title: Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets.
abstract: OBJECTIVE
  Perineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements - saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.
  
  
  METHODS
  Together with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.
  
  
  RESULTS
  Excitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.
  
  
  CONCLUSIONS
  Our findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Scott D Z
authors.initials: SD
authors.lastname: Eggers
authors.affiliation: Institute of Anatomy and Cell Biology I, Ludwig-Maximilians University, Munich, Germany; German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Anja K E
authors.initials: AK
authors.lastname: Horn
authors.affiliation: German Center for Vertigo and Balance Disorders, Ludwig-Maximilians University, Munich, Germany; Institute for Neuropathology and Prion Research, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Roeber
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Härtig
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Govind
authors.initials: G
authors.lastname: Nair
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
authors.affiliation: Department of Neurology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: R John
authors.initials: RJ
authors.lastname: Leigh
mesh_terms: D000368:Aged; D060833:Cellular Microenvironment / Q000502:physiology*; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000473:pathology*; D009886:Ophthalmoplegia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D010320:Parvalbumins / Q000032:analysis; D011149:Pons / Q000473:pathology / Q000503:physiopathology*; D065821:Pontine Tegmentum / Q000473:pathology / Q000503:physiopathology; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011509:Proteoglycans / Q000032:analysis; D012438:Saccades / Q000502:physiology*; D013569:Synapses / Q000648:ultrastructure; D016708:Synaptophysin / Q000032:analysis
chemical_list: D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D011509:Proteoglycans; C569014:SYP protein, human; D016708:Synaptophysin; D006820:Hyaluronic Acid