Profound hypoxemia and hypotension during posterior spinal fusion in a spinal muscular atrophy child with severe scoliosis: a case report.

BACKGROUND: Anesthesia for spinal muscular atrophy (SMA) patients undergoing spinal deformity surgery is challenging. We report an unusual case of an SMA girl who developed severe intraoperative hypoxemia and hypotension during posterior spinal fusion related with surgical positioning. CASE PRESENTATION: A 13-yr-old girl diagnosed with SMA type 2, severe kyphoscoliosis and thoracic deformity was scheduled for elective posterior spinal fusion. She developed severe hypoxemia and profound hypotension intraoperatively in the prone position with surgical table tilted 45° to the right. Though transesophageal echocardiography (TEE) could not be performed due to limited mouth opening, her preoperative computed tomography revealed a severely distorted thoracic cavity with much reduced volume of the right side. A reasonable explanation was when the surgeons performed surgical procedure with the tilted surgical table, the pressure was directly put on the shortest diameter of the significantly deformed thoracic cavity, causing severe compression of the pulmonary artery, resulting in both hypoxemia and hypotension. The patient stabilized when the surgical table was tilted back and successfully went through the surgery in the leveled prone position. CONCLUSIONS: Spinal fusion surgery is beneficial for SMA patients in preventing scoliosis progression and improving ventilation. However, severe scoliosis and thoracic deformities put them at risk of both hemodynamic and respiratory instability during surgical positioning. When advanced monitoring like TEE is not practical intraoperatively, preoperative imaging may help with differential diagnosis, and guide the surgical positioning to minimize mechanical compression of the thoracic cavity, thereby helping the patient complete the surgery safely.

Genetic therapies and respiratory outcomes in patients with neuromuscular disease.

PURPOSE OF REVIEW: Genetic therapies made a significant impact to the clinical course of patients with spinal muscular atrophy and Duchenne muscular dystrophy. Clinicians and therapists who care for these patients want to know the changes in respiratory sequelae and implications for clinical care for treated patients. RECENT FINDINGS: Different genetic therapy approaches have been developed to replace the deficient protein product in spinal muscular atrophy and Duchenne muscular dystrophy. The natural history of these conditions needed to be understood in order to design clinical trials. Respiratory parameters were not the primary outcome measures for the clinical trials. The impact of these therapies is described in subsequent clinical trial reports or real-world data. SUMMARY: Genetic therapies are able to stabilize or improve the respiratory sequelae in patients with spinal muscular atrophy and Duchenne muscular dystrophy. Standardized reporting of these outcomes is needed to help inform the future revisions of clinical standards of care and practice guidelines.

Pseudo-obstructive sleep disordered breathing - definition and progression in Spinal Muscular Atrophy.

BACKGROUND: Obstructive sleep disordered breathing (SDB) is prevalent in patients with Spinal Muscular Atrophy (SMA) and possibly reduced by disease modifying treatment (DMT) such as nusinersen. We hypothesized that some obstructive events may in fact be pseudo-obstructive, reflecting the imbalance of chest wall weakness with preserved diaphragmatic function, rather than true upper airway obstruction. If confirmed, these events could represent SMA-specific outcome measures. We aimed to report on the pattern observed in respiratory polygraphies (PG) in paediatric patients with SMA type 2 resembling obstructive SDB. We defined pseudo-obstructive SDB and assessed its changes throughout disease progression. METHODS: Retrospective review of 18 PG of 6 SMA type 2 patients naïve from DMT across 3 timepoints (first study, one-year follow-up, latest study). RESULTS: At first study patients aged 3-13 years. Four patients were self-ventilating in room air and one of them required non-invasive ventilation (NIV) after the 1-year study. Two patients were on NIV since the first study. The features of pseudo-obstructive SDB included a. paradoxical breathing before, after, and throughout the event, b. the absence of increased respiratory rate during the event, c. the absence of compensatory breath after the event with a return to baseline breathing. Pseudo-obstructive events were progressively more prevalent over time. The derived pseudo-obstructive AHI increased at each timepoint in all patients self-ventilating, whilst it dropped after NIV initiation/adjustments. CONCLUSIONS: Pseudo-obstructive SDB is prevalent in SMA type 2. Its number progresses along with the disease and is treatable with NIV. Prospective studies in larger SMA cohorts are planned.

[A challenging dental treatment of a patient with spinal muscular atrophy]. / Een uitdagende tandheelkundige behandeling van een patiënt met spinale musculaire atrofie.

After a fall from his wheelchair, a 23-year-old wheelchair-dependent patient with spinal muscular atrophy type 1 was initially seen by an emergency dentist, who repositioned and splinted the luxated teeth number 31 and 32. For stabilization, the patient was subsequently referred to a centre for special dental care. In the past, few treatments had been carried out on the patient. A jaw defect and very limited mouth opening compromised dental treatment. In addition, due to the muscle disease, the patient had respiratory and breathing problems, for which he used respiratory equipment. This case describes the importance of a multidisciplinary team in the treatment of patients with spinal muscular atrophy, and the options for performing minimally invasive dental treatment, where the priority is a painless dentition.

Inaugural dropped head syndrome and camptocormia in inflammatory myopathies: a retrospective study.

OBJECTIVES: Inaugural axial muscle involvement, defined as dropped head syndrome (DHS) and/or camptocormia (CC), is poorly described in inflammatory myopathies (IM). This study aimed to further characterize IM patients with inaugural DHS/CC, their outcome and care management. METHODS: This retrospective study included IM patients diagnosed between 2000 and 2021. The main inclusion criterion was IM revealed by axial muscle deficit (DHS/CC). RESULTS: Twenty-seven patients were included; median (IQR) age at first symptoms was 66.0 years (55.5-75.0); 21 were female (77.8%). There were nine IBM, 33.3%, nine overlap myositis (OM, 33.3%), five DM, 18.5%, two immune checkpoint inhibitor-related myositis (7.4%), one focal myositis (3.7%) and one myositis with anti-Hu antibodies (3.7%). Age at first symptoms was ≤70 years in 16 patients (59.3%), including all DM patients and 8/9 OM patients (88.9%). In this group, partial remission of the disease was obtained in 9/16 (56.3%) and complete remission in 1/16 patients (6.3%); regression of DHS/CC was achieved in 3/16 patients (18.8%). Conversely, in the group of 11 patients aged >70 years at first symptoms, there were eight IBM (72.7%). Partial remission was obtained in 5/11 patients (45.5%), the disease was stable in 6/11 patients (54.5%); no complete remission was obtained nor regression of DHS/CC. CONCLUSION: The analysis of IM patients with inaugural DHS/CC delineates two groups of patients according to the age at first symptoms in terms of clinical and outcome specificities, and proposes an adapted diagnostic and care management approach to prevent long-term complications.

A preliminary study on self-care telemonitoring of dysarthria in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease which may cause impairments in oro-facial musculature. Most of the individuals with SMA present bulbar signs such as flaccid dysarthria which mines their abilities to speak and, as consequence, their psychic balance. To support clinicians, recent work has demonstrated the feasibility of video-based techniques for assessing the oro-facial functions in patients with neurological disorders such as amyotrophic lateral sclerosis. However, no work has so far focused on automatic and quantitative monitoring of dysarthria in SMA. To overcome limitations this work's aim is to propose a cloud-based store-and-forward telemonitoring system for automatic and quantitative evaluation of oro-facial muscles in individuals with SMA. The system integrates a convolutional neural network (CNN) aimed at identifying the position of facial landmarks from video recordings acquired via a web application by an SMA patient.Clinical relevance- The proposed work is in the preliminary stage, but it represents the first step towards a better understanding of the bulbar-functions' evolution in patients with SMA.

Systematic Literature Review of the Natural History of Spinal Muscular Atrophy: Motor Function, Scoliosis, and Contractures.

BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications, such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA. METHODS: Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Data sets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves. RESULTS: Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (3 on the probability of sitting in patients with types 2 and 3 SMA and 8 on the probability of walking/ambulation in patients with type 3 SMA). The median time to loss of sitting (95% CI) was 14.5 years (14.1-31.5) for the type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for type 3a SMA (disease onset at age younger than 3 years) and 44.2 years (43.0-49.4) for type 3b SMA (disease onset at age 3 years or older). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data. DISCUSSION: The results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. In addition, data suggest that untreated patients with types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes.

Profile of cognitive abilities in spinal muscular atrophy type II and III: what is the role of motor impairment?

There has recently been some concern on possible cognitive impairment in patients with Spinal Muscular Atrophy (SMA). The aim of this study was to assess cognitive profiles in type II and III SMA with a focus on individual indexes and possible correlations with motor function. 57 type II and III individuals, aged 3.5-17 years, were consecutively enrolled in a prospective, multicentric study. Cognitive function was assessed using age-appropriate Weschler Scales. Motor function was concomitantly assessed using disease-specific functional scales. Only 2 individuals (3%) had a intellectual disability of mild degree while the others were within normal range, with no significant difference in relation to SMA type, gender or functional status. While the overall quotients were mostly within normal range, some indexes showed wider variability. A significant positive medium correlation was found between Processing Speed Index and motor functional scores. Working memory had lower scores in type III patients compared to type II. Intellectual disability is uncommon in type II and III SMA. Motor functional abilities may play a role in some of the items contributing to the overall cognitive profile.

Sleep architecture and Nusinersen therapy in children with Spinal Muscular Atrophy type 1.

BACKGROUND: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder, the phenotype of the disease is caused by the mutation of the SMN1 (survival motor neuron 1) gene which encodes for the SMN protein. Innovative treatments for SMA have become available and the first molecule approved is Nusinersen, an antisense oligonucleotide that increases the production of SMN protein. Nusinersen has been shown to be associated with a significant motor improvement and an increase of the event-free survival. For these reasons the aim of the present study is to assess if Nusinersen is able modify sleep architecture and microstructure and to improve sleep structure in these patients. METHODS: Sixteen patients affected by SMA1 were enrolled in the study (4 boys, 12 girls; median age 72.5 months, intelligence quotient range 24-84). All patients underwent complete nocturnal PSG before the start of the treatment trough intrathecal injections with Nusinersen (T0) and after the fifth infusion (day 180, T180). PSG recordings were visually scored and interpreted according to the indications of the American Academy of Sleep Medicine (AASM) and and microstructure by means of the Cyclic Alternating Pattern (CAP). RESULTS: After 6 months therapy we found a significantly reduced sleep latency and a significantly increased sleep efficiency. Regarding sleep microstructure parameters (CAP), we did not find any significant change after therapy however, it is worth mentioning that a moderate effect size was observed for the increase in CAP A3 index. CONCLUSIONS: We observed short-term effects of Nusinersen on sleep with an improvement in sleep efficiency and reduction in sleep onset latency; regarding sleep microstructure, a moderate effect size was found for the number of CAP A3 subtypes that slightly increased, possibly indicating a slightly higher arousability. This finding points at a probably overall better sleep pattern organization associated with the treatment, but they need to be confirmed by larger studies with patients treated earlier in life and for a longer period.

Case Report: A case of spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia treated with nebulization combined with intravenous polymyxin B: experience and a literature review.

Spinal muscular atrophy (SMA) is a neurodegenerative disease that results in progressive and symmetric muscle weakness and atrophy of the proximal limbs and trunk due to degeneration of spinal alpha-motor neurons. Children are classified into types 1-3, from severe to mild, according to the time of onset and motor ability. Children with type 1 are the most severe, are unable to sit independently, and experience a series of respiratory problems, such as hypoventilation, reduced cough, and sputum congestion. Respiratory failure is easily complicated by respiratory infections and is a major cause of death in children with SMA. Most type 1 children die within 2 years of age. Type 1 children with SMA usually require hospitalization for lower respiratory tract infections and invasive ventilator-assisted ventilation in severe cases. These children are frequently infected with drug-resistant bacteria due to repeated hospitalizations and require long hospital stays requiring invasive ventilation. In this paper, we report a case of nebulization combined with intravenous polymyxin B in a child with spinal muscular atrophy with extensively drug-resistant Acinetobacter baumannii pneumonia, hoping to provide a reference for the treatment of children with extensively drug-resistant Acinetobacter baumannii pneumonia.

Characterizing Camptocormia in Parkinson's Disease Using Muscle Ultrasonography.

BACKGROUND: Camptocormia (CC) is the forward-bending of the spine of more than 30 degrees that can be found in Parkinson's disease (PD) as a disabling complication. Detection of changes in paraspinal lumbar musculature in CC is of value for choosing treatment strategies. OBJECTIVE: To investigate whether these changes can be detected using muscle ultrasonography (mUSG). METHODS: Age and sex-matched groups comprised 17 PD patients with CC (seven acute, PD-aCC; 10 chronic PD-cCC), 19 PD patients with no CC, and 18 healthy controls (HC). Lumbar paravertebral muscles (LPM) on both sides were assessed using mUSG by two different raters blinded to the group assignment. Groups were compared with regard to the linear measurements of the muscle thickness as well as semi-quantitative and quantitative (grayscale) analyses of muscle echogenicity using a univariate general linear model. RESULTS: All assessments showed substantial interrater reliability. The PD-cCC group had significantly thinner LPM compared to groups with no CC (PD and HC). Groups of PD-aCC and PD-cCC differed from the groups of no CC in quantitative and semi-quantitative analyses of LPM echogenicity, respectively. CONCLUSION: Assessment of LPM in PD patients with CC can be reliably performed using mUSG. Also, mUSG may be used as a screening tool to detect CC-related changes in thickness and echogenicity of the LPM in patients with PD.

Subjective Sleep Quality as it Relates to Cognitive and Physical Function in Spinal Muscular Atrophy Patients.

Sleep quality and its association with cognition has been widely studied in some neurodegenerative diseases, but less is known about this association in spinal muscular atrophy (SMA). In adult SMA (n = 21) patients and age-matched controls (n = 23), we assessed subjectively measured sleep quality and daytime somnolence. Cognition was assessed with a multi-domain neuropsychological battery. Further, we investigated the association between clinical functional scores and sleep questionnaire scores. Among SMA patients, better motor and limb function was associated with better subjective sleep quality (p's< 0.05). Clinicians should consider sleep quality in patient care and future studies are needed to better understand these relationships.

[Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses].

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Swallowing Problems in Spinal Muscular Atrophy Types 2 and 3: A Clinical, Videofluoroscopic and Ultrasound Study.

BACKGROUND: Spinal muscular atrophy (SMA) is a hereditary motor neuron disorder, characterized by the degeneration of motor neurons and progressive muscle weakness. There is a large variability of disease severity, reflected by the classification of SMA types 1-4. OBJECTIVE: The aim of this cross-sectional study was to determine the nature of swallowing problems and underlying mechanisms in patients with SMA types 2 and 3, and the relationship between swallowing and mastication problems. METHODS: We enrolled patients (aged 13-67 years) with self-reported swallowing and/or mastication problems. We used a questionnaire, the functional oral intake scale, clinical tests (dysphagia limit, and timed test swallowing, the test of mastication and swallowing solids), a videofluoroscopic swallowing study (VFSS), and muscle ultrasound of the bulbar muscles (i.e. digastric, geniohyoid and tongue muscles). RESULTS: Non-ambulant patients (n = 24) had a reduced dysphagia limit (median 13 ml (3-45), and a swallowing rate at the limit of normal (median 10 ml/sec (range 4-25 ml). VFSS revealed piecemeal deglutition and pharyngeal residue. We found pharyngo-oral regurgitation in fourteen patients (58%), i.e. they transported the residue from the hypopharynx back into the oral cavity and re-swallowed it. Six patients (25%) demonstrated impaired swallowing safety (i.e. penetration aspiration scale > 3). Muscle ultrasound revealed an abnormal muscle structure of the submental and tongue muscles. Ambulant patients (n = 3), had a normal dysphagia limit and swallowing rate, but VFSS showed pharyngeal residue, and muscle ultrasound demonstrated an abnormal echogenicity of the tongue. Swallowing problems were associated with mastication problems (p = 0.001).

Scoliosis Treatment With Growth-Friendly Spinal Implants (GFSI) Relates to Low Bone Mineral Mass in Children With Spinal Muscular Atrophy.

BACKGROUND: Children with spinal muscular atrophy (SMA) frequently develop neuromuscular scoliosis at an early age, requiring surgical treatment with growth-friendly spinal implants (GFSI), such as magnetically controlled growing rods. This study investigated the effect of GFSI on the volumetric bone mineral density (vBMD) of the spine in SMA children. METHODS: Seventeen children (age 13.2±1.2 y) with SMA and GFSI-treated spinal deformity were compared with 25 scoliotic SMA children (age 12.9±1.7 y) without prior surgical treatment as well as age-matched healthy controls (n=29; age 13.3±2.0). Clinical, radiologic, and demographic data were analyzed. For the calculation of the vBMD Z-scores of the thoracic and lumbar vertebrae, phantom precalibrated spinal computed tomography scans were analyzed using quantitative computed tomography (QCT). RESULTS: Average vBMD was lower in SMA patients with GFSI (82.1±8.4 mg/cm 3) compared with those without prior treatment (108.0±6.8 mg/cm 3 ). The difference was more prominent in and around the thoracolumbar region. The vBMD of all SMA patients was significantly lower in comparison with healthy controls, especially in SMA patients with previous fragility fractures. CONCLUSIONS: The results of this study support the hypothesis of reduced vertebral bone mineral mass in SMA children with scoliosis at the end of GFSI treatment in comparison with SMA patients undergoing primary spinal fusion. Improving vBMD through pharmaceutical therapy in SMA patients could have a beneficial effect on the surgical outcome of scoliosis correction while reducing complications. LEVEL OF EVIDENCE: Therapeutic Level III.

Muscle Ultrasound Changes Correlate With Functional Impairment in Spinal Muscular Atrophy.

OBJECTIVE: We investigated ultrasound patterns of muscle involvement in different types of spinal muscular atrophy (SMA) and their correlation with functional status to determine the pattern of muscle compromise in patients with SMA and the potential role of ultrasound to evaluate disease progression. METHODS: We examined muscles (biceps brachii, rectus femoris, diaphragm, intercostals and thoracic multifidus) of 41 patients with SMA (types 1 to 4) and 46 healthy age- and sex-matched control individuals using B-mode ultrasound for gray-scale analysis (GSA), area (biceps brachii and rectus femoris) and diaphragm thickening ratio. Functional scales were applied to patients only. We analyzed ultrasound abnormalities in specific clinical subtypes and correlated findings with functional status. RESULTS: Compared with controls, patients had reduced muscle area and increased mean GSA for all muscles (p < 0.001), with an established correlation between the increase in GSA and the severity of SMA for biceps brachii, rectus femoris and intercostals (p = 0.03, 0.01 and 0.004 respectively) when using the Hammersmith Functional Motor Scale Expanded. Diaphragm thickening ratio was normal in the majority of patients, and intercostal muscles had higher GSA than diaphragm in relation to the controls. CONCLUSION: Ultrasound is useful for quantifying muscular changes in SMA and correlates with functional status. Diaphragm thickening ratio can be normal even with severe compromise of respiratory muscles in quantitative analysis, and intercostal muscles were more affected than diaphragm.

Mechanical Insufflation-Exsufflation: The Rest of the Story.

Mechanical insufflation-exsufflation has been reported to decrease pneumonia rates by about 90% for patients with Duchenne muscular dystrophy now living into their 40s and 50s without tracheotomy tubes. It greatly reduces respiratory complications and hospitalization rates to less than one per 10 patient-years for advanced spinal muscular atrophy type 1, through 25-30 years of age. It is most successful from the point at which small children become able to cooperate with it, generally from 3 to 5 years of age. However, since the 1950s, successful use to extubate and decannulate ventilator "unweanable" patients with little to no measurable vital capacity without resorting to tracheostomy has always been at pressures of 50-60 cm H2O via oronasal interfaces and at 60-70 cm H2O via airway tubes when present. It must usually also be used in conjunction with up to continuous noninvasive positive pressure ventilatory support. Centers that use these effectively have eliminated need to resort to tracheotomies for people with muscular dystrophies and spinal muscular atrophies, including unmedicated patients with spinal muscular atrophy type 1. Barotrauma has been rare despite dependence on it and noninvasive ventilatory support. Despite this, noninvasive respiratory management continues to be widely underutilized.

Longitudinal Assessment of Timed Function Tests in Ambulatory Individuals with SMA Treated with Nusinersen.

BACKGROUND: Ambulatory individuals with spinal muscular atrophy experience weakness and impairments of speed and endurance. This leads to decreased motor skill performance required for daily living including transitioning from floor to stand, climbing stairs, and traversing short and community distances. Motor function improvements have been reported in individuals receiving nusinersen, but changes in timed functional tests (TFTs) which assess shorter distance walking and transitions have not been well documented. OBJECTIVE: To evaluate changes in TFT performance over the course of nusinersen treatment in ambulatory individuals with SMA and identify potential factors [age, SMN2 copy number, BMI, Hammersmith Functional Motor Scale Expanded (HFMSE score), Peroneal Compound Motor Action Potential (CMAP) amplitude] associated with TFT performance. METHODS: Nineteen ambulatory participants receiving nusinersen were followed from 2017 through 2019 (range: 0-900 days, mean 624.7 days, median 780 days); thirteen of 19 (mean age = 11.5 years) completed TFTs. The 10-meter walk/run test, time-to-rise from supine, time-to-rise from sitting, 4-stair climb, 6-minute walk test (6MWT), Hammersmith Expanded and peroneal CMAP were assessed at each visit. Linear mixed-effects models were used to evaluate unadjusted and adjusted changes in these outcomes over time. RESULTS: Apart from time to rise from sitting and from supine, all TFTs were found to improve over the course of treatment after adjusting for baseline age and BMI. CONCLUSIONS: Improvement in TFTs over time in patients with SMA treated with nusinersen suggests that shorter TFTs may have value to assess individuals with SMA who have or later gain ambulatory function during treatment.