Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by progressive motor neuron degeneration, leading to symmetrical proximal weakness, bulbar dysfunction, and respiratory involvement. Although extraocular muscles (EOMs) are typically spared, there are conflicting reports regarding oculomotor abnormalities in SMA. This study aimed comprehensively to assess eye movement function in patients with SMA types II and III using videonystagmography (VNG). We included 18 SMA patients and 21 healthy subjects of similar ages and sexes. All participants underwent an otoscopic/audiological examination before the VNG recording. In VNG testing, we analyzed and compared optokinetic nystagmus (OKN), saccade parameters, and smooth pursuit movement (SPM) gain. There were no statistical differences between the OKN gain and saccade velocity between groups. There was a lower percentage of saccade accuracy in the SMA group than in the control group (p = 0.017). SPM gain was lower in the SMA group than in the control group (p < 0.0001). The correlation analyses revealed a positive correlation between age and saccade latency (r = 0.613, p < 0.0001) and a negative correlation between age and SPM gain (r = -0.487, p = 0.003). In this study, we performed a comprehensive evaluation of eye movement function with VNG in patients with SMA. Our findings indicate that while extraocular muscles remain unaffected in SMA, subtle central oculomotor control abnormalities-likely involving supranuclear and/or cerebellar pathways-may accompany the disease and can be quantitatively detected using VNG.

Background: Spinal muscular atrophy type 1 (SMA1) is a severe neuromuscular disorder characterized by progressive muscle weakness and atrophy, including the muscles of the oral cavity and esophagus. Eosinophilic esophagitis (EoE), a chronic, allergic disease, presents with eosinophilic infiltration of the esophagus, leading to esophageal dysmotility. Feeding difficulties may occur in both conditions. So far, the coexistence of EoE and SMA1 has not been described; we present the first such case. Case presentation: The patient was a girl with SMA1 diagnosed shortly after birth, treated with nusinersen and onasemnogene abeparvovec, and fed a standard industrial diet through a gastrostomy. In her second year of life, she developed increasing symptoms: distress during feeding, regurgitation, vomiting, and weight loss. She was treated with proton pump inhibitors without clinical improvement. Gastroscopy was performed, revealing superficial epithelial damage with bleeding in the proximal esophagus. Histopathology showed chronic inflammation with up to 150 eosinophils per high-power field, microabscesses, spongiosis, and basal layer hypertrophy. The girl was diagnosed with EoE. Her diet was switched from a standard industrial formula to an amino acid-based formula, which led to marked clinical improvement, the resolution of symptoms, and appropriate weight gain. Conclusions: This case report highlights the challenges of diagnosing EoE in SMA1 patients and emphasizes the need for multidisciplinary approaches and further investigation of allergic manifestations in SMA1 patients.

The surgical treatment of scoliosis in type 2 spinal muscular atrophy (SMA2) is challenging and little described in the literature due to its rarity and fragility of the patients. The aim of this study was to review the surgical strategies and outcomes in patients with SMA2 who underwent surgery for scoliosis at a French reference neuromuscular center. All consecutive patients with genetically confirmed SMA2 who underwent spinal surgery between 2009 and 2022 at our French reference center were retrospectively analyzed. They were divided into 2 groups, according to their primary surgery: either magnetically controlled growing rods (MCGR) or posterior spinal fusion (PSF). Demographic, respiratory, and radiologic parameters were collected preoperatively and at the latest follow-up. All complications were reported. Patients and/or caregiver-reported outcome questionnaires were also used to assess the improvement of sitting posture. Seventeen patients underwent MCGR, and 9 patients underwent PSF during the inclusion period. Mean follow-up was 5.3±1.8 years in the MGCR group, and 8.0±4.5 years in the PSF group. The average age at surgery was 9.7±1.6 years in the MCGR group and 12.6±1.7 years in the PSF group. Pelvic fixation was performed using a Tconstruct (2 sacral and 2 iliac screws). PSF was performed with all levelled pedicle screws. In the MGCR group, upper thoracic fixation was lateral ribs (n=4), vertebral on three levels (n=9), or hybrid costo-vertebral (n=4). No blood transfusion was required. No differences were found between preoperative and postoperative lung function tests for the 2 surgical procedures. The major curve correction rate was 44% in the MCGR group and 55% in the PSF group. The pelvic obliquity at last follow-up was <5 degrees in all patients. Three unplanned surgeries occurred: 1 MGCR change after lengthening and 2 PSF-one for proximal hook migration and one for infection. All patients improved their ability to sit. In this series, PSF and MGCR allowed stable radiographic and respiratory results, with a reduced rate of global complications. Pelvic fixation with T-construct was a reliable and effective technique to correct pelvic obliquity in this population of patients.

Proximal spinal muscular atrophy (SMA) is caused by deficiency of the ubiquitously expressed survival motor neuron protein. Although primarily a hereditary lower motor neuron disease, it is probably also characterized by abnormalities in other organs. Brain abnormalities and cognitive impairment have been reported in severe SMA. We aimed to systematically investigate brain structure in SMA using MRI. We acquired high-resolution T1-weighted images of treatment-naive patients with SMA, age- and sex-matched healthy and disease controls with other neuromuscular diseases, on a 3 T MRI scanner. We performed vertex-wise whole brain analysis and region of interest analysis of cortical thickness (CT), and volumetric analysis of the thalamus and compared findings in patients and controls using multiple linear regression models and Wald test. We correlated structural abnormalities with motor function as assessed by the Hammersmith Functional Motor Scale Expanded (HFMSE) and SMA Functional Rating Scale (SMA-FRS). We included 30 patients, 12-70 years old, with SMA type 2 and 3, 30 age- and sex-matched healthy controls and 17 disease controls (with distal SMA, hereditary motor and sensory neuropathy, multifocal motor neuropathy, progressive muscular atrophy and segmental SMA). We found a reduced CT in patients with SMA compared to healthy controls at the precentral, postcentral and medial orbitofrontal gyri and at the temporal pole (mean differences -0.059(p = 0.04); -0.055(p = 0.04), -0.06(p = 0.04); -0.17 mm(p = 0.001)). Differences at the precentral gyrus and temporal pole were most pronounced in SMA type 2 (mean differences -0.07(p = 0.045); -0.26 mm(p < 0.001)) and were also present compared to disease controls (mean differences -0.08(p = 0.048); -0.19 mm(p = 0.003)). There was a positive correlation between CT at the temporal pole with motor function. Compared to healthy controls, we found a reduced volume of the whole thalamus (mean difference -325 mm3(p = 0.03)) and of the anterior, ventral and intralaminar thalamic nuclei (mean differences -9.9(p = 0.02); -157(p = 0.01); -24.2 mm3(p = 0.02) in patients with SMA and a positive correlation between these volumes and motor function. MRI shows structural changes in motor and non-motor regions of the cortex and the thalamus of patients with SMA type 2 and 3, indicating that SMA pathology is not confined to motor neurons.

Hereditary proximal spinal muscular atrophy (SMA) is characterized by abnormal alpha motor neuron function in brainstem and spinal cord. Bulbar dysfunction, including limited mouth opening, is present in the majority of patients with SMA but it is unknown if and how these problems change during disease course. In this prospective, observational, longitudinal natural history study we aimed to study bulbar dysfunction in patients with SMA types 2 and 3. We included 44 patients with SMA types 2 and 3 (mean age was 33.6 (95% CI 28.4;38.9) and re-examined them after on average 4 years. None were treated with SMN-modulating treatments before or during the course of this study. Longitudinal assessments included a questionnaire on mandibular and bulbar function, the Mandibular Function Impairment Questionnaire (MFIQ), and a clinical examination of masticatory performance, maximum voluntary bite force, and mandibular movements including the active maximal mouth opening. We found significant higher MFIQ scores and a significant decrease of all mandibular movements in patients with SMA type 2 (p < 0.001), but not in SMA type 3. Masticatory performance and maximum voluntary bite force did not change significantly. Mean reduction of active maximal mouth opening at follow-up was 3.5 mm in SMA type 2 (95% CI: 2.3; 4.7, p < 0.001). SMA type 2 was an independent predictor for a more severe reduction of the mouth opening (β= -2.0 mm (95% CI: -3.8; -0.1, p = 0.043)). Bulbar functions such as mandibular mobility and active maximum mouth opening decrease significantly over the course of four years in patients with SMA type 2.