Language Skills in Patients With Alexander Disease

Area of Science:

• Neuroscience
• Genetics
• Pediatric Neurology

Background:

• Alexander disease (AxD) is a rare genetic leukoencephalopathy characterized by mutations in the glial fibrillary acidic protein (GFAP) gene.
• Language development is often affected in neurodegenerative disorders, but specific patterns in AxD subtypes are not well-defined.

Purpose of the Study:

• To investigate the language skills of children diagnosed with Alexander disease (AxD).
• To determine if specific AxD disease subtypes (cerebral, intermediate, bulbospinal) or patient age influence language performance.
• To correlate language assessment scores with disease progression markers.

Main Methods:

• Eighty-two participants with confirmed AxD (GFAP testing) were categorized into cerebral (n=56), intermediate (n=9), and bulbospinal (n=17) phenotypes.
• Language abilities were assessed using the Preschool Language Scale-Fifth Edition (PLS-5), Clinical Evaluation of Language Fundamentals-Fifth Edition (CELF-5), and Peabody Picture Vocabulary Test-Fourth Edition (PPVT-4).
• The Communication Function Classification System (CFCS) evaluated functional communication; statistical analyses included Wilcoxon signed-ranks and Kruskal-Wallis tests.

Main Results:

• Mean PLS-5 Total Language Score (TLS) was 70.10 (SD=17.62).
• CELF-5 Core Language Scores (CLS) differed significantly by phenotype: cerebral (M=57.22), intermediate (M=92.50), and bulbospinal (M=91.56).
• Cerebral AxD patients showed a negative correlation between PLS-5 TLS and age at first visit (rho=-.367, p=.017). CELF-5 CLS and PPVT-4 scores correlated with age at first neurological symptom (rho=.576, p=.003 and rho=.336, p=.011, respectively).

Conclusions:

• Significant language deficits were observed in the cerebral AxD phenotype.
• Intermediate and bulbospinal AxD subtypes generally demonstrated stronger language abilities, though some patients exhibited deficits.
• Findings highlight the functional impact of communication deficits in AxD, informing tailored interventions and accommodations in patient treatment plans.