Summary Hypereosinophilic syndrome may rarely involve the central nervous system and mimic an intraventricular tumour. Marked eosinophilia in peripheral blood and cerebrospinal fluid may provide a critical clue to a nonneoplastic aetiology. Imaging findings may closely resemble choroid plexus tumours, leading to diagnostic challenges.
Early institutions of enzyme replacement therapy (ERT) for infantile-onset Pompe disease (IOPD) greatly improved patients' outcome. However, the long-term prognosis of patients' muscular and respiratory systems has not been fully elucidated. We conducted a longitudinal study for a cohort of early-treated IOPD patients with continuous monitoring of motor and respiratory functions (spirometry and polysomnography). Statistical analyses were performed for the relationship between Gross Motor Function Measure (GMFM), forced vital capacity (FVC), apnea-hypopnea index (AHI), and oxygen desaturation index (ODI). Sixteen patients (13 classical and 3 nonclassical IOPD) were followed up to a median age of 16.0 years (range 7.5-19.6), providing approximately 244 patient-years of observation and 132 polysomnographic assessments. Eleven of the 16 patients developed an AHI greater than 5 events/hour (indicating moderate obstructive sleep apnea, with nearly all events being obstructive apneas or hypopneas) at a Kaplan-Meier-estimated median age of 7.8 years. Night-time respiratory support was prescribed for 7 patients at a median age of 17.5 years. Data analyses revealed that FVC and AHI deteriorated faster in patients who became non-ambulatory than in other patients with better motor outcome. However, although FVC and AHI correlated slightly (r = -0.48), cases with sleep apnea were observed in patients with relatively normal gross motor or FVC. Nocturnal sleep abnormalities can occur in early-treated IOPD patients before frank deterioration of motor and respiratory function. Polysomnography is recommended for all those patients, and night-time respiratory support may be necessary to prevent morbidity and mortality.
This study aims to characterize pain in patients with facioscapulohumeral muscular dystrophy (FSHD) and determine the interactions between pain and quality of life, mental health, and physical function. We analyzed data from the prospective, international, observational ReSolve study, with primary analyses focused on baseline assessments. Of 219 patients, 83% reported having pain at baseline, most commonly located in the lower back and shoulders. Most baseline characteristics did not differ significantly between patients with and without pain or between those with higher versus lower pain severity. However, patients experiencing more pain had more self-reported psychological problems and reduced performance of resistance exercise. Multivariable linear regression models revealed that both continuous pain intensity (range 0-10) and binary pain status (yes vs. no) were associated with Patient-Reported Outcome Measures Information System (PROMIS) 57 domains: Pain intensity was associated with all domains, including physical function, anxiety, depression, fatigue, sleep disturbance, and pain interference (all p-values <0.05), whereas binary pain status was associated with worse physical function, fatigue, sleep disturbance, and pain interference. Models were adjusted for age, sex, and Clinical Severity Score. These data highlight the significance of pain and the importance of optimizing therapies to treat pain in patients with FSHD.
Type 2 myofiber atrophy is a clinically significant manifestation of muscle wasting. Its detection at autopsy depends on recognition of fiber size variation on routine hematoxylin and eosin (H&E) staining-a potentially subtle finding that may be missed without neuropathological training. Its prevalence is therefore likely to be under-reported, particularly in autopsy populations which are enriched for chronic illness, malignancy, and therapeutic high dose steroids. We conducted a prospective diagnostic accuracy study using a hospital autopsy cohort signed out by a board-certified neuropathologist, in which myosin fast immunohistochemistry was ordered prospectively as a reference standard. A non-neuropathology-trained pathologist's retrospective autopsy cohort, in which IHC was not ordered, served as a comparison. Diagnostic accuracy measures were calculated for fiber size variation as a predictor of type 2 atrophy. Logistic regression was performed to identify clinical predictors of type 2 atrophy. Diagnostic histopathological findings were present in 58.0% of prospective cases and included type 2 atrophy, necrosis and metastatic calcification. Type 2 fiber atrophy was identified in 52.2%. Fiber size variation as a predictor of type 2 atrophy had a sensitivity of 90.2%, specificity of 89.3%, positive predictive value of 92.5%, and negative predictive value of 86.2%. The non-neuropathology-trained pathologist identified type 2 atrophy in 10.5% of cases. Longer hospital stay was significantly associated with type 2 atrophy (median 19.0 vs. 4.0 days; p=0.0004; OR=6.37). In a hospitalized autopsy population, fiber size variation on H&E is a highly accurate proxy for clinically significant type 2 fiber atrophy. Type 2 atrophy may be substantially underdiagnosed at routine hospital autopsy, with a five-fold detection gap between neuropathology-trained and autopsy pathologists. Universal muscle sampling and targeted H&E evaluation for fiber size variation can achieve efficient and cost-effective detection of important diagnoses in the autopsy setting.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscular dystrophies and the focus of rapidly expanding therapeutic development. Yet several longstanding assumptions continue to shape discussions among researchers, clinicians, regulators, and industry stakeholders in ways that may not fully reflect the experiences of people living with FSHD. In this Patient Forum, FSHD Europe presents perspectives arising from extensive engagement with the patient community and participation in international initiatives. We address three commonly cited assumptions: that FSHD is a slowly progressive disease, that it can be divided into infantile and classic forms, and that no treatments are available. We argue that FSHD is better described as a progressive disease with a highly variable course, reflecting the heterogeneity of patient experiences and disease burden. We also highlight recent international consensus that childhood-onset FSHD represents part of a continuous disease spectrum rather than a distinct subtype. Finally, although disease-modifying therapies remain under development, evidence-based symptomatic and multidisciplinary care already provides meaningful treatment and should remain central to care alongside future molecular therapies. These perspectives emphasize the importance of integrating lived experience into research, drug development, health technology assessment, and healthcare decision-making, ensuring that future therapies address outcomes that matter most to people with FSHD.
