Central Nervous System involvement in Late Onset Pompe Disease (LOPD): clues from neuroimaging and neuropsychological analysis.

BACKGROUND: Late Onset Pompe Disease (LOPD) is a rare, multisystem disorder, that is well established to mainly impair skeletal muscle function. Systematic studies exploring brain functions in LOPD are lacking. Aim of this study is to detect morphological and functional brain alterations as well as neuropsychological impairment in LOPD.

MATERIALS AND METHODS: We studied 21 patients (10M, 11F, mean-age 49±18,4years), with defined diagnosis of LOPD, divided in two groups: one with presymptomatic hyperCKemia with no muscle weakness and the second with Limb-Girdle Muscle Weakness (LGMW group). All patients performed 3TMRI to obtain morphological/angiographic evaluation as well as normalized cortical brain volume and Resting-state functional MRI (Rs-fMRI). To quantify white matter lesions Fazekas score wasapplied whereas Smoker's criteria were used to examine dolichoectasia. A complete neuropsychological assessment was performed.

RESULTS: MRI data showed that 12/21 patients (57%) demonstrated signs of cerebral vasculopathy, with a Fazekas score >2 in the 67%. According to Smoker's criteria, 11/21pts (52%) had a dolichoectasia of the vertebrobasilar system; in 3/21pts (14%) an intracranial aneurysm was detected. Rs-fMRI evidenced significantly decreased brain connectivity in Salience Network (SN) with a more relevant reduction in the bilateral middle and superior frontal gyrus. A grey matter atrophy correlated with age and disease duration. A mild impairment in executive functions was also identified.

CONCLUSION: In this LOPD cohort the results showed morphological and functional brain alterations with mild neuropsychological dysfunction, mainly in the LGMW group. Cerebrovascular alterations seem not related to common risk factors, suggesting a major role of enzymatic deficiency in the pathogenesis of brain abnormalities. This article is protected by copyright. All rights reserved.