3 research outputs found
Fatigue after a first attack of suspected multiple sclerosis
Background: Fatigue is reported by more than 75% of multiple sclerosis (MS) patients. In an earlier study, we showed that fatigue is not only a common symptom in patien
Distal muscle weakness is a common and early feature in long-term enzyme-treated classic infantile Pompe patients
Background: Enzyme replacement therapy (ERT; alglucosidase alfa) has improved the prospects for patients with
classic infantile Pompe disease considerably. However, over time we noticed that many of these children exhibit
distal muscle weakness at an early age, which is in contrast to the primarily proximal and axial muscle weakness in
patients with late-onset Pompe disease. This was reason to study the prevalence and severity of distal muscle
weakness, and the sequence of muscle involvement over time in patients that had learned to walk under ERT.
Methods: In this prospective, single-center cohort study, we studied 16 classic infantile patients. We used video
recordings that were made during regular standardized assessments to investigate distal muscle function (active
dorsiflexion of the feet during walking; ability to use a pincer grasp/actively extend the fingers) and proximal
muscle function (standing up from a supine position; raising the arms above the head).
Results: Median age at start of ERT was 3.2 months (0.1–5.8 months), median age at study end was 5.6 years (2.9–
18.2 years). Six patients (6/16, 38%) initially had no evident signs of distal muscle weakness and developed a gait
with active dorsiflexion of the feet. The other 10 patients never exhibited active dorsiflexion of the feet during
walking. At study-end two patients showed no loss of distal muscle function. A subset of five patients (5/16, 31%)
developed also weakness of the hands, particularly of the extensors of the 3rd and 4th digit.
Conclusions: We found that the majority (14/16, 88%) of patients who had learned to walk exhibited distal muscle
weakness of the lower extremities, while a subset (5/16, 31%) also developed weakness of the hands. The distal
muscle weakness was often more serious than, and preceded the development of, the proximal muscle weakness
Effects of higher and more frequent dosing of alglucosidase alfa and immunomodulation on long-term clinical outcome of classic infantile Pompe patients
The aim of this study was to compare the long-term outcome of classic infantile Pompe patients treated with 20 mg/kg alglucosidase alfa every other week (eow) to those treated with 40 mg/kg/week, and to study the additional effect of immunomodulation. Six patients received 20 mg/kg eow and twelve 40 mg/kg/week. Five patients were cross-reactive immunologic material (CRIM)-negative, two in the 20 mg, three in the 40 mg group. We compared (ventilator-free) survival, motor outcome, infusion associated reactions (IARs), and antibody formation. From 2012 on patients >2 months in the 40 mg group also received immunomodulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in an enzyme replacement therapy (ERT)-naïve setting. Survival was 66% in the 20 mg group and 92% in the 40 mg group. Ventilator-free survival was 50% and 92%. Both CRIM-negative patients in the 20 mg group died, whereas all three are alive in the 40 mg group. In the 20 mg group, 67% learned to walk compared with 92% in the 40 mg group. At the age of 3 years, 33% and 92% were able to walk. Peak antibody titers ranged from 1:1250 to 1:31 250 in the 20 mg group and from 1:250 to 1:800 000 in the 40 mg group. Five patients of the 40 mg group of whom two CRIM-negative also received immunomodulation. B-cell recovery was observed between 5.7 and 7.9 months after the last dose of rituximab. After B-cell recovery titers of patients with and without immunomodulation were similar (ranges 1:6 250-1:800 000 and 1:250-1:781 250). This study shows that classic infantile patients treated with 40 mg/kg/week from the start to end have a better (ventilator-free) survival and motor outcome. Immunomodulation did not prevent antibody formation in our study