Long-term observation of patients with advanced late-onset Pompe disease undergoing enzyme replacement therapy: A 15-year observation in a single center.

BACKGROUND: There have been few descriptions in the literature on long-term enzyme replacement therapy (ERT) in patients with advanced late-onset Pompe disease (LOPD). OBJECTIVES: This study aimed to assess the efficacy and limitations of ERT in advanced LOPD patients. METHODS: We retrospectively reviewed the clinical courses of patients with advanced LOPD (two juvenile-onset and five adult-onset patients) who were treated with recombinant human alglucosidase alfa to examine improvements achieved with and limitations of ERT until their death or when switching to avalglucosidase alfa occurred. RESULTS: All patients were non-ambulant and ventilator dependent. The duration of follow-up ranged from 3.7 to 15.0 years (median 9.0 years). All patients reported improvements in their lives during the first two or three years of ERT. Vital capacity was clearly improved in patients with relatively spared respiratory function, although it deteriorated after respiratory complications such as pneumothorax. Pinch and grip power tended to be preserved during the treatment period. Muscle CT revealed progression of atrophy and fatty replacement predominantly in the proximal limb muscles without improvement after ERT. Four patients died due to aspergillosis, respiratory failure, ileus, and sudden death of unknown cause. CONCLUSIONS: Our findings demonstrate that patients undergoing ERT show certain improvements, even in the advanced stage of Pompe disease. Respiratory complications are lethal even during ERT, and early diagnosis and induction of therapy are critical. Muscle wasting progressed more severely in the proximal limbs, even after ERT.

Comparison of 3D Magnetization-transfer- and Spectral-presaturation-with-inversion-recovery-based Neuromelanin Imaging.

PURPOSE: Neuromelanin is visualized by optimizing the conditions of longitudinal relaxation (T1)-weighted imaging (T1WI). Although it was originally developed in 2D imaging, 3D imaging has been also reported, and T1WI sequences with magnetization transfer (MT) pulses are now widely used in 3D gradient echo (GRE) sequences. In this study, we assert that the use of spectral presaturation with inversion recovery (SPIR) may also be useful as an alternative to MT pulses, and we optimize SPIR and compare it with MT. METHODS: Neuromelanin images with MT pulse and SPIR (flip angles [FAs] = 19º, 22º, and 25º) were acquired from 30 healthy volunteers. To achieve the same acquisition time of 5 min, the slab thickness of the MT images was less than 1/3 of those of the SPIR images; the acquisition areas for MT and SPIR were the brainstem and the whole brain, respectively. Visual and quantitative evaluation was performed and compared on the four sequences acquired for the substantia nigra pars compacta (SNc) and the locus coeruleus (LC). For visual assessment, we used the mean score from a 3-point scale by two evaluators. For quantitative evaluation, the contrast ratios of SNc and LC were calculated in comparison with the background tissue signal. RESULTS: In visual assessments, the mean scores of the SPIR FA19º and FA22º images were better than others in the SNc. Regarding LC, the SPIR FA22º image yielded the best mean score. In quantitative evaluations, the MT image was significantly lower than the other three images in SNc. Regarding LC, there were no significant differences among the four acquired images (MT and SPIR FA19º, FA22º, and FA25º). CONCLUSIONS: Detection of neuromelanin in SNc and LC was improved by the use of SPIR compared to MT pulse in 3D neuromelanin imaging.

Quick MR Neuromelanin Imaging Using a Chemical Shift Selective Pulse.

Not only magnetization transfer contrast (MTC) pulse, but also chemical shift selective (CHESS) pulse would be a useful additional one for shortening the scan time of neuromelanin imaging. We compared three sequences among turbo-spin echo (TSE) images with CHESS, MTC, and without an additional pulse in the same short time, 3 min 20 s. The TSE with CHESS image was the most useful for the diagnosis of neuromelanin within the limited time.