Neurofilament Light and Its Association With CNS Involvement in Patients With Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy (ERT) has substantially improved the outcome of classic infantile Pompe disease, an inheritable muscle disease previously fatal at infancy. However, under treatment, patients develop white matter abnormalities and neurocognitive problems. Therefore, upcoming therapies also target the brain. Currently, biomarkers reflecting CNS involvement are lacking. We aimed to study the association of neurofilament light (NfL) and CNS involvement. METHODS: To investigate the potential of NfL, we analyzed serum samples of patients with classic infantile Pompe disease who were treated with ERT. The samples were collected at ages of <1, 5, and 10 years, as well as around MRI scans. We compared the outcomes with levels in age- and sex-matched peers. Control samples were originally collected as part of routine blood work in children who underwent small surgeries and stored in the biobank of the Erasmus MC/Sophia Children's Hospital. RESULTS: We analyzed 74 serum samples of 17 patients collected at ages ranging from 22 days to 21.2 years (1-8 samples per patient) and compared these with outcomes of 71 matched peers. In the first year of age, NfL levels in patients and controls were similar (10.3 vs 11.0 pg/mL), but mixed linear model analysis showed a yearly increase of NfL of 6.0% in patients, compared with a decrease of 8.8% in controls (p < 0.001). Higher NfL was associated with lower IQ scores (p = 0.009) and lower processing speed scores (p = 0.001). DISCUSSION: We found significant differences in NfL levels between patients and controls and a good association between NfL and cognition. NfL deserves further exploration as a biomarker for CNS involvement in patients with classic infantile Pompe disease.

Quantitative CT imaging analysis to predict pathology features in patients with a congenital pulmonary airway malformation.

BACKGROUND: Risk for infection and potential malignant degeneration are the most common arguments for resecting asymptomatic Congenital Pulmonary Airway Malformations (CPAM). We aimed to investigate if CT- imaging characteristics can be used to predict histopathological features, by using an objective quantitative CT scoring method. METHODS: Archival CPAM tissue samples were histologically re-assessed and patients who had a pre-operative volumetric CT-scan were included. Lung disease was quantified using the newly-developed congenital lung abnormality quantification(CLAQ) scoring method and obtained percentages were used to predict histopathological signs of inflammation and presence of mucinous proliferation (MP). Because MP is presumed a precursor for mucinous adenocarcinoma in situ (AIS) this method was also used to compare CT-scans of patients with AIS to those with only CPAM. RESULTS: Thirty-three CPAM patients were included of which 13(39%) had histological signs of inflammation and 8(24%) had a MP. Patients with inflammation had a significantly smaller lesion (14% vs 38%) while those with MP had more extensive disease (54%vs17%). Patients with AIS had a significantly smaller lesion compared to CPAM patients (5%vs29%). Significant predictors for inflammation were smaller lesion size and percentage hypodensity within lesions while a larger lesion size and percentage parenchymal hyperdensity (solid lung tissue components) were predictors for MP as well as AIS. CONCLUSIONS: Smaller CPAM lesions may be more susceptible to inflammation while larger lesions may be associated with the presence of MP. Parenchymal hyperdensity is found as a predictor for MP as well as AIS and should therefore elicit more extensive gross sampling. LEVEL OF EVIDENCE: Level III.