Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy.

BACKGROUND: Recombinant human acid α-glucosidase (rhGAA) enzyme replacement therapy (ERT) has prolonged survival in infantile Pompe disease (IPD), but has unmasked central nervous system (CNS) changes. METHODS: Brain imaging, consisting of computed tomography (CT) and/or magnetic resonance imaging (MRI), was performed on 23 patients with IPD (17 CRIM-positive, 6 CRIM-negative) aged 2-38months. Most patients had baseline neuroimaging performed prior to the initiation of ERT. Follow-up neuroimaging was performed in eight. RESULTS: Sixteen patients (70%) had neuroimaging abnormalities consisting of ventricular enlargement (VE) and/or extra-axial cerebrospinal fluid accumulation (EACSF) at baseline, with delayed myelination in two. Follow-up neuroimaging (n=8) after 6-153months showed marked improvement, with normalization of VE and EACSF in seven patients. Two of three patients imaged after age 10years demonstrated white matter changes, with one noted to have a basilar artery aneurysm. CONCLUSIONS: Mild abnormalities on brain imaging in untreated or newly treated patients with IPD tend to resolve with time, in conjunction with ERT. However, white matter changes are emerging as seen in Patients 1 and 3 which included abnormal periventricular white matter changes with subtle signal abnormalities in the basal ganglia and minimal, symmetric signal abnormalities involving the deep frontoparietal cerebral white matter, respectively. The role of neuroimaging as part of the clinical evaluation of IPD needs to be considered to assess for white matter changes and cerebral aneurysms.

Characterization of gait in late onset Pompe disease.

The skeletal muscle manifestations of late-onset Pompe disease (LOPD) cause significant gait impairment. However, the specific temporal and spatial characteristics of abnormal gait in LOPD have not been objectively analyzed or described in the literature. This pilot study evaluated the gait of 22 individuals with LOPD using the GAITRite® temporospatial gait analysis system. The gait parameters were compared to normal reference values, and correlations were made with standard measures of disease progression. The LOPD population demonstrated significant abnormalities in temporospatial parameters of gait including a trend towards decreased velocity and cadence, a prolonged stance phase, prolonged time in double limb support, shorter step and stride length, and a wider base of support. Precise descriptions and analyses of gait abnormalities have much potential in increasing our understanding of LOPD, especially in regards to how its natural history may be modified by the use of enzyme replacement therapy (ERT) and other interventions. Gait analysis may provide a sensitive early marker of the onset of clinical symptoms and signs, offer an additional objective measure of disease progression and the impact of intervention, and serve as a potentially important clinical endpoint. The additional data from comprehensive gait analysis may personalize and optimize physical therapy management, and the clarification of specific gait patterns in neuromuscular diseases could be of clinical benefit in the ranking of a differential diagnosis.