title: Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II.
abstract: OBJECTIVE
  To identify early clinical markers of neurologic involvement in mucopolysaccharidosis type II.
  
  
  METHODS
  A retrospective review of neurobehavioral standardized assessments of patients with mucopolysaccharidosis type II evaluated at the Program for Neurodevelopmental Function in Rare Disorders was completed. Patients were grouped based on the presence or absence of central nervous system (CNS) involvement at the most recent evaluation. Differences in early signs and symptoms between resulting cohorts were tested for significance, and an index severity score was developed.
  
  
  RESULTS
  Between December 2002 and November 2010, clinical evaluations of 49 patients and 151 patient encounters were reviewed. Thirty-seven patients exhibited neurologic deterioration. Of the 25 signs evaluated, 7 early clinical markers were strongly correlated with subsequent cognitive dysfunction: sleep disturbance, increased activity, behavior difficulties, seizure-like behavior, perseverative chewing behavior, and inability to achieve bowel training and bladder training. A new severity score index was developed, with a score ≥3 indicating a high likelihood of developing CNS disease.
  
  
  CONCLUSIONS
  Seven early clinical markers and a severity score index of CNS involvement can be used for initial screening of children who might benefit from CNS-directed therapies.
authors.affiliation: Medical School at the University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Holt
authors.forename: Michele D
authors.initials: MD
authors.lastname: Poe
authors.forename: Maria L
authors.initials: ML
authors.lastname: Escolar
mesh_terms: D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000503:physiopathology*; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology*; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D016532:Mucopolysaccharidosis II / Q000150:complications* / Q000503:physiopathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012890:Sleep / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult