of either of the two muscles that insert in the middle ear: tensor tympani and stapedius. MEM has been characterized through heterogeneous case reports in the otolaryngology literature, where clinical presentation is variable, phenomenology is scarcely described, the pathogenic muscle is usually not specified, natural history is unknown, and the presumptive definitive treatment, tensor tympani or stapedius tendon lysis, is inconsistently effective. It is not surprising that no unique acoustogenic mechanism or pathophysiologic process has been identified to explain …

Radiation Therapy Quality In Ccg/Pog Intergroup 9961: Implications For Craniospinal Irradiation And The Posterior Fossa Boost In Future Medulloblastoma Trials, Bernadine Donahue, Mary A.H. Marymont, Sandra Kessel, Matthew K. Iandoli, Thomas Fitzgerald, Emiko Holmes, Mehmet Kocak, James M. Boyett, Amar Gajjar, Roger J. Packer

Neurology Faculty Publications

Purpose: Associations of radiation therapy (RT) deviations and outcomes in medulloblastoma have not been defined well, particularly in the era of reduced-dose craniospinal irradiation and chemotherapy. The aim of this study is to evaluate the quality of RT on Children’s Cancer Group/Pediatric Oncology Group 9961 and analyze associations of RT deviations with outcome.

Materials and Methods: Major volume deviations were assessed based on the distance from specified anatomical region to field edge. We investigated associations of RT deviations with progression-free survival (PFS), overall survival (OS), and explored associations with demographics and clinical variables.

Results: Of the 308 patients who were …

Risk Factors Associated With Death In In-Hospital Pediatric Convulsive Status Epilepticus, Tobias Loddenkemper, Tanvir U. Syed, Sriram Ramgopal, Deepak Gulati, Sikawat Thanaviratananich, Sanjeev V. Kothare, Amer Alshekhlee, Mohamad Z. Koubeissi

Neurology Faculty Publications

Objective

To evaluate in-patient mortality and predictors of death associated with convulsive status epilepticus (SE) in a large, multi-center, pediatric cohort.

Patients and Methods

We identified our cohort from the KID Inpatient Database for the years 1997, 2000, 2003 and 2006. We queried the database for convulsive SE, associated diagnoses, and for inpatient death. Univariate logistic testing was used to screen for potential risk factors. These risk factors were then entered into a stepwise backwards conditional multivariable logistic regression procedure. P-values less than 0.05 were taken as significant.

Results

We identified 12,365 (5,541 female) patients with convulsive SE aged …

Iron Accumulation In Deep Cortical Layers Accounts For Mri Signal Abnormalities In Als: Correlating 7 Tesla Mri And Pathology, Justin Y. Kwan, Suh Young Jeong, Peter Van Gelderen, Han-Xiang Deng, Martha M. Quezado, Laura E. Danielian, John Butman, Lingye Chen, Elham Bayat, James Russell, Teepu Siddique, Jeff H. Duyn, Tracey A. Rouault, Mary Kay Floeter

Neurology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T2-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or …