Journal Article

Clinical relevance of brain volume changes in patients with cerebrotendinous xanthomatosis

Federico, A, Guerrera, S, Stromillo, M L, Marino, S, Di Perri, C, Mignarri, A, De Stefano, N, Dotti, M T, Battaglini, M

2010

Overview

ObjectiveTo quantify total and regional brain damage in subjects with cerebrotendinous xanthomatosis (CTX) using MR based quantitative measures.BackgroundCTX is a rare inherited disorder characterised by progressive neurological impairment. Appropriate therapy can slow disease progression. Measures of brain volume changes have been used in several neurological disorders due to their value in assessing disease outcome and monitoring patients' evolution.Methods24 CTX patients underwent conventional MRI to measure total and regional brain volumes. In five CTX patients who started therapy at baseline, clinical and MRI examinations were repeated after 2 years. Clinical disability, overall cognitive performance and cerebellar function were evaluated using the modified Rankin Scale (RS), Mini Mental Status Examination (MMSE) and cerebellar functional system score (CB-FSS).ResultsMeasures of normalised brain, cortical and cerebellar volumes were lower in CTX patients than in healthy controls (p<0.01). Instead, there were no differences in normalised white matter volumes between the two groups (p=0.1). At regional analysis, a significant volume decrease was found in each cortical region (p<0.01 for all regions). Normalised cortical volumes correlated closely with age (r=−0.9, p<0.0001), RS (r=−0.65, p<0.001) and MMSE (r=−0.60, p<0.01). Normalised cerebellar volumes correlated closely with CB-FSS scores (r=−0.58, p<0.01). In the five CTX patients followed over time, the annual brain volume decrease was −1.1±0.2%.ConclusionsCortical volume, rather than white matter volume, is diffusely decreased in CTX patients and correlates closely with the patient's clinical status. These data provide evidence for the presence of clinically relevant neuronal–axonal damage in the brains of CTX patients.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Acids / Adolescent / Adult / Atrophy / Biological and medical sciences / Cerebellum - pathology / Cerebral Cortex - pathology / Female / Follow-Up Studies / Humans / Magnetic Resonance Imaging / Male / Medical sciences / Middle Aged / Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis / Nerve Fibers, Myelinated - pathology / Neurology / Neurons - pathology / Neuropsychological Tests / Patients / Software / Sterols / Xanthomatosis, Cerebrotendinous - pathology / Young Adult