ABSTRACT Spinal and bulbar muscular atrophy (SBMA; Kennedy disease) is a rare X‐linked neuromuscular disorder caused by a CAG repeat expansion in the androgen receptor gene. Leuprorelin acetate, a luteinizing hormone–releasing hormone agonist, suppresses androgen signaling and is approved for SBMA‐associated dysphagia in Japan; however, evidence regarding efficacy remains heterogeneous. PubMed and Embase were searched from inception through June 18, 2026, for studies evaluating leuprorelin in genetically confirmed SBMA. Randomized trials, observational cohorts, natural history–controlled studies, extension studies, and safety case reports were included, and findings were synthesized narratively because of substantial heterogeneity. Eleven studies met inclusion criteria, including eight efficacy studies (460 patients) and three safety‐focused case reports. Leuprorelin reduced pathogenic androgen receptor accumulation and improved biochemical markers, including serum creatine kinase and creatinine decline. Although neither pivotal randomized trial demonstrated significant short‐term functional improvement at 48 weeks, longer‐term studies showed slower decline in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS‐R), Limb Norris, and Norris Bulbar scores and improved event‐free survival from pneumonia and death. Benefits were greatest with earlier treatment, particularly disease duration < 10 years. Leuprorelin was generally well tolerated; common adverse effects included hot flushes, sexual dysfunction, and decreased bone mineral density. Leuprorelin may slow long‐term functional deterioration in SBMA, with greater benefit following early initiation and prolonged treatment.
ABSTRACT Introduction/Aims Valosin‐containing protein (VCP) myopathy is a rare multisystem disorder with variable clinical onset and progression. While region‐focused imaging studies have provided partial information on muscle involvement, how involvement is distributed across body regions and whether this pattern is characteristic remain unclear. We aimed to characterize disease‐specific spatial patterns of muscle involvement. Methods Twelve patients from eleven unrelated families with genetically confirmed VCP myopathy underwent CT or T1‐weighted MRI. Fat replacement in 43 muscles across shoulder, trunk, pelvis, and lower limbs was graded using the modified Mercuri score (mMS). Uniform manifold approximation and projection (UMAP) dimensionality reduction and hierarchical clustering analyses identified characteristic patterns. Clinical correlations were assessed. Results UMAP visualization of 43 muscles showed that VCP myopathy cases tended to occupy a relatively distinct region compared with other myopathies. Hierarchical clustering identified Mild ( n = 9) and Severe ( n = 3) groups, which differed significantly in total mMS ( p = 0.009). Both groups showed fatty replacement in trunk muscles (including iliocostalis lumborum, longissimus, and external abdominal oblique) and adductor magnus, with relative sparing of sternocleidomastoid, infraspinatus, subscapularis, trapezius, rhomboid, and rectus femoris. Substantial asymmetry occurred only when both sides were affected. Total mMS showed no correlation with age at imaging or disease duration. Discussion This study demonstrates that VCP myopathy exhibits a characteristic pattern of muscle involvement on whole‐body multi‐region assessment. Although clinical heterogeneity was observed, consistently affected trunk muscles and adductor magnus, which may be involved early after symptom onset, may provide supportive imaging clues when VCP myopathy is suspected.
ABSTRACT Introduction/Aims Grading sensory neuropathy severity on nerve conduction studies (NCS) is operator dependent, which limits comparisons across patients, laboratories, and studies. We aimed to develop an objective severity classification to standardize NCS reporting and support clinical decision‐making. Methods We retrospectively analyzed NCS performed at IRCCS San Raffaele Hospital (2018–2024), extracted with a validated parser. Adult studies with sensory involvement were selected using sural sensory nerve action potential ( SNAP ) amplitude thresholds after excluding motor abnormalities. Hierarchical clustering combined normalized sural and “best” upper‐limb ( UL ) SNAP amplitudes with binary indicators for absent responses. Classes were ordered by an NCS severity index and validated against clinical scales. Results Among 15,744 consecutive examinations, 308 met inclusion criteria. Three well‐separated NCS severity classes emerged: mild (reduced but present sural and present UL SNAPs ), moderate (absent sural, present UL SNAPs ), and severe (absent sural and UL SNAPs ). Clinical severity increased monotonically across classes. Patients in the severe class had younger age at symptom onset than those in mild‐moderate classes and were more disabled (modified Rankin scale ≥ 2: 50.0% in severe vs 30.4% in moderate vs 16.2% in mild). The severe class was enriched in immune/paraneoplastic (12.5%) and genetic (40.6%) causes. Discussion By stratifying patients based on SNAP amplitudes, we identified a differential etiologic enrichment rather than a continuum of disease progression. Severe electrophysiology with motor sparing should prompt RFC1 testing and immune/paraneoplastic work‐up, whereas mild to moderate abnormalities should lead to assessment for diabetes and toxic or nutritional exposures.
ABSTRACT Introduction/Aims Amyotrophic lateral sclerosis (ALS) results in respiratory muscle weakness causing hypoventilation, retention of carbon dioxide (CO 2 ), and chronic hypercapnic respiratory failure. In this pilot study, we performed a 12‐month assessment of daytime and home nocturnal CO 2 to track respiratory progression, determine relationships with surrogate respiratory measures, and assess the impact of non‐invasive ventilatory support. Methods Adults with forced vital capacity (FVC) less than 90% predicted secondary to ALS were recruited from two sites in the northeast US. Participants were followed up at standard visits every 3 months for up to five visits. Spirometry, functional scores, and patient‐reported outcomes of dyspnea were recorded. Each visit included a 15‐min, seated measurement of transcutaneous CO 2 (PtcCO 2 ) while in clinic, followed by 3 nights of home overnight PtcCO 2 monitoring. Linear mixed‐effects models were employed to describe the changes that occurred longitudinally and resulting from the initiation of non‐invasive ventilation (NIV). Results Sixteen subjects were enrolled, with nine completing the full study. Strength and FVC declined over time, while daytime PtcCO 2 remained stable. Five individuals demonstrated nocturnal hypercapnia that preceded FVC < 50% predicted normal. Transition to NIV was associated with a 7 mmHg decrease in nocturnal PtcCO 2 . Discussion Home nocturnal PtcCO 2 assessment in ALS may identify respiratory insufficiency prior to FVC. Transcutaneous CO 2 may play a role in the respiratory management of patients as a biomarker for hypoventilation risk and NIV titration. However, equipment availability and data quality limitations would benefit from professional assistance rather than independent in‐home use.
