Spinal Muscle Atrophy 

Updated: Nov 05, 2018
Author: Ashish S Ranade, MBBS, MS, MRCS; Chief Editor: Jeffrey A Goldstein, MD 

Overview

Background

Spinal muscle atrophy (SMA; also known as spinal muscular atrophy) is an autosomal recessive hereditary disease characterized by progressive hypotonia and muscular weakness.[1] The characteristic muscle weakness occurs because of a progressive degeneration of the alpha motor neuron from anterior horn cells in the spinal cord. The weakness is more severe in the proximal musculature than in the distal segments.

In certain patients, the motor neurons of cranial nerves (especially cranial nerves V-XII) can also be involved. Sensation, which originates from the posterior horn cells of the spinal cord, is spared, as is intelligence. Several muscles are spared, including the diaphragm, the involuntary muscles of the gastrointestinal system, the heart, and the sphincters.[2, 3, 4, 5]

In 1890, Werdnig described for the first time the classic infantile form of SMA.[6] Many years later, in 1956, Kugelberg and Welander described the less severe form of SMA.[7] Werdnig, in 1890,[6] and Hoffman, in 1891,[8] reported cases of muscular dystrophy occurring in infants that were otherwise similar to cases of muscular dystrophy found in older children and adults (eg, Duchenne muscular dystrophy).

SMA is the most common diagnosis in girls with progressive weakness. It is one of the most common genetic causes of death in children.

Pathophysiology

SMA is caused by a mutation in the survival motor neuron (SMN) gene. This gene is normally inactive during the fetal period and allows normal apoptosis in the developing fetus. The gene becomes active in the healthy mature fetus to stabilize the neuronal population. In a healthy person, this gene produces a protein that is critical to the function of the nerves that control our muscles; without it, those nerve cells cannot properly function and eventually die, leading to debilitating and often fatal muscle weakness. In the absence of the gene, programmed cell death persists.[9] The mechanism and timing of abnormal motor neuron death remain unknown.[10, 11]

Classification

SMA is commonly divided into four types on the basis of the patient's age at onset and the highest physical milestone achieved, as follows:

  • Type I (Werdnig-Hoffmann disease) - Onset between birth and age 6 months
  • Type II - Onset between the ages of 6 and 12 months
  • Type III (Kugelberg-Welander disease) - Onset between the ages of 2 and 15 years
  • Type IV - Adult onset

Etiology

Patients with SMA have a homozygous deletion of the telomeric SMN gene SMN1, which is found in arm 5q (bands q11.2-13.3).[10]  This deletion has been demonstrated in as many as 98% of patients with SMA.

SMN1 encodes the SMN protein, which is part of a multiprotein complex required for the biogenesis of small nuclear ribonucleoproteins.[12, 13]  The SMN protein is critical to the health and survival of the nerve cells in the spinal cord that are responsible for muscle contraction (motor neurons). SMN1 has been linked to pre-mRNA splicing, spliceosome biogenesis, and the nucleolar protein fibrillarin. The absence or dysfunction of SMN is reflected by an enhanced neuronal death. A heterozygous deletion leads to an asymptomatic carrier state.[14]

There is a second gene that also plays a role in producing the SMN protein—namely, SMN2, often called the SMA "backup gene." The protein produced by SMN2 is more labile and is unable to compensate fully for the absence of SMN1.[15]  The severity of SMA is dependent on the number of copies of SMN2. Most severely affected individuals will have fewer copies of this gene.[16]

A significant increase in nuclear DNA vulnerability was detected in fetuses with SMA at 12-15 weeks' gestational age. It reflected a decrease in the number of anterior horn neurons. This vulnerability is no longer seen in the rest of the prenatal or postnatal period. Abnormal cell morphology was seen only in the postnatal period.[17]

Epidemiology

United States statistics

The incidence of SMA is about 1 case in 10,000 live births. The prevalence of persons with the carrier state is 1 in 50. SMA can affect any race or gender.

In North Dakota, the incidence is about 1 case in 6720 (15 per 100,000) live births, the prevalence is 1.5 cases in 10,000, and the prevalence of persons with the Werdnig-Hoffman disease carrier state is 1 in 41.[18] SMA appears to be three to 10 times more common in North Dakota than in other areas.

SMA is the most common degenerative disease of the nervous system in children. After cystic fibrosis, it is the second most common disease inherited in an autosomal recessive pattern that affects children. It is the leading heritable cause of infant mortality.[19]

International statistics

The incidence of SMA is generally higher in Central and Eastern Europe than in Western Europe.

In England, the incidence is 1 case in 24,100 (4 per 100,000) live births. Prevalence is 1.2 cases per 100,000 population. In Italy, the incidence is 7.8 cases in 100,000 live births (all types). In Germany, the incidence of Werdnig-Hoffmann disease is 1 case in 10,202 (9 per 100,000) live births.[20] The incidence of SMA in Slovakia is 1 case in 5631 (18 per 100,000) live births (all types). In Poland, the incidence of Werdnig-Hoffmann disease is 1 case in 19,474 (5 per 100,000) live births.

Age-related demographics

The three different types of SMA that occur in the pediatric population are genetically similar but differ with respect to patient age at presentation and clinical course, as follows:

  • Type I (Werdnig-Hoffmann disease) - This acute infantile SMA is usually identified in patients from birth to age 6 months; this is the most severe and common form of the disease, accounting for 60% of all cases of SMA, and it is often fatal early in life
  • Type II - This chronic infantile SMA is diagnosed in infants aged 6-24 months
  • Type III (Kugelberg-Welander disease) - This type of SMA is diagnosed in children aged 2-15 years

Sex-related demographics

Males are more commonly affected with SMA than females are. The male-to-female ratio is 2:1. The clinical course in males is more severe. Life expectancy has not been demonstrated to be influenced by sex.[21] As the age at onset increases, incidence of SMA in females decreases. With age at onset older then 8 years, females are affected much less frequently. In cases in which the patient is older than 13 years at onset, incidence in females is the exception.

Race-related demographics

The incidence of SMA in black Africans is very low.

Prognosis

As a general rule, the younger the patient at disease onset, the worse the prognosis. The overall median age at death exceeds 10 years. Intelligence is unaffected by SMA. Patients with type I SMA usually die by age 2 years. Patients with type II SMA have a greater expected life span than patients with type I SMA. Some patients with type II SMA live into the fifth decade of life. Patients with type III SMA have nearly normal life expectancy.

Death occurs as a result of respiratory compromise. The life span of affected individuals has significantly increased with the use of intermittent positive-pressure ventilation, with or without a tracheostomy.

Patient Education

Prenatal diagnosis in the first trimester and proper genetic counseling are possible with DNA analysis. This enables more accurate carrier detection.[22] Not all parents of children with SMA are obligate carriers.[23]  Carrier testing is important for reproductive decision-making. Approximately 3% of cases are sporadic.

A potential medicolegal pitfall is poor counseling of parents and patients regarding possible complications before surgical treatment. These patients lose function after spinal stabilization, and their ability to ambulate may be hindered. The possibility of recurrence or worsening of the hip dislocation must be emphasized; the risk of recurrent deformity is present even with foot and ankle procedures.

 

Presentation

History

With type I spinal muscle atrophy (SMA; also known as spinal muscular atrophy), most mothers report abnormal inactivity of the fetus in the latter stages of pregnancy. Babies with type I SMA face many physical challenges, including muscle weakness, trouble breathing, coughing and swallowing. The patient with type I SMA is unable to roll over or sit. Progressive clinical deterioration occurs. Death usually occurs from respiratory failure and its complications in patients by age 2 years.

Patients with type II SMA have normal development for the first 4-6 months of life. They may be able to sit independently, but they are never able to walk. They require a wheelchair for locomotion. They have a longer life span than patients with type I SMA. Some patients with type II SMA live into the fifth decade of life.

In patients with type III SMA, the presenting complaint is difficulty climbing stairs or getting up from the floor (due to hip extensor weakness). Individuals affected by SMA type III are initially able to walk, but as they grow, their mobility is increasingly limited, and they eventually may need to use a wheelchair. The life span is nearly normal.[24]

Physical Examination

SMA is often diagnosed clinically on the basis of the child's physical appearance. The diagnosis may be suspected when children are noted to be weak or to have a delay in their developmental milestones, such as holding their head up, rolling over, sitting independently, standing, or walking later than would be expected.

After a thorough medical history is reviewed and a physical examination is performed, the primary care provider may order genetic testing through a blood sample, or the child may be referred to a neurologist who will also perform an examination and then order genetic testing (again through a blood sample) to confirm the diagnosis. 

Type-specific findings

Newborns with type I SMA are floppy and inactive. They move the extremities little, if at all. The hips are flexed, abducted, and externally rotated. The knees are flexed. Because the distal musculature is usually spared, the fingers and toes move. Infants cannot control or lift the head. Areflexia is universal.

Patients with type II SMA have head control, and 75% of these patients can sit independently. Muscular weakness is greater in the lower extremities than in the upper extremities. Patellar reflex is absent. The young may demonstrate bicipital and triceps tendon reflexes. Tongue fasciculations are present, as are upper-extremity tremors. Scoliosis is universal, and most patients develop hip dislocation, either unilateral or bilateral, when younger than 10 years.

Patients with type III SMA walk early in life and maintain their ambulatory capacity into adolescence. Weakness may cause foot drop, and patients have limited endurance. A third of the patients become wheelchair bound as adults (mean age, 40 years).

Other findings

A long C-shaped thoracolumbar scoliotic curve is present in patients with type II SMA and in half of patients with type III SMA. The curve progresses to a severe and incapacitating deformity if not treated. About 30% of patients have kyphotic deformities as well.

Pseudohypertrophy of the calf is present, which may confound the diagnosis (ie, with Duchenne muscular dystrophy and Becker muscular dystrophy). Bouwsma reported that this finding was associated with elevated serum creatine kinase (CK).[25]  This combination was only observed in males; no females in his series had hypertrophy of the calves.[25]

Tongue fasciculations are pathognomonic of SMA (all types), as opposed to all other neuromuscular diseases of infancy. The presence of tongue fasciculations can aid in the diagnosis, in that 56% of patients exhibit this symptom.

 

DDx

Diagnostic Considerations

Other problems to be considered include the following:

Differential Diagnoses

 

Workup

Laboratory Studies

A simple blood test can confirm whether the child has a mutation that causes spinal muscle atrophy (SMA; also known as spinal muscular atrophy). If the survival motor neuron (SMN) gene test is positive, the diagnosis is confirmed. However, 5% of children with the symptoms of SMA can have a negative SMN gene test and may require additional diagnostic testing. These tests can include electromyography (EMG), a nerve conduction study (NCS), or muscle biopsy and additional blood tests to help rule out other forms of muscle disease.

In contrast to findings in patients with Duchenne muscular dystrophy and Becker muscular dystrophy, aldolase and serum creatine kinase (CK) findings are within reference ranges in patients with SMA. In later-onset SMA, these muscle enzymes may be slightly elevated.

Imaging Studies

On anteroposterior (AP) and lateral views of the pelvis, most patients with type II SMA are found to have developed hip dislocations. (See the images below.) The dislocations are only temporarily symptomatic and do not influence function in these patients, because they are nonambulatory.

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.

A complete spine and scoliosis series is indicated. All patients with type II SMA and most patients with type III SMA develop a long C-shaped scoliotic curve. (See the images below.)

Spinal muscle atrophy. At age 4 years, this boy's Spinal muscle atrophy. At age 4 years, this boy's chest radiograph already reveals presence of significant 32° left thoracic scoliosis. Diagnosis is type I spinal muscle atrophy (Werdnig-Hoffmann disease). This radiograph captures the lumbar curvature incompletely.
Spinal muscle atrophy. By age 6 years, child's cur Spinal muscle atrophy. By age 6 years, child's curve is starting to decompensate. Note development of right-side truncal shift. He now has 40° thoracic curve and 60° lumbar curve.
Spinal muscle atrophy. Spine anteroposterior view. Spinal muscle atrophy. Spine anteroposterior view. Spinal curvature is progressing. Lumbar curve now is 70°, and thoracic curve is 35°. It is now clearly apparent that right hip is dislocated. Also note marked pelvic obliquity in this patient.
Spinal muscle atrophy. By age 9 years, this patien Spinal muscle atrophy. By age 9 years, this patient with type I spinal muscle atrophy now has thoracic curve of 60° and lumbar curve of 110°. Note that patient has tracheostomy tube and nasogastric tube as well.

Other Tests

Findings from electromyography (EMG) in patients with SMA are characteristic of a neuropathic disorder, revealing fibrillation potentials, denervation, and increased amplitude. However, nerve conduction velocity test results are normal.

Prenatal DNA analysis is available to diagnose the deletion of arm 5q.[27, 28]

Biopsy

In patients with SMA, incisional muscle biopsies reveal a uniform smaller diameter of all fibers. This contrasts with biopsy findings for other muscular dystrophies, which consist of degenerating muscle with variable muscle fiber sizes. Biopsies in patients with hypotonic cerebral palsy reveal normal muscle fibers.

Histologic Findings

Two subtypes of SMA deserve special mention with regard to their typical histologic appearance. The first, Werdnig-Hoffmann disease (type I SMA), is typically diagnosed in patients from birth to age 6 months. Its histologic pattern is usually one of extremely small and reasonably uniform small muscle fibers (see the images below).

Spinal muscle atrophy, Werdnig-Hoffman disease. Sm Spinal muscle atrophy, Werdnig-Hoffman disease. Small muscle fibers within separate muscle fascicles.
Spinal muscle atrophy, Werdnig-Hoffman disease. Ma Spinal muscle atrophy, Werdnig-Hoffman disease. Marked variation in muscle fiber size, as well as relative increase in associated connective tissue.

The second subtype, Kugelberg-Welander disease (type III SMA), is usually diagnosed in patients aged 2-15 ears. The same tendency toward small muscle fiber diameter is seen but with much less uniformity (see the images below). Substantial variation, with intermixing of larger and smaller muscle fibers, may be observed.

Spinal muscle atrophy, Kugelberg-Welander disease. Spinal muscle atrophy, Kugelberg-Welander disease. Marked variation in muscle fiber size, along with increased perimysial connective tissue.
Spinal muscle atrophy, Kugelberg-Welander disease. Spinal muscle atrophy, Kugelberg-Welander disease. Muscle-fiber variation with some demonstrating internal nuclei.

In both forms of SMA, substantial increases in muscular connective tissue lead to both characteristic histologic findings and clinical findings such as increased muscle firmness. Centrally migrated or otherwise internalized nuclei are considered pathologic if they are present in more than about 3% of muscle fibers. Such nuclear findings are common in a variety of muscle diseases, including SMA.

 

Treatment

Approach Considerations

No two children with spinal muscle atrophy (SMA; also referred to 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.

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.

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.

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.

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.

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]

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]

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.

 

Medication

Medication Summary

In December 2016, the US FDA approved nusinersen, the first drug approved to treat children (including newborns) and adults with spinal muscular atrophy (SMA).

Antisense Oligonucleotides

Class Summary

Antisense oligonucleotides (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency may be considered for treatment.

Nusinersen (Spinraza)

In 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. It is indicated for SMA in pediatric and adults patients.

 

Questions & Answers

Overview

What is spinal muscle atrophy (SMA)?

What is the pathophysiology of spinal muscle atrophy (SMA)?

What are the types of spinal muscle atrophy (SMA)?

What causes spinal muscle atrophy (SMA)?

What is the prevalence of spinal muscle atrophy (SMA) in the US?

What is the global prevalence of spinal muscle atrophy (SMA)?

Which age groups have the highest prevalence of spinal muscle atrophy (SMA)?

What are the sexual predilections of spinal muscle atrophy (SMA)?

What are the racial predilections of spinal muscle atrophy (SMA)?

What is the prognosis of spinal muscle atrophy (SMA)?

What is included in patient education about spinal muscle atrophy (SMA)?

Presentation

Which clinical history findings are characteristic of spinal muscle atrophy (SMA)?

How is spinal muscle atrophy (SMA) diagnosed?

Which physical findings are characteristic of type I spinal muscle atrophy (SMA)?

Which physical findings are characteristic of type II spinal muscle atrophy (SMA)?

Which physical findings are characteristic of type III spinal muscle atrophy (SMA)?

What is the prevalence of a long C-shaped thoracolumbar scoliotic curve in spinal muscle atrophy (SMA)?

What conditions are included in the differential diagnoses of spinal muscle atrophy (SMA) when pseudohypertrophy of the calf is present?

What is the prevalence of tongue fasciculations in spinal muscle atrophy (SMA)?

DDX

Which conditions are included in the differential diagnoses of spinal muscle atrophy (SMA)?

What are the differential diagnoses for Spinal Muscle Atrophy?

Workup

What is the role of lab testing in the workup of spinal muscle atrophy (SMA)?

What is the role of imaging studies in the workup of spinal muscle atrophy (SMA)?

What is the role of EMG in the workup of spinal muscle atrophy (SMA)?

What is the role of genetic testing in the workup of spinal muscle atrophy (SMA)?

What is the role of biopsy in the workup of spinal muscle atrophy (SMA)?

Which histologic findings are characteristic of spinal muscle atrophy (SMA)?

Treatment

What can be done to optimize treatment outcomes for spinal muscle atrophy (SMA)?

How is spinal muscle atrophy (SMA) treated?

What is the role of genetic therapy in the treatment of spinal muscle atrophy (SMA)?

How are the pulmonary manifestations of spinal muscle atrophy (SMA) treated?

What is the role of physical therapy in the treatment of spinal muscle atrophy (SMA) treated?

What is scoliosis treated in spinal muscle atrophy (SMA) treated?

How are pulmonary infections prevented in spinal muscle atrophy (SMA)?

What are the cognitive and educational needs of children with spinal muscle atrophy (SMA)?

What is the role of posterior spinal fusion and segmental instrumentation in the treatment of spinal muscle atrophy (SMA)?

How are contractures treated in spinal muscle atrophy (SMA)?

What is the role of pelvic stabilization procedures in the treatment of spinal muscle atrophy (SMA)?

How are fractures treated in spinal muscle atrophy (SMA)?

What are the possible complications of spinal muscle atrophy (SMA)?

Which dietary modifications are used in the treatment of spinal muscle atrophy (SMA)?

Which activity modifications are used in the treatment of spinal muscle atrophy (SMA)?

Which specialist consultations are beneficial to patients with spinal muscle atrophy (SMA)?

What is included in long-term monitoring of spinal muscle atrophy (SMA)?

Medications

Which medications are FDA-approved for the treatment for spinal muscle atrophy (SMA)?

Which medications in the drug class Antisense Oligonucleotides are used in the treatment of Spinal Muscle Atrophy?