title: Cognitive phenotype in ataxia-telangiectasia.
abstract: BACKGROUND
  Pediatric cerebrocerebellar neurodegenerative disorders such as ataxia-telangiectasia (AT) have not been examined in detail for neuropsychologic changes. Such studies may contribute to the further understanding of ataxia-telangiectasia and to the role of the cerebrocerebellar system in the development of cognitive function in childhood.
  
  
  METHODS
  Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features. Results were compared with those of healthy control subjects and with standard norms.
  
  
  RESULTS
  Patients in AT-I group scored low average compared with standard norms on all tests and were impaired compared with healthy control subjects for verbal intelligence quotient (P < 0.001), vocabulary and comprehension (P = 0.007), processing speed (P = 0.005), visuospatial processing (P = 0.020), and working memory (P = 0.046). Patients in AT-II group scored below average compared with standard norms on all tests and were impaired compared with control subjects for attention (P < 0.001), working memory (P < 0.001), and abstract reasoning (P < 0.001). Comprehension scores were lower for patients in AT-II than in AT-I group (P = 0.002), whereas vocabulary scores showed no difference between groups (P = 0.480).
  
  
  CONCLUSIONS
  Cognitive impairments in ataxia-telangiectasia present early, coinciding with cerebellar pathology and are characteristic of the cerebellar cognitive affective syndrome. Widespread and deeper cognitive deficits manifest in later stages of ataxia-telangiectasia when additional noncerebellar pathology develops. These results are the first indications of distinct cerebellar and extracerebellar and/or subcortical contributions to the range of cognitive domains affected in ataxia-telangiectasia and need to be confirmed in future studies.
authors.affiliation: Cognitive Behavioral Neurology Unit, Ataxia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany. Electronic address: fhoche@mgh.harvard.edu.
authors.forename: Franziska
authors.initials: F
authors.lastname: Hoche
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Emily
authors.initials: E
authors.lastname: Frankenberg
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rambow
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Theis
authors.affiliation: Cognitive Behavioral Neurology Unit, Ataxia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jessica Ann
authors.initials: JA
authors.lastname: Harding
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Mayyada
authors.initials: M
authors.lastname: Qirshi
authors.affiliation: Dr. Senckenberg Chronomedical Institute, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Seidel
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Barbosa-Sicard
authors.affiliation: Department of Pediatric Neurology, Children's Hospital, Goethe-University Frankfurt am Main, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Porto
authors.affiliation: Cognitive Behavioral Neurology Unit, Ataxia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Schmahmann
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kieslich
mesh_terms: D000293:Adolescent; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000473:pathology / Q000523:psychology*; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D010641:Phenotype; D012189:Retrospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
keywords: ATM; ataxia-telangiectasia; basal ganglia; cerebellar cognitive affective syndrome; cerebellum; cognition; cognitive development; striatum