title: Eye Movement Deficits Are Consistent with a Staging Model of pTDP-43 Pathology in Amyotrophic Lateral Sclerosis.
abstract: BACKGROUND
  The neuropathological process underlying amyotrophic lateral sclerosis (ALS) can be traced as a four-stage progression scheme of sequential corticofugal axonal spread. The examination of eye movement control gains deep insights into brain network pathology and provides the opportunity to detect both disturbance of the brainstem oculomotor circuitry as well as executive deficits of oculomotor function associated with higher brain networks.
  
  
  OBJECTIVE
  To study systematically oculomotor characteristics in ALS and its underlying network pathology in order to determine whether eye movement deterioration can be categorized within a staging system of oculomotor decline that corresponds to the neuropathological model.
  
  
  METHODS
  Sixty-eight ALS patients and 31 controls underwent video-oculographic, clinical and neuropsychological assessments.
  
  
  RESULTS
  Oculomotor examinations revealed increased anti- and delayed saccades' errors, gaze-palsy and a cerebellary type of smooth pursuit disturbance. The oculomotor disturbances occurred in a sequential manner: Stage 1, only executive control of eye movements was affected. Stage 2 indicates disturbed executive control plus 'genuine' oculomotor dysfunctions such as gaze-paly. We found high correlations (p<0.001) between the oculomotor stages and both, the clinical presentation as assessed by the ALS Functional Rating Scale (ALSFRS) score, and cognitive scores from the Edinburgh Cognitive and Behavioral ALS Screen (ECAS).
  
  
  CONCLUSIONS
  Dysfunction of eye movement control in ALS can be characterized by a two-staged sequential pattern comprising executive deficits in Stage 1 and additional impaired infratentorial oculomotor control pathways in Stage 2. This pattern parallels the neuropathological staging of ALS and may serve as a technical marker of the neuropathological spreading.
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gorges
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Müller
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Lulé
authors.affiliation: Section Clinical Neuroanatomy, Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
authors.affiliation: Center for Neurodegenerative Disease Research (CNDR), University of Pennsylvania School of Medicine, Philadelphia, PA, United States of America.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brettschneider
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Keller
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Pfandl
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Kassubek
authors.affiliation: Department of Neurology, University of Ulm, Ulm, Germany.
authors.forename: Elmar H
authors.initials: EH
authors.lastname: Pinkhardt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005133:Eye Movements / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests
chemical_list: D004268:DNA-Binding Proteins