Spinal Muscular Atrophy Overview

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Questions and Answers

What is the method of administration for Nusinersen (Spinraza)?

Intramuscular injection

Intrathecal injection (correct)

Inhalation

Intravenous injection

Which drug is a gene therapy treatment for spinal muscular atrophy (SMA)?

Vitamin E

Nusinersen (Spinraza)

Onasemnogene abeparvovec-xioi (Zolgensma) (correct)

Risdiplam (Evrysdi)

What is the primary effect of Risdiplam (Evrysdi)?

Slows disease progression

Increases SMN protein production from SMN2 gene (correct)

Delivers SMN1 transgene to cell nuclei

Provides nutritional support

For which age group is Zolgensma indicated?

Children less than 2 years Signup and view all the answers

Which of the following interventions is NOT a preventive treatment for SMA?

Stem cell transplant Signup and view all the answers

Which type of SMA generally has the best prognosis?

SMA Type III Signup and view all the answers

What is one of the goals for physical therapy (P.T.) in SMA treatment?

Improve/maintain muscle strength Signup and view all the answers

What can contribute to a poorer prognosis in SMA?

Earlier onset of symptoms Signup and view all the answers

Which form of Spinal Muscular Atrophy is considered the most severe and can be evident before birth?

SMA Type 0 Signup and view all the answers

What is the primary gene involved in 99% of all cases of Spinal Muscular Atrophy?

SMN1 gene Signup and view all the answers

Which SMA type usually shows an onset between 6 and 18 months of age?

SMA Type II Signup and view all the answers

What is the most common clinical feature in individuals with SMA Type I?

Flaccidity and hypotonia Signup and view all the answers

Which of the following accurately describes the progression of SMA Type III?

Slow, continued developmental progression Signup and view all the answers

What diagnostic method can identify specific mutations for SMA in the majority of cases?

Genetic testing Signup and view all the answers

Which type of SMA typically allows individuals to achieve independent sitting but they may still require a mobility device?

SMA Type II Signup and view all the answers

In Spinal Muscular Atrophy, which muscles are generally spared from weakness?

Eye muscles and anal sphincter Signup and view all the answers

What clinical feature is most associated with SMA Type IV (Adult-Onset SMA)?

Tremors and fasciculations Signup and view all the answers

Which SMA type has the best prognosis for achieving a normal lifespan?

SMA Type IV Signup and view all the answers

Which feature characterizes SMA Type I concerning respiratory function?

Significant risk of respiratory failure Signup and view all the answers

In terms of incidence, how common is Spinal Muscular Atrophy?

1 in 10,000 live births Signup and view all the answers

What best describes the muscle weakness observed in SMA?

Bilateral and symmetrical with proximal dominance Signup and view all the answers

Study Notes

Spinal Muscular Atrophy (SMA)

SMA is a group of inherited disorders, characterized by the degeneration and loss of anterior horn cells (AHC) in the spinal cord and brainstem.
AHC degeneration leads to progressive muscle weakness and atrophy.
Proximal muscles are typically more affected than distal muscles.

Objectives

Describe the etiology, pathophysiology, signs, and symptoms of Spinal Muscular Atrophy (SMA).
Detail the various forms of SMA and compare/contrast their signs and symptoms.
Identify diagnostic parameters and tests used for SMA diagnosis.
Describe the general course and prognosis of different SMA forms.
Discuss the medical and/or surgical management of SMA.
Identify key rehabilitation considerations for individuals with SMA.

SMA - Definition

SMA is a group of inherited disorders characterized by the degeneration and loss of anterior horn cells (AHCs) in the spinal cord and brainstem.
This AHC degeneration results in progressive muscle weakness and atrophy.

SMA - Incidence and Etiology

SMA is an autosomal recessive disorder.
It is the second most common fatal autosomal recessive disorder, following cystic fibrosis.
A gene deletion on chromosome 5 is the most common cause of a general form of SMA (referred to as Classic SMA or SMN-related SMA/chromosome 5 SMA).
Various subtypes of SMA exist (SMA 0, SMA I, SMA II, SMA III, Adult SMA (IV)).
The incidence is approximately 1 in 10,000 live births, and about 1 in 50 people carry the genetic defect.

SMA - Etiology (Less Common Forms)

Less common SMA forms are caused by mutations in genes other than chromosome 5.
Examples include VAPB gene on chromosome 20, DYNC1H1 gene on chromosome 14, BICD2 gene on chromosome 9, and UBA1 gene on the X chromosome.
These variants can affect different parts of the body differently compared to the common chromosome 5 SMA form.

SMA - Pathogenesis

The SMN1 gene is defective in 99% of SMA cases.
AHC degeneration in SMA appears to result from the persistence of programmed cell death.
The SMN1 gene mutation decreases the intracellular levels of survival motor neuron (SMN) protein, which is essential for preventing neuronal cell death.
The SMN2 gene is also present and can partially compensate for the absence of SMN1 by producing SMN protein, but it's less efficient than SMN1.
The severity of SMA symptoms correlates with the number of SMN2 gene copies present: More SMN2 copies lead to more SMN protein production, resulting in less severe forms of SMA

SMA - General Clinical Picture - Onset

Onset varies from early in utero to late in life.
The majority of cases occur during infancy or early childhood.
Adult forms of SMA are rare.

SMA - General Clinical Picture - Weakness

Weakness is bilateral and symmetrical.
Proximal muscles are more affected than distal muscles.
Facial muscles may also be affected.
Eye muscles and the anal sphincter are generally spared.

SMA - General Clinical Picture - Other features

Progressive atrophy with significant flaccidity (floppy infants).
Diminished deep tendon reflexes (DTRs).
Normal sensory function and intellectual function.
Restrictive lung disease.
Common skeletal deformities include scoliosis, kyphosis, lordosis, contractures, and joint dislocation.

SMA - Types

Types are categorized based on age at onset and rate of progression.
Childhood SMA types (0, I, II, and III).
Adult-onset SMA (Type IV).

SMA Type 0

Rarest and most severe form.
Can be evident before birth with reduced fetal movement, joint deformities, contractures, and congenital heart defects.
Severe hypotonia is present at birth with very weak respiratory muscles.
Often do not survive past infancy due to respiratory failure.

SMA Type I

Acute, severe form.
Onset typically between birth and six months of age.
Infants may appear normal at birth, but gradually develop severe weakness, poor posture (frog-like position), poor head control, and diminished newborn movements.
Respiratory problems are common and result in reduced lifespan without treatment.
Also known as Werdnig-Hoffmann disease.

SMA Type II

Intermediate severity.
Onset usually between 6 and 18 months.
The majority of infants may be able to sit with limited trunk control, but standing and walking usually are not possible.
Individuals typically require wheelchairs.
Lifespan is typically at least 10 years, and some cases up to 25 years.

SMA Type III

Mild form; onset after 18 months to adolescence.
Individuals can sit and develop some ambulatory abilities but frequently require wheelchairs as they age.
Slow progression over time.
Often known as Kugelberg-Welander disease.

SMA Type IV

Often known as adult-onset SMA.
Rare since it is mostly diagnosed later in life, ( after 30 - 35 years of age).
Mild muscle weakness.
Gradual development of proximal limb weakness.
Individuals are typically slow-progressing and may not require assistive devices at younger ages, but as they progress, assistive devices may be required.
Typically have a normal lifespan.

SMA - Diagnosis

Clinical evaluations are crucial, including muscle biopsy for structural analysis.
Electromyography (EMG) detects decreased motor action potentials.
Nerve conduction studies (NCVs) indicate slowed motor conduction velocities.
Genetic testing can identify specific mutations responsible for SMA in most cases.
Newborn screening for SMA is becoming more common.

SMA - Medical Treatment

Disease-modifying pharmacologic therapies, not a cure:
Nusinersen (Spinraza), FDA approved in 2016.
Onasemnogene abeparvovec-xioi (Zolgensma), FDA approved in 2019 for infants.
Risdiplam (Evrysdi), FDA approved in 2020 for oral use.
Symptomatic care and preventative treatment, such as respiratory support, management of skeletal complications (e.g. scoliosis treatment or hip dislocation surgery), and maintaining head and sitting posture, as well as feeding assistance.

SMA - Prognosis

Prognosis varies significantly depending on the type and age of onset.
Earlier onset and faster progression of weakness can lead to respiratory distress and a shorter lifespan.
Types III and IV typically have a better prognosis.

Rehabilitation Considerations

Goals of physical therapy: Achieve the highest level of independent living and mobility possible.
Improve/maintain muscle strength and aerobic capacity.
Prevent or delay complications such as contractures, skeletal deformities, respiratory failure.
Physical therapy interventions include strengthening exercises, aerobic exercises, developmental skill training, aquatic therapy, standing programs, management of complications like scoliosis and contractures as well as prescription/training with assistive devices

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Description

This quiz focuses on Spinal Muscular Atrophy (SMA), exploring its etiology, pathophysiology, and various forms. It outlines the diagnostic parameters, prognosis, and management strategies for SMA, emphasizing rehabilitation considerations. Engage with this quiz to enhance your understanding of SMA and its impact on muscle function.