Neuropsychological assessment of patients with Duchenne Muscular Dystrophy

Author(s)

Elaine Cristina Zachi

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Psicologia (IP/SBD)
• Defense date: 2009-12-01

Examining board members

Dora Selma Fix Ventura; Paulo Sérgio Boggio; Rochele Paz Fonseca; Elizeu Coutinho de Macedo; Luiz Eduardo Ribeiro do Valle

• Advisor: Dora Selma Fix Ventura

Abstract

Duchenne Muscular Dystrophy (DMD) is caused by mutations in the dystrophin gene. This gene codes for dystrophin, a protein important for maintaining the stability of muscle-fiber membranes. The objectives of the study were to examine neuropsychological performance in patients with DMD and the influence of deletions in the dystrophin gene (the Dp140 regulatory region) on neuropsychological function. General intelligence was investigated in 63 DMD patients using the Wechsler Intelligence Scale or the Raven\'s Matrices Test. The age range for DMD participants was from 6 to 26 years, with a range of 1 to 16 years of formal education. The participants who had intellectual scores in the normal range (n=34) were compared to controls in terms of neuropsychological function. The control group was composed of 34 male age-matched subjects. Patients were divided into groups according to the region of mutation in the dystrophin gene and those with delection downstream of exon 45 were also compared to controls. The battery included the Wechsler scale subtests and measures of verbal memory (Rey Auditory Verbal Learning Test), viso-perceptual skills (Hooper Visual Organization Test), executive function (FAS, animals and Wisconsin Card Sorting Test). The assessment also included tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine reaction time (Simple Reaction Time and Choice Reaction Time), sustained attention (Rapid Visual Processing), working memory (Spatial Span, forward and reverse), short and long term visual memory (Pattern Recognition Memory), recognition memory for complex stimuli presented simultaneously or after short interval (Delayed Matching to Sample), spatial memory (Spatial Recognition Memory), and decision making (Information Sampling Task). The Beck Depression Inventory (BDI) was administered for depression symptoms assessment and the Child Behavior Checklist (CBCL) was used as a measure of disruptive behavior. Analysis of variance (one-way ANOVA) was used. Covariates were controlled statistically. The DMD patients had mean IQs about one standard deviation lower than population means. Verbal IQ was significantly lower than Performance IQ. After controlling for covariates, significant difference (p<0.05) appeared between DMD patients and controls and DMD was associated to lower IQs (Full Scale, Verbal, and Performance) and worse performances on Arithmetic, Vocabulary, Comprehension, Digit Span, Wisconsin Test (total errors, perseverative errors, conceptual level responses, and categories completed), Spatial Span (forward and reverse recall), and on the number of correct trials on Information Sampling Task. They also showed slower simple reaction times (Simple Reaction Time). The proportion of patients with dystrophin gene deletions was 54% (34/63). No relationship was established between intelligence results and genetic data. Compared to controls, 14 patients with delection downstream of exon 45 and normal IQs showed more specific deficits. Reaction time was discussed in terms of complexity of the task. Controls showed significant higher BDI and CBCL scores than DMD patients. Possible related factors were discussed. There is evidence to indicate that delections downstream of exon 45 (related to cerebral dystrophin isoform Dp140) are involved in decision making impairment in patients with DMD. The findings suggest that DMD may be related to frontal dysfunction. (AU)