Spinal Muscle Atrophy Treatment & Management

Updated: Jan 03, 2017
  • Author: Ashish S Ranade, MBBS, MS, MRCS; Chief Editor: Jeffrey A Goldstein, MD  more...
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Treatment

Approach Considerations

No two children with spinal muscle atrophy (SMA; also known as spinal muscular atrophy) will be exactly the same. Accordingly, treatment and care plans for each family should be tailored to meet specific individual needs.

It is also important to remember that the brains of children with SMA are not affected at all and that cognitive abilities therefore remain normal. Children with SMA are usually very intelligent, and they should be encouraged to participate in as many age-appropriate and developmentally appropriate activities as possible, with adaptations made whenever necessary. It is essential that children with SMA be assisted in reaching their utmost potential in school, at home, and in their communities.

Ideally, a team-based approach to care optimizes outcomes in these children. The team should consist of a neurologist, a pulmonologist/intensivist, an orthopedic surgeon, a nutritionist, genetic counselors, social workers, an orthoptist, and occupational and physical therapists.

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Medical Care

Curative therapy for SMA has been elusive. The survival rate is poor among young patients. Interest has arisen in the use of inhibitors of gamma-aminobutyric acid (GABA) synthesis, with promising results. Developments in the use of antisense-based therapy have been described. [29, 30]

 

In December 2016, the US Food and Drug Administration (FDA) approved nusinersen (Spinraza), the first drug approved for treatment of children (including newborns) and adults with SMA. Nusinersen is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Through in-vitro assays and studies in transgenic animal models of SMA, nusinersen was shown to increase exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein. [31]

FDA approval was based on the ENDEAR trial, a phase 3 randomized, double-blind, sham-controlled study (N=121) in patients with infantile-onset (most likely to develop type 1) SMA. [32] At a planned interim analysis, the rate of achieving a motor milestone response was higher in infants treated with nusinersen (40%) than in those not so treated (0%), as measured by the Hammersmith Infant Neurological Examination (HINE). Additionally, a smaller percentage of patients died in the nusinersen group (23%) than in the untreated group (43%).

Interim findings from CHERISH, another phase 3 trial, involved 126 nonambulatory patients with later-onset SMA (consistent with type 2), including those with the onset of signs and symptoms at 6 months or later and an age of 2-12 years at screening. [33] Prespecified interim analysis demonstrated a difference of 5.9 points at 15 months between the treatment arm (n=84) and the sham-controlled arm (n=42), as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE). From baseline to 15 months of treatment, patients in the nusinersen group achieved a mean improvement of 4.0 points in the HFMSE, whereas those in the control group showed a mean decline of 1.9 points.

Research into genetic therapies, as well as molecular and stem cell–mediated therapies, is ongoing. [34, 35, 36]  The Cure SMA drug pipeline has identified four possible treatment targets [37] :

  • Replacement or correction of the faulty  SMN1 gene
  • Modulation of the low-functioning  SMN2 “backup gene”
  • Neuroprotection of the motor neurons affected by loss of survival motor neuron (SMN) protein
  • Muscle protection to prevent or restore the loss of muscle function in SMA

Proper care can improve quality of life for those with SMA.

Patients with SMA often have impaired cough, respiratory insufficiency, dysphagia, gastroparesis, constipation, and evolving orthopedic issues (eg, scoliosis). To address these problems, various types of equipment may be used, from respiratory support during sleep (eg, bilevel positive airway pressure [BiPAP] and mucus clearance devices) to gastrostomy tubes to wheelchairs and braces. Cognitive development typically is not affected. Usual primary care practices (especially care coordination and family support), along with routine pediatric care immunizations, developmental surveillance, and monitoring of growth, contribute to the overall well-being of the child and the family.

Care management includes optimizing breathing and coughing, addressing nutrition and feeding issues, managing mobility and activities of daily living (ADLs), and preparing for illness.

Patients with type 1 SMA have difficulty in coughing and breathing and will require respiratory care (eg, insufflator-exsufflator/cough assist, oxygen saturation monitor) and support (either noninvasive [BiPAP/ventilator] or invasive [tracheostomy]). They also lose their ability to chew and swallow food and water and will require nutrition (eg, nutritional modification or supplementation) and feeding support (eg, via a nasogastric tube, gastrostomy, or gastrojejunostomy).

Physical therapy (including aquatherapy and hippotherapy) and occupational therapy are required for optimizing positioning, seating, and mobility. Patients with type I SMA, because of their short life span, require little, if any, involvement on the part of an orthopedist. Splinting is used for fractures.

For patients with type II or type III SMA, physical and occupational therapy may be employed for maintaining range of motion of joints, preventing contractures, and optimizing positioning, seating, and ADLs. These patients also require orthotics, standing and walking aids, and mobility devices  (see Surgical Care below). [38, 39, 40]  Nutritional support and respiratory care and support are important as well. Because children with SMA may have decreased bone density, optimizing bone health (eg, with supplemental calcium and vitamin D) is necessary to prevent insufficiency fractures. Bisphosphonates may be considered for cases of decreased bone density.

Scoliosis (curvature of the spine) occurs at some point in virtually all children with type I or II SMA and in some with type III SMA. The degree of the scoliosis is a factor in determining how to treat it. Because scoliosis can restrict breathing and pulmonary function, necessary treatment measures should be implemented early. Options for managing scoliosis include custom seating systems, seating aids, and a body jacket. Later, spinal surgery may have to be considered.

Bracing plays only a limited role in scoliosis associated with SMA. There is a paucity of literature on the subject. In one study, the Garches brace was studied in children with type 1b SMA. [41] In this group, use of the brace was shown to help with sitting and upright head posture, thereby contributing to an improvement in quality of life. In 25 children, Garches brace treatment was started at an early age; subsequently, 72% needed spinal fusion after a mean of 10.6 years.

To avoid pulmonary infections or prolonged postoperative intubations, aggressive preoperative pulmonary care must be provided to patients with SMA. In cases of pulmonary compromise in patients with SMA, transfer to the pediatric pneumology service for stabilization and treatment of complications should be considered.

All children with SMA have cognitive and educational needs. SMA does not affect the brain or its development and thus does not limit an individual’s ability to learn and succeed academically. Children with SMA will need early intervention during infancy and early childhood, an individualized educational plan in childhood, and classroom modifications to accommodate their physical needs.

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Surgical Care

Posterior spinal fusion and segmental instrumentation

The most common orthopedic problem is scoliosis, which is often severe. [42] It is universal among nonambulatory patients, in whom the curve progression is about 8° annually, despite brace treatment. Half of ambulatory patients develop scoliosis as well, but at a slower rate of progression.

Posterior spinal fusion with segmental instrumentation is indicated in young patients whose curve cannot be controlled with a brace and in patients older than 10 years with curves greater than 40° and forced vital capacities 40% above normal. The entire thoracic and lumbar spine down to the pelvis should be fused to obtain a balanced trunk and a leveled pelvis. As a rule, concomitant anterior spinal fusion to prevent crankshaft phenomenon is avoided; the risk of potential problems with anterior spinal surgery in a patient with SMA outweighs the benefits.

In ambulatory patients, spinal surgery that excludes the pelvis is preferred. Compensatory lumbar lordosis and pelvic motion have been observed to compensate for the proximal motor weakness in these patients. The ambulatory capacity of some of these patients may be lost after surgery.

Surgery should be delayed as long as medically possible. It should be kept in mind that curve progression is slower in patients with type III SMA and that these patients present later in life. However, when surgery is necessary, it should be performed while the patient is still ambulatory. This is in contrast to the preferred timing for surgery in patients with Duchenne muscular dystrophy. (See the images below.)

Spinal muscle atrophy. Immediate postoperative ant Spinal muscle atrophy. Immediate postoperative anteroposterior radiograph of patient at age 9 years. Thoracic curve is now at 18°, and lumbar curve is 35°, which represents more than 67% curvature correction.
Spinal muscle atrophy. Immediate postoperative lat Spinal muscle atrophy. Immediate postoperative lateral view with good sagittal balance.

Scoliosis correction in children younger than 10 years remains a challenge. Various growing systems (eg, growing rods and the vertical expandable prosthetic titanium rib [VEPTR] have been used. [43, 44, 45]  In a study by Chua et al, scoliosis correction was shown to have a beneficial effect on pulmonary function at a mean follow-up of 11.6 years. [46] Before surgery, the rate of decline of the predicted forced vital capacity was 5.31% per year; after surgery, it was reduced to 1.77% per year.

Physical therapy or surgery for contractures

Joint flexion contractures of the hips and knees are associated with nonambulatory status. Surgical releases are performed; the rate of recurrence is extremely high, especially in sitting patients. Equinus is occasionally present. Ambulatory patients rarely have equinus or cavovarus deformities. Surgical releases are rarely needed for patients with type II or III SMA, because the loss of function is due to weakness and not to contractures. Some form of tendon transfer may be needed in patients with type III SMA to correct foot or ankle functional defects.

Careful patient selection is important for optimal results. Postoperative immobilization should be of shorter duration; prolonged immobilization leads to a decline in motor function. [47, 48]

Pelvic stabilization procedures

Hip subluxations or dislocations are due to proximal musculature weakness that leads to coxa valga and loss of femoral head coverage. Half of ambulatory patients have hip pathology. (See the images below.) Unilateral dislocation in nonambulatory patients invariably leads to pelvic obliquity (which may be manifested in uneven sitting pressure sores). Hip reconstruction may be successful, but recurrence of the problem even after surgical stabilization is a concern. Therefore, surgical correction is not indicated in most patients, and treatment remains controversial.

Spinal muscle atrophy. Anteroposterior radiograph Spinal muscle atrophy. Anteroposterior radiograph of pelvis demonstrating right hip dislocation.
Spinal muscle atrophy. Lauenstein lateral view of Spinal muscle atrophy. Lauenstein lateral view of hips on patient with spinal muscle atrophy type I. Note near-universal pelvic dysmorphology (eg, widened obturator foramina) in addition to dislocated right hip.

Management of fractures

Fractures can occur in patients with type II or III SMA, and congenital fractures may be seen in type I SMA. [49]  They occur at an earlier age in type II SMA than in type III SMA. Supracondylar femur and ankle fractures are common in type II SMA, whereas in type III SMA, upper-extremity fractures are common. [50]  Nonoperative treatment is preferred for nonambulatory patients. For ambulatory patients, osteosynthesis is considered in order to maintain walking/standing ability.

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Complications

The most common medical complications associated with SMA are recurrent respiratory system infections.

One of the drawbacks to posterior spinal fusion in patients with SMA is the patients' decreased ability to perform ADLs. The now rigid and straight spine creates several difficulties. Independent feeding and hygiene are impaired, in that the patient can no longer bring the hands to the face because of the proximal upper-extremity weakness. This possibility must be discussed with the family and patient before surgery.

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Diet

A history of nutritional intake, nutritional needs, and associated medical conditions, in conjunction with a thorough physical examination, anthropometric measures, body composition, and biochemical markers, should be included in the assessment of patients with SMA. [51, 52] Intervention may include increase or decrease of energy intake. For example, dysphagia may be treated with position changes, volume changes, or thickening of liquids. Percutaneous endoscopic gastrostomy was found to be safe with minimal risks in almost all situations.

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Activity

Physical therapy should be instituted for gentle motion exercises to prevent joint contractures. Physical and occupational therapy may be beneficial for maintenance of strength and endurance, independence in self-care, and educational, social, psychological, and vocational activities. [53, 54]

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Consultations

A preoperative pulmonology consultation for pulmonary function tests (PFTs) is necessary. There is a clear consensus that curve progression correlates with deterioration of pulmonary function. However, there is no clearcut consensus that surgery improves or halts the pulmonary deterioration in SMA. It is evident, though, that in order to avoid pulmonary infections or prolonged postoperative intubations, aggressive preoperative pulmonary care must be offered.

Consultation with physical and occupational therapists should be considered. Physical therapy may be employed for joint contracture prevention or stretching. Occupational therapy may be employed for adaptive equipment for ADLs.

A geneticist may be consulted for DNA evaluation of the patient and parents for counseling purposes.

An orthotics consultation may be necessary for splinting and spine bracing (eg, with a soft, custom-molded thoracolumbosacral orthosis [TLSO]) for young children with flexible curves of 20-40°. [55, 56]

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Long-Term Monitoring

Pediatric patients with SMA must be monitored periodically by a pediatric orthopedic surgeon to assess their nutritional status and their spine and hips, as well as to evaluate for contracture development. (See the image below.)

Spinal muscle atrophy. Follow-up radiographs in pa Spinal muscle atrophy. Follow-up radiographs in patient at age 13 years reveal some spinal decompensation. Note so-called coathanger appearance of ribs in dysplastic right hemithorax.

Physical therapy is useful for joint contracture prevention and stretching. Occupational therapy is useful for adaptive equipment for ADLs.

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